ISSN 2055-7612 • May 2017

GOVERNMENTOPEN ACCESS

NORTH AMERICA ANALYSIS

CHRIS BENTLEY, AGRICULTURAL RESEARCH SERVICE –USDA, EXPLAINS WHY RESEARCH MUST CONTINUE TO PROTECT CROPS FROM PESTS AND INSECTS

32KEEPING PESTS UNDER CONTROLREQUIRES ONGOING RESEARCH

Carrie Bourassa, Scientific Director,CIHR-IAPH outlines the issue of poorhealth among Indigenous communities

Canadian Cancer Society’s Rob Nuttall& Shawn Chirrey explain how ongoingsupport is needed to fight breast cancer

The opportunities provided by fusionenergy should not be overlooked, saysMichael Delage of General Fusion Inc.

IN THIS ISSUE

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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.

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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.

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Welcome to this summer editionof Adjacent Open Access –North America Analysis. In

this supplement we highlight severalarticles from organisations within theU.S and Canada. We focus on topicssuch as healthcare, the environmentand energy, highlighting a couple fromeach country.

The U.S section starts with an interviewwith Dr Percy Ivy of the National CancerInstitute (NCI), National Institutes ofHealth (NIH). The interview outlines theimportance of clinical trials withincancer research and the NCI’s NationalCancer Programme. Gynaecologic healthand research is also highlighted in afeature by Lisa Halvorson of the EuniceKennedy Shriver National Institute ofChild Health and Human Development(NICHD), NIH. Halvorson answers ourquestions about why gynaecologichealth is important and the targetareas of research for the institute.

We also shed light on agricultural pro-duction in the U.S and the importanceof pest control. An article from ChrisBentley at the Agricultural ResearchService (ARS), USDA explains whyresearch must continue to protectcrops from pests and insects. Otherarticles from General Fusion and theCanadian Nuclear Association detailthe opportunities provided by fusionenergy and its potential as an energysource.

In the Canada section, Carrie Bourassa,Scientific Director of the Canadian Institutes for Health Research (CIHR),Institute of Aboriginal People’s Health

writes about the issue of poor healthamong Indigenous communities andhow research is key to tackling it.

We also look at Cancer research inCanada, with an article from Rob Nuttalland Shawn Chirrey of the CanadianCancer Society. The article outlines howfighting the disease requires ongoingsupport for research and screening. Wealso look at how Health Minister, JanePhilpott aims to improve the lives ofCanadians through the governmentsHealth Accord Plan.

Further thought is given to renewableenergy sources in Canada. Minister forNatural Resources, Jim Carr, sets out inhis article how Canada’s clean energystrategy is charting a clear course byaccelerating the transition to renew-ables. The article highlights how Canadais increasingly focused on developingrenewable energy resources, as well asoil and gas.

I do hope that you find this NorthAmerica Analysis thought provokingand useful and as always I welcomeany comments you may have. ■

Laura EvansEditor

@Laura_AdjDigPol

HEALTHCARE ENVIRONMENT & ENERGY

CONTENTS

06 Cancer research and trainingtake centre stage in NCI’s work

Open Access Government spoke to the USNational Cancer Institute’s Dr S Percy Ivyabout the importance of clinical trials andthe agency’s role in cancer research andtraining

10 Asbestos exposure can causesignificant risks to health

Dr. Christopher P. Weis of the NationalInstitute of Environmental Health Sciences(NIEHS), shares with Editor Laura Evans thedangers of long term asbestos exposure

16 Gynaecologic research:Improving health for women

Dr. Lisa Halvorson, U.S. National Institutesof Health discusses the importance ofgynaecologic research to develop newtreatments and keep women healthy

20 Early learning and behaviourresearch at the US NICHD

Research on early learning and behaviourtranslates into effective interventions andcare, Dr James A Griffin of the NICHD atthe US National Institutes of Health

28 Out of sight: Low vision is aNational Eye Institute priority

Low vision can be a blight on the lives ofthose it affects, which is why it’s a NationalEye Institute priority, as Dr Cheri Wiggstold Open Access Government

32 Keeping pests under controlrequires ongoing research

Chris Bentley, Agricultural ResearchService – U.S. Department of Agriculture,explains why research must continue toprotect crops from pests and insects

36 Fusion energy: Unlocking thezero-emission grid

The opportunities provided by fusionshould not be overlooked. Here, MichaelDelage, of General Fusion Inc. explainsthe potential of the energy source

38 Fusion energy could be thefuture of power production

Neil Alexander for the Canadian NuclearAssociation shares why society should belooking to fusion energy to power homesand businesses in the future

HEALTHCARE ENVIRONMENT & ENERGY

40 Helping Indigenous communitiesbecome healthier

Carrie Bourassa, Scientific Director, CIHR-IAPH discusses the issue of poor healthamong Indigenous communities and saysresearch is the key to tackling it

44 Health Accord: Healthcare for all

Open Access Government highlights howHealth Minister, Jane Philpott aims toimprove the lives of all Canadians throughtheir new Health Accord Plan

48 Fighting against breast cancerin Canada

Canadian Cancer Society’s Dr Rob Nuttalland Shawn Chirrey explain how fightingagainst breast cancer requires ongoingsupport for research and screening

54 An ounce of prevention, apound of cure: What makes

successful obesity policies?Philip Sherman, Mary-Jo Makarchuk andKeeley Rose at the Canadian Institutes ofHealth Research, highlight the need forresearch to inform successful obesity policies

58Clear trajectory for Canada’sclean energy strategy

By accelerating the transition to renewables,Canada’s clean energy strategy is chartinga clear course, as Natural ResourcesMinister Jim Carr sets out here

62 POLAR: Investigating the issuesArctic communities face

Polar Knowledge Canada, a new federalorganisation, brings together indigenousand scientific expertise to look at theissues Arctic communities face today

NORTH AMERICA ANALYSIS | MAY 2017

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U.S HEALTHCARE

6

Cancer research and training takecentre stage in NCI’s work

The National Cancer Institute (NCI) is one of 27institutes that make up the National Institutes ofHealth (NIH). The NCI is the US federal govern-

ment’s primary agency for cancer research and training,and coordinates with the National Cancer Program,which supports research, training, health informationdissemination, and other programmes with respect tothe cause.

Cancer is a term that everyone worldwide is aware of,with new research suggesting that 1 in 2 people will bediagnosed with cancer in their lifetime. The NCI estimatedthat in 2016 1,685,210 new cases of cancer would be diagnosed in the US and that 595,690 people woulddie from the disease. However, the number of peopleliving beyond cancer diagnosis reached nearly 14.5 mil-lion in 2014 and is expected to rise to almost 19 millionby 2024.

Research is an integral (but not the only) part of thework conducted at the NCI. Research helps to learnmore about various forms of cancer and how to treatand prevent the disease. Clinical trials are research thatinvolves people, in order to help find to find new waysto improve treatments and the quality of life for peopleliving with the disease.

Here Editor Laura Evans speaks to Dr S Percy Ivy at theNCI, about the role of clinical trials and how cancerresearch has evolved over the years.

“Cancer clinical trials are essential for advancing thetreatment of patients. These trials are a controlledframework in which selected populations of patientswith cancer can be treated in a clinical research setting,based on results of earlier studies,” explains Dr Ivy.“Essentially, for patients the goal is to prolong their lifeand, hopefully, be cured of the disease.

“The trial accomplishes several objectives from a medical and scientific point of view; we hope it changesthe standard of care and improves the care and man-agement of cancer patients. Patients are looking forresponse, slowing of their disease and improvement intheir overall quality of life, and in some instances evenremission and cure.

“I believe that clinical trials are essential for theadvancement of cancer treatment. Networks of clinicalinvestigators allow clinical researchers to evaluate largecohorts of patients, and more efficiently evaluate newtreatments together across the country,” Dr Ivy adds.

Developing new cancer treatmentsThe Cancer Therapy Evaluation Programme is one ofthe many programmes within the NCI and is focusedon developing new cancer treatments. The clinicaltrials are made up of different phases which are usedto detect how cancer responds to specific treatments.

As Dr Ivy outlines further: “Within the Cancer TherapyEvaluation Programme there are 2 very large pro-grammes. The first is the Experimental TherapeuticsClinical Trials Network, made up of academic investi-gators across the US and Canada, who perform early phase clinical trials. The goal of those trials is todetermine how to use a drug, what the drug propertiesare, and how it should be used in humans, as well asdeveloping preliminary information on how the cancerresponds to specific therapeutic interventions.

“The other large group in the US is the National ClinicalTrials Network,” she adds. “This is a group of more than3,000 investigators who perform much larger ran-domised phase 2 and phase 3 trials. They are lookingfor signs of activity, efficacy and survival or responseto a treatment or combination treatment that will lead

Open Access Government spoke to the US National Cancer Institute’s Dr S Percy Ivy about the importance of clinical trials and the agency’s role in cancer research and training

U.S HEALTHCARE

7

to a pivotal trial. The goal is to move to phase 3 trialsthat may result in licensing the treatment for a specificdisease indication.”

Orphan diseases and rare types of cancerThe NCI is aiming to find treatments for all types ofcancer; however, they also focus on rare forms of thedisease besides what are known as the big 4 – coloncancer, breast cancer, lung cancer and prostate cancer.The rare forms are ones that are not as actively studiedor used in clinical trials by pharmaceutical companiesand have less than 200,000 cases per year, althoughthis landscape is changing.

“I believe that clinical trials are essential for theadvancement of cancer treatment. Networks of

clinical investigators allow clinical researchers toevaluate large cohorts of patients, and moreefficiently evaluate new treatments together

across the country.”

“Orphan diseases, are defined as affecting fewer than200,000 cases a year, and have not been as activelystudied,” says Dr Ivy. “In the past these orphan cancershave been much less attractive targets for pharmaceu-tical companies, so the NCI has filled this niche as anunmet medical need. Pharma is also changing andstarting to work more in niche diseases. As we find thatcancers, for example breast cancer, are really made upof a group of biologically distinct diseases that requiredifferent treatments, the challenge is to provide effec-tive treatments for all different kinds of cancer and the challenge for pharma is to define a sustainableniche market.

“The goal of the NCI is to provide those treatmentopportunities to the U.S public. The US Congressrecently passed a bill called the ‘21st Century Cures Act’that will fund $4.8bn in medical research with approxi-mately $1.8bn cancer related research. This means thatwe are able to develop synergies between programmesand initiatives that can effectively use that money inservice of the public. We will do that collaboratively with researchers, organisations and companies andwith our academic co- investigators, with the primarygoal to make treatment for cancer widely available andaccessible no matter how rare your disease is.”

A revolution in cancer research and trainingAs our knowledge of cancer evolves, new ways to treatthe disease are also established. Along with new tech-nology and key innovations, research and clinical trialsare able to understand the best treatment for a specifictype of cancer. Dr Ivy explains that cancer research isin the middle of a revolution, with new therapies suchas precision medicine and immunotherapy coming tothe forefront.

“With the exception of immunohistochemistry for PDL1,there are no biomarkers to select patients to receive antiPD-1/PDL-1 immunotherapy,” she says. “The tumoursthat have responded to these so-called checkpointinhibitors have been those that were treated in the pastwith other immunotherapy agents, especially melanomaand renal cell carcinoma.

“However, there are areas in immunotherapy treatmentthat clearly stand out for the favourable response ratesthat have been seen, including lung cancers andHodgkin’s lymphoma, as well as some rare diseases,such as Merkel cell tumours. However, the utility of thePD-1 biomarker to identify patients who are likely torespond is limited, and more work is needed to developmore robust biomarkers. What is becoming very clearwith immunotherapy, as is the case for most effectivecancer treatments, is that it needs to be combined withother therapies, including chemotherapy, moleculartherapies and radiation therapy.

“Cancer treatment globally will be changing. In additionto the scientific challenges, the high cost of treatingcancer patients with immunotherapies and other therapiesremain an issue. We must ensure that academic clinicalresearch in the public interest is available widely andnot simply to those who can afford it.” ■

Dr S Percy IvyProgram Director, NCI Experimental Therapeutics Clinical Trials Network (ETCTN)National Cancer Institute, National Institutes of Healthivyp@ctep.nci.nih.gov www.cancer.gov

Doctors and patients usuallydo not know that a problemwas even there. It is estimated

that millions of people have pancreaticcysts (2% to 13% of the general popu-lation in the United States undergoingimaging). Because of the prevalenceof these cysts, physicians often seethem in patients undergoing diagnosticimaging, but the patients commonlydo not have any symptoms from thecyst itself. This usually represents aconundrum for the doctor and patientbecause the cysts were not expected.The imaging is usually ordered for rea-sons unrelated to the pancreas (likegallbladder stones or other benign ormalignant conditions). The challengelies with the fact that the vast majorityof pancreatic cysts are benign, but asmall proportion of cysts can turn intopancreatic cancer, one of the deadliestdiseases that afflicts humans.

The common initial reaction:How do I get rid of it?Currently, the only way to cure pan-creatic cysts is with major surgery thatmay involve removal of part of thestomach and bowel, along with thepancreatic cyst(s). The surgery can belife-altering, and the procedure carriesa small risk of death. Even after con-sidering the morbidity and mortalityof the surgery, many patients receivetoo much treatment (also describedas over diagnosis) for an otherwisebenign condition, largely out of fearthat a cancer might be lurking.

Refocusing the question: What are the needles in thehaystack?Techniques to characterise thesepancreatic cysts are urgently neededto spare patients with benign cystsfrom unnecessary surgery and toidentify the patients with potentiallymalignant cysts who need surgery. In

our analogy, the haystack representsall the patients with pancreatic cysts.The needles represent the smallnumber of patients who have cyststhat may turn into cancer.

There are multiple forms of pancreaticcysts. The most common types thatcan turn into pancreatic cancer are

There are many challenges associated with identifying potentially cancerouspancreatic cysts. Here, Dr. Annabelle L. Fonseca et al explain

Identifying pancreatic cysts that might turn into cancer

8

PROFILE

intraductal papillary mucinous neo-plasms (IPMNs) and mucinous cysticneoplasms (MCNs). Studies haveshown that surgical removal of IPMNsor MCNs when they have not yetturned into cancer results in 5-yearsurvival rates of 90-100%. Conversely,if any cancer component is found inthe cyst after surgery, the survival rateis reduced by half. The current think-ing by experts is that benign cystsexhibit a cellular pattern known as lowgrade dysplasia, and that cysts with ahigher likelihood of becoming cancerhave high grade dysplasia. Currently,the only reliable method to get the cor-rect diagnosis involves major surgeryso that a pathologist can see the entiretissue specimen; a small biopsy is notusually sufficient for an accurate diag-nosis. So how do we select patientswith pancreatic cysts for surgery?

The current approach: More hay than needlesThe current approach to decidingwhich patients should receive surgeryinvolves the use of consensus guide-lines: If a patient meets the criteria,

which a group of experts decide on,then the patient is recommended toundergo surgery. This approach doesnot involve evidence based clinicaltrials, unfortunately. Although theconsensus guidelines have a relativelyhigh sensitivity of around 90% ormore (it can detect most cysts withcancer), there is a relatively low speci-ficity of 50-60% (it incorrectly classifiesbenign cysts as high risk), feeding theover diagnosis problem. How can weaccurately identify the high risk pan-creatic cysts non-invasively?

A multi-faceted, biophysicalapproach to the problem In the next few articles, we will explorethe approaches to better identify highrisk pancreatic cysts. Our approachinvolves the use of genetics, proteomics,physics, and math to overcome the cur-rent challenges that pancreatic cystspose to physicians, patients, and thegeneral healthcare system.

Vittorio CristiniCenter for Precision BiomedicineBrown Foundation Institute of Molecular MedicineUniversity of Texas Health Science Center atHouston (UTHealth) McGovern Medical SchoolTel: +1 713 486 2315Vittorio.Cristini@uth.tmc.eduwww.med.uth.edu

Eugene J. KoayDepartment of Radiation Oncology, Sheikh Ahmed Center for Pancreatic CancerResearch, MD Anderson Cancer CenterTel: +1 713 563 2000ekoay@mdanderson.orghttps://www.mdanderson.org/research/de-partments-labs-institutes/labs/fleming-koay-laboratory.html

Additional authors:

Annabelle L. Fonseca – Department of Surgical

Oncology, MD Anderson Cancer Center

Anirban Maitra – Departments of Pathology and

Translational Molecular Pathology, Sheikh Ahmed

Center for Pancreatic Cancer Research, MD Anderson

Cancer Center

9

PROFILE

Fig 1: Image A shows an IPMN with low grade dysplasia. Image B shows an IPMN with high grade dysplasia. Both cysts have smooth walls andlook generally “benign”. The challenge lies in differentiating between these 2 pre-operatively, so that the patient in Image A can be preventedfrom having a potentially unnecessary operation.

A B

“This work was sponsored by the MD Anderson Cancer Moonshots

program, Sheikh Ahmed Center for Pancreatic Cancer Research,

and National Institutes of Health grant U01CA196403.”

U.S HEALTHCARE

10

Asbestos exposure can cause significant risks to health

Asbestos is a term used to describe a group of 6naturally occurring minerals that were minedand commercially marketed for a wide variety

of products. Asbestos is just a small subset of dozensof naturally occurring elongated minerals that cancause disease if people come into contact with themon a daily basis. In the U.S exposure to these materialsis fast becoming a major health problem. Although the6 commercial forms of asbestos are regulated in theU.S for occupational exposure, some people argue thatthose regulations don’t go far enough to protect thepublic because they are outdated.

Open Access Government Editor, Laura Evans spoketo Dr. Christopher. P. Weis, Toxicology Liaison andSenior Science Advisor for the National Institute ofEnvironmental Health Sciences (NIEHS) in Bethesda, MD,about the many health problems asbestos exposurecan cause and the importance of raising awareness.

“Commercial asbestos is a silicatious mineral containingmagnesium and oxygen that can exist in a variety ofmineral forms,” explains Weis. “It is made up of longthin fibrous forms of minerals or rock. It’s the shapeof those minerals, their long, thin nature, along withother physical-chemical characteristics, which causesthem to be very poisonous.

“The shape is important because these long particlescan make their way deep into the lung by travellingalong the laminar flow of the air, as it is breathed in.Since they are made out of rock, they don’t dissolveeasily, so the lung has a very difficult time removing,dissolving and eliminating them. When the materialsthat contain asbestos are disturbed or damaged, fibresare released into the air. Once these particles are thenbreathed in, they can have a devastating impact on aperson’s health. Although sometimes the health prob-

lems do not arise until later in life so it’s often hard totell where the exposure occurred or if it was evenasbestos exposure in the first place.

“When someone breathes in asbestos, it causes aseries of inflammatory reactions in the lung. When thecells that normally remove particles from the lungcannot remove these elongated mineral particles, theysend out signals called cytokines, that trigger inflam-mation and the formation of reactive oxygen species,which results in fibrosis or scar tissue forming in thelung,” Weis says.

“Essentially, when asbestos is breathed in it causes aseries of biochemical responses that further aggravatethe problem. This can lead to a variety of diseasesincluding asbestosis, lung cancer, and a very lethal andaggressive form of cancer called mesothelioma.

“Importantly and frequently, asbestos may causenon-cancer diseases that progress and become debil-itating later in life and that we see a lot of that goingon today, in several areas, there seems to be an epi-demic of that non-cancerous disease associated withasbestos,” he adds.

Problems caused by asbestos exposureMesothelioma is an extremely aggressive form ofcancer that is almost exclusively related to asbestosexposure - often referred to as Meso. If someone getsMeso it’s almost certainly because they were exposedto asbestos. One of the main problems with diagnosisis not always knowing when exposure happened andhow, as Weis explains.

“Like most exposures there is a dose-response rela-tionship, the higher the dose the more quickly andmore severe the disease. That said, there are many

Dr. Christopher P. Weis of the National Institutes of Health, shares with Editor Laura Evans the dangers of long term asbestos exposure

U.S HEALTHCARE

11

cases of short term exposure that result in diseaselater in life, the time between exposure and disease is called a latency period. Exposure can occur today or tomorrow, and they don’t see the effects of thatexposure for months or years and sometimes evendecades, which can be problematic for many reasons.

“It’s often difficult for physicians to diagnose the causeof the disease because the patient affected doesn’teven remember being exposed in some cases. Theymay never even know that they were exposed untilthey are much older and could develop lung cancer ora non-cancer disease that could be lethal.”

Asbestos-related diseases from exposure havebecome a major problem in the U.S. People assumethat because the mineral is regulated that the problemis under control, however this couldn’t be further fromthe truth. There are still many ongoing exposures tonon-regulated asbestos that can cause debilitating orlethal diseases.

“There is a growing epidemic of asbestos-related disease in the U.S and worldwide that is going on un-addressed,” says Weis. “This is because we are stillmeasuring asbestos the same way we did back in thelate 1800’s. The Environmental Protection Agency,under recent revisions to the Toxic Substances ControlAct has proposed regulation of the 6 forms of asbestosusing assumptions that came into play decades ago.Unfortunately, regulations have not evolved with ourunderstanding of how the disease has occurred.

“Many elongated mineral forms that occur naturallypose public health hazards,” adds Weis. “They justsimply have never fallen under any regulatory map inthis country and that’s unfortunate because the expo-sure to these non- regulated forms is increasingnation-wide.

