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Supplementary Table 1. Included countries according to obesity prevalence (proportion of body mass index{greater than or equal to}30kg/m2) quartiles in 2008 by sex. Supplementary Table 2a. Countries by obesity (proportion of body mass index{greater than or equal to}30kg/m2) and smoking (approximated by lung cancer mortality in 2012) tertiles, males. Supplementary Table 2b. Countries by obesity (proportion of body mass index{greater than or equal to}30kg/m2) and smoking (approximated by lung cancer mortality in 2012) tertiles, females. Supplementary Table 3. Age-standardized incidence rate ratios by smoking (approximated by age-standardized lung cancer mortality in 2012) and obesity prevalence (proportion of body mass index{greater than or equal to}30kg/m2) in tertiles (1-3, from lowest to highest), using 1st tertile (lowest level of exposure to both risk factors) as reference. Supplementary Figure 1. Age-standardized incidence rates (ASR) of esophageal and gastric cancers by sex and obesity (proportion of body mass index{greater than or equal to}30kg/m2) quartile, excluding China, Japan and Korea. Supplementary Figure 2. Age-specific incidence rates of esophageal and gastric cancers by sex and obesity (proportion of body mass index{greater than or equal to}30kg/m2) quartile, excluding China, Japan and Korea. Supplementary Figure 3. Male-to-female ratios of esophageal and gastric cancer by age and obesity (proportion of body mass index{greater than or equal to}30kg/m2) quartile, excluding China, Japan and Korea. Supplementary Figure 4. Correlations between obesity prevalence (%) and age-standardized incidence of esophageal and gastric cancers by sex.

Background: Esophageal and gastric cancers differ in their epidemiology but have several risk factors in common. The aim of this study was to assess age and sex differences in the burden of esophageal and gastric cancers in the context of the global obesity epidemic.Methods: Data from 50 countries were obtained from Cancer Incidence in Five Continents Volume X and GLOBOCAN 2012. Age-specific and age-standardized incidence rates of esophageal adenocarcinoma and squamous cell carcinoma (ESCC), as well as cardia (CGC) and noncardia (NCGC) gastric cancer, were estimated. Countries were grouped and analyzed according to their obesity prevalence.Results: A gradient across quartiles of obesity prevalence was found for esophageal adenocarcinoma, with the highest incidence rates in high prevalence countries (ASR 3.0 vs. 0.8 per 100,000 in highest vs. lowest obesity quartiles, males). In contrast, for ESCC as well as for CGC and NCGC the reverse was true, with the highest rates observed in countries with the lowest obesity prevalence (ESCC, 2.2 vs. 11.5; CGC, 2.8 vs. 7.8; NCGC, 3.9 vs. 17.4 in highest vs. lowest obesity quartiles, males). Although for esophageal adenocarcinoma, sex and age differences in incidence were most pronounced in countries with a high prevalence of obesity, these differences were much smaller for the other cancer sites assessed.Conclusions: Variation in obesity prevalence may partly explain age and sex differences in the incidence of esophageal adenocarcinomas.Impact: Ecologic studies can help assess relationships between risk factors and cancer, and generate new hypotheses that may be pursued through more directed research. Cancer Epidemiol Biomarkers Prev; 25(1); 90–97. ©2015 AACR.

Background Community-driven projects that aim to address public concerns about health risks from H. pylori infection in Indigenous Arctic communities (estimated H. pylori prevalence = 64%) show frequent failure of treatment to eliminate the bacterium. Among project participants, treatment effectiveness is reduced by antibiotic resistance of infecting H. pylori strains, which in turn, is associated with frequent exposure to antibiotics used to treat other infections. This analysis compares antibiotic dispensation rates in Canadian Arctic communities to rates in urban and rural populations in Alberta, a southern Canadian province. Methods Project staff collected antibiotic exposure histories for 297 participants enrolled during 2007–2012 in Aklavik, Tuktoyaktuk, and Fort McPherson in the Northwest Territories, and Old Crow, Yukon. Medical chart reviews collected data on systemic antibiotic dispensations for the 5-year period before enrolment for each participant. Antibiotic dispensation data for urban Edmonton, Alberta (average population ~ 860,000) and rural northern Alberta (average population ~ 450,000) during 2010–2013 were obtained from the Alberta Government Interactive Health Data Application. Results Antibiotic dispensation rates, estimated as dispensations/person-years (95% confidence interval) were: in Arctic communities, 0.89 (0.84, 0.94); in Edmonton, 0.55 (0.55, 0.56); in rural northern Alberta, 0.63 (0.62, 0.63). Antibiotic dispensation rates were higher in women and older age groups in all regions. In all regions, the highest dispensation rates occurred for β-lactam and macrolide antibiotic classes. Conclusions These results show more frequent antibiotic dispensation in Arctic communities relative to an urban and rural southern Canadian population.

