Challenges in Community-Research Relationships: Learning from Natural Science in Nunavut

The context and conduct of Arctic research are changing. In Nunavut, funding agencies, licensing bodies, and new regulatory agencies established under the Nunavut Land Claims Agreement require researchers to engage and consult with Inuit communities during all phases of research, to provide local training and other benefits, and to communicate project results effectively. Researchers are also increasingly expected to incorporate traditional knowledge into their work and to design studies that are relevant to local interests and needs. In this paper, we explore the challenges that researchers and communities experience in meeting these requirements by reviewing case studies of three natural science projects in Nunavut. Together, these projects exemplify both success and failure in negotiating research relationships. The case studies highlight three principal sources of researcher-community conflict: 1) debate surrounding acceptable impacts of research and the nature and extent of local benefits that research projects can and should provide; 2) uncertainty over who has the power and authority to dictate terms and conditions under which projects should be licensed; and 3) the appropriate research methodology and design to balance local expectations and research needs. The Nunavut research licensing process under the Scientists Act is an important opportunity for communities, scientists, and regulatory agencies to negotiate power relationships. However, the standards and procedures used to evaluate research impact remain unclear, as does the role of communities in the decision-making process for research licensing. The case studies also demonstrate the critical role of trust and rapport, forged through early and frequent communication, efforts to provide local training, and opportunities for community members to observe, participate in, and derive employment from project activities. Clarifying research policies in Nunavut is one step to improving relations between scientists and communities. In addition, steps need to be taken at both policy and project levels to train researchers, educate funding programs, mobilize institutions, and empower communities, thus strengthening the capacity of all stakeholders in northern research.Le contexte et la réalisation des travaux de recherche dans l’Arctique sont en pleine évolution. Au Nunavut, les organismes de financement, les organismes de délivrance de permis et de nouveaux organismes réglementaires mis sur pied en vertu de l’Entente sur la revendication territoriale du Nunavut exigent des chercheurs qu’ils recourent aux services des collectivités inuites et les consultent à toutes les étapes des travaux de recherche, qu’ils assurent la formation des personnes auxquelles ils font affaire et leurs fournissent d’autres avantages, puis qu’ils communiquent bien les résultats des projets réalisés. Par ailleurs, on s’attend de plus en plus à ce que les chercheurs intègrent les connaissances traditionnelles à leur travail et conçoivent des études qui se rapportent aux intérêts et aux besoins cernés dans la région. Dans ce document, nous nous penchons sur les défis que doivent relever les chercheurs et les collectivités pour répondre à ces exigences en nous appuyant sur les études de cas de trois projets en sciences naturelles réalisés au Nunavut. Ensemble, ces projets exemplifient tant la réussite que l’échec en matière de négociation de relations de recherche. Ces études de cas mettent en évidence trois sources principales de conflits entre les chercheurs et la collectivité : 1) le débat concernant les incidences acceptables de la recherche de même que la nature et l’étendue des avantages ressentis à l’échelle locale découlant ou susceptibles de découler des projets de recherche; 2) l’incertitude quant à savoir à qui revient le pouvoir et l’autorité de dicter les modalités en vertu desquelles les projets de recherche devraient se voir accorder un permis; et 3) le caractère adéquat de la méthodologie et de la conception de la recherche en matière d’équilibre des attentes des gens de la région et des besoins de la recherche. En vertu de la Loi sur les scientifiques, le processus de délivrance des permis de recherche au Nunavut constitue une manière importante pour les collectivités, les scientifiques et les organismes réglementaires de négocier des rapports de force. Cependant, les normes et les méthodes servant à évaluer les incidences des projets de recherche ne sont toujours pas claires, ce qui est également le cas du rôle des collectivités dans le processus de prise de décisions en matière de délivrance des permis de recherche. Les études de cas font également ressortir le rôle critique de la confiance et des relations, ceux-ci étant le résultat de communications qui se font fréquemment et sans tarder, d’efforts pour fournir de la formation à l’échelle locale et d’occasions, pour les membres de la collectivité, d’observer ce qui se passe, de participer et de se trouver du travail dans le cadre des activités de recherche. Au Nunavut, la clarification des politiques de recherche constitue une manière d’améliorer les relations entre les scientifiques et les collectivités. De plus, des mesures doivent être prises sur le plan des politiques et des projets pour former les chercheurs, sensibiliser les responsables des programmes de financement, mobiliser les établissements et habiliter les collectivités et ce, afin de renforcer la capacité de tous les intervenants touchés par les travaux de recherche dans le Nord

Research on the Human Dimensions of Climate Change in Nunavut, Nunavik, and Nunatsiavut: A Literature Review and Gap Analysis