“One example of this is a tragedy that occurred in asmall mountain town in Montana called Libby. Severalhundred people were killed and thousands injured bya form of asbestos that was not regulated. There arealso cases of similar exposure that are not as focusedas the occurance in Libby, such as the use of asbestos-bearing gravel on roads and for construction materialsin California, Nevada, and in the upper United States,for example. The dust from the roads can contaminate

vehicles, migrate into homes, and provide a source ofongoing exposure that may last for years.”

Raising awareness to the risks of asbestosexposureRaising awareness of the health problems caused byasbestos exposure is key to ensuring people are awareof the risks. Especially as there is such a close linkbetween exposure and lung disease. Some people willbe unaware, for example, that if you smoke and work inplaces where you are likely to be exposed to asbestos,you run a greater risk of developing lung cancer.

Without people knowing the true damage thatasbestos exposure could cause, they are at risk. Weishighlights how the incorrect assumption that asbestosis regulated puts people at risk.

“Awareness is probably one of the most importantthings, but the only way to really reduce the risk is tobreak the exposure pathway. For example if there is aresidential development in an area known to haveasbestos – we have one just south of Washington DC forexample – and one is aware of the fact that basementsand houses are being built on naturally occurringasbestos, there are many steps that can be taken tominimise or eliminate the exposure. However, withoutknowing about this problem and without taking thenecessary actions to understand what the exposuresare, there is really no way to eliminate the exposureand therefore the disease.

“The key thing to remember and think about is thatasbestos exposure occurs to a wide variety of elongatedminerals outside of the 6 that are regulated. Until weunderstand that and take active measures to protectpublic health for the un-regulated forms of asbestos,the health epidemic that is increasing worldwide andin this country will continue,” Weis concludes. ■

Dr Christopher P. WeisToxicology Liaison and Senior AdvisorOffice of the Director – National Institutes of Health/NIEHSchristopher.weis@nih.govwww.niehs.nih.gov

The community of primary inter-est to the Penn SuperfundResearch and Training Program

(SRP) Center is surrounded andpotentially impacted by the BoRit EPAregion 3 Superfund site. The site islocated in the Ambler Borough, UpperDublin and Whitpain townships inPennsylvania.

This community has a long history ofimpact from hazardous asbestos waste.The waste disposal site is proximateto at least 2 very different types ofcommunities: the relatively poor communities of West (predominantlyAfrican American) and South (Italianimmigrant) Ambler which adjoins thesite raising issues of environmentaljustice. The asbestos fiber used waspredominantly chrysotile, which is thefiber considered to be a major causeof mesothelioma in the US.

It is of significant concern that in theAmbler zip code 19002, where theBoRit site is located, a cluster ofmesotheliomas has been observed. In1881, Henry G. Keasbey and Dr RichardMattison moved their pharmaceuticalcompany to Ambler, known initiallyfor the production of milk of magnesia.Dr Mattison discovered that milk ofmagnesia (magnesium carbonate)could be combined with asbestos tomake pipe insulators and shingles.The Keasbey and Mattison Co. wasthe leading manufacturer of asbestostextiles and products until it wasacquired by England’s largest asbestos

company, Turner Newhall, Ltd., whichmanufactured asbestos textiles andproducts in Ambler from 1934 to 1962.Asbestos-containing waste from theplant was dumped in several surround-ing areas, a practice that continuedwhen CertainTeed Corporation andNicolet Industries took over in 1962.CertainTeed ceased operations in 1974,followed by Nicolet in approximately1988. Site remediation by the EPAunder the Superfund Programmebegan in 1993. This remediation hasinvolved capping the asbestos piles,adding a soil layer and hydroseeding.However, 3 other contaminated sites,in total about 32 acres and up to 42feet deep, collectively known as theBoRit Site, and the abandoned plantsite itself continue to present an un-remediated hazard. The BoRit site wasadded to the EPA’s National Priorities

List of the most hazardous waste siteson April 9, 2009, making it eligible forcleanup, using the federal SuperfundProgramme funding.

Research to reduce effects ofhazardous asbestos in the Penn SRP CentreDespite clean-up efforts, there isconsiderable residual communityconcern about the effectiveness of theremediation and the health effects ofpotential exposure to chrysotileasbestos. This has led to 6 major con-cerns being brought to the attentionof Penn’s Centre of Excellence in Environmental Toxicology (CEET). DrTrevor Penning as Director of the CEETengaged his long-term collaborator Dr Ian Blair to establish a SRP programme configured around thesecommunity concerns (Figure 2).

Hazardous asbestos waste causes serious problems in communities in the U.S.,Ian A Blair, Penn Superfund Research and Training Program Center details

Adverse health effects of hazardous asbestos waste

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PROFILE

• Can asbestos be remediated?

• Is asbestos transported by water?

• Why is there a cluster of mesotheliomas amongwomen in Ambler?

• Is there a genetic pre-disposition to asbestos-inducedmesothelioma?

• Can asbestos-induced mesothelioma be prevented?

• Is it possible to develop blood tests for asbestos exposure and mesothelioma?

Figure 1: Six questions posed by BoRit Community Advisory Group to Penn’s Center of Excellencein Environmental Toxicology (CEET)

Project 1, which is one of the 2 envi-ronmental science projects, underpinsall the other projects.

Project 2 assesses the physics thatgovern how asbestos fibers movethrough and become trapped in soil.The project works closely with Project 3,as community exposure to remediatedasbestos in Ambler (and other areas)is strongly determined by the transportpathways of asbestos fibers in theenvironment.

Project 4will enhance our understand-ing of the pathogenesis of asbestos-related disease, specifically malignantmesothelioma, using genetically definedmouse models.

Project 5will develop chemopreventionstrategies to prevent mesothelioma.

Project 6 will develop sensitive andspecific serum biomarkers of asbestosexposure to assess potential inter-individual risks of developingmesothelioma or lung cancer. Thesix projects are supported by fourconventional Cores as well as theResearch Core in Biostatistics.

Relevant PublicationsSalamatipour A, Mohanty SK, Pietrofesa RA, Vann DR, Christofidou-

Solomidou M, Willenbring JK. Environ Sci Technol Lett.

2016;3(7):270-274.

Wu L, Ortiz CP, Jerolmack DJ. Langmuir. 2017;33(2):622-629.

Clapp JT, Roberts JA, Dahlberg B, Berry LS, Jacobs LM, Emmett EA,

Barg FK. Soc Sci Med. 2016;170:143-151.

Kadariya Y, Menges CW, Talarchek J, Cai KQ, Klein-Szanto A J, Pietro-

fesa RA, Christofidou-Solomidou M, Cheung M, Mossman BT,

Shukla A, Testa JR. Cancer Prev Res (Phila). 2016 May;9(5):406-14.

Pietrofesa RA, Velalopoulou A, Arguiri E, Menges CW, Testa JR,

Hwang WT, Albelda SM, Christofidou-Solomidou M. Carcinogene-

sis. 2016;37(2):177-87.

Mesaros C, Worth A J, Snyder NW, Christofidou-Solomidou M,

Vachani A, Albelda SM, Blair IA. Bioanalytical techniques for detect-

ing biomarkers of response to human asbestos exposure. Bioanal-

ysis. 2015;7(9):1157-73.

Ian A Blair PhDProgram DirectorPenn Superfund Research and Training Program CenterTel: +1 215 573 9880ianblair@upenn.eduwww.med.upenn.edu/asbestos/

13

PROFILE

Core A: Admin Core

Core B: Community Engagement

Core C: ResearchTranslation

Core D: Biostatistics

Research Support

Core E: Interdisciplinary

Training

CEET Administration, Translational Biomarker Facility Core, and Integrative Health Sciences Facility Core, Certificate Program, and T32 Training Program

Project 6: Biomarker of

asbestos exposure

Project 5: Chemoprevention of asbestos-

induced lung diseases

Project 4: Mesotheliomarodent models

Project 3: Social determinants ofasbestos exposure

Project 2: Asbestos mobilityand transport

Project 1: Asbestos remediation

Remediation Engineering

Mechanistic Toxicology

Health effects

Epidemiology

Environmental Justice

Hydrogeology

Fate and Transport

Figure 2: Organization of the Penn SRP Center

Immunotherapy is starting to playa major role in cancer treatmentand it was named as “the break-

through treatment of the year” in2013. Cancer immunotherapeuticagents have earned over $60 billionrevenues in 2016 and is expected tohave a market value of about $80 bil-lion in 2020. Thus, pharmaceuticalcompanies are evaluating new waysto use immunotherapy to treat cancers and develop a wide range ofimmunotherapeutic drugs for variouscancers.

Cancer immunotherapy can be definedas “use of a person’s immune systemto fight against cancer either by teach-ing it to work smart or stimulatingthe immune system by man-madeimmune components to attack cancercells”. It can also be defined as a “treatment for cancer by inducing,enhancing, or suppressing an immuneresponse”. However, the therapeuticoutcome of the immunotherapeuticagents highly depends on the type ofcancer, type of the immunotherapy,and treatment modality (mono orcombination therapy).

Whilst the immune system is sup-posed to eliminate cancer cells withinthe body, it is not able to differentiatecancer cells from normal healthy cells.Cancer cells also express CD47 (Clusterof Differentiation 47) as healthy cellsdo. CD47 is also known as integrin-associated protein (IAP) and it producesa protein named signal-regulatory

protein alpha (SIRPα) that sends don’teat me signals to the macrophages, atype immune cells, and do not activateto attack me signals to T-cells, anothertype of immune cells. On the otherhand, if it recognised that the responsemight not be strong enough todestroy the cancer cells. Moreover,cancer cells recruit immune cells suchas tumour-associated macrophages, asubtype of immune cells, which keepthe immune system in check andchase away T-cells that come to attackthe cancer cells.

Cancer immunotherapeutic agentscan mainly be classified into 4 majorcategories: Monoclonal antibodies,immune checkpoint inhibitors,cancer vaccines, and non-specificimmunotherapies.

Monoclonal antibodies in theimmunotherapeutic sector can bedefined as man-made antibodiesthat induce antibody-dependent cellmediated cytotoxicity (ADCC), byrecruiting immune cells or activatingthe complement system to attacktumour cells. Recruitment of immunecells can also be accomplished bydesigning a bispecific antibody thathas 2 different monoclonal antibodieswith one to recognise biomarker oncancer cells and a second to recognisebiomarkers on immune cells. Blincyto(Blinatumomab) is a bispecific antibodythat is used to treat acute lymphocyticleukaemia or B-cell lymphoma. It bindsto the CD19 protein on B-lymphocytes

and to CD3 on T cells. By binding toboth of these biomarkers, blinatu-momab brings T cells closer to cancercells and eliciting an immuneresponse to diminishing cancer cells.Blincyto was developed by Micrometand then later acquired by Amgen,which has conducted further clinicaldevelopment and is predicted to generate sales revenues of over $1.5billion in 2019.

The second class of immunothera-peutic agents is immune checkpointinhibitors that take the ‘brakes’ off theimmune system to attack the cancercells. The immune system has check-point proteins, such as programmedcell death protein 1 (PD-1) and cyto-toxic T-lymphocyte-associated protein(CTLA), that help to keep it fromattacking other normal cells in thebody. Unfortunately, cancer cells takeadvantage of these checkpoints toavoid being attacked by the immunesystem. A joint effort by Bristol-MyersSquibb and Ono Pharmaceutical yieldto launch blockbuster PD-1 inhibitor,Opdivo (nivolumab), in Japan formelanoma in 2014 and it expects togenerate sales revenues of $4.3 billionin 2019. Keytruda (pembrolizumab),PD-1 inhibitor developed by Merck formelanoma, is predicted to generatesales revenues of $2.9 billion in 2019.Yervoy (ipilimumab) is an example ofa monoclonal antibody that activatesthe immune system by targetingCTLA-4, a protein receptor that down-regulates the immune system. While

Dr. Kularatne, vice president of Research and Development at On Target Laboratorieshighlights cancer immunotherapy as the treatment of next generation to cure cancer

Cancer immunotherapy: Are weready to take the next big step?

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Yervoy was developed by James Allison,clinical development of anti-CTLA4was initiated by Medarex, which waslater acquired by Bristol-Myers Squibb.Industry experts have predicted thatYervoy will generate sales revenues of$1.5 billion in 2019.

Cancer vaccines are made fromaltered cancer cells that have beenremoved from the patient duringsurgery, immune cells that have beenisolated from the patient’s blood, orantigen such as protein, peptide orhapten that have been used to boostimmune cells. Cancer vaccines can beused as prevention or therapeuticmethods for cancer. In the case ofcancer cell vaccines, cells are alteredchemically in the lab to ensure theyare recognised and attacked by theimmune system and then injectedback into the patient. On the otherhand, isolated immune cells from thepatient are exposed to cancer cells,cancer antigens, or chemicals to acti-vate and then injected back into the

patient, where they should cause animmune response to cancer cells inthe body. Sipuleucel-T (Provenge) is adendritic cell (a type of immune cells)vaccine manufactured by Dendreonand received FDA approval to treatmetastatic prostate cancer in 2010.Provenge generated $303.8 millionrevenue in 2014.

The fourth category can be classifiedas non-specific immunotherapeuticmodalities that boost the immunesystem in a general way. Chimericantigen receptor (CAR) T-cell therapyis promising non-specific immuno -therapeutic modality to fight cancer.In this technique, T cells are removedfrom the patient’s blood and geneti-cally engineered in the lab to expressCAR. The T cells are then multiplied ina culture dish and infused back intothe patient’s blood. Theoretically,these T-cells should seek out thecancer cells and launch a preciseimmune attack against them. JunoTherapeutics, Kite Pharma, Novartis,

and Cellectis are conducting clinicaltrials on CAR-T cell therapies for differ-ent types of cancers. While somepatients have shown promisingresults with high remission rates, alarge number of patients have experi-enced untoward toxicities due to non-specific nature of this treatment. It’sObvious that recent deaths in the JunoROCKET trial are creating uncertaintiesabout CAR-T technology, researchersare currently trying to improve toovercome challenges of current CAR-T cell therapies.

We have to get immune cells ready tobattle against cancer cells. To out-compete the intelligence of cancercells, we have to prepare immune systems well by recognising weaknessand strengths of cancer cells. Due totumour heterogeneity, we have toprepare immune cells differently foreach cancer type.

“Every battle is won before it is fought” –Sun Tzu, The Art of War, 400 B.C. That’show I see cancer immunotherapy.

Sumith A Kularatne PhDVP of R&DOn Target Laboratories, LLC1281 Win Hentschel BlvdWest Lafayette IN 47906Tel: +1 765 588 4547skularatne@ontargetlabs.comwww.researchgate.net/profile/Sumith_Kularatnehttp://bit.ly/1Q4Ji8Vhttps://twitter.com/SumithKularatnehttp://bit.ly/GooglePlusSumithhttp://bit.ly/FacebookSumith

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In 2012, the Eunice Kennedy Shriver National Instituteof Child Health and Human Development (NICHD)established the Gynecologic Health and Disease

Branch to serve as the epicenter of gynaecologicresearch at the National Institutes of Health (NIH).Gynaecologic disorders affect women’s quality of lifein ways distinct from reproduction and infertility and,therefore, require an independent research focus andsupport. Here, Dr. Lisa Halvorson, Chief of the branch,answers Open Access Government’s questions on theimportance of gynaecologic health and of research toadvance our understanding of gynaecologic disorders.

What is gynaecologic health and why is itimportant? Gynaecologic health includes the health, structure, andfunction of internal organs, including those in the pelvis,and external genitalia that allow for normal menstrua-tion, sexual function, and reproduction without chronicor recurrent pain. Many disorders, although not fatal,can impact gynaecologic health. These include men-strual abnormalities, ovarian cysts, uterine fibroids,endometriosis, and pelvic floor disorders (pelvic organprolapse, urinary incontinence, and fecal incontinence),to name a few. In addition, there are several gynaecologicpain syndromes, such as chronic pelvic pain, chronicpain in the area around the opening of the vagina (vulvodynia), pain associated with menstrual cycles (dysmenorrhea), and painful sexual intercourse (dys-pareunia). Obstetric fistula, defined as a hole in the birthcanal, and female genital cutting also are important.

Gynaecologic disorders are fairly common and have far-reaching health and societal impacts. For instance,the most common non-cancerous gynaecologic tumorin women is uterine fibroids, with a lifetime prevalenceof 70 to 80%, of which 30% are symptomatic. Anotherdisease, endometriosis, affects approximately 10% of

reproductive-age women. Also, it is estimated that several million women in the United States suffer from vulvodynia alone, although the true prevalenceof this and other gynaecologic pain syndromes remainsunknown.  Pelvic floor disorders affect almost 25% ofU.S. women between ages 20 and 80 years. As the U.S.population ages, the number of women with pelvicfloor disorders is expected to increase substantially.The detrimental health effects of gynaecologic disor-ders can range from abnormal uterine bleeding, pelvic pain, infertility, and sexual dysfunction to substantial psychosocial illness and limitations in daily activities.The financial burden of these conditions is also veryhigh, with endometriosis and fibroids alone costing theUnited States billions of dollars every year in healthcare resources and lost work hours.

How important is research to develop newmethods for prevention and diagnosis?Despite the health and financial burdens of gynaeco-logic diseases, large gaps remain in our understandingof the key processes contributing to the developmentand progression of these disorders. Without ongoing

Dr. Lisa Halvorson, U.S. National Institutes of Health discusses the importance of gynaecologic research to develop new treatments and keep women healthy

Gynaecologic research: Improvinghealth for women

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research, the gaps will remain, leaving millions ofwomen without evidence-based prevention methods,diagnosis, or treatment.

What key target areas comprise the focus ofresearch in the NICHD Gynecologic Health andDisease Branch?Current efforts aim to support research in selectedgynaecologic areas that have traditionally been over-looked or underfunded, such as socioeconomic, racial,and ethnic disparities in reproductive health outcomes.Although NICHD funding is allocated for studies offibroids, endometriosis, pelvic floor disorders, andgynaecologic pain, our goal is to expand our portfolio toaddress a wider range of problems.

Over the past year, branch research has focused onthe following:

Supporting longitudinal studies to better understand•the natural history of gynaecologic disorders, partic-ularly in adolescents, to help identify risk factors, possible prevention strategies, and treatments;

Fostering partnerships with experts in relevant clinical•and basic science fields (e.g., neurobiology, musclebiology, cell biology, and immunology) to enhanceknowledge and resource-sharing across disciplines;

Applying powerful “-omics” approaches (e.g.,•genomics, epigenomics, and proteomics) to gynaeco-logic conditions;

Investigating stem cells as a cause and potential •therapy for gynaecologic disorders, from studies oftheir role in causing such disorders to projects thatutilise stem-cell based therapies to treat the disorders;

Developing new, non-hormonal pharmacologic treat-•ments to improve gynaecologic health;

Applying novel imaging methods and biomarkers to•gynaecologic disorders.

How does your branch support such researchand help raise awareness for gynaecologichealth?The NICHD Gynaecologic Health and Disease Branchfunds basic, translational, and clinical research toinvestigate gynaecologic diseases. We also identifyresearch needs and develop grant opportunities toaddress new or underdeveloped areas of investigation.To ensure that we have our fingers on the pulse of thevarious fields within gynaecologic health, branch staffparticipate in national and international meetings andmaintain ongoing communication with the scientificcommunity, advocacy organisations, related govern-ment agencies, and the general public.

“Gynaecologic disorders are fairly common and have far-reaching health and societal impacts. Forinstance, the most common non-cancerous

gynaecologic tumor in women is uterine fibroids, with a lifetime prevalence of 70 to 80% of which

30% are symptomatic.”

These contacts enable us to distribute informationrelated to research aims, funding opportunities, andstudy results to better convey the importance of gynae-cologic health. The branch also supports research train-ing and career development programs to create a futureof excellence in women’s health research. In short, thebranch serves as a link between the scientific commu-nity, the public, health practitioners, and different levelsof government with the ultimate goal of advancinggynaecologic research and health. ■

Dr. Lisa HalvorsonBranch ChiefGynecologic Health and Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Healthlisa.halvorson@nih.govwww.nichd.nih.gov/about/org/der/branches/ghdb/Pages/overview.aspxwww.twitter.com/NICHD_NIH

Uterine leiomyomas (fibroids)represent the most commongynaecological tumours in

women. These tumours disrupt thefunctions of the uterus and can causeexcessive uterine bleeding, anaemia,defective implantation, recurrentpregnancy loss, pelvic discomfort andurinary incontinence, as well as possi-bly mimicking or masking malignanttumours in many U.S. women at sometime during their reproductive life. Byage 50, nearly 70% of Caucasianwomen and more than 80% ofAfrican-American women bear at leastone fibroid and 15 to 30% of thesewomen develop severe symptoms.Uterine fibroids disproportionatelyaffect African-American women, whodevelop significantly larger fibroids ata higher rate and earlier ages, havemore severe symptoms and sustaintumour growth for longer periodscompared with Caucasian women.