An analysis of drawings made by Indigenous children in the Arctic hamlet of Fort McPherson, Canada, serves the dual purpose of contributing children’s perspectives to community-driven research on H...

Background Worse health outcomes are consistently reported for First Nations people in Canada. Social, political and economic inequities as well as inequities in health care are major contributing factors to these health disparities. Emergency care is an important health services resource for First Nations people. First Nations partners, academic researchers, and health authority staff are collaborating to examine emergency care visit characteristics for First Nations and non-First Nations people in the province of Alberta. Methods We conducted a population-based retrospective cohort study examining all Alberta emergency care visits from April 1, 2012 to March 31, 2017 by linking administrative data. Patient demographics and emergency care visit characteristics for status First Nations persons in Alberta, and non-First Nations persons, are reported. Frequencies and percentages (%) describe patients and visits by categorical variables (e.g., Canadian Triage and Acuity Scale). Means, medians, standard deviations and interquartile ranges describe continuous variables (e.g., age). Results The dataset contains 11,686,288 emergency care visits by 3,024,491 unique persons. First Nations people make up 4% of the provincial population and 9.4% of provincial emergency visits. The population rate of emergency visits is nearly 3 times higher for First Nations persons than non-First Nations persons. First Nations women utilize emergency care more than non-First Nations women (54.2% of First Nations visits are by women compared to 50.9% of non-First Nations visits). More First Nations visits end in leaving without completing treatment (6.7% v. 3.6%). Conclusions Further research is needed on the impact of First Nations identity on emergency care drivers and outcomes, and on emergency care for First Nations women.

Increasingly, public health research standards call for engaging communities who live with health issues under investigation to help ensure that results translate into effective public health measures. Here, we share guiding principles for community-driven epidemiologic research developed over a decade conducting research sought and controlled by participating communities. These principles provide a roadmap for epidemiologic research that effectively addresses community priorities while meeting academic standards: research questions are developed collaboratively in community-university partnerships; knowledge takes shape from information donated by participants through methods that turn information into scientifically useful data and analysis that reveals data patterns that address research questions; thus, knowledge is generated collaboratively by academic researchers and community partners; academic researchers are bound by ethical, professional, scientific, contractual, and other legal standards to be responsible stewards of information donated by participants; community review protocols ensure that interpretation and presentation of research results reflect the voices of all partners; meaningful community review creates the trust needed for open access to research results as required of academic researchers; all partners share credit for achievements. Lacking models for operationalizing these principles, we developed specific guidelines for research project initiation, data use, authorship, acknowledgment, and data dissemination. Conventions in academia present formidable challenges to effective community engagement and are often at odds with calls from community organizations and funding agencies to conduct research driven by community priorities and values. We hope others can benefit from time and effort we have spent crafting solutions that bridge this divide.

Community H. pylori (Hp) projects conducted by the CANHelp Working Group during 2007- 2018 generated local evidence of relevance to clinical decision-making about Hp infection in Arctic Indigenous communities. We used this information to adapt current Canadian guidelines for northern and Indigenous populations in Canada. Following the guidelines, we present the context and rationale for their development. Because evidence is limited for many of the recommendations we present, due weight should be given to the individual patient’s motivation, values, preferences, and circumstances.