Research on the human dimensions of climate change (HDCC) in the Canadian Arctic has expanded so rapidly over the past decade that we do not have a clear grasp of the current state of knowledge or research gaps. This lack of clarity has implications for duplication of climate policy and research, and it has been identified as a problem by communities, scientists, policy makers, and northern organizations. Our review of current knowledge about the HDCC in Nunavut, Nunavik, and Nunatsiavut indicates that the effects of climate change on subsistence harvesting and other land-based activities and the determinants of vulnerability and adaptation to such changes are well understood. However, the effects of climate change on health are less known. In the nascent research on this topic, studies on food security and personal safety dominate, and little peer-reviewed scholarship focuses on the business and economic sector. Published research shows a strong bias toward case studies in smaller communities, especially communities in Nunavut. Such studies have focused primarily on negative impacts of climate change, present-day vulnerabilities, and adaptive capacity, but studies proposing opportunities for adaptation intervention are beginning to emerge. While documenting the serious risks posed by climate change, they also highlight the adaptability of northern populations and the effects of economic-political stresses on vulnerability to changing climate. We note the absence of studies that examine how Northerners can benefit from new opportunities that may arise from climate change, or assess how the interaction of future climatic and socio-economic changes (specifically, resource development and enhanced shipping) will affect their experience of and response to climate change, or discuss the broader determinants of vulnerability and adaptation.L’étude des dimensions humaines du changement climatique (DHCC) dans l’Arctique canadien a pris de l’ampleur ces dix dernières années au point où nous n’avons pas une idée claire de l’état actuel des connaissances ou des lacunes en matière de recherche. Cette absence de précision a des incidences sur le plan du dédoublement des politiques et des études sur le climat, ce qui est considéré comme problématique par les collectivités, les scientifiques, les décisionnaires et les organi­sations se trouvant dans le Nord. Nous avons passé en revue les connaissances actuelles en matière de DHCC au Nunavut, au Nunavik et au Nunatsiavut, ce qui nous a permis de constater que les effets du changement climatique sur les récoltes de subsistance et sur d’autres activités rattachées aux ressources naturelles sont bien compris, tout comme le sont les déterminants de la vulnérabilité et de l’adaptation à ces changements. Cela dit, les effets du changement climatique sur la santé sont moins bien connus. Dans le cadre des recherches à l’état naissant à ce sujet, les études portant sur l’innocuité alimentaire et la sécurité personnelle dominent, et peu d’études évaluées par les pairs sont axées sur le secteur commercial et économique. Les travaux de recherche dont les résultats ont été publiés indiquent un fort penchant pour des études de cas visant de plus petites collectivités, surtout les collectivités du Nunavut. Ces études portent principalement sur les incidences négatives du changement climatique, sur les vulnérabilités actuelles et sur la capacité d’adaptation, quoi que des études proposant des possibilités d’intervention adaptative commencent à faire surface. Bien que des études se trouvent à documenter les risques sérieux que pose le changement climatique, elles font également ressortir l’adaptabilité des populations nordiques et les effets des stress politiques et économiques sur la vulnérabilité au climat changeant. Nous avons aussi remarqué l’absence d’études qui examinent comment les gens du Nord peuvent bénéficier des retombées du changement climatique, d’études qui évaluent comment l’interaction des changements climatiques et socioéconomiques futurs (plus précisément en ce qui a trait à la mise en valeur des ressources et à l’amélioration des voies d’expédition) toucheront leur expérience du changement climatique et leur réaction à celui-ci, ou d’études qui discutent des plus grands déterminants de la vulnérabilité et de l’adaptation

What is Effective Research Communication? Towards Cooperative Inquiry with Nunavut Communities

Communication is recognized as the foundation of developing partnerships in science. In this study, we assess the effectiveness of several communication processes, practices, and tools used by wildlife researchers in northern communities in Arctic Canada. A case study was conducted in the communities of Cape Dorset and Coral Harbour (Salliq), Nunavut, Canada, to assess the effectiveness of research communication approaches carried out by the northern marine bird research group of Environment and Climate Change Canada, which has a long-standing research relationship with these two communities. Our objectives were to 1) explore local experiences with research—marine bird research in particular, 2) examine what communication approaches and tools Nunavummiut viewed as most effective for learning about research activities and feeling engaged in the process, and 3) identify new and emerging communication needs in Nunavut communities to support more effective research partnerships. Our findings indicate that several communication methods used by wildlife researchers, such as community meetings, have become less effective because of changing information-sharing practices at the community level. Other communication practices, such as using social media, hold much promise, but as of yet are underutilized by researchers, though of interest to northern communities. Acknowledging that every northern community is unique, with context-specific priorities, capacities, and needs, effective research partnerships should be built upon communication approaches that foster cooperative inquiry and learning. In progress towards this goal, we explore two emerging and related themes: first, access to information and communication technologies in the two communities, and second, the engagement of youth in Arctic research communication and delivery.La communication est reconnue comme le fondement de la formation de partenariats en science. Dans le cadre de cette étude, nous évaluons l’efficacité de plusieurs processus, méthodes et outils de communication employés par les chercheurs de la faune dans des collectivités nordiques de l’Arctique canadien. Une étude de cas a été réalisée dans les collectivités de Cape Dorset et de Coral Harbour (Salliq), au Nunavut, Canada, afin d’évaluer l’efficacité des approches de communication en matière de recherches mises en œuvre par le groupe de recherche des oiseaux aquatiques du Nord relevant d’Environnement et Changement climatique Canada, qui effectue des recherches depuis plusieurs années dans ces deux collectivités. Nos objectifs étaient les suivants : 1) explorer les expériences locales en matière de recherche, plus particulièrement en ce qui a trait aux recherches sur les oiseaux aquatiques; 2) examiner quelles approches de communication et quels outils les Nunavummiuts considèrent comme les plus efficaces pour se familiariser avec les activités de recherche et pour se sentir engagés dans le processus; et 3) déterminer les besoins en communication nouveaux et émergents des collectivités du Nunavut afin de donner lieu à des partenariats de recherche plus efficaces. Selon nos constatations, plusieurs méthodes de communication employées par les chercheurs de la faune, comme les rencontres communautaires, ont perdu de leur efficacité en raison de l’évolution des pratiques de partage de l’information à l’échelle communautaire. D’autres méthodes de communication, comme les médias sociaux, s’avèrent prometteuses, mais les chercheurs ne s’en servent pas encore beaucoup même si elles revêtent de l’intérêt au sein des collectivités du Nord. Reconnaissant le caractère unique des collectivités nordiques, qui ont des priorités, des capacités et des besoins propres à leur contexte, la réalisation de partenariats de recherche efficaces doit se fonder sur des approches de communication favorisant l’apprentissage en collaboration. Dans l’optique de cet objectif, nous explorons deux thèmes émergents et connexes : premièrement, l’accès aux technologies de l’information et de la communication des deux collectivités, et deuxièmement, l’engagement des jeunes en matière de communication et de réalisation des recherches dans l’Arctique

