ISSN 2516-3817 • May 2018

GOVERNMENTOPEN ACCESS

NORTH AMERICA ANALYSIS

DENISE CALDWELL, DIRECTOR, DIVISION OF PHYSICSAT THE U.S. NATIONAL SCIENCE FOUNDATION (NSF)

PROVIDES A FASCINATING PERSPECTIVE ON HOW THE ORGANISATION IS PURSUING PHYSICS TO THE

FOREFRONT OF KNOWLEDGE

38PURSUING PHYSICSAT THE FOREFRONT

OF KNOWLEDGE

Michael Gill, IATA Director Aviation Environmentimparts his expertise on sustainable aviationfuels and why he believes these are the nextfrontier for today’s air transport

Carmen Rottenberg, Acting Deputy UnderSecretary for Food Safety at the USDA explainshow the Food Safety and Inspection Serviceprotects Americans from foodborne illness

IN THIS ISSUE

Supported by

Catherine McKenna, Minister of Environmentand Climate Change in Canada details thecountry’s plan to reduce carbon emissions andstrengthen their clean growth economy

Imag

e: ©

Pre

cisio

n G

raph

ics

Paul

Kw

iat U

IUC/

NSF

Gene expression andHuntington’s diseaseNaoko Tanese from New York University explores how monitoring gene expression can be used to treatneurodegenerative diseases such as Huntington’s.

Naoko Tanese, PhDAssociate Dean for Biomedical SciencesDirector, Sackler Institute of GraduateBiomedical Sciences

Gene expression andHuntington’s disease

Click here to view our ebook

INTRODUCTION

The editor does not necessarily agreewith or endorse any of the views orcontents of the articles and featureswithin this document. All articles andeditorials remain the copyright of theauthors, organisations and otherrelevant authorities by whose kindpermission they are reproduced. Allinformation has been checked and iscorrect at the time of going to press.The publisher will not be liable for anyloss suffered directly or indirectly asa result of the use of or reliance onthe information contained herein.

© Adjacent Digital Politics Ltd 2018

Adjacent Digital Politics Ltd and itssuppliers collect and process personalinformation for the purposes ofcustomer analysis and market research.Our group/affiliate companies mayalso wish to contact you about ourproducts or services, or the productsof carefully selected third parties thatwe think you may be interested in.

Adjacent Digital Politics LtdDatum HouseElectra WayCrewe Business ParkCrewe Cheshire CW1 6ZF

Registered in England & Wales. Company Reg No. 8667479. VAT Registration No. 169 9152 64.

Jonathan MilesEditor

Production CoordinatorNick Wilde

DesignersAndrew BosworthBen Green

Welcome to the May 2018 edition ofNorth America Analysis. One of themany highlights of this bumper editionis from Denise Caldwell, Director of theDivision of Physics at the U.S. NationalScience Foundation (NSF). In a com-pelling opinion article, she shares a fascinating perspective on how theorganisation is pursuing physics inAmerica to the forefront of knowledge.

Staying on science, absorbing analysiscomes from Sebastien Moranta, coordi-nator of studies at the European SpacePolicy Institute (ESPI) who sheds light onEurope’s potential to explore the Moonin co-operation with other great worldpowers, including, of course, America.

One of the highlights of the agriculturesection comes from Acting DeputyUnder Secretary for Food Safety at theUnited States Department of Agricul-ture (USDA), Carmen Rottenberg whoexplains how the Food Safety andInspection Service protects Americansfrom foodborne illness.

We are also delighted to include com-ment from Greg Rosenthal of the U.S.Department of Agriculture’s (USDA)Animal and Plant Health InspectionService who explains how right-sizingregulation can optimise plant protection.

In addition to the many Americanthemed articles here, we also have aninteresting Canada section, headed upMinister of Environment and ClimateChange, Catherine McKenna, who

details the country’s plan to reducecarbon emissions and strengthen theirclean growth economy.

I would also like to mention an excel-lent piece from Vice President of theCanadian Society for the Study of Education, Dwayne Donald who giveshis expert view on Canadian educationand research concerning Indigenouspeoples.

I trust that you find this publication bothabsorbing and insightful. Do feel free tocontact me about any suggestions forstimulating content you may have in thefuture, or perhaps you’d like to just get in touch to provide any remarks onthis edition.

Jonathan MilesEditor

@Jonathan_AdjDig

CONTENTS

HEALTH & SOCIAL CARE

06Dyspnea: Shortness of breath

Donald A. Mahler from the Geisel School of Medicine at Dartmouth and ClinicalResource Center of the Alpha-1 Foundationand Valley Regional Hospital, on behalf ofthe CHEST Foundation, provides an expertview on shortness of breath (dyspnea)

12Huntington’s disease –accessing hope

Sorcha McPhillips, Chief Executive of theHuntington’s disease (HD) Association forNorthern Ireland, raises awareness of HDand discusses the impact of hope on thecommunity in the face of new treatments

16Cancer research and trainingin the United States

The work of the National Cancer Institute(NCI), the federal government’s principalagency for cancer research and training in the United States, is profiled here byOpen Access Government

30Cloud computing in medicalimaging: Not a matter of if,

but whenNadim Michel Daher, industry principal at Frost & Sullivan reveals his views on thevital role of Cloud computing in medicalimaging

32Arthritis, musculoskeletal and skin diseases including

muscular dystrophyThe work of the National Institute ofArthritis and Musculoskeletal and SkinDiseases, including muscular dystrophy(MD), is placed under the spotlight byOpen Access Government

36Nanomaterials in the healthcaresector: The navigation paradox

applied to healthcareCecilia Van Cauwenberghe from Frost & Sullivan shares her expertise onnanomaterials in today’s healthcaresector, including therapeutic precisionversus nanotoxicology risk

RESEARCH & INNOVATION

38Pursuing physics at theforefront of knowledge

Denise Caldwell, Director, Division ofPhysics at the U.S. National ScienceFoundation (NSF) provides a fascinatingperspective on how the organisation ispursuing physics to the forefront ofknowledge

42Next steps to the Moon: What role for Europe?

Sebastien Moranta, coordinator of studiesat the European Space Policy Institute(ESPI) sheds light on Europe’s potential toexplore the Moon in co-operation withother great world powers

46Space: Reaching out to newheights to benefit mankind

Open Access Government reveals theexciting mission of the National Aeronauticsand Space Administration (NASA) and howthe United States aims to reach out to newheights to benefit mankind when it comesto exploring space and beyond

48Developmental biology: Fulfillingthe promise of Organoids

Professor of Developmental Mechanics atthe Department of Genetics, University ofCambridge, Alfonso Martinez Arias shareshis expert view on Organoids, within thefield of developmental biology

52Biology: Enabling discoveriesfor understanding life

The mission of the Directorate forBiological Sciences (BIO) at the U.S.National Science Foundation (NSF), is toenable discoveries for understanding life,as Open Access Government discovers

56The health effects of exposure tochemicals and other substances

Open Access Government details the workof the National Toxicology Program, a worldleader in providing scientific information tohelp evaluate and better understand thepotential health effects of exposure tochemicals and other substances

NORTH AMERICA ANALYSIS | MAY 2018

USA

26The role of advancedtechnologies in healthcare

The role of advanced technologies inhealthcare, including the work of theNational Institute of BiomedicalImaging and Bioengineering (NIBIB) inthis area, is placed under the spotlightby Open Access Government

CANADA

98Canada’s plan to reduce carbonemissions and strengthen their

clean growth economyMinister of Environment and ClimateChange in Canada, Catherine McKennadetails the country’s plan to reducecarbon emissions and strengthen theirclean growth economy

100Canadian education andIndigenous peoples

Vice President of the Canadian Society forthe Study of Education, Dwayne Donaldshares his expert perspective on Canadianeducation and research on Indigenouspeoples

AGRICULTURE

62How right-sizing regulation can optimise plant protection

Greg Rosenthal of the U.S. Department ofAgriculture’s (USDA) Animal and PlantHealth Inspection Service explains howright-sizing regulation can optimise plantprotection

66USDA: Protecting Americansfrom foodborne illness

Acting Deputy Under Secretary for FoodSafety at the United States Department ofAgriculture (USDA), Carmen Rottenbergexplains how the Food Safety andInspection Service protects Americansfrom foodborne illness

78Finding new solutions toagricultural problems in the U.S.

Open Access Government looks at thework of the Agricultural Research Service(ARS) in finding new solutions toagricultural problems in the United States

ENVIRONMENT

80Protecting human health and the environment

The work of the U.S. EnvironmentalProtection Agency and the Office ofEnvironmental Information, to protecthuman health and the environment, isunveiled by Open Access Government

90Supporting the earth sciencesin the United States

The Earth Sciences (EAR) Division of theNational Science Foundation (NSF) isplaced under the spotlight by Open AccessGovernment

ENERGY

92The priorities of the U.S.Energy Department

Open Access Government charts thehistory of the U.S. Energy Department andsome of its present-day priorities, includingclean energy and solar manufacturing

TRANSPORT

96Sustainable aviation fuels, thenext frontier for air transport

Michael Gill, IATA Director AviationEnvironment imparts his expertise onsustainable aviation fuels and why hebelieves these are the next frontier fortoday’s air transport

104From wheelchair to high heels: Realising the

potential of stem cellsDr Michael A Rudnicki, CEO & ScientificDirector at the Stem Cell Network gives anexpert view on a new era in health care,powered by stem cells

110Medical cannabis advocacyand education

Board Member for Canadians for FairAccess to Medical Marijuana (CFAMM),Peter Thurley, shares his views on medicalcannabis advocacy and education issues

74National Institute of Foodand Agriculture (NIFA)

The work of the National Institute ofFood and Agriculture (NIFA) is examinedhere by Open Access Government

106Cannabis developments in North America

Writer, medical cannabis patient, agrower and budtender for GrassRootsMedicinal in Squamish, Caleb McMillan,provides his thoughts on cannabisdevelopments in North America today

HEALTH & SOCIAL CARE

6

Dyspnea: Shortness of breathDonald A. Mahler from the Geisel School of Medicine at Dartmouth and Clinical Resource Centerof the Alpha-1 Foundation and Valley Regional Hospital, on behalf of the CHEST Foundation,

provides an expert view on shortness of breath (dyspnea)

Ahealthy person breathes 12-14 times everyminute without a thought. Breathing is auto-matic as the medulla in the brain stem sends

electrical signals to the respiratory muscles to controlhow often and how deep to breathe. Receptors in therespiratory system provide information about how thelungs are working to the brain. Based on a neurobio-logical model, shortness of breath results from animbalance or mismatch between the demand tobreathe and the ability to breathe.

Dyspnea (dys – difficult; pnea – breathing) is the medicalword for shortness of breath. The three major qualitiesare: work/effort of breathing; chest tightness; andunsatisfied inspiration. Those who experience breathingdifficulty often report the feeling as, “I am short ofbreath,” or “I feel like I can’t get enough air in.” Theseexperiences are a warning signal that the interactionbetween the respiratory system and the brain is notworking properly.

Causes of shortness of breathShortness of breath is frequently classified by how itdevelops – acute (sudden onset) and chronic (overweeks to months). The most common causes of acuteand/or chronic dyspnea are diseases of the heart (congestive heart failure, valve dysfunction and cardiomyopathy), of the lung [asthma, chronic obstructivepulmonary disease (COPD) and interstitial lung disease],of the pulmonary blood vessels (pulmonary embolismand pulmonary hypertension) and advanced cancer.

Other possibilities for chronic shortness of breathinclude anemia, deconditioning (“out of shape”) andpsychological conditions, such as anxiety or depres-sion. Although a low oxygen level in the body increases

Figure A: simplified model for shortness of breath. Themedulla sends an efferent signal (downward arrow) to therespiratory muscles that control breathing. Receptors inairways, lung parenchyma and respiratory muscles sendafferent signals (upward arrow) to the brain about rate anddepth of breathing.

7

ventilation and causes shortness of breath, a personmay experience breathing difficulty despite a normaloxygen level.

Risk factors for heart disease include smoking, hyper-lipidemia, hypertension, diabetes, obesity, physicalinactivity and a family history of heart disease at anearly age. Risk factors for lung disease are smoking,inhalational exposures both occupational and recreational and a family member with a specific lungcondition. Deconditioning is a direct result of reducedphysical activities due to a sedentary lifestyle or possiblyan illness, injury, or surgery.

The diagnosisFor evaluation of acute shortness of breath, the persontypically goes to an emergency department, whereasa complaint of chronic breathing difficulty is usuallyaddressed in an out-patient facility. Assessment by ahealth-care professional includes a medical history,physical examination and appropriate testing thatincludes pulse oximetry.

For acute shortness of breath, a chest x-ray and electrocardiogram are essential. Two blood tests canbe helpful. Prohormone brain natriuretic peptide (pro-BNP), secreted by the myocardium, is elevated inheart failure; and D-dimer, a product of fibrin degra-dation in the blood, is elevated with pulmonaryembolism. Computed tomography (CT) scanning maybe considered for further evaluation.

“Dyspnea (dys – difficult; pnea – breathing) is the medical word for shortness of breath.

The three major qualities are: work/effort ofbreathing; chest tightness; and unsatisfiedinspiration. Those who experience breathing

difficulty often report the feeling as, “I am short ofbreath,” or “I feel like I can’t get enough air in.”These experiences are a warning signal that theinteraction between the respiratory system and the

brain is not working properly.”

For chronic shortness of breath, pulmonary functiontesting and a chest x-ray are typically ordered. Other

HEALTH & SOCIAL CARE

HEALTH & SOCIAL CARE

8

diagnostic testing may include a complete blood count,an echocardiogram and cardiopulmonary exercisedepending on the individual’s specific features.

Getting treatmentThe following diagram provides a general approach torelieving shortness of breath.

Medications are usually prescribed as treatment forthe specific disease that can relieve breathing difficulty.Oxygen therapy is provided if the individual’s oxygensaturation is 88% or below. As many individuals withchronic heart or lung diseases are inactive due to theirshortness of breath, referral to a cardiac or pulmonaryrehabilitation program is important.

Studies show that supervised exercise training willrelieve shortness of breath, improve quality of life andenhance functional ability. Anxiety and/or depressionshould be treated to improve an individual’s mentalhealth which may also alleviate breathing difficulty.

Non-pharmacological strategies for relief of dyspneainclude a fan blowing air on the face, pursed lips-breathing (puckering the lips during exhaling in thosewith asthma and COPD), the leaning forward positionwith forearms resting on the thighs or hands on ashopping cart, listening to music, meditation, mindfulbreathing (an awareness of each breath so that thefocus is on the present and breathing becomesrelaxed) and yoga.

The priorities for future researchThe following recommendations are proposed toadvance the treatment of shortness of breath.

Educate the public about the importance of shortness•of breath as a symptom of heart and lung disease. Itshould not be considered a consequence of aging.

Develop a new scale or instrument for individuals •to rate shortness of breath related to daily and recre-ational activities. An ideal scale would be valid, reli-able and responsive to treatments, would be used inclinical practice and would be accepted by regulatoryagencies for approval of new therapies.

Provide research support to develop new treatments.•Possibilities include acupuncture, chest wall vibrationand a custom engineered opioid that does notdepress the respiratory drive to breathe. ■

References

1 Parshall MB, Schwartzstein RM, Adams, L, Banzett RB, Manning HL,

Bourbeau J, et al.

An official American Thoracic Society statement: Update on the

mechanisms, assessements and management of dyspnea.

Am J Respir Crit Care Med 2012; 185:435-452.

2 Mahler DA, O’Donnell DE (Editors). Dyspnea: Mechanisms,

Measurement and Management, 3rd Ed. 2014. CRC Press

(imprint of Taylor and Francis Group, LLC),

Boca Raton, FL.

3 Mahler DA. Evaluation of dyspnea in the elderly. Clin Geriatr Med

2017; 33:503-521.

Donald A. Mahler, M.D. Emeritus Professor of Medicine, Geisel School of Medicine at Dartmouth, Director of Respiratory Services.Director of Clinical Resource Center of the Alpha-1 FoundationValley Regional Hospital.mahlerdonald@gmail.comwww.alpha1.org.ukhttps://geiselmed.dartmouth.edu/www.twitter.com/GeiselMed/www.twitter.com/Alpha1UKSupport

CHEST FoundationTel: +1 224 521 9527chestfoundation@chestnet.orghttps://foundation.chestnet.org/

Treat the Specific Disease

Oxygen Therapy

Cardiac or Pulmonary Rehabilita on

Treat Anxiety or Depression

Non-pharmacological Strategies

Our ebooks can be used by you to targeta specialised readership with informativecontent. They can be 8, 12 or even 16pages promoting your profession andservices.

Our production, editorial and designteams will work with you to identify anddevelop your message before delivering it

electronically to a targeted audienceusing the latest digital publishingtechnology for ease of reading.

We have access to an extensive databaseof contacts within specialised areas, soyou can be confident that your messagewill be delivered to the right people atthe right time.

TAILOR-MADEPROMOTION

Get in touch today to plan your communication strategy.

Tel: 0843 504 4560

www.openaccessgovernment.org GOVERNMENTOPEN ACCESS

As part of our package of information services, Open Access Governmentare proud to present the option of a bespoke publication.

Patients coming to the EmergencyDepartment (ED) with shortnessof breath may have character-

istics that impede intravenous (IV)access. Such characteristics may includehypotension, dialysis dependence,morbid obesity, history of diabetes,sickle cell disease, or IV drug use. One prospective observational studyidentified nearly 1 in every 9 to 10 adultscoming to an urban ED had difficultvenous access requiring 3 or moreIV attempts.1 If peripheral IVs are notestablished, patients may need acentral venous catheter placed forlife-saving medications administered.In addition to requiring physician skill,central venous catheter insertion car-ries a risk of complications includinginfection, arterial puncture or ananeurysm, and pneumothorax. Ultra-sound-guidance for peripheral IVplacement (UGPIV) has prevented theneed for central venous catheterplacement in 85% of patients with difficult intravenous access.2 UGPIV hasbeen performed by Emergency MedicalTechnicians (EMTs) in prehospital settings, as well as nurses and physicians. Patients who have beenidentified as having difficult accesshave higher patient satisfactionscores when ultrasound is used inperipheral IV access attempts.3

Frequently, the large veins of the ante-cubital fossa are sufficient to placelarge bore peripheral IVs needed forresuscitation. The brachial and basilic

veins are easy to locate. The brachialartery is generally flanked by 2 smallerveins and the median nerve. Anatom-ically, these structures are medial tothe insertion of the medial bicepstendon. This tendon is palpable in theantecubital fossa as the patient flexesthen extends the elbow. The basilicvein is located medial to the brachialvessels. Generally, it is more superfi-cial, larger, and does not have anaccompanying artery or nerve at thelevel of the antecubital fossa. As youmove proximally up the arm (towardsthe head) the basilic vein dives deepertoward the humerus, and longerangiocatheters may be required forcannulation.

When considering vascular access,there is 2 views, a short and long axisview. Cannulation from the short axisis considered ‘out of plane’ since theneedle is perpendicular to the probe.A short axis approach ‘looks’ at a crosssection of the vessel. Long axis usesand ‘in plane’ approach with the needleentering from the probe marker end,and ‘looks’ along the length of thevessel. Figure 1 identifies a vesselusing colour Doppler in the short axisview. Figure 2 demonstrates a longaxis view with a hyperechoic angio-catheter. Figure 3 is the same vesselin long axis with the angiocatheterplaced. While both approaches maybe used for UGPIV placement, the

Virginia M Stewart, MD outlines when intravenous access may be neededand how the skilful process should be undertaken

Understanding the process ofintravenous access

10

PROFILE

Figure 1: Short axis view of a peripheral vessel visualised with Colour Doppler (blue). The scaleon the right of the screen demonstrates a total depth of 2.6 cm. A guide (white dots) in the centreof the screen marks each 0.5cm of depth. Therefore the depth of the vessel is between 1-1.5cmdeep to the skin surface.

benefit for the short axis is the abilityto identify target veins as well asaccompanying non-target (arteriesand nerve) structures.

Identify the vein: rememberthe two C’sThe two C’s to remember for UGPIVaccess or for central venous cannula-tion are compression and colour (orPower) Doppler. Veins are thinner-walled and more easily compressedthan arteries. This author advocatesfor finding a vessel first in the shortplane, and compressing the vessel toensure it is indeed a vein, rather thana less or non-compressible artery.Colour or Power Doppler may beutilised to determine if the pulsatileflow is consistent with an artery orvein. Colour Doppler uses red andblue to determine flow towards oraway from the probe respectively.Power Doppler detects flow withoutconcern for direction. Colour shouldnot be relied on alone to determinearterial or venous flow due to thecolour scale setting can be flipped orreversed, or aliasing can occur. Arte-rial flow is more pulsatile than venous.Venous flow may require distal aug-mentation (by squeezing the forearmdistal to the probe) to appreciate theblush of colour.

Once the target vein is identified, the

depth from the skin surface should benoted. A common mistake is to use anangiocatheter that is too long or tooshort. A general rule of thumb is touse a catheter length that is morethan twice the depth of the vessel toensure at least half the catheter lieswithin the vein. Sterile ultrasound gelshould be used, with a covered probeto prevent infection. To prevent therisk of multiple punctures, this authoradvocates for first bouncing theneedle on the skin over the point ofentry. The tissue should deform at thetop of the screen, and confirm theneedle is over the target vessel. Oncethe skin is punctured, the needle tip iskept in view by angling the ultrasoundprobe until the target vessel is punctured.

To confirm placement, either a‘bubble study’ with agitated salinemay be performed or Colour (orPower) Doppler utilised to visualisesaline flow through the cannulatedvessel. A vessel that is not properlycannulated will demonstrate extrava-sation of saline around the vessel intothe tissue before the tissue swells toa degree which is palpable on the sur-face of the skin. Figure 4 demonstratesconfirmation of intraosseous (IO) linesutilise Power Doppler. A 10cc salineflush is rapidly pushed through theline, and flow is demonstrated beneath

Virginia M Stewart, MDForsythe Emergency Services, PAPO Box 25447Winston-SalemNC27114 askdrstewart@gmail.comwww.fespagroup.com

11

PROFILE

Figure 2: Long axis view of a peripheralvessel. The hyperechoic needle is visualizedapproaching from the top left of the screeninto the vessel lumen.

Figure 3: In this long axis view of a peripheralvessel the catheter has been threaded and isseen within the lumen of the vessel.

Figure 4: Power Doppler (orange) confirmsplacement of an intraosseus line within thedistal tibia. The bright white line of the tibiacortex (in long axis view) is visualised at thetop of the screen, with flow confirmationfrom a 10cc saline flush immediately distal(below) to the hyperechoic cortex.

the bony cortex in this adult tibia. Ifthe line is improperly placed, theblush of colour using Doppler wouldappear in the soft tissues. For furtherinformation about UGPIV placement,visit: http://rmgultrasound.com/piv-access/

References:

1 Fields, J.M., Piela, N.E., Au, A.K., Ku, B.S., Risk factors associated

with difficult venous access in adult ED patients. Am J Emerg Med.

2014 Oct; 32(10):1179-82.

2 Au, A.K., Rotte, M.J., Grzybowski, R.J., Ku, B.S., Fields, J.M.,

Decrease in central venous catheter placement due to use of

ultrasound guidance for peripheral intravenous catheters.

Am J Emerg Med. 2012 Nov;30(9):1950-4.

3 Schoenfield, E., Shokoohi, H., Boniface, K. Ultrasound-guided

peripheral intravenous access in the emergency department: a

patient-centered survey. West J Emerg Med. 2011 Nov;12(4):475-7.

HEALTH & SOCIAL CARE

12

Huntington’s disease – accessing hope

Huntington’s disease (HD) is described as a‘neuro-degenerative’ disorder as it damages orkills the neurons in the brain. It is a genetic

disease affecting males and female equally. Every childof an affected parent has a 50% chance of inheritingthe gene mutation which causes the disease. A simpleblood test indicates whether a person has tested positive or negative for the gene mutation. If testedpositive, the individual will develop the disease at somepoint in their lifespan.

HD affects approximately 1 in 10,000 individuals inEurope and is sometimes referred to as a ‘rare’ or‘orphan’ disease, although a recent statistical reportfrom 2016 indicates that the prevalence of HD in theUK has been severely underestimated and that forevery person with the faulty gene there are as many as5 people at risk of inheritance.1

HD usually affects adults between the ages of 30-50and is often described as an “adult-onset disease”.Although it can occur anywhere from age 2-70, it is lesscommon in children and older people. It is said thatthose who develop HD earlier in life may find their illness progresses at a faster rate.

Life expectancy from the onset is approximately •15-20 years.

HD causes progressive deterioration – physically, •cognitively and emotionally until the individualbecomes dependent on the help of others.

No two patients’ condition progress in exactly the•same way.

Symptoms can vary widely, and the rate of progression•is difficult to predict with any real accuracy.

HD is referred to as a ‘disease of families’ where •several family members from different generationsmay be symptomatic at the same time.

As a ‘disease of families’ no family member is leftuntouched because if they do not have symptomsthemselves or have tested negative they are stillaffected by the emotional and practical implications ofthe disease on the family with many people having acaring role to play.

Most of the, approximately 200, HD sufferers in NorthernIreland are cared for at home by family membersalthough many will require the assistance of homecare workers, respite in care homes and eventuallynursing home care. It is essential for carers, both familyand professionals, to develop an understanding of thecomplexities of HD and how it can impact on all members of the family.

There is no known cure for HD, however, this is anunprecedented time for Huntington’s disease families.HD is among the 25% of rare diseases with a knowngenetic cause and so to some extent, those with HDare among the lucky ones. They can access a diagnosisby blood test and since the cause is known, treatmentsare possible.  The first-ever human trial is underway ofa drug that aims to reduce the brain’s production ofthe mutant protein HTT – the known cause of HD.Phase 1/2 of this Ionis/Roche trial has just concludedwith 46 patents across nine global sites with partici-pants shown to tolerate increasing doses of a drugdelivered by a monthly lumbar puncture.

The results are incredibly positive with significant dose-dependent reductions in the level of the mutantprotein – basically the higher the dose administered,the lower the level of protein detected. This trial will

Sorcha McPhillips, Chief Executive of the Huntington’s disease (HD) Association for Northern Ireland, raisesawareness of HD and discusses the impact of hope on the community in the face of new treatments

HEALTH & SOCIAL CARE

13

now expand to include more participants to monitorthe effect on a larger patient group for a longer period.The hope is that this drug could delay or even preventthe onset of HD symptoms. Several other drugs to dothe same thing by different approaches are underdevelopment and expected to reach trials soon. Thereare currently 15 clinical trials of different treatmentscurrently underway so there is real hope for a cure.2

These developments bring real hope to families currently living with the symptoms or the future threatof this devastating disease. However, in Northern Ireland, they also bring questions, anxiety and frustration.Participants for clinical trials are usually recruitedthrough Enroll HD study sites. Enroll HD is an innovativeway of gathering data on HD patients and their familymembers, including biological samples, which are thencoded and uploaded anonymously on to a globalresearch database which is freely accessible to anyoneworking on HD research.3

There is an Enroll HD site in Ireland and 28 sites acrossScotland, England and Wales, but not a single site in

Northern Ireland. Although we have some limited neurological, psychiatric, nursing and genetic expertisein Huntington’s disease locally, they do not have thecapacity or the administrative support to establish asite here. Families are asking, and rightly so, how canwe access these clinical trials before it’s too late for us?The postcode lottery is something many are sadly alltoo aware of as in Northern Ireland only those livingwithin two of the five healthcare Trusts can access aspecialist HD nurse. This is an issue which HDANI continues to lobby for but when you have no functioninggovernment where do you lobby? There has been noMinister for Health in Northern Ireland since January2017 and with that a vacuum against which to push foran end to the inequality of care which exists and theneed to promote access to HD research and clinicaltrials. It truly is a time of hope for Huntington’s Diseasefamilies around the globe and hope can do exceptionalthings to the human body and spirit but for familiesliving in Northern Ireland, it seems like hope is justbeyond their grasp. ■

To learn more about HD in Northern Ireland watch ourvideo https://tinyurl.com/y7dudr7m

1 Baig, S.S., Strong, M. and Quarrell, O.W.J. (2016) The global prevalence

of Huntington’s disease: a systematic review and discussion.

Neurodegenerative Disease Management, 6 (4). ISSN 1758-2024

https://doi.org/10.2217/nmt-2016-0008

2 For up to date information on HD drug and treatment developments

see https://en.hdbuzz.net/

3 https://www.enroll-hd.org/

Sorcha McPhillipsChief ExecutiveHuntington’s Disease Association Northern Ireland (HDANI)Tel: +44 (0)79 8284 3907info@hdani.org.uk www.hdani.org.uk www.twitter.com/hdassocni

Sorcha McPhillips, Chief Executive

Huntington’s disease (HD) is arare hereditary neurodegen-erative disease that strikes

patients in mid-life. American physicianGeorge Huntington first described thedisease in 1872 after seeing affectedresidents in East Hampton, New York.Patients generally experience a progressive decline in cognitive, psychiatric, and motor functions. Thedisease is fatal. In 1993 an interna-tional team of scientists discoveredthe gene that causes the disease.Despite years of intense research, nocures or treatments to delay the onsetor prevent the progression of the disease are available.

HD is caused by an inherited domi-nant mutation in the Huntingtin gene,HTT. This means an offspring of aparent who carries a mutant HTTgene has a 50% chance of inheritingthe mutant gene. The mutation resultsin an increased number of repeats(greater than 40) of the amino acidglutamine in the encoded Huntingtinprotein (HTT).

A normal HTT protein has between 7and 35 glutamines. Increased numberof glutamine repeats changes theproperty of the protein and rendersit toxic to cells. The HTT protein is present throughout the body andthroughout life. However, mutant HTTis toxic to select cells. Postmortemexamination of the brains of affectedindividuals shows massive cell loss incertain parts of the brain, leaving

other cells and tissues intact. This indicates that some neurons are par-ticularly sensitive to the toxic effectsof mutant HTT.

The normal HTT protein has beenimplicated in many cellular functions.However, we have an incompleteunderstanding of how mutant HTTcauses the disease. A better under-standing of the functions of thenormal and mutant HTT protein isparamount, if effective therapies orcures are to be developed.

Proteins made in cells maintain certainstructures dictated by their biochemicaland biophysical properties. This is

referred to as protein folding. Whenproteins misfold, they often lose theirnormal functions. Cells have developedelaborate mechanisms to remove suchaberrant, misfolded proteins. Thisprotects the cells from potentialharmful effects of misfolded proteins.

However, misfolded proteins canaccumulate over time and form irreversible aggregates that impair cellular homeostasis. These aggregatesare a hallmark of many neurodegen-erative diseases. They are found inpostmortem brain tissues of affectedindividuals. Age-associated diseasessuch as Alzheimer’s disease, arelinked to protein misfolding. HD is

Naoko Tanese from New York University School of Medicine outlines their work aroundHuntington’s disease (HD) and effective new targets for therapeutic intervention

What’s in an aggregate? Therapeuticintervention in Huntington’s

14

PROFILE

Naoko Tanese, PhD, Associate Dean forBiomedical Sciences, and Director, SacklerInstitute of Graduate Biomedical Sciences

also considered a protein misfoldingdisease although many other mecha-nisms are thought to play a role in thedisease pathogenesis.

Decades of research have uncoveredintriguing properties of different typesof protein aggregates, some of whichare RNA-protein granules found innormal cells. Each granule appears tohave distinct properties and its forma-tion is driven by specific sets of proteinsand RNA. Some granules are formedin response to stress. This mechanismserves to halt energy-consuming cellular activities, by sequestering proteins involved in key biochemicalprocesses. Upon removal of the stress,granules disassemble and the releasedproteins resume their normal functions.

Interestingly, mutant proteins linkedto several neurodegenerative diseaseshave been located within these typesof granules. They include mutant RNA binding proteins associated with amyotrophic lateral sclerosis, spinalmuscular atrophy, and fragile X syndrome. These RNA binding proteins normally play a role in RNA transport, translation of RNA to make proteins, and formation ofRNA-protein complexes.

Mutant RNA binding proteins, however,show altered biophysical properties.They have increased propensity tointeract with one another and affectthe formation and function of granules.There is increasing evidence that overtime mutant RNA binding proteins inthese granules steadily accumulateand become converted to irreversibleaggregates that are toxic to cells. Neurons are vulnerable to aberrantproteins that accumulate becauseneurons do not divide. Ultimately themachinery in the cell fails to removetoxic proteins, causing cell death.

Since the functions of normal HTT andthe mechanisms by which its mutantcounterpart contributes to HD remainunclear, my lab began investigatingthe role of HTT in RNA metabolism.New imaging techniques have helpedus determine the location of thenormal HTT protein inside neurons.

Strikingly, we discovered that HTTcould be found near neuronal RNAgranules. RNA granules are large RNA-protein assemblies responsible fortransporting RNA to specific locationsin the neuron. To determine whetherHTT influences RNA localisation, wereduced the level of normal HTT inneurons grown in a culture dish andexamined its effect on transport ofRNA. We found that the reduction ofHTT in cells disrupts RNA localisation.The result points to HTT contributingto the integrity of RNA granules duringRNA transport.

New experiments in HTTTo further investigate cellular processesthat HTT is involved in and how theymight differ in mutant HTT, wedesigned experiments to purifynormal and mutant HTT proteins fromcells and tissues. We next identifiedproteins that interacted with eachform of HTT. By identifying the func-tions of the proteins that co-purifiedwith HTT, we uncovered new functionsfor HTT. Analysis of the binding partnersof HTT proteins revealed that bothnormal and mutant HTT interact withproteins involved in RNA metabolismand protein synthesis.

We have thus uncovered new roles fornormal and mutant HTT in RNAmetabolism. The findings have severalimplications for the development ofHD. We have located mutant HTT inneuronal granules, similar to thoseassociated with aforementioned RNA

binding proteins linked to neuro -degenerative diseases. Our results suggest HTT has a role in the formationof RNA-protein granules.

Unlike normal HTT, mutant HTT has apropensity to interact with oneanother through the increased repeatsequence. At high concentrations,mutant HTT alters biophysical proper-ties of RNA-protein assemblies andshifts the equilibrium in favour offorming aggregates.

Furthermore, a recent study reportedstable formation of RNA aggregatescontaining repeat sequences. Collec-tively, the findings suggest thatmutant HTT together with repeatsequence-containing RNA forms granules that become converted toirreversible toxic aggregates overtime. The development of chemicalagents that prevent aggregation ordisrupt aggregates may serve toreverse the toxicity associated withthe mutant protein and RNA. Throughunderstanding of how HTT supportsneurons with these functions, wehope to reveal effective new targetsfor therapeutic intervention.

15

PROFILE

Naoko Tanese, PhDAssociate Dean for Biomedical Sciences,Director, Sackler Institute of GraduateBiomedical SciencesNew York University School of MedicineTel: +1 212 263 8945tanesn01@med.nyu.edu https://med.nyu.edu/faculty/naoko-tanesewww.twitter.com/nyuschoolofmedhttp://sackler.med.nyu.edu

HEALTH & SOCIAL CARE

16

Cancer research and training in theUnited States

The National Cancer Institute (NCI) is the federalgovernment’s principal agency for cancerresearch and training in the United States today.

Their impressively sized team of around 3,500 peopleis part of the National Institutes of Health (NIH), one of11 agencies that make up the Department of Healthand Human Services (HHS) in the United States. In particular, NCI has two broad roles: cancer researchplus training and support for cancer researchers.

NCI’s mission statement is as follows: “NCI leads, conductsand supports cancer research across the nation toadvance scientific knowledge and help all people livelonger, healthier lives.” (1)

NCI is a leader of the cancer research enterprise, collectively known as the National Cancer Program andis the largest funder of cancer research in the wholeworld. It’s true to say that NCI manages a vast array ofresearch, training and information dissemination activ-ities that reach across the entire United States, meetingthe needs of all demographics – urban and rural, rich andpoor, urban and rural and all ethnic-racial/populations.

When it comes to funding, NCI receives its funds fromCongress. The bulk of NCI’s budget supports extramuralgrants and cooperative agreements to facilitateresearch taking place at universities, hospitals, medicalschools, cancer centres, research laboratories and private firms in the United States and further afield.

On the impact that NCI’s investments have had, weknow that this has led to declines in the rates of newcancer cases and cancer deaths as a whole in theUnited States over the last few decades. In keepingwith this impressive improvement, the number ofcancer survivors in the country has more than doubled

from 7 million in 1992 to more than 15 million in 2016and unfortunately, it is predicted to rise to more no lessthan 26 million by 2040. These trends reflect advancesin the detection of cancer detection, diagnosis andpatient care which have led to people living longer andhealthier lives than has been known previously.

The PanCancer AtlasOne example of research taking place, that is fundedby the National Institutes of Health concerns the com-pletion of a detailed genomic analysis, known as thePanCancer Atlas, on a data set of molecular and clinicalinformation from over 10,000 tumours – that represent33 types of cancer.

“This project is the culmination of more than a decadeof ground-breaking work,” says NIH Director Francis S.Collins, M.D., Ph.D. “This analysis provides cancerresearchers with an unprecedented understanding ofhow, where and why tumours arise in humans,enabling better-informed clinical trials and future treatments”, she adds.

“TCGA was the first project of its scale to characterise– at the molecular level – cancer across a breadth ofcancer types”, adds Carolyn Hutter, Ph.D., director ofNHGRI’s Division of Genome Sciences and the NHGRIteam lead for TCGA. “At the project’s infancy 10 yearsago, it wasn’t even possible, much less on such a scale,to do the types of characterisation and analysis that were being proposed. It was a hugely ambitiousproject.”

The project focuses on cancer genome sequencing andon different types of data analyses, for example, inves-tigating gene and protein expression profiles, as wellas associating them with clinical and imaging data.(2)

The work of the National Cancer Institute (NCI), the federal government’s principal agency for cancerresearch and training in the United States, is profiled here by Open Access Government

HEALTH & SOCIAL CARE

17

Sorafenib improves progression-freesurvival for patients with rare sarcomasIn other news, interim results from a randomised clinicaltrial for patients with desmoid tumours or aggressivefibromatosis (DT/DF) show that the drug sorafenibtosylate (Nexavar) extended progression-free survival,compared with a placebo. The trial was sponsored bythe National Cancer Institute (NCI), designed and conducted by researchers with the Alliance for ClinicalTrials in Oncology (Alliance) and supported by BayerHealthCare AG, which provided the study drug.