Background: Esophageal and gastric cancers differ in their epidemiology but have several risk factors in common. The aim of this study was to assess age and sex differences in the burden of esophageal and gastric cancers in the context of the global obesity epidemic. Methods: Data from 50 countries were obtained from Cancer Incidence in Five Continents Volume X and GLOBOCAN 2012. Age-specific and age-standardized incidence rates of esophageal adenocarcinoma and squamous cell carcinoma (ESCC), as well as cardia (CGC) and noncardia (NCGC) gastric cancer, were estimated. Countries were grouped and analyzed according to their obesity prevalence. Results: A gradient across quartiles of obesity prevalence was found for esophageal adenocarcinoma, with the highest incidence rates in high prevalence countries (ASR 3.0 vs. 0.8 per 100,000 in highest vs. lowest obesity quartiles, males). In contrast, for ESCC as well as for CGC and NCGC the reverse was true, with the highest rates observed in countries with the lowest obesity prevalence (ESCC, 2.2 vs. 11.5; CGC, 2.8 vs. 7.8; NCGC, 3.9 vs. 17.4 in highest vs. lowest obesity quartiles, males). Although for esophageal adenocarcinoma, sex and age differences in incidence were most pronounced in countries with a high prevalence of obesity, these differences were much smaller for the other cancer sites assessed. Conclusions: Variation in obesity prevalence may partly explain age and sex differences in the incidence of esophageal adenocarcinomas. Impact: Ecologic studies can help assess relationships between risk factors and cancer, and generate new hypotheses that may be pursued through more directed research. Cancer Epidemiol Biomarkers Prev; 25(1); 90–97. ©2015 AACR.

Background Despite the existence of human papilloma virus (HPV) vaccines with demonstrated safety and effectiveness and funded HPV vaccination programs, coverage rates are persistently lower and cervical cancer burden higher among Canadian Indigenous peoples. Barriers and supports to HPV vaccination in Indigenous peoples have not been systematically documented, nor have interventions to increase uptake in this population. This protocol aims to appraise the literature in Canadian and global Indigenous peoples, relating to documented barriers and supports to vaccination and interventions to increase acceptability/uptake or reduce hesitancy of vaccination. Although HPV vaccination is the primary focus, we anticipate only a small number of relevant studies to emerge from the search and will, therefore, employ a broad search strategy to capture literature related to both HPV vaccination and vaccination in general in global Indigenous peoples. Methods Eligible studies will include global Indigenous peoples and discuss barriers or supports and/or interventions to improve uptake or to reduce hesitancy, for the HPV vaccine and/or other vaccines. Primary outcomes are documented barriers or supports or interventions. All study designs meeting inclusion criteria will be considered, without restricting by language, location, or data type. We will use an a priori search strategy, comprised of key words and controlled vocabulary terms, developed in consultation with an academic librarian, and reviewed by a second academic librarian using the PRESS checklist. We will search several electronic databases from date of inception, without restrictions. A pre-defined group of global Indigenous websites will be reviewed for relevant gray literature. Bibliographic searches will be conducted for all included studies to identify relevant reviews. Data analysis will include an inductive, qualitative, thematic synthesis and a quantitative analysis of measured barriers and supports, as well as a descriptive synthesis and quantitative summary of measures for interventions. Discussion To our knowledge, this study will contribute the first systematic review of documented barriers, supports, and interventions for vaccination in general and for HPV vaccination. The results of this study are expected to inform future research, policies, programs, and community-driven initiatives to enhance acceptability and uptake of HPV vaccination among Indigenous peoples. Systematic review registration PROSPERO Registration Number: CRD42017048844 Electronic supplementary material The online version of this article (10.1186/s13643-018-0692-y) contains supplementary material, which is available to authorized users.