Approximately 200,000 hysterec-tomies, 30,000 myomectomies, andthousands of selective uterine arteryembolisation’s and high-intensityfocused ultrasound procedures areperformed annually to remove ordestroy uterine fibroids with an estimated total annual cost to the U.Sof $5.9-34.4 billion. It would not be anexaggeration to state that uterinefibroids represent the most importantand prevalent benign gynaecologicproblem in the U.S. There is a criticalneed to identify alternative therapeutic

approaches for leiomyomas that donot involve surgical intervention.

Surgery, either hysterectomy ormyomectomy, is currently the primaryavenue of treatment for leiomyomas,since effective non-surgical treatmentoptions are extremely limited. Uterineartery embolisation is effective only inspecific subgroups of patients withsmall fibroids and is not recommendedfor patients who intend to becomepregnant. Gonadotropin-releasing hormone (GnRH) analogues, which suppress steroid hormones have significant side effects that restricttheir use. There is also a high rate ofrecurrence of leiomyomas once GnRH analogue treatment is discontinued.Success is now being achieved withthe use of the selective progesteronemodulator ulipristal acetate. Severalrecent clinical studies have shownthat ulipristal treatment was able tocontrol myoma-associated uterinebleeding in over 90% of cases and significantly reduce myoma volume inmore than 80% of women. This treat-ment is considered safe, even at thelevel of endometrial changes and isviewed as a promising alternativedrug therapy.

Uterine fibroids are stillmisunderstood Currently available treatments forfibroids are limited due in large part tothe fact that the mechanisms regulat-ing the development and growth of

these tumours are still not well under-stood. Many investigators in the fieldhypothesise that leiomyomas developin the uterine myometrium as aresponse to inflammation or injurycaused by local hypoxia during men-struation or the presence of bacterialor other pathogens. We and othersalso hypothesise that dietary interven-tion, with compounds known to inhibitinflammation-associated pathways,will decrease growth of fibroids lead-ing to decreased size and ameliorationof symptoms and this is now a veryactive area of research.

Several studies from the laboratory ofDr. Al-Hendy and colleagues havesupported the use of vitamin D as adietary intervention for leiomyomas.His group reported that the vitamin Dreceptor activator, paracalcitol, inhib-ited leiomyoma tumour formation ina rat model and that vitamin D alsoinhibited proliferation and collagenproduction in cultured human leiomyoma cells. Dr. Al-Hendy hasalso shown that green tea extract,given orally to women with fibroids,caused a reduction in fibroid volumeand symptoms. Green tea is a naturalproduct, commonly used as a nutritional supplement for multiplepurposes. Epigallocatechin gallate, themajor catechin in green tea, exhibitsseveral useful biological effects,including anti-inflammatory, antipro-liferative, and antioxidant effects.Studies carried out in animal models

Uterine fibroids represent a prevalent benign gynaecologic problem inthe U.S, here Romana A. Nowak of the University of Illinois explains

Uterine fibroids: Where is research heading?

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have tested the potential benefits ofadding lycopene to the diet to slowthe growth of fibroid tumours.

Lycopene is a major carotenoid present in tomatoes and has beenshown to be a powerful antioxidant.The results show that treatment withlycopene reduced the size and incidence of leiomyomas in quail byapproximately 45-52%. Recently ourlab has characterised oviductalleiomyomas that occur spontaneouslyin hens as they age, as a relativelyinexpensive, naturally occurringanimal model for fibroids. We nowhave preliminary data showing thathens fed a flaxseed diet showed adecrease in the size of the fibroidscompared to hens fed the normalcorn-based diet. Thus, dietary inter-vention for treatment of symptomaticfibroids has great potential but thereis a critical need for larger scaledietary trials in naturally occurringanimal models as well as in women.

Fibroid tumours represent manygenotypes and somatic mutationsand are also strongly influenced byepigenetic factors including inflamma-tion, ethnicity, parity, metabolism anddiet, and hormonal environment. Several physiological pathways havebeen implicated in the developmentof leiomyomas. However, geneticmutation is strongly thought to be theroot cause of leiomyomas. Approxi-mately 40% of leiomyomas have non-random chromosomal abnormalities.These cytogenetic abnormalities likelyreflect general genomic instability,however mutations in leiomyomasthat may underlie such genomic instabilities are only beginning to beunderstood. Mutations in a smallnumber of genes including fumaratehydratase (FH), the high mobility

group AT-hook 2 (HMGA2) gene,tuberin (TSC2) and mediator complexsubunit 12 (MED12) have been implicated in the initiation of thesetumours. Several studies have nowbeen published demonstrating thatMED12 mutations are present in 56-73% of uterine fibroids. Polymor-phisms in genes such as CYP17 andcathechol-O-methyltransferase, havealso been associated with a higherrisk of developing leiomyomas.Recent studies have indicated a rolefor miRNAs in that many miRNAsincluding miR-21, miR-363, miR-490,and miR-137 have been shown to bedifferentially expressed in leiomyomas.As new therapies are developed, theheterogeneity of this disease becomestherapeutically relevant, and a broaderknowledge of its genetic basis is vitalfor tailoring specific therapies topatients. Identification of previouslyunknown genes whose altered expres-sion and function may contribute tothe initiation and growth of fibroidtumours will lead to better therapeutictreatments.

In contrast to other areas of tumourbiology, the number of publishedstudies reporting whole-genome orwhole-exome deep sequencing ofleiomyomas is relatively few. Thesestudies have confirmed the highprevalence of MED12 mutations inleiomyomas and have also confirmedaberrations in HMGA2 and TSC2. How-ever, the populations studied appearto have limited diversity, and the datasets from most of these papers arenot freely available to the scientificcommunity, leaving a significant gap inour understanding of the genetic andmolecular underpinnings of this dis-ease. Thus there is a critical need toprovide better insight into leiomyomabiology through the identification of

previously unknown genes whosealtered expression and function maycontribute to the initiation and growthof leiomyoma tumours. This includesinvestigating the potential role ofviruses in leiomyoma pathology, byusing RNAseq methods to detectactively transcribed viral genes.

“By age 50, nearly 70% of Caucasianwomen and more than 80% ofAfrican-American women bear at leastone fibroid and 15 to 30% of thesewomen develop severe symptoms.”

The Eunice Kennedy Shriver NationalInstitute of Child Health and HumanDevelopment (NICHD) has establishedthe Gynaecologic Health and DiseaseBranch whose focus is on gynaecolog-ical diseases and women’s reproduc-tive health. One of the priority areasfor NICHD is uterine fibroids andthere have recently been fundingannouncements for proposals focusingon gene sequencing studies and onnew therapeutic approaches to treatfibroids. The next 3-5 years will likelylead to major advances in the treat-ment of uterine fibroids as a result ofthese studies.

Romana A. Nowak, PhDDepartment of Animal SciencesUniversity of IllinoisTel: +1 217 244 3902ranowak@illinois.eduhttp://ansc.illinois.edu/

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Early learning and behaviour research at the US NICHD

The National Institute of Child Health and HumanDevelopment, at the National Institutes for Health(NIH), was established with support of Congress,

to study the ‘complex process of human developmentfrom conception to old age’. Here, Dr James Griffin,Deputy Chief, Child Development & Behavior Branch, atthe NICHD answers Open Access Government’s ques-tions with regards to early learning research and theimpact this can have on a child’s development.

How does research help us to furtherunderstand child development and theimportance of this?Research funded by the Child Development andBehavior Branch (CDBB) within the Eunice KennedyShriver National Institute of Child Health and HumanDevelopment (NICHD), helps us to understand andmake sense of child development in all its complexi-ties. Basic research helps us to understand the com-plex relationship between genetic and environmentalfactors as they interact to shape brain developmentand early learning and behaviour. This basic research,in turn, helps to inform translational research thataddresses topics ranging from how to promote optimalhealth and development over time to how to createand implement interventions addressing the needs ofchildren at-risk for language and learning delays andbehavioural difficulties.

How does the NICHD support research in childdevelopment, particularly in early learning? The Early Learning and School Readiness Research Program within CDBB funds a range of research studiesseeking to understand the influences that cometogether to support or hinder early childhood develop-ment and how they impact early learning opportunitiesand affect a child’s ability to make the successful tran-

sition to school. Studies supported include: descriptivestudies of how early care environments (home, familyand centre-based child care) are associated with laterschool achievement and adjustment; intervention stud-ies in paediatric primary care settings that examine theimpact of early developmental interventions duringwell baby/child visits on parent and child behaviors(e.g., increased parent reading to the child, decreasesin problem child behaviours); and preschool interven-tion studies that attempt to boost school readinessskills, including early language, pre-literacy, earlynumeracy, and self-regulation, social-emotional andsocial skills prior to entering kindergarten.

“Several studies that have followed children fromdisadvantaged backgrounds who received a

preschool intervention continue to show positiveeffects on academic performance and behaviour

well into adulthood.”

How important is early learning for a child’s development?Early learning is both the result of and shapes the over-all development of a child. Parents, siblings and otherfamily members, and caretakers are an infant’s firstteachers, and interaction with them provides essentiallearning opportunities, as well as influencing the phys-ical health and safety of an infant. Infants learn how tointeract with the world from these early experiences,developing early gestures and vocalisations leading tolanguage, and the capacity to better regulate their ownemotions and behaviour. Lack of appropriate stimula-tion (unresponsive caretakers, lack of reciprocal language exchanges, unmet physical and emotionalneeds) can result in less developed early language andlearning skills and difficulties regulating their ownimpulses and behaviours. Such deficits will make it

Research on early learning and behaviour translates into effective interventions and care, Dr James A Griffin of the NICHD at the US National Institutes of Health

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more difficult to interact with family members andpeers and may make it difficult for a child to transitionto a school environment.

How does early learning impact childrenlater in life?Several studies that have followed children from dis-advantaged backgrounds who received a preschoolintervention continue to show positive effects on academic performance and behaviour well into adulthood. These interventions commonly employeda stimulating preschool environment coupled withhome outreach focused on parent skill training andsupport. The current hypothesis is that these interven-tions, above and beyond enhancing immediate schoolreadiness skills, produced long-term effects by promot-ing children’s early executive function (EF) skills. Theseskills, developed in the first three years of brain devel-opment and then again in late adolescence, help children to regulate their own behaviours by teachingthem impulse control, the ability to shift and focustheir attention, and other abilities necessary for bothlearning and social interactions. These EF skills likelyhelp children in their transition to school, providingthem with an increased ability to learn in school, makefriends, and engage in fewer problematic and disrup-tive behaviours. The cumulative effect increases thelikelihood of a positive outcome in adulthood, relativeto peers raised in the same disadvantaged environ-ments who did not receive a preschool intervention.

How does research help to figure out thebest ways for parents and caregivers to helpchildren develop early skills?NICHD has funded research ranging from observationalstudies of parenting behaviours in home and laboratorysettings to intervention studies that attempt to teachearly parenting skills. Both types of studies have resultedin recommendations regarding: talking and reading withchildren from infancy onward; how to interact with themto promote their early language skills and promotecuriosity about the world around them; providing asecure attachment relationship that provides a safe basefrom which a child can explore the world from infancyonwards; and sensitive support from dependence toindependence and a greater capacity for self-regulationand social exploration with peers.

How can areas such as home life/theenvironment/economic stability impact achild’s early development?NICHD has supported a range of studies examining howstability in home life, family income, and neighbourhoodconditions etc. impact children’s early development.Fluctuations in income and neighbourhood conditionsare often beyond the control of parents, but earlysources of stress for infants and young children oftencan be changed once parents understand how suchstress negatively impacts their children’s developmentand capacity to learn. Examples of home environmentstressors include constant loud music, television orcomputer sounds that may make it difficult for a youngchild to focus their attention or which disrupt theirsleep, lack of space for a child to safely move about andplay, and lack of safe and age-appropriate toys andhousehold items for the child to manipulate and playwith. Chronic exposure to stressors may negativelyimpact a child’s development of executive function andschool readiness skills. ■

Dr James A GriffinDeputy Chief, Child Development & Behavior Branch – EarlyLearning and School Readiness Research ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthJames.Griffin@NIH.GOV www.nichd.nih.gov/Pages/index.aspx www.twitter.com/NICHD_NIH

Judith Mercer and Debra-Erickson Owens have found positive changes after ashort delay in cord clamping, indicating the benefits of umbilical cord blood

Umbilical cord blood: A life enhancer for all babies

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When cord clamping isdelayed at birth (DCC), aninfant receives a placental

transfusion and benefits from a 30%increase in blood volume and a 50%increase in red cell volume, resultingin increased iron stores over the first6 months of life. Red blood cells hold80% of the iron in our bodies, makingthis added volume of red blood cellsresponsible for the observed increasein iron stores. Thus, DCC results in lessiron deficiency in early infancy.

Iron deficiency in infancy has beenshown to adversely affect cognitive,motor, socio-emotional, and behavioural

development. These first 6 months oflife coincide with the most criticalperiod of brain growth and myelindevelopment, during which most ofthe brain’s eloquent neural pathwaysare established and refined. Iron is anessential component of myelinationwhich is critical for normal braindevelopment and function.

Mercer and Erickson-Owens decidedto take the current research a stepfurther and look at the effect of DCCon brain development and myelinationover the first 2 years of life in infantsreceiving either DCC, or immediatecord clamping (ICC) at birth. They

wondered if the higher iron storesfrom DCC would result in greater brainmyelin content at 4 months of age.

Significant positive changein brain myelinationMyelin is a fatty white substance thatis wrapped around nerve cells in thebrain to form an insulating layer andcreates the white matter in our brains.Myelinated white matter is a corner-stone of human neurodevelopment,establishing and maintaining efficientcommunication pathways across specialised neuronal systems. Ironplays an essential role in the formationof the cells responsible for producing

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myelin. Animal studies clearly link low levels of brain myelin with irondeficiency and neurodevelopmentalimpairment. Also, abnormal myelina-tion underlies a variety of childhooddevelopmental disorders, includingconditions such as dyslexia andautism, thus making it a key area ofstudy. Through their research, Mercerand Erickson-Owens hope to fill theknowledge gap on the effects of cordclamping time, at this critical anddynamic period of infant neurodevel-opment.

“We chose to do this study because ahigh percentage of babies world-wideare anaemic or iron deficient (ID) by 6to 9 months of age. Cord blood is anexcellent source of iron and is readilyavailable to every infant via placentaltransfusion at the time of birth.Anaemia and ID in infancy are alsoassociated with decreased cognitiveabilities, and behavioural problems.And, there is good evidence for thesafety and benefits of DCC.”

After receiving US National Institutesof Health funding, Mercer and Erickson-Owens were joined by Dr Sean Deonito launch their latest study known asthe ‘Infant Brain Study’. Deoni broughtexpertise in using MRI scanning toexamine myelin and normal braindevelopment in infants and children.Normal healthy women delivering atterm with healthy foetuses wererecruited and randomised to eitherICC (within 20 seconds) or DCC (5 ormore minutes). [If the provider feltthat they could not delay cord clamping,they were instructed to milk the cord 3to 5 times – a safe alternative to DCC].At 4 months of age, blood sampleswere collected and MRI quantitativemyelin scans were done with accom-

panying developmental assessments(within one week of scanning). Currentlythese researchers are reporting thestudy’s 4-month MRI scan results andare awaiting the 12 and 24-monthresults to be finished later this year.

Most of the MRI scans were conductedin the evening so infants could bescanned during natural sleep. Mothersput infants to sleep in a comfortableroom and they were then placed onthe scanner table and inserted intothe MRI scanner. Several techniques –ear covers, special headphones, slow-ing the scanner, and noise insulation –were used to reduce noise. The imagingtimes ranged from 20 to 30 minutes.Parents were invited stay in the MRIroom or wait outside. If the childwoke, mothers attempted to get them back to sleep and the scan wasrestarted.

Haemoglobin higher afterdelayed clampingThere were no significant differencesbetween the mothers or infants ineach group – an important finding inany clinical trial. Drainage of the placental blood showed that infantswho had ICC left about 30% moreblood in the placenta. Blood levels ofhaemoglobin were higher in thoseinfants who received DCC, withoutany adverse effects. Ferritin levels (aproxy for iron stores) at 4 months ofage were higher in the DCC infants, asexpected.

There was significantly more myelincontent in several areas of the brain inthe infants with DCC, compared tothose with ICC. Differences occurredin the earliest myelinating brainregions such as the cerebellum, theinternal capsules, and the motor

cortex. As the infants were just 4months old at the time of scanningand these are the brain areas that arerapidly myelinating during this stageof development, DCC appears to havea significant impact on myelinationacross the brain. Thus, placentaltransfusion (DCC & milking) facilitatesthe transfer of residual placentalblood without adverse effects andsupports increased brain myelinationat 4 months of age.

This study, in its fifth year, will be completed in December 2017. Currently,Mercer and Erickson-Owens areawaiting the results of the MRI scansof brain myelin content and paralleldevelopmental testing at 12 and 24-months. They expect differences at2 years of age when data on younginfants is more robust. A Swedishstudy that reported no differences indevelopment at one year for childrenwho had DCC or ICC at birth, foundsignificantly better outcomes at 4years in fine motor skills and social-emotional functioning.

Dr Mercer began her research exam-ining DCC for preterm infants as theyhave the most serious life-threateningproblems. In 2006, she reported lessbleeding in the brains of infants whohad only a brief delay in cord clamping(30 to 45 seconds), compared toinfants who had immediate cordclamping. Her work has been repli-cated by others and these findings arethe major reason DCC is beingadopted at the time of birth of prema-ture infants. Erickson-Owens joinedher in 2005 and added her researchwhich examined umbilical cord milkingin term infants. Her study showedthat milking the cord at caesareansection was safe and resulted in

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better haematocrit levels at 2 days ofage – a marker of better iron levelslater in infancy.

Umbilical cord blood andstem cellsIn the future, these researchers planto explore stem cells in umbilical cordblood. Stem cells augment the infant’sown healing system in ways that maybenefit the child not only in infancybut over his lifetime. Umbilical cordblood contains many millions of stemcells that help to protect the infant. Ifthe cord is cut right away, the infantwill leave about 80 millilitres of blood,containing approximately 1 billionnucleated cells behind in the placenta.However, both human and animalsstudies demonstrate the immensehealing power of stem cells.

Human umbilical cord blood stemcells, used for transplants in humandiseases, are remarkably successful in

promoting healing. In the UnitedStates and Japan, scientists areextracting stem cells after birth andplacing them back into the bodies ofinfants afflicted with a life threateningcondition known as hypoxic-ischemic-encephalopathy. They have had somesuccess in reducing mortality. Mercerand Erickson-Owens believe theseprecious stem cells should be allowedto transfuse into every infant’s body atthe time of birth and that they mighthelp prevent or lessen the severity ofthis devastating disease. There is,however, a dilemma. The infants whomay need their stem cells the mostoften receive ICC. Current neonatalresuscitation policies demand ICC sothat infants can be quickly moved towarming tables, denying a placentaltransfusion to the very babies whomay benefit the most.

To address this problem, scientists inthe UK and the US are conducting

research on resuscitating infants nearthe mother with the umbilical cordintact to allow the placental transfu-sion to continue. In order to examinewhether obtaining cord blood at birthwould help these infants, a team fromVirginia is conducting a large trial inwhich they will resuscitate preterminfants without clamping the cord. Ifsuccessful, this will encourage transi-tioning of all infants with an intact cord.

Umbilical cord blood donationis not the answer But shouldn’t parents be altruistic anddonate their infant’s umbilical cordblood? In 2017, experts still do notknow how to prevent most newborndiseases, such as cerebral palsy,hypoxic-ischemic-encephalopathy,and persistent pulmonary hyperten-sion. While some treatments such ashead cooling for encephalopathy haveimproved outcomes, still over half theinfants who develop this condition are

Judith Mercer PhDProfessor EmeritaUniversity of Rhode IslandResearch ScientistWomen & Infants HospitalTel: +1 401 480 1542jsmercer@uri.edu

Debra-Erickson Owens PhDAssociate ProfessorUniversity of Rhode IslandResearch ScientistWomen & Infants HospitalTel: +1 401 874 5344debeo@uri.edu

www.womenandinfants.org

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PROFILE

either permanently disabled or die intheir first 2 years of life.

Mercer and Erickson-Owens do notsupport cord blood donation at thistime except in rare cases such asblood for a sibling in need. Instead,they urge scientists to continue tolearn how to make the umbilical cordstem cells proliferate or expand in thelaboratory so they can be used fortransplantation. Some modest successhas resulted in reproducing stem cellsbut they are not yet as potent whentransplanted as the stem cells fromcord blood. The race to find the perfectmedium continues. Even after a longdelay in cord clamping, there is still asmall amount of blood remaining inthe placenta, which could providemany stems cells via successfulexpansion techniques. Meanwhile,scientists have identified stem cells inthe umbilical cord tissue itself, inamniotic fluid, and in the placenta. Allof the sources are under intensestudy to develop them as alternativesto cord blood stem cells.

It is true that the usual obstetricalpractice of ICC, a practice lacking evidence-based support, denies aninfant up to 50% of its iron rich redblood cells and stem cells. The birthsetting can influence the timing of cordclamping. Historically, obstetriciansdelayed cord clamping in hospital.However, in the middle of the last century there was a major shift to ICC.The shift in practice led to institutionalpolicies and the adoption of ICC whichwe now know does not benefit theinfant’s well-being. Many midwiveshave used DCC throughout history,often in birth centres and home birthsettings, but institutional policiesoften prevent this practice.