“Sorafenib is a novel way of treating this rare cancer,”comments lead investigator and study chair Mrinal M.Gounder, M.D., sarcoma medical oncologist at MemorialSloan Kettering Cancer Center in New York City. “Thepromising results of this phase 3 trial represent a paradigm shift in the approach to treatment ofpatients with desmoid tumours.”

“Currently, there is no standard treatment for this raredisease and the effectiveness of the treatments thatare used for it – for example, surgery, radiation andchemotherapy – is generally limited,” adds Jeff Abrams,M.D., clinical director of NCI’s Division of Cancer Treat-ment and Diagnosis. “But the interim results of thistrial are promising and may offer a new treatmentalternative.” (3)

The development of vaccines for thehuman papillomavirus (HPV)In other noteworthy news, Douglas R. Lowy, M.D. andJohn T. Schiller, Ph.D., of the Center for Cancer Researchat the NC) were recognised for their contributionstoward the development of vaccines for the humanpapillomavirus (HPV) in February.

On winning the 2018 Szent-Györgyi Prize for Progressin Cancer Research, Sujuan Ba, Ph.D., co-chair of the2018 prize selection committee and president of theNational Foundation for Cancer Research (NFCR),which awards the annual prize, said that Drs Schillerand Lowy: “have made monumental impacts in the fieldof cancer sciences and could not be more deserving ofthis award.”

NCI Director Ned Sharpless, M.D. adds: “We at NCI arevery proud to see Dr Lowy and Dr Schiller awarded thisprestigious prize for their important work in cancer

research. Their receipt of the Szent-Györgyi Prize fortheir extraordinary research recognises how importantdiscoveries come from building on earlier work andhow those efforts can lead to major breakthroughs inpublic health.” (4)

Looking aheadLooking to the future, everybody at some point in theirlives has been touched by cancer, perhaps through aloved one dealing with it by the experience of a personal diagnosis. While incredible strides have beenmade in advancing scientific knowledge of the disease,there remains a great deal more to be done. In thisvein, NCI will always support the most innovative lab-oratory research and clinical trials to transform thedata we have today into tomorrow’s most revolutionaryclinical discoveries.

The last word goes to NCI who explain in their ownwords how they are leading the way in understanding,preventing and treating cancer: “From basic science toclinical science, from implementation science to cancercare delivery and from advanced technology develop-ment to data-sharing and analysis systems, NCI is leading the way in how we understand, prevent andtreat cancer.” ■

References

1 https://www.cancer.gov/about-nci/overview

2 https://www.cancer.gov/news-events/press-releases/2018/TCGA-

PanCancer-Atlas

3 https://www.cancer.gov/news-events/press-releases/2018/sorafenib-

desmoid-trial

4 https://www.cancer.gov/news-events/press-releases/2018/lowy-

schiller-szent-gyorgyi-prize

Open Access GovernmentJMiles@openaccessgovernment.orgwww.openaccessgovernment.orghttps://twitter.com/OpenAccessGov

Sunlight-induced carcinogenesishas become a concern since the1980s when the depletion of

the ozone layer was first noticed.Long-term exposure to ultraviolet B(UVB) component of sunlight is a riskfactor for both non-melanoma andmelanoma skin cancers. The incidenceof skin cancers is increasing, with 2-3million non-melanoma skin cancersand 132,000 melanoma cases occurringglobally each year. Skin is sensitive tophotodamage even after short-termexposures to UVB.

As with other cancers, angiogenesis is critically important in skin cancerprogression and UVB-induced vascularchanges in the skin have beenattributed to increased production ofpro-angiogenic cytokines and chemo -kines, such as vascular endothelialgrowth factor (VEGF), cyclooxygenase(Cox)-2, basic fibroblast growth factor(bFGF) and interleukin-8 (IL-8).

Thrombospondin-1 (TSP1), a large glycoprotein abundant in healthyadult tissues is a major inhibitor ofangiogenesis. Loss of TSP1 has beenimplicated in the progression of manycancers including breast and coloncarcinomas and skin cancers. In theskin, TSP1 produced by keratinocytes inthe epidermis acts as a gatekeeper ofthe vascular changes associated withand required for cancer progression.

Therefore, TSP1 seems an obviouscandidate for prevention or treatment

of cancer. However, a very large pro-tein with complex functions is difficultto manufacture for clinical purposes.What if there was a compound thatimpedes subcutaneous angiogenesisby keeping normal, high TSP1 levels inthe skin? There may be such a com-pound coming from a medicinal orculinary plant, chamomile or parsley.

Chamomile flowers are known sinceantiquity, for their healing properties.Apigenin, an active ingredient foundin chamomile, has potent chemopre-ventive properties against UVB-induced skin cancer. In addition to itscytotoxic effects, potentially useful forarresting the growth of rapidly multi-plying tumour cells, apigenin inhibitsangiogenesis.

Using cultures of human and mouse

keratinocytes, as well as mouse models,Dr Volpert and colleagues carried outstudies confirming the anti-angiogeniceffects of apigenin and showed that itcan reverse TSP1 loss in the UVB-exposed skin. This is the first knownreport of apigenin directly controllingendogenous anti-angiogenic protein.Treatment with apigenin, before or afterUVB irradiation, restored TSP1 levels incultured cells and in the skin.

They also found that, like apigenin, anactive TSP1 peptide inhibited the production of Cox-2 and VEGF andreduced UVB-induced cancer-relatedvascular effects, angiogenesis and epidermal thickening. These studiesstrongly suggest the benefits of apigenin for therapy or prevention ofskin cancer and provide mechanisticinsights into its protective action.

Dr Olga V Volpert’s work on sunlight-induced carcinogenesis at the MD Anderson Cancer Centeris explored here, including why angiogenesis is critically important in skin cancer progression

Sunlight-induced carcinogenesis:Angiogenesis in skin cancer progression

18

PROFILE

Figure 1. Loss of TSP1 blunts the anti-cancer effects of apigenin. (a) Wild type and TSP1 null micewere treated as indicated at the top of the panel for 22 weeks. TSP1 null mice develop multiple skintumors despite apigenin treatment. (b) Bone marrow of wild type and TSP1 null mice treated withUVB and apigenin was analyzed by flow cytometry, to measure the neutrophil (Ly6G-high, green)and monocytes (Ly6C-high, purple) cells. In TSP1 null mice apigenin does not block mobilisation ofinflammatory cells.

Angiogenesis inhibitoralters the immunelandscape in skin Further studies by the Volpert group,indeed, showed that apigenin effi-ciently inhibits the UVB-induced skincarcinogenesis in wild-type mice butloses its anti-cancer effect, in whichTSP1 gene is disrupted (TSP1 null) (Fig.1a). Surprisingly, the most dramaticchange in TSP1 null mice is in theinflammatory component of a tumour.It appears that TSP1 interferes with theUVB-induced production of inflamma-tory cytokines IL-6 and IL-12 and thatin mice null for TSP1 far more inflam-matory cells – neutrophils and inflam-matory monocytes are recruited frombone marrow to skin where they pro-duce growth factors to support cancerprogression (Fig. 1b).

Angiogenesis Inhibitor istransferred by exosomes tobolster innate immunesurveillanceExosomes are tiny physiological vesi-cles (50-150 nanometres in diameter)formed through the endosomal path-way and released by all cells in the body.Exosomes and carried in biologicalfluids, like serum and urine. Studies of

the past decade have identified exo-somes as natural vehicles assistingcommunications between cells anddistant tissues.

These natural nanovesicles bioactivemolecules to the recipient cells andchange their properties or behaviour.Most studies show that exosomesreleased by cancer cells promotemetastasis by creating permissiveenvironments at the sites of theirarrival (metastatic niches).

One of the major effects of cancerexosomes is immunosuppression. By transferring immunosuppressivecytokines and immune checkpointinhibitors, cancer exosomes can incapacitate natural killer and cytotoxicT cells. This deficient host immuneresponse serves to protect dissemi-nating cancer cells and facilitatemetastasis.

In a recent study, Dr Volpert and colleagues determined that cancercells can also activate early immunesurveillance. Working with melanomaas a model, they have demonstratedthat at an early stage, melanoma cellsalert the immune system of the host

to the presence of metastasis bysending out exosomes, which activatehighly specialised cells calledpatrolling monocytes.

In the absence of cancer, patrollingmonocytes constantly scan the bloodvessel to seek out and eliminate damaged or dying cells. In case ofmetastatic cancer, the patrollingmonocytes can detect and destroylurking cancer cells. The Volpert groupshowed that one of such exosome-associated activators of patrollingmonocytes is a known angiogenesisinhibitor, pigment epithelium-derivedfactor (PEDF).

Once activated with PEDF-containingexosomes, patrolling monocytes kill and engulf cancer cells on theirown or recruit other cancer-killingimmune cells, called natural killercells. This is yet another case whereanti-angiogenic protein ‘doubles’ as anactivator of immune response andstops the spreading of cancer cells tothe distant organs (Fig. 2).

Dr Olga V VolpertAssociate Professor MD Anderson Cancer CenterTel: +1 832 750 1521ovolpert@mdanderson.orghttps://mdanderson.influuent.utsystem.edu/en/organisations/cancer-biology

19

PROFILE

Figure 2. Early stage (PEDF-positive) exosomes block melanoma metastasis to the lung. Mice weretreated as indicated at the top of the panel and melanoma cells injected in the bloodstream. Twoweeks later, lungs were examined for metastasis (B16F10 pigmented melanoma can be visualizeddue its dark coloring).

Noexosomes

Late-stageexosomes

Early-stageexosomes

Non-invasive radiofrequencyhyperthermia (NiRFH), is anoncologic intervention that is

being used as an adjunct to cytotoxicchemotherapy or ionising radiation [1].It involves the application of high-frequency electromagnetic fields toproduce mild hyperthermia (39-45°C)in malignant tumours.

While NiRFH has been extensivelyinvestigated clinically for severaltumours (e.g. central nervous system,lungs, breast), clinical studies of NiRFHfor hepatic malignancies remain elusive [2]. This is primarily due to tech-nical challenges associated with theanatomic location of the liver and thehigh energy cost of transmitting theelectromagnetic field through adiposetissue, which often leads to insuffi-cient heating of the liver, overheatingof subcutaneous fat and chest wallstructures and skin burns.

In our own work, we have demonstratedsignificant problems and highly variable results when attempting toproduce low-level hyperthermia innormal liver in a porcine model usinga single capacitive end-fire antennaand receiving plate [2]. The skin andsubcutaneous tissue experiencedrapid heating and clinically relevanthyperthermia in the liver was attainedin less than 40% of the animals tested.

We hypothesise that the currentlyavailable NiRFH field equipment isinadequate to heat tumour tissues inliver reliably and reproducibly. Wehave developed a mechanistic math-ematical model of NiRFH treatmentfor primary hepatic tumours and livermetastases. The model, built on basicprinciples of physics, takes intoaccount the narrow therapeutic indexof hyperthermia, i.e., the constraintsof the maximum tolerated dose bythe fat and minimum effective dosefor a tumour.

Using known human tissue frequency-dependent specific absorption rates(SAR) of RF energy, we produced anovel closed-form solution (Equation 1)of the heat equation describing theenergy transfer in tissue and thentested the model to evaluate variablesincluding frequency, increasing subcu-taneous fat thickness and differentialelectrical properties of liver andmalignant liver tumours. The modelindicates that clinically effective tem-perature increases in liver (to 43-45°C)are physically unattainable due to theexcessive heating of fat tissue at allfrequencies and powers currently used.

The model demonstrates that, while itis possible to limit temperatureincreases in the fat by acting on anumber of variables, including cross-

section of the beam, power, timeduration of the RF treatment and frequency, the relative increase intemperature in the liver is always afraction of the corresponding temper-ature increase in the fat at all frequen-cies. The model solution for thechange in temperature (∆T ) with ∆TLfor liver and ∆TF for fat is:

(1) where ci repre-sents the specific heat in fat (i = F) andliver (i = L), xF is the thickness of fattissue and L F is a characteristic lengthscale of the tissue, which depends onthe relative SAR therein. It is found thatthe ratio of length scales underall conditions. Since the ratio in SAR ( ) is approximately 1/10 at all fre-quencies (Figure 1, adopted from Hoet al. [2]) and the ratio in specific heats( ) is approximately 1/2, it follows that a number of converging beams of theorder of n> 24 is predicted to be nec-essary just to achieve equal tempera-ture increases in the fat and liver.

This does not take into account thefurther penalty of significant heat dis-sipation coming from the vascularheat sink effect due to the high bloodflow rate in the liver (17 ml/min/kg =1,190 ml/min flow rate in a 70 kghuman) [3], or even higher flow rates ina hypervascular liver cancer (shown tobe higher than normal liver due to

Steven Curley from the Michael E. DeBakey Department of Surgery, Baylor College of Medicineand a group of experts from Brown Foundation Institute of Molecular Medicine, McGovernMedical School, University of Texas Health Science Center share their expertise on non-invasiveradiofrequency hyperthermia (NiRFH)

Non-invasive radiofrequencyhyperthermia

20

PROFILE

xF___LF

cF___cL

SARL________SARF

<<1

∆ TL________∆ TF

cF___cL

= xF___LF

1– SARL________SARF

( )

increased hepatic arterial flow rates inhepatocellular carcinoma) [4].

To develop a model for predicting RFtherapy efficacy, we will integrate ourenergy transfer model with a spatio -temporal tumour response model [5],which has been used to understandand predict tumour response tochemotherapeutic drugs in patients.The energy transfer model will solvefor energy deposition into the tumourtissue and feed this information intothe tumour response model, whichwill then predict the extent of tumourkill by solving a system of differentialequations with tissue- and treatment-specific parameters. The resultingintegrative model, based on a combi-nation of physical transport and elec-tromagnetic theories (accounting fortissue heating for different tissuetypes), will be calibrated and validatedwith patient data and then prospec-tively used to optimise RF treatmentfor individual patients.

We recommend, based on our prelim-inary analysis, that a large number ofmultiphase array variable frequency(patient-specific) RF beams be used

clinically. Precision cancer care basedon patient-specific genetic, proteomicand metabolomic analyses willbecome the standard of care; NiRFHshould also be designed to meet apatient’s cancer-specific and bodymass-related electrical propertiesusing mathematically determined fre-quency, power and treatment dura-tion parameters.

Another possible approach to over-come the high adipose tissue SAR ofRF (while avoiding heating and injuryto fat-bearing tissues or adjacentorgans) is to use nuclear magneticresonance (NMR) Fourier decomposi-tion techniques to focus the intensityof the RF at a desired depth in a livertumour, thus bypassing the fat [4].Finally, the use of RF-absorbing metal-lic-nanoparticle-based sensitisers thatspecifically localise in liver malignan-cies and are shielded from ioniccharge buffering offers another possi-ble means to achieve targeted hyper-thermia [6].

References

1 Van der Horst A, Versteijne E, Besselink MGH, Daams JG, Bulle

EB, Bijlsma MF, et al. The clinical benefit of hyperthermia in

pancreatic cancer: a systematic review. International journal of

hyperthermia: the official journal of European Society for Hyper-

thermic Oncology, North American Hyperthermia Group. 2017:

1-11. Epub 2017/11/24. doi: 10.1080/02656736.2017.1401126.

PubMed PMID: 29168401.

2 Ho JC, Nguyen L, Law JJ, Ware MJ, Keshishian V, Lara NC, et al.

Non-Invasive Radiofrequency Field Treatment to Produce Hepatic

Hyperthermia: Efficacy and Safety in Swine. IEEE journal of trans-

lational engineering in health and medicine. 2017;5:1500109.

Epub 2017/05/17. doi: 10.1109/JTEHM.2017.2672965. PubMed

PMID: 28507824; PubMed Central PMCID: PMC5411244.

3 Carlisle KM, Halliwell M, Read AE, Wells PN. Estimation of total

hepatic blood flow by duplex ultrasound. Gut. 1992;33(1):92-7.

Epub 1992/01/01. PubMed PMID: 1740284; PubMed Central

PMCID: PMC1373871.

4 Chen YW, Pan HB, Tseng HH, Hung YT, Huang JS, Chou CP. Assess-

ment of blood flow in hepatocellular carcinoma: correlations of

computed tomography perfusion imaging and circulating angiogenic

factors. International journal of molecular sciences. 2013;14(9):

17536-52. Epub 2013/08/30. doi: 10.3390/ijms140917536.

PubMed PMID: 23985826; PubMed Central PMCID: PMC3794740.

5 Wang Z, Kerketta R, Chuang YL, Dogra P, Butner JD, Brocato TA, et

al. Theory and Experimental Validation of a Spatio-temporal

Model of Chemotherapy Transport to Enhance Tumor Cell Kill.

PLoS computational biology. 2016;12(6):e1004969. Epub

2016/06/11. doi: 10.1371/journal.pcbi.1004969. PubMed PMID:

27286441; PubMed Central PMCID: PMC4902302.

6 Tamarov KP, Osminkina LA, Zinovyev SV, Maximova KA, Kargina JV,

Gongalsky MB, et al. Radio frequency radiation-induced hyper-

thermia using Si nanoparticle-based sensitizers for mild cancer

therapy. Scientific reports. 2014;4:7034. Epub 2014/11/14. doi:

10.1038/srep07034. PubMed PMID: 25391603; PubMed Central

PMCID: PMC5382688.

Steven CurleyMichael E. DeBakey Department of Surgery,Baylor College of Medicine, Houston, Texas

Prashant Dogra Joseph D. Butner Zhihui Wang Vittorio CristiniBrown Foundation Institute of MolecularMedicine, McGovern Medical School, University of Texas Health Science Center at Houston, Texas

21

PROFILE

Figure 1. Relative SAR for subcutaneous fat and liver from 10 MHz to 3 GHz as measured withdirect permittivity probes placed into tissue during variable frequency RF treatments in a largeanimal (pig) model. Adopted from Ho et al. [2] with permission

Acute myeloid leukaemia (AML)represents 1.3% of all newcancer cases, with 21,380 new

cases anticipated in the United Statesin 20171. AML is a clinically challengingand heterogeneous disease that canbecome rapidly fatal if untreated.Despite continuing advances in treat-ment options, global 5-year survivalrates are approximately 27% for adultpatients and 60% for paediatric AMLpatients2.

The heterogeneous nature of AML ischaracterised by the presence ofnumerous genetic lesions and chro-mosomal abnormalities present in itsmany subtypes. Although the mostcommon mutations in AML have beendefined, there is still a gap in ourunderstanding of the molecularmechanisms underlying the variationin survival outcomes.

Due to these challenges, there is anongoing search for molecular markersthat can improve prognosis assign-ment and prediction of treatment andsurvival outcomes in AML patients. Forthe most part, studies conducted toidentify these predictive markers havebeen focused on genomics and epige-nomics based methods. However, thegrowing field of metabolomics hasshown significant results in manyforms of cancer and haematologicalmalignancies. In the case of AML,metabolomics research has been verylimited, but the results have been

promising. This article reviews the literature currently available for AMLmetabolomics.

In vitro metabolomics of drugresponseOne of the earliest studies in AMLmetabolomics, was an in vitrometabolomics study conducted onAML cell lines3. The objective of thisstudy was to use nuclear magnetic res-onance (NMR) metabolomic profiling tostudy the effect of bezafibrate (BEZ)and medroxyprogesterone acetate(MPA) on AML cell lines and provide evi-dence for the underlying mechanism ofaction of BEZ and MPA. The cell linesshowed significant changes to tricar-boxylic acid (TCA) cycle intermediatesfollowing exposure to BEZ and MPA inthe form of an increased conversion ofalpha-ketoglutarate to succinate. Thisstudy shows the potential benefit ofconducting in vitro metabolomics studies to explore the impact of drugtreatment in AML cell lines. Specifically,these results highlight the importanceof energy production pathways forAML cells, an ongoing area of focus inAML metabolism studies.

Application of glucose targetedmetabolomics in AML prognosisRapid cellular proliferation is a majorfeature of many forms of cancer,including AML. This feature of elevatedproliferation requires AML cells toupregulate multiple metabolic path-ways involved in energy production,

such as glycolysis and the TCA cycle4.A particular feature of TCA cycle repro-gramming in AML involves mutationsin the gene encoding for isocitratedehydrogenase 1 and 2 (IDH1 andIDH2). IDH isoforms normally catalysethe decarboxylation of isocitrate toform α-ketoglutarate, an essential stepin the TCA cycle. However, mutantforms of IDH gain an additional func-tion of catalysing the conversion of α-ketoglutarate to 2-hydroxyglutarate(2-HG). These changes to glucosemetabolism have been of particularinterest in AML metabolomics studies.

Recently, two major metabolomicsstudies have been conducted for adultAML patients, targeting glucose relatedmetabolites for investigation. In thefirst study, patients were enrolled in aclinical trial to evaluate the prognosticvalue of serum 2-HG levels in AMLpatients5. Results showed that 2-HGcould be used effectively as a prognos-tic factor in patients that were positivefor IDH1/2 mutation.

A follow up study was conducted bythe same group to evaluate the prog-nostic value of 10 different metabo-lites related to glucose metabolism inadult AML patients6. The investigatorsdetermined that increased abundanceof five of these glucose metabolites,including lactate, 2-oxoglutarate, pyru-vate, 2-hydroxyglutarate and glycerol-3-phosphate, were significantlyassociated with worsened survival

The current state of metabolomics research and application in Acute Myeloid Leukaemiais placed under the spotlight by Bradley Stockard and Jatinder Lamba from Department ofPharmacotherapy and Translational Research, University of Florida

Acute myeloid leukaemia (AML)research and application

22

PROFILE

outcomes. The investigators usedthese metabolites to develop a prog-nosis risk score for each study patient.Ultimately, the results showed thatprognosis risk scoring was able to pre-dict poor survival outcomes in lowscoring patients without the use ofother prognostic factors. Together,these studies have helped confirm the importance of altered glucosemetabolism in AML and they supportthe potential clinical relevance ofmetabolomics for AML patients.

Global metabolic profiling in AMLWhile the exploration of altered glu-cose metabolism in AML continues toyield significant results, the changesto many other metabolic pathwaysare not as well understood. Toaddress this, multiple studies havetaken a more untargeted approach toAML metabolic profiling to evaluateglobal changes to metabolism. Astudy by Wang, Y et al. using 1H NMRspectroscopy found significant differ-ences in multiple metabolic pathwaysbetween healthy controls and AMLpatients, including glycolysis, TCAcycle, protein and lipoprotein biosyn-thesis, fatty acid metabolism and cellmembrane component metabolism7.

Another study by Musharraf et al.involved the global metabolic profilingof AML patients, as well as acute lymphoblastic leukaemia and aplasticanaemia patients. 27 metaboliteswere found to be significantly differ-ent between leukaemia patients andhealthy controls8. Related metabolicpathways included fatty acid andketone body metabolism and steroidhormone biosynthesis.

Finally, a more recent study conductedby Tan et al. focused on differentiatingmetabolic profiles of AML patients who achieved complete remission with cytarabine and anthracycline

chemotherapeutic regimens as com-pared to those who were non-respon-ders9. The study identified twodifferential metabolites of interest,dodecanamide and leukotriene B4dimethylamide, which the investigatorswere able to use to differentiatepatients according to clinical responsesuccessfully. Ultimately, globalmetabolomics studies of AML havehelped reinforce the role of glucosemetabolism in AML disease progressionand establish the importance of othermetabolic pathways associated withAML, such as fatty acid metabolism.

Conclusion and future directionsOverall, the current body of researchfor AML metabolomics shows that thistype of study can be successfullyapplied to improve our understandingof AML disease progression and char-acteristics, as well as the significantvariation in clinical outcomes betweenAML patients. Many of these studieshave identified glucose metabolismand fatty acid metabolism asmetabolic pathways significantly asso-ciated with AML. However, there havebeen relatively few AML metabolomicsstudies published, even compared tomany other cancer types.

Additional research is needed to fur-ther elucidate the metabolic pathwayslinked to the AML disease state. Ideally,metabolomics data can be integratedwith additional ‘omics’ data to fullyexplain the path from gene to pheno-type and help contribute to personal-ising AML evaluation and treatment for the individual patient. The currentcontributions of metabolomics tounderstanding AML are promising andits potential continues to be realisedwith growing interest in the field.

Acknowledgements

Funding from National Cancer Institute –R01-CA132946 supports

AML research in Lamba Lab.

References

1 “Surveillance, Epidemiology, and End Results Program.”

Leukemia. National Cancer Institute, May 2016.

2 Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the

World Health Organization (WHO) classification of myeloid

neoplasms and acute leukemia: rationale and important changes.

Blood. 2009; 114:937–951.

3 Tiziani S, et al. “Metabolomic Profiling of Drug Responses in Acute

Myeloid Leukaemia Cell Lines.” PLoS ONE 4.4 (2009).

4 Hanahan D, Weinberg RA. “Hallmarks of cancer: the next

generation.” Cell. 2011;144(5):646-674.

5 Wang JH, et al 2013. “Prognostic Significance of 2-hydroxyglutarate

Levels in Acute Myeloid Leukemia in China.” Proceedings of the

National Academy of Sciences 110.42 (2013): 17017-7022.

6 Chen, et al. “A Distinct Glucose Metabolism Signature of Acute

Myeloid Leukemia with Prognostic Value.” Blood 124.10 (2014):

1645-654.

7 Wang Y, et al. “Rapid Diagnosis and Prognosis of de novo Acute

Myeloid Leukemia by Serum Metabonomic Analysis.” J. Proteome

Res. 2013, 12, 4393−4401.

8 Musharraf S G, et al. “SERUM metabolomics of acute lymphoblastic

leukaemia and acute myeloid leukaemia for probing biomarker

molecules.” Hematol Oncol. 2016.

9 Tan G, et al. “Pharmacometabolomics identifies dodecanamide and

leukotriene B4 dimethylamide as a predictor of chemosensitivity

for patients with acute myeloid leukemia treated with cytarabine

and anthracycline.” Oncotarget. 8.51: 88697-88707. 2017.

Bradley Stockard Jatinder LambaDepartment of Pharmacotherapy and Translational ResearchUniversity of Floridahttp://ptr.pharmacy.ufl.edu/

23

PROFILE

The moment we hear the wordcancer, the thought that imme-diately crosses anyone’s mind is

death. So, everyone collapses bothphysically and mentally. If we learn todrop this inner conflict and accept thereality, we can experience and adorethe life without fear. Moreover, we will learn that there is no differencebetween a so-called healthy personand a cancer patient.

As humans, we all are immersed in ourcircadian lives to feed our personalegos and desires like machines. As inthe movie The Matrix, most of us maynot be able to perceive this dual natureof the mind while living in the matrixand feeding illusory dreams. Accordingto Vedic teaching, this state of mind iscalled “the divine game of Lila.” Wewere all born into this world with personal identity or “self” (a physicalbody and a soul). We have not onlyforgotten that cancer conquered thesoul well before it attacked the body,but also life and death are inseparable.So, every living being including cancer patients is barcoded with anexpiration date.

According to the American CancerSociety, ~1,400,000 Americans werediagnosed with cancer during 2008,leading to ~560,000 deaths. On theother hand, about 1,735,350 Americanswill be diagnosed with cancer in 2018and ~610,000 will die. If modern sci-ence and technology can cure cancer,

what is the rationale for increasingnumber of cancer incidence in eachyear? Whilst the immune system issupposed to eliminate cancer cellswithin the body, it is not able to differ-entiate cancer cells from normalhealthy cells. As healthy cells, cancercells also express receptors that signalimmune cells to prevent an attack orto keep the immune system in check.

While the treatment of invasive ormetastatic cancer is often limited tochemotherapy, scientific ingenuity hascreated novel therapeutic agents onlyto find cancer has evolved to developdrug resistance. Cancer may havestarted from a singularity and spiralledout as “the primordial Om” or mayhave evolved from a single cancerstem cell as Darwin’s theory and thenmetastasize to distant organs. Whilecuring metastatic disease may be elusive, we may able to use the ideaof the fractal to explain metastaticpatterns as Benoit Mandelbrot used itto describe geometrical patterns innature.

Moreover, no matter what treatmentis used for the cancer patient, cancerrecurs at any time without a warning.In Greek mythology, the gods com-manded Sisyphus to infinitely push aboulder up a mountain, only to haveit roll down. So, are we futilely rollinga boulder uphill by searching imper-manent solutions for a permanentproblem?

J. Krishnamurti has famously said that“it is no measure of [one’s] health tobe well-adjusted to a profoundly sicksociety.” So, a drug’s mechanism ofaction may be the least to worry. AsKohlberg pointed out in “the Heinzdilemma,” we must evaluate the valueof human life over the pharma-com-panies’ greed for money. According tothe Heinz dilemma, a woman whowas in near death from a special kindof cancer was prescribed a new drugthat the doctors thought might saveher. While the drug was expensive tosynthesize, the druggist was chargingten times what the drug cost him tomake. Left with no other option, thesick woman’s husband, Heinz, stolethe drug for his wife.

Although Kohlberg developed theHeinz dilemma to evaluate moralethics, cancer drugs are extremelyexpensive when compared to the pro-duction cost. On the other hand, mostof the drugs are discovered in sweat-shops using scientists. As we learnedfrom the Stanford prison experiment,management always likes to have morecontrol, more power, more recognition,more money, and more of everything.Plato’s Chariot analogy, as well asFreud’s model, explains the nature ofthese human behaviours.

In Plato’s Chariot analogy, a chariot(one’s soul) is driven by two powerfulwinged horses whereas, in Freud’sstructural model, the soul is driven by

Sumith A Kularatne, PhD, discusses his thoughtson the illusion of cancer and death

The illusion of cancer and death:Illusion of the self

24

PROFILE

consciousness and unconsciousness.One horse is noble, rational and moralin nature (mirroring consciousness)while the other horse is wild in char-acter (mirroring unconsciousness) anddriven by basic instinct such as aggres-siveness, sexuality and control.

In today’s world, there are manypeople seeking spiritual enrichmentby engaging in religious activities suchas rituals, chanting, praying, singing,etc. However, most of those can beseen as human performing some conditioned activities rather thansearching for one’s self. As humans,while following religious habits onSundays, we ride the wild horse comfortably during the rest of theweek. We are waiting for The SecondComing of the saviour; however, noone willing to get up on the crossexcept partaking in the sacrament.

As Ludwig Feuerbach depicted, we mayhave already realised that “we createGod in our own image by uncon-sciously projecting our idealised perfec-tion as a divine being.” On the otherhand, Gaunilo’s may have convinced usof the non-existence of God by his “LostIsland” analogy. In contrary, how are we going to explain the existence of

evilness, discrimination, abuse, naturalcalamities, death from cancer, etc. Inthe allegory of the cave by Plato, threeprisoners lived chained in a cave fromtheir birth. The only thing they couldsee were shadows cast on a blank wall by the objects passing on a raisedwalkway behind them.

Plato showed the misconceptionsabout knowledge and wisdom, such asrestored organised religions throughfalse prophets, using the prisoners’guessing game from the shadows. Hemade the story more intriguing byallowing the escape of one prisonerinto the real world, represents aphilosopher who searches for wisdom,who ultimately comes back to the caveto relay the reality to remaining two.However, the two prisoners not onlydisbelieved him, but also threatenedanyone who tried to free them fromthe cave. Although Plato wrote theallegory of the cave in ~400BC, it lookslike; humanity is still searching thepath to escape from the cave.

Although Rene Descartes, the fatherof modern philosophy, developed a“method of doubt” to objectively eval-uate all that he believed to be true, heis famous for the saying “Cogito ErgoSum” (English: “One thing I know forsure, I exist”) without a doubt. He wasa devout dualist in the sense that theself consists of an immaterial soul thatis absolutely distinct from a finite,material body.

On the other hand, David Hume, adevout empiricist, claimed there is noself. Most of us may have neverrealised the no-self (minimal self), orwhat the Buddha called anatta. It goesbeyond the body and the soul. Basedon Buddhist philosophy, self can bedefined as an impermanent (anicca)flow of energy (desire) through the

continual interaction of five aggregates(i.e. physical form, sensation, concep-tualisation, disposition to act and con-sciousness) with right assembly thatbrings continual suffering (dukkha). Wewere named by the parents and toldwho we are by the society. If there is aself, we should have control over ofsickness, ageing, death, social impacts,authoritative influences and naturalcalamity.

Once we realise the true nature of lifeand death and at the same time, thereality of self, we all will learn to diebefore we die. We will learn to let goof our ego construct by identifying theroot for suffering. The intention of thisarticle is not to make cancer patientswalk away from medicine or their religious beliefs, but to inspire them to find the middle path (according toBuddha) or the golden mean (accord-ing to Aristotle). Simultaneous treat-ment of both soul and body may givea better outcome for the therapy andyour soul will remain cancer free.

Sumith A Kularatne, PhDTel: +1 858 539 5901sumithanuk@outlook.com www.researchgate.net/profile/Sumith_Kularatnehttp://bit.ly/1Q4Ji8Vhttps://twitter.com/SumithKularatnehttp://bit.ly/GooglePlusSumith

25

PROFILE

26

On the website of, National Institutes of Health(NIH), we learn that for most of the history of medicine, doctors have relied on their

senses – that is vision, hearing and touch – to diagnoseillness and monitor a patient’s condition.

However, NIH’s investment in research over the periodof a whole century has helped to completely changemedical diagnostics. The new technologies of todayallow doctors to find out an increasing amount ofdetailed information about both the progression andtreatment of disease and can even offer personalisedtreatment based on a patient’s genes, we discover.

In addition, NIH-funded scientists have helped to pioneerthe development of magnetic resonance imaging (MRI),but they have also made important strides towarduncovering the medical potential of stem cells and assuch, they have developed new tools for genomesequencing. With these advanced technologies inplace, scientists are finding out how genes affecthuman health and how a genetic approach can helpdoctors tailor treatments and prevention strategies foreach patient. Certainly, millions of individuals have

already been touched by the exciting era of personalisedmedicine that has grown directly from this research,we learn. (1)

Advances in medical imagingOne area that concerns the NIH is medical imaging, anarea they are thoroughly committed to. Indeed, theyhave an entire institute, the National Institute of Biomedical Imaging and Bioengineering (NIBIB), whoseek to improve health by leading the development,acceleration and application of biomedical technologies.

NIBIB is devoted to integrating the physical and engineering sciences, with the life sciences, to furtherbasic research and medical care. This ambitious aim isachieved through:

Research and development of new biomedical imag-•ing and bioengineering techniques and devices toimprove the prevention, detection and treatment ofdisease;

Furthering present imaging and bioengineering•modalities;

The role of advanced technologies in healthcare, including the work of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) in this area, is placed under the spotlight

by Open Access Government

HEALTH & SOCIAL CARE

The role of advanced technologies in healthcare

HEALTH & SOCIAL CARE

27

Supporting relevant research in the physical and•mathematical sciences;

Encouraging research and development in multidis-•ciplinary areas;

Supporting studies to assess the effectiveness and•outcomes of new biologics, processes, materials,devices and procedures;

Developing technologies for the early detection and•assessment of health status where diseases are concerned and;

Developing advanced imaging and engineering •techniques for carrying out biomedical research atmultiple scales. (2)

Below, we explore just two examples of the excellentresearch NIBIB is supporting, where medical technolo-gies are concerned.

Thermo-chemotherapy combo eradicatesprimary and metastatic tumours in miceIn recent news, we find out that bioengineers at NIBIBdeveloped a smart anti-cancer nanoparticle with pre-cisely targeted tumour-killing activity, which was foundto be superior to the previously available technologies.

We are told that state-of-the-art nanoparticle featuresa very sturdy shell, which is capable of carrying largeloads of chemotherapeutic drugs through the circula-tory system to a tumour – that is without the leakagethat can damage healthy tissue. The nanomedicine isphotothermal-responsive, so the cancer-killing load ofthe particle is released only when it enters the tumourcells and is activated by laser light, we discover.

Reported in the February issue of Nature Communica-tions, this cancer-killing technology is the latest andmost effective created by members of the Laboratoryof Molecular Imaging and Nanomedicine (LOMIN) atNIBIB, which is led by Xiaoyuan (Shawn) Chen, SeniorInvestigator.

Fluorescent nanoparticles track cancermetastasis to multiple organsResearchers funded by the NIBIB have developed fluorescent nanoparticles that light up to track the

progress of breast cancer metastasis, we find out. Theyare currently testing the particles in mice, with thehope of one day using them in humans, we are told.

Prabhas Moghe, Ph.D., professor of Biomedical Engi-neering and Chemical and Biochemical Engineering atRutgers University and his team are developingnanoparticles that can help identify and track cancermetastasis early on, even when a tumour is really small.

“There are still significant hurdles to be overcomebefore this imaging technique could be used inhumans, but it is an important step in moving opticalimaging cancer diagnosis forward,” says BehrouzShabestari, Ph.D., director of the NIBIB Program inOptical Imaging and Spectroscopy. “It has the potentialto help doctors to identify tiny cancer cells and tracktheir spread more effectively, leading to early detectionand potentially improved treatment planning.”

As well as tracking the spread of cancer, the nanopar-ticles could potentially be used to differentiate cancertissue from healthy tissue for surgeons who are remov-ing tumours. Moghe and his team are hopeful that thetechnology could be positioned for use in humanswithin the next 10 years. (3)

Final thoughtsYou can find many more examples of how NIBIB isimproving human health, by leading the developmentand accelerating the application of biomedical tech-nologies in the US today, which this article provides aflavour of. ■

For more information, please visit www.nih.gov .

References

1 https://www.nih.gov/about-nih/what-we-do/nih-turning-discovery-

into-health/personalized-medicine-new-technologies

2 https://www.nih.gov/research-training/advances-medical-imaging

3 https://www.nibib.nih.gov/news-events/newsroom/fluorescent-

nanoparticles-track-cancer-metastasis-multiple-organs

Open Access GovernmentJMiles@openaccessgovernment.orgwww.openaccessgovernment.orghttps://twitter.com/OpenAccessGov

Medical imaging has trans-formed the entire spectrumof healthcare, from enabling

discoveries in medical science anddirecting the development of thera-peutic interventions, to providing themost optimal and efficient managementof diseases in individuals. Yet conven-tional medical imaging modalities haveparticular limitations, especially whenit comes to the paediatric populationsin whom diagnosis and treatmentarguably may have the greatest long-term benefit.

Whether it be the ionising radiation of computed tomography (CT) or x-ray imaging; the radioactivity of radionuclide-based imaging agents innuclear imaging; the long scanningtimes of magnetic resonance imaging(MRI); or the need to administer substantial amounts of iodinated orgadolinium-based contrast agentswhose long-term effects are question-able in adults, much less in infantsand children; conventional medicalimaging does not advance discoveriesin paediatric medicine in the samemanner it does in adult medicine.