Summary Introduction Indigenous people have disproportionally worse health and lower life expectancy than their non-indigenous counterparts in high-income countries. Cancer data for indigenous people are scarce and incidence has not previously been collectively reported in Australia, New Zealand, Canada, and the USA. We aimed to investigate and compare, for the first time, the cancer burden in indigenous populations in these countries. Methods We derived incidence data from population-based cancer registries in three states of Australia (Queensland, Western Australia, and the Northern Territory), New Zealand, the province of Alberta in Canada, and the Contract Health Service Delivery Areas of the USA. Summary rates for First Nations and Inuit in Alberta, Canada, were provided directly by Alberta Health Services. We compared age-standardised rates by registry, sex, cancer site, and ethnicity for all incident cancer cases, excluding non-melanoma skin cancers, diagnosed between 2002 and 2006. Standardised rate ratios (SRRs) and 95% CIs were computed to compare the indigenous and non-indigenous populations of each jurisdiction, except for the Alaska Native population, which was compared with the white population from the USA. Findings We included 24 815 cases of cancer in indigenous people and 5 685 264 in non-indigenous people from all jurisdictions, not including Alberta, Canada. The overall cancer burden in indigenous populations was substantially lower in the USA except in Alaska, similar or slightly lower in Australia and Canada, and higher in New Zealand compared with their non-indigenous counterparts. Among the most commonly occurring cancers in indigenous men were lung, prostate, and colorectal cancer. In most jurisdictions, breast cancer was the most common cancer in women followed by lung and colorectal cancer. The incidence of lung cancer was higher in indigenous men in all Australian regions, in Alberta, and in US Alaska Natives than in their non-indigenous counterparts. For breast cancer, rates in women were lower in all indigenous populations except in New Zealand (SRR 1·23, CI 95% 1·16–1·32) and Alaska (1·14, 1·01–1·30). Incidence of cervical cancer was higher in indigenous women than in non-indigenous women in most jurisdictions, although the difference was not always statistically significant. Interpretation There are clear differences in the scale and profile of cancer in indigenous and non-indigenous populations in Australia, New Zealand, Canada, and the USA. Our findings highlight the need for much-improved, targeted programmes of screening, vaccination, and smoking cessation, among other prevention strategies. Governments and researchers need to work in partnership with indigenous communities to improve cancer surveillance in all jurisdictions and facilitate access to cancer data. Funding International Agency for Research on Cancer–Australia Fellowship.

Globally, gastric cancer incidence shows remarkable international variation and demonstrates distinct characteristics by the two major topographical subsites, cardia (CGC) and non-cardia (NCGC). Because global incidence estimates by subsite are lacking, we aimed to describe the worldwide incidence patterns of CGC and NCGC separately.Using Cancer Incidence in Five Continents Volume X (CI5X), we ascertained the proportions of CGC and NCGC by country, sex and age group (65 and ≥65 years). These derived proportions were applied to GLOBOCAN 2012 data to estimate country-specific age-standardised CGC and NCGC incidence rates (ASR). Regional proportions were used to estimate rates for countries not included in CI5X.According to our estimates, in 2012, there were 260,000 cases of CGC (ASR 3.3 per 100,000) and 691,000 cases of NCGC (ASR 8.8) worldwide. The highest regional rates of both gastric cancer subsites were in Eastern/Southeastern Asia (in men, ASRs: 8.7 and 21.7 for CGC and NCGC, respectively). In most countries NCGC occurred more frequently than CGC with an average ratio of 2:1; however, in some populations where NCGC incidence rates were lower than the global average, CGC rates were similar or higher than NCGC rates. Men had higher rates than women for both subsites but particularly for CGC (male-to-female ratio 3:1).This study has, for the first time, quantified global incidence patterns of CGC and NCGC providing new insights into the global burden of these cancers. Country-specific estimates are provided; however, these should be interpreted with caution. This work will support future investigations across populations.

Methylmercury is a neurotoxicant that is detrimental to the development and physiology of the nervous system. One possible mechanism for methylmercury's toxicity stems from its ability to interfere with the signaling of the neurotrophins nerve growth factor and brain derived neurotrophic factor. In this study, we examine the effect of methylmercury to determine if it interferes with neurotrophin conformation in a manner similar to Hg(2+), or if it occurs via an alternate mechanism. Our findings indicate that although MeHg inhibits neurotrophin signaling, its toxic effects are not mediated via an induced conformational change, as seen with other metal ions, including Hg(2+).