Mercer and Erickson Owens are pas-sionate about umbilical cord clampingand present their work nationally andinternationally. Their ongoing researchsupports the idea that DCC (or milking)is a low tech, no cost approach that is valuable for all infants of all gesta-tional ages across the globe.

“Our knowledge about the value ofcord blood for infants is akin to whatwe knew about colostrum fifty yearsago when most people thought it didnot matter and could be discarded!Now we know of its great value tonewborns. All babies can benefit froma placental transfusion.”

General References

(2017). “Committee Opinion No. 684: Delayed Umbilical Cord

Clamping After Birth.” Obstet Gynecol 129(1): e5-e10.

Andersson, O., B. Lindquist, M. Lindgren, K. Stjernqvist, M. Domel-

löf and L. Hellström-Westas (2015). “Effect of delayed cord clamp-

ing on neurodevelopment at 4 years of age: A randomised clinical

trial.” JAMA Pediatrics 169(7): 631-638.

Erickson-Owens, D. A., J. S. Mercer and W. Oh (2012). “Umbilical

cord milking in term infants delivered by caesarean section: a ran-

domised controlled trial.” J Perinatol 32(8): 580-584.

Gonzales-Portillo, G. S., S. Reyes, D. Aguirre, M. M. Pabon and C.

V. Borlongan (2014). “Stem cell therapy for neonatal hypoxic-is-

chemic encephalopathy.” Front Neurol 5: 147.

Lawton, C., S. Acosta, N. Watson, C. Gonzales-Portillo, T. Diamandis,

N. Tajiri, Y. Kaneko, P. R. Sanberg and C. V. Borlongan (2015). “En-

hancing endogenous stem cells in the newborn via delayed umbil-

ical cord clamping.” Neural Regen Res 10(9): 1359-1362.

Lozoff, B., J. B. Smith, N. Kaciroti, K. M. Clark, S. Guevara and E.

Jimenez (2013). “Functional significance of early-life iron deficiency:

outcomes at 25 years.” J Pediatr 163(5): 1260-1266.

McDonald, S. J., P. Middleton, T. Dowswell and P. S. Morris (2013).

“Effect of timing of umbilical cord clamping of term infants on ma-

ternal and neonatal outcomes.” Cochrane Database Syst Rev 7:

Cd004074.

Mercer, J. S. and D. A. Erickson-Owens (2014). “Is it time to rethink

cord management when resuscitation is needed?” J Midwifery

Womens Health 59(6): 635-644.

Rabe, H., J. L. Diaz-Rossello, L. Duley and T. Dowswell (2012). “Effect

of timing of umbilical cord clamping and other strategies to influ-

ence placental transfusion at preterm birth on maternal and infant

outcomes.” Cochrane Database Syst Rev 8: Cd003248.

Sanberg, P. R., R. Divers, A. Mehindru, A. Mehindru and C. V. Borlongan

(2014). “Delayed Umbilical Cord Blood Clamping: First Line of Defense

Against Neonatal and Age-Related Disorders.” 21(6): 243-249

Todorich, B., J. M. Pasquini, C. I. Garcia, P. M. Paez and J. R. Connor

(2009). “Oligodendrocytes and myelination: the role of iron.” Glia

57(5): 467-478

Winter, J., J. Kattwinkel, C. Chisholm, A. Blackman, S. Wilson and

K. Fairchild (2016). “Ventilation of Preterm Infants during Delayed

Cord Clamping (VentFirst): A Pilot Study of Feasibility and Safety.”

Am J Perinatol.

Research into cognitive development in infancy has thrived over recent years,but there’s still a lot we don’t know, as UCLA Professor Scott P Johnson writes

What do we know about cognitivedevelopment in infancy?

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Our research focuses on theorigins of knowledge inhumans. The past several

decades have witnessed a blossomingin research on perceptual and cognitivedevelopment in infancy, and a viewhas emerged that infants take in farmore information, and are moreaware of their surroundings, than weoften give them credit for.

By the end of the first year after birth,infants seem to know many of thebasics of the world around them:Objects tend to behave in certainways (e.g., they persist when they arehidden), people interact with eachother using language and gesture,and moving around and handlingobjects are good ways of obtainingmore knowledge.

Despite these advances, fundamentalquestions remain concerning how thisstate of knowledge comes to be. TheUCLA Baby Lab explores these ques-tions with preferential looking and eyetracking paradigms, as well as connec-tionist modelling of developmentalphenomena. Because the focus is on origins, we are less interested inparticipating in traditional “nature vs.nurture” debates (though we do itanyway), than in understanding andelucidating precise developmentalmechanisms: Endogenous prenatal orpostnatal organisation; the role ofexperience in shaping responses torecurring patterns; contributions ofperceptual (i.e., low-level) skills to

cognitive (i.e., high-level) functions;and the context of the family and widersocial environment. The question oforigins of knowledge lies at the inter-section of developmental psychology,social psychology, vision science, cognitive science, and developmentalneurobiology.

Cognitive development ininfancyMany “smart” mechanisms emergefrom simple mechanisms, given theright environment. Infants are bornwith rudimentary perceptual andlearning skills and a handful ofreflexes, but there is little evidencethat “knowledge” is available toneonates, beyond the ability toacquire information quickly and retainit over short intervals.

Within several months, however, thesituation is radically different. Thegoal of our research is to explaindevelopmental phenomena, first bydescribe age-related changes in visualperception and early learning abilities,and then by revealing the mechanismsresponsible for these changes. Wedistil a question to its fundamentalessence, see how and when infantsrespond to the simplest possible version of a cognitive challenge, andfrom there, develop new theory.

We devote a lot of time and energy tonew methodological advances, suchas computer-controlled experimentsand eye movement recordings ininfants. Computer-controlled experi-ments give us precise management ofstimulus generation and presentation.

Scott P Johnson, PhDProfessor of Psychology, Professor ofPsychiatry & Biobehavioral SciencesUCLATel: +1 310 825 5537scott.johnson@ucla.eduwww.babylab.ucla.edu

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Recording eye movements is technicallychallenging but the resulting data areincomparable in their precision, and, Ibelieve, bring us as closely as possibleto what infants are thinking. We alsouse imaging techniques such as fMRIand EEG (functional magnetic resonanceimaging and electroencephalography)in studies of cortical correlates of perception and learning, and compu-tational models of perception.

Our research programme currentlyinvolves studies of infant social atten-tion and infant statistical learning.

Infant social attentionThe means by which humans acquireand represent knowledge of otherpeople is fundamental to social andcognitive science, and a central questionasked by developmental psychologistsconcerns how infants learn so muchin so little time in the absence ofexplicit instruction. The rapidity andapparent ease with which infants andyoung children understand and produce speech, recognise faces, andinterpret others’ mental states, forexample, have led to suggestions thatinnate cognitive mechanisms providesome knowledge in each of thesesocial domains.

Yet such views may risk neglecting the potential roles of perception,attention, learning, and experience inguiding social development. Recenttheoretical proposals that account forsuch skills, such as social-orientingmodels, hold tremendous promise forelucidating the nature and origins ofhuman social cognition. Central tothese models is the possibility thatsocial attention in infancy serves toidentify targets that afford social relationships which in turn promotenormative brain and behaviouraldevelopment. This cycle acts like apositive feedback loop, affecting

subsequent social development.Social attention, therefore, is the initial“gateway” through which the socialenvironment is engaged.

Social attention develops in context,and a central research question iswhether differences in social context– for example, language background orracial composition of the family – yieldspecific “downstream” consequencesfor categorisation, just as social categories, once formed, have conse-quences for impressions, attitudes,stereotypes, and prejudice. A series ofstudies currently underway examinesinfants’ ability to discriminate or cate-gorise various properties such asgender and emotion from face andbody stimuli. We recently discoveredvisual preferences for minority faces(African-American and Hispanic) vs.White faces in Hispanic and White 11-month-old infants, a finding thatmay bear important implications forthe origins of social cognition andsocial categories.

Infant statistical learning“Statistical learning” refers to the ability to detect associations amongitems such as visual stimuli or words,eventually leading to grouping anddetection of coherence among itemsand the acquisition of sophisticatedknowledge structures, such as wordsand sentences. That is, statisticalcomputation mechanisms may contribute to early language acquisitionby segmenting the speech stream intounits.

Statistical learning exists broadlyacross sensory modalities. Certainanimal species have been found tolearn statistically structured speechstreams, and human infants canparse streams of musical tones basedon statistical probabilities and detectstatistical information in sequences of

discrete, looming shapes. These resultsimply a domain-general statisticallearning device that is available earlyand operates across modalities,across time and space, and acrossspecies, suggesting that statisticallearning might be a predisposed, general associative mechanism. Thishypothesis is supported by reports ofstatistical learning of visual and linguistic sequences in newborns,constituting evidence for sensitivity tostatistical information at birth in atleast two modalities.

However, more recently, research in theUCLA Baby Lab has revealed strikinglimits in infants’ visual statisticallearning, and revealed some of thefundamental perceptual mechanismsunderlying learning performance.Current evidence suggests that statis-tical learning actually consists of thegradual accrual of “chunks” of structure,not specific computations. Alternatively,statistical computations might contribute the first steps in patternlearning, to be superseded by achunking mechanism that does notretain statistical information.

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Out of sight: Low vision is a National Eye Institute priority

Low vision can be a blight on the lives of those it affects, which is why it’s a National Eye Institute priority, as Dr Cheri Wiggs told Open Access Government

Around 4.2 million people in America are visuallyimpaired, which is expected to increase to 7.2million in 2030. Of those 7.2 million in 2030, 5

million will have what is known as low vision. Lowvision is an impairment characterised by partial sightthat cannot be corrected or treated by wearing glasses,contact lenses or through surgery. With people livinglonger it has now become a major public health concernin America.

Having low vision can have a devastating impact onsomeone’s life. The impact on day-to-day activities can leave people feeling depressed and anxious. Lowvision sufferers may struggle to carry out everydaytasks, such as reading, shopping, cooking, driving andeven matching up clothes when getting dressed.Although the majority of people who suffer from lowvision are said to be 65 years and older, younger peopleand even children can also suffer from this health issue.

There are a wide range of causes of low vision, from eyediseases, cataracts to glaucoma. Health problems suchas diabetes can also lead to low vision developing. TheNational Eye Institute (NEI) in America, part of theNational Institutes of Health (NIH), supports researchand other programmes, relating to visual disordersincluding low vision.

Causes of low vision issues Dr Cheri Wiggs, Program Director for the Low Visionand Blindness Rehabilitation Programme at the NEI,speaks to Editor Laura Evans about the importance ofraising awareness for people with low vision and howadvances in science have helped over the years.

“The majority of low vision issues are caused by eyediseases and/or injury, but brain damage can also leadto visual impairment”, explains Dr Wiggs.

“There has been more attention recently on corticalblindness, or cortical visual impairment. This is wherepeople can still see, but they have difficulty interpretingthat visual information. Some people have double ortunnel vision, or their vision is extremely blurred. Thiscan be caused by traumatic brain injury, and we areseeing a lot of people that come back from combat andcomplain about these visual issues after a situationwith an IED.

“Cortical visual impairment can also be caused by insultsto the brain at birth. Vision loss due to neurologicaldamage to the brain affects both children and adults,”adds Dr Wiggs.

Age-related macular degenerationAs the majority of people with low vision are over theage of 65, this could become a bigger problem due toageing populations. One of the most common causesof low vision is age-related macular degeneration. How-ever, there are a few studies being done to ascertainhow to prevent low vision in later life.

“There have been a few studies on vitamin regimens tokeep these eye health problems at bay.” says Dr Wiggs.

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“In particular, a clinical trial examined whether takingantioxidants and zinc would reduce the risk of develop-ing advanced age-related macular degeneration (AMD).The results showed that the dietary supplements, whilenot a cure for AMD, could help at risk older people keeptheir remaining vision.

“However, it is also integral to ensure that the publicare aware of the importance of regular eye examina-tions that include looking at the retina. Because if you can catch it early you may be able to start sometherapy that can at least decrease the probability thatit will advance.

“The biggest problem is how low vision can impact dayto day life,” adds Dr Wiggs. “It really does impact people’squality of life and their independence. People who havelow vision are at an increased risk of falls, which meansfractures, time spent in bed and limited mobility for anumber of reasons. If part of your vision is absent thenits difficult manoeuvring around, including driving buteven just walking. People with low vision are at anincreased risk for depression, and it can also complicatethe management of other health issues.”

Understanding the mechanisms behind low vision Research is integral in order to better understand the mechanisms behind the problem and to developtherapies and rehabilitation that are tailored to helppeople who have low vision cope with everyday living.As science has evolved, technology is key to this areaand has led the way to develop a number of assistivedevices that help people with low vision carry outeveryday tasks, such as reading.

“Part of the mission of the National Eye Institute (NEI)is to address the special health requirements of thevisually impaired,” Dr Wiggs says. “We have encouragedcollaborations between vision scientists and peoplefrom both engineering and computer science back-grounds to help develop creative strategies to addresssome of the issues faced by people with low vision.”

As well as assistive devices, rehabilitation plays a majorrole in helping people to adapt and maintain their cur-rent lifestyle. It can help them to feel more confident

and comfortable with their vision loss, by teaching themhow to move safely around the home, continue to read,cook and do other activities, and find resources, adap-tive devices, and support. Rehabilitation is somethingthat the National Eye Institute supports. The low visionand blindness rehabilitation programme at the NEI aimsto develop further understanding about those alreadyliving with low vision.

“In addition to the applied translational work thatdevelops assistive devices and rehabilitation strategies,NEI also supports basic science on the impact of visionloss,” explains Dr Wiggs.

“For example, neuroscience research indicates that thebrain reorganises functionally after losing sensoryinputs; for instance, areas of the brain used for process-ing visual information get recruited for other functions,such as touch. The long-term impact of visual impair-ments on brain structures and functions remain unclearand could be very useful for informing rehabilitationefforts,” she adds.

“We have a lot of behavioural studies which we alsosupport that target the types of changes you see in crucial activities, such as navigation, driving, readingstrategies, and movement in people who are losingtheir vision. So, even though that’s more on the basic science side, it’s always with the understandingthat information can inform whatever rehabilitationstrategies you might develop.”

February was Low Vision Awareness Month at the NEIwith the aim of raising awareness for people living withlow vision, as well as their family and friends. ■

Dr Cheri WiggsProgram Director – The Low Vision and Blindness Rehabilitation ProgrammeNational Eye Institute, National Institutes of Health Cheri.Wiggs@nih.gov www.nei.nih.govwww.twitter.com/NatEyeInstitute

Innovative device for cataract surgery in sight

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In 1950, the British ophthalmologistSir Harold Ridley performed theworld’s first implantation of an arti-

ficial intraocular lens (IOL) to restore apatient’s vision after cataract surgery.This innovation rose from his observa-tion of WWII pilots, who suffered eyeinjuries in which acrylic pieces fromshattered cockpit windows lodgedwithin their eyes.

The realisation that artificial IOLs canreplace the diseased lens removedduring cataract surgery, has arguablybeen one of the medical technologiesthat have benefited the greatestnumber of patients worldwide. Today,IOL innovation continues at a rapidpace, and many believe that a quantumleap in IOL performance may be just around the corner and bring reju-venated, perfect vision to an ageingpopulation.

One hurdle, however, is the delicatecapsule that surrounds the lens. Incataracts, the normally optically clearlens becomes cloudy and, if leftuntreated, it can result in blindness.During surgery, an opening is madeby the surgeon using forceps in thepaper-thin capsule bag that encasesthe lens. This capsulotomy procedureallows the physician to remove thediseased lens through the capsulotomyopening, while preserving the bag tohold the IOL.

Performing the perfectcapsulotomyCapsulotomy is one of the most diffi-cult steps of surgery, and a perfectlyround, accurately sized and well-

centred capsulotomy is required foroptimal patient visual outcome. This iswell-recognised for advanced multifocalIOLs currently on the market, whoseperformance is significantly degradedif misaligned. New IOLs under devel-opment place an even greater premiumon a perfect capsulotomy, as theyeither stretch the capsulotomy openingto its limits or depend completely on thecentration of the capsulotomy positionfor IOL alignment on the visual axis.

While some physicians are well-prac-tised in capsulotomy, others are notand may struggle with technique. Allagree, however, that making consis-tently perfect capsulotomies by handis difficult. Five years ago, femtosec-ond laser systems were introducedfor automated capsulotomies. Whileeffective in making accurate capsulo-tomies, the femtolaser equipmentsuffers from its considerable financialoutlay that requires the physician topass on significant costs to the patientand also limit technology accessibilityto the majority of surgeons andpatients. In addition, the femtolaseradds time to each surgery, interruptspatient flow and operating theatrethroughput, making this technologyless attractive to surgical practices.Lastly, the medical literature indicatesa higher capsule tear rate and othercomplications after femtolaser capsu-lotomy. The adoption of femtosecondlasers for cataract surgery has slowedsignificantly since its introduction.

The realisation of upcoming IOL inno-vations may instead hinge on Zepto, adisposable automated capsulotomy

device about to enter the market(Mynosys Inc. Fremont, California, USA).(Zepto is the metric unit of measure-ment 1 million times smaller thanfemto). Zepto comes as a handpieceattached to a small control console.The handpiece’s tip comprises of asoft, clear silicone suction cup thathouses a nitinol super elastic capsulo-tomy ring, which compresses to entera small corneal incision and re-expandswithin the eye to its native circularshape. Suction is applied through thecup to oppose the bottom edge ofthe capsulotomy ring to the capsulesurface, trapping a very thin layer ofwater. A 4-millisecond pulse traincauses a quick phase transition ofthe water molecules into vapour, andthe accompanying volume expansionresults in the cutting effect, whichoccurs simultaneously everywherealong the circular capsulotomy path.The tip is then withdrawn and the surgeon continues with the remainderof the cataract surgery.

Reaching for ZeptoZepto requires no change to the stepsof cataract surgery or patient flow.Instead of forceps, the surgeon simplyreaches for Zepto to obtain quick,consistent, perfectly circular capsulo-tomies of the desired size (~5.2mmdiameter). To date, Zepto has beenused in over 200 cases worldwide withconsistently excellent results. Patientfollow-ups 8 months after surgeryhave shown stable capsulotomieswith well-centred IOLs.

Test data and surgical experiencehave highlighted a number of unique

John HendrickPresident and CEOMynosysTel: +1 510 396 1531jhendrick@mynosys.com www.mynosys.com/

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and noteworthy Zepto capabilities.Biomechanical testing showed theZepto capsulotomy edge to be muchstronger and more tolerant of stretch-ing than from the manual method orby femtolaser, due in part to an inno-vative capsule collagen re-modellingeffect that results in a slight upturn ofthe capsulotomy edge. This upturningprovides a rounded capsulotomyedge that presents the undisturbedundersurface of the capsule as thefunctional edge encountered duringsurgery. Zepto therefore potentiallyprovides a greater surgical safetymargin. Importantly, Zepto’s resilientcapsulotomy edge is also critical forthe safe implantation of the upcominggeneration of larger IOLs, designed tochange shape in response to the eyefocusing at different distances.

Zepto’s product design and mecha-nism of action also help the surgeonavoid potential complications. The useof suction stabilises the lens duringcapsulotomy and eliminates stretch-ing the delicate zonular tissues that isinherent in the manual capsule tearingmethod. This significantly benefitspatients with weakened zonules fromdisease or trauma. As Zepto’s capsu-lotomy action also occurs simultane-ously everywhere along a circular path,Zepto can be used to instantaneouslyrelieve pressure underneath the capsule in advanced cataracts, andthe potential for explosive capsulerupture is eliminated. Thus, patientswith these and other co-morbiditiesbenefit when complicated surgerybecomes easy with Zepto in the surgeon’s hands.

Zepto is the only technology thatallows the surgeon to place the capsu-lotomy intraoperatively precisely onthe patient’s visual axis. The eye’scomplex anatomy exists to ensure

that images are focused along thevisual axis onto the fovea, the retinalarea with the highest visual acuity. Intoday’s surgery, despite availableimaging technologies, surgeons are –at best – still guessing at the locationof the visual axis when performingcapsulotomy. Surgeons are alreadyaware of this limitation for multifocalIOLs that require proper centration.The same limitation presents itselfeven more acutely for new IOLs thatare anchored to the capsulotomy edge.Surgeons can interact with patientslooking through the transparentZepto suction cup and use Purkinjereflections to align the capsulotomyon the patient’s visual axis. Zepto willbe a real game changer as visually-centred capsulotomies are increasinglyused to specify effective lens position.

ZACSThese advantages and unique capa-bilities of Zepto have engenderedmuch interest in the concept of Zeptoassisted cataract surgery (ZACS), as apotential new gold standard in cataractsurgery. With ZACS, physicians canoffer their patients not only a dimen-sionally perfect capsulotomy, but alsoone that has added safety. Compli-cated cataract cases will become routine while providing patients withthe best possible results regardingIOL performance and stability. ZACS,for the first time, allow surgeons toprecisely locate the capsulotomy onthe patient’s functional visual axis.This ability to tailor capsulotomies tothe specific patient’s ocular anatomypromises to be a new paradigm ofpersonalised cataract surgery withoptimised visual outcome.