Under development in our laborato-ries, near-infrared fluorescence (NIRF)imaging may uniquely meet therequirements for paediatric medicalimaging. The technique dependsupon administering a trace dose ofnon-radioactive dye that fluoresces inthe near-infrared wavelength range

and illuminating tissue surfaces withdim near-infrared (NIR) light that penetrates several centimetres toexcite the dye, causing it to fluoresce.The resulting fluorescence is emittedfrom the tissues and is captured by animaging system, consisting of military-grade night vision technology coupledto a digital image capture device.

Because of the superior sensitivityoffered by the coupling of these twotechnologies, trace doses of fluores-cent dye can be rapidly imaged withsub-second exposures at tissuedepths as great as 3-4 centimetres.This unprecedented performanceenables NIRF imaging to be used as apoint-of-care diagnostic and removesthe need for sedation otherwiseneeded for paediatric patients. Futuredevelopments include extending thisdepth and generating 3-D imaging,similar to CT or MR angiography.

Owing to its 60 year-record of safe usein humans at much larger doses, wecurrently employ indocyanine green

(ICG) as the NIRF contrast agent, butother far brighter and more usefuldyes remain to be translated intohumans. ICG strongly associates withplasma proteins, making it an excellenthemovascular contrast agent and inour work, an excellent lymphovascularcontrast agent that, when coupled withthe NIRF imaging devices, has allowedsome of the first glimpses of lymphaticvascular function in disorders of adultsand children.

The lymphatic vascular system haslargely escaped routine medical imag-ing and as a result, comparatively littleis known about its role in health anddisease. The open and unidirectionallymphatic system begins with the ini-tial lymphatics that lie beneath theepidermis and line all organs. Wasteproducts, immune cells and excessfluid (capillary filtrate) that enter theinitial lymphatics are actively pumpedthrough series of “lymph hearts” orcontractile lymphangions that transitlymph through lymph nodes to thesubclavian vein where the fluid

E.M. Sevick and J.C. Rasmussen from The University of Texas Health Science Center, The Brown Foundation Institute of Molecular Medicine discuss non-radioactive, non-ionisingradiation for safe, paediatric imaging

28

PROFILE

Non-radioactive, non-ionisingradiation for safe paediatric imaging

Figure 1: A schematic of the open andunidirectional lymphatic system which beginsat the initial lymphatics (lower left panel) thatline all organs and carries lymph throughlymph nodes and the thoracic duct beforeemptying into the supraclavicular vein (upperright panel). The system includes series oflymphangions or “lymph hearts” which propellymph unidirectionally through the lymphatics(upper left panel). The abnormal lymphaticfunction may be a result of lack of pumpingand/or the degradation or malformation oflymphatic vessels (lower right panel). Figurereproduced from O’Donnell, et al., J Vasc SurgVenous Lymphat Disord, 2017.

returns to the blood vasculature(Figure 1).

There are few procedures to imagethe lymphatics: (i) lymphoscintigraphy,in which a radioactive colloid isinjected to image lymphatic transportover several minutes to hours usingnuclear imaging and (ii) lymphangiog-raphy, in which several millilitres of aniodinated or gadolinium-based con-trast agent is injected into lymphnodes or into surgically isolated lym-phatic vessels for MR or x-ray imaging,provide invasive and cumbersomediagnostic techniques. As a result,there is little understanding of howthe lymphatic vasculature mediatesimmune response and returns fluidand lipids absorbed from the gut backinto the hemovascular system.

Today, despite the paucity in proce-dures to image the lymphatics, it is gen-erally accepted that it plays a critical rolein several chronic conditions in adults,including autoimmune diseases, suchas rheumatoid arthritis, cancer metas-tasis, peripheral vascular disease andneurodegenerative diseases. In chil-dren, lymphatic dysfunction has beenhypothesized to accompany neurologi-cal diseases, such as specific forms ofAutism, vascular malformations andcardiovascular deformities.

In translational studies funded in partby the National Institutes of Health andconducted under investigational newdrug applications from the FDA, wehave used the NIRF technology todynamically image the lymphatics ofover 400 subjects, including 30 infantsand children. The imaging begins withan intradermal injection of 0.05- 0.1 mLof saline containing microgramamounts of ICG into the region of inter-est. ICG administration on the top ofthe foot results in immediate uptakeinto the main conducting vessels(Figure 2A) that proximally “pumps”

ICG-laden lymph into the inguinalnodes before entering the centrallymph channel that collects mesentericand peripherally generated lymph forits return to the hemovascular system.

In children and adults with suspectedlymphatic dysfunction, we haveobserved abnormal lymph drainageto the bottom of feet (Figure 2B), aswell as pelvic, lymphatic congestionwhich in adolescents and youngadults is associated with lowerextremity lymphedema (Figure 2C)and, in some infants, with surgery-induced chylothorax (Figure 2D).

In other studies, concerning infants,we have uncovered impaired lym-phatic pumping and imaged retro-grade lymphatic drainage into thepleural cavity to ascertain the natureof impaired lymphatic return. Theseimaging observations, when coupledwith genetic and immune profiling,could provide critical clues to developeffective treatments for the paediatricpopulation suffering immune or cardiovascular disorders.

While we have used NIRF to interro-gate lymphatic function in children

and adults, it also has the unfulfilledpotential to interrogate hemovascularfunction as well as cerebral spinalfluid production and drainage toaddress some of our most challengingproblems in paediatric patients. Inaddition, the development of molecu-larly targeted NIRF agents expandsthe repertoire of imaging diagnosticsin the paediatric population toadvance therapeutic discoveries.

For more information on NIRF imaging in paediatrics and congenitaldiseases:

Greives, M.R., Aldrich, M.B., Morrow, J.R., Sevick-Muraca, E.M., andJ.C. Rasmussen, “Near-infrared fluorescence imaging of a toddler withcongenital lymphedema,” Pediatrics, 139(4), 2017 PMID: 28356336.

Rasmussen, J.C., Aldrich, M.B., Guilloid, R., Fife, C.E., O’Donnell,T.F., and E.M. Sevick-Muraca, “NIRF lymphatic imaging in a patienttreated for venous occlusion,” Journal of Vascular Surgery Cases,4(1): 9-17, 2016.

Gonzalez-Garay, M.L., Aldrich, M.B., Rasmussen, J.C., Guilliod, R., King,P.D., and E.M. Sevick-Muraca, “A novel mutation in CELSR1 ispathogenic for a new phenotype of hereditary lymphedema,” VascularCell, 8:1, 2016 PMID: 26855770.

Tan, I.C., Balaguru, D., Rasmussen, J.C., Guilliod, R., Bricker, J.T.,Douglas, W.I., and E.M. Sevick-Muraca, “Investigational lymphaticimaging at the bedside in a pediatric postoperative chylothorax patient,” Pediatric Cardiology, 2014, PMID: 24972649.

Agollah, G.D., Gonzalez-Garay, M.L., Rasmussen, J.C., Tan, I-C.,Aldrich, M.B., Darne, C., Fife, C.E., Guilloid, R., Maus, E.A., King,P.D., and E.M. Sevick-Muraca, “Evidence for SH domain-containing5’-inosotil phosphatase-2 (SHIP2) contributing to a lymphatic dysfunction,” Plos One, 10;9(11):e112548, 2014. PMID: 25383712.

E.M. Sevick-Muraca, “Translation of near-infrared fluorescenceimaging technologies: emerging clinical applications,” Ann RevMed, 63: 217-31, 2012, Epub 2011 Oct 27. PMID: 22034868.

Burrows, P.E.*, Gonzalez-Garay, M.L.*, Rasmussen, J.C.*, AldrichM.E., Guilliod R., Maus, E.A., Fife, C.E., Kwon, S., Lapinski, P.E.,King, P.D., and E.M. Sevick-Muraca, “Lymphatic abnormalities areassociated with RASA1 mutations in mouse and man,” Proc NatlAcad Sci, 110(21): 8621-6, 2013. PMID: 23650393.

E.M. Sevick J.C. RasmussenThe University of Texas Health Science Center, The Brown Foundation Institute ofMolecular Medicinehttps://www.uth.edu/imm/

29

PROFILE

Figure 2: Conducting lymphatics on the top (A)of the right foot and (B) abnormal drainageon the bottom of the left foot of a 17-year girlwith congenital lymphedema; Lymphaticcongestion in the pelvis of (C) a 16-year girlwith congenital lymphedema and (D) a 23-dayold male infant with surgery-inducedchylothorax.

HEALTH & SOCIAL CARE

30

Cloud computing in medical imaging:Not a matter of if, but when

In the minds of healthcare IT decision-makers, asseveral surveys have shown, Cloud-based solutionshave long been associated with data security and

data ownership concerns. The apprehension doeshave a strong rationale: Why would anybody moveconfidential patient data off-premises and willinglybecome dependent on the network or on a vendor tobe able to access and utilise data they own?

While this perception has caused lasting resistance toCloud adoption in healthcare, especially in the govern-ment hospital segment, it has been changing graduallyover the last few years. Years that also happened to bepunctuated by regular Cloud outages and cybersecurityattack horror stories.

Recognising the Cloud’s benefitsThe benefits of Cloud solutions, such as their cost-effectiveness and predictability, unlimited scalabilityand deployment flexibility, have started to outweighthe perceived risks. Cloud proponents even go as faras to admit that vendors are in a better position thantheir own IT organisations, to proactively protect datawhile leveraging the latest data security advances. Theyrealise that there are waste and inefficiency inherentto the conventional siloed on-premises IT models andthat they could use freed-up time to focus on higher-valueenterprise initiatives. Therefore, as they contemplatethe second or third generation of various health ITsolutions, the standard model of buying, operating andmaintaining that in-house is naturally coming intoquestion.

Medical imaging, a precursorThis is especially true in medical imaging, where theunending growth in image data volumes, coupled withlong-term data retention policies in place, makes traditional storage upgrade and scale-up mechanisms

clearly unsustainable over the long run. This is why,since the early 2000s, Cloud-based solutions have pro-vided a viable alternative to tape- and truck-basedsolutions for the long-term archival of medical imagestudies. While this early adoption has enabled manyproviders to get their feet wet with Cloud solutions,there is actually so much more today to Cloud use thanmere back-office data storage support.

Cloud storage is only the beginning, Cloudcomputing is nextTwo simultaneous and complementary market trendsare advancing Cloud-based imaging informatics intonew use cases: the continuous expansion of medicalimaging applications into niche subspecialty clinicalareas and the ongoing diversification in the points ofcare where medical multimedia content is producedand consumed by various enterprise imaging stake-holders. This is driving the development of the followingfour core application areas:

Cloud-based image archiving, which has been•advancing beyond “deep” archival towards real-timeonline accessibility.

Cloud-based image distribution (for inter- and cross-•enterprise image exchange, image-enabled electronichealth records (EHRs), patient portals and healthcareinformation exchanges (HIEs)).

Cloud-based image diagnosis (RIS, PACS, Teleradiology,•Reporting), which can complement or completelyreplace on-premises image management solutions.

Cloud-based imaging analytics, with various types of•applications that can be delivered on-demand as software-as-a-service (SaaS) or on a subscription basisas part of Cloud-based ecosystems or marketplaces.

Nadim Michel Daher, industry principal at Frost & Sullivan reveals his views on the vital role ofCloud computing in medical imaging

31

A fast-developing but fragmented marketOn the vendor front, the industry players can be categorised into three groups as follows:

The speciality early-movers, who have embraced the•Cloud early-on as the core enabling platform for theirsolutions, built some of their own data centres andwho can be credited for the inception of this emergingmarket.

The large cross-industry Cloud infrastructure vendors•(led by Amazon, Microsoft and Google), who are nowfully proactive in developing their industry partnershipsas well as native solutions in healthcare, including inimaging.

The established imaging IT vendors, many of which•have been fairly conservative in transitioning theircustomers to Cloud solutions, but some of which arepreparing a major realignment around Cloud-basedmodels.

Double-digit growth rate projectionsCloud-based imaging informatics still represents a relatively small market, totalling $285.4 million in revenuein 2016 globally. It accounts for 8.5% of the total Cloud-based health IT market and to 3.8% of the total imagingIT market. However, while fairly niche, the market isexpected to remain on a very strong growth trajectoryover the next few years, growing to $830.5 million in2021, or an impressive compound annual growth rateof 23.8%.

New dimensions via enablement andsynergiesTransitioning to a Cloud-based imaging IT model is noeasy shift, whether for healthcare providers or for vendors. Both have to align with the new purchasing,business, management and governance models thatthis shift entails and to be able to absorb its unconven-tional operational, security and financial risk profiles.Yet, as we have moved past the innovator stage andwell into the early adopter phase of the Cloud in imaging,now is the time for Cloud solutions to unleash theiruntapped potential.

For their greatest value is fact not in Cloud technologyper se, but in its synergies with the field’s most impactfuldevelopments: by enabling greater data usability foradvanced imaging analytics (big data, radiomics andmachine learning), accelerating interoperability imagingresearch initiatives, or converging with healthcareblockchains, the Cloud will be, without a doubt, a pervasive actor in the ongoing transformation of themedical imaging value chain. ■

Nadim Michel DaherIndustry Principal, Medical Imaging and InformaticsFrost & SullivanTel: +33 (0)1 42 81 54 50enquiries@frost.comww2.frost.comwww.twitter.com/Frost_Sullivan

HEALTH & SOCIAL CARE

HEALTH & SOCIAL CARE

32

Arthritis, musculoskeletal and skindiseases including muscular dystrophy

The National Institute of Arthritis and Muscu-loskeletal and Skin Diseases (NIAMS) is one of 27institutes and centres at the National Institutes

of Health (NIH) in America today.

By way of background, NIAMS started in 1986 andstrongly supports research into the causes, treatmentand prevention of arthritis and musculoskeletal andskin diseases; as well as the training of basic and clinical scientists to undertake such research; plus, thedissemination of information on how research onthese diseases is progressing.

NIAMS underlines that most households in Americaare affected by diseases of the bones, joints, musclesand skin. Indeed, these common and rare diseasesimpact on people of all ages, racial and ethnic populationsand economic status. Unfortunately, many of theseconditions affect women and minorities disproportion-ately and as such, NIAMS is committed to uncoveringthe reasons for these disparities and therefore comingup with effective strategies to treat and even preventthem.

Also, NIAMS works to understand and treat a vast arrayof diseases and conditions, such as:

Autoinflammatory diseases;•Back pain;•Connective tissue diseases, such as Marfan syndrome;•Fibromyalgia;•Hair loss disorders, such as alopecia areata;•Lupus;•Muscular dystrophy (MD);•Osteoarthritis;•Osteoporosis;•Rheumatoid arthritis;•Scleroderma and;•Skin diseases, such as psoriasis, eczema and acne.•

Muscular dystrophy (MD)Another branch of the National Institutes of Health,The National Institute of Neurological Disorders andStroke (NINDS) provides further details about one ofthe above-mentioned areas, muscular dystrophy (MD).Before we look at this, however, it’s important to consider the wider work of NINDS.

In summary, we know that the NINDS supports a broadprogramme of research studies on MD. The goals ofthese studies are to gain an understanding of MD andto develop techniques to diagnose, treat, prevent, andultimately cure the disorder. It’s also worth highlightingthat NINDS is a member of the Muscular DystrophyCoordinating Committee (MDCC).

The work of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, includingmuscular dystrophy (MD), is placed under the spotlight by Open Access Government

Human skeletal muscle

HEALTH & SOCIAL CARE

33

We know that the muscular dystrophies (MD) are agroup of more than 30 genetic diseases characterisedby progressive weakness and degeneration of theskeletal muscles that control our movement. Someforms of MD are evidenced in infancy or childhood,while others may not appear until middle age or later.The disorders vary in terms of the distribution andextent of muscle weakness (some forms of MD alsoaffect cardiac muscle), the age of onset, the rate of progression and the pattern of inheritance.

The most common form of MD that primarily affectsboys is known as Duchenne MD. It is caused by theabsence of dystrophin, a protein involved in maintainingmuscle integrity. The onset of Duchenne MD is between3 and 5 years old and the disorder, unfortunately, pro-gresses rapidly. Most boys cannot walk by age 12 andat a later stage, they require a respirator to breathe.Girls in these families have a 50% chance of inheritingand passing on the defective gene to their offspring.Boys with Becker MD, which incidentally is very similarthan Duchenne MD, but is less severe have faulty ornot enough dystrophin.

“We know that the muscular dystrophies (MD) are a group of more than 30 genetic diseasescharacterised by progressive weakness and

degeneration of the skeletal muscles that control our movement.”

The website of NINDS also informs us aboutFacioscapulohumeral MD, which normally beginsduring the teenage years. It causes progressive weak-ness in muscles of the face, arms, legs and around theshoulders and chest area. While it progresses slowly, itcan vary in symptoms from mild to disabling.

The most common of the disorder in adult form isknown as Myotonic MD, which is typified by prolongedmuscle spasms, cardiac abnormalities cataracts andendocrine disturbances. Individuals with myotonic MDcan be described as having long, thin faces, droopingeyelids and a swan-like neck.

TreatmentAt the time of writing, there is, unfortunately, no specifictreatment to stop or reverse any form of MD. However,current treatments for MD may include respiratory

therapy, physical therapy, speech therapy, orthopaedicappliances used for support, as well as correctiveorthopaedic surgery.

Drug therapy is also used to treat MD and includes:

Antibiotics to fight respiratory infections;•

Anticonvulsants to control seizures and some muscle•activity;

Corticosteroids to slow muscle degeneration and;•

Immunosuppressants to delay some damage to•dying muscle cells.

Also, some individuals may benefit from occupationaltherapy, as well as assistive technology. Some patientsmay need assisted ventilation to treat respiratorymuscle weakness and a perhaps pacemaker for cardiacabnormalities.

PrognosisIn closing, it’s worth highlighting that the prognosis forpeople with MD varies according to both the type andprogression of the disorder. Some cases can be mildand progress very slowly over a normal lifespan, whileothers produce functional disability, severe muscleweakness and loss of the ability to even walk. Whilesome children with MD die in infancy, others live intoadulthood with only a moderate disability. ■

For additional information on the issues discussed here, please visit

https://mdcc.nih.gov/ and www.niams.nih.gov.

Open Access GovernmentJMiles@openaccessgovernment.orgwww.openaccessgovernment.orghttps://twitter.com/OpenAccessGov

Duchenne muscular dystrophy(DMD) is a debilitating, pro-gressive muscle weakening

disease. Currently, there are no curesand no effective treatments for muscular dystrophy (MD). However,there are multiple highly promisingtherapeutics in the pipeline that shouldgive patients and their families’ signif-icant hope. One exciting avenue ofresearch is identifying novel methodsof immune inhibition.

Immune inhibition is a promisingtherapeutic avenue because of thelarge body of data (from both lab animals and patients) that indicatesreducing the chronic inflammationthat always accompanies DMD is significantly beneficial (reviewedEvans 2009 and Tidball 2005). In MDmice, various scientists depletedCD8+ T-cells, or CD4+ T-cells, ormacrophages, or neutrophils and havedemonstrated significant improvementof pathology (reviewed in Evans). Now, researchers must achieve theseimmune-cell reductions in humansand without side effects.

MD pathobiology initiates with musclecell membrane permeability, immuneinfiltrate, myofibre loss and fibrosis.Despite the complicated characteristicsof the immune system, its role in acutemuscle wounds and MD pathologycan be described. In muscle wounds,the immune system is responsible to

clean the wound, create scar tissue tohalt bleeding, remodel the scar tissueand then terminate the immunesystem response. Neutrophils andtype 1 macrophages initiate theimmune infiltration followed byeosinophils and T-cells.

The type 1 macrophages then transi-tion to the anti-inflammatory type 2macrophages. The disease is so devastating because of the chronic,ongoing nature of the membranedamage and the resultant asynchro-nised healing response. One cell maybe at the correct stage to repair itsmembrane and is secreting appropriateanti-inflammatory cytokines, while aneighbouring cell is secretingcytokines to attract macrophages and T-cells and thereby inhibit the first cell’s repair process. Interestingdata even indicates that the immunecell infiltrate precedes diseasehistopathology (Spencer 2001), pro-viding more impetus for inhibition ofthe immune system to treat MD.

In fact, the current standard of care –corticosteroids – is beneficial becauseit inhibits the immune response.Steroid therapies postpone thepatient’s need for a wheelchair. How-ever, the steroids cause significantside-effects and other therapeuticsmust be identified. Among the latest,clinically-relevant, immune inhibitiontherapeutics are:

1) Antibodies against NFκb;

2) All-trans retinoic acid;

3) TGFβ inhibition;

4) IL-10 injections;

5) Identifying the best dose andschedule for corticosteroid régime;and

6) Fingolimod.

Each of these compounds has astrong scientific rationale for its inclu-sion in trials against MD. However, myreal optimism for these treatments tobe effective against MD is that theycan be combined with each other andtherapeutics that target other MDmolecular mechanisms. Thereby, clin-icians can tailor-make therapies foreach patient and minimise the dosesto avoid patient-specific side effects,while still achieving maximum benefits.

MD research has been made possibleand greatly accelerated due to theavailability of many mouse models.The most commonly used mouse isthe naturally occurring dystrophindeficient mdx mouse (muscular dys-trophy on the X-chromosome). Inaddition, the individual sarcoglycanshave been genetically mutated to makethe range of sarcoglycanopathies,including the gamma-sarcoglycan

Associate Professor and Director of Medical School Curriculum at the University of Illinois,Dr Ahlke Heydemann underlines Duchenne muscular dystrophy (DMD) – a debilitating,progressive muscle weakening disease

Duchenne muscular dystrophy (DMD)

34

PROFILE

mutations (Sgcg-/-). Both of thesemodels, the mdx and the Sgcg-/-, havebeen breed onto the highly fibroticDBA/2J mouse strain. Through thisbreeding, the mice closely resemblethe pathology seen in patients.

My lab has focused on immune inhi-bition strategies because of the strongbenefits are seen by this strategy. Themechanism my lab has focused uponis the use of the FDA approved sphin-gosine-1-phosphate receptor modula-tor Fingolimod. Fingolimod is FDAapproved to treat relapsing multiplesclerosis (MS) and has proven veryeffective for these patients. MS is anauto-immune disease in which thebodies’ antibodies attack and oftendestroy the myelin sheaths surround-ing the nerves. This causes profoundmuscle weakness and lesions in thebrain. Many MS patients have beentaking Fingolimod (Gilenya, Novartis)for six years, with few side effects. Fingolimod’s mechanism of actionsequesters immune cells in theperipheral lymph tissue and therebyinhibits further damage.

This mechanism is very different fromthe immune inhibition provided bythe steroids, thereby allowing the possibilities of co-therapy combiningthese two strategies. The most impor-tant, although rare side effects of Fingolimod are transient bradycardiaafter the first dose and lymphopeniaafter prolonged use. The lymphopeniais reversed with treatment discontin-uation. Although MD is not a trueauto-immune disease, the chronicimmune response is pathogenic andmust, therefore, be reduced. In addi-tion to its immune inhibition, we havedemonstrated that sphingosine-1-phosphate receptor modulation

with Fingolimod provides additionalbenefits against MD.

In both the Sgcg-/- DBA/2J and themdx DBA/2J mouse strains my lab has identified that Fingolimod haspleiotropic beneficial effects upon MDdisease progression and even initia-tion. We have demonstrated that athree-week treatment course admin-istered to young animals reduced thedisease-proximal membrane perme-ability, reduced the immune infiltrate,reduced the resulting fibrosis andincreased some of the respiratoryfunctional parameters (Heydemann2017).

Based on published research studies,our initial hypothesis was that Fin-golimod would inhibit the pathogenicimmune response and thereby reducethe necrosis-induced fibrosis. We hadhoped that a slight improvement ofmembrane strength would also beachieved because of the reduction incytokines. However, we were very surprised at the data demonstratingsuch a large reduction in membranepermeability. The treatment reducedthe membrane permeability to notsignificantly different from wildtypelevels.

As with most research studies, thisstudy produced more questions thananswers. Our current experiments aredesigned to answer the most impor-tant of these questions. Therefore, we are examining how Fingolimodstrengthens the muscle membrane. Inthis pursuit, we have preliminary datathat indicates that treatment with Fin-golimod re-establishes the remaining– non-mutated – members of the dystrophin glycoprotein complex. We will now establish if this is through

increases in transcription, translation,protein stability or complex stability.We are also conducting additionalpreclinical trials, such as dose-response curves, longer treatmenttimes, prevention and reversal strate-gies and co-therapy trials.

Further reading

Evans NP, Misyak SA, Robertson JL, Bassaganya-Riera J, Grange RW.

2009. Immune-mediated mechanisms potentially regulate the

disease time-course of Duchenne muscular dystrophy and provide

targets for therapeutic intervention. Physical Medicine and Reha-

bilitation, 1(8).

Heydemann A. 2017. Severe murine limb-girdle muscular dystrophy

type 2C pathology is diminished by FTY720 treatment. Muscle

Nerve, 56(3).

Spencer MJ, Montecino-Rodriguez E, Dorshkind K, Tidball JG. 2001.

Helper (CD4(+)) and cytotoxic (CD8(+)) T cells promote the pathol-

ogy of dystrophin-deficient muscle. Clin Immunol. 98(2).

Tidball JG, Villalta SA. 2010. Regulatory interactions between muscle

and the immune system during muscle regeneration. Am J Physiol

Regul Integr Comp Physiol. 298(5).

Dr Ahlke Heydemann Associate ProfessorDirector of Medical School CurriculumUniversity of Illinois, ChicagoTel: +1 312 355 0259ahlkeh@uic.edu http://physiology.uic.edu/index.html

35

PROFILE

HEALTH & SOCIAL CARE

36

Nanomaterials in the healthcare sector: The navigation paradox applied to healthcare

The navigation paradox affirms that increasednavigational precision may result in increasedcollision risk. In fact, improved positioning sys-

tems have gained significant precision at the expenseof a greater probability of occupying the same spaceon the shortest distance line between two navigationalpoints. According to Drlickova et al., 2017, althoughnanomedicines potential has revolutionised precisionmedicine approaches, the unique properties ofnanoparticles capable of penetrating inscrutable biolog-ical barriers can induce unintended adverse effects onhuman health and environment, thereby adding somecomplexity to the balance between therapeutic efficacydue to impressive technological advances and safetydue to nanotoxicity issues. Gkika et al., 2018, also depictthe conflict between science advocating for the use ofhigh-risk, potentially toxic nanomaterials due to theirhigher therapeutic target precision and being societyreticent to the utilisation of certain nanotechnologies.

Risk assessment and decision-making toolsChemical and biological risk evaluation, life cycleassessment, safety-by-design, stakeholder engagementand risk governance, among many additional criteria,constitute key items in an effort to address the needsof emerging technologies such as nanomaterials.

The design of new decision support frameworks toassist the solution of the aforementioned paradox hasbeen analysed by Rycroft et al., 2018. The researchersintend to derive a complete characterisation of the risksand benefits that a given nanomaterial may profferwithin a specific nanomedical application, based onmulticriteria decision analysis. Conscious of the double-edged sword of risks and benefits of nanomedicines,the authors analysed the risks and benefits of a wholedecade of nanomedicines development in order to builda valuable, knowledge-based framework focused on

nanotoxicology and risk assessment interventions. Thistool not only enriches multicriteria decision analysisapproaches but also introduces risk-based decision-making and alternatives-based governance criteria foremerging technologies beyond nanomedicines.

The road ahead: Introducing more scienceOccupational exposure limitsSpecific occupational recommended exposure limits(REL) for nanomaterials are limited. The National Insti-tute for Occupational Safety and Health (NIOSH) and theOccupational Safety and Health Administration (OSHA)recommend to workers do not exceed the exposure to1.0 micrograms per cubic meter (μg/m3) as an 8-hourtime-weighted average to respirable carbon nanotubesand carbon nanofibres, as an example.

Workplace design optimisationThe NIOSH advice companies for controlling possibleexposure of their workers to nanomaterials in the work-

Cecilia Van Cauwenberghe from Frost & Sullivan shares her expertise on nanomaterials in today’shealthcare sector, including therapeutic precision versus nanotoxicology risk

HEALTH & SOCIAL CARE

37

place through a series of new workplace design solutiondocuments. These four deliverables strategically helpoptimise the workplace design to guarantee workers’safety during nanomaterials handling.

Bioprotective complexes administrationAccording to a recent publication authored by Leso etal., 2017, challenges faced during nanotechnologytranslation to the healthcare industry are numerous.The researchers highlight the high level of uncertaintyrelated to the physicochemical properties of nanoma-terials regarding potential toxicity, the difficulty inextrapolating dose-response correlations and the complexity in measuring nanomaterial exposure.

“Specific occupational recommended exposure limits(REL) for nanomaterials are limited. The National

Institute for Occupational Safety and Health (NIOSH)and the Occupational Safety and Health

Administration (OSHA) recommend to workers do notexceed the exposure to 1.0 micrograms per cubic

meter (µg/m3) as an 8-hour time-weighted average torespirable carbon nanotubes and carbon nanofibers,

as an example.”

However, Privalova et al., 2017, demonstrated thathighly adverse effects of metallic nanoparticles atorgan-systemic level can be manifestly mitigated bybackground administration of suitable combinationsof bioactive agents in innocuous doses aiming forimproving the body’s resistance to the adverse effectsof nanoparticles. These bio-protectors principally con-sist of pectin, vitamins, glutamate, glycine, N-acetylcys-teine, omega-3 PUFA and different essential traceelements. They are suggested by the authors as an effi-cient auxiliary instrument of health risk management,according to the beneficial results exhibiting interfer-ence with toxicokinetics and toxicodynamics of metalnanoparticles.

Artificial intelligent solutionsPonce and Krop, 2018, illustrate the launch of the EUObservatory for Nanomaterials as a form of impactassessment. The broad goal is to build a framework totrace where nanomaterials are being produced andhow they are used and how they are disposed of. Withthe advent of digital technologies, artificial intelligence,robots, new materials and new processes, nanomedi-cines are supposed to lead significant progress in the

industry. Therefore, artificial intelligent and smarthealthcare solutions must serve to regulate and pro-vide transparency at all levels of nanomaterials manip-ulation in order to shape the future of technologysynergy over solid health and safety bases.

AcknowledgementsI would like to thank all contributors from industryinvolved with the development and delivery of this article, in particular, Bhargav Rajan, Industry Analystand Debarati Sengupta, Senior Research Analyst, fromthe TechVision Group at Frost & Sullivan. ■

Further reading

Gkika, D.A., Magafas, L., Cool, P. and Braet, J., 2018. Balancing nanotoxicity

and returns in health applications: The Prisoner’s Dilemma. Toxicology,

393, pp.83-89.

Drlickova, M., Smolkova, B., Runden-Pran, E. and Dusinska, M., 2017.

Health Hazard and Risk Assessment of Nanoparticles Applied in

Biomedicine. In Nanotoxicology (pp. 151-173).

Leso, V., Fontana, L., Chiara Mauriello, M. and Iavicoli, I., 2017. Occupa-

tional risk assessment of engineered nanomaterials: limits, challenges

and opportunities. Current Nanoscience, 13(1), pp.55-78.

National Institute for Occupational Safety and Health, 2018. Workplace

Safety & Health Topics. Nanotechnology. https://www.cdc.gov/niosh/top-

ics/nanotech/pubs.html .

Occupational Safety and Health Administration (OSHA), 2018. Safety and

Health Topics. Nanotechnology. https://www.osha.gov/dsg/nanotechnol-

ogy/index.html .

Ponce, A. and Krop, H., 2018. EU Observatory for Nanomaterials: A

Constructive View on Future Regulation.

Privalova, L.I., Katsnelson, B.A., Sutunkova, M.P., Minigalieva, I.A., Gurvich,

V.B., Makeyev, O.H., Shur, V.Y., Valamina, I.E., Klinova, S.V., Shishkina, E.V.

and Zubarev, I.V., 2017. Looking for Biological Protectors against Adverse

Health Effects of Some Nanoparticles that Can Pollute Workplace and

Ambient Air (A Summary of Authors’ Experimental Results). Journal of

Environmental Protection, 8(08), p.844.

Rycroft, T., Trump, B., Poinsatte-Jones, K. and Linkov, I., 2018. Nanotoxi-

cology and nanomedicine: making development decisions in an evolving

governance environment. Journal of Nanoparticle Research, 20(2), p.52.

Cecilia Van Cauwenberghe, PhD, MSc, BAAssociate fellow and senior industry analystTechVision Group, Frost & Sullivancecilia.vancauwenberghe@frost.comww2.frost.comwww.twitter.com/Frost_Sullivan

RESEARCH & INNOVATION

38

Pursuing physics at the forefront of knowledge

On September 14th, 2015, the twin detectors ofthe National Science Foundation’s (NSF) LaserInterferometer Gravitational-Wave Observa-

tory (LIGO) registered a gravitational wave as it passedthrough the Earth. The distortion of space-time – pre-dicted by Albert Einstein one hundred years earlier –was generated as two black holes merged into one,releasing the energy of three suns in the process.

The LIGO observation marked the first time scientistshad ever directly observed a gravitational wave, anachievement that even Einstein himself did not believepossible. LIGO’s success is the result of a high-risk,high-impact investment made over four decades byNSF through its Physics Division, a commitment tobuild what is arguably the most sensitive detectioninstrument ever constructed.

Since that first observation, LIGO has witnessed fouradditional black-hole mergers, followed in August oflast year by the first gravitational wave detection ofpaired neutron stars. That detection was immediatelyfollowed by observations from 70 telescopes aroundthe world, providing new insight into the collision fromvisible light, ultraviolet light, radio waves, x-rays andgamma rays.

The complementary observations brought togethertwo of the three elements in multi-messenger astro-physics: explore the cosmos through observations ofgravitational waves, while collecting radiation acrossthe entire electromagnetic spectrum. The third element,an observation that combines data from elementaryparticles such as neutrinos with electromagnetic data,is on the horizon. As the elements of multi-messengerastronomy are united, humanity will have an unprece-dented, comprehensive view of the most powerfulevents in the universe.

Searching for answers to some of science’s most chal-lenging questions is a core goal for the NSF PhysicsDivision. The study of physics as an intellectual pursuitunderpins all the other physical sciences and increasingly,the life sciences as well, as physicists and biologistsincreasingly cooperate to address problems coveringa range of scales, from molecule to organism.

Since 1975, scientists supported by the NSF PhysicsDivision have made seminal contributions to advancingthe frontiers of the field, from the vast reaches of theuniverse to the tiniest particles of matter, helpingsecure U.S. leadership across science.

We support scientists working at the ATLAS and CMSdetectors, part of the Large Hadron Collider at theCERN laboratory in Switzerland, where three yearsprior to the LIGO discovery, scientists participated inthe discovery of the Higgs boson, the last remainingelementary particle needed to complete the StandardModel of particle physics. Our division also supportsthe National Superconducting Cyclotron Laboratory atMichigan State University and IceCube, an NSF-fundedneutrino detector located at the South Pole.

Those efforts are complemented by our support of NSFPhysics Frontiers Centers, which focus on addressingthe most compelling frontier science questions. In thatsetting, research progresses through the concertedefforts of large, often interdisciplinary, groups workingtogether.

While large facilities are important for discovery, ourdivision’s primary mechanism of support is to individualresearchers and small groups. Our funding almostexclusively supports faculty research programmeshoused at universities and in this way, we foster scien-tific progress while ensuring the propagation of ideas

Denise Caldwell, Director, Division of Physics at the U.S. National Science Foundation (NSF) provides a fascinating perspective on how the organisation is pursuing physics to the forefront of knowledge

RESEARCH & INNOVATION

39

to students and early career faculty, the next generationof researchers. Significant support for students andjunior scientists is inherent to our portfolio, as it is critical to prepare the next generation of researchersfor advanced, high-tech work and innovative new technologies that arise in the quest to answer some ofthe hardest questions that nature can pose.

Through our portfolio of awards, NSF’s Physics Divisionpursues its primary goal “to promote the progress ofscience”, as expressed in the legislation that foundedour agency, the National Science Foundation Act of1950. The awards support research necessary toaddress scientific questions at the frontier of currentknowledge, while at the same time extending andredefining that frontier.

For example, crucial discoveries made by NSF granteeshelped launch and lay the groundwork for quantuminformation science. That effort continues and con-tributes to current, rapid progress toward 21st Centuryquantum-based breakthroughs, from quantum computers to high-resolution sensors that could revolutionise measurement technology.

Across NSF there are examples of investment thatbegin with new ideas generated by the physics com-munity. Those are further informed through workshops,

input from advisory committees, proposal reviews andthe scientific expertise of a group of top-flight pro-gramme directors, each a scientist in his or her ownright. NSF relies on these community-based resourcesto decide where to direct our physics investment.

The breadth of investments is extensive. Through thePhysics of Living Systems program, the division hashelped establish and grow a community of physicistswho look at the living world as a laboratory throughwhich to learn new physics while at the same timeinforming breakthroughs in biological understanding.For example, a study of sand lizards moving throughsand served as a paradigm for motion in granularmedia in general, an important concept for the designof robots for exploration.

Through the Nuclear Physics program, scientists areenhancing our understanding of the forces that drivethe formation of the elements in the universe. And mostrecently, a telegram from the NSF IceCube NeutrinoObservatory (supported both by the Physics Divisionand the NSF Office of Polar Programs) announced thedetection of a high-energy extragalactic neutrino. Thatdetection was quickly followed by observations from asuite of telescopes across the globe, which reportedhigh-energy electromagnetic radiation from the samelocation as the neutrino, yet another breakthrough inmulti-messenger astrophysics.

As such science progresses – whether it be neutrinos,cold atoms, Bose-Einstein Condensates, astrophysicalplasmas, or the origin of the elements in the universe –the Physics Division has had and continues to have, amajor role to play in driving scientific knowledge. ■

Denise CaldwellDirector, Division of PhysicsU.S. National Science Foundation (NSF)Tel: +1 (703) 292 5111https://www.nsf.gov/div/index.jsp?div=PHYwww.twitter.com/NSF

Gravitational waves

Imag

e: N

CSA

Gra

vity

Gro

up

The search for an understandingof the elusive dark matter is oneof the great scientific quests of

our age. In the 1930s, astronomersfirst made determinations of the grav-itational mass of galaxies that weresignificantly larger than expectedfrom the observed luminosities andwrote of dunkle Materie1. Almost 90years later, there is collective evidencethat is substantial and consistentacross seven orders of magnitude indistance scale2, that an unknown substance (dark matter) shapes thelarge-scale structure of the universe.