Interleukin-17A expression in patients presenting with nasal polyposis

Sinonasal polyposis (SNP) is a chronic inflammatory pathology of the nasal/paranasal cavities which affects from 1%-4% of the population. Although polyps seem to be a manifestation of chronic inflammation of nasal/paranasal sinus mucosa in both allergic and non-allergic subjects, the pathogenesis of nasal polyposis remains unknown. Interleukin-17A (IL-17A) is a key inflammatory cytokine in many disorders. Little attention has been paid to the role of IL-17A in chronic inflammatory disorders.OBJECTIVE:To investigate the expression of IL-17A in the SNP and verify if this expression is a marker of good or bad prognosis.METHOD:Prospective study with 25 patients presenting with SNP were subjected to the immunohistochemistry technique. After a skin prick test, all patients were divided into atopic and nonatopic groups, and asthmatic or non-asthmatic.RESULTS:The IL-17A expression was observed in both atopic and nonatopic patients. The numbers of IL-17A positive cells were greater in nasal polyps of atopic patients than nonatopic (p = 0.0128).CONCLUSION:These results indicate that IL-17A may play an important role in the pathology of SNP. Considering the inflammatory properties of IL-17A, this study suggests that it could increase susceptibility to atopy and asthma.Polipose nasossinusal (PNS) é uma afecção inflamatória crônica das cavidades nasais/paranasais que afeta 1%-4% da população. Pólipos parecem ser uma manifestação inflamatória crônica da mucosa do seio nasal/paranasal em indivíduos alérgicos e não alérgicos; porém, a patogênese da PNS permanece desconhecida. A interleucina-17A (IL-17A) é uma citocina chave em muitas doenças inflamatórias. Pouca atenção tem sido dada ao papel da IL-17A em distúrbios inflamatórios crônicos.OBJETIVO:Investigar a expressão da IL-17A na PNS e verificar se ela é um marcador de bom ou mau prognóstico.MÉTODO:Estudo prospectivo de 25 pacientes com PNS foram submetidas à técnica de imuno-histoquímica. Após realizarem teste cutâneo, todos os pacientes foram divididos em grupos atópicos e não atópicos e classificados em asmáticos ou não asmáticos.RESULTADOS:A expressão de IL-17A foi observada nos pacientes atópicos e não atópicos; porém, o número de células positivas com IL-17A foi maior nos pólipos nasais de pacientes atópicos que nos não atópicos (p = 0,0128).CONCLUSÃO:Os resultados indicam que a IL-17A pode desempenhar papel importante na patologia da PNS. Considerando as propriedades inflamatórias da IL-17A, este estudo sugere que a IL-17A pode aumentar a susceptibilidade a atopia e asma.Universidade Federal de GoiasUniversidade Estadual de GoiasPontificia Universidade Catolica de GoiasUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators

We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT)-incorporated photo-cross-linkable gelatin methacrylate (GelMA) hydrogels. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework are the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell–cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity.United States. Army Research Office. Institute for Soldier NanotechnologiesNational Institutes of Health (U.S.) (HL092836)National Institutes of Health (U.S.) (EB02597)National Institutes of Health (U.S.) (AR057837)National Institutes of Health (U.S.) (HL099073)National Science Foundation (U.S.) (DMR0847287)United States. Office of Naval Research (ONR PECASE Award)United States. Office of Naval Research (Young Investigator award)National Research Foundation of Korea (grant (NRF-2010-220-D00014)

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)