As an easy-to-use tool that automatesthe most demanding step in cataractsurgery, Zepto and ZACS offer some-thing for every surgeon. For the surgeon

less confident in capsulotomy, it offersquick and perfect results. For surgeonscontemplating offering premium IOLsto their patients, it offers capsulotomyquality along with personalised visualcentration, to support practice expan-sion. For the high volume practitioner,Zepto and ZACS offer safety, consis-tency and efficiency in both simpleand complex cases, while at the sametime ensuring premium outcomes forpatients via visual centration.

Zepto is expected by physician leadersto significantly impact cataract surgery,not only by being a highly versatileclinical tool, but also by being a lowcost disposable tool that is easy tolearn and integrate into routinecataract surgery. Of note, Zepto can beplaced easily into phacoemulsificationmachines, and is commercially attrac-tive not only as a standalone device,but also as a platform product thatcan be offered together with premiumIOLs, viscoelastics, and cataract surgicalpacks. Be prepared to see Zepto and ZACS broadly disseminated andpotentially become a new gold standard in the years to come.

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Keeping pests under control requiresongoing research

Agricultural production in the U.S. and aroundthe world is under constant attack. One of manyenemies standing at the gate: thousands of

different insect species. Left unchecked, they competefor the food we eat and represent threats that coulddecimate our natural, agricultural, and urban land-scapes. If not for today’s pest control measures, insectswould ruin many of the crops grown in the U.S.

Scientific research has provided a palette of measuresand strategies to help farmers and ranchers, as well asgardeners, homeowners, and the general public, con-trol these insect pests. Many of these innovative toolsand techniques are the direct result of the U.S. Depart-ment of Agriculture’s (USDA) Agricultural ResearchService (ARS).

Thanks to ARS scientists, many large-scale insect-relatedproblems – like screwworm infestations of livestock –are no longer on America’s “need-to-worry-about” list. Ifnot for the sterile-male insect release technique pioneered by ARS researchers Drs. Edward F. Kniplingand Raymond C. Bushland more than 6 decades ago,the flesh-eating screwworm would have decimated U.S.livestock production – just as it does today for many ofour Central and South American neighbours.

Unfortunately, science can’t rest on past successes.That’s because insects continue to invade, whichresearchers often learn about by comparing specimensto those maintained in the hundreds of ARS scientific col-lections. These collections provide a definitive resourcesfor agricultural research to include the identification ofinvasive insects. Pests also evolve and are quite adept atdeveloping countermeasures to overcome control meth-ods designed for them. In turn, that requires ARS scien-tists to find newer and better approaches for controllinginsects, a few of which are mentioned here.

Don’t let the harlequin bug’s red and black clown suitfool you. There is nothing funny about the way thispest can destroy a whole field of broccoli, Brusselssprouts, cauliflower, and other vegetables popular withurban and organic growers, as well as conventionalfarmers. ARS researchers are supercharging harlequinbug control.

It all involves a synthetic version of the insect’s ownaggregation pheromone to use as a lure to either trapthe bug directly or make so-called “trap crops” workefficiently. Pheromones are chemicals that triggersocial responses in others of the same species. In thiscase, when a male harlequin bug finds food, hereleases a pheromone to alert others to gather andfeast – much like ringing a dinner bell.

When researchers tested a synthetic version of thepheromone on plants under conditions similar to farmfields, harlequin bugs – old and young, male and female– came crawling and flying from many yards away.

The technique allows growers to make trap crops – alower-value alternative grown to lure pests away fromhigher-value crops – even more attractive.

Chris Bentley, Agricultural Research Service – U.S. Department of Agriculture, explains why research must continue to protect crops from pests and insects

Clown-colored harlequin bugs are no joke – H3ARS scientistsdeveloped a synthetic version of a harlequin bug pheromoneto lure the bugs to traps

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Protecting cotton from stink bugs Forget for a minute about the invasive brown mar-morated stink bug that has become such a commonpest in homes, backyards, and farms in recent years.Cotton growers in the U.S. are concerned about nativestink bugs that have attacked cotton and other cropsfor decades.

ARS scientists have found environmentally friendlyalternatives to insecticides for the 3 native stink bugs– namely, green (Chinavia hilaris), southern green(Nezara viridula), and brown (Euschistus servus) stinkbugs – that continue to threaten U.S. cotton.

Thanks to ARS research, growers are now planting trapcrops such as grain sorghum to lure stink bugs awayfrom cotton. They’re using pheromone-baited traps tocapture and kill stink bugs, and are planting nectar-pro-ducing plants – such as milkweed and buckwheat – tofeed the stink bugs’ native enemy, a parasitoid wasp.

Applying beneficial nematodes to peach trees Peach growers are facing a formidable insect foe: thelesser Peachtree borer, a native insect first reported in1868 in Pennsylvania. ARS scientists have developedsustainable and cost-effective ways to combat thisdestructive pest.

Enter Steinernema carpocapsae, a tiny beneficialroundworm (or nematode) that can protect peach andother stone fruit trees by attacking borer pests. Theyare “beneficial” in that they control insect pests in anenvironmentally friendly way. But the sun’s ultravioletrays and heat can dry and kill the roundworms afterthey’ve been applied. To survive the sun’s rays and dotheir job, these nematodes need protection.

ARS entomologists developed a way to protect thenematodes by using the type of “fire gel” that preventsthe spread of fire in residential and commercial struc-tures. In tests, they first sprayed nematodes onto treelimbs infested with lesser Peachtree borers and thenapplied the fire gel over them.

An initial drawback to that approach was overcomewhen one application (containing both nematode andprotective gel) was developed. The treatment hasproven as effective as the standard chemical approach

to combating the problem. These are but a few exam-ples of the many ways ARS researchers across thecountry are working to stay one step ahead of insects– all while tackling other issues that affect the produc-tivity and wellbeing of our agricultural and naturalresources.

As the sterile-male insect release technique mentionedearlier illustrates, a good piece of innovation can go along, long way. This will become especially important asthe world population swells to an estimated 8.5 billionby 2030. Fortunately, the spirit of scientific and techno-logical excellence of ARS pioneers like Dr. Knipling andDr. Bushland continues to burn brightly in today’s ARSresearchers. ■

Christopher S. BentleyDirector of CommunicationsAgricultural Research Service – U.S. Department of Agriculturewww.ars.usda.gov

A lesser peachtree borer larva on a damaged peach tree

Imag

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Peg

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U.S ENVIRONMENT & ENERGY

36

Fusion energy: Unlocking the zero-emission grid

Acornerstone of any realistic path to overcomingclimate change is developing sources of energythat are emission-free, on-demand and econom-

ically viable. Such sources would sustain the world’sgrowing population and broaden the opportunity foreconomic prosperity. The need for these sources isurgent: global electricity demand is forecast to increaseby 69% in the next 20 years, and while renewables aregrowing rapidly, the majority of this demand nonethelesslooks set to be fulfilled by fossil fuels.1

The clean energy grid will need a mix of generatingtechnologies to supply the diverse needs of consumers.When it comes to sectors with high energy intensity,such as industry or dense urban areas, fusion energyis a very attractive option. Fusion has the potential toprovide clean, safe and on-demand power worldwide.It also has the potential to demonstrate the best energypayback ratio (EPR) and lowest carbon life cycle foot-print of any source, making it a powerful tool to tackleclimate change.

Fusion: a national priority The potential of fusion has long been recognised by thescientific community. Over 30 years of investment bygovernments in research and development has broughttremendous scientific advancements, and a number ofcountries now consider further development of fusionto be a national priority.

In addition to their involvement in the 35-nation ITERfusion project, China also plans to train 2,000 newfusion scientists by the end of this decade, and SouthKorea is investing heavily in the field.2, 3 These projectsare demonstrating the scientific understanding that isenabling fusion to move from lab experiments toapplied engineering projects.

Now is an innovative time in fusion, both in governmentand the private sector. New ideas are springing up: pro-posals for fusion system designs that are more practicalto implement, at lower capital cost, and which will leadus to commercially viable power plants sooner than theearlier concepts.

This renewed wave of enthusiasm is the result of acombination of factors. The scientific knowledgegained through decades of research has provided uswith an excellent understanding of the principlesunderpinning fusion. Fields such as plasma physics,key to achieving the extreme temperatures needed tofuse the hydrogen nuclei fuel, have been intensivelystudied and the parameter space we must work withinhas been established.

In parallel, substantial technological advances havetaken place in fields complementary to fusion. Comput-ing power and electronics, simulation, and materialsscience have progressed dramatically since the earlydays of fusion research in the 1960’s. Previously onlyfeasible on the most powerful of national laboratorysupercomputers, simulation of the behaviour of fusionplasmas is now possible on commercially availablecloud computing platforms.

These advances provoked a vanguard of private fusioncompanies such as General Fusion, Tri Alpha Energyand Lockheed Martin to enter the space, capitalising onnew technologies to push forward the development ofinnovative new approaches. With parallels to the emer-gence of companies such as Blue Origin and SpaceX inthe aerospace industry, serious private sector investorsare funding sophisticated efforts to pursue practicalsolutions with the goal of advancing the timeline for acommercial solution to fusion by decades.

The opportunities provided by fusion should not be overlooked. Here, Michael Delage, of General Fusion Inc. explains the potential of the energy source

U.S ENVIRONMENT & ENERGY

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Backed by venture capital, these firms are developingnew, power plant-focused approaches at a pace notpreviously seen. In the coming years we will see the firstdemonstration prototypes emerge, which will marshalthe energy industry to drive fusion’s commersialisation.

These advances come not a moment too soon. Thelatest figures show that while the deployment of cleanenergy infrastructure is growing rapidly, it is being outpaced by the staggering level of new demand.Some perspective: In 2015, China alone was responsi-ble for 40% of global renewable power growth, but thatrepresented only half of the country’s electricitydemand increase4.

Much as we see a mix of technologies supplying our energy needs today, de-carbonising the world’selectrical networks will require a new mix of generatingtechnologies incorporating distributed renewables,large scale storage, and high output, on-demandsources. Energy companies, corporate partners andgovernments around the world are recognising theability of fusion to make a significant contribution to

this mix, and are investing to unlock the full potentialof the zero-emission grid. ■

1 US Energy Information Agency, May 11, 2016. International Energy

Outlook 2016. Figures 5-1 & 5-3

2 University of Science and Technology China Newsroom, March 24,

2011. National Design Panel for Magnetic Confinement Fusion

Reactors Established at USTC

3 Nature, January 21, 2013. South Korea makes billion-dollar bet on

fusion power.

4 International Energy Agency Newsroom, October 25, 2016. IEA raises

its five-year renewable growth forecast as 2015 marks record year.

Michael DelageChief Technology OfficerGeneral Fusion Incinfo@generalfusion.comhttp://generalfusion.com/www.twitter.com/GeneralFusion

Private companies such as General Fusion (pictured here) are drawing on 30 years of research in fusion to develop newapproaches focused on commercial power plants

U.S ENVIRONMENT & ENERGY

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Fusion energy could be the future of power production

Modern society loves energy. Whether it islighting our offices, heating our homes ordelivering our goods, it all takes energy.

But delivering the energy we need is becoming a prob-lem. Fossil fuels have been the backbone of our devel-opment but we now realise burning fossil fuels isunsustainable and we must wean ourselves off them assoon as possible. There are alternatives but each comeswith its own advantages, disadvantages and limitations.Nuclear fission has been delivering cost-effective powerfor decades but has barriers to entry that can restrict itsapplication. Renewables, such as wind and solar have alarge physical footprint, but are often not close to wherethe energy is needed and are intermittent. Biomasslocks up large quantities of land, is hard to transport andstill leads to the release of greenhouse gases. Lots ofnew energy models have been tried but none have beenan unqualified success and none can be freely and sustainably replicated. Fusion could change that.

“It may well have taken time to get where we are today but with few constraints on deploymentand a massive demand for what it delivers, fusioncould easily be the next great step in mankind’s

development. And it may come sooner than you think.”

Fusion as a source of energy Fusion would be a high-density energy source entirelyunder mankind’s control with an affordable, easilyavailable fuel. It could be easily replicated in almost anyjurisdiction and doesn’t have environment damagingcarbon emissions.

That is why economic fusion is the holy grail of theenergy industry.

When matter condensed out of energy after the bigbang, an electron combined with a proton to form oursimplest element, hydrogen. That is why it is by far themost common element in our universe.

But it is not the lowest energy atom. That title belongsto Iron 56. If the repulsive forces that keep light nucleiapart can be overcome they will fuse and give outenergy, and lots of it.

This is where the energy of the Sun comes from. Every day when the Sun rises we are reminded thatfusion works.

The issue of creating power from fusion is then, notone of its fundamental science, but rather one of engi-neering, materials science and control. The Sun usesits massive gravity to confine the fuel and the energyproduced just dissipates into space. Controlled fusion,here on earth, requires us to find another way to contain fuel at a hundred million degrees Celsius andthen to collect the energy and convert it into some-thing useful. The Sun is self-sustaining. We begin witha cold fuel that we need to heat before the reaction canstart by putting massive amounts of energy veryquickly into a very small target.

Mankind has risen to the challenge, imagining manyways in which this might be done and then provingthat it can. Historically the experiments have beenlarge, as magnetic confinement has been used to holda hot plasma (a state of matter where electrons havebeen stripped from the atoms) or powerful lasers havebeen used to create shock waves in solid fuel pellets.Notable experimental facilities include the Joint Euro-pean Torus ( JET) in the UK, National Ignition Facility(NIF) in the U.S. or more recently the Wendelstein 7-X

Neil Alexander for the Canadian Nuclear Association shares why society should be looking to fusion energy to power homes and businesses in the future

U.S ENVIRONMENT & ENERGY

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stellarator in Germany. Thirty-five countries have cometogether to support the next phase of the Tokamakdevelopment known as the International ThermonuclearExperimental Reactor (ITER) in France. Construction ofthis large and complex facility will take some time and isexpected to cost in excess of $20billion.

It has been a hard slog for fusion as it has had to overcome many challenges at the very edges of ourknowledge and capability. Without the benefit of theSun’s gravity the temperatures needed for ignition are6 times higher than the Sun’s core and at the moment,Tritium and Deuterium (isotopes of hydrogen) have tobe used rather than much more available hydrogenitself. The fusion process kicks out a lot of radiationand the materials used must be able to tolerate that radiation.

At times people have joked that commercial fusionpower was 30 years away when it was first consideredand it is still 30 years away. But there is powerful evidence to suggest that technologies develop expo-nentially and that fusion is now lifting off that initial flatpart of the curve so that from here on in progresscould accelerate away. Certainly, this can be seen in theannouncements of technological progress on the big

projects, but just as importantly it can be seen in thesurge of spin-off commercial concepts such as Vancou-ver’s General Fusion or First Light Fusion in the UK.Even ex Google executives are getting in on the game,with Mike Cassidy recently announcing the creation ofApollo Fusion.

It may well have taken time to get where we are todaybut with few constraints on deployment and a massivedemand for what it delivers, fusion could easily be thenext great step in mankind’s development. And it maycome sooner than you think.

Dr. Alexander is also a Principal Consultant atBucephalus Consulting, and was one of the signatoriesto Fusion – 2030, a roadmap for reinstating Canada’sNuclear Fusion Research program. ■

Dr. Neil AlexanderEngaged memberCanadian Nuclear Association info@cna.cahttps://cna.ca/www.twitter.com/talknuclear

Modern society loves energy but delivering that energy is becoming a problem

CANADA HEALTHCARE

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Helping Indigenous communitiesbecome healthier

The Canadian Institutes of Health Research-Insti-tute of Aboriginal Peoples’ Health (CIHR-IAPH) isone of the 13 founding institutes of CIHR, estab-

lished in 2000. My recent appointment as the latest Sci-entific Director of the CIHR-IAPH allows me the chanceto consider our mandate and our opportunities to bol-ster the self-determination of Indigenous communitiesto become healthier Nations, groups and individuals.As researchers, we are committed to working with thepriorities Indigenous communities see for themselvesin order to advance their progress in becoming health-ier communities.

The IAPH fosters the advancement of a national healthresearch agenda to promote and improve the health ofFirst Nations, Inuit and Métis Peoples in Canadathrough research, knowledge translation and capacitybuilding. The Institute’s pursuit of research excellenceis enhanced by our respect for community research pri-orities and Indigenous knowledge, values and cultures.Our goal is to contribute to the improvement of thehealth and wellbeing of Indigenous people in every partof Canada. We will stimulate health research with andfor Indigenous communities, build a community ofIndigenous researchers who can engage in “two-eyedseeing” research (conducted using Indigenous researchparadigms side by side with other paradigms such asthose involving Western epistemologies), form researchpartnerships with organisations in Canada and abroad,involve Indigenous communities respectfully in everyproject undertaken, and create new knowledge.

Addressing the issue of poor health Canada’s recent Truth and Reconciliation Commission(TRC) presented all Canadians with 94 Calls to Action.Some of these are calls to the government to addressthe issue of the poor health of Indigenous Peoples inCanada. The TRC calls upon governments to acknowl-

edge that the current state of Indigenous health is adirect result of previous Canadian government policies,including Aboriginal residential schools, and to recogniseand implement the healthcare rights of Indigenouspeople as identified in international law, constitutionallaw, and under the Treaties. Other calls to action includehaving the federal government identify measurablegoals to determine the gaps and to report on progresstoward closing those gaps in health outcomes betweenIndigenous and non-Indigenous Peoples, increasing thenumber of Indigenous healthcare professionals, andcompelling those who can effect change within theCanadian healthcare system to recognise the value ofIndigenous healing practices and to make them availablewhen treating Indigenous clients.

Good research can inform good policy and practiceand thereby help to achieve good results for people inneed. Good research into Indigenous health requiresus to see the Indigenous communities we want to workwith as partners in Indigenous health research fromthe early stage of setting research priorities rightthrough to reporting on our research in a way that isaccessible, meaningful and, therefore, useful to Indigenous communities. We must be guided by the

Carrie Bourassa, Scientific Director, CIHR-IAPH discusses the issue of poor health among Indigenous communities and says research is the key to tackling it

CANADA HEALTHCARE

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Indigenous communities that are our research part-ners. These communities are not subjects of research;they are active participants in the entire researchenterprise. Indigenous communities have protocols forsharing knowledge, and researchers must learn andrespect these protocols when undertaking research.

Building research capacity An important part of the CIHR-IAPH mission is to buildresearch capacity in the First Nations, Inuit and Métiscommunities. We will do this by mentoring, supporting,and encouraging a new generation of Indigenouspeople to become health researchers and to createnew knowledge that will improve the health and wellbeing of Indigenous communities. We will also helpto negotiate partnerships and alliances betweenIndigenous communities and non-Indigenous healthresearch organisations and institutes at the local,regional, national and international levels.

It is central to our mission and our values that, in creatingnew knowledge to benefit Indigenous peoples, the CIHR-IAPH supports health research that respects Indigenouscultures. Part of our task is to make sure that this is howall CIHR-funded health research is conducted and to act

as a resource for all of the other CIHR institutes, toensure that all researchers understand the Indigenousperspectives on the issues they are researching andinclude the Indigenous perspectives in their work.

The challenges to helping to create healthier IndigenousPeoples and communities are large, but the benefits ofdoing good research in a way that respects and con-tributes to Indigenous communities and actively involvesIndigenous communities in the research project makethe effort worthwhile. I look forward to seeing what wecan accomplish with Indigenous communities in myyears as Scientific Director. ■

Carrie Bourassa, PhDScientific Director The Canadian Institutes of Health Research Institute of Aboriginal Peoples’ ResearchCarrie.Bourassa@cihr-irsc.gc.cawww.cihr-irsc.gc.ca/e/193.htmlwww.twitter.com/CIHR_IRSC

Dr. Janet McElhaney, Dr. Jennifer Walker and Dr. Carrie Bourassa

Canada’s Indigenous populationis composed of First Nation(FN), Inuit and Métis peoples.

They often suffer from a greaterburden of disease, notably chronic (e.g. diabetes1,2) and infectious ones(e.g. tuberculosis3), than the rest of thenon-Indigenous Canadian population.

Part of the health problems faced byCanadian Indigenous populationsstems from the cultural disconnect thatexists between the health care and ser-vices offered by public sanitary organi-sations, on the one hand, and theworldview of several Indigenous peo-ples, on the other4. Thus, North Ameri-can Indigenous populations are deeplyconnected to the Earth and nature.Their health is therefore intuitivelymore holistic and interconnected withtheir communities and their environ-ment. Consequently, health care andthe response to disease also call to amore holistic approach.

Aside from being morally and sociallyreprehensible, the health inequitiesafflicting Indigenous Canadians put asignificant burden on the Canadianhealth care system. Apart from highhealth care costs related to the severityof afflictions, considerable travel andliving costs are required by individualsresiding in more remote areas, whomust be transferred to major centersin order to receive appropriate care.

As will be argued in the next sections,Indigenous traditional medicine rep-

resents a valuable avenue to explorein order to reduce the burden ofhealth inequities, the cultural discon-nect of modern therapeutics, and thehigh economic cost of Indigenoushealth care.