We believe that dark matter interactsgravitationally and that its non-gravi-tational coupling is of order the weakinteraction3, or less. We expect thatthere must be some new interactionvia a mediator between dark matterand atomic nuclei for dark matter tobe in equilibrium with other matter inthe early universe. We know theapproximate density and velocity ofdark matter in our galaxy. Dark matterdoes not form tightly bound systemslarger than about 1,000 solar masses,but it appears to account for about25% of the mass of the universe, thatis about five times larger than thematter we can see.

The known, uncharged particles, forexample, the neutron or neutrino,cannot account for dark matter. Thefocus over several decades has been tolook for a weakly interacting massive

particle (WIMP) via a rare scatteringfrom an atom in a large detector, typically located deep underground to minimise the rate of backgroundevents. The recoil atom’s energy isdetected. Thus far, no conclusive evidence for WIMPs has been found.The present experiments set theWIMP-atom interaction limit lower thanthe rate of a low-energy4 neutrinointeracting with atoms5. Searches forWIMPS will continue for at leastanother decade. However, there is afundamental limit to this approachdue to the inability to distinguishbetween a neutrino-atom interactionand a WIMP-atom interaction. TheWIMP mass region explored by theunderground experiments typicallyranges from about three protonmasses to about 10,000 of the same.

A complementary experimental thrustin the quest to understand darkmatter, is to search for evidence ofthe mediator of a new interactionbetween our visible world, success-fully described in terms of four forces(gravity, electricity and magnetism,nuclear force and weak force) and theworld of dark matter. This new inter-action would constitute the fifth force.

The simplest mediator widely consid-ered is a dark photon that couples tothe known particles via their electriccharges. The searches involve experi-ments using particle beams deliveredby accelerators to produce the medi-

ator. The mediator decays either into(a) known, detectable particles that aresought (visible decays) or (b) into thedark sector, which are undetectable,but whose presence is deduced byobservation of a large missing energyand momentum in the final-state(invisible decays). The results of thesearches are usually summarised interms of their ability to constrain themediator-to-known-matter couplingstrength and the mediator mass. At the Large Hadron Collider at CERN, Geneva, Switzerland, searchingfor evidence of dark matter is a major activity at the three principalexperiments6.

Recently, there has been a focus onsearching for a mediator with a masslower than the proton mass. Astro-physical observations and observedanomalies in measurements involvingthe muon and nuclear transitions hintat this possibility. Existing experiments,primarily using the decay of the neu-tral pion, have searched inconclusivelyfor evidence of a dark photon. However,a more general fifth force, where thecouplings are no longer simply thecharges, remains a viable possibility.

Our MIT group is focused on search-ing for evidence of a fifth-force, with amediator of mass less than about 10%of the proton’s mass. In collaborationwith colleagues, we have proposedthe DarkLight experiment7 at JeffersonLaboratory8, Newport News, Virginia,

Richard G. Milner from the Department of Physics and Laboratory for Nuclear Science atMassachusetts Institute of Technology provides an absorbing insight into the search for anunderstanding of the elusive dark matter, one of the great scientific quests of our age

Physics: Understanding the elusive dark matter

40

PROFILE

USA to produce the mediator in elec-tron-nucleus scattering and searchingfor visible decays into a positron andelectron. DarkLight requires an intense,bright and halo-free electron beampossible only with a new acceleratortechnology, called an Energy-RecoveryLinac (ERL).

A phase-1 DarkLight experiment hasbeen funded and a search, focused in a specific mediator mass region suggested by a reported anomaly, isin preparation. Jefferson Laboratorypioneered the development of ERLsusing superconducting acceleratortechnology and next-generation ERLsare at present under construction atCornell University, USA9 and at MainzUniversity, Germany10. Searches forevidence of dark matter via low-energysignals in electron scattering are beingplanned at both machines.

In summary, the search for evidenceand understanding of dark matter isan intensive, worldwide researchendeavour by physicists using state-

of-the-art accelerator and detectortechnology on, above11 and beneaththe Earth. Calculations by theoreticalphysicists are essential for the designof experiments with maximum sensi-tivity to uncovering new physics. Thisresearch drives technology develop-ment in high-intensity accelerators,detectors and high-rate data acquisition.

There are major new initiatives under-way worldwide and this area will continue to be a forefront activity forthe foreseeable future, attractingsome of the best and brightest youngminds. This curiosity-driven, funda-mental research into understandingour universe is made possible by the generosity of the taxpayer via government support of fundamentalresearch12.

1 F. Zwicky, Helvetica Physica Acta, 6, 110 (1933)

2 From 1 kpc to 10 Gpc: 1 pc = 3.26 light years = 3.1 x 1016 m.

3 The weak interaction initiates the fusion process in the sun and

drives beta-decay.

4 10 keV.

5 Present best cross-section limit is about 10-46 cm2 at a WIMP mass

of about 50 proton masses.

6 ATLAS, CMS and LHC: home.cern.

7 DarkLight experiment: arxiv.org/abs/1412.4717.

8 Jefferson Laboratory: www.jlab.org.

9 CBETA project: www.classe.cornell.edu/Research/CBETA/Web-

Home.html

10 MESA project: www.prisma.uni-mainz.de/mesa.php.

11 Alpha Magnetic Spectrometer experiment: ams.nasa.gov.

12 The author gratefully acknowledges the support of both the

Office of Nuclear Physics of the Department of Energy and the

National Science Foundation of the United States.

Richard G. MilnerDepartment of Physics and Laboratory for Nuclear ScienceMassachusetts Institute of Technologymilner@mit.eduhttp://web.mit.edu/lns/

41

PROFILE

42

With an extension of operations beyond 2024under discussion and promising opportuni-ties of partnership with the private industry

under development, the long-term future of the Inter-national Space Station (ISS) is not yet written.

Notwithstanding, the preparation of the post-ISS era isa central topic for the partners (U.S., Russia, Europe,Japan and Canada) who, despite multiple exchanges ofideas, declarations and precursor programmes, hadbeen, so far, struggling to build a steady, robust andcommonly-shared vision for the future of humanspaceflight and space exploration. Recent events andannouncements suggest, however, that the state ofaffairs is now progressing as agencies seem to be

converging toward a shared enthusiasm for the Moonand moving ahead with preliminary steps.

In ESPI Brief n 1̊2 “Making Exploration Great Again”,ESPI highlighted the important step forward made bythe American administration in the field of spaceexploration with the signature of NASA’s TransitionAuthorization Act by President Donald Trump in March2017. The document underlined a strong willingnessof the U.S. to engage more actively in human spaceexploration with the development of a Deep SpaceGateway (DSG) in cis-lunar orbit as the next program-matic step to prepare the journey to Mars.

Although building on past projects ( e.g. the Space

Next steps to the Moon: What role for Europe?

RESEARCH & INNOVATION

Sebastien Moranta, coordinator of studies at the European Space Policy Institute (ESPI) sheds lighton Europe’s potential to explore the Moon in co-operation with other great world powers

RESEARCH & INNOVATION

43

Launch System and Orion capsule), U.S. plans markeda turn from the Obama administration’s “Low EarthOrbit-Asteroid-Mars” path and a come back to theformer “Low Earth Orbit-Moon-Mars” Constellationprogramme, supported by the Bush administration.Two major announcements recently highlighted asolidification of this renewed U.S. posture and con-firmed the emergence of an international cooperationdimension.

Firstly, during the meeting of the re-established U.S.National Space Council on 5 October 2017, Vice-PresidentMike Pence delivered an engaging speech calling for areturn to the Moon in cooperation with international andcommercial partners under American leadership. The

Council directed NASA to develop a plan within 45 daysto carry out that revised policy. This presidential decla-ration and the development of a plan by NASA furtherconsolidate both political support and programmaticimplementation of the rehabilitated U.S. strategy.

Secondly and perhaps more importantly, the DSGgained an official international dimension with the signature of a joint statement by Roscosmos and NASAon 27 September 2017 at the 68th International Astronautical Congress in Adelaide, Australia. AlthoughNASA had already been discussing technical optionsfor the DSG concept with ISS partners through the ISS Exploration Capabilities Study Team (IECST) andInternational Spacecraft Working Group (ISWG) duringmeetings in Japan, Canada and Europe in 2017, thejoint statement, focusing at the moment on prelimi-nary studies, marks a noticeable milestone in thedevelopment of an international cooperation structurearound the DSG project.

Regardless of the U.S.’s considerable financial and technical resources, international cooperation will becritical to achieving ambitious objectives, to secure programme stability and to consolidate U.S. leadershipon the global scene. From this perspective, the accel-eration observed recently suggests that the DSG pro-vides a more fertile environment for internationalpartners to contemplate a financially and technicallyconceivable contribution to the programme, than previous plans developed under the Obama adminis-tration did.

This being said, it is important to recall at this stagethat, despite a strong political support, the programmestill has to face major hurdles before becoming a reality.This includes the definition of an architecture meetingvarious objectives from different partners, the allocationof an appropriate budget (which may be challenged by the willingness to also expand ISS operations) and eventually an official endorsement by U.S. andinternational partners’ establishments.

Nevertheless, partners can now build on an existingand robust multinational cooperation framework, suchas the one of the ISS, which will undoubtedly simplifyfuture political and programmatic progress. Overall,

RESEARCH & INNOVATION

44

in a context where drivers seem to outweigh barriers,the DSG seems particularly close to becoming the next stage of international cooperation in space exploration.

Another interesting factor that will certainly have to beclosely looked into is the role that China may play inthe future. As of today, with the Chinese programmeramping up toward the Moon and multiple legal andpolitical constraints for NASA to engage in cooperationwith China, the situation suggests that, following ColdWar competitive era and ISS cooperation era, the thirdera of space exploration will very likely give way to amix of cooperation and competition for leadership.

Regardless of the U.S’s considerable financial and technical resources, international cooperation will becritical to achieving ambitious objectives, to secure

programme stability and to consolidate U.S.leadership on the global scene.

What role for Europe? Europe is already engaged, through ESA (The EuropeanSpace Agency) and at a national level, in technical discussions with NASA and other partners and organisedvarious consultations about the DSG. Maintaining suchactive dialogue will be essential to get an informedunderstanding of the evolution of the project and ofEuropean industrial and scientific communities’ interestand to secure an active participation in the conceptdefinition. Assuming that Europe intends to play aprominent role in the DSG, as it did for the ISS, theacceleration of the project on both the American andinternational scene now requires Europe to bring thetopic to a higher level and to reach a political momentum.

As a partner, European decision-making processobviously depends on the progress of programmeapproval by U.S. institutions; yet, reaching a sharedEuropean position will require a preliminary effort tobuild a political consensus, if not unanimity, among the Member States. Achieving this consensus shortlyis a necessary condition to secure Europe capacity toreact timely to future evolutions on the American andinternational scene and to already position Europe asa key partner.

When looking at the rehabilitated Moon objective andtaking into account that current DSG plans foreseerobotic and human Moon landings, one cannot overlookthe renewed light that is shed on ESA Director General’sMoon Village vision. Indeed, the current dynamic of theinternational space exploration scene could offer aninteresting springboard for Europe to implement, atleast partially, this ambitious vision.

With the declared objective to prepare a journey toMars, the deployment of a Moon Base as a potentiallyEuropean-led component of an international DSG programme would certainly offer a relevant test bedfor the development and validation of key capabilitiesfor future Mars mission such as in-situ resource utili-sation, robotic-human cooperative operations orground base assembly among many others. In general,the role that Europe will hold within the next interna-tional partnership framework will be first and foremostframed by the financial and technical resources it isready to commit. ■

Available for download from the ESPI website at:www.espi.or.at

Sebastien MorantaCoordinator of studiesEuropean Space Policy Institute (ESPI)Tel: +43 1 718 11 180office@espi.or.atwww.espi.or.atwww.twitter.com/ESPIspace

CLICK HERE TO SUBSCRIBEYou can choose from a variety of newsletters from our selection of subject areas

SUBSCRIBE FOR FREEOpen Access Government is pleased to offera FREE subscription service to all our products including our regular newsletters.

We can offer you news and features focusing on a specific topic plus a monthly round-up.

www.openaccessgovernment.org GOVERNMENTOPEN ACCESS

RESEARCH & INNOVATION

46

Space: Reaching out to new heights to benefit mankind

The National Aeronautics and Space Administra-tion (NASA) prides itself in the collaboration oftechnology, science and unique global Earth

observations to provide societal benefits andstrengthen the United States. NASA’s succinct vision forthe past and present has always remained the same.“We reach for new heights and reveal the unknown forthe benefit of humankind.” (1)

Leading the way back to the MoonIn February 2018, NASA Administrator Robert Lightfootspoke about the Fiscal Year 2019 agency budget proposaland remarked how it reflects the US administration’sconfidence that through the leadership of NASA, Americawill lead the way back to the Moon and take the nextgiant leap from where they made that first small stepalmost 50 years ago. Firstly, he explained how thebudget focuses NASA on its core mission and how itwill help to place a renewed focus on the U.S.’s humanspaceflight activities.

“This budget focuses NASA on its core exploration mission and reinforces the many ways that we returnvalue to the U.S. through knowledge and discoveries,strengthening our economy and security, deepeningpartnerships with other nations, providing solutions totough problems and inspiring the next generation. Itplaces NASA and the U.S. once again at the forefrontof leading a global effort to advance humanity’s futurein space and draws on our nation’s great industrialbase and capacity for innovation and exploration.

“This proposal provides a renewed focus on our humanspaceflight activities and expands our commercial andinternational partnerships, while also continuing ourpursuit of cutting-edge science and aeronautics break-throughs at the core of our mission.”

Lightfoot then went on to explain how the UnitedStates is once again on the path to return to the Moon,also with an eye towards Mars. He said that NASA iscalled to refocus existing activities towards exploration,by redirecting funding to innovative new programmes,as well as support for new public-private initiatives.Here, he expands on these ambitious goals in his ownwords, as well as explaining how the InternationalSpace Station (ISS) will be the cornerstone for pushinghuman presence further into space.

“Webb is the highest priority project for theagency’s Science Mission Directorate and the largestinternational space science project in U.S. history.

All the observatory’s flight hardware is nowcomplete, however, the issues brought to light withthe spacecraft element are prompting us to take the

necessary steps to refocus our efforts on thecompletion of this ambitious and complex

observatory.”

“We are leveraging multiple partners both here athome and internationally in developing a sustainableapproach where the Moon is simply one step on our trulyambitious long-term journey to reach out farther into thesolar system to reap the economic, societal and expand-ing knowledge benefits such an endeavour will bring.

“We’ve used the International Space Station (ISS) as thecornerstone for pushing human presence farther intospace, with a horizon goal of humans to Mars. Thisincludes learning about the human physiology ofspaceflight and enabling new industry partners tobring to bear their capabilities and emerge as leaders…to help us on this journey. The commercial cargo andcrew work continues through the life of the Interna-tional Space Station in the budget.” (2)

Open Access Government reveals the exciting mission of the National Aeronautics and SpaceAdministration (NASA) and how the United States aims to reach out to new heights to benefit mankind

when it comes to exploring space and beyond

RESEARCH & INNOVATION

47

Lightfoot adds that while the Fiscal Year 2019 agencybudget proposal does not provide funding for anOffice of Education, NASA’s mission successes will nevertheless continue to inspire the next generationto take up studies in science, technology, engineeringand mathematics. Lightfoot believes that the next generation will become the diverse workforce of thefuture, where aerospace careers are concerned. Hewent on to develop this point, adding that NASA willhelp the United States lead the way in the space sector,despite the hard choices that have had to be made.

“We will use every opportunity to engage learners inour work and the many ways it encourages educators,students and the public to continue making their owndiscoveries.

“We can’t do everything and as always, we’ve had tomake hard choices, but we will continue to forge newpaths and partnerships that strengthen our industrialbase and our engagement with other nations toachieve challenging goals that advance our capabilitiesand increase our security and economic strength.NASA will continue to deliver on the promise of U.S.ingenuity and proven leadership in space.”

In other interesting news, we also find out that NASA’sJames Webb Space Telescope is undergoing final integration and test phases that will require more timeto ensure a successful mission. Following an independentassessment of remaining tasks for the highly complexspace observatory, the launch is now targeted foraround May 2020.

Lightfoot comments more on this ambitious aspect ofNASA’s work: “Webb is the highest priority project forthe agency’s Science Mission Directorate and thelargest international space science project in U.S. history. All the observatory’s flight hardware is nowcomplete, however, the issues brought to light with thespacecraft element are prompting us to take the nec-essary steps to refocus our efforts on the completionof this ambitious and complex observatory.”

Also, worth noting is that Webb has already completedextensive tests to make sure it reaches its orbit safely,

at almost one million miles from Earth. As with allNASA projects, rigorous testing takes time, which ofcourse, increases the likelihood of the mission beingsuccessful. Thomas Zurbuchen, an associate adminis-trator for NASA’s Science Mission Directorate, comments on this point: “Considering the investmentNASA and our international partners have made, wewant to proceed systematically through these lasttests, with the additional time necessary, to be readyfor a May 2020 launch.” (3)

NASA believes that the James Webb Space Telescopewill be the world’s premier infrared space observatoryand the biggest astronomical space science telescopeever built, complementing the scientific discoveries ofNASA’s exciting missions, such as the Hubble Space Telescope. Webb will explain the mysteries of the solarsystem, look beyond to distant worlds around otherstars probe the mysterious origins and structures of theuniverse, as well as our place in it. This fits in perfectlywith NASA’s mission to: “reach for new heights andreveal the unknown for the benefit of humankind.” ■

References

1 https://www.nasa.gov/about/whats_next.html

2 https://www.nasa.gov/press-release/nasa-acting-administrator-

statement-on-fiscal-year-2019-budget-proposal

3 https://www.nasa.gov/press-release/nasa-s-webb-observatory-

requires-more-time-for-testing-and-evaluation-new-launch

Open Access GovernmentJMiles@openaccessgovernment.orgwww.openaccessgovernment.orghttps://twitter.com/OpenAccessGov

RESEARCH & INNOVATION

48

Developmental biology: Fulfilling thepromise of Organoids

Afew years ago, a headline and a picture capturedthe imagination of the world: scientists had beenable to grow a miniature version of a human

brain in a dish in the lab. Understandably, such a featunleashed the imagination and the hope of people,particularly those with disease. It did not matter thatsimilar findings had been made and reported with themouse before, the adjective ‘human’ always has animpact on anything science related. Soon the word wasout that this would revolutionise the study of mentalhealth, pave the way to cure disease and, of course,there were the inevitable claims to the cure of cancer.

These ‘mini brains were part of a menagerie of coun-terfeits of human organs and tissues grown in the labincluding disembodied eyes, livers, intestines and pancreas that came to light with this finding. How wasit possible? What does it mean? It is sometimes difficultto disentangle hype and hope in scientific research but,in this area, one needs to, as the potential gains areenormous but only if they are built on sound founda-tions and not on false expectations. For the moment,understanding mental health with mini brains is not onthe cards, though understanding something about howcells make brains is. If you want to build tall edifices youneed good foundations.

What are Organoids?The structures reportedly grown in the lab are knownas ‘organoids’, because they are imperfect replicas ofreal organs. They result from remarkable and still littleunderstood, abilities of special cells, stem cells. Cells donot live forever, and most tissues of our body require aconstant replenishment. This is what stem cells do.They manage to keep themselves going, while providinga constant stream of material to repair damage andkeep organs functioning.

For example, every day your body produces 200 trillionred blood cells to keep you fit and stem cells in yourintestine 30 billion cells to deal with your digestion; thisis the awesome power of these cells. The ultimate stemcells are embryonic stem cells (ESCs), derived from veryyoung embryos they can be grown almost indefinitelyin culture and, at any time, any single one of them cangenerate a whole organism.

Organoids are the result of the potential of stem cells.It is not yet possible to grow blood in the laboratory, butintestinal and embryonic stem cells are paving the wayfor much of what we shall be able to do in the future. Asingle intestinal stem cell can produce a rough copy ofthe adult intestine, an intestinal organoid, in vitro andsteering ESCs in defined environments with specificchemicals, can produce rudimentary kidneys and lungs.It is these ESCs that were used to build mini brains.However, for now, we cannot control these processesjust watch them unravel.

The promiseIt is early days. Organoids are, in most instances, tooimperfect to be of use but the goal is to use these cellular contraptions to understand the disease, testdrugs and even one day, create replacements for sometissues and organs.

One of the main problems of regenerative medicine, inwhich we can replace a damaged organ or tissue for ahealthy one, is the matching of tissues between a donorand a patient. The work with organoids promises tosolve this problem with the use of so-called inducedpluripotent stem cells (iPSCs): ESCs generated by con-verting adult cells from an individual into ESCs whichthen, in principle, can be transformed into any tissueand organ.

Professor of Developmental Mechanics at the Department of Genetics, University of Cambridge, Alfonso Martinez Arias shares his expert view on Organoids, within the field of developmental biology

RESEARCH & INNOVATION

49

Thus, iPSCs allow generating tissue matches for thepatient as the donor is genetically the same. There islittle question that this will happen in the future, but itwill not happen faster because of ill-founded claimsthat it can happen, and we should avoid listening tosiren chants that are so frequent in this field.

One of the roadblocks to progress is ‘reproducibility’.In biology, when something works it is capable of makingmany good copies of itself; behold embryos buildingorganisms. Unfortunately, most organoids now are lowfrequency, heterogeneous and not functional. To breakthis impasse, we need more basic research. Two fieldswill have an impact in progress: developmental biology – that teaches us how animals develop – andengineering – that tells us how to control processesand make them efficient.

The way to the promiseFor now, however, while we realise the promise ofiPSCs, intestinal organoids, probably the mostadvanced and reproducible in the field of humanorganoids, are providing a reference for some of thework that can be done. In a recent landmark study, sci-entists made intestinal organoids from cancer patientsthat were undergoing treatment and observed that the

in vitro avatars responded to the treatments as theindividuals did. This opens enormous possibilities forthe use of these organoids to rapidly test drugs andtreatments highlighting the potential that lies ahead.

The emerging organoid field at the crossroads of stemcell, developmental biology and engineering will trans-form our understanding of how cells build organs andtissues and in doing so will pave way for significantapplications in biomedical research. For this to fulfil itspotential we should resist the allure of statements thatpromise much in a short-term present and investing insolid knowledge for a long-term future. ■

Alfonso Martinez AriasProfessor of Developmental MechanicsDepartment of Genetics, University of Cambridge, UKTel: +44 (0)1223 766 742ama11@hermes.cam.ac.ukhttp://bsdb.org/www.twitter.com/AMartinezArias

It is increasingly clear that electricalimpulses – action potentials – haveprofound effects on virtually all

organs regulated through neurons thatcommunicate through such impulses.One such target organ that is regulatedby nerve-dependent electrical impulsesis the skeletal muscle in vertebrate ani-mals. In fact, the induction and mainte-nance of many properties of skeletalmuscle are evident by the dramaticwasting and debilitating conditions thatresult in humans affected by geneticand degenerative diseases, trauma,injury and the ageing of the neuromus-cular system1.

Conversely, we know that the applica-tion of neuromuscular electrical stimu-lation evokes involuntary musclecontractions and supports musclemass maintenance in conditions ofmuscle disuse2. To date, research frommany labs continues to uncover waysby which the phenotypic and functionalproperties of skeletal muscle respondto changes in innervation – under dif-ferent environmental conditions fromearly development to ageing.

One fundamental question thatremains largely unanswered is how dothe amounts or patterns of electricalactivation regulate the diversity of themany muscle fibre types? Specifically,how is neural input, coupled to the

regulation of transcriptional and post-transcriptional changes of musclegenes that affect metabolism, mor-phology and contractility is unknown?

Moreover, the role that electrical activ-ity patterns may plan in the extremetransformation of skeletal musclefrom a force-generating tissue to aspecialised energy-producing, but notforce-generating, tissue has onlyrecently been addressed. Here, anevolutionary myogenic “novelty” ishighlighted to raise interest in pheno-typic outcomes of distinct nerve-myo-genic tissue systems maintained byunique electrical impulse patterns.

In the electric fish Sternopygus macru-rus, some skeletal muscle fibres exhibitan extreme phenotypic plasticity by

losing their contractility during normaldevelopment to give rise to electro-cytes (ECs), the specialised cells thatgenerate electricity and make up theelectric organ (EO)3. ECs are also uniquein that they are electrically driven by apopulation of spinal motoneuronscalled electromotoneurons (EMNs)4 ata continuous rate of 50-200 Hz5.

By comparison, somatomotoneurons(SMNs) in teleost fish innervatemuscle fibres that are driven intermit-tently and at frequencies lower than 8Hz6. We tested the idea that differ-ences in activation patterns betweenSMNs and EMNs account for the dif-ferences in muscle and EO pheno-types in the adult7, by eliminating allmotoneuronal activity to the muscleand EO tissues in adult fish.

Intro: The electrical activity as a regulator of induction and the maintenance of specialisedtissues is placed under the spotlight by Graciela A. Unguez at the Department of Biology,New Mexico State University in the United States

50

PROFILE

Electrical activity as a regulator of induction and the maintenance of specialised tissues

Figure 1. Electrically inactive electrocytes make new sarcomeres. A: Electron micrograph showsa sarcomere bundle in the electrocyte after spinal transection (see cartoon depicting inactivationof EMNs and SMNs). N, nucleus. B: Clustered anti-MHC labelling pattern inside electocyte (EC),a pattern corresponding to sarcomeric clusters shown in electron micrographs. Mitochondria(arrows) are located peripherally near the cell membrane. (Unguez and Zakon, 1998b).

Interestingly, this treatment resulted in the re-expression of sarcomericcontractile proteins and formation ofsarcomeres de novo within matureelectrocytes (Fig 1). Furthermore, inthe absence of neural input themuscle-to-electrocyte conversion doesnot take place8.

To directly test the role of electricalactivity on EC and its myogenic proper-ties, we have pioneered a 3D-printedwearable backpack system that allowsunderwater chronic in vivo electricalstimulation (Fig 2)9. The stimulationpattern can be remotely controlledusing infrared light with a TV remotecontroller. The stimulation pattern isadjustable by programming a micro-controller. The stimulator circuit isplaced on a printed circuit board,which is placed in a waterproof circuitcase attached to the backpack9.

Immunolabeling experiments of tailsreceiving different activity patternssuggest an upregulation of sarcomericmyosin heavy chain in ECs in shamcontrols (spinal transected only; Fig 2)

and stimulated (spinal transected andstimulated; Fig 2) tails. The ability toimpose a wide range of electrical activation patterns will further ourknowledge of how specific features ofelectrical stimulation may affect dif-ferentiation, maintenance and trans-differentiation of the skeletal muscleprogram.

Other myogenically derived tissueswith unique non-force producingfunctions such as the heater organ inbillfishes10 and sound organ in toad-fish11 also receive neural input, that isdifferent from that of skeletal musclefibres. Whether specific electricalimpulse patterns induce and maintainthe muscle-to-heater cell and muscle-to-sonic muscle cell phenotypes inthese tissues will be interesting withrespect not only the degree of plastic-ity of the skeletal muscle phenotype,but also the evolution of “novel” ver-tebrate tissues. Learning more aboutthe electrical activity patterns in awide range of nerve-target organ phe-notypes is particularly relevant in thecurrent interest in the development

and use of electroceuticals – the useof electrical impulses to modulate thefunction and repair of body tissues12.

Funding source

This research supported by NIH grant 1SC1GM092297-01A1 andNSF INSPIRE Award CNS-1248109 (GAU).

References

1 Robinson LR. (2000). Traumatic injury to peripheral nerves. Muscle& Nerve. 23:863-873.

2 Dudley-Javoroski S and Shields RK. (2008). Muscle and bone plasticity after spinal cord injury: review of adaptations to disuseand to electrical muscle stimulation. J Rehabil Res Dev. 45:283-96.

3 Unguez GA and Zakon HH. (1998a). Phenotypic conversion of distinct muscle fiber populations to electrocytes in a weakly electricfish. J. Comp. Neurol. 399:20-34.

4 Bennett MVL. (1971). Electric Organs. In Hoar, WS. and Randall,DJ., eds., Fish Physiology, Vol. 5, Academic Press, pp. 347-491.

5 Mills A, Zakon HH, Marchaterre MA and Bass AH. (1992). Electric organmorphology of Sternopygus macrurus, a wave-type weakly electricfish with a sexually dimorphic EOD. J. Neurobiol. 23:420-432

6 Rome LC, Syme DA, Hollingworth S, Lindstedt SL and Baylor SM.(1996). The whistle and the rattle: the design of sound-producingmuscles. Proc. Natl. Acad. Sci. USA 93:8095-8100.

7 Unguez GA and Zakon HH. (1998b). Reexpression of myogenicproteins in mature electric organ after removal of neural input. J.Neurosci. 18:9924-9935.

8 Unguez GA and Zakon HH. (2002). Skeletal muscle transformationinto electric organ in S. macrurus depends on innervation. J Neurobiol. 53:391-402.

9 Unguez GA, Duran C, Valles-Rosales D, Harris M, Salazar E, McDowell M, and Tang W. (2015). 3D-Printed Wearable BackpackStimulator for Chronic in vivo Aquatic Stimulation. Conf Proc IEEEEng Med Biol Soc. 2147-2150.

10 Block BA. (1991): Evolutionary novelties: How fish have built aheater out of muscle. Amer. Zool., 31: 726-742.

11 Nuki A and Somiya H. (2007): Innervation of sonic muscles inteleosts: occipital vs. spinal nerves. Brain, Behavior and Evolution,69: 132-141.

12 Famm K, Litt B, Tracey KJ, Boyden ES and Slaoui M. (2013). Drugdiscovery: A jump-start for electroceuticals. Nature, 496: 159-161.

Graciela A. Unguez, PhD Professor of BiologyNew Mexico State UniversityTel: +1 (575) 646 7963gunguez@nmsu.edu

51

PROFILE

Figure 2. Wearable 3D printed backpack by free-swimming fish with remote controlledstimulation. Top left: Fish wearing a backpack. Bottom left: Real-time recorded electric field inreal-time when changing stimulation patterns and testing remote control of stimulator. Rightpanel: Immunolabeling for sarcomeric myosin (arrows) in sham and tails electrically stimulatedwith an electric organ-like (EO) or a slow-twitch muscle like (Slow) pattern. mm, muscle.

4-day Sham

4-day Stim “EO”

4-day Stim “Slow”

RESEARCH & INNOVATION

52

Biology: Enabling discoveries forunderstanding life

The clear mission of the Directorate for BiologicalSciences (BIO) at the U.S. National Science Foundation (NSF) is to enable discoveries for

understanding life. BIO-supported research furthersthe frontiers of biological knowledge, increases ourunderstanding of complex systems and provides a the-oretical basis for original research in various scientificdisciplines.

BIO supports research to advance our understandingof the principles and mechanisms that govern lifeitself. The research studies of BIO extend across sys-tems that encompass biological molecules, cells, com-munities, tissues, organs, organisms, populations andecosystems up to and including, the global biosphere.In addition, it is worth noting that BIO is divided intofive divisions, which are:

The Division of Biological Infrastructure (DBI); •

The Division of Environmental Biology (DEB); •

The Division of Integrative Organismal Systems (IOS); •

The Division of Molecular and Cellular Biosciences•(MCB) and;

The Emerging Frontiers (EF) Division. •

To deal with ecological questions that cannot be resolvedwith short-term observations or experiments, NSF estab-lished the Long Term Ecological Research Program (LTER)way back in 1980. This research is located at specific siteschosen to represent major ecosystem types or naturalbiomes. It places focus on the study of ecological phe-nomena over long periods of time. According to the NSF,long-term studies are crucial to arrive at an integratedunderstanding of how populations, communities and

other components of ecosystems interact, as well as totest ecological theory.

One recent example of LTER’s work can be found con-cerning scientists at the National Science Foundation(NSF) Bonanza Creek Long-Term Ecological Research(LTER) site in Alaska, one of 28 such LTER sites. Here,they are working to understand interactions betweenchanging tree lines and plant-eating animals, like thesnowshoe hare.

“This study is a reminder that there will be winners andlosers as climate changes and that species’ interactionswith their environments will play a critical role in howthe landscape changes,” said Colette St. Mary, an NSFLTER programme director.1

Another example of LTER’s research is when scientistswanted to find out where the greatest risk of a mos-quito bite is if you live in Baltimore, Maryland. Studyingin Baltimore neighbourhoods where residents havelow, median or high incomes, the scientists concludedthat people are most at risk in areas with medianincomes.

Providing insight into this fascinating area of research,Doug Levey, a director of the National Science Founda-tion’s (NSF) Long-Term Ecological Research (LTER) program says: “Nature is all around us, including indowntown Baltimore. In this case, urban landscapesprovide excellent habitat for rats and mosquitoes.Understanding how they live can help protect us from diseases.”

Shannon LaDeau, a scientist at the Cary Institute ofEcosystem Studies in Millbrook, New York and co-authorof the paper, explains that: “Mosquitoes are a globalthreat to public health. We’re interested in knowing how

The mission of the Directorate for Biological Sciences (BIO) at the U.S. National Science Foundation(NSF), is to enable discoveries for understanding life, as Open Access Government discovers

53

urban landscape features and social patterns influencemosquito biting behaviour.”

“Our findings suggest that median-income areas arewhere people are most at risk of being bitten,” addsLaDeau. “There are plenty of people for mosquitoes tobite and residents may be more likely to spend time incommunity gardens and shared green spaces, whichmakes them available to mosquitoes.”2

Staying on the subject of ecology, it’s worth looking atanother example of NSF’s Long-Term EcologicalResearch (LTER) Program’s recent research. It concernsa study which ties phosphorus loading in lakes toextreme precipitation events. Going into more detail,the study shows that April showers contribute to toxicalgae blooms, dead zones and declining water qualityin U.S. coastal waters, reservoirs and lakes.

“This is an important example of how changes in oneaspect of the environment, in this case, precipitation,can lead to changes in other aspects, such as phospho-rus load,” says Tom Torgersen, director of the NationalScience Foundation’s (NSF) Water, Sustainability and Climate program, which, along with NSF’s Long-TermEcological Research (LTER) program, funds the research.

David Garrison, chair of NSF’s LTER Working Group,comments: “This study’s findings, which depend on

long-term data, are important to maintaining waterquality not only today, but into the future.”3

The above examples tell us about the guiding principlesof LTER, in that long-term studies are vital to gain an inte-grated understanding of how populations, communitiesand other components of ecosystems interact. They alsobring us back to the fundamental point that BIO researchalways aims to increase our understanding of the principles and mechanisms that govern life on earth. ■

References

1 https://www.nsf.gov/discoveries/disc_summ.jsp?cntn_id=244505&

org=NSF&from=news

2 https://www.nsf.gov/discoveries/disc_summ.jsp?cntn_id=244938&

org=NSF&from=news

3 https://www.nsf.gov/news/newsmedia/ENV-discoveries/LTER-discove-

ry-series.jsp

Open Access GovernmentJMiles@openaccessgovernment.orgwww.openaccessgovernment.orghttps://twitter.com/OpenAccessGov

RESEARCH & INNOVATION

If you ask most people whethermammals can regenerate or notthey would surely answer no. After

all, many people have scars on theirskin from wounds, burns or surgery,amputated limbs do not regenerate,tumour removal leaves large tissuedefects and many people die from thefibrosis resulting from a heart attack.But if you scour the scientific literaturefor regenerative ability in mammalsthere seems to be quite a number ofdiverse reports. The annual replace-ment of deer antlers is surely one ofthe most conspicuous examples ofregeneration and shows many fea-tures typical of complex tissue regen-eration, such as limbs in lowervertebrates including the formation ofa blastema (see The Champion ofRegenerative medicine – the Axolotl).

The digit tips of children, mice, ratsand monkeys also regenerate by theformation of a blastema. Holespunched through the ears of rabbits,cows, pigs, chinchillas, pikas, haresand bats are said to regenerate so thisincludes cartilage in the middle of theear and skin over the top. Mostimpressively for a mammal, new-bornmice can regenerate cardiomyocytesfollowing a myocardial infarction,although this ability is lost by sevendays after birth.

And of course, the mammalian liverregenerates (as the ancient Greeks inthe legend of Prometheus knew), notby the formation of a blastema, but by

a process known as compensatoryhypertrophy, such that if a lobe of theliver is removed the remaining liverlobes grow and expand to replace thelost function. This process involves thecoordinated up-regulation of cytokine,growth factor and metabolic networksresembling true regeneration. Simi-larly, the lung can undergo compen-satory hypertrophy after the removalof one or more of the lobes, in exactlythe same manner as the liver.

Although tantalising, these regenera-tive abilities are too sporadic to provideus with a new model of mammalianregeneration which we clearly need forregeneration studies so that directcomparisons between the damagedorgans (e.g. the skin or the heart) of anadult regenerating mammal and anadult non-regenerating organ (e.g. thelab mouse or human) can be made. Weneed these directly equivalent compar-isons to eliminate differences due todevelopmental age or evolutionary dis-tance to identify the molecules that arecausing scarring and fibrosis in the typ-ical mammal and may not be presentin a regenerating mammal. We wouldthen want to counteract these fibroticmolecules in a human with the inten-tion of inducing regeneration and/orpreventing scarring.

Excitingly, it now appears that we mayhave discovered an adult mammalwhich can regenerate many organs,namely the spiny mouse of the genusAcomys (Fig. 1A). There are several

species of these mice which inhabitdesert areas in North Africa, the east-ern Mediterranean and southwardsinto Kenya. Along with several col-leagues (Ashley Seifert, Megan Seifert,Jake Goheen) we found that thesespecies could frequently be trappedwith large segments of skin missingfrom their backs and when these ani-mals were kept the wounds regener-ated perfectly and replaced the hairs,sebaceous glands, erector pili musclesof the hairs and the dermis withoutscarring (Fig. 1B).

“Excitingly, it now appears that wemay have discovered an adultmammal which can regenerate manyorgans, namely the spiny mouse of thegenus Acomys.”

In contrast, a similar wound in the labmouse produces a scar covered by ahairless, glassy wound epithelium (Fig.1C) just as humans do. In further skinexperiments using full thickness ther-mal injuries rather than a physicalwound, the Acomys skin regeneratesperfectly with a full complement ofhairs and no scar (Fig. 1D), whereasthe lab mouse produces a hairlessscar (Fig. 1E). Histologically theserepairing skin tissues look remarkablysimilar in terms of the dermis. A sec-tion of Mus dermis four weeks after aburn injury is shown in Fig. 1F coveredby a uniform epithelium.