Increasingly, health scientists are becoming aware that research collaborations that include community partnerships can be an effective way to broaden the scope and enhance the impact of research aimed at improving public health. Such collaborations extend the reach of academic scientists by integrating a variety of perspectives and thus strengthening the applicability of the research. Communication challenges can arise, however, when attempting to address specific research questions in these collaborations. In particular, inconsistencies can exist between scientists and community members in the use and interpretation of words and other language features, particularly when conducting research with a biomedical component. Additional challenges arise from differing perceptions of the investigative process. There may be divergent perceptions about how research questions should and can be answered, and in expectations about requirements of research institutions and research timelines. From these differences, misunderstandings can occur about how the results will ultimately impact the community. These communication issues are particularly challenging when scientists and community members are from different ethnic and linguistic backgrounds that may widen the gap between ways of talking and thinking about science, further complicating the interactions and exchanges that are essential for effective joint research efforts. Community-driven research that aims to describe the burden of disease associated with Helicobacter pylori infection is currently underway in northern Aboriginal communities located in the Yukon and Northwest Territories, Canada, with the goal of identifying effective public health strategies for reducing health risks from this infection. This research links community representatives, faculty from various disciplines at the University of Alberta, as well as territorial health care practitioners and officials. This highly collaborative work will be used to illustrate, from a researcher’s perspective, some of the challenges of conducting public health research in teams comprising members with varying backgrounds. The consequences of these challenges will be outlined, and potential solutions will be offered.Keywords: Aboriginal health; Helicobacter pylori; cancer; circumpolar regions(Published: 5 August 2013)This paper is part of Supplement 1, 2013, ICCH15 Proceedings. More papers from this Supplement can be found here.Citation: Int J Circumpolar Health 2013, 72: 21232 - http://dx.doi.org/10.3402/ijch.v72i0.21232

Background . Cancer has been identified as a major cause of morbidity and mortality in Canada over the last decade. However, there is a paucity of information about cancer patterns in Aboriginal people, particularly for Metis. This study aims to explore cancer incidence and mortality burden among Metis and to compare disease estimates with non-Metis population. Methods . This population-based descriptive epidemiological study used cancer incidence and mortality data from 2007 to 2012 obtained from Alberta Health Care Insurance Plan (AHCIP) – Central Stakeholder Registry – and Alberta Cancer Registry (ACR). To identify cancer cases in Metis, the ACR was linked with the Metis Nation of Alberta (MNA) Identification Registry. In Metis and non-Metis people, age-standardized cancer incidence and mortality rates were estimated and subsequently compared between both groups. Results . A higher incidence of bronchus/lung cancer was found among Metis men compared with their non-Metis counterparts (RR=1.69, CI 1.28–2.09; p=0.01). No other statistically significant differences in cancer incidence or mortality were found between Metis and non-Metis people living in Alberta over the course of the 6 years studied. Conclusions . Overall incidence and mortality associated with cancer were not higher among Metis people compared with non-Metis people. However, special efforts should be considered to decrease the higher incidence of bronchus/lung cancer in Metis men. Further development and maintenance of new and existing institutional collaborations are necessary to continue cancer research and health status surveillance in Metis population. Keywords: Aboriginals; Canada; cancer; incidence; Metis; mortality (Published: 1 February 2016) Citation: Int J Circumpolar Health 2016, 75: 30059 - http://dx.doi.org/10.3402/ijch.v75.30059