Indigenous traditionalknowledge and traditionalmedicine: Valuable opportunitiesfor improved indigenous healthIndigenous traditional knowledge (TK)in general, and traditional medicine(TM) in particular, has shown remark-able resiliency in most CanadianIndigenous communities5, eventhough its transfer to younger genera-tions is currently critically threatened.Indigenous TM is a science that isrooted in so-called “Natural Laws” andinvolves a close contact with nature, aswell as a deep understanding of its ele-ments and their uses for human healthand wellbeing. It is also a common misconception to consider IndigenousTK and TM as static or retrograde. TMis a true science and as such evolvescontinuously. Elders are notably wellaware of the precariousness of TK andTM, while they also fully understandthe urgent need to help their fellowcommunity members dealing withchronic or infectious diseases.

It is therefore both timely and perti-nent to consider Indigenous TM as afeasible and, strangely enough, innova-tive means to reduce health inequitiesthroughout Canadian Indigenous pop-ulations. Firstly, Indigenous TM has

proven to be safe and efficient, both inhistorical and contemporary terms6.Secondly, Indigenous TM is very cultur-ally connected. It is thus plausible that Indigenous people will complybetter with treatments originatingfrom their own culture than they dowith “modern” medicine. It must alsobe stressed that Indigenous TM is aholistic paradigm whereby not only thephysical part of the diseased individualis encouraged to participate in thehealing process (for instance, by takinga traditional medicinal plant prepara-tion), but also the mental, emotionaland spiritual parts.

“Aside from being morally and sociallyreprehensible, the health inequitiesafflicting Indigenous Canadians put asignificant burden on the Canadianhealth care system. Apart from highhealth care costs related to theseverity of afflictions, considerabletravel and living costs are required byindividuals residing in more remoteareas, who must be transferred tomajor centers in order to receiveappropriate care.”

Including Indigenous TM in health carealso carries great potential to reducethe economic burden of healthinequities. Indeed, through the use oflocal human and natural resources, thecost of therapeutic regimens can bereduced. This holds true even if Indige-nous people continue using both con-temporary pharmaceutical treatmentsand TM. Indeed, it is conceivable that

Professor Pierre S. Haddad shares the challenges of overcoming health inequalityfor Canadian indigenous populations and highlights solutions to the issue

Ensuring health equity for Canadian indigenous populations

42

PROFILE

combining TM with modern drugs mayreduce the dose and length of treat-ment required with pharmaceuticals. IfIndigenous TM can mitigate, even par-tially, the impact of several chronic orinfectious diseases, a greater fractionof the population will remain healthyor will develop less severe forms ofchronic diseases and their complica-tions. This in turn should diminish thenumber of Indigenous patients thatneed to be sent to large urban centersto be treated.

Lastly, Indigenous elders or knowledgeholders will get recognition and couldpotentially derive a non-negligibleincome from their practice. Of course,this raises the question of the “profes-sional” framework within which Indige-nous TM will need to be practiced, butthis issue is beyond the scope of thepresent discussion. Given that Indige-nous TM should be delivered in a safe,efficient and ethical way, additionalwealth could be generated from itspractice and related activities (forinstance, collecting medicinal plantsand preparing traditional remedies).The consequence should also involvea reduction of poverty, one of themajor social determinants of Indige-nous health.

Challenges and solutions Turning to Indigenous TM to reducehealth inequities comprises a fairshare of challenges. Major ones are: 1)Historical devaluation of IndigenousTM, with ensuing skepticism from themedical establishment; 2) Mistrust byseveral Indigenous peoples of theestablished order, with associatedconcrete fear of misappropriation ofTK and TM and biopiracy; 3) Potentially

harmful herb-drug interactions; and 4)The development of appropriatemodels to include Indigenous TM intocurrent healthcare systems.

Many call for the integration of Indige-nous TM in Indigenous health care.However, the word “integration” raisessome profound questions in many FN,Inuit and Métis minds. Indeed, integra-tion may lead to a form of assimilationor subordination that many Indige-nous people fear. Given the powerimbalance between the establishedgovernment-run medical system andthe parallel practice of Indigenous TM,such fears are legitimate.

Although these challenges can appearquite daunting, a number of fruitfulendeavors have nevertheless seen thelight in Canada and abroad, wherebyIndigenous TM is being used safely andefficiently alongside modern healthcare. The key issues related to success-ful outcomes in such projects includethe following: 1) Indigenous and non-Indigenous stakeholders must be engaged in truly equitable andempowering partnerships; 2) Theagenda must be set by and for Indige-nous communities; 3) Partnershipsneed to be based on mutual trust,mutual respect and mutual apprecia-tion; and 4) Cultural brokers need to beinvolved to ensure proper knowledgetransfer and exchange.

In short, Indigenous TK and TM areviable tools to consider for the reduc-tion of health inequities afflictingIndigenous populations, notably interms of chronic and infectious diseases. Because of the cultural and paradigm gaps that exist between

current health care approaches andIndigenous TM, it is highly recom-mended that partnerships be devel-oped among stakeholders and thatthese include culturally competentpartners.

References

1 Dyck, R, Osgood, N, Lin, TH, Gao, A, Stang, MR (2010). Epidemi-

ology of diabetes mellitus among First Nations and non-First Na-

tions adults, Can Med Assoc J, 182(3): 249-255.

2 Cree Diabetes Information System Annual Report.

( http://www.creehealth.org/fr/node/1551; consulted April 12,

2017).

3 Inuit Tapiriit Kanatami. (2013). Inuit-Specific Tuberculosis (TB) Strategy.

( http://assembly.nu.ca/library/Edocs/2013/001010-e.pdf; consulted

April 12, 2017).

4 Grim, JA (2001). “Cosmology and Native North American Mystical

Traditions”, Théologiques, 9(1): 113-142.

5 Kirmeyer, LJ, Dandeneau, S, Marshall, E, Phillips, MK, Williamson,

KJ (2011). Rethinking resilience from Indigenous Perspectives.

Can J Psychiatry, 56(2): 84-91.

6 World Health Organization Traditional Medicine Strategy.

( http://www.who.int/medicines/publications/traditional/trm_strat-

egy14_23/en/; consulted April 12, 2017).

Professor Pierre S. HaddadDepartment of Pharmacology and PhysiologyUniversité de Montréal and Canadian Institutesof Health Research (CIHR) Team in IndigenousAntidiabetic MedicinesTel: +1 514 343 6590pierre.haddad@umontreal.cahttp://pharmacologie-physiologie.umon-treal.ca/english/

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In September 2016, Canada’s Health Minister, TheHonourable Jane Philpott, revealed plans forCanada’s new Health Accord Plan to the CANADA

2020 Health Summit. The Summit was in partnershipwith the Canadian Medical Association, aimed to opendebate and discover solutions to help Canadians leadbetter and healthier lives – particularly for the moreelderly population of the country.

In the opening of her speech, she stated that, “Already,Canada is one of the world’s highest spenders onhealthcare and yet we are not achieving the kind ofresults Canadians need and deserve.”

This is evident from in the CMA National Report Card2016, where only 37% of Canadians assigned a lettergrade of A to the “overall quality of health care servicesavailable”.

Philpott went on to outline the Federation’s “sharedpriorities for health”, which include homecare, phar-maceuticals, mental health, and improved healthcarefor the Indigenous population. Overall, the FederalGovernment’s priorities for healthcare spending alignwith aspects of the healthcare system that Canadiancitizens prioritised in the National Report Card.

Homecare One of the key priorities for the Health Accord is improv-ing investment for homecare. The Minister outlined howin Canada $10 billion, around 5% of total health spend-ing is spent on home and community care.

“That’s a lot of money, but it’s probably not enough,especially since our population is aging and burdenedby increasing rates of chronic disease,” Philpottstated.

Open Access Government highlights how Health Minister, Jane Philpott aims to improve the lives of all Canadians through their new Health Accord Plan

Health Accord: Healthcare for all

CANADA HEALTHCARE

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Philpott went on to say, “Today, some 15% of hospitalbeds are occupied by patients, who might be better offat home or in long-term care. This has a huge financialimpact. For example, in Ontario, basic homecare costs$42 a day, compared to a minimum of $840 a day in ahospital.

“More importantly, it’s not the best way to care forthem – we know the hospital it not where they want tobe, unless it’s absolutely necessary. We have a goldenopportunity to put in place robust systems of servicesand supports that will address these gaps.”

Not only was Philpott’s argument for better invest-ment, she also stressed the importance of puttingmore resources into homecare, so that patients,carers, and families have more support and “don’tburn out”.

Mental Health The National Report Card stated that 83% of Canadiansplaced mental health services within the top fundingconsiderations. This emphasis on mental health is nosurprise when the Canadian Centre for Association andMental Health (CAMH) found that by the time Canadian’sreach the age of 40, half have, or have had, experiencesof mental illness. Furthermore, a third of people whohad reported mental health issues in the past year saidthat their needs had not been met.

At the Health Summit, Philpott added mental health toher priorities as part of the Health Accord Plan toimprove healthcare across the country. She highlightedmental health as something that needs to be discussedopenly between families and even communities.

The Minister said, “For too long, mental illness was something to be hidden, something to beashamed of. Today, we talk about it somewhat moreopenly in our families and in our communities, andthat is a good thing.

“But as the full extent of the burden of mental illnessin Canada becomes clear, it’s become obvious that oursystems are not well-equipped to heal the traumacaused by mental illness.”

She also admitted that while “doctors and other frontline workers do their best”, they “often don’t have adequate training”.

However, she did mention plans to “build systemswhere mental health services are widely available andsupportive”.

Indigenous populations Canadians placed better healthcare for the Indigenouspopulations below many other healthcare improve-ments, with only 64% of people believing it to be animportant area of funding.

However, Philpott clearly stated that this was an important issue for the Government. She argued thatchallenges within the healthcare system are “magnifiedmany times over for Indigenous peoples in Canada”.

Evidence for this includes the 2017 life expectancy sta-tistics that found that life expectancy among the totalCanadian population is 79 years for men and 83 yearsfor women. However, for the Indigenous populations,the projected life expectancy is much lower, 64 years formen and 73 years for women.

Philpott summarises this gap in healthcare by saying“If you are an Indigenous, your life expectancy is up toa decade shorter than for other Canadians. Your ratesof diabetes are 3 times that of the national average. InFirst Nations, rates of tuberculosis are 33 times that ofother Canadians. For Inuit, the rates of tuberculosis are375 times higher than those for non-Indigenous Cana-dians”.

In her speech at the Health Summit, Philpott ended byemphasising the “need to adapt to new ideas” andrenew Canada’s “approach to health policy”, concludingwith the message that “by working together, Canadacan be a world leader to ensure our ultimate collectivegoal, that is, health for all”.

The full speech from the Minister at the Canada 2020Health Summit can be found here. ■

Georgina RyanWriterOpen Access Governmenteditorial@adjacentopenaccess.orgwww.adjacentopenaccess.orgwww.twitter.com/OpenAccessGov

Breast cancer accounts forapproximately 26% of all can-cers diagnosed today. One in 8

women are expected to be diagnosedwith breast cancer in their lifetimes.According to the National Cancer Insti-tute, in 2016 there were 246,660 newcases and 40,450 deaths from breastcancer in the U.S alone. Like othercancers, breast cancer is most suc-cessfully treated if the disease isdiagnosed early. In addition to betterhealth outcomes, there are economicbenefits to accurate screening andearly diagnosis of the disease. It isestimated that the cost of treatingearly stage breast cancer is about$12,000, while late stage treatmentcosts start at around $150,000.

Common practice for breast cancerscreening is x-ray mammography forwomen over 50. Unfortunately, for toomany women, x-ray mammography istoo ambiguous to detect their diseasein time for effective treatment. Theproblem is that the specificity of mam-mography suffers from its difficulty indistinguishing between benign andmalignant masses: dense breast tissueappears similar to cancer on x-raymammograms, leading to inconclusiveimaging results. Patients with suspi-cious mammograms are prone toeither unnecessary biopsies or lateidentification of serious disease. Ofthe women that are screened withmammography, roughly 18% have asuspicious but inconclusive findingand a third of these are sent for

biopsy. Roughly 75% of biopsiesprompted by mammography comeback negative and in the U.S alonethese account for 1.5 million unneces-sary biopsies that could be preventedwith more cancer-specific diagnosticimaging. The situation is the mosturgent for women with a known highand intermediate lifetime risk forbreast cancer. High-risk patients haveto be screened at a significantlyyounger age than average risk women.Younger high-risk women tend tohave denser breast tissue which doesnot produce accurate images whenscanned using x-ray mammography.

The inconclusive nature of breastcancer detection with either mam-mography or its combination with MRImeans that a large cohort of women(especially, high-risk patients) cannotrely on imaging to start disease treat-ment at the early stage. These womenare forced to contemplate prophylacticmastectomy because the predictivepower of current imaging is so poor.

Early detectionRadialis Medical Corporation, a jointventure (spin-off) of the Thunder BayRegional Health Research Institute(TBRHRI) and Lakehead University,Ontario, Canada, addresses thisimportant unmet patient’s need. Radi-alis is manufacturing an advancedPositron Emission Mammography (PEM)system for molecular (or functional)imaging of breast cancer. PEM detectssmall cancerous breast lesions based

on their increased glucose metabolismand in such its imaging performanceis inherently independent on breasttissue density.

The core technology of the PEM systemwas developed in Dr. Alla Reznik’sresearch laboratory at Lakehead University and TBRHRI. Radialis PEMemploys 2 planar high-resolutiondetector heads placed on both sidesof gently steadied breast (Figure 1).Each detector head contains a largefield-of-view (17cm x 22cm) gamma-photon sensor based on the noveltype of solid-state (silicon) high-gaindetection technology. During imageacquisition, detectors fully cover theentire breast that allows for improvedsensitivity capable of significant radi-ation dose reduction (by the factor of4) in comparison with commerciallyavailable scanners.

Another advantage of Radialis’s designis its slim detector head and minimised“dead area” (the distance between theimaging part of the detector and itshousing). This comparatively small stepallows for significant clinical benefitssince it tremendously improves visualisation of deep chest lesions,provides more options for detectorheads positioning around the patientbreast and access to lymph nodes toevaluate its possible metastaticinvolvement.

The assembly and imaging perfor-mance evaluating of Radilis’s PEM are

Dr Alla Reznik, Canada Research Chair in Physics of Medical Imaging, explains howPositron Emission Mammography is effective when detecting breast cancer

Using Positron Emission Mammographyto detect breast cancer

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underway. Initial results with phantomsmimicking breast lesions of differentsizes demonstrate that tumours assmall as 1.2mm in size will bedetectable in a clinical setting. Theultra-high resolution achieved com-bined with a large field-of-view detec-tor design enables high-resolution,low-dose molecular breast imaging.

Additionally, large area stationarysolid-state sensor design means thatthere will be less radiation that willescape Radialis’s device.

In addition to improved early breastcancer detection for a large cohort ofpatients, the use of PEM for screeningof the high risk population will allow

for significant improvement in patients’compliance for frequent tests. Indeed,at the current stage of mammo-graphic detector technology, extremebreast compression is applied. Theassociated pain and anxiety is sostrong that a large number of patientrefuse mammography after their firstexperience. In contrast, PEM onlyrequires breast immobilisation ratherthan compression and hence com-pletely eliminates pain. This has the potential to significantly improvecompliance and the effectiveness ofcancer detection.

Overall, once implemented in clinicalpractice, Radialis’s PEM technologycan be used as (1) an adjuvant tech-nique for breast cancer detection, and(2) an integral part of the surveillanceprotocol of women at high and inter-mediate lifetime risk of breast cancer.In addition, the technological advancesused will reduce manufacturing costfor PEM devices facilitating their wide-spread clinical usage, thus positivelyinfluencing people health.

Dr Alla ReznikLakehead UniversityThunder Bay Regional Health Research InstituteTel: +1 807 343 8571http://rezniklab.lakeheadu.ca/

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Dr Alla ReznikDr Alla Reznik is a Canada Research Chair in Physics of Molecular Imaging andan Associate Professor in the Physics Department, Faculty of Science and Envi-ronmental Studies, Lakehead University. She is also affiliated as a Senior Scientistin the Thunder Bay Regional Health Research Institute (TBRHRI). Dr. Reznik hascompleted her PhD in solid-state physics at the Technion- Israel Institute of Tech-nology. After several years as a Senior Physicist at the GE Medical Systems shedecided to return to academia and accepted a Research Associate position at theUniversity of Toronto, Canada. In 2008 she was appointed a Canada ResearchChair in Physics of Molecular Imaging and in 2013 re-appointed as a CanadaResearch Chair in Physics of Medical Imaging. She is a specialist in photoconductivematerials and technologies for radiation medical imaging. The focus of her workis on solid-state technology for organ-specific Positron Emission Tomography(PET). The goal is an improvement in resolution and sensitivity over commerciallyavailable PET imagers. Another focus of her work is on advanced low-dose directconversion x-ray imaging detectors based on novel x-ray-to-charge transducers.Reznik group’s PET research has led to the launch of Radialis Medical – the firstjoint Lakehead – TBRHRI spin-off-company, which will produce a commercial version of the technology for breast cancer detection.

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Fighting against breast cancer in Canada

In 2016, an estimated 26,000 Canadian women and230 Canadian men were diagnosed with breastcancer. Breast cancer occurs when cells change and

no longer grow or behave normally. A Canadian womanhas a 1 in 9 chance of getting breast cancer during her lifetime.

Research in Canada and across the world has managedto boost survival rates from 70% in the early 1970s to87% today. Thanks to this research and advances inscreening, today we know more about how to diagnoseand treat breast cancer than we ever have.

“Thanks to organised screening programmes,research, improved treatment options and

prevention recommendation we now have morebreast cancer survivors than ever. We’re grateful tonow be able to turn more attention to survivorshipand how we support women who are able to live

their lives thanks to research.”

What increases my risk of getting breast cancer? In general, about half of all cancers can be prevented bynot smoking, exercising and maintaining a healthy bodyweight. The same goes for breast cancer – if you’re ableto lead a healthier lifestyle, then your chances of gettingbreast cancer will go down.

While the risk of breast cancer increases with age, apersonal or family history of breast cancer may furtherincrease your risk. Additionally, studies have shownthat women with inherited BRCA1 or BRCA2 genemutations have up to an 80% chance of developingbreast cancer in their lifetime. Women with theseinherited mutations also have a higher risk of develop-ing breast cancer at a younger age (usually beforemenopause) than other women.

Drinking alcohol also increases a woman’s risk for breastcancer. Even low levels of alcohol consumption (justover 1 drink per day) can increase a woman’s risk. Therisk increases with the amount of alcohol consumed.One possible reason for this is that alcohol is thought tocause higher levels of estrogen. Other factors that canincrease a woman’s risk of breast cancer include obesityand hormone replacement therapy.

Are there tests for breast cancer? In Canada, there are breast cancer screening pro-grammes in each province and most territories. Forwomen at average risk for developing breast cancer,mammogram screening is most effective every 2 years,between the ages of 50 and 74. It’s important to notethat breast cancer risk varies from woman to woman,so you should make a point of discussing your personalrisk with your doctor. If you have family members whohave had breast cancer, or you carry a certain genemutation, then you may be recommended to startbreast cancer screening earlier and more often. If youhave high breast density (75% or greater) you may beasked to screen annually.

Breast cancer screening is done via a mammography. Ascreening mammogram is used to look for breastcancer in women who don’t have any symptoms of thedisease. It may be done in a clinic, screening centre ormobile screening mammography unit. During a mam-mogram, a plastic plate will be slowly pressed down toflatten your breast and hold it in place for a few secondswhile two images of each breast are taken. You will feelsome pressure on your breast during the x-ray.

Like most screening tests, there are benefits and limi-tations to mammography. Scientific evidence tells usthat regular mammography screening leads to fewerdeaths in women with breast cancer. This is because it

Canadian Cancer Society’s Dr Rob Nuttall and Shawn Chirrey explain how fighting against breast cancer requires ongoing support for research and screening

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helps finding breast cancer when it is smaller and moretreatable, which increases the chances of survival. Limitations of mammography include having false positives, false negatives, or finding cancers that maynever cause any symptoms (over-diagnosis).

If you want to learn whether a mammogram is right foryou, then we encourage you to use our screening-deci-sion aid tool called My Breasts, My Test. Launched lastyear, the tool will help you understand what factors toconsider and help you to ask questions of your health-care provider.

Supporting more survivors than ever before Thanks to organised screening programmes, research,improved treatment options and prevention recom-mendation we now have more breast cancer survivorsthan ever. We’re grateful to now be able to turn moreattention to survivorship and how we support womenwho are able to live their lives thanks to research.

Since merging with the Canadian Breast Cancer Foun-dation earlier this year, CCS is better equipped than

ever to fund more research, prevent more diagnosesand support more Canadians affected by breast cancer.