In contrast, a regenerated Acomysburn injury at the same time point is

Malcolm Maden, Department of Biology & UF Genetics Institute, Gainesville, Florida, USA shareshis expert opinion on the amazing spiny mouse, the champion of mammalian regeneration

The amazing spiny mouse, thechampion of mammalian regeneration

54

PROFILE

shown in Fig. 1G and many regenerat-ing hair follicles spread across thewound epithelium can be clearly seen.However, there are molecular differ-ences in the dermis of the regenerat-ing and scarring dermis in terms ofthe collagens and other extracellularmatrix molecules that are deposited,which may play an important role.

In the same series of experiments, wealso showed that large 4mm holespunched through the Acomys earcould regenerate completely, replacingnot only the skin but also the cartilagein the middle of the ear (Fig. 2A, B). Thisprocess of ear punch regenerationinvolves the formation of a blastema(Fig. 2C) which shows a remarkablesimilarity to the blastema of the regen-erating amphibian limb (Fig. 2D andThe Champion of Regenerativemedicine – the Axolotl). This shows the truly epimorphic nature of thismammalian regenerative event.

An even more surprising result wasseen in these skin regeneration stud-ies because unlike the human skin,the rodent skin has a layer of skeletalmuscle at the base called the pannicu-lus carnosus (Fig. 2E). Normally, skele-tal muscle cannot regenerate inmammals when a hole is madethrough the tissue. This is known as avolumetric muscle loss and frequently

occurs after injuries such as gunshotwounds. But when the spiny mouseskin regenerates the missing segmentof the panniculus carnosus regener-ates as well (Fig. 2F). This is a veryexciting result and may lead to discov-eries in how to regenerate missingmuscle segments in humans.

In addition to the skin, the ear andskeletal muscle the Acomys heart alsoshows regenerative properties. In the lab mouse and humans after amyocardial infarction the damageimmediately causes a huge drop inthe ability of the ventricle to pumpblood, known as the ejection fractionfrom which it does not recover. Heartcells at the site of the ischemia die andlocal fibroblasts proliferate and laydown a scar.

The reduced ejection fraction inducesthe ventricle to pump more blood andas a result, the ventricle wall thins dra-matically. In adult Acomys, however,the immediately decreased ejectionfraction caused by the myocardialinfarction recovers over a period of 14days to return to pre-MI levels. Themissing capillaries are regeneratedand there is a vastly reduced level ofscarring. Future studies will be aimedat determining whether heart cellscan divide and replace the ischemictissue.

Our studies to date on the regenera-tive properties of the adult Acomysskin, skeletal muscle, ear and hearthave revealed a striking lack of fibrosisin each tissue at the site of damageand this allows the natural regenera-tive abilities of cells and tissues to takeplace unhindered. We suggest thatAcomys is a great candidate for anadult mammalian regeneration modelfor use in regenerative medicine withthe ultimate aim of discovering whythis genus can regenerate and extrap-olating this knowledge to generatetherapies for the benefit of humans.

Malcolm MadenProfessorDepartment of Biology & UF Genetics InstituteTel: +1 352 273 7875malcmaden@ufl.edu

55

PROFILE

Figure 1 Figure 2

RESEARCH & INNOVATION

56

The health effects of exposure tochemicals and other substances

The National Toxicology Program is a world leaderin providing scientific information to help evaluateand better understand the potential health

effects of exposure to chemicals and other substances.

The National Toxicology Program (NTP) was establishedin 1978 to strengthen the science base in toxicology,support the development of improved testing methodsand provide information about potentially toxic chem-icals to health and research agencies, scientific andmedical professionals and the public.

Based at the National Institute of Environmental HealthSciences (NIEHS) in North Carolina, the NTP coordinatestoxicology and testing across the US Department ofHealth and Human Services.

Over the years, it has become a world leader in thedevelopment of techniques and testing regimes toevaluate the health-related effects of environmentaland occupational substances. This includes short andlong-term toxicology/carcinogenicity studies to addressthe gap in knowledge concerning the toxicity of substances in the environment, along with chemicaldisposition and toxicokinetic studies, which assess theabsorption, distribution, metabolism and excretion ofsubstances in laboratory animals.

The long-term goal of these studies is to gather datato better assess the structure-activity relationships thatdetermine chemical disposition in the test subjectsand, ultimately, better interpret the significance of thisdata to humans.

The NTP has also developed a range of genetic toxicologytesting regimes to evaluate the potential of environ-mental and occupational substances to damage DNA,

as well as toxicogenomic studies to examine howchemicals can change the expression of genes, proteinsand metabolites in living cells. Measuring genome-widechanges in affected tissues can help to identify markersof toxicity or disease and improve understanding howgenetic variations between individuals can influencetheir sensitivity to substances.

In addition, the NTP has established techniques fortesting the potential of substances to affect the devel-opment of and cause damage to, reproductive organsystems and tests to determine the toxic effects ofexposure on the immune and nervous systems.

In recent years, a key focus for the NTP has been thedevelopment of new, alternative methods of toxicologyresearch that will reduce, replace or refine the use oflaboratory animals. Systems currently under develop-ment include computer-based predictive toxicologymodels, genetically engineered in vitro cell systems,microchip array technology, non-mammalian speciesand transgenic species.

In March, at the Society of Toxicology’s 57th AnnualMeeting and ToxExpo in San Antonio, Texas, the Inter-agency Coordinating Committee on the Validation ofAlternative Methods (ICCVAM), a committee under theNTP Interagency Centre for the Evaluation of Alterna-tive Toxicological Methods (NICEATM), continued therollout of a strategic roadmap for establishing newmethods to evaluate the safety of medical and chemicalproducts while reducing or eliminating the need foranimal testing.

The roadmap, which was drawn up with input from 16federal agencies, multiple interagency work groupsand the public, aims to create a framework to support

Open Access Government details the work of the National Toxicology Program, a world leader inproviding scientific information to help evaluate and better understand the potential health effects

of exposure to chemicals and other substances

RESEARCH & INNOVATION

57

the development of, foster confidence in and ensurethe adoption of these new approach methodologies(NAMs). The implementation of the roadmap is currentlyfocused on three areas: acute systemic toxicity; eyeand skin irritation; and skin sensitisation.

Temporary, ad hoc work groups are playing a key role in implementation by undertaking specific tasksidentified by the ICCVAM as being important for thedevelopment or validation of NAMs.

Chairs representing agencies that use or require datafrom an area of interest set their group’s scope andcharge. Once approved by the ICCVAM, member agen-cies and partners from the International Cooperationon Alternative Test Methods (the European Union Reference Laboratory for Alternatives to Animal Testing,the Japanese Centre for the Evaluation of AlternativeMethods, the Korean Centre for the Evaluation of Alternative Methods and Health Canada) are invited toparticipate.

The work groups will develop detailed implementationplans to meet the roadmap’s goals based on four keyelements: definition of testing needs; identification ofany available alternative tests and computer models;a plan to develop integrated approaches to testing and

assessment and defined approaches for interpretingdata; and a plan to address both scientific and non-sci-entific challenges, including regulatory issues such asinternational harmonisation.

“This roadmap represents a coordinated effort by federal government agencies to proactively developand adopt new approaches to toxicity testing, ratherthan having changes driven by external influences”, saysWarren Casey, PhD, director of the NTP InteragencyCentre for the Evaluation of Alternative ToxicologicalMethods.

“If actionable progress in this area is going to happen,the agencies need to take the lead and that is exactlywhat they are doing with this roadmap.” ■

For more information, please visit https://ntp.niehs.nih.gov/

Open Access GovernmentJMiles@openaccessgovernment.orgwww.openaccessgovernment.orghttps://twitter.com/OpenAccessGov

Worldwide, the frequencyand severity of wildfires areincreasing due to changes in

temperature and precipitation patternsconsistent with climate change andchanges in land use, particularly at therural-urban interface. The fire problemis particularly acute in Northern California, which has experienced asignificant increase in wildfire fre-quency over the past few decades. Inaddition to the risk of injury, loss oflife and destruction of property, thereis increasing appreciation that wild-fires pose significant environmentalhealth threats.

Much of the research on adverse healthimpacts of wildfires has focused onwildfire smoke and recent reviews of this scientific literature concludethere is strong evidence that wildfiresmoke exacerbates respiratory ail-ments, including asthma and chronicobstructive pulmonary disease andcontributes to cardiovascular disease.What is less well understood, however,is the potential impacts of wildfiredebris on human, animal and ecosys-tem health.

Debris from urban wildfires is partic-ularly worrying because these firesinvolve the combustion of buildingmaterials, electronic equipment,chemicals and industrial equipmentthat contain toxic chemicals such asmetals, pesticides and persistentorganic pollutants (POPs).

POPs of concern include the polychlo-rinated biphenyls (PCBs) and poly-brominated diphenyl ethers (PBDEs).PCBs are man-made chemicals thatwere widely produced for diverseindustrial applications beginning inthe 1930s until their production wasbanned in 1979 because of their carcino -genic potential and developmentalneurotoxicity.

PCBs are found in older electricaltransformers, capacitors and light bal-lasts still in use today and in caulkingmaterial, paints and sealants used toconstruct municipal buildings andhomes prior to the 1979 ban. PBDEsare also man-made chemicals thatwere widely used as flame retardantsin various consumer products includ-ing foam, plastics and textiles.

Due to health concerns, the state ofCalifornia began prohibiting the man-ufacture, distribution and processingof flame-retardant products containingpenta- and octa BDEs in 2006. However,human exposure continues becausemany households have products pro-duced prior to the ban. Moreover,PBDEs are not chemically bound tomaterials and therefore, leach out ofhousehold products into the environ-ment. Like PCBs, PBDEs persist in theenvironment and biomagnify up thefood chain.

Pyrolysis results in the release of PCBsand PBDEs into the environment.

Increased PCB concentrations havebeen documented in air masses asso-ciated with fires. The ash from theSeptember 11th 2001 World TradeCenter fire in New York City was foundto contain excessive PBDE levels. Thecombustion of man-made materials,particularly electronic equipment, isalso associated with the mobilisationof metals. For example, ash debrisfrom the California wildfires from 2007contained toxic metals, specifically,arsenic, cadmium, copper and lead, atlevels associated with long-term healtheffects in animals and humans.

Urban wildfires not only release toxicchemicals, but also generate haz-ardous compounds, such as dioxinsand dibenzofurans, which are formedby the combustion of organic matter,such as paper and wood. Once theburning has stopped, re-volatilisedchemicals distribute out of the atmo-sphere onto soils, vegetation and surface water, while non-volatilechemicals are deposited as ash. Theincreased environmental availabilityof these chemicals increases the riskof groundwater contamination, theuptake by plants and ingestion by animals, culminating in increased riskof human exposure for months toyears. Thus, a question of growing con-cern is whether urban wildfires posea significant long-term environmentalhealth risk via chemical contaminationof home-grown produce or animal-derived foods.

Birgit Puschner and Pamela Lein from the University of California, Davis share their expert viewson the impacts of urban wildfire on chemical contamination in small backyard agriculture

The potential long-term environmental healthconsequences of urban wildfire debris

58

PROFILE

This concern is heightened by lay articles in the New York Times andSan Francisco Chronicle and peer-reviewed publications reportingincreased human exposure to lead(Pb) through consumption of eggsproduced by backyard chickens. Eggs and eggs products are one of the most consumed foods worldwide.In the United States, individuals con-sume an average of 24 grammes ofeggs per day. Backyard chicken own-ership has grown in the United Statesin part because the eggs from back-yard hens are perceived to be healthierthan commercially produced eggs.

However, recent studies have identi-fied concerning levels of Pb in eggsproduced by chickens raised in areaswith significant Pb contamination ofthe soil, usually as the result of theweathering of older buildings with Pb-based paints. The consumption ofone average size 50-60 gramme eggfrom Pb-contaminated environmentcan exceed the safe threshold dose of6µg of Pb per day from all combined

dietary sources. What about PCBs andPBDEs? These are very fat-solublechemicals and egg yolk is rich in lipidsresulting in an average fat content inan egg of 10%. Thus, the potential forsignificant contamination of eggs inregions with increased soil levels ofthese POPs is not unreasonable, assuggested by recent data reportingthe detection of PCBs and PBDEs inmilk from dairy cows of California.

The overwhelming majority of foodsafety research associated with backyard poultry and other home-produced food products has largelyfocused on microbial contamination.Human illness from most foodbornepathogens is limited to transient gas-trointestinal symptoms; in contrast,human exposure to unsafe levels ofPCBs, PBDEs or metals has the poten-tial to cause long-term adverse healtheffects. Currently, urban and backyardfarmers have no way of knowingwhether eggs or other home-grownfood products are contaminated withtoxic chemicals unless they are lab

tested. There is, therefore, an urgentneed to study environmental chemi-cals in home-produced food in geo-graphic regions that have experiencedurban wildfires to assess the potentialfood safety risk and to generate infor-mation needed to inform rational riskmanagement.

In conclusion, the increase in wildfireshas potentially serious long-termhealth consequences for communi-ties and ecosystems. One importantconcern is the generation or releaseof chemicals into the soil and waterenvironment and the risk for chemicalcontamination of home-grown pro-duce, eggs and other animal-derivedfood products. To more accuratelypredict the risk to humans, it will benecessary to obtain data regardingthe actual levels of toxic chemicals ofconcern in the environment beforeand after urban wildfires and to modelthe transfer of these contaminantsthrough the food chain.

Pamela J. LeinProfessor and Vice-ChairDepartment of Molecular BiosciencesDirector, UC Davis CounterACT Centerof Excellencepjlein@ucdavis.edu

Birgit PuschnerProfessor and ChairDepartment of Molecular Biosciences

University of California, DavisTel: +1 530 752 1970http://www.vetmed.ucdavis.edu/lein-lab/

59

PROFILE

Wildfire aftermath on Cobb Mountain during the Valley fire in northern California

Around the world young chil-dren are expected to learn the language they overhear in

conversations around them. This is arobust, spontaneous ability of humans,unlike, for example, reading, whichmust be explicitly taught. One promi-nent scholar of children’s languageacquisition once put it this way: “…there is virtually no way to prevent itfrom happening short of raising a childin a barrel.”1

Although true of most children, chil-dren with Specific Language Impair-ment (SLI) are the exceptions to thisassumption. These are children who donot have overt neurodevelopmentaldisorders, hearing impairments, orother obvious causes of developmentaldisorders and who live in ordinaryfamilies. Yet they are later than otherchildren in learning a language andare at risk for persistent low languageabilities into adulthood. The best estimates for the prevalence of SLI are7-10% of children at school entry (5-6years).2,3

SLI is often confused with SpeechSound Disorders (SSD) in children.Between one and five years of agechildren are learning two distinctly different parts of the human languagecapacity. One is the production ofspeech sounds needed in their nativelanguage. In the beginning, childrencan produce more sounds than theyneed for the language or languages

they are hearing. Their first job is torefine them to match the ones theyneed and to drop the ones that maynot matter and to develop the motorcontrol needed to do that.

Humans at birth are equipped withmotor movements for breathing,sucking and swallowing (basic func-tions for survival), along with a widerange of sounds. Some vocalisationsserve communicative purposes, andsome are biological (such as burps orcoughs). Between one and two yearsof age, babies master more refinedtongue, lips and palatal movementsneeded for speaking the words andsentences of a language. Thisrequires a fine-tuned synchrony ofmuscles, sound perception and thecognitive centres of the brain. Theoutput is a sequenced speech pattern, such as what we hear in aphone conversation.

The second part of the human language capacity is more covert, amatter of cognitive processes in thebrain that do not require a speechproduction system. For example, deafchildren can acquire a languagesystem that can be expressed in phys-ical signs of the hands, face and bodypostures. Language emerges in youngchildren first in short utterances that lengthen with age. In English, lan-guage emerges as one or two wordsat a time, which relatively quicklyexpand to phrases or sentences.

SSD can be obvious to adult listenersof young children. Young children’sattempts to talk can be unintelligible,especially when they are very young.If unintelligibility persists as childrenage, it becomes noticeable and amatter of concern because it is not “typical.” Some mispronunciationsare understandable but regarded asimmature, such as “wabbit” for “rabbit”,“thoup” for “soup”, or “bawoon” for“balloon.” Scholars have tracked theorder in which children learn theirspeech sounds and have developedage norms for evaluating whether achild meets age expectations4. Theprevalence of SSD in 4-6-year-old children in population-based cohortsis approximately 3-6%5 and the condi-tion appears to resolve in 75% of children by age 66.

People often assume SSD is the sameas SLI, such that children’s speechabilities reflect their underlying language abilities or vice versa. This isnot true. In the most precise study ofa population-based sample of 5-year-old children, the co-occurrence ofspeech and language impairments,once adjusting for age expectations,was estimated at less than 2%5. Forthe children with SLI, speech impair-ment was evident in approximately 5-8% of the children. The authors concluded that SSD and SLI are inde-pendent; they are not likely to co-occur.Thus, SSD is not a diagnostic markerof SLI and presumably, the two condi-

The important differences between Specific Language Impairment (SLI) in children and SpeechSound Disorders (SSD) in children are placed under the spotlight by Mabel L. Rice, Fred & VirginiaMerrill Distinguished Professor of Advanced Studies at the University of Kansas

Specific Language Impairment (SLI)versus Speech Sound Disorders (SSD)

60

PROFILE

tions do not share a common causalpathway.

The non-overlap of SLI and SSD carriesimplications for public health servicesand for scientific studies of the natureand origins of SLI and SSD.

A big issue for public health services•is that children with SLI are likely tobe overlooked as needing languageintervention services, perhaps in partbecause of the fact that SSD may beobvious to adults/caregivers, but SLIis not7.

SSD is likely to resolve with age •(children are likely to “outgrow” it)whereas SLI is likely to persist intoadulthood7.

At school entry, SLI predicts later•reading impairments8 whereas SSDpredicts weakly, if at all, onceadjusted for co-occurring languageimpairments.9,10

Scientific studies of children’s com-•munication problems in medical con-ditions should differentiate betweenSLI and SSD. A recent study of childrenexposed to Human Immunodefi-ciency Virus (HIV) is the first report ofSSD outcomes compared to primarylanguage impairments (i.e., withoutother developmental disorders). Therisk for language impairments in thechildren was higher than populationnorms but the risk for SSD was notelevated.11

Examples of how children talk canillustrate the differences between SLIand SSD. Consider two 5-year-oldboys. They are talking about a pictureof red rabbits. One, dressed in purple,has an SSD, apparent in his mispro-nunciations of the speech soundsneeded to say “why are the rabbitsred.” Within his speech system, he

says “why ah de wabbits wed?” Thesubstitution of w/r in “rabbit” and“red”, along with the omission of thefinal /r/ in the word “are,” are notunusual speech errors in the speechof young boys.

Such errors are quite noticeablealthough they often do not interferewith adults’ understanding of theintended meanings. The other boy,dressed in green, asks a question formulated in the adult grammar as:“why is/are that rabbit/those rabbitsred?” The boy says “Why that red?”, asentence consistent with the gram-mar rules for children this age withSLI7. He demonstrates a deficiency insentence structure, with the omissionof the obligatory copula form of BE(“is”’ or “are”) and the substitution of apronoun (“that”) for the commonnoun “rabbit.” Furthermore, the specification of singular versus pluralfor the noun phrase is vague becausethe noun information is underspeci-fied. His articulation of speech soundsis at adult levels and his meaning iseffectively conveyed.

Although the speech sound errors ofthe child with SSD are likely to benoticed and to generate attempts byadults to correct the problem, thegrammar errors of the child with SLIare less likely to be noticed or under-stood as flags for concern. Yet it is thechild in green who is at higher risk ofadverse developmental outcomesthan the child in purple, who is morelikely to “outgrow” the SSD and lesslikely to encounter problems with literacy, school achievement, or long-term persistence of subtle butvery important elements of grammarand vocabulary. Our research and our service systems will be improvedby increased recognition of the important differences between SLIand SSD.

References

1. Pinker S. Language learnability and language development. Cam-bridge, MA: Harvard University Press; 1984.

2. Tomblin JB, Records NL, Buckwalter P, Zhang X, Smith E, O'BrienM. The prevalence of specific language impairment in kinder-garten children. J Speech Hear Res. 1997;40:1245-1260.

3. Norbury CF, Gooch D, Wray C, et al. The impact of nonverbal abilityon prevalence and clinical presentation of language disorder:evidence from a population study. Journal of Child Psychology &Psychiatry. 2016;57(11):1247-1257.

4. Goldman R, Fristoe M. Goldman Fristoe Test of Articulation-2(2nd Edition). Circle Pines, MN: American Guidance Service;2000.

5. Shriberg LD, Tomblin JB, McSweeny JL. Prevalence of speechdelay in 6-year-old children and comorbidity with language impairment. J Speech Lang Hear Res. 1999;42:1461-1481.

6. Shriberg LD. Five subtypes of developmental phonological disorders. Clinical Communication Disorders 1994;4:38-53.

7. Rice ML. Specific Language Impairment in Children. https://ww-wopenaccessgovernmentorg/specific-language-impairment-in-chi 2017.

8. Catts HW, Fey ME, Weismer SE, Bridges MS. The relationship between language and reading abilities. In: Tomblin JB, NippoldMA, eds. Understanding individual differences in language development across the school years New York City, New York:Psychology Press; 2014:144-165.

9. Sices L, Taylor HG, Freebairn L, Hansen A, Lewis B. Relationshipbetween speech-sound disorders and early literacy skills inpreschool-age children: Impact of comorbid langauge impair-ment. J Dev Behav Pediatr,. 2007;6:438-447.

10. Hayiou-Thomas ME, Carroll JM, Leavett R, Hulme C, SnowlingMJ. When does speech sound disorder matter for literacy? Therole of disordered speech errors, co-occurring language impair-ment and family risk of dyslexia. Journal of Child Psychologyand Psychiatry. 2017;58(2):197-205.

11. Rice ML, Russell JS, Frederick T, et al. Risk for speech and languageimpairments in pre-school aged HIV-exposed uninfected childrenwith in utero combination antiretroviral exposure. The PediatricInfectious Disease Journal. Accepted Dec 2017.

Mabel L. RiceFred & Virginia Merrill DistinguishedProfessor of Advanced StudiesUniversity of KansasTel: +1 785 864 4570mabel@ku.edu

61

PROFILE

AGRICULTURE

62

How right-sizing regulation can optimiseplant protection

The idea of right-sizing regulation is a guiding forcefor USDA’s Animal and Plant Health InspectionService (APHIS). Part of our mission is safeguarding

U.S agriculture and natural resources against invasivepests and diseases and facilitating the safe trade ofagricultural products. The scale and complexity of thiswork is vast. In 2017, APHIS helped safeguard morethan $98 billion worth of U.S. agriculture productionand facilitate agricultural exports valued at over $138billion.

The role of regulationsAPHIS’ regulations are a crucial tool for mission success.Our regulations prevent devastating foreign pests anddiseases from entering the United States on importedagricultural products. Should a pest or disease enterour country, regulations or other regulatory meansallow us to take decisive action to prevent its spread.

The balance: most effective, leastrestrictiveOf course, there is another side to regulations. Someregulatory actions can create burdens on producers andthe industries they supply. That is why we constantlyseek the most effective – and least restrictive –approach possible.

To make sure we are hitting the mark, APHIS officialsmeet yearly with representatives from various commodity sectors to discuss the opportunities andchallenges they face. We also reduce burdens by constantly applying cutting-edge science, technologyand data analysis to streamline inspection methods,commodity treatments, pest detection, pest manage-ment and export certification. In addition, APHIS usesexisting regulatory flexibilities and non-regulatory solutions to right-size regulation.

Regulatory flexibilityThe status of plant and animal pest and disease conditions worldwide constantly changes and importrequirements must keep up. That can be challenging,however, when each change requires a time-consumingrulemaking process. To respond faster, APHIS hasbegun moving specific import requirements for certaincommodities out of the Code of Federal Regulations(CFR) and into online regulatory manuals. More generalimport requirements remain in the CFR and the CFR

Greg Rosenthal of the U.S. Department of Agriculture’s (USDA) Animal and Plant Health InspectionService explains how right-sizing regulation can optimise plant protection

Inspectors with USDA’s Animal and Plant Health InspectionService ensure that imported plant parts comply with science-and risk-based regulations that are designed to keep invasivepests and diseases out of the United States.

63

refers to the manuals for specific requirements. Thatallows us to change these requirements when neededthrough a much faster notice-based process, whichincludes a public comment period.

Non-regulatory solutionsWe are eager to look beyond rulemaking to solve plantand animal health problems through other meanswhenever possible, using solid science and industrybest practices. In 2016, we used this approach whenwe confirmed that bacterial leaf streak, a diseaseaffecting corn plant leaves, was present in severalstates throughout the U.S. Corn Belt. We knew that regulating the disease would be neither practical norpossible.

Instead, APHIS worked with our partners to identifybest management practices to effectively control thedisease. At the same time, APHIS gathered scientificevidence on this little-known pathogen to help build astrong case for the safety of U.S. corn, protecting $6.3 billion in U.S. corn exports from trade disruption.

We also collaborate with industry, states, academiaand others to promote voluntary programmes that protect U.S. agriculture. For example, APHIS and theseed industry are developing a Seed Health Regulatory

Framework. It will make international seed movementsafer by promoting the worldwide use of consistentand equivalent requirements that reduce pest risk.

Through our Offshore Certification Programs, we verifythat overseas nurseries and other facilities that exportlarge-volume, high-demand plants, cuttings, seeds andother products to the United States meet minimumproduction and sanitation standards. This offshorework is an effective way to prevent harmful plant pestsand diseases from entering our country.

Everyone winsAPHIS constantly strikes that critical balance of takingthe most effective and least restrictive approach. Thisallows us to regulate at the speed of commerce andrelieve industry burdens wherever possible – withoutcompromising our mission. ■

Greg RosenthalCommunications SpecialistUnited States Department of Agriculture (USDA)Animal and Plant Health Inspection Servicewww.aphis.usda.gov/aphis/homewww.twitter.com/USDA

Invasive pests can infest the millions of sea containers that carry agricultural commodities around the world. USDA, working withour Canadian partners and the maritime industry, have formed the North American Sea Container Initiative to develop and promotethe use of voluntary guidelines for effectively cleaning and disinfecting sea containers to reduce this risk.

AGRICULTUREIm

age:

USD

A Ph

oto

by R

. Ans

on E

aglin

Crop yield and quality of mar-ketable fruit are corner stonesof any farmers’ business model.

To that end, chemicals have beenwidely deployed in agriculture to fer-tilise soils and plants or to kill pestsand pathogens that are limiting factorsto optimum productivity.

However, the 20th century dogmathat chemicals could be used blindlywithout restrictions has found itslimits in today’s era. Concerns abouttheir excessive use on human healthand environmental pollution haveshifted the farming philosophy to amore sustainable approach. Here, wewill review some of the key discoveriesthat have advanced the field of biolog-ical pesticides and discuss how newtechnologies could shape the futureof sustainable agriculture.

Synthetic agrochemical products havebeen successful for decades to managepests and pathogens. An agrochemicalis categorised by its active ingredientand metabolic target. One the majornegative side effect of over-usingchemicals with a similar mode ofactions is the selection of resistantstrains within microbial populations.Examples of resistance to fungicidesand bactericides in fungal and bacterialpathogen populations are well docu-mented, but often growers manage theproblem by rotating their chemistries,adopting disease forecast models toreduce chemical input and adapting

their management practices to min-imise disease pressure.

However, in extreme events, farmershave no chemical alternatives tomanage a disease. For example, resis-tance to the neonicotinoid insecticidein psyllid populations has been clearlyestablished in the United States and itno longer suppresses populations ofpsyllids below desirable levels. Thishas become a major threat to thecitrus and potato industries becausethis insect feeds on plants and trans-mits bacterial pathogens (Candidatusliberibacter species) that cause diseasesknown as Huanglongbing and ZebraChip, respectively.

In recent years, there has been a shift in consumer mentality, with an

increased demand for organic foodand food products. US farms producedand sold $7.6 billion (up 23% from2015) in certified organic commodities,according to the U.S. Department ofAgriculture’s National AgriculturalStatistics Service. As a result, there hasbeen an increase of organic farms(over 14,000; up 11% from 2015) and atotal acreage (5 million acres, up 15%from 2015).

Conventional farms also tend to bemore mindful of their farming prac-tices. To that end, biological pesticideapplication, which consists of usingbeneficial microbes or microbial prod-ucts to control disease, improves soiland crop health and has beendeployed in a broader capacitybecause of their low environmental

Cooperative Extension Specialist at the Department of Botany and Plant Sciences,University of California Riverside, Dr Philippe E. Rolshausen shares his thoughts onbiological pesticides and the future of sustainable agriculture

Biological pesticides and the futureof sustainable agriculture

64

PROFILE

impact. For example, one of the manybenefits is that resistance cannotdevelop against microbes.

The first biological control ever discov-ered in the early 20th century was thebacterium Bacillus thuringiensis. Somestrains produce toxins that are lethal toinsect pests and those have been commercialised, as either a biologicalinsecticide or an insect-resistant genet-ically modified crops. Because of thetoxin host-specificity, it is regarded asenvironmentally friendly.

Another key example of biological pes-ticide is Agrobacterium radiobacterstrain K84 registered in the late 20thcentury as a biological control agent ofgrown gall caused by Agrobacteriumtumefasciens, a soil-borne pathogenthat affects a broad spectrum of crops.A. radiobacter strain K84 releases atoxin that alters the ability of thepathogen to reproduce.

Despite those key scientific discoveriesthat became commercial successes,biological pesticides only remainedadopted in niche markets where syn-thetic chemicals were not registered,not effective, or not economical. Thus,the discovery of new biological pesti-cides remained marginal because ofthe widespread adoption of cost-effec-tive synthetic chemicals. Nowadays,this trend is reversed. The commercial-isation of chemical pesticides is declin-ing whereas biopesticide has becomea booming market.

One of the major game changers forbiological pesticides discoveries wasthe advent of ‘Omics’ technologies. Thetraditional microbiological techniquesthat were utilised in the 20th centurydid not allow for a high throughputscreening of organisms. In addition,

most organisms are not culturable, sothe microbial techniques only recov-ered a small range of the plant-associ-ated microbes and most bacteria andfungi were overlooked. Plants host aninfinite number of microorganismsand looking for the ‘good ones’ at the time was comparable to finding aneedle in a haystack.

“In recent years, there has been a shift in consumer mentality, with anincreased demand for organic food andfood products. US farms produced andsold $7.6 billion (up 23% from 2015)in certified organic commodities,according to the U.S. Department ofAgriculture’s National AgriculturalStatistics Service.”

In today’s era, ‘Omics’ technologieshave allowed us to profile the microbialcommunities living inside and outsideof plants and better understand thecomplex plant-microbe and microbe-microbe interactions and their biologi-cal functions. These new technologiescan reveal in a high throughput capac-ity taxa, genes, metabolites or proteinsthat have potential antimicrobialattributes.

In my laboratory, we are using thesetechnologies to identify solutions totwo important bacterial diseases ofgrapes and citrus, namely Pierce’s Dis-ease and Huanglongbing, respectively.Those global emerging diseases arehuge threats to crop productionbecause they can rapidly kill a vine ortree. We have been exploiting a naturalphenomenon occurring in vineyardsand orchards whereby some vines ortrees under high disease pressure arenot symptomatic.

Because plants are of the same geneticmake-up (same variety grafted on the

same rootstock) we hypothesise thatthe residing microbial communitiescause the disease tolerance that weobserve. Our approach is to collectplant tissue samples from both symp-tomatic and asymptomatic plants anddeploy a culture-dependent approachwith traditional microbial techniquesand culture-independent approachusing a next generation sequencing-based platform, so we capture all theorganisms associated with those plants.

The computational analyses of theDNA-database provide the seeds forobtaining a greater understanding ofthe factors that shape the plant micro-biome, as well as identifying themicrobes that potentially play a role inplant health and disease suppressionor exacerbation. Those potential bene-ficial microbes can be cross-referencedin our culture collection and recoveredfor downstream evaluation in in vitroand in planta bioassays. This approachprovides opportunities for the patent-ing of novel technologies and for thedevelopment and commercialisation ofnew science-based bioproducts.

Dr Philippe E. RolshausenCooperative Extension Specialist Department of Botany and Plant Sciences,University of California RiversideTel: +1 951 827 6988philrols@ucr.eduhttp://plantbiology.ucr.edu/http://ucanr.edu/sites/Rolshausen

65

PROFILE

66

USDA: Protecting Americans from foodborne illness

The Food Safety and Inspection Service (FSIS) isthe public health agency in the United StatesDepartment of Agriculture (USDA) responsible

for protecting the public’s health by ensuring the safetyof the nation’s commercial supply of meat, poultry andprocessed egg products. (Our partner agency, the U.S.Department of Health and Human Services’ Food andDrug Administration, has jurisdiction over other foods,such as fruits, vegetables and dairy products.)

FSIS ensures food safety through the authorities ofseveral federal laws. The Federal Meat Inspection Act(FMIA) was passed in 1906. The FMIA requires thatslaughter and processing take place under sanitaryconditions and bans the sale of adulterated or

misbranded meat and meat products. The FMIA wasfollowed by the Poultry Products Inspection Act (PPIA)in 1957.

Both laws require continuous federal inspection ofslaughter operations and that state inspection programs be at least equal to federal standards. TheEgg Products Inspection Act (EPIA) of 1970 and theHumane Methods of Slaughter Act (HMSA) of 1978complete the set of major laws, providing FSIS with theauthority and obligation to carry out its mission to protect public health and prevent foodborne illness.

Secretary of Agriculture, Sonny Perdue, has made agricultural trade a key priority of his tenure at USDA.

Acting Deputy Under Secretary for Food Safety at the United States Department of Agriculture (USDA),Carmen Rottenberg explains how the Food Safety and Inspection Service protects Americans from

foodborne illness

AGRICULTURE

67

As the U.S. continues to expand into markets overseas,at FSIS we are keenly aware of the role that food safetyplays in an increasingly global agricultural marketplace.Food safety is the critical underpinning of this globaleconomy.

As we look to imported product, FSIS has a robustequivalence system in place to ensure that countriesseeking to export to the U.S. meet the same rigorousstandards we expect of our domestic producers. Formeat, poultry and processed eggs to be imported into the United States, a foreign country’s inspectionsystem must be found to be equivalent to the U.S.system. This equivalency status is not permanent butmust be confirmed by periodic audits. 100% of meat,poultry and processed egg products imported into theU.S. is re-inspected at point-of-entry. This inspectionmay also include sampling to test for pathogens andbanned chemical substances.

At FSIS, we never lose sight of our mission to protectpublic health by preventing foodborne illness. In hisfirst speech as Secretary of Agriculture, SecretaryPerdue named food safety as one of the top priorities.Our mission and goals line up perfectly with SecretaryPerdue’s vision and the new USDA Motto to “Do Rightand Feed Everyone!” ■

Carmen RottenbergActing Deputy Under Secretary for Food SafetyUnited States Department of Agriculture (USDA)www.fsis.usda.govwww.twitter.com/USDAFoodSafety/

Carmen RottenbergActing Deputy Under Secretary for Food Safety

AGRICULTURE

Climate change and beef cattleHeat stress is the principal factor limiting production of animal proteinand negatively affecting the healthand welfare of cattle in subtropicaland tropical regions. Detrimentaleffects on livestock productivity asso-ciated with heat stress are expected tointensify and expand into currentlytemperate zones upon the realisationof predicted climate change (Figure 1).The Intergovernmental Panel on Cli-mate Change (IPCC), which includesmore than 1,300 scientists from theUnited States and other countries,forecasts a temperature rise of 2.5 to10 degrees Fahrenheit over the nextcentury. Most animal-producing areasin the US are predicted to experienceextreme summer conditions and by2100, average temperatures in the USare projected to increase 2° to 6°C,depending on the emissions scenarioand climate model applied. Thenumber of days with maximum temperatures above 32°C (90°F) isexpected to increase. The SE and SWareas of the US currently average 60such days per year but is projected toexperience at least 150 such days ayear by the end of the century.

Importance of genomics forimproved thermotoleranceDevelopment of effective strategies toimprove the ability to cope with heatstress is imperative to enhance theproductivity of the US livestock indus-try and secure global food supplies.Although swine, poultry and dairy

cattle are more severely affected byheat stress than beef cattle, their con-finement and intensive productionsystems make climate control viahousing design and managementinterventions feasible. Beef cattle,particularly those in the cow-calf seg-ment, are typically reared in extensivesystems with limited opportunities forcontrolling environmental stress(Figure 2). Genetic improvement isone of few feasible strategies forensuring adequate and sustainableproduction of beef protein in anincreasingly hot world. Substantial differences in thermal tolerance existamong breeds and among animalswithin breeds indicative of opportuni-ties for selective improvement. Forexample, Bos indicus cattle exhibitincreased resistance to many environ-mental stressors relative to Bos taurus,

but tend to have slower growth, lowerfertility and meat quality as they havenot been as intensively selected forthese traits as specialised Bos taurusbreeds. Use of genomic tools to pro-duce an animal with superior ability forboth thermal adaptation and food pro-duction represents an energy-efficientsustainable approach to meet the challenge of global climate change.

What is thermoregulation?Thermoregulation is a process in whichenvironmental information provokesan appropriate response (e.g., vaso-constriction, panting), to maintainbody temperature within the narrowrange necessary for optimal cellularand molecular function. This is accom-plished by jointly regulating heat production and heat loss. Beef cattleregulate internal heat production (by

Developing genomic tools for increased thermotolerance in beef cattle is imperative,says University of Florida’s Associate Professor Raluca Mateescu

Climate change and its impacton beef cattle

68

PROFILE

Figure 1: Projected Temperature Change. Warming is projected for all parts of the nation duringthis century. In the next few decades, this warming will be roughly 2°F to 4°F in most areas. By theend of the century, U.S. warming is projected to correspond closely to the level of global emissions:roughly 3°F to 5°F under lower emissions scenarios (B1) involving substantial reductions inemissions, and 5°F to 10°F for higher emissions scenarios (A2) that assume continued increases inemissions. (Figure source: NOAA NCDC / CICS-NC)

modulating basal metabolic ratethrough thyroid hormone actions andchanging feed intake, growth, lactation,and physical activity) and heatexchange with the environment (by increasing blood flow to the skin,and increasing evaporative heat loss through sweating, panting andbehavioural wetting of the skin).Hyperthermia results when theseadjustments are not able to mitigatethe environmental heat stress andbody temperature increases. Improve-ments in production, such as increasedgrowth rate, lead to increasedmetabolic heat production and exacer-bate the problem of thermoregulation.Thus, for example, there is a negativegenetic correlation between milk yieldand ability to regulate body tempera-ture during heat stress in dairy cattle.Unless accompanied by changes thatincrease heat loss capacity, improve-ments in production make animalsmore susceptible to hyperthermiaduring heat stress.