The neurotrophin nerve growth factor (NGF) binds to two receptor types: the tyrosine kinase receptor TrkA and the common neurotrophin receptor p75(NTR). Although many of the biological effects of NGF (such as neuronal growth and survival) are associated with TrkA activation, p75(NTR) also contributes to these activities by enhancing the action of TrkA when receptors are coexpressed. The NGF antagonist PD90780 [7-(benzolylamino)-4,9-dihydro-4-methyl-9-oxo-pyrazolo[5,1-b]quinazoline-2-carboxylic acid] interacts with NGF, preventing its binding to p75(NTR). In this study, the actions of this compound are further explored, and it is found that PD90780 is not able to inhibit the binding of either brain-derived neurotrophic factor or neurotrophin-3 to p75(NTR), consistent with the direct interactions of the antagonist with NGF. In addition, we demonstrate that the ability of PD90780 to inhibit NGF-p75(NTR) interactions is lower when receptors are coexpressed, compared with when p75(NTR) is the only neurotrophin receptor expressed. These results suggest that the interaction between NGF and the p75(NTR) receptor is altered when TrkA is coexpressed. This alteration can be exploited in the development of antagonists that will selectively inhibit the pro-apoptotic actions of p75(NTR) when expressed in the absence of TrkA, although having less effect on the pro-survival effects of p75(NTR) mediated by enhanced TrkA activation.

Background: Population health data are vital for the identification of public health problems and the development of public health strategies. Challenges arise when attempts are made to disseminate or access anonymised data that are deemed to be potentially identifiable. In these situations, there is debate about whether the protection of an individual’s privacy outweighs potentially beneficial public health initiatives developed using potentially identifiable information. While these issues have an impact at planning and policy levels, they pose a particular dilemma when attempting to examine and address community concerns about a specific health problem. Methods: Research currently underway in northern Canadian communities on the frequency of Helicobacter pylori infection and associated diseases, such as stomach cancer, is used in this article to illustrate the challenges that data controls create on the ability of researchers and health officials to address community concerns. Results: Barriers are faced by public health professionals and researchers when endeavouring to address community concerns; specifically, provincial cancer surveillance departments and community-driven participatory research groups face challenges related to data release or access that inhibit their ability to effectively address community enquiries. The resulting consequences include a limited ability to address misinformation or to alleviate concerns when dealing with health problems in small communities. Conclusions: The development of communication tools and building of trusting relationships are essential components of a successful investigation into community health concerns. It may also be important to consider that public wellbeing may outweigh the value of individual privacy in these situations. As such, a re-evaluation of data disclosure policies that are applicable in these circumstances should be considered. Keywords: Aboriginal health; Canada; Helicobacter pylori; cancer; circumpolar regions; confidentiality (Published: 8 May 2012) Citation: Int J Circumpolar Health 2012, 71 : 18414 - http://dx.doi.org/10.3402/ijch.v71i0.18414

Human plasma contains a myriad of proteins with specialized functions. Of these, proteinase inhibitors represent 10% of the total protein and can be classified as the third major group in this fluid, after albumin and the immunoglobulins. Their functions are to regulate proteolytic enzymes which are normally utilized in coagulation, fibrinolysis, complement activation, phagocytosis, etc. Thus, since these processes involve a variety of proteinases with vastly different specificities it is only logical that specific inhibitors must also be utilized to regulated each system on an individual basis.

Nerve growth factor (NGF) promotes neuronal survival and differentiation and stimulates neurite outgrowth. NGF is synthesized as a precursor, proNGF, which undergoes post-translational processing to generate mature beta-NGF. It has been assumed that, in vivo, NGF is largely processed into the mature form and that mature NGF accounts for the biological activity. However, we recently showed that proNGF is abundant in CNS tissues whereas mature NGF is undetectable, suggesting that proNGF has biological functions beyond its role as a precursor. To determine whether proNGF exhibits biological activity, we mutagenized the precursor-processing site and expressed unprocessed, cleavage-resistant proNGF protein in insect cells. Survival and neurite outgrowth assays on murine superior cervical ganglion neurons and PC12 cells indicated that proNGF exhibits neurotrophic activity similar to mature 2.5S NGF, but is approximately fivefold less active. ProNGF binds to the high-affinity receptor, TrkA, as determined by cross-linking to PC12 cells, and is also slightly less active than mature NGF in promoting phosphorylation of TrkA and its downstream signaling effectors, Erk1/2, in PC12 and NIH3T3-TrkA cells. These data, coupled with our previous report that proNGF is the major form of NGF in the CNS, suggest that proNGF could be responsible for much of the biological activity normally attributed to mature NGF in vivo.