For those in Canada, if you’d like to speak with some-one about yours or a loved one’s breast cancer diag-nosis, you can visit www.cbcf.org/support to speakwith a CCS representative, or call 1-888-939-3333 tospeak with someone from CCS’s Cancer InformationService. ■

Dr Rob NuttallAssistant Director, Health Policy

Shawn ChirreySenior Manager, Health Promotion and Community Engagement

Canadian Cancer Societywww.cancer.ca www.twitter.com/cancersociety

Viruses and cancer: Integratinglarge-scale data to identify uniquegene signatures

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Cancer is a terrible disease thattouches the lives of millions ofindividuals every year. With

cancer being the second leading causeof death in adults, most people havelost a parent, a loved one, or a friendto cancer. The most recent statisticsfrom the American Cancer Societyestimate that roughly 40% of peoplewill develop cancer in their lifetime.Cancer is a disease that originates inour cells. Our bodies are made up ofmillions of cells, grouped together toform tissues and organs such as the lungs, the pancreas, the liver. Ourgenes order our cells to grow, func-tion, reproduce and eventually die.Normally, our cells obey these rulesand we remain healthy. But some-times things go wrong, causing thecells to multiply uncontrollably, form-ing lumps or tumours, and spreadingthrough the bloodstream to otherparts of the body (metastases). Withthe recent advances in medicalresearch, many of these can now bebetter diagnosed and treated. Althoughsignificant progress has been made intreating many cancers over the past25 years, a number of cancers such aspancreatic and brain cancers, continueto have high case fatality rates afterdiagnosis thereby creating havoc in that person’s life as well as theirloved ones.

Viruses and cancer It is nearly impossible to identify whatcauses a cancer in any individual,because most cancers have multiple

possible causes. There are numerouscauses and risk factors for cancersuch as genetic mutations, hormonalchanges, immune dysfunctions, tobaccouse, alcohol use, obesity, dietary fac-tors, physical inactivity, environmentalpolluants, and radiations. One of themost fascinating cause of cancer thatis often overlooked is infection byviruses. Indeed, human viruses playan important role in cancer. Aroundthe world, cancer-inducing viruses areestimated to cause 15 to 20 percent ofall cancers in humans. With theadvent of new technologies allowinggenetic identification, it is very likelythat this number will continue toincrease. Although only a small pro-portion of virus-infected individualsdevelop cancers, the total burden ofinfection-associated cancer is verylarge, with an estimated 2 million newcases of virally-induced cancer world-wide each year. To date, Epstein-Barrvirus (EBV), Kaposi’s sarcoma-associ-ated herpesvirus (KSHV), humanpapillomaviruses (HPV), Merkel cellpolyomavirus (MCPV), hepatitis Bvirus (HBV), hepatitis C virus (HCV) andHuman T-cell Lymphotropic virus type1 (HTLV-1) have been classified ascancer-inducing infectious agents.Cancer-inducing viruses are implicatedin many types of human cancer suchas liver cancer (hepatitis B and Cviruses), cervical cancer (HPV), Burkitt’slymphoma and nasopharyngeal carcinoma (EBV), leukemia (HTLV-1),stomach cancer (EBV), skin cancer(MCPV), and Kaposi’s sarcoma (KSHV).

Over the past fifty years there has also been considerable interest indetermining whether a virus may playan important causative role in othertypes of cancer, such as breast cancer,but no consensus has been definitelyreached.

How do viruses cause cancer?Viruses typically initiate cancer byaltering the expression of the genes inthe cells that they infect or by integrat-ing their genetic materials in keyregions of our DNA. They can alsoinduce inflammation or produce viralproteins which will eventually lead theinfected cells to start multiplyinguncontrollably. The process by whicha virus can cause cancer is complexand requires multiple steps in addi-tion to virus infection. Therefore, thelatency period (from viral infection tothe appearance of the virus-positivetumor) can be many years. Cancer-causing viruses frequently maintainchronic infections in which there isabsence or little production of viralparticles. However, in many cases, theexact mechanisms by which theseviruses cause cancer remain largelyunexplored.

During viral infections, the expressionof cellular genes is subjected to alterations that are induced by both viral and antiviral mechanisms.Interestingly, cancer cells also harbormodifications in the expression of theirgenes. It is therefore not surprisingthat many laboratories are entering

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the personalised medicine era byfocusing their studies on identifyingunique genetic signatures which allowscientists to distinguish between verysimilar cancers. For instance, infectionby EBV is associated with at least 10%of all cases of stomach cancer. Nearly80,000 patients worldwide are estimated to develop EBV-associatedgastric carcinoma (EBVaGC) annually.Interestingly, EBVaGC has uniquemorphological, genetic, and phenotypicfeatures, compared to EBV-negativegastric cancer tissues, and treatmentis therefore different for these twosimilar types of cancer. Correctly and rapidly identifying these types ofcancer is therefore crucial for theeffective treatment of patients withstomach cancer.

Alternative RNA splicing and cancer Traditional profiling of global geneexpression has resulted in several sets

of biomarkers capable of detectingcancer subtypes. However, mostexpression profiling techniques havefocused on changes in the levels ofgene expression and have simplyignore changes in the transcript archi-tecture resulting from a molecularmechanism called alternative splicing.Our genetic information is stored ingenes, located in DNA in the nucleusof cells. This information is transcribedfrom DNA into a messenger RNA(mRNA) template by a process calledtranscription. These mRNAs are thencoverted into proteins by a processcalled translation. However, beforethe mRNA can be translated into proteins, non-coding portions of themRNA sequence, called introns, mustbe removed and protein-coding parts,called exons, joined together by amechanism called RNA splicing to produce a mature mRNA. Scientistsquickly discovered alternative patternsof mRNA splicing that produced differ-

ent mature mRNAs containing variouscombinations of exons from a singleprecursor mRNA. Recent studies indi-cate that almost every human genecan produce different combinations(or isoforms) through alternative splicing. Indeed, the vast majority ofgene products (~90%) use alternativesplicing (Figure 1). In humans, alterna-tive splicing plays a central role in protein diversity by generating multi-ple and functionally diverse proteinisoforms. In the last few years the contribution of alternative splicing tohuman diseases, particularly in cancer,has been widely recognised. It is now evident that the unbalancedexpression of splicing variants or thefailure to properly express the correctisoforms is part of the biology ofcancer cells.

Genome-wide approaches are start-ing to reveal that tumorigenesis, the process by which cells become

Fig. 1: Alternative RNA splicing. Alternative splicing is a regulated process during gene expression that results in a single gene codingfor multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final mRNA producedfrom that gene. Consequently the proteins translated from alternatively spliced mRNAs will contain differences in their amino acidsequence and, often, in their biological functions. Only a few examples of alternative splicing are presented

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cancerous, often involves large-scalealterations in alternative splicing. Suchapproaches have been valuable inproviding insight into the regulation ofsplicing in cancer, and have revealedto be useful in the classification oftumors. In fact, alternative splicingevents can now be used as specificbiomarkers, as was recently shown inthe case of breast cancer tissues. Inthe case of prostate cancer, it hasbeen shown that alternative splicingsignatures derived from microarray-

based profiling are more reliable fordiagnostic purposes than are signa-tures derived from mRNA expressionprofiling. Frequently the function ofthe alternative splicing isoform isunknown, but it appears that main-taining a subtle balance betweensplicing variants is vital to cellularfunction and dynamics. However, onemajor challenge still resides in abetter molecular understanding ofsplicing programs which are found indifferent types of cancer.

Can viruses modify thealternative splicing program of infected cells?During the past year, my researchgroup has been actively investigatingthe ability of viruses to modify the alternative splicing program ofinfected cells. The study of alternativesplicing in mRNAs encoded by cellulargenes during infection by humanviruses remains sparse. Only a fewspecific examples of cellular mRNAsfor which alternative splicing is modified upon viral infection hadbeen previously identified. We reliedon a technique called RNA sequencing(or RNA-seq) to provide a comprehen-sive portrait of global changes in theRNA splicing signatures that occur incells following infection with a humanvirus. This technology uses the capa-bilities of next-generation sequencingto reveal a snapshot of all the mRNAsfrom a cell at a given moment,thereby providing the ability to look atchanges in alternative splicing andgene expression. We designed asimple experiment where we infectedcells with a model virus (called reovirus)and looked at all the cellular mRNAsfollowing infection. This initial studyallowed us to identify modifications inthe alternative splicing patterns of 240cellular mRNAs. Interestingly, thesemodifications seemed to occur onmRNAs which encode for proteinswith important roles in viralinfection/immunity. Among the tran-scripts for which alternative splicingwas significantly affected upon viralinfection, many splicing events wedocumented affect important proteindomains. This led us to hypothesise

Fig. 2: Global profiling of alternative splicing event modifications in gastric cancer.Alternative splicing event modifications in gastric cancer tissues are presented. Thecircular representation of the human genome is shown. The localisation of significantalternative splicing events is shown by a histogram where each bars represent analternative splicing event that is modified between normal and cancer tissues. Positivedifferences are represented in green whereas negative differnces are represented in red.The inner circle represents the statistically significance of each spliced genes where theouter dots show statistical p-value of 0.05 and the inner dots represent a p-value of 0.0001

Martin BisaillonChair and ProfessorUniversité de SherbrookeTel: 1 819 821 8000 Ext: 75287Martin.Bisaillon@USherbrooke.ca

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that viruses might target specific cellular mRNAs in order escape cellular immunity.

We next investigated alterations tothe global RNA splicing landscape ofcellular genes in the context of a virus-induced cancer. We chose gastriccancer as a model since two distincttypes of gastric cancer can be easilyidentified: EBV-negative, and EBV-pos-itive associated gastric cancer. Usinghigh-throughput RNA sequencingfrom 295 primary gastric adenocarci-nomas, we identified alterations in theAS patterns of more than 1700 genes(Figure 2). Interestingly, the vastmajority of these genes encode forproteins with are known to be impor-tant for the development of cancers(such as tumor suppressor genes,transcription factors, and kinases).This study also allowed us to identifyunique gene signatures for whichalternative splicing is misregulated inEBV-negative, and EBV-positive asso-ciated gastric cancer. Analysis of thealternative splicing landscape revealednumerous gastric cancer–specificmarkers, which significantly increasesthe number of potential biomarkersthat can currently be identified bystandard expression profiling alone.We also showed that a specific proteinfrom EBV, called EBNA1, interacts withcellular splicing factors and modifiesthe alternative splicing profile of cellular genes. The currently availablegastric cancer markers available todaymainly detect advanced gastriccancer, for which only palliative treat-ment is available. The current identifi-cation of unique signatures for genes

in which alternative splicing is misreg-ulated in the different types of gastriccancer clearly constitutes a step towardthe identification of other useful gastriccancer-specific markers.

The future?Cancer has been around for a verylong time being mentioned in papyridating to around 1500 BCE. However,the global cancer burden is growing atan alarming pace. It is estimated thatin 2030, about 22 million new cancercases and 13 million cancer deathswill occur, simply due to the growthand aging of the population. The futureburden may be further increased bythe adoption of behaviors andlifestyles frequently associated witheconomic development and urbanisa-tion such as smoking, exposure to polluants, and physical inactivity. Fortunately, there has never been abetter time for researchers to work onfinding a cure for cancer. With somany new technologies and theadvent of personalised medicine,medical decisions and practices willlikely transform the way we fight thisdisease. A number of challenges willsurely arise in this new era, includingintellectual property rights, patientprivacy and confidentiality as well asregulatory oversight. Alternative splicing profiling of tumors, such aswe and others are currently perform-ing, is one of the multiple genomicapproaches currently being used tobetter diagnose and treat cancerpatients. Interestingly, strategies tomodulate alternative splicing bysplice-switching oligonucleotides inorder to correct aberrant alternative

splicing events are currently beingdeveloped. It is therefore tempting tospeculate that such a strategy couldbe applied to many different cancers,including cancers induced by viruses.Our identification of extensive changesin the cellular alternative splicing landscape in gastric cancer likely rep-resents a first step toward the devel-opment of such anticancerous agents.

ProfilePr Martin Bisaillon is an expert in Biochemistry and viral enzymes. Heobtained a PhD in Microbiology andImmunology at the Université deMontréal in 1999. He then completedhis post-doctoral training at the Sloan- Kettering Institute in New YorkCity before directing a research team in the pharmaceutical industryaimedat developing antiviral agents.He is currently Chair of the Biochem-istry Department at the Université deSherbrooke.

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An ounce of prevention, a pound of cure:What makes successful obesity policies?

Obesity is a chronic condition in which excessbody fat is associated with impaired health.Rates of obesity have risen in Canada over the

last 2 decades1; it is estimated that 1 in 4 Canadian adultsand 1 in 7 Canadian children are now obese2. Rates ofobesity vary by geographical area and in specific popula-tions, such as in Indigenous Peoples1, 3.

Concern about obesity rates is not limited to Canada.Worldwide obesity rates have been rising globally since1980, with an estimated 600 million people globallyestimated to now be obese4. Although obesity is gen-erally associated with higher income countries, ratesof obesity are also increasing in low and middle incomecountries4. Recognising the impact of rising obesityrates around the world, in April 2016 the UN GeneralAssembly declared a Decade of Action on Nutrition(2016-2025), calling for the reversal of rising trends inoverweight and obesity and reducing the burden ofdiet-related, non-communicable diseases across allage groups5.

Obesity is a risk factor for the development of chronicdiseases such as stroke, heart disease, type 2 diabetes,osteoarthritis, and cancer,2, 4 which have the potentialto negate health advances that have contributed toincreased life expectancy over the last century. In addi-tion, those with obesity face physical and emotionalconsequences of stigma and discrimination associatedwith their body weight6. In Canada, the significant economic costs of obesity include direct costs such asthe costs to treat obesity-related health conditions,and indirect costs such as workplace absenteeism, disability, and premature mortality1, 2.

It is recognised that multiple factors – including biolog-ical, behavioural, and societal factors – contribute toobesity. As a result, interventions at multiple levels

(including individual, organisational and communitylevels) will be required to address the challenges ofobesity1, 7. Additional research is needed to supportthis multi-tiered approach, with focus on understand-ing the underlying causes of obesity and developingmore effective preventative strategies and treatmentinterventions. For example, numerous animal studiessuggest a role for the gut microbiome in obesity, butmore work needs to be done to establish the role ofmicrobiome in human obesity and determine whethermicrobiome-based interventions can be used to eitherprevent or treat obesity. Evidence to inform the devel-opment of effective population health interventions isalso greatly needed, particularly evidence to informeffective interventions that target health inequities.

Translating research into policyThe Canadian Institutes of Health Research (CIHR), theGovernment of Canada’s health research investmentagency, supports health research across 4 healthresearch themes (biomedical, clinical, health services,and population health research). Obesity has been astrategic focus of the CIHR Institute of Nutrition Metab-olism and Diabetes (INMD) since 20018. As a result oftargeted investments in research, Canada is now inter-

Philip Sherman, Mary-Jo Makarchuk and Keeley Rose at the Canadian Institutes of Health Research,highlight the need for research to inform successful obesity policies

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nationally recognised for producing excellent and highlyimpactful research in the field of obesity9. To supportthe development of evidence to inform policy and treat-ment, CIHR will continue to fund research on obesityand healthy body weight and to mobilise knowledge foreffective preventive and therapeutic interventions andpublic health policies.

“Concern about obesity rates is not limited toCanada. Worldwide obesity rates have been risingglobally since 1980, with an estimated 600 million

people globally estimated to now be obese4.Although obesity is generally associated with higher

income countries, rates of obesity are alsoincreasing in low and middle income countries4.”

The Government of Canada is taking actions to addressthe challenges of obesity in Canada, including initiativesrelated to nutrition. For example, in October 2016, theHonourable Jane Philpott, Canada’s Minister of Health,launched the Healthy Eating Strategy for Canada thatcontains elements to support the maintenance ofhealthy body weight, including the revision of Canada’sdietary guidance, improving food labelling, and restrict-ing the marketing of unhealthy food and beverages tochildren. In addition, CIHR and Health Canada, have part-nered to support research on dietary sugars and healthoutcomes, as well as population level approaches thatcould contribute to reduced consumption of sugars. ■

1 Public Health Agency of Canada and Canadian Institute for Health Infor-

mation. Obesity in Canada: A joint report from the Public Health Agency

of Canada and the Canadian Institute for Health Information. Ottawa,

ON: Her Majesty the Queen in Right of Canada; 2011. Available from:

https://secure.cihi.ca/free_products/Obesity_in_canada_2011_en.pdf

2 Bancej, C., Jayabalasingham, B., Wall, R.W. et al. (2015) Trends and pro-

jections of obesity among Canadians. Health Promot Chronic Dis Prev

Can. 35(7): 109-12. Available from: http://www.phac-aspc.gc.ca/pub-

licat/hpcdp-pspmc/35-7/ar-02-eng.php

3 Tanya Navaneelan and Teresa Janz (2014) Adjusting the scales: Obesity

in the Canadian population after correcting for respondent bias.

Health at a Glance. May. Statistics Canada Catalogue no. 82-624-X.

Available from: http://www.statcan.gc.ca/pub/82-624-x/2014001/arti-

cle/11922-eng.htm

4 World Health Organization. Obesity and overweight fact sheet. Retrieved

from: http://www.who.int/mediacentre/factsheets/fs311/en/

5 World Health Organization. United Nations Decade of Action on Nutri-

tion. Retrieved from: http://www.who.int/nutrition/decade-of-action/en/

6 Alberga, A.S., Russell-Mayhew, S., Von Ranson, K.M. et al. (2016)

Weight bias: a call to action. Journal of Eating Disorders 4:34 doi:

10.1186/s40337-016-0112-4

7 Payne, G.H., James, S.D., Hawley, L., et al. (2015) CDC’s health equity

resource toolkit: disseminating guidance for state practitioners to

address obesity disparities. Health Promot Pract. 16(1): 84–90. doi:

10.1177/1524839914538967.

8 Sherman, P.M., Rose, K. and Makarchuk, M.-J. (2017) Refreshed Strate-

gic Plan for the Canadian Institutes of Health Research Institute of

Nutrition, Metabolism and Diabetes. Can J Diabetes. Accepted

9 Canadian Institutes of Health Research. Bibliometric Study of Obesity

Research in Canada, 1998-2007. Ottawa, ON: Her Majesty the

Queen in Right of Canada; 2009. Available from: http://www.cihr-

irsc.gc.ca/e/41601.html

Philip ShermanScientific Director

Mary-Jo Makarchuk Assistant Director

Keeley RoseProject Manager

Institute of Nutrition, Metabolism and Diabetes – Canadian Institutes ofHealth Research (CIHR)

www.cihr-irsc.gc.ca/e/12043.htmlwww.twitter.com/cihr_irscwww.twitter.com/CIHR_INMD

Researchers at the Human Performance Laboratory are separating the fact fromthe fiction when it comes to optimising the menstrual cycle of female athletes

Optimising the menstrual cycle: Fact not fiction

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Athletes, coaches, and sportphysiologists know that themenstrual cycle can impact

athletic performance, positively andnegatively, despite limited research. In the mid-80s, female athletes were overlooked for research studiesbecause of the challenges and complexity of measuring hormones. I wanted to investigate biomarkersassociated with overtraining inrowers, specifically females. An important research component wouldbe understanding how hormonalresponses impact the metabolic stressof exercise. My graduate supervisor,however, said it would be too difficultand costly to measure the many factors affecting menstrual cycle characteristics.

Menstrual ‘cycle’A quick review highlights that the idealised model of cycle length is 28days. In the follicular phase, days 1-13,the pituitary gland stimulates eggdevelopment through estrogen pro-duction. After the egg is released theovary produces the hormone proges-terone to ready the uterine lining forimplantation. Days 13-15 are the ovu-latory phase. The luteal phase, days16-28, is dominated by progesteroneand follows post ovulation. Ovulatorydisturbances include cycles where noegg is released, (anovulation) or shorteror longer follicular and luteal phases.Throughout the cycle, the luteinising hormone (LH) is secreted and con-trolled by the hypothalamic-pituitary-

ovarian (HPO) axis. Energy balance factors associated with caloric intake,low body fat and weight restriction,influence the ability of the HPO-axis towithstand the stress brought on byexercise (Loucks & Horvath, 1985).Subsequently, a negative energy bal-ance results in ovulatory disturbancesincluding amenorrhea (periods areabsent), which often associated withthe Female Athlete Triad.

The female athlete ‘triad’ The triad is a combination of energydeficiency, ovulatory disturbances,and bone loss (osteoporosis) or boneweakening (osteopenia). Triad researchin the early 90s was focused on athletesparticipating in aesthetic (gymnastics,figure skating, and ballet) andendurance sports (cross countryskiing and running). At the time, I wasthe sport physiologist for the nationalice hockey team. We investigatedenergy expenditure and the metabolic-hormonal profiles of elite ice hockeyplayers (HG) and non-athlete but activeuniversity students (CG) (MacDonald& Doyle-Baker, 2000, 2001). We mea-sured luteal phase length using basalbody temperature (BBT). This methodcoupled with keeping a menstrualcycle diary was too time intensive forthe HG, with only a 28% completionrate versus 70% with the CG. Our datasuggested that although HG and CGwere in a chronic state of negativeenergy balance, they did not exhibit aloss of body weight or percent bodyfat, commonly associated with disor-

dered eating practices and the triad.But they did have varying cyclelengths.