Genomics for climate smart beefThe strategy we are undertaking is toreveal the genetic architecture of traitsdefining thermal tolerance using Bos

indicus influenced cattle, in particular,Brangus (Brahman x Angus). In com-parison to straight Bos taurus popula-tions, we expect that the major geneticvariants controlling thermal tolerancewill be segregating in these indicine-influenced populations due to thelength of time since divergence of thetwo subspecies, natural adaptation todifferent environments, and exposureto an artificial selection of differentintensities and with different objec-tives. Our goal is to discover geneticvariants responsible for thermal tolerance and use this knowledge todevelop genomic tools to improvethermal tolerance in cattle popula-tions at risk of exposure to heat stress.

Our research will use a system biologyapproach by integrating genomicsand phenomics with additional -omicsdata to understand the genetic archi-tecture of thermal tolerance. Frequentbody temperature measurements,skin temperature, and perspirationrate in free ranging cattle will berecorded during heat stress on 2,000Brangus heifers genotyped with the250K functional SNP chip. Phenomicsfor thermal tolerance and genomic

data will be integrated to identifychromosomal regions associated withregulation of body temperature. Wewill use this information to developtools to be used in selection and management programs designed tomitigate the effect of heat stress inindicine-influenced beef cattle popu-lations that predominate in hot andhumid regions of the US and globally.

In depth knowledge of the genomicvariants with major effect on thermalregulation and the maturation of tech-nologies for gene, editing means thatthermotolerance genes can be rapidlyintroduced into thermally-sensitivebreeds such as Angus, Simmental, andHolstein to allow producers to exploitgenetic lines of cattle selected for highproductivity with minimal disruptionby heat stress. Development of ‘thecow of the future’ with high productiv-ity and resistant to heat stress will berealised through the use of genomicselection within indicine-influencedbreeds and through the application ofgene editing technologies that allowgenetic variants conferring thermaltolerance to be rapidly incorporatedinto non-adapted breeds.

Raluca MateescuAssociate Professor of QuantitativeGenetics & GenomicsGraduate Program DirectorMateescu’s Animal Genetics and Genomics LabTel: +1 352 392 2367raluca@ufl.edu www.ralucamateescu.com

69

PROFILE

Figure 2: Bos Indicus cattle are naturally adapted to survive in tropical andsubtropical environments

Eggshell temperature has beenroutinely used in commercialsettings to pragmatically esti-

mate internal egg temperature(Lourens et al. (2005) and to serve as asubsequent indicator of embryo bodytemperature (Janke et al., 2004). How-ever, because eggshell temperature isinfluenced by the thermal conductivityof the eggshell and the pattern andvelocity of air flow within the incubator(Lourens et al., 2011; Ozcan et al.,2010), it may not precisely reflectactual internal egg temperature.

“Further technological advancementsand refinements of transponderimplantation and temperaturerecording procedures may increase thepracticality of temperature transponderuse in commercial settings.”

Direct measurement of the internaltemperature of eggs has been used tomore accurately assess the level ofheat production and the body tem-perature of embryos during incuba-tion ( Janke et al. (2004). Variousmethods that have been employed to directly measure internal egg orembryo temperature have exhibitedcertain limitations, which includephysiological invasiveness, egg con-tamination, the alteration of embryometabolism and an increase inembryo mortality ( Janke et al., 2004;Turner, 1990).

Nevertheless, Pulikanti et al. (2011a)have successfully inserted transpon-ders into the air cells of broiler hatchingeggs between 12 and 14 days of incu-bation without any associated adverseeffects on eggshell porosity or embryo-genesis or any noted physiologicalstress to the embryo. This relativelynon-invasive procedure has allowed forthe accurate determination of embryotemperature through the last week ofthe incubational period. This procedurealso enables investigators to detectvariations in embryo metabolism andsubsequent heat production that otherexternal methods, such as those usedfor measuring eggshell temperature,are unable to detect.

Relationship of embryotemperature to the functionalcharacteristics of eggshellsPulikanti et al. (2011b) used tempera-ture transponders to record the tem-perature of the air in the incubatorimmediately surrounding the egg. Atthe same time, they implantedtransponders in the air cells of thosesame eggs to record their internaltemperature. These concurrent tem-perature readings were used to moreaccurately calculate the water vapourpressure gradient across the shell andfor the subsequent precise calculationof absolute and relative (adjusted toegg weight) eggshell water vapourconductance.

Dr E. David Peebles from the Poultry Science Department at Mississippi State Universitydetails the accurate determination of embryo temperature and its relationship to the functionalcharacteristics of broiler hatching eggs

Techniques for monitoring broilerembryo temperature

70

PROFILE

Pulikanti et al. (2012b) later employedthese same methods to further com-pute the conductance constants ofeggs, in which the length of incubationwas included as a variable in the cal-culation. Accurate determinations ofthe above variables are necessary inresearch studies where the specificfunctional properties of the eggshellare required.

“Further work conducted by Pulikantiet al. (2012a) showed that a higherrelative eggshell conductance,calculated using internal eggtemperature from transponderreadings, results in an increase inembryonic metabolism which thenleads to an increase in growth andyolk sac absorption.”

Relationship of embryotemperature and the functionalcharacteristics of eggshells to thephysiological characteristics ofembryos and posthatch broilersPulikanti et al. (2011b) reported thatthe internal temperature of liveembryonated eggs exceeded those ofnon-embronated eggs between 10.5and 18 days of incubation. The tem-perature difference increased fromapproximately 0.025°C on day 10.5 to0.80°C on day 18, with the average dif-ference over the entire period being0.50°C. The semicircadian patterns intemperature observed were moreaccurately detected by transpondersthat were implanted in the air cells ofthe eggs.

Further work conducted by Pulikantiet al. (2012a) showed that a higher rel-ative eggshell conductance, calculatedusing internal egg temperature fromtransponder readings, results in anincrease in embryonic metabolismwhich then leads to an increase ingrowth and yolk sac absorption.

Pulikanti et al. (2013) also later con-firmed that embryo temperature andsubsequent relative eggshell conduc-tance can influence physiological vari-ables in birds during both the middleand late posthatch grow out periods.For example, it was shown that rela-tive body and breast muscle weightson day 48 posthatch were positivelycorrelated with relative eggshell con-ductance and eggshell conductanceconstant values and that relativebreast muscle weight was negativelycorrelated with embryo temperature.These reports indicate that accuratedeterminations of embryo tempera-ture and associated eggshell func-tional characteristics are necessary indetermining the physiological statusof the embryo and in predicting theposthatch performance of broilers.

SummaryFurther technological advancementsand refinements of transponderimplantation and temperature record-ing procedures may increase the prac-ticality of temperature transponder usein commercial settings. This methodol-ogy has the potential to provide com-mercial hatchery managers with a moreaccurate means by which to regulateincubation conditions to better suit thebroiler embryo and to subsequentlylead to increased production profits.

References

Janke, O., B. Tzschentke, and M. Boerjan. 2004. Comparative

investigations of heat production and body temperature in embryos

of modern chicken breeds. Avian Poult. Biol. Rev. 15: 191-196.

Lourens, A., H. van den Brand, R. Meijerhof, and B. Kemp. 2005.

Effect of eggshell temperature during incubation on embryo

development, hatchability, and posthatch development. Poult. Sci.

84:914-920.

Lourens, A., R. Meijerhof, B. Kemp, and H. van den Brand. 2011.

Energy partitioning during incubation and consequences for embryo

temperature: A theoretical approach. Poult. Sci. 90:516-523.

Ozcan, S. E., S. Andriessens, and D. Berckmans. Computational

study of the heat transfer of an avian egg in a tray. 2010. Poult. Sci.

89:776-784.

Pulikanti, R., E. D. Peebles, L. W. Bennett, W. Zhai, and P. D. Gerard,

2013. Physiological relationships of the middle and late post-hatch

performance of broilers to their embryo and eggshell characteristics.

J. Poult. Sci. 50(4):375-380.

Pulikanti, R., E. D. Peebles, and P. D. Gerard, 2011a. Physiological

responses of broiler embryos to in ovo implantation of temperature

transponders. Poult. Sci. 90:308-313.

Pulikanti, R., E. D. Peebles, and P. D. Gerard, 2011b. Use of

implantable temperature transponders for the determination of

air cell temperature, eggshell water vapor conductance, and their

functional relationships in embryonated broiler hatching eggs.

Poult. Sci. 90:1191-1196.

Pulikanti, R., E. D. Peebles, W. Zhai, L. W. Bennett, and P. D. Gerard,

2012a. Physiological relationships of the early post-hatch performance

of broilers to their embryo and eggshell characteristics. Poult. Sci.

91:1552-1557.

Pulikanti, R., E. D. Peebles, W. Zhai, and P. D. Gerard, 2012b. Deter-

mination of embryonic temperature profiles and eggshell water vapor

conductance constants in incubating Ross x Ross 708 broiler hatching

eggs using temperature transponders. Poult. Sci. 91:55-61.

Turner, J. S. 1990. The thermal energetics of an incubated chicken

egg. J. Therm. Biol. 15: 211-216.

Dr E. David PeeblesPoultry Science Department, MississippiState UniversityTel: +1 662 325 3379d.peebles@msstate.eduwww.poultry.msstate.edu

71

PROFILE

As a field agronomist fromNorthwest Kansas, I’m attend-ing the 15th Ogallala Aquifer

Program workshop in Lubbock, TXwith irrigation engineers, hydrologists,economists and other water scien-tists, focused on extending the life ofthe aquifer to sustain rural economies(https://ogallala.tamu.edu/). The ten-sion in the conference is palpable.“164 days since last measurable pre-cipitation in the Texas High Plains.”“This wheat crop is on the ropes.” “If we don’t get rain soon…”

We all recognise drought. The dullgreen vegetation; the pallor of dust-filled skies; the dry scratchy throatand persistent cough. Agriculture?Drought stops agriculture in its tracks.Here in the High Plains, agricultureaffects a third of the regional econ-

omy. In Sub-Saharan Africa, droughtaffects the core food supply, leadingto rural exodus and civil unrest. InNorthwest India, drought amplifiesthe frequency of heat-related deaths.In Cape Town, South Africa, a two-yeardrought threatens the water supplyfor the four million residents. Droughttouches our lives and communities inmyriad ways.

Wayne Palmer published his droughtindex in 1965, considering droughtcycles of the 1930s and 1950s. Hismetric uses monthly precipitation andatmospheric demand for water, con-trived to report the deviation of soilwater supply from ‘normal’ conditions.The concept of ‘normal’, or the long-term average weather is central tomany drought indices used today. TheUnited States Drought Monitor

displays its index using fire colours –yellow, orange, red. Drought metricsprovide early warning of impendingdisasters.

The American Meteorological Societyhosted four sessions on drought andfood security in its 2018 meetings.One of several global-scale droughtmonitoring programmes utilises satellite imagery to calculate and mapthe energy balance for land surfaces.This accounting scheme uses physicsto sum inputs and outputs in terms ofradiation, evaporation and warming/cooling of air and land. The thermalband from satellites, representing thesurface temperature, conveys criticalinformation of surface water availabil-ity. Warmer sectors indicate dry sur-faces, while the wet regions displaycooler temperatures.

Professor Robert Aiken, Research Crop Scientist from Northwest Research–Extension Centerprovides his expert thoughts on the fascinating global research taking place on drought,including the vital role of satellite imagery

72

PROFILE

Global research on drought

Texas 2012: An entire field of corn islost due to drought conditions

Globally, agencies use these tech-niques to detect and report incipientand ongoing drought. These earlywarnings and updates inform emer-gency drought responses. Earth scien-tists recognise drought as an integralcomponent of the hydrological cycle.The question remains: Has climatechange affected the frequency, dura-tion or extent of drought?

Zach Zambreski, a young, bright, dedi-cated meteorologist, tackled the prob-lem of long-term drought dynamics inhis graduate research (Kansas StateUniversity, Agronomy). He employedEmpirical Orthogonal Functions (EOF, atype of principal component analysis)to characterise monthly drought metrics of the U.S. Great Plains over the 20th century (1903 to 2015). Hethen correlated the EOF with each of thelocalised time series of drought metrics

to identify regions with similar historicpatterns of wetting and drying cycles.Analyses such as this provide bench-marks against which climate changetrends can be usefully compared.

This afternoon our groundwater conference closes. The overnightthunderstorm relieves the tension –for the moment. We muse about LaNina effects, the wet winter conditionsin the Northern Great Plains andprospects for wheat harvest. Likely,there are similar conversations withinthe railroad companies, consideringwhere to position their box cars totransport the wheat crop to exportshipping terminals. As earth scientists,we recognise the tools at our disposalto identify and quantify drought. Collectively, as a global society, are we prepared to mitigate the effects of drought?

1 Harris, I., P. D. Jones, T. J. Osborn, and D. H. Lister, 2014: Updated

high-resolution grids of monthly climatic observations - the CRU

TS3.10 Dataset. International Journal of Climatology, 34, 623-642,

doi: 10.1002/joc.3711.

2 Vicente-Serrano, S. M., S. Beguería, and J. I. López-Moreno, 2010:

A Multiscalar Drought Index Sensitive to Global Warming: The

Standardized Precipitation Evapotranspiration Index. Journal of

Climate, 23, 1696-1718, doi: 10.1175/2009jcli2909.1.

Professor Robert AikenResearch Crop ScientistNorthwest Research–Extension CenterTel: +1 785 462 6281raiken@ksu.eduhttps://www.northwest.k-state.edu/

73

PROFILE

(a) Two selected sub-regions in the Great Plains for spring drought variability and (b) their corresponding drought time series (filtered usinga 10-year running average) for the period 1903-2015. Climate data used to calculate the drought index was retrieved from the ClimaticResearch Unit (CRU) TS v. 3.24.01 (Harris et al. 20141). The drought index is the Standardized Precipitation Evapotranspiration Index (SPEI) ona three-month time scale (Vicente-Serrano et al. 20102). Positive values of the SPEI represent wetter than average conditions and negativevalues represent drier than average conditions. There are notable differences in the drought conditions of these adjacent sub-regions duringthe 1930s (Dust Bowl era) and the period 2010-2015 (b). These temporal differences in drought variability across relatively short spatialdistances provide evidence for the delineation of each sub-region and consideration in drought monitoring and climate change analyses.

74

National Institute of Food andAgriculture (NIFA)

The National Institute of Food and Agriculture(NIFA) is a federal agency within the UnitedStates Department of Agriculture (USDA). The

agency administers federal funding to address theagricultural issues impacting people’s daily lives andthe nation’s future. To provide both leadership andfunding for programmes that advance the progressionof agriculture-related sciences, NIFA invest in and support initiatives that ensure the long-term viabilityof agriculture. They do this while applying an integratedapproach to ensure that ground-breaking discoveriesin agriculture-related sciences and technologies reachthe people who can put them into practice.

NIFA collaborates with leading scientists, policymakers,experts and educators in organisations throughout theworld to find innovative solutions to the most pressinglocal and global problems. These collaborations create

spaces for constant scientific progress, made throughdiscovery and application. Among the most importantprogressions in 2018 NIFA focuses on:

The advances in the competitiveness of American•agriculture;

Bolstering the U.S. economy; •

Enhancing the safety of the nation’s food supply; •

Improving the nutrition and well-being of American•citizens;

Sustaining natural resources and the environment•and;

Building energy independence.•

The work of the National Institute of Food and Agriculture (NIFA) is examined here by Open Access Government

AGRICULTURE

AGRICULTURE

75

It is clear to see that NIFA programmes aim to cover awide spread of issues, while also serving as a vital contributor to science policy decision-making. NIFA hastaken significant strides toward enhancing the impactof food agriculture, natural resources and human sci-ences in recent years and now more than ever it is vitalto strike the balance between practising sustainableagriculture while also increasing productivity and pro-duction efficiency. The U.S. Department of Agricultureis propelling its scientists to develop research-basedtechnologies that can make this possible.

February 2018 marked the announcement of The U.S.Department of Agriculture’s (USDA) NIFA support forthe Alfalfa Forage and Research Program (AFRP) withapproximately $2.1 million in available funding to support AFRP. This programme funds research andextension programmes that improve alfalfa forage,seed yields and helps producers apply best practices.

“Alfalfa research helps ensure there are dependableand affordable supplies of forage available for dairyand other livestock producers around the country,”states NIFA Director, Dr Sonny Ramaswamy. “This cropis also a part of conservation production systems thathelp protect fields from water erosion and provide anatural supply of nitrogen to the soil for use by othercrops.” Their principal goals are to increase alfalfayields and quality; improve harvest and storage sys-tems; develop methods to estimate forage yield andquality to support marketing while reducing producerrisks and; explore new and novel uses for alfalfa.

Success in previous projects across America spurs onscientists to become innovators who explore new waysof tackling problems from all angles. For example, January 2017 saw several announcements regardingNIFA and the diverse allocation of funding and collab-orative research:

Four grants totalling more than $13.6 million allocated•to combat a scourge on the nation’s citrus industry,citrus greening disease, aka Huanglongbing.

$18.9 million in funding for eligible 1890 land-grant•colleges and universities to obtain or improve agricul-tural and food sciences facilities and equipment. The1890 Facilities Grant Program helps the eligible institutions educate the future workforce in the food;agricultural and human sciences job sectors.

The availability of $8.8 million in funding to support•agricultural science education at Hispanic-servinginstitutions (HSIs). “Hispanic students earn only 8% of the degrees awarded in science, technology, engineering and math (STEM)”, states DirectorRamaswamy. “These investments help HSIs promoteSTEM education and agricultural industry careers toall their students, including Hispanic students.”

In the same vein, NIFA tackles a few “challenge areas”using collaborative research and funding. The AFRIResilient Agroecosystems in a Changing Climate Chal-lenge Area is one of these and focuses on understandingthe interaction between climate variability and agricul-tural production systems, so that we can develop theplants, animals and management systems that will berobust and productive under changing environmentalconditions.

Research results from this challenge area will lead toimproved management systems and crop varietiesthat consider the risks associated with a more variableenvironment. Another long-term outcome of this challenge area is reducing the environmental impact,while maintaining a productive food, feed, fibre and fuelsystem. This is a prime example of studies exploringmaximised productivity alongside minimised environ-mental damage, it is becoming more and more obviousto the agricultural sector that environmental impactsneed to be minimised, while also developing new waysto deal with the results.

Overall, it is evident that these above initiatives andprogrammes support their aims. In a press release, wefind out that: “NIFA’s mission is to invest in and advanceagricultural research, education and extension thatsolve societal challenges.” Their programmes propelcutting-edge discoveries from research laboratories to farms, classrooms, communities and back again.Through three main federal-funding mechanisms, NIFA supports programmes that address key nationalchallenge areas. ■

https://nifa.usda.gov/announcement/usdas-national-institute-food-and-agriculture-announces-support-increasing-alfalfa

Open Access GovernmentJMiles@openaccessgovernment.orgwww.openaccessgovernment.orghttps://twitter.com/OpenAccessGov

Cowpea, Vigna unguiculataWalp., is an important sourceof protein and vitamins. It is

widely grown in the Southern USA andin most tropical and subtropical coun-tries worldwide. Cowpea was histori-cally used as a forage crop for horsesand cattle (speculated source of thename cowpea), and is utilised primarilyas a fresh market and frozen orcanned vegetable in Southern USA but is consumed mostly as a dry pea(for example “blackeye pea”) on aglobal basis.

In the Southwestern USA, especially inCalifornia and Texas, about 45,000 t of dry cowpea (“blackeye” and othertypes) is produced annually, on about20,000 ha. Roughly a third of the pro-duction is exported to Europe, MiddleEast and elsewhere; North Carolinagrows only about 2,000 acres, muchbelow its actual potential.

Cowpea has other uses, including ascover crop (especially in organic sys-tems) for soil health enhancementand as an animal feed supplement.Cowpea consumption by humans andlivestock is known to have significanthealth attributes, some yet to be fullyunderstood or exploited; for example,the potential for cowpea extract toreduce proliferation of triple negative

breast cancer, a very aggressive form ofcancer, as well as increasing immunesystem defense in ruminants againstgastrointestinal parasites among othereffects (Adjei-Fremah, 2017).

Cowpea is also attractive to pollina-tors, such as honey bees and otherpollinating arthropods foraging fornectar as they carry out important ecological services that are critical fora productive and sustainable agroe-cosystem. Many varieties of cowpeahave high-yield potential (>3,500kg/ha), superior seed quality and various levels of resistance to insectpests and diseases.

Both small and commercial productioncan be profitable; fresh market produc-tion is primarily by small growers, whiledry seed production is mainly a largecommercial enterprise. However, thevarious benefits and uses of cowpeacannot be realised without adequatecontrol of field and storage pests thatcan destroy an entire crop.

Production constraintsPests on cowpea are indeed a baneworldwide. Realising the potential ofcowpea as a crop, soil health enhancer,livestock feed or any other use will bedifficult to achieve without our abilityto minimise the damage and preva-

lence of insect pests and diseases.Entomologists, Drs Louis Jackai andBeatrice Dingha and their colleagues atNorth Carolina A&T State University inthe USA have been working on thepest problems of small organic andconventional growers who produce95% of the cowpeas in North Carolina.

The university is the only institution inthe state that has a cowpea researchprogramme focused exclusively on pestmanagement. There is a good reasonfor this focus. Results from recent stud-ies (funded by USDA-NIFA and USDA-ARS) to determine the factors that limitthe expansion and use of cowpea indi-cate that insect pests, especially pen-tatomid pests, such as the brownmarmorated stink bug (BMSB) and aweevil, the cowpea curculio (Cpc), maybe among the most limiting challenges.

Cowpea as a trap crop for anemerging invasive pestResearch conducted at two locations,Greensboro, NC (in the Piedmont) andGoldsboro, NC (in the Coastal Plain)revealed that BMSB, a severe pest onfruit, ornamentals and vegetables andthe Cpc present inverse populationtrends, with the former limiting produc-tion in the Piedmont zone and the latterin the Coastal Plain. This was most evident in 2014, when our research

Louis E. N Jackai and Beatrice N. Dingha from the Department of Natural Resources andEnvironmental Design at North Carolina A&T State University discuss their transformativeresearch on Cowpea for increased and sustained production and use in the USA, with thisfirst article focussing on innovative trap crop development and deployment

76

PROFILE

Transformative research on Cowpea:Innovative trap crop developmentand deployment

showed a near crop failure from BMSBdamage in the Piedmont and from theCpc in the Coastal Plain region.

A broad range of laboratory and fieldexperiments (Fig. 1) have since shownthat a few cowpea varieties are particu-larly attractive to BMSBs and as such,can be used as decoys to attract anddivert the pest away from a desired maincowpea crop, thus serving as a sink. Thisis the textbook definition of the trap cropconcept (Hokkanen, 1991; Shelton andBadenes-Perez 2006; Parker et al., 2013),in this case an intra-specific trap cropthat uses the same crop species both astrap and main crop.

This finding has many small vegetablegrowers excited about the long-termpossibilities of minimising the use ofhigh-risk pesticides leading to increasedfood safety and farm profits. In a spin-offfrom the initial grant, we started toexamine the potential of using cowpeaas a trap crop in other cropping systemsto divert populations of BMSB fromhigh-value crops (such as soybean, corn,sunflower and possibly peppers, tomatoand fruit trees – the latter have not yetbeen tested) to a cowpea trap crop on

which the pest can then be killed, withan appropriate insecticide or othermethod that would result in less envi-ronmental and human health risks,while obtaining reasonable crop yield.

The future of trap cropping and other pest managementapproaches for BMSB suppressionCrop protection using tactics such astrap cropping can take a long time to figure out where (field location; conventional wisdom of peripherytrap placement may not always beoptimal), when (time of trap crop introduction) and how much/and forhow long (trap density/retention).

In some situations, multiple trap cropshave produced better yields (Parker etal., 2016); using both perimeter andstrip trap crops, our work and that ofothers, has produced great success inusing a single trap crop variety. Traps work because of the olfactoryresponses that are triggered bysemiochemicals (plant odours) thatguide the insects to the trap crop.

The same compounds (single or mix-tures) may also be present in the main

crop, as in crucifer trap cropping, buttheir concentrations and gene expres-sion may make all the difference.Ongoing work in our laboratories willtry to understand these dynamics tomake trap cropping more efficient andpredictable. This approach is the nexusto sustainable pest management inorganic systems and overall ecosystemsustainability; indeed, continuedresearch funding from USDA and othersources as well as innovative ideashold the key to future success of thisand similar pest management tactics.

References

Adjei-Fremah, S. 2017. Molecular Effects of Cowpea Polyphenolson Mammalian Transcriptome, Proteome, and Microbiome. Doc-toral Dissertation, North Carolina Agricultural and Technical StateUniversity. https://search.proquest.com/docview/1916583456?pq-origsite=gscholar.

Hokkanen, HMT. 1991. Trap cropping in pest management. AnnualReview of Entomology 36: 119–138.

Parker, JE, C. Rodriguez-Saona, GC Hamilton &WE Snyder. (2013). Com-panion planting and insect pest control: INTECH Open Access Publisher.

Parker, JE, DW Crowder, SD Eigenbrode and WE Snyder. 2016. Trapcrop diversity increases yield. Agriculture, Ecosystems and Environment232: 254-262.

Shelton, AM., FR Badenes-Perez. 2006. Concepts and applicationsof trap cropping in pest management. Annual Review of Entomology51: 285–308.

Louis E. N. Jackai, PhDProfessor and IPM SpecialistDepartment of Natural Resources and Environmental Design, North Carolina A&TState UniversityTel: +1 336 285 4837lejackai@ncat.edu http://www.ncat.edu/faculty/lejackai.html

Beatrice N. Dingha, PhDResearch ScientistDepartment of Natural Resources and Environmental Design, North Carolina A&TState UniversityTel: +1 336 285 4864bndingha@ncat.eduhttp://www.ncat.edu/caes/facultystaff/profiles/bndingha.html

77

PROFILE

Figure 1: The brown marmorated stink bug (A) causes severe damage to cowpea (B). Severalfield and laboratory techniques are used in the discovery of a suitable trap crop for this insectincluding response to plant odors (Y-tube (C) and 4-arm (D) olfactometers and other behaviorsrelated to attraction to a host plant source (using the Noldus Observer XT video system, E).One of the best cowpea trap crop varieties (ES) is shown in F as a 2-row peripheral trap.

AGRICULTURE

78

Finding new solutions to agriculturalproblems in the U.S.

The Agricultural Research Service (ARS) is the U.S.Department of Agriculture’s (USDA’s) chief scien-tific in-house research agency. ARS is one of four

agencies in USDA’s Research, Education and Economicsmission area. Their principal purpose is finding newsolutions to agricultural problems that affect Americansevery day from the field to the table, with the vision to“lead America towards a better future through agricul-tural research and information.”

Their methods to solving agricultural problems arefocalised through their four national programme areas:nutrition, food safety and quality; animal productionand protection; natural resources and sustainable agri-cultural systems; and crop production and protection.Formed in 1953, the ARS has come a long way sincethen, rapidly growing in scope. Today, the organisationincludes 690 research projects within 15 national programmes, 2,000 scientists and post docs, 90+research locations, including overseas laboratories anda $1.1 billion fiscal year budget.

The ARS states that each dollar invested in agriculturalresearch results in $20 of economic impact.

ARS scientists regularly collaborate with research part-ners from universities, companies, large organisationsand numerous different countries. An example of thisis the $1 million Funded International Consortium toSeek Honey Bee Disease Controls, which took place inMarch of this year. Agricultural Research Service (ARS)entomologist Steven Cook is leading this consortiumof scientists, who together are attempting to seek newcontrols for Varroa mites, the honeybees’ number oneproblem.

Along with the Bee Research Laboratory, (a part ofARS’s Beltsville (Maryland) Agricultural ResearchCentre), Cook will be the principal investigator of agroup that will include scientists from the UnitedStates, Canada and Spain. ARS is the in-house researchagency of the U.S. Department of Agriculture (USDA).Laboratory and field studies will be conducted at

Open Access Government looks at the work of the Agricultural Research Service (ARS) in finding new solutions to agricultural problems in the United States

AGRICULTURE

79

facilities in Alabama, Georgia, Maryland and Ohio, aswell as in Alberta, Canada.

In addition, laboratories in Nebraska and Spain will seescientists using advanced methods to work out anunderstanding of the molecular mechanisms by whichVarroa mites develop resistance to various chemicalcontrols. Honey bees specifically pollinate about 100crops in the United States. Varroa mites have becomeresistant to many commercially available chemical control agents in recent years.

Recent additional research conducted by the ARSincludes the work to counter the resistance of acommon soil bacterial compound named Tunicamycin,which causes infection in both humans and animals.The ARS Website printed a press release on March29th, 2018 regarding this research and stated that:“Researchers have known of tunicamycin for decadesand were initially excited by its medical and veterinaryprospects – especially to overcome the resistance ofsome germs to penicillin-based drugs like oxacillin andmethicillin.

The problem was, tunicamycin also blocked a key protein in human and animal cells, undercutting itspotential use in the ground war on germs.” An ARS-ledteam of scientists and colleagues at the agenciesNational Centre for Agricultural Utilization Research(NCAUR) in Peoria, Illinois and the Chinese Academy ofSciences are working to devise a method to retool the

compound so that it poses little to no danger to humanor animal cells, but can still kill germs.

“Honey bees specifically pollinate about 100 cropsin the United States. Varroa mites have become

resistant to many commercially available chemicalcontrol agents in recent years.”

The ARS pride themselves on their mission, that is constantly striving to ensure high-quality, safe foodand other agricultural products; assessing the nutri-tional needs of Americans; sustaining a competitiveagricultural economy; and enhancing the naturalresource base and the environment. Furthermore, theyhope to provide economic opportunities for rural citizens, communities and society as a whole; andsupply the infrastructure necessary for creating andmaintaining a diversified workplace.

With the recent death of the ARS Hall of Fame ScientistErnest James Harris, we are called to remember someof the terrific work that has been done in the past, notjust in the present day. Harris was internationallyknown for finding innovative ways to control fruit fliesthat threaten crops around the world and his technolo-gies have been key to eradicating foreign fruit flies inCalifornia, Florida and other U.S. mainland states, aswell as keeping areas free of these pests that wouldrequire costly quarantines and interfere with millionsof dollars of agricultural exports.

The ARS website itself stated that: “he was a particularlystrong role model for other African-American scientistsand was known to his ARS colleagues in Hawaii for hispositive attitude, kindness, gentle demeanour andhumility”. These kinds of scientists are exactly the kindof hard-working innovators that the ARS trust to carryout their research and make progress in the U.S.Department of Agriculture. ■

Open Access GovernmentJMiles@openaccessgovernment.orgwww.openaccessgovernment.orghttps://twitter.com/OpenAccessGov

Varroa mites are external parasites of the honey bee.Although they can feed and live on adult bees, they mainly

feed and reproduce on the larvae and pupae, this causesmalformation and weakening of honey bees as well as

transmitting numerous viruses.

80

Protecting human health and the environment

The United States Environmental ProtectionAgency (EPA) was formed on December 2nd,1970 as an agency of the federal government of

the U.S. During these 47 years, their concrete missionhas remained the same – to protect human health andthe environment. Headed as 14th administrator of theEPA, Scott Pruitt believes that promoting and protectinga strong and healthy environment is among thelifeblood priorities of the government and that the EPAis vital to that mission.

The mission itself is supported by the Office of Environmental Information (OEI), which manages thelife cycle of information surrounding the EPA’s mission.Stated clearly on its website, the OEI is proud to support the EPA, by identifying and implementing

innovative information technology and informationmanagement solutions that strengthen EPA’s ability toachieve its goals. They ensure the quality of EPA’s information and the efficiency and reliability of EPA’stechnology, data collection, exchange efforts and accessservices. The OEI also strives to provide technologyservices and manage EPA’s IT investments.

Together, the EPA and the OEI act, by developing andenforcing regulations, giving grants, both teaching andstudying environmental issues, sponsoring partner-ships and publishing information to accomplish thisimportant goal.

A recent illustration of some of these actions cameabout in January 2018, with the release of a report

The work of the U.S. Environmental Protection Agency and the Office of Environmental Information, to protect human health and the environment, is unveiled by Open Access Government

ENVIRONMENT

ENVIRONMENT

81

outlining recommendations to promote agriculture,economic development, job growth, infrastructureimprovements, technological innovation, energy securityand the quality of life in rural America. As a memberof the USDA Task Force on Agriculture and Rural Pros-perity Release Recommendations to Revitalize RuralAmerica, the Environmental Protection Agency (EPA)plays an important role in revitalising rural America.Pruitt confirmed his commitment to empowering ruralAmerica by stated that it will contribute to improvingthe “environmental outcomes across the country”.

“Together, the EPA and the OEI act, by developingand enforcing regulations, giving grants, bothteaching and studying environmental issues,

sponsoring partnerships and publishing informationto accomplish this important goal.”

In addition, EPA awards numerous grants to supportstate pesticide regulatory programmes ensuring theseproducts are used properly, agricultural works are protected, and farmers can provide safe, healthy foodfor all Americans. More specifically, in May 2017 the EPAawarded $574k to the Washington State Departmentof Agriculture to support state-wide pesticide pro-grammes. Administrator Pruitt states: “We are pleasedto support the pesticide programs in ensuring that pesticides are used properly, agricultural workers areprotected, and Washington’s diverse agricultural landscape can thrive and remain a provider of safe,healthy food.”

The U.S. agriculture sector itself is somewhat robust,producing nearly $330 billion per year in agriculturalcommodities. The U.S. is also unsurprisingly currentlythe world’s leading exporter of agricultural products;the sector plays a critical role in the global economy.However, aspects of this are constantly under threatand with climate change becoming an ever-growingfactor in the well-being of the agriculture sector, andas such, laws and regulations must be enforced to prevent lost capital.

On March 21, 2011, the EPA issued its final emissionstandards to reduce emissions of toxic air pollutantsfrom industrial, commercial and institutional boilerslocated at area source facilities. An area source facilityemits or has the potential to emit less than 10 tonnes per

year of any single air toxic or less than 25 tonnes peryear of any combination of air toxics. This final rulecovers boilers located at area source facilities that burncoal, oil, or biomass, but not boilers that burn onlygaseous fuels or any solid waste.

An area under threat in today’s climate and toxic air pollution is forestry. While perhaps not the mostobvious means of exportation, forests, in fact, provideseveral important goods and services, includingtimber, recreational opportunities, cultural resourcesand habitat for wildlife. They also create numerousopportunities to reduce future climate change by capturing and storing carbon by providing resourcesfor bioenergy production.

Both agricultural and forestry production are sensitiveto changes in climate, including changes in temperatureand precipitation, more frequent and severe extremeweather events as well as increased stress from pestsand diseases. However, certain adaptation measures,such as changes in crop selection, field and forest management operations and use of technologicalinnovations, have the potential to delay and reducesome of the negative impacts of climate change andcould create new opportunities that benefit the sector.

Clearly, both the EPA and the OEI take their roles veryseriously as responsible for human health and theenvironment. A drastic change in the climate could notonly be dangerous to both the environment and itsinhabitants, but also drastically change the potentialyields of agricultural and forestry products, shiftingland allocation, crop mix and production practicesthroughout the U.S. It is, therefore, important to pro-tect the environment through means such as grantsand education to enable it to thrive, benefitting all. ■

Open Access GovernmentJMiles@openaccessgovernment.orgwww.openaccessgovernment.orghttps://twitter.com/OpenAccessGov

The world’s population is increas-ingly urban. In the United Statesalone, 85% of the population

lives in urban areas and that trend isexpected to continue. If we value thegreen spaces and trees in our citiesand parks for all the benefits they giveus, we need to choose the best treesthat will thrive in challenging sites.

“By far, the most stressful urbancondition for trees is the lack ofaccessible soil. This is caused byinadvertent and purposeful soilcompaction. When any new road orbuilding is built or demolished, the soilwithin the area inadvertently becomescompacted due to the use of heavymachinery and moving of earth.”

There are four basic principles ofurban tree selection:

Trees should be pest resistant and•adapted to urban environmentalconditions.

Trees should be highly diverse, includ-•ing native and non-native species, butavoiding invasive species.

Trees should meet functional and•design objectives.

Trees should match management•limitations.

When we investigate these principles,it is worthwhile to delve into specifics.

Pest resistant – adapted toenvironmental stressDue to the inherently heterogeneousnature of the urban environment, treeplanting sites are subject to microcli-mates caused by buildings and pavedsurfaces and the aftereffects of urbandevelopment written in the soil. On awarm sunny day when the air temper-ature is 24°C, the surface tempera-tures of pavement or building wallscan reflect 40-52°C temperatures.Taken altogether, this increased heatgives rise to the urban heat islandwhere inner cities are considerablywarmer than surrounding rural areas.With increased air temperatures, treeslose water from their leaves morerapidly than a rural tree. Coupled withoften-restricted planting spaces or soil

that is paved over, trees experiencedrought stress even during whatwould be considered normal summertemperatures and rainfall.

With the addition of climate change,cities experience longer periods with-out rain and then heavy downpours.The negative effects of too muchwater can also be stressful for treeswhen air-filled pores in the soil arefilled with water depriving the treeroots of needed oxygen. Aboveground, trees also have to competewith utility wires, streetlights, trafficand business signage. These causeconflicts if sight lines or electricitydelivery is disrupted requiring drasticpruning to squeeze the tree’s canopyinto the allotted space.

Nina Bassuk from the Urban Horticulture Institute, School of Integrative Plant ScienceCornell University shares her thoughts on the value of green spaces in inner cities and howwe should choose the best trees for this purpose

Greening the inner city: How do we choose the best trees?

82

PROFILE

Tree roots escape a confined space by growing under a sidewalk into a neighbouring lawn

By far, the most stressful urban con-dition for trees is the lack of accessiblesoil. This is caused by inadvertent andpurposeful soil compaction. Whenany new road or building is built ordemolished, the soil within the areainadvertently becomes compacteddue to the use of heavy machineryand moving of earth. Once compactedand crushed, it is difficult to bringback the soil so that it can supportplant life. Moreover, when any pave-ment is laid, the soil beneath it mustbe purposefully compacted to bearthe load of the new pavement to prevent subsiding or cracking.

Tree roots provide, water, nutrientsand oxygen for healthy tree growth.When soil volume is restricted these

basic building blocks for tree growthcan be severely restricted. Combinedwith reflected heat from building andpavement, poor water infiltration dueto impervious surfaces, waterloggedsoils that don’t drain and often poornutrient availability, it is no wonderthat urban trees live a shortened life.

However, most people who enjoy atree covered street would say thatthings cannot be that bad. After allmany trees get big and provide manyof the benefits we enjoy.

Where are the roots?Whenever there is a large tree, there isa corresponding large, wide-spreadingroot system that supports that tree tosupply water and nutrients.

With the use of air excavating tools,we have peeled back the soil to findwhere roots are growing. In manynarrow, green, planting areas adjacentto roads, tree roots break out of thelimited soil by exploiting the area ofweakness at the interface betweenthe sidewalk and underlying soil.When they do this, roots find accessi-ble soil in someone’s front or back-yard or nearby vacant lot. Inevitablythe roots of a large tree may not bewhere you think they are. When rootsgrow under pavement and increase ingirth by radial growth, sidewalks maybe raised causing tripping hazards,which set up a conflict between treesand municipalities.

“The one factor that no tree isadapted to is compacted soil.Compaction physically restricts rootgrowth and prevents the acquisition ofwater, nutrients and oxygen. Whenthis occurs, soil remediation mustoccur to engineer a more sustainablesoil condition.”

We can select trees that are adaptedor tolerant of to:

Small planting envelopes (above and•below ground) by choosing smalltrees;

Heat and cold temperatures;•

Dry and wet soils;•

Poor nutrient availability and salts•and;

Insect and diseases.•

Each one of these conditions is a filterreducing the potential trees that may bechosen. It is notable that the more wecan reduce the stress on trees, thegreater the choices we can make will be.

83

PROFILE

Using air excavation tools we uncover roots

84

PROFILE

The one factor that no tree is adaptedto is compacted soil. Compaction phys-ically restricts root growth and preventsthe acquisition of water, nutrients andoxygen. When this occurs, soil remedi-ation must occur to engineer a moresustainable soil condition.

“It is clear that the urban environmenthas been fundamentally altered bydevelopment and human habitation.The choices of trees must considerthese environmental conditions andchoose plants that are adapted tothem.”

Highly diverse, non-invasiveI am often asked, “What is the besturban tree.” There are many commonstreet trees that are preferentiallygrown in cities worldwide. In the east-ern United States, maples (Acer spp.)make up about 40% of the urban treepopulation. In Scandinavia and otherparts of Europe, lindens (Tilia spp.)make up a very large percent of theurban tree population. The problemwith growing just a few tried and truespecies is that if they become suscepti-ble to an insect or disease (andinevitably there is always some newinsect or disease!) the demise of thesetrees causes an enormous negativeeffect on the urban landscape. We havethe example of Dutch Elm Disease dec-imating elms, Emerald Ash Borerskilling all the ash trees, Asian LongHorned Beetles destroying maples anda host of other species, as well as otherexamples. The only true defenceagainst pests is to plant a very diverseurban forest.

Native or non-native?It is clear that the urban environmenthas been fundamentally altered bydevelopment and human habitation.The choices of trees must considerthese environmental conditions andchoose plants that are adapted tothem.

The popular ideology promotingnative species only disregards the factthat urban conditions are nothing likenative conditions where many treesevolved.

The best choice is to use both nativeand non-native trees when they areadapted to urban site conditions. A fewspecies have become invasive, causingeconomic and environmental harm, aswell as harm to human health. Identi-fying these trees varies on a local leveland should be avoided.

Trees provide ecosystem andaesthetic benefitsIncreasingly we are recognising andquantifying the benefits that trees pro-vide in the urban environment includ-ing reducing storm water runoff andpollution, providing habitat for pollina-tors, sequestering carbon, reducing airpollution and providing significantenergy conservation in summer andwinter. Tree choice affects the accrual ofbenefits. Trees with large canopies pro-vide the greatest amount of energy con-servation, storm water runoff reductionand carbon sequestration. A diversity oftrees that flower from spring throughfall will provide the greatest benefit topollinators and other urban fauna.

What about the cost of treemanagement? Many cities have quantified the bene-fits they receive from healthy trees. Inall cases, the cost of management(preparing sites, choosing good treesand providing reasonable aftercare) isfar outweighed by the ecosystem benefits that are gained.

We take trees for granted. Only whenmany trees are removed do peoplerealise the difference trees make intheir lives. Continued research focusingon better tree selection for challengingurban sites will provide long-term benefits that we can all enjoy.

Dr Nina BassukProfessorUrban Horticulture Institute, School of Integrative Plant ScienceCornell University, New York, USATel: +1 607 255 4586nlb2@cornell.edu www.hort.cornell.edu/uhi

www.openaccessgovernment.org acts as a platform for discussion and debate providingnews and topical features with cutting edge policy analysis.

We welcome contact from all experts with an interest in making an editorial contribution, and from those with an opinion to express.

CONTACTeditorial@openaccessgovernment.org

NEWS, VIEWSAND OPINION

www.openaccessgovernment.org GOVERNMENTOPEN ACCESS

At one time the Antarctic Oceanwas home to a temperate fishfauna which included sharks,

rays and bony fishes (teleosts). About20 million years ago the Antarctic watersbegan to cool and all the temperatefishes died out, except for a bottom-dwelling fish that probably looked likea northern hemisphere sculpin. Thishypothetical ancestor gave rise to agroup of closely related fishes thatsurvived the cooling waters, whichtoday are known as the notothenioidfishes: (a sub order Notothenioideinested within the modern bony fishes(Perciforms). Some of the shared features of this group are the lack of aswim bladder making them negativelybuoyant in seawater, paired pelvic andpectoral fins positioned one above theother and just distal of the operculaand mostly benthic species.

This suborder includes eight familiesmost of which are found in the South-ern Ocean south of the Antarctic con-vergence. Members of five of the eightfamilies are primarily confined to thenarrow shelf region of the Antarcticcontinent. The families include theNototheniidae, Channichthyidae,Bathydraconidae, Artedidraconidaeand Harpagiferidae. They make upabout 90% of the fish biomass of theshelf and the populations of some ofthe species are huge. The other threefamilies (fig 1) are confined to the

waters of the sub-Antarctic islandsand the Patagonian region of SouthAmerica.

When the waters surrounding theAntarctic continent began freezing – anovel trait evolved in some of theprogeny of the notothenioid ancestor– which permitted them to avoidfreezing; this trait was a blood-bornglycoprotein which had antifreezeproperties. This antifreeze glycopro-tein (AFGPs) lowered its blood freezingpoint a few tenths of a degree belowthe freezing point of seawater (-1.9°C).The antifreeze trait allowed them tosurvive and diversify into manyspecies which filled the ecologicalniches vacated by the extinction of thetemperate fish fauna. Presently, thereare a variety of body morphs. Some ofthe nototheniids and harpagiferidsresemble north temperate bottomdwelling thorny sculpins (Cottids).

Other species of the nototheniidfamily are like smelt and salmonids inbody form with a fusiform shape. Thenototheniid, Trematomus borch-grevinki inhabits the waters at theunderside of the fast ice and findsrefuge in the platelet layer and has abody form similar to a codfish. Thetwo nototheniid fishes, Pleura-gramma antarctica (Antarctic smelt)and giant Antarctic toothfish, Dissos-tichus mawsoni inhabit the water

column and are neutrally buoyanteven though they lack a swim bladder.They have achieved neutral buoyancyby reducing mineralisation of theirskeletons and scales and accumulat-ing lipids which are less dense thanseawater. The smelt accumulates sacsof clear lipid under its skin andbetween its dorsal vertebral spines.Neutral buoyancy adaptations allowthese two species to cruise throughthe water column expending energyonly for directional swimming ratherthan swimming to counteract sinking.

Channichthyids, often called crocodilefishes because of their large mouthsas adults are sit and wait predatorsand can gulp and swallow a fish halftheir size. The most amazing traitfound in this family is the lack of redblood cells and hence hemoglobin theoxygen transport pigment. Oxygentaken up at the gills is transported only as dissolved oxygen in theirhemoglobinless blood.

However, they have evolved adapta-tions to partly overcome the lack ofhemoglobin such as larger gills for alarger gas exchange surface to absorboxygen, a larger blood volume with alarger heart and the absence of scaleswhich allows some gas exchangethrough the thin skin. Despite theseadaptations, they do not toleratestress like their red-blooded relatives

Arthur L. DeVries, from the University of Illinois provides a comprehensive insightinto a unique marine species flock, the Antarctic notothenioid fishes

86

PROFILE

The Antarctic notothenioid fishes:An especially interesting and uniquemarine species flock

and are therefore at a physiologicaldisadvantage relative to the othernotothenioids.

However, they have been able to sur-vive for millions of years because thecold Antarctic Ocean contains moreoxygen than warm temperate watersbecause oxygen solubility is greater incold water than warm water. Thepresence of one species of the chan-nichthyid species in 12°C waters ofTierra del Fuego exemplifies the cre-ativity of evolution as this one speciescan tolerate temperatures well abovethose ice fish species endemic to theAntarctic Ocean which fail to surviveat temperatures higher than +6°C.Although this South American fishappears to exist near it physiologicallimit, it does attest to its evolutionarysuccess despite having to competewith many coexisting red bloodedspecies, such as salmonids and othernon-Antarctic fish species.

The notothenioid group is an excellentexample of a marine species flock.That is, a closely related clade ofspecies that arose from a commonancestor and underwent an adaptiveradiation that gave rise to a variety ofspecies with unique morphologicaland physiological characteristics thatallowed them to successfully invadeand fill most of the underutilised eco-logical niches that were vacated by theextinct temperate fauna. Becausethey are closely related the similaritiesand differences in some of their bio-chemical, physiological and morpho-logical traits can be more easilycompared without having to deal witha phylogenetic signal that would bepresent if they originated from unre-lated ancestors.

Thus, a clearer picture can be gleanedfrom comparative studies of theirmorphological, biochemical, physio-logical adaptations and the underlying

genomic changes that gave rise tothem. This marine species flock is likethe African Rift cichlids which also arosefrom a common ancestor and evolvedinto hundreds of species which exhibitmorphological, behavioural and repro-ductive differences and utilise differentecological niches in the fresh waterlakes.

Arthur L. DeVriesDepartment of Animal Biology, University of IllinoisTel: +1 217 333 4245adevries@life.illinois.edu

87

PROFILE

Adaptive Radiation of Antarctic Notothenioid Fishes! Major groups of fish taxa

disappeared at ~40 mya.

! Rise of the notothenioid fishes :

! ~45% of all species in Southern Ocean; 90-95% of fish individuals on continental shelf.

Basal taxaNon-Antarctic

Endemic Antarctic taxa

AFGP appears

Figure 1. Cladogram of Antarctic fishes of the Suborder Notothenioidei and characteristics of the group

Biodiversity – the extraordinaryvariety of life on Earth – is fundamental to a healthy, sus-

tainable planet, yet the connectionsbetween biodiversity, ecosystem func-tion and services that contribute tohuman well-being are less well under-stood. These ‘ecosystem services’derive from healthy ecosystems andinclude clean air, clean water, floodresistance, protection from weatherextremes, pollinators of crops, sourcesof foods, fibres and medicines, recre-ational opportunities and spiritual and cultural experiences, to name afew (Fig. 1).

The current concept of ecosystem ser-vices traces to the 2005 United NationsMillennium Ecosystem Assessment.Classification of ecosystem services –by function or other properties – pro-vides a basis for quantifying and valu-ing these contributions. For example,the U.S. Environmental ProtectionAgency (EPA) defines ‘final ecosystemgoods and services’ as components ofnature, directly enjoyed, consumed, orused to yield human well-being, in con-trast to ‘intermediate ecosystem ser-vices’, which are benefits that lead tothe final service. The recognition ofecosystem services as final versus theintermediate is important for assigningeconomic value to these benefits.

Ecological economists note the effect ofinvasive species (>$120 billion annuallyin the U.S. alone) and have begun to

quantify the economic benefit ofecosystem services, but the valuationof ecosystem services is complex andincludes both market and non-marketvalues. For example, both a market (ordollar) value assigned to a specificecosystem or component thereof andnon-market values, such as societalpreferences, intrinsic value andimproved public health, may contributeto the value of an ecosystem service.

Increasingly, representatives of localto national governments, as well asnon-government organisations andthe private sector, are incorporatingthe economic impact of ecosystemservices into policy. Thus, soundresearch that integrates biodiversityand environmental science, social science and economics is required forappropriate valuation of ecosystemservices. To this end, the U.S. Presi-dent’s Council of Advisors on Scienceand Technology (PCAST) in 2011 calledfor the improved accounting of

ecosystem services and greater pro-tection of environmental capital, citingthe need for further biodiversity science and application of informaticsto enhance our understanding ofecosystem services and developappropriate policy to protect them.

More recently, the International Plat-form on Biodiversity and EcosystemServices (IPBES), with 118 membernations and modelled after the Intergovernmental Panel on ClimateChange (IPCC), has begun assessingthe scientific and social knowledge ofEarth’s biological diversity and howenvironmental change will impactecosystems and human societies.Integrated, accessible science andtechnology platforms are needed to leverage novel planetary data,models and tools to create and linkknowledge to policy.

To meet the scientific and societalchallenges of a changing planet,

Pamela S. Soltis, Director of the University of Florida Biodiversity Instituteprovides a fascinating analysis of her department’s research on biodiversity – that is, the extraordinary variety of life on Earth

Biodiversity: The extraordinaryvariety of life on Earth

88

PROFILE

including the identification and valua-tion of ecosystem services, the Uni-versity of Florida (UF) BiodiversityInstitute promotes interdisciplinary,integrative biodiversity science. Themission of the UF Biodiversity Instituteis to conduct high-quality research anddevelop programs to advance threeprimary goals:

1. Initiate and lead large-scale, collaborative biological surveys todocument and monitor biodiversityon a global scale;

2. Conduct collaborative and interdis-ciplinary research on biodiversity, withan emphasis on the use of Big Data;

3. Translate biodiversity science tosolve major societal problems.

Research on ecosystem services ofFlorida’s forests, grasslands and springs

is quantifying the economic value of these important resources anddeveloping methods for valuation ofecosystem services that can beexported to other regions andresources worldwide.

By working with scientists, economistsand social scientists at UF, elsewherein the U.S. and abroad, we hope tobring greater appreciation for themany benefits that we derive fromhealthy ecosystems and demonstratethe significant cost – financial and otherwise – of lost biodiversity anddeteriorating ecosystems.

The UF Biodiversity Institute wasintroduced in the August 2017, issueof Adjacent Government. Launched in2016 to bring together scientists,social scientists and policy experts toaddress critical societal issues of the21st century related to biodiversity,

the interdisciplinary UF BiodiversityInstitute is accelerating syntheticresearch on biological diversity toserve stakeholders in Florida (a biodi-versity hotspot) and globally throughefforts to understand and managebiodiversity, develop relevant conser-vation, educational and outreach pro-grams and shape policy to protect andenhance environmental capital. Newlysynthesised knowledge from the UFBiodiversity Institute is available toindividuals and organisations seekingvalidated biodiversity information.

Previous articles in this series have (1)introduced the UF Biodiversity Insti-tute, (2) described how iDigBio, theU.S. national centre for digitisation ofnatural history collections, promotesdigitisation of collections, serves digi-tised data (including images and othermedia) for biodiversity research andeducation, enables the use of digitiseddata in biodiversity science andengages with biodiversity resourcesworldwide and (3) outlined a strategyfor integrated training in biodiversityand data sciences to meet the needsof a global 21st-century workforce.

Note: Supported by the UF Biodiversity Institute.

Pamela S. SoltisDirectorUniversity of Florida Biodiversity InstituteTel: +1 352 273 1964psoltis@flmnh.ufl.edu https://biodiversity.institute.ufl.edu/

89

Figure 1. Diagrammatic representation of ecosystem services, showing the benefits themselves,the natural resources that provide the benefits and the drivers of change. (From the United StatesEnvironmental Protection Agency. EnviroAtlas. Ecosystem Services in EnviroAtlas. Retrieved: April5th, 2018 from www.epa.gov/enviroatlas/ecosystem-services-enviroatlas)

NaturalResource

s

Benefits

Drivers of Change

StrongEconomyWater

Land Well-being

Soil

Air Public Health

Food, Water & Materials

Policy

Climate Pollution

Land Use

EcosystemServices

PROFILE

ENVIRONMENT

90

Supporting the earth sciences in the United States

The National Science Foundation (NSF) is an inde-pendent federal agency in the United States thatsupports fundamental research and education

across all disciplines of science and engineering. Infiscal year (FY) 2018, its budget is $7.8 billion. NSFfunds research throughout all 50 states to almost 2,000colleges, universities and other institutions. Each year,NSF receives no less than 50,000 competitive proposalsfor funding and funds around 12,000 projects to keepthe United States at the leading edge of discovery inareas from astronomy to geology to zoology.

The Division of Earth Sciences (EAR)The Division of Earth Sciences (EAR), part of the NSF,gives unwavering support to proposals for researchthat intends to improve our understanding of thestructure, composition and evolution of the earth itself,the life it supports and the processes that govern theformation and behaviour of the earth’s materials.

The results of such research will clearly create a betterunderstanding of the earth’s changing environments,as well as the natural distribution of its mineral, biota,water and energy resources, not to mention providingmethods for predicting and mitigating the effects ofgeologic hazards, such as volcanic eruptions, earth-quakes, floods and landslides.

In a nutshell, we know that earth science is the studyof the earth’s structure, properties, processes and in theview of the NSF, it is also the study of four and a halfbillion years of biotic evolution. Certainly, understandingsuch phenomena is essential to the maintenance of lifeitself on the planet. The increasing world populationdemands more resources; heightens losses from naturalhazards and creates more pollution.

The NSF website also points us to the way earth science

benefits society. We learn that the knowledge gained,as well as the work of earth scientists, help society copewith its environment in many ways. The knowledge ofearth scientists concerns the structure, stratigraphyand chemical composition of the earth’s crust andhelps us locate resources that sustain and advance ourquality of life. The NSF’s website explains this point inmore detail to us: “Understanding the forces in thecrust and the natural processes on the surface allowsus to anticipate natural disasters such as volcanoesand earthquakes and geologic environments, such asdamaging mining practices or improper waste disposal,gives us information to correct such practices anddesign more benign procedures for the future.” (1)

“In a nutshell, we know that earth science is thestudy of the earth’s structure, properties, processes

and in the view of the NSF, it is also the study offour and a half billion years of biotic evolution.Certainly, understanding such phenomena is

essential to the maintenance of life itself on theplanet. The increasing world population demandsmore resources; heightens losses from natural

hazards and creates more pollution.”

Petrology and Geochemistry (CH) DivisionWithin the Division of Earth Sciences at the NSF, lies thePetrology and Geochemistry (CH) Division. Their workspecifically involves the support of basic research concerning the formation of planet earth, including its early differentiation and subsequent petrologic andgeochemical modification via igneous and metamorphicprocesses.

Proposals in this programme generally address thepetrology and high-temperature geochemistry ofigneous and metamorphic rocks (including mantlesamples), volcanology, mineral physics and economic

The Earth Sciences (EAR) Division of the National Science Foundation (NSF) is placed under the spotlight by Open Access Government

ENVIRONMENT

91

geology. The Division’s website explains that they focuson the development of analytical tools, theoretical andcomputational models and experimental techniquesfor applications by the igneous and metamorphicpetrology, as well as geochronology communities andhigh- temperature geochemistry. (2)

Examples of NSF-supported research onvolcanologyAn interesting example of how NSF supports and fundsresearch into the earth sciences, for example, isaround volcanology. In news from the field, the NSFwebsite draws our attention to Frank Spear of Rensse-laer Polytechnic Institute who thinks he’s found thesource of water that fuels earthquakes in volcanoes insubduction zones. This can be done by applying a newspectroscopy technique to garnet containing frag-ments of quartz, metamorphic petrologist, we are told.Spear’s research is supported by a three-year $419,247grant from the NSF.

“The real culprit in powerful volcanoes and earth-quakes is water, but scientists have been unable todetermine where that water comes from,” said Spear,a professor and head of the Rensselaer Department ofEarth and Environmental Sciences. “Conventional thermodynamic equations predict that water is releasedat too shallow a depth to occur at the known locationsof volcanoes and earthquakes. But when you factor in the overstepping we’ve discovered, the locationscoincide. The idea of overstepping is an enormous paradigm shift” he explains. (3)

In closing, it’s worth noting another fascinating area ofvolcanology research supported by NSF, which can befound in detail about a study from New Zealand volcano by Brown University, which suggests that a volcanic system’s response to tidal forces could providea tool for predicting a certain type of eruption.

Prior to a surprise eruption of New Zealand’s Ruapehuvolcano in 2007, a seismic tremor near its craterbecame tightly correlated with twice-monthly changesin the strength of tidal forces, the new study reveals.The research suggests that signals associated with tidalcycles could provide advanced warning of kinds of

volcanic eruptions. This interesting point is explainedfurther by Társilo Girona, the study’s lead author.

“Looking at data for this volcano spanning about 12years, we found that this correlation between theamplitude of seismic tremor and tidal cycles developedonly in the three months before this eruption. Whatthat suggests is that the tides could provide a probefor telling us whether or not a volcano has entered acritical state.”

The research was funded by the National ScienceFoundation (1454821). Professor Christian Huber, alsoinvolved in this project said that they’d like to collectmore data from other eruptions and other volcanos tosee if this tidal signal shows up elsewhere “Then we canstart to think about using it as a potential means ofpredicting future eruptions of this kind”, he says. (4)

Closing remarksSuch research is an excellent example of why NSF wascreated by Congress in 1950, one of the reasons ofwhich was: “to promote the progress of science” andto fulfil the vital task of keeping the United States atthe leading edge of discovery in numerous areas ofexciting scientific discovery. ■

References

(1) https://www.nsf.gov/div/index.jsp?div=EAR

(2) https://www.nsf.gov/funding/pgm_summ.jsp?pims_id=13683

(3) https://news.rpi.edu/content/2018/03/15/garnet-reveals-source-

water-fuel-powerful-volcanoes-and-earthquakes

(4) https://news.brown.edu/articles/2018/01/volcano

Jonathan MilesEditorOpen Access GovernmentJMiles@openaccessgovernment.orgwww.openaccessgovernment.orghttps://twitter.com/OpenAccessGov

ENERGY

92

The priorities of the U.S. Energy Department

The mission of the U.S. Energy Department,according to their website, is: “To ensure America’ssecurity and prosperity by addressing its energy,

environmental and nuclear challenges through trans-formative science and technology solutions.” (1) Thisarticle will look at the background to the Department’swork, including some of its present-day work, includingdriving energy-efficient technologies and promotingclean energy, as well as solar manufacturing.

By way of background, the U.S. Energy Department issaid to have one of the most diverse histories in theU.S. Federal Government. While it began its life in 1977,the U.S. Energy Department’s lineage can be tracedback to the Manhattan Project effort to develop theatomic bomb during World War II and to other energy-related programmes that were covered by several federal agencies.

During its long history, the U.S. Energy Department hasshifted its emphasis and focus in accordance with thechanging needs of the nation. In the late 1970s, theemphasis was very much on energy development andregulation. During the 1980s, the priorities changedtowards nuclear weapons research, development andproduction. Following the end of The Cold War, thefocus turned to the environmental clean-up of thenuclear weapons complex and the non-proliferationand stewardship of the nuclear stockpile.

After the millennium, the U.S. Energy Department’sobjective has been to ensure the nation’s prosperityand security. This is achieved by addressing its energy,environmental and nuclear challenges by means ofinnovative science and technology solutions. The U.S.Energy Department seeks to transform the U.S.’senergy system and secure leadership in clean energytechnologies, pursue world-class science and engineeringand enhance nuclear security through defence, non-proliferation and environmental efforts.

Driving energy productivity improvementsand efficient technologiesA more recent example of the U.S. Energy Department’swork is evidenced in an announcement on 10th April2018 about their partnership with the National Associ-ation of Manufacturers (NAM). This intends to help U.S.manufacturers drive energy productivity improvementsand accelerate the adoption of energy-efficient technologies.

“Working alongside our private sector partners, weare driving cost savings and a stronger, more secureU.S. industrial base,” says Secretary of Energy in theU.S., Rick Perry. “The Department’s partnership withthe National Association of Manufacturers will furtherspotlight industrial leadership and boost awarenessof the resources across the DOE enterprise to boost manufacturing competitiveness throughenergy savings.”

NAM President and CEO Jay Timmons adds: “Manufac-turers accept the responsibility to better the future ofour communities, our environment and our children,which is why over the past decade, we have reducedemissions by 10% even as our value to the economyhas increased 19%. This initiative is another exampleof the Trump Administration’s true partnership withmanufacturers in America and it will take our sustain-ability efforts to a new level of progress.” (2)

Clean energy policy and solarmanufacturingToday, a clean energy revolution is said to be takingplace across America, underlined by a steady expansionof the U.S. renewable energy sector. The clean energyindustry is predicted to continue the trend of rapidgrowth in the future. There is a marvellous economicopportunity ahead for the countries that invent, manufacture and export clean energy technologies, weare told.

Open Access Government charts the history of the U.S. Energy Department and some of itspresent-day priorities, including clean energy and solar manufacturing

ENERGY

93

The responsible development of all of America’s richenergy resources – including geothermal, bioenergy,solar, wind, water, & nuclear – will help ensure America’scontinued leadership in the field of clean energy.Moving forward, the U.S. Energy Department aims todrive strategic investments in the transition to acleaner, domestic and more secure energy future.

In January 2018, the U.S. Energy Departmentannounced a $3 million prize competition to revitaliseinnovation in U.S. solar manufacturing. The aim of thisis to incentivise the nation’s entrepreneurs to developnew products and processes that will reassert Ameri-can leadership in the solar marketplace. U.S. Secretaryof Energy Rick Perry explains more about this, in hisown words.

“The United States possesses the talent, expertise andvision to surpass the rest of the world in solar tech-nologies and forge a new solar energy landscapearound the globe. The American Made Solar Prize willgalvanise our country’s entrepreneurs, allow them toutilise technologies and innovations developedthrough DOE’s early-stage research and developmentand, ultimately, bring new American-made products tomarket.”

In addition, this solar prize brings together the coun-try’s research base with its entrepreneurial supportsystem which is made up of energy incubators, univer-sities and the U.S. Energy Department’s 17 national

laboratories, who together cancreate a sweeping portfolio ofinnovations primed for privateinvestment and commercialscale up. (3)

Reducing the costs ofsolar energyThe U.S. Department of Energyhas a Solar Energy TechnologiesOffice, who support early-stageresearch and development toimprove the affordability, per-formance and reliability of solarenergy technologies on the grid.This includes investment ininnovative research aimed atsecurely integrating more solar

energy into the grid, enhancing the use and storage ofsolar energy and to lower the costs of solar electricity.

To end this article on a positive note, we know that withthe dramatic reduction in the cost of solar, installationsin the U.S. have risen dramatically. This encouragingdevelopment, of course, creates fresh challenges forthe country’s ageing electricity grid. To cater for thesechanging needs, the office announced in September2017 a continued focus on solar energy research anddevelopment efforts that aid the country’s criticalenergy challenges, which are: grid reliability, resilienceand affordability. ■

References

1 https://www.energy.gov/about-us

2 https://www.energy.gov/articles/us-department-energy-and-national-

association-manufacturers-announce-sustainability

3 https://www.energy.gov/articles/department-energy-announces-

prize-competition-accelerate-us-based-solar-manufacturing

Open Access GovernmentJMiles@openaccessgovernment.orgwww.openaccessgovernment.orghttps://twitter.com/OpenAccessGov

Research into plasma self-organ-isation lies at the intersectionof fusion energy, astrophysics

and space propulsion. The aim is tounderstand the ability of plasmas tospontaneously re-arrange themselvesinto different shapes. Harnessing thisremarkable property can make fusionpower plants more compact, thereforemore economical and lead to fusionrocket engines. Fusion energy is abreakthrough technology for producinglimitless clean energy on Earth and forcolonising the Solar System.

Plasmas are ionized gases, heated totemperatures beyond 11,000ºC. Abovethese temperatures, the gas particlesare broken into ions and electronsthat interact with electric and mag-netic fields. We can, therefore, keepthe plasma away from cold walls oraccelerate it to provide thrust withsuitable arrangements of electric andmagnetic fields.

This is how conventional concepts forfusion energy or plasma rocket enginesoperate. For example, the world’slargest fusion energy experiment,ITER in the south of France, usesdoughnut-shape magnetic fieldsarranged in a special configurationcalled a tokamak to confine theplasma. Then, just like a microwaveoven, radio-frequency electromagneticwaves then heat the plasma to morethan 150 million degrees, whereupondeuterium and tritium particles fuseto create helium and release neutrons.

The neutrons are captured to heatsteam, turn turbines and generateelectricity. The experiment, currentlyunder construction, aims to demon-strate 500 MW of fusion power from50 MW of heating with a gigantic16,000 m3 apparatus that weighs23,000 tonnes and holds an 840 m3

burning plasma.

Plasma rocket engines use electricityto accelerate the plasma and generatethrust for spacecraft propulsion.Examples include ion thrusters usedon the soon-to-launched Bepi-Colombo mission to Mercury or Hallthrusters used in the Deep Space 1spacecraft. The primary benefit ofusing plasmas for in-space rocketengines is that the propellant can beejected at velocities much greaterthan is possible with chemicals, soless propellant is needed to fly faster.

These engines are limited by the available electricity, so solar electricpropulsion is limited by the size andmass of solar panels compounded bythe decreasing amount of sunlightavailable farther out of the SolarSystem.

How do we make power plantssmaller and how do we break thesolar power limit? One possibility is toexploit the spontaneous interactionbetween plasmas and magnetic fieldsto generate large flows or magneticstructures. With the right conditions,plasmas suddenly form flows in themagnetic doughnut that doubled theplasma confinement time. This fortu-itous discovery in the 1980s madefusion reactors smaller than wouldotherwise have been the case andforms the basis of operation of theITER tokamak.

Setthivoine You from the Department of Aeronautics & Astronautics at the University ofWashington shares his insights into the intriguing world of self-organisation in plasmas

Research on self-organisation in plasmas

94

PROFILE

Another discovery shows that with theright conditions, the plasma can forma different kind of magnetic doughnutthat can also confine the plasma.These other doughnuts are variouslycalled spheromaks, or field-reversedconfigurations and are smaller thanthe equivalent tokamak. Merging twoof these configurations generates

strong flows and converts magneticfield energy into heat. This could beexploited to heat plasma to fusiontemperatures without using microwavesnor compression. The spontaneousconversion of magnetic fields to flowsor vice-versa while generating heat ornew magnetic configurations is a signature of plasma self-organisation.

In nature, this property is observed overa wide range of scales. Reconnectionof magnetic fields and re-arrangementof magnetic tubes are at the heart ofsolar prominences, the mystery ofsolar coronal heating and the origin ofmagnetic fields around planets andstars throughout the Universe. Astro-physical jets are manifestations ofmatter rotating around stars linked bymagnetic fields.

The Mochi.LabJet experiment is thusdesigned to observe the self-organisa-tion of plasmas in a simple experimentdesigned to mimic an astrophysicaljet. Using technology derived fromfusion and plasma space propulsionexperiments, nested electrodes withmagnetic fields produce long stablejets of plasma that travel at 80 km/s.The experiment demonstrates howastrophysical jets can be remarkablystable, collimated and straight.

Setthivoine YouAssistant ProfessorDepartment of Aeronautics & Astronautics,University of WashingtonVisiting Associate ProfessorGraduate School of Frontier SciencesUniversity of TokyoCEO and Co-FounderHelicity Space CorpBerkeley, California

syou@aa.washington.eduyou@ts.t.u-tokyo.ac.jpwww.aa.washington.edu/research/youlab

95

PROFILE

Setthivoine You

TRANSPORT

96

Sustainable aviation fuels, the nextfrontier for air transport

Air transport is going through an astonishingperiod of growth. Ten years ago, there were 2.5billion passengers’ journeys a year. In 2017,

there were more than 4 billion. In 20 years’ time, weanticipate the number will have almost doubled, to 7.8billion. Each new journey offers opportunities to openup new business markets, generate social and educa-tional possibilities, bring far-flung families and friendstogether and provide a chance for people to exploreand understand our wonderful, diverse world.

But such growth in air transport brings a huge environ-mental challenge – one that the industry is aware ofand planning for. A decade ago, the aviation industryset out clear goals for carbon emissions, includingcarbon-neutral growth from 2020 and to cut CO2 emis-sions in half by 2050, compared to 2005 levels. Behindthese goals lies a comprehensive four-pillar strategy,encompassing new technology and operations, betterinfrastructure and a global carbon offset and reductionscheme (called CORSIA), which is scheduled to comeinto effect in 2021.

One of the key components of the technology pillar issustainable aviation fuels (SAF). These offer an excitingpath to carbon reduction, potentially cutting emissionsby 80% over the carbon lifecycle compared to conven-tional jet fuel. Progress on using SAF has alreadymoved faster than many predicted. In the 2000s, whenthe aviation and carbon debate began in earnest,many experts felt that SAF flights wouldn’t happenbefore the mid-2010s. In fact, the first SAF flightoccurred in February 2008, when a Virgin Atlantic 747flew a test flight from London to Amsterdam.

In the decade since, a number of airlines have con-ducted test flights that have ensured several different

types of SAF – everything from algae to jatropha plants,to municipal waste – can now be turned into certifiedaviation fuel. In recent years, sufficient amounts of SAFhave become available that some airports, notably inNorway and Australia and several airlines, such asCathay Pacific, United and KLM, have been able tosecure a continuous supply, albeit for the time beingin limited quantities.

The result of all this work has been that the number offlights using a SAF-JetA1 blend has moved from 1 in2008, to 100,000 in 2017 and we hope to reach 1 millionflights in 2020. But this is just the start. The next step isto move into large-scale production in order to createa lasting and increasing reduction in aviation’s carbonemissions.

This is where public policy becomes crucial. Biofuelsfor the automotive sector have long received encour-agement or even outright subsidy from the publicsector to incentivise production. It is now high timethat SAF is put on the same pedestal. This is all themore crucial as aviation, unlike automotive, has noalternative to liquid-energy fuels in the short-mediumterm. Hitherto, fuel refiners have not had sufficientincentive to generate aviation fuels at price levels theindustry could afford.

Why should they, when the policies encouraged themto go for automotive biofuels? Slowly, this is changing.In the United States, policies exist to ensure that a pro-portion of alternative fuels refined must be for aviationuse. And in Europe, the Renewable Energy Directive isbeing revised. Already the European Parliament hasindicated that aviation biofuels should be encouraged.Now we’re urging the European Commission and theEuropean Council to agree to this enhancement.

Michael Gill, IATA Director Aviation Environment imparts his expertise on sustainable aviation fuels and why he believes these are the next frontier for today’s air transport

TRANSPORT

97

In addition, globally we are calling for measures including:

Implementing the policy to de-risk investments into•SAF production plants, including loan guarantees andcapital grants for production facilities;

Support for brokering aviation off-take agreements;•

Support for SAF demonstration plants and supply•chain research and development;

Tax incentives for public-private partnerships for•early-stage plant development and;

Developing a harmonised transport and energy policy•including inter-department coordination, such asagriculture, transport, energy and military.

We recognise that in the past, the biofuel sector has notbeen without controversy. First generation automotiveand biomass fuels were criticised for encouraging defor-estation or promoting agri-monoculture. Fortunately,lessons have been learned. Most aviation biofuels arecertified by the Roundtable on Sustainable Biomaterials.

“In the United States, policies exist to ensure that aproportion of alternative fuels refined must be foraviation use. And in Europe, the Renewable EnergyDirective is being revised. Already the European

Parliament has indicated that aviation biofuels shouldbe encouraged. Now we’re urging the European

Commission and the European Council to agree tothis enhancement.”

Even more importantly, following unanimous adoptionof a resolution at the 2017 IATA AGM, the aviationindustry is, in the words of our Director General andCEO Alexandre de Juniac: “Clear, united and adamantthat we will never use a sustainable fuel that upsets theecological balance of the planet or depletes its naturalresources.” We are in a process of defining new sustain-ability criteria for SAF to understand how it might playa role in the CORSIA scheme, which would be a big fillipfor SAF take-up if it were approved.

If policies can be aligned to ensure aviation biofuels geta fair chance, then we believe it is possible that 1 billion

people would have the opportunity to fly on a planepowered by a mix of traditional jet fuel and SAF by2025. That is a fabulous prize to aim for.

Sustainability is the next great frontier for the industry.But aviation has a history of taming frontiers – and forproviding opportunities for people to explore their ownpersonal frontier, whether for work or pleasure. Weare confident that with the correct policy support, wecan continue that great tradition. We all owe it to futuregenerations, who expect to fly and expect to do so withminimal impact on the planet. ■

Michael GillDirector Aviation EnvironmentInternational Air Transport Association (IATA) Tel: +1 514 874 0202www.iata.orgwww.twitter.com/iata

Av Av Su of fly

Av A

F F at viation Fue ustainable

ying with

tio o in

v a a ai

via sta us us b b

F bl l b b

n a na n u ue Fu

els (SAF)e

s s e e els e

3 0003 00020131

Commercial flights

200820082008K100

2013

the first test flight in 2008We’ve come a long way since

operated on SAF ghts

0 major part in reaching to rise, it will play a consumption continueIf production and ct prod f p

ed n SAF erated on SAF AF on SAF ed o

0

2008 since

rt in reaching will play a

tion continue tion and tio o

by airlinesforward purchase agreements Liters of SAF are in current

billionLit

billion5L

555.555.555.s of SAF are in current ters of SAF are in current

5.

agreements n current n

1,02020 target100 0100,00020183,0002013 ,

2018 ,

2020 target 1,0

22008

0

K50

000,000

000

0

to 2005 levels.by 50%, compared CO2 emissions to reduce net our 2050 goal: major part in reaching

000

000 000000,000

2012

SAF can be made from

2010

evels. ompared

ssions net

goal: rt in reaching

2016

can be made from

2014

what? so what? 2018

here’s what

conventional fuel.directly withble it can beOnce

80% les SAF produces up to

Dom almost anything, evenSAF can be made from

entional fuel.tly with

ended be

processed,

s CO the wno now t

mestic waste!st anything, even

can be made from

way y that’s

na atural resourcesand avoid the depletion of nd avoid the depl conserve an ecological balance, We only use sources that No deforeNo palm oil.

c

letion of gical balance,

ces that estation. oil.

aviation fuel is required

conventional jet fuel.to over its lifecycle, compared

More production of sustainable

80% les

What can we do even better?W

innovative policies suppo And we urge governments to

red

uel. mpared

2

sustainable

s COto fl

etter?

the w

ative policies ort them with incentives and

we urge governments to

!y ly ! l way

ment incentives and impleGovernments create

d

eployment of SAF-uction and commer

ucers accelerate

engers to fly on a billion

up to pportunity for

effective policies-tives and imple

rnments create

TAVIA

De

S

Demand

Supplyuuuu

emand

upplyuu

p

cial deployment of SAFprodu Producers accelerate

passe 1 b the opportunity for

S pppSSuuuuupppp ypp ypuppppplypplyplyuuSuuup

SAF fl

light by 2025

CANADA

98

Canada’s plan to reduce carbon emissionsand strengthen their clean growth economy

In mid-February, thousands of Canadians gatheredin Ottawa for the 40th edition of Winterlude, one ofthe country’s most famous winter festivals.