‘Cycle’ lengthThe mean cycle length for both groupswas within the defined range of a typical length, 21-36 days (Munster et al.,1992). The maximum cycle length ofboth groups, however was suggestiveof the occurrence of oligomenorrhea,i.e. greater than 36 days. Similarly, theminimum cycle length was indicativeof polymenorrhea, i.e. less than 21days, but was only observed in theHG. Both groups were classified ashaving short luteal phases (less than10 days), with the mean luteal phaselength for the CG slightly less thanthat of the HG. Anovulation occurredin 50% of HG and 43% of CG cycles.Overall, the HG group exhibitedslightly longer cycle lengths whencompared with the CG. These resultsloosely supported Loucks and Thuma’sseminal research to show that lowenergy availability, not necessarily thestress of exercise or athletic involve-ment, was the factor responsible foraltering the LH pulsatility in exercisingwomen (2003).

Energy availability We continued to ponder the idea ofenergy availability in the menstrualcycle from a substrate utilisation andfuel perspective for a decade beforeembarking on more research. Estrogenis well known to reduce carbohydrateoxidation and increase free fatty acid

Dr P K Doyle-Baker, Dr PH, CSEP-CEPAssociate ProfessorHuman Performance LaboratoryFaculty of KinesiologyUniversity of CalgaryTel: +1 40 322 07034 Fax: +1 403 284 3553pdoyleba@ucalgary.cawww.doylebakerlab.com/www.twitter.com/knowthyhealth

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availability, and progesterone promotesprotein catabolism. Therefore, hormonefluctuations high or low during themenstrual cycle may influence: 1)endurance and high intensity exerciseperformance and 2) the trainability ofmuscle strength and increase inmuscle mass. Hormones also play arole in fluid regulation measured byblood plasma volume (hematocrit).When hormones are high, estrogenand progesterone may contribute to adecreasing plasma volume resulting inblood viscosity changes (hemoglobin).Based on the above, we hypothesisedthat in a 4-week training study aerobicfat oxidation would be improvedduring the luteal phase when comparedto the follicular phase (Minichiello etal., 2016).

Training studyRecreationally trained eumenorrheic(menstruating) cyclists (n=8, 46.0 ±5.1years) were recruited in CalgaryAlberta. Weekly performance testingwas accompanied by ‘day of cycle’,urine colour selection, body composi-tion, hematocrit and hemoglobin mea-sures. To mimic training intensities two

workloads below ventilatory (anaero-bic) threshold were used maximizingfat burning (approximately 60% VO2max)and two mean max power (MMP) tests(6 and 60 second) were used for poweroutput measures. Fat oxidation meanresults were significantly different(p<0.05) over the four weeks specifi-cally between week 1 and 4 and week3 and 4. The six second MMP testshowed no significant difference withmeans of 747.25 watts, 718.00 watts,751.88 watts, and 715.63 watts forweeks one through 4 respectively.Although inconsistencies occurredthroughout the 4-weeks, these findingssuggest a trend towards improved fatburning during the luteal versus thefollicular phase. More training studieswith larger numbers are needed tofully understand the effect of menstru-ation on sport performance determi-nants such as fat oxidation and poweroutput.

Menstruation and sport performance The combined research and anecdotalevidence I have heard as a sport phys-iologist identifies that the menstrual

cycle effect on sport performance is not science fiction. After threedecades of menstrual cycle researchthere is no clear consensus but agree-ment exists that substrate availabilityand fluctuating hormone levels playan important role particularly inendurance performance (Abdollahporet al., 2013; Oosthuyse and Bosch, 2010).There is complexity in measurement,which is influenced by individual vari-ability, a fact identified in the 80s bymy supervisor. Verification difficultiesin hormones and cycle length havebeen lessened with cost effectivemobile device apps that chart BBT andurine based ovulation tests. Despitethese advances the underrepresenta-tion of females in sport researchrelated to the perceived barrier inmenstruation, unfortunately stillexists (Costello et al. 2014).

CANADA ENVIRONMENT & ENERGY

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Clear trajectory for Canada’s clean energy strategy

By accelerating the transition to renewables, Canada’s clean energy strategy is charting a clear course, as Natural Resources Minister Jim Carr sets out here

When most people think of Canada’s energyresources, they are likely to think about ourvast stores of oil and gas. What they might

not realise is that Canada is increasingly focused ondeveloping our renewable energy resources as well.

As the world undergoes a historic transition tocleaner forms of energy, countries are positioningthemselves to capitalise in a clean growth century.They’re realising that climate action is now a compet-itive advantage. The environment and the economyare now two complementary elements of a singleengine of innovation.

Canada’s strategy is to leverage the fossil fuelresources we have today to deliver clean-energy solu-tions for tomorrow. This means making significant newinvestments in clean energy technology, acceleratingits adoption at home and exporting it abroad.

We already have one of the cleanest electricity mixesin the world. Approximately 80% of our electricitycomes from non-greenhouse gas emitting sources, pri-marily hydro (59%) but also nuclear, solar, wind energy,and biomass.

A first for solar heatingRecently, we announced plans to accelerate the phaseout of coal-fired power from our electricity mix, whichwill significantly improve the air quality and the healthof Canadians. This initiative will move Canada closer to90% from non-emitting sources by 2030.

Canadians have already seen exciting developments inclean energy. Last winter, for instance, a community justsouth of Calgary – the Drake Landing Solar Community– became the first community in the world to meet itsheating requirements entirely through solar energy.

Our government is working to accelerate the transitionto renewable energy by investing in the research anddevelopment of innovative clean energy technologies,energy efficiency programs, alternative transportationinfrastructure, and electricity infrastructure interties thatpromote electricity cooperation across our vast nation.

Smart grid technologiesSince 2001, our renewable energy programs have sup-ported almost 5.4 gigawatts (GW) of new renewableelectricity capacity and reduced greenhouse gas emis-sions in the electricity sector.

Our investments will support the development of cleantechnologies to increase the supply of renewableenergy from sources such as solar and wind energy, aswell as that of new and emerging sources, includingwave, in-stream tidal, geothermal and biomass. Further,the use of smart grid technologies and grid connectionswill provide off-grid communities, such as those in thenorth, with cleaner energy.

Based on existing federal, provincial and territorial policies and initiatives, the International Energy Agencyestimates that Canada’s renewable capacity is expectedto grow by around 13 GW over 2015-2021, led by windenergy (7 GW) and solar (2.7 GW). An additional 2.4 GW

Jim Carr, Minister ofNatural Resources

CANADA ENVIRONMENT & ENERGY

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of hydroelectric capacity could also come on line by 2021.

Progress on Canada’s clean energy strategy We are proud of the progress we've made, but there'sstill much more to do. Climate change is among thegreat challenges of our time, and we must make invest-ments that reflect this reality. That’s why we’re invest-ing an unprecedented $180 billion in infrastructure.This includes green infrastructure investments of $5billion announced in the Budget 2016 and a commit-ment to provide an additional $21.9 billion over thenext decade. These investments will help supportgreenhouse gas emission reductions; enable climatechange adaptation and resilience; and, help communi-ties have clean air and safe water.

We’re investing in new low-carbon and renewablepower projects; expanding smart grids to make moreefficient use of existing power supplies; and, deployinginfrastructure for alternative transportation fuels,including re-charging/re-fuelling stations for electricand alternative fuelled vehicles. In order to meet our

emissions reduction target and grow the economy, wehave also adopted the Pan-Canadian Framework forClean Growth and Climate Change – a plan whichincludes a pan-Canadian approach to pricing carbonpollution, and measures to achieve reductions acrossall sectors of the economy.

While the transition to a lower-carbon economy maybe long, its trajectory is clear. Canada is determined toseize the opportunities presented by the new cleanenergy economy by acting decisively and investingwisely, and creating jobs and opportunities for gener-ations to come. ■

Jim CarrMinister of Natural ResourcesGovernment of Canadawww.nrcan.gc.ca/home www.twitter.com/NRCan

Ingenuity Lab is a unique organisa-tion, designed and created to solvemany of the grand challenges

facing a modern world. Ingenuity Labis a research organisation that focuseson the development and deploymentof effective solutions to seeminglyintractable challenges.

It works using a formal connect-and-develop process which involves buildingteams from members of government,industry, and academia. Central to thisprocess is problem identification andthe visualisation of the ideal solution.Often the identified problem is not theproblem, but a symptom. Symptomstend to be obvious, but quite often pro-vide little insight into the most effectivesolution. With the recent intense discus-sion surrounding the newly imposedcarbon tax in Canada, I think that it istime to extract ourselves from the emo-tion of the issue surrounding climatechange, examine the impact of human-ity on our environment, and identify thesalient challenges needed to ensureglobal sustainability.

The unassailable fact is that the Earth’sclimate is changing. But the Earth’s climate has been changing since its creation. The Earth’s atmosphere, gov-erned by complex, non-linear physicalprocesses is easily perturbed. Changesin solar radiation, volcanic activity,deforestation, construction of cities androads, large-scale irrigation and, yes, the release of CO2 into the atmosphere,can all impact the Earth’s climate. The

challenge is teasing out the climate vari-ations caused by natural phenomenawhich we cannot manage from theimpacts caused by anthropomorphicactivities.

Firstly, we need to understand theimpact of human activity versus naturalprocesses on the climate. Then, isolatethe impact of different human activitiesto further identify the effect that eachactivity has on the environment, especially when many of the activitiesoccur simultaneously. For example, thechange in albedo – the amount of solarenergy absorbed/reflected – caused bythe expansion of population centres is usually accompanied by an increasein CO2 emissions. Which of the twoimpacts is more important? Are theircollective impacts additive or multi-plicative? There are many questions yet unanswered. If we cannot clearlydefine and quantify the “cause”, howcan we craft an effective solution?

Disagreeing with MalthusThe bottom line is that human activityhas impacted the Earth’s environmentsince our society transitioned fromhunter-gatherers. In 1798, ThomasMalthus postulated that humans werequickly going to exceed the carryingcapacity of the Earth and that the posi-tive population checks of starvation,disease, and war were necessary. Healso dismissed the idea that technolog-ical advances in agriculture would pro-vide the solution to the Earth’s resourcelimits. I hear echoes of Malthus in much

of the dialogue surrounding climatechange. While no one is proposingeugenic behaviour for addressingman’s impact on the environment,there is a distinct tenor in the dialoguethat humankind must accept a lowerquality of life and reduced opportunityfor future generations. There is also theimplied truth that the human racecannot address the challenges associ-ated with man’s impact on the environ-ment through advances in technology.I soundly reject both premises.

When I was growing up one of myfavorite TV shows was Get Smart. Ialways waited for the moment in theshow when Maxwell Smart would usehis shoe phone. It was hilariousbecause most people perceived it asridiculous. The concept of portablecommunication was outlandish. Nineyears ago when Apple introduced theiPhone, it revolutionised global com-munication. In just 30 years, the tech-nologies of science fiction fantasytransformed the way we engage incommerce, deliver healthcare, andinteract as people. It effectivelyshrunk the world, making the Earth asingle village where virtually everyvoice can be heard.

Popularism politics and bumpersticker scienceUnfortunately, not every voice shouldbe heard at the same volume. The cultof personality has enabled individualswithout the requisite gravitas to seedpopularism politics and bumper sticker

Popularism and bumper sticker science should not stop us tackling sustainabilitythrough technology, argues Ingenuity Lab Director Carlo Montemagno

Sustainability through technology:The power of N

60

PROFILE

science. By feeding personal preju-dices, rational discussion has beenkicked to the curb and has beenreplaced by intensely polarised emo-tion. Culturally, Canadians have anintense connection to the environ-ment. I believe that it is fair to say thatthe wonder of nature is strongly woveninto the fabric of Canadian society. Thisis why Canadians feel compelled tolead the charge against global warmingand why Canada has acted to imposea significant tax on the use of carbon.The question that many are asking,both inside and outside of Canada is,is this an effective path for addressingthe global warming challenge?

Canada is currently responsible forreleasing approximately 1.6% of all ofthe global CO2 emissions. The Euro-pean Union, China, India, Russia, Japan,and the United States are collectivelyresponsible for releasing over 70% ofthe global CO2 emissions. It is doubtfulthat even a 50% reduction of CanadianCO2 emissions would have any materialimpact on global warming. To have anyreal effect on global warming, CO2

emission reductions must occur in con-cert with all six of the major emitters.Even with over 10 years of significanteffort, it has not been possible toachieve a meaningful coordinatedglobal response to CO2 emissions.Acting in isolation will only stress theCanadian economy and place anunnecessary burden on Canadianswithout achieving the desired goal ofreducing man’s impact on global warm-ing. There is a better path forward.

We must recognise that humankindhas impacted and will continue toimpact the Earth. It is our responsibil-ity to access the Earth’s bounty in asustainable way. Our ultimate goalshould be to consume each of Earth’sresources within cyclic processes tomaximise the utility of all of the

resources that we harvest. The eco-nomic reusing of resources wouldensure their continued availability forfuture generations. Achieving thisvision can only be accomplishedthrough technological innovation.

Examining the challenge of CO2 emis-sions you find opportunity. Let’s flip ourperspective; instead of labeling CO2 asa waste product we should recognise itas a valuable raw material. Carbon isthe foundation, the building block of allliving organisms. At the very core of theglobal ecosystem, nature uses theSun’s energy to assemble all livingorganisms from CO2. Visioning the solu-tion to CO2 atmospheric emissions,suppose we can generically insert ourindustrial processes within the web ofnature’s carbon cycle. We take the CO2

which would normally be emitted intothe atmosphere, such as from an elec-trical power generating plant, andinstead, using light, repurpose the CO2

into valuable products. Effectively weinsert the carbon that would have beenwasted and transform it into the fabricof our society. Ingenuity Lab is currentlycommercialising this new technology.

Using the power of N – inspirationfrom nature to guide the manipula-tion of matter using nanotechnologyto build networks – Ingenuity Lab succeeded in replicating the naturalprocess of carbon assembly andtranslated it into an industrial process.The process required learning how toconvert light into the various chemicalfuels of life and the ability to cheaplyfabricate nano-compartmented sys-tems to assemble an artificialmetabolism that fixes and transformsCO2 into valuable products. While notthe total solution to the global climatewarming challenge, it does pull backthe curtain to display the possible. Itshows that the potential for techno-logical achievement is boundless.

Advancing sustainabilitythrough technology We must consider the past technolog-ical achievements of modern man asgovernments assess the optimumstrategy for addressing global sustain-ability challenges. These achievementsspeak loudly about the human poten-tial for creative innovation. Canadaneeds to occupy the position of a lead-ing global steward of the environment,but must achieve it as a champion ofsustainability through technology. It isthe path forward.

Set the stage for a bright future forcoming generations by embracing thepotential of the possible, as well asunderstanding that technologicalachievement can drive market forcesthat lead to a more sustainable world.World leaders need to focus on provid-ing an environment that supports thecrafting of solutions to the globalwarming challenge and not at regula-tory instruments as the primaryweapon of choice. This strategy willaccelerate economic and societal pros-perity and has a much higher likelihoodof long-term success. Canada, believein the inventiveness and creativity ofyour citizenry. Provide the needed envi-ronment, and the people will deliver.The future belongs to the bold.

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PROFILE

Carlo Montemagno, PhDDirector Ingenuity LabTel: 1 780 641 1617montemag@ingenuitylab.cawww.ingenuitylab.cawww.twitter.com/MontemagNANO

CANADA ENVIRONMENT & ENERGY

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POLAR: Investigating the issues Arctic communities face

Polar Knowledge Canada (POLAR) is primed to set Canada at the forefront of the search fornew knowledge of the Polar Regions. Based in

Nunavut, the new federal organisation emphasisesbringing together indigenous and scientific expertiseto create that knowledge – and helping transform itinto action on some of the urgent issues that Arcticcommunities face.

To Inuit and northern First Nations peoples, whoseknowledge of the Arctic is built on centuries of experi-ence and close observation, the Arctic is an intimateand familiar home. Scientists consider the Arctic one ofthe least studied and understood regions on the planet.Both groups are concerned at the significant changesthey see occurring there. Whether in terms of sea ice,permafrost, or wildlife, the impacts are being felt todayin northern communities – and also in distant cornersof the globe, as the Arctic is connected to the rest of theplanet via atmospheric and ocean currents.

Learning and sharing opportunities The purpose of Polar Knowledge Canada is to createnew knowledge that decision makers in northern andsouthern Canada can use to improve economic oppor-tunities, environmental stewardship and quality of lifefor Northerners and all Canadians. Its headquarters,once construction is completed, will be at the CanadianHigh Arctic Research Station (CHARS) campus in Cam-bridge Bay, western Nunavut. With its state-of-the-artlaboratories and generous public space, the uniquefacility is designed to welcome Cambridge Bay resi-dents while ensuring that visiting researchers, educa-tors, and students – from PhD level all the way downto elementary school – have ample opportunity tolearn, and share information and perspectives.

POLAR’s current research programme is focusing on 4

areas: (1) alternative and renewable energy for thenorth; (2) increasing baseline information to prepare fornorthern sustainability; (3) predicting impacts of chang-ing ice, permafrost and snow conditions and how theyaffect shipping, infrastructure, and communities; and (4)improving design, construction and maintenance ofnorthern built infrastructure. These will be revisited in 2019, and every 5 years thereafter.  This regularreassessment and renewal will allow POLAR to adapt tochanging research needs, and remain at the forefrontof knowledge creation that matters in the Arctic.  

One project that POLAR is supporting, SmartICE, bringstogether the expertise of Inuit hunters and ice scien-tists to make ice travel safer. SmartICE, which startedin Nunatsiavut and has expanded to Pond Inlet,Nunavut, is installing thickness sensors in the ice alongroutes in places that hunters have identified as poten-tially unsafe. The measurements are sent to a websitewhere they can be retrieved locally, in Pond Inlet’s caseby ice expert Andrew Arreak. Sensors have also beenmounted on a qamutiik (sled), in order to take meas-urements while travelling. The technology is reliableand easy to operate, and can be passed from one community to the next.

Another key focus is helping northern communitiesmove away from dependence on fossil fuels for electric-ity and heat. In the Northwest Territories, this meanssupport for a community-led wood-pellet district heatingproject in Whati, and 2 community solar power demon-stration projects in Inuvik. In Sanikiluaq, Nunavut, a windmonitoring tower will provide data for potential futurewind power developments in the community.

Gaps in our Arctic understandingThe size, remoteness, and complexity of the Arcticmeans that despite decades of excellent research,

Polar Knowledge Canada, a new federal organisation, brings together indigenous and scientific expertise to look at the issues Arctic communities face today

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there are still plenty of gaps in scientific understandingof the region. Those 3 factors also make Arctic researchvery costly. POLAR intends to create a world class hubfor science and technology research in Canada’s Arctic,with partnerships an integral part of its success.

“Most Arctic science is only possible because researcherswork together, combining their resources,” says DavidScott, president of Polar Knowledge Canada. “And we’veheard from research organisations from around theworld who are keen on collaborating with Canadianresearchers. They’re excited about the possibilities thatthe CHARS research campus and our programme offer.”

One of those is the US National Aeronautics and SpaceAdministration (NASA). NASA’s Arctic Boreal Vulnerabil-ity Experiment is using on-the-ground scientific teams,satellites, and aircraft to monitor and study environ-ments in the arctic and boreal regions of westernCanada and Alaska, which are changing rapidlybecause of a warming climate.

“We are trying to gain a better understanding of howthese northern ecosystems function, how they might

alter under a changing climate and what that meansfor both northerners and the planet as a whole,” saysMike Gill, Senior Science Officer with POLAR. “This willhelp answer such questions as: Will there be caribouavailable to harvest? How will the global carbon budgetbe altered under a warming Arctic and the potentialrelease of methane? Will natural disturbances, such asfire, become an increasing threat?”

Answering these questions affects northernersdirectly, says Scott, and so it makes sense that northerners be involved in research at all levels. “We’relooking to a future where more northerners are in the driver’s seat,” says Scott, “asking the questions,developing and doing research projects – and findingthe answers they need.” ■

Polar Knowledge Canadawww.canada.ca/en/polar-knowledge/index.htmlwww.twitter.com/POLARCanada

The main research building of the Canadian High Arctic Research Station campus in Cambridge Bay, Nunavut, during themidwinter darkness

64

Brock University – Faculty of Social Sciences. . . . . . IFCCotton Incorporated. . . . . . . . . . . . . . . . . . . . . . . . . 34-35Department of Pharmacology & Physiology –Universite de Montreal. . . . . . . . . . . . . . . . . . . . . . . . 42-43Faculte de Medecine et des Sciences de la Sante. . . . . . . . . . . . . . . . . . . . . . . . . 50-53Ingenuity Lab. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60-61Mynosys. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30-31National Soil Dynamics Laboratory. . . . . . . . . . . . . OBCOn Target Laboratories (OTL). . . . . . . . . . . . . . . . . 14-15

Penn Superfund Research and Training Program Cente. . . . . . . . . . . . . . . . . . . . . . 12-13The University of Texas Health Science Center at Houston. . . . . . . . . . . . . . . . . . . . . . . . . . . . 8-9Thunder Bay Regional Research Institute . . . . . . 46-47UCLA Baby Lab. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26-27University of Calgary – Faculty of Kinesiology. . . 56-57University of Illinois. . . . . . . . . . . . . . . . . . . . . . . . . 18-19Women & Infants Hospital. . . . . . . . . . . . . . . . . . . 22-25

INDEX

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