They skated along the Rideau Canal, the UNESCOWorld Heritage Site that runs through the heart of thenational capital. They fuelled their excursions with cinnamon-flavoured deep-fried dough called Beaver Tailsand tire d’érable, a dessert of frozen maple syrup.

And at Ottawa City Hall, they attended an exhibit ofphotos of Sirmilik National Park, a 22,000-square-kilo-metre protected area on Baffin Island in Canada’sextreme north. The photos were taken by studentswho travelled through that magnificent region lastsummer. They captured Sirmilik’s unquestionablebeauty. But they also served as a sobering reminder.

It is in this region where the unprecedented challengeof climate change is most readily visible. WhileCanada’s temperature increases are outpacing theglobal average, temperatures are rising even faster inthe country’s northern areas.

While Winterlude celebrates Canada’s unique, winterculture – Canada’s High Arctic is warming at threetimes the rate of the rest of the country. So, the Sirmilikexhibit was a perfect complement to Winterludebecause Canadians see climate change with increasingawareness and concern.

The Government of Canada is committed to doing itspart to achieve the global goals set out in the 2015Paris Agreement. Canada was one of the first countriesto sign and ratify the historic pact.

Our country’s goal? To reduce greenhouse gas emis-sions by 30% below 2005 levels by 2030.

As a first step, Canada undertook a broad process thatinvolved all provincial and territorial governments, aswell as Indigenous leaders. We wanted to develop acomprehensive national plan to address climatechange.

People across the country helped inform this ground-breaking strategy through town hall meetings fromcoast to coast and an interactive website.

The result was the Pan-Canadian Framework on CleanGrowth and Climate Change, which was adopted onDecember 9, 2016. The Pan-Canadian Framework outlines over fifty concrete measures to reduce carbonpollution and help us adapt and become more resilientto the impacts of a changing climate.

The Framework will foster clean technology solutionsand create good jobs that contribute to a strongereconomy. A plan to price carbon pollution is at itscentre. Our national carbon-pricing approach,announced two years ago, will require all Canadianjurisdictions to have prices on carbon pollution in placeby the end of 2018.

Of course, the Framework includes other components.For example, last December, we outlined a design forCanada’s Clean Fuel Standard. It will lead to new regu-lations requiring the use of cleaner fuels in vehicles,industries and buildings.

The Clean Fuel Standard is the single largest emission-reduction policy in Canada’s climate and clean-growthplan. It could reduce Canada’s greenhouse gas emissionsby 30 million tonnes a year, by 2030.

In 2017, we also announced plans to accelerate thephase-out of traditional coal-fired electricity by 2030.

Minister of Environment and Climate Change in Canada, Catherine McKenna details the country’s plan to reduce carbon emissions and strengthen their clean growth economy

CANADA

99

And to encourage countries around the world to takesimilar action, we launched the international PoweringPast Coal Alliance with the United Kingdom.

Today, pollution from coal power contributes close to10% of Canada’s total greenhouse gas emissions. We also published draft regulations to cut methaneemissions from the oil and gas sector by 40-45% by2025. Reducing methane emissions will achieve thesame reductions as taking about 5 million passengervehicles off the road each year.

This is the lowest cost GHG reduction opportunity inthe energy sector. Through the new methane regula-tions, Canada’s oil and gas sector will become a globalleader in responsible energy production.

Then there are our investments in infrastructure tosupport electric vehicles. Canada is investing $182.5million in green infrastructure and clean technologiesand partnering with the private sector to supportdemonstration and deployment of new charging stations for electric vehicles, as well as refuelling stations for alternative fuels such as hydrogen and natural gas.

These measures take advantage of the fact that over80% of Canada’s grid is powered by non-emitting electricity. The Pan-Canadian Framework also commitsprovincial and territorial governments to work toimprove efficiency in Canadian buildings and developnew building codes. The goal is to develop the net-zerobuildings of the 21st century.

And in the area of clean technologies, our governmentwill make smart and strategic investments in researchand development and in supporting commercialisation.

The global market for clean technology is projected toincrease significantly. Canadian companies are poisedto provide solutions to global challenges.

Canada is home to 13 of the 2018 Global Cleantech Top100 list that was recently revealed at the annual Clean-tech Forum San Francisco. The government is workingto help our private sector seize new opportunities withlarge investments in clean energy, green infrastructureand clean technology.

Meeting our climate commitments and investing inclean growth are central to our plan to grow our economyas we achieve our environmental goals.

Canada will continue to advance global momentum onclimate action through its international efforts. ThePowering Past Coal Alliance, which we helped kick-startis only the most recent such example.

Last year, we published final regulations of the KigaliAgreement – an amendment to one of the most successful environmental treaties ever, the MontrealProtocol, which Canada helped organise 30 years ago.

Kigali will reduce hydrofluorocarbons used in refriger-ators and air conditioners that can be thousands oftimes more powerful than carbon dioxide in inducingclimate change.

Canada is also helping developing countries accessclean energy and climate solutions. In 2016, we com-mitted to contributing $2.65 billion over the next fiveyears to this goal.

Governments everywhere want to protect their citizensfrom climate risks. They want to build resilient commu-nities, protect investments, reduce costs and ensurepeople thrive in a changing climate.

Climate change is as much an economic issue and asocial one as it is environmental. It is as much abouttransitioning to ways of living and working that do no environmental harm as it is about protecting ournatural world from further damage. ■

Catherine McKennaMinister of Environment and Climate Change, CanadaGovernment of CanadaTel: +1 819 938 3860ec.enviroinfo.ec@canada.cawww.canada.ca/en/environment-climate-change.htmlwww.twitter.com/cathmckenna

CANADA

100

Canadian education and Indigenous peoples

Over the past decade in Canada, Canadians andIndigenous peoples have together been criti-cally scrutinising the character of the historic

and current relationships linking them. This broadsocial, cultural, educational and political movement wasinstigated by the Truth and Reconciliation Commissionon Indian Residential Schools that began in 2010. TheCommission brought focus on the painful history ofIndian Residential Schools in Canada and the multipleintergenerational traumas suffered by the peoples andcommunities subjected to them.

Indian residential schools were founded in the 1880s inCanada based on the belief that Indigenous childrenneeded to be removed from their families and commu-nities and forced to assimilate to more modern ways ofliving if they were to become useful citizens. In this way,their usefulness as citizens was understood as depend-ent on how well they could learn to imitate Canadians.

This institutional and societal practice of pathologisingIndigenous peoples and their children is deeply rootedin Canadian culture and tremendously influential in theformation of policies and initiatives intended toaddress the educational needs of Indigenous peoplesand communities. Up until very recently, most educa-tional initiatives focused on Indigenous themes andissues were couched in logic that denies the oppressivehistory and instead characterise the educational struggles of Indigenous peoples as resulting from theirown separate cultural preoccupations. Such work isfounded on the assumption that Indigenous studentswill be more motivated to stay in school if they are pro-vided opportunities to connect in some way with theirown cultures and languages.

Ironically, however, failure in school is also considereda consequence of Indigenous children clinging to

ancestral cultures that render school meaningless tothem. By persistently framing the educational strugglesof Indigenous children as their own strange culturalproblem, Canadian educational policymakers and lead-ers have effectively hidden their own complicity in theperpetuation of colonial violence against Indigenouspeoples. By fixating on the problematics of Indigenouscultures, they have failed to consider Canadian cultureas also part of the problem.

“…there is an urgent need to expand the realm ofteaching and learning in Canadian educationalinstitutions so that people can be provided with

meaningful opportunities to come to terms with thedifficult implications of the Calls.”

Canadian educational policymakers and institutionshave recently been challenged to shift this unethicalrelationship and initiate a different kind of relationshipwith Indigenous peoples when the Truth and Reconcil-iation Commissioners issued 94 Calls to Action toredress the damaging legacies of the residential schoolsand advance processes of reconciliation in Canada.

The Calls to Action (2015) seek to facilitate depthengagement with Indigenous themes, experiences andworldviews as a societal commitment while simultane-ously fostering ethical exploration of the possibilitiessuch engagement provides in imagining new ways ofliving together that are not fully circumscribed by colo-nial logics. Educational institutions across the countryand at all levels are expected to implement measuresin response to the Calls on an ongoing basis.

Thus, there is an urgent need to expand the realm ofteaching and learning in Canadian educational institu-tions so that people can be provided with meaningfulopportunities to come to terms with the difficult impli-

Vice President of the Canadian Society for the Study of Education, Dwayne Donald shares his expert perspective on Canadian education and research on Indigenous peoples

101

cations of the Calls. There are three general ways tounderstand this need. First, Canadians have not beentaught oppressive colonial histories involving their owncountry and naturally resist seeing themselves and theirnation implicated in them. This resistance, its variousmanifestations and the pedagogies associated withhelping people unlearn colonialism in the Canadian context need to be better understood.

“Indian residential schools were founded in the1880s in Canada based on the belief that Indigenouschildren needed to be removed from their familiesand communities and forced to assimilate to moremodern ways of living if they were to become usefulcitizens. In this way, their usefulness as citizens wasunderstood as dependent on how well they could

learn to imitate Canadians.”

Second, thoughtful attentiveness needs to be given tothe experiences of Indigenous students participatingin these reconciliation processes and how it feels forthem to be the subjective data of their own studies.

Third, careful consideration needs to be given to thepossibility that foundational Indigenous wisdom tradi-tions can provide insightful reconciliatory guidance onhow to reimagine education and reconceptualise thehuman being at the heart of the educative processesin Canada. The hope is that responses to the Calls toAction from educational institutions and policymakersin Canada can be inspired by the very knowledge systems that the Indian Residential Schools weredesigned to eradicate. ■

Dr Dwayne DonaldVice President, Canadian Society for the Study of EducationAssociate Professor, Faculty of Education, University of AlbertaTel: +1 780 492 5639dwayne.donald@ualberta.cahttps://csse-scee.ca/www.twitter.com/cssescee

CANADA

As a non-Indigenous scholarworking in the area of Indige-nous education, I spend a lot

of my time thinking about my ownrole in perpetuating inequality withinhigher education and answeringquestions posed by non-Indigenousfaculty, staff, and students. Thesequestions usually fall into two broadcategories. The first category consistsof questions about why I am raisingan issue or why something is impor-tant, while the second category tendsto focus on questions about whatindividuals can do now, so that theyknow about the inequities that exist.These two categories of questionspoint to some interesting aspectsabout the responsibilities of non-Indigenous individuals’ within highereducation settings. One of the firstresponsibilities is to become educatedabout the realities of Indigenous peoples and related the systems ofinequality. The second responsibilitythat I will focus on is what to do withthe knowledge that you gain whenyou become educated.

Starting with myself, I am a several-generations-removed immigrant tothe ancestral lands on which I resideand I have experienced a position ofsome privilege in the mainstreamstructures of society, such as educa-tion, health services, and other gov-ernmental systems. While I grew up ina blue-collar home and experienced

the discrimination that can be associ-ated with class and being a girl, I wasafforded many privileges and rarelyhad cause to question that I belongedin the classrooms that I occupied. Ifrequently saw myself and my lifeexperiences reflected in the classroomand my experiences within society.From a young age, I had a questioningmind and often challenged teachersabout why some voices and some lifeexperiences were not represented inthe curriculum or were represented invery narrow and proscribed ways.Through my own search for knowledgeand the generous teachings of myIndigenous colleagues, I became awareof the systems of racism and inequityexperienced by individuals who are

minoritised by the mainstream sys-tems of privilege and discriminationthat continue to be reinforcedthroughout society and particularlywithin systems of education. In myrole as a university professor, I amalso responsible for exposing under-graduate and graduate students tothese systems of inequity and to challenge their taken-for-grantedassumptions.

Some of my students resist any challenges to their understanding ofsociety and the status quo and remainfacing the first responsibility of educa-tion. Other students engage in theteaching but sink into guilt and seemparalysed by the immensity and

Dawn Zinga, from the Department of Child and Youth Studies at Brock Universityexplore the responsibilities of non-Indigenous individuals within higher educationsettings and the inequalities that exist

Non-Indigenous individuals’ responsibilitieswithin higher education contexts

102

PROFILE

complexity of the issues thy have justlearned exist. The second responsibilityof what to do with the knowledgeonce you have learned it is easier toaddress than the resistance to learningthat the world does not necessarilyoperate in a way that you thought thatit did, and that with or without yourknowledge, you have occupied a posi-tion of power and privilege. The firstthing for non-Indigenous individualsto realise is that guilt is an emotionthat will not be helpful. It must beexperienced but in the end we are notresponsible for the actions of thosewho preceded us, but we are respon-sible for how we address the legacy

that was left behind. Essentially, non-Indigenous individuals must focus onhow to act on the knowledge that hasbeen gained.

Non-Indigenous individuals have achoice. They can choose to close theireyes to uncomfortable realities andcontinue on perpetuating them orthey can chose to use their individualvoices to make a difference. Usingone’s voice can be as simple as speak-ing up when an inequality is beingperpetuated, or challenging a policythat negates other people’s experi-ences or lived realities. It can beexposing others to knowledge they

may not be aware of or supportingsomeone when that person’s view-point is being shut down as invalid orirrelevant. Sometimes it can be listen-ing to another perspective and beingopen to being challenged and educatedabout how your own actions or lack ofaction may have reinforced inequalitiesor alienated Indigenous individuals.

Addressing these two responsibilitieswithin educational contexts can leadto educational settings in whichIndigenous students and other Indige-nous individuals feel welcome andaccepted. It can open up importantspaces to talk about ways of movingforward together towards positivechange that does not reproduce orperpetuate systems of inequality.While I have focused on higher educationcontexts, this can also be extended toother educational contexts. Making achoice to address these responsibilitiesdaily is a choice to move beyond resis-tance and guilt to positive action andstrong relationships that can help us all negotiate a new future ofeducation for all students.

Dawn ZingaAssociate Professor and ChairDepartment of Child and Youth StudiesBrock UniversityTel: +1 905 688 5550 ext. 3152dzinga@brocku.cahttps://brocku.ca/social-sciences/depart-ments-and-centres/child-and-youth-studies

103

PROFILE

CANADA

104

From wheelchair to high heels: Realisingthe potential of stem cells

In 1996, a 21-year-old aspiring police officer, JenniferMolson, was diagnosed with aggressive multiplesclerosis (MS). Within five years, Jennifer was unable

to manage everyday tasks, including cutting her foodand taking a shower. The prognosis was that she wouldlive her life in a wheelchair and require constant care.Dr Mark Freedman from The Ottawa Hospital was Jennifer’s neurologist. He and his research partner DrHarry Atkins, a clinician/researcher, enrolled Jenniferin a clinical trial that took her stem cells, purified andfortified them and after extreme chemotherapy toknock out her immune system, returned the stem cellsto rebuild a new, disease-free immune system. Today,with all traces of the disease eradicated, Jennifer hasbeen cured. She has her life back – she works, enjoysfamily, skis and wears her high heels proudly. Jennifer’sstory is extraordinary and is a demonstration of whatcan be achieved through the application of stem cells.

Stem cells are powering a new and exciting scientific field– regenerative medicine – and this field is expected tohave a global market value of $53.7 billion by 2021. Stemcells are special, as they can make many copies of them-selves and give rise to more specialised, or “adult” cells.We now know that most tissues contain their own rarepopulations of adult stem cells that help with mainte-nance and repair. One particular type of stem cell isespecially powerful: known as the pluripotent stem cell,it is akin to a blank slate, capable of making any cell typein the body. Stem cells are invaluable to researchers fortheir ability to model development and diseases thatmay otherwise be difficult to study and have vastlyexpanded our understanding of how the body heals orsuccumbs to disease. This knowledge is fuelling thedelivery of new ways to regenerate or repair cells, tissuesand organs. The potential is extraordinary for fightingchronic diseases and illnesses that cost the Canadianhealthcare system upwards of $190 billion annually.

In Canada, stem cell-based treatments are beingutilised to fight severe blood disorders such asleukaemia, as well as aggressive multiple sclerosis andsome rare diseases. And this is just the beginning. Withsupport from the Stem Cell Network, clinical trials areunderway in British Columbia and Alberta that are test-ing a novel stem cell therapy for type 1 diabetes. Theresearch from these trials may change the way thosewho have type 1 manage the disease by eliminatingconstant measuring of blood sugar levels and eliminat-ing insulin dependence.

“Regenerative medicine is at a tipping point inCanada. It’s time to build on our foundation ofscientific excellence and harness the benefits ofregenerative medicine for the health of Canadians

and the economic prosperity of our nation.”

In Montreal, researchers and clinicians are workingwith a specialised molecule and state-of-the-art tech-nology that allows stem cells found in cord blood to beexpanded or grow. This is critically important work fordeveloping a stem cell product that is not only afford-able but safe and effective for the treatment of blooddiseases, particularly for patients who are currentlyineligible or do not respond well to current therapies.

Jurisdictions around the world recognise the benefits ofinvesting in stem cells – economic, population healthand individual patient outcomes. California, Japan andthe United Kingdom are all fighting to lead the field thatmatters the most for health. Canada is well positionedto compete; in fact, it was two Canadians who provedthe existence of stem cells in the early 1960s. And it wastwo more Canadian scientists who were behind the2016 launch of BlueRock Therapeutics – a multi-nationalbiotech supported with a USD$225 million Series Ainvestment. BlueRock is focused on bringing forward

Dr Michael A Rudnicki, CEO & Scientific Director at the Stem Cell Network gives an expert view on a new era in health care, powered by stem cells

CANADA

105

stem cell-based therapies for the treatment of cardio-vascular and neurological conditions. Powered withCanadian ingenuity, we know this company will succeed.

“Stem cells are special, as they can make manycopies of themselves and give rise to more

specialised, or “adult” cells. We now know that mosttissues contain their own rare populations of adultstem cells that help with maintenance and repair.”

It is just the beginning for stem cells and regenerativemedicine. The challenge is to ensure the regulatoryenvironment will allow for stem cell therapies to movethrough the clinical trials process effectively. We alsorequire stable and predictable funding for research so that next generation therapies can be realised.Canada’s small but growing regenerative medicinesector requires support to scale-up and commercialiseits products. It also requires access to a skilled and talented labour pool. And of course, the healthcaresystem must evolve and be able to integrate innovativetherapies as the new standard of care.

Regenerative medicine is at a tipping point in Canada.It’s time to build on our foundation of scientific excel-lence and harness the benefits of regenerative medi-cine for the health of Canadians and the economicprosperity of our nation. ■

Dr Michael A Rudnicki, O.C., FRSCCEO & Scientific DirectorStem Cell Networkmrudnicki@stemcellnetwork.castemcellnetwork.cawww.twitter.com/stemcellnetwork

Imag

e: ©

Dw

ayne

Bro

wn

Stud

io /

The

Otta

wa

Hos

pita

l

106

American states nullifying federal laws oncannabis prohibition. Canada poising to legalisethe herb sometime this year. There is a sense

of moving forward. But a scratch below the surfacereveals another story.

Alcohol companies, police unions and private prisonshave all lobbied against legalisation in California. Apharmaceutical company gave $500,000 to a groupopposing legalisation in Arizona, only to later get DEAapproval for a synthetic form of cannabis. Coupledwith an unfriendly administration in Washington DC,complete with an Attorney General who has vowed toaxe the policy of leaving legalised states be, the outlookin America is grim and uncertain.

In Canada, former police chiefs and politicians arelicensed commercial sellers of medical cannabis. Whilean already existing market, colloquially known as “BC Bud,” are so-far locked out and referred to asorganised crime, indistinguishable from biker gangs.

Yet, despite this, cannabis continues to provide relief topatients and recreational consumers alike. Whether oneuses for therapeutic or medicinal purposes, everyonehas cannabinoid receptors in their body. The scientificliterature is quite clear we’re dealing with a substancefar removed from tobacco or alcohol.

For these reasons and others, cannabis should be fullyembraced by the global medical profession. Cannabidiol(CBD) oil is already halting seizures within minutes ofingestion. From my experience working at a dispen-sary, countless patients have weaned off medicationthat treats inflammation but with damaging sideeffects. I, myself, reversed anxiety and depression withthe non-psychoactive CBD oil. But a holistic approachto the plant includes Tetrahydrocannabinol (THC), thecomponent that gets users “high” or “stoned.” It is THCthat shows promise in treating cancer tumours.

If the medical community requires clinical studies anddrug identification numbers before cannabis can go

Writer, medical cannabis patient, a grower and budtender for GrassRoots Medicinal in Squamish, Caleb McMillan, provides his thoughts on cannabis developments in North America today

Cannabis developments in North America

CANADA

CANADA

107

mainstream, then so be it. Clinical trials and cannabistesting are already underway by companies like CannaTech Global, CI Therapeutics, EndoCRO andSteep Hill.

The idea is simple: put government money towardsresearch and ram through legalisation in a highly controlled and regulated manner. One that considersliability issues since the medical profession needs tobe able to study and test cannabis without health risksto their patients or broader public health and safety.

But the issue is complex. The standard steps drug companies take from research to market don’t applyhere. Aside from its centuries-old history as a medi-cine, prohibition has stunned our knowledge ofcannabis and (in consequence) has made the plant aspecial “bottom-up” grassroots medicine rather than atraditional “top-down” pharmaceutical.

Meaning, it requires looking at government policy differently rather than trying to shoehorn cannabisinto traditional regulatory models.

Cannabis is simple and effective. Whether vaped, con-sumed as an oil, or in a tincture — anecdotal evidenceis abundant. It is now time for the medical professionto catch up. But having governments throw money atthe issue is like trying to hammer in a screw.

Public policy would be better served to cultivate theunderground cannabis industry that exists in NorthAmerica. These are your cannabis experts, after all.Additionally, gutting some regulations governing theactions of medical professionals and patients will pro-mote risk-taking and thus innovation and opportunity.But a culture overly concerned with legal liability makesthis suggestion a hard sell. ■

Caleb McMillanWriter, medical cannabis patient, a grower and budtender for GrassRoots Medicinal in Squamish, British ColumbiaCannabis Life Networktips@cannabislifenetwork.comhttps://cannabislifenetwork.com/www.twitter.com/CannaLifeNet

“Cannabidiol (CBD) oil isalready halting seizures withinminutes of ingestion. From my

experience working at adispensary, countless patientshave weaned off medicationthat treats inflammation butwith damaging side effects.”

Jane Carter is an active youngwoman in her 30s who works as asoftware engineer, likes the out-

doors and is planning to raise a family.Jane also has epilepsy.

As someone who has dealt with thecondition her whole life, Jane is accus-tomed to maintaining control over herseizures. However, when her usualmedication started to feel less effective, Jane confessed her concernsto a friend, who suggested medicalcannabis as a potential treatment.Jane had never considered this possi-bility, but when she tried to learnmore about it, she struggled to findtrustworthy sources. Therefore, sheturned to her physician, Dr Lisa.

Dr Lisa told Jane that although the ben-efits of cannabis have been discussedamong doctors for a few years, sheherself hadn’t yet seen any evidencefrom reputable studies showing clinicalbenefits of cannabis. The doctorexplained that as a practitioner and ascientist, she liked to have solid evi-dence and clinical experience beforeshe prescribed medication to herpatients; therefore, she would not pre-scribe cannabis to treat Jane’s epilepsy.

Jane’s story is not unique and illustratesthe medical cannabis paradox.

The medical cannabisparadoxThe medical benefits of cannabis –including pain management, seizure

remediation, muscle spasms manage-ment and others – have been wellknown for centuries. However, overthe past century, cannabis hasbecome a proscribed substance and treated as a law-enforcementchallenge. As a result, it has becomedifficult for researchers to getapproval and funding for properlycontrolled cannabis studies and usersare unable, or unwilling, to share theirexperiences. Consequently, doctorsand other practitioners lack trustedinformation on which to base clinicaldecisions.

Altogether, these factors have led to significant under-prescription of medical cannabis, there has been alarge, unfilled demand for qualityresearch, new product delivery meth-ods and consumer information on theuses and effects of this substance.

The Citizen GreencommunityIn an effort to bring together theglobal medical cannabis communityand motivate its members – includingpatients, practitioners, scientists, cultivators and manufacturers – toshare their knowledge of and experi-ences with medical cannabis, GlobalCannabis Applications Corporation(GCAC) has developed the CitizenGreen platform. This cutting-edgeplatform will facilitate the sharing ofinformation between consumers,caregivers and researchers, as well asregulators and members of other

industries, such as healthcare andcosmetics.

The Citizen Green platform is poweredby the following technologies: Can-naCube database, artificial intelligence(AI), mobile apps and blockchain.

AI, Chatbot and CannaCubeArtificial intelligence provides GCACwith the ability to bring to life all of thedata collected and managed.

AI is used for multiple applications inour platform: chatbot, advanced ana-lytics, predictive analysis and machinelearning tools. And its capability tointegrate observational and clinicalresearch findings allows us to offerdeeper insights and better outcomesfor patients and the entire community.

The AI models the relationshipbetween patients’ demographics andmedical conditions, medical cannabisfeatures and treatments effectiveness,thereby closing the loop between“pain and strain”. (TM pending)

Sanna, GCAC’s proprietary chatbot,facilitates stronger engagement withits adaptive user experience and per-sonalised recommendations via ourapps, CannaLife and Prescriptii. Thechatbot will grow smarter over time asit will bridge missing information inusers’ profiles.

CannaCube is GCAC’s medicalcannabis database. Equipped with

Bradley Moore, CEO of GCAC discusses how artificial intelligence and blockchain (trusted data)solve the paradox of limited medical cannabis data and anecdotal user information

How trusted data is helping to liberatethe power of medical cannabis

108

PROFILE

world-class data encryption and storage, this database curates ‘noisy’data aggregated from CG apps, doctorreferences, social listening and vari-ous industry inputs against thousandsof clinical study reports for validationand expansion of the data sets.

Mobile AppsThe client-facing components of CitizenGreen are two easy-to-use mobile apps:CannaLife and Perscriptii. Connected bythe CannaCube database, these appscollect and share 360-degree data relating to medical cannabis production,research, prescription and usage.

CannaLife is an app for networking,sharing peer-to peer-feedback andsearching experiential user datarelated to cannabis consumption andconsumer behaviour. Using screencapture technology, users can findinformation on medical cannabis,create a post and share it with otherlike-minded users. Then, when seek-ing information, users can call uponCitizen Green’s chatbot, Sanna, who,coupled with the world’s firstcannabis-specific Google searchengine, helps them find answers tospecific health and cannabis queries.

Prescriptii is the first consumer-facing app for medical cannabislicense holders. It takes users throughan ailment-related questionnaire and

based on CannaCube analysis, recom-mends the appropriate products tothe condition described. An interac-tive map helps users to find nearbyretailers that offer the recommendedproducts.

Sanna, the chatbot, encourages usersto evaluate their experience with thecannabis prescription. Fed back toCannaCube this information optimisesfurther recommendations and canhelp patients and their practitioners to assess.

BlockchainThe GCAC blockchain gives medicalcannabis users ownership over theirdata in a secure and encrypted envi-ronment. Unlike centralised applica-tions, blockchain uses a distributed,decentralised digital ledger to record alltransactions. GCAC recently released aWhite Paper discussing the digitaltoken it is introducing on theblockchain to incentivise users.

How CannaLife ChangedJane’s LifeWhen Jane saw a news report aboutthe CannaLife app, she was intriguedenough to install it and as she famil-iarised herself with the Citizen Greencommunity, she found many storiesfrom other epilepsy sufferers. Thismade her reconsider how cannabismight help her own condition.

Jane presented Dr Lisa with CannaLife,showing her the large database ofanecdotal patient information, as wellas research studies and manufactur-ers’ results. After reading a largenumber of consumer testimonials andsome of the research, Dr Lisa felt confident enough to prescribe Jane amedical cannabis license, using thePrescriptii app as a guide. Threemonths later, Jane’s epilepsy symp-toms had decreased considerably, andshe very rarely had seizures.

As she works with Jane on her progressin Prescriptii, Dr Lisa is getting a feel forwhat other treatments work best withmedical cannabis. She will definitely beusing the app as part of her diagnostictoolkit going forward.

Jane, meanwhile, has returned to amuch-improved quality of life. She isback to coding, rock-climbing and considering with her husband whetherit is time to try for a baby.

Bradley MooreCEOGCACTel: +1 514 561 9091bmoore@cannappscorp.comcannappscorp.comwww.twitter.com/GlobalCannApp

109

PROFILE

CANADA

110

Medical cannabis advocacy andeducation

Canadians for Fair Access to Medical Marijuana(CFAMM) is a patient-run medical cannabisadvocacy and education organisation that

began when founder and outgoing Executive DirectorJonathan Zaid ran into access barriers in obtaining hislegal medicine. Suffering with a condition known asnew daily persistent headache (NDPH), Zaid found thatof the myriad of options offered by various doctors,only cannabis provided him with the relief he needed.Instead of taking away his ability to function (a recur-ring criticism of cannabis-use), it provided him withnew ways to thrive.

While attending the University of Waterloo in 2014, hesuccessfully petitioned his student union to include hismedical cannabis in their health care coverage plan,becoming the first person to obtain insurance cover-age for cannabis in Canada. Since then, he has grownCFAMM into the leading patient advocacy group inCanada. With a large advisory team of patients andworking with leaders from across both activist circlesand industry boardrooms, CFAMM has highlightedaffordability and access issues within the current med-ical cannabis regime, as well as worked with govern-ment, official cannabis growers known as licensedproducers and the insurance industry to set up insur-ance best practices.

While CFAMM has been successful in many measures,there is still a lot of work to do, particularly aroundaffordability issues. Recently, the most pressing issuehas been the Liberal government’s stated intention toapply either a $1/gramme or 10% excise tax to boththe existing medical market and the recreationalmarket, set to come online in early fall 2018.

Medical cannabis has been legal in Canada for morethan 15 years, won largely through hard fought court

battles, several of which were heard in the SupremeCourt of Canada. Because of longstanding prohibitionistpolicies dating back to the 1930s, cannabis has notundergone the usual series of clinical trials that areusually required to prescribe a product as a medicine.

Unlike other legal medications, there is no HealthCanada approved Drug Identification Number (DIN) forthe product, meaning that it is not eligible for anyprovincial or federal drug coverage. As a result, cannabisis the only medicine in Canada to which sales taxesapply. With scarce insurance coverage and averagecosts between $7 - $11/g, costs for patients add up fast,especially for persons with chronic illness(es) who liveon a fixed government income.

“If there are any lessons the global communityshould take from the Canadian cannabis

experiment, it should be that placing stigma at thefeet of medical patients in a half-witted attempt tomake an example out of them is a poor way to earnthe trust of existing patients. At the end of the day,it will always be medical cannabis patients who willform the backbone of any future open global

cannabis markets. Governments risk crossing themat their peril.”

Claiming a desire to maintain a fully functional medicalmarket, Finance Minister Bill Morneau introduced theexcise tax by explicitly saying that the Government ofCanada does: “not want the taxation levels to be anincentive for people to utilise [the medical] systeminappropriately.”

There is limited evidence to suggest that recreationalconsumers rely on the existing legal medical system toprovide the product they want, choosing instead abroken illicit market. Indeed, this new tax accomplishes

Board Member for Canadians for Fair Access to Medical Marijuana (CFAMM), Peter Thurley, shares his views on medical cannabis advocacy and education issues

CANADA

111

little else than to further increase costs for patients whorely on cannabis as a medication and risks subjectingthem to further stigma.

In response to this, CFAMM launched a National #Dont-TaxMedicine campaign to soften the Finance Minister’sposition before the 2018 budget. Joining together withthe Arthritis Society of Canada, Jonathan Zaid and teamamassed more than 16,000 signatures in two months,sending a letter and petition to each signatories’ localMember of Parliament, as well as the Minister ofFinance. By using a collaborative approach with industrypartners and health care patient agencies, CFAMMeffectively harnessed the online support of hundredsfor visits with local elected officials, where each persondelivered the consistent message that cannabis is animportant part of their medical treatment.

Despite this work, which also included a protest infront of the Minister’s constituency office, the 2018budget contained little relief for patients acrossCanada. While token overtures, such as the exemptionof low-THC and CBD only cannabis products, weremade, Prime Minister Justin Trudeau and his Ministerof Finance stuck to the party line.

In a recent column in the Ottawa Citizen, Dr JennaValleraini, a post-doctoral researcher whose workfocuses on cannabis markets in Canada, notes that theLiberal government’s approach is ultimately “wrappedup in ideas of stigma and distrust of cannabis’ potentialas a medicine, likely tied to its “recreational” use. …cannabis comes with a relatively low risk profile and itreportedly helps many patients achieve a better qualityof life. We should support responsible access to medicalcannabis, rather than exacerbate issues around access,affordability and coverage.”

If there are any lessons the global community shouldtake from the Canadian cannabis experiment, it shouldbe that placing stigma at the feet of medical patientsin a half-witted attempt to make an example out ofthem is a poor way to earn the trust of existingpatients. At the end of the day, it will always be medicalcannabis patients who will form the backbone of anyfuture open global cannabis markets. Governmentsrisk crossing them at their peril.

As Jonathan Zaid prepares to pass the reins over tonewly appointed President and CEO James O’Hara,CFAMM remains committed to keeping the rights ofmedical cannabis patients front and centre.

If you are Canadian and haven’t already, please registeryour support for the #DontTaxMedicine campaign bysigning the petition over at http://donttaxmedicine.ca.If you need support visiting your elected officials, sendCFAMM a note at info@cfamm.ca and we would be happy to provide you with some resources for aproductive meeting.

“Medical cannabis has been legal in Canada formore than 15 years, won largely through hard fought

court battles, several of which were heard in theSupreme Court of Canada. Because of longstandingprohibitionist policies dating back to the 1930s,cannabis has not undergone the usual series of

clinical trials that are usually required to prescribe aproduct as a medicine.”

Peter Thurley became a cannabis patient in 2015 afterthe removal of a 25lb desmoid tumour that burst hisbowels and left him with significant neuropathicchronic pain, a panic disorder and PTSD. After seeinga reduction in opioid use and an increase in quality oflife, Peter became an accidental medical cannabisadvocate. He lives in Kitchener, ON and has recentlybeen appointed to CFAMM’s Board of Directors. ■

Peter ThurleyBoard MemberCanadians for Fair Access to Medical Marijuana (CFAMM)https://cfamm.ca/www.twitter.com/CFAMMcan

112

Brock University – Faculty of Social Sciences. . 102-103, OBC

Center for Molecular Imaging. . . . . . . . . . . . . . . . . . . . . . 28-29

Department of Animal Biology – University of Illinois . . 86-87Department of Biology & UF Genetics Institute . . . . . . . 54-55Department of Biology – New Mexico State University. . 50-51Department of Botany and Plant Sciences . . . . . . . . . . . 64-65Department of Emergency Medicine –BRIPPED Project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10-11Department of Natural Resources and Environmental Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76-77Department of Pharmacotherapy and Translational Research . . . . . . . . . . . . . . . . . . . . . . . . . . . 22-23

Global Cannabis Application Corp . . . . . . . . . . . . . . . . 108-109

Mateescu’s Animal Genetics and Genomics Lab. . . . . . 68-69Massachusetts Institute of Technology . . . . . . . . . . . . . . 40-41MD Anderson Cancer Center . . . . . . . . . . . . . . . . . . . . . . . 18-19

New York University School of Medicine. . . . . . . . . IFC, 14-15Northwest Research – Extension Center . . . . . . . . . . . . 72-73

On Target Laboratories (OTL) . . . . . . . . . . . . . . . . . . . . . . 24-25

Poultry Science Department . . . . . . . . . . . . . . . . . . . . . . . 70-71

School of Integrative Plant Science . . . . . . . . . . . . . . . . . 82-84

The University of Texas Health Science Center at Houston . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20-21

UC Davis Department of Molecular Biosciences . . . . . . 58-59University of Florida . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88-89University of Illinois, Chicago. . . . . . . . . . . . . . . . . . . . . . . 34-35University of Kansas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60-61

William E.Boeing Department of Aeronautics & Astronautics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94-95

INDEX

CLICK HERE TO SUBSCRIBEYou can choose from a variety of newsletters from our selection of subject areas

SUBSCRIBE FOR FREEAdjacent Open Access is pleased to offer aFREE subscription service to all our products including our regular newsletters.

We can offer you news and features focusing on a specific topic plus a monthly round-up.

www.adjacentopenaccess.org GOVERNMENTOPEN ACCESS

www.openaccessgovernment.org GOVERNMENTOPEN ACCESS

Whether you agree, disagree, or have anotherviewpoint with any news and features on our website, we want to hear from you.

Leaving a comment on any item on our website iseasy, so please engage and join the debate today.

YOUR OPINIONMATTERS

Department of Child & Youth Studies

www.brocku.ca

Child and Youth Studies (CHYS) is one of the most popular programs at Brock. Studentslearn from a broad-based approach that considers the individual child or youth withinthe context of the family, school, peer group and community. With interdisciplinaryroots in psychology, education, sociology, cultural studies and criminology, the degreegives academic background to pursue a wide variety of careers or to pursue furtherstudies in a Master's program and the new transdisciplinary PhD program.

CHYS will be hosting a multidisciplinary conference on conceptualizing children andyouth October 11-13, 2017.

Watch the CHYS website for more details:

https://brocku.ca/social-sciences/departments-and-centres/child-and-youth-studies