Breast cancer microenvironment and obesity: challenges for therapy.

Women with obesity who develop breast cancer have a worsened prognosis with diminished survival rates and increased rates of metastasis. Obesity is also associated with decreased breast cancer response to endocrine and chemotherapeutic treatments. Studies utilizing multiple in vivo models of obesity as well as human breast tumors have enhanced our understanding of how obesity alters the breast tumor microenvironment. Changes in the complement and function of adipocytes, adipose-derived stromal cells, immune cells, and endothelial cells and remodeling of the extracellular matrix all contribute to the rapid growth of breast tumors in the context of obesity. Interactions of these cells enhance secretion of cytokines and adipokines as well as local levels of estrogen within the breast tumor microenvironment that promote resistance to multiple therapies. In this review, we will discuss our current understanding of the impact of obesity on the breast tumor microenvironment, how obesity-induced changes in cellular interactions promote resistance to breast cancer treatments, and areas for development of treatment interventions for breast cancer patients with obesity.

Alterations in the mammary gland and tumor microenvironment of formerly obese mice.

BACKGROUND: Obesity is a risk factor for breast cancer, and women with obesity that develop breast cancer have a worsened prognosis. Within the mammary gland, obesity causes chronic, macrophage-driven inflammation and adipose tissue fibrosis. Weight loss is a recommended intervention to resolve obesity, but the impact of weight loss on the mammary gland microenvironment and in tumors has not been well identified. METHODS: To examine the effects of weight loss following obesity, mice were fed a high-fat diet for 16 weeks to induce obesity, then switched to a low-fat diet for 6 weeks. We examined changes in immune cells, including fibrocytes, which are myeloid lineage cells that have attributes of both macrophages and myofibroblasts, and collagen deposition within the mammary glands of non-tumor-bearing mice and within the tumors of mice that were transplanted with estrogen receptor alpha positive TC2 tumor cells. RESULTS: In formerly obese mice, we observed reduced numbers of crown-like structures and fibrocytes in mammary glands, while collagen deposition was not resolved with weight loss. Following transplant of TC2 tumor cells into the mammary glands of lean, obese, and formerly obese mice, diminished collagen deposition and cancer-associated fibroblasts were observed in tumors from formerly obese mice compared to obese mice. Within tumors of obese mice, increased myeloid-derived suppressor cells and diminished CD8+ T cells were identified, while the microenvironment of tumors of formerly obese mice were more similar to tumors from lean mice. When TC2 tumor cells were mixed with CD11b+CD34+ myeloid progenitor cells, which are the cells of origin for fibrocytes, and transplanted into mammary glands of lean and obese mice, collagen deposition within the tumors of both lean and obese was significantly greater than when tumor cells were mixed with CD11b+CD34- monocytes or total CD45+ immune cells. CONCLUSIONS: Overall, these studies demonstrate that weight loss resolved some of the microenvironmental conditions within the mammary gland that may contribute to tumor progression. Additionally, fibrocytes may contribute to early collagen deposition in mammary tumors of obese mice leading to the growth of desmoplastic tumors.

An introduction to decision science for conservation.

Biodiversity conservation decisions are difficult, especially when they involve differing values, complex multidimensional objectives, scarce resources, urgency, and considerable uncertainty. Decision science embodies a theory about how to make difficult decisions and an extensive array of frameworks and tools that make that theory practical. We sought to improve conceptual clarity and practical application of decision science to help decision makers apply decision science to conservation problems. We addressed barriers to the uptake of decision science, including a lack of training and awareness of decision science; confusion over common terminology and which tools and frameworks to apply; and the mistaken impression that applying decision science must be time consuming, expensive, and complex. To aid in navigating the extensive and disparate decision science literature, we clarify meaning of common terms: decision science, decision theory, decision analysis, structured decision-making, and decision-support tools. Applying decision science does not have to be complex or time consuming; rather, it begins with knowing how to think through the components of a decision utilizing decision analysis (i.e., define the problem, elicit objectives, develop alternatives, estimate consequences, and perform trade-offs). This is best achieved by applying a rapid-prototyping approach. At each step, decision-support tools can provide additional insight and clarity, whereas decision-support frameworks (e.g., priority threat management and systematic conservation planning) can aid navigation of multiple steps of a decision analysis for particular contexts. We summarize key decision-support frameworks and tools and describe to which step of a decision analysis, and to which contexts, each is most useful to apply. Our introduction to decision science will aid in contextualizing current approaches and new developments, and help decision makers begin to apply decision science to conservation problems.

Las decisiones sobre la conservación de la biodiversidad son difíciles de tomar, especialmente cuando involucran diferentes valores, objetivos multidimensionales complejos, recursos limitados, urgencia y una incertidumbre considerable. Las ciencias de la decisión incorporan una teoría sobre cómo tomar decisiones difíciles y una variedad extensa de marcos de trabajo y herramientas que transforman esa teoría en práctica. Buscamos mejorar la claridad conceptual y la aplicación práctica de las ciencias de la decisión para ayudar al órgano decisorio a aplicar estas ciencias a los problemas de conservación. Nos enfocamos en las barreras para la aceptación de las ciencias de la decisión, incluyendo la falta de capacitación y de conciencia por estas ciencias; la confusión por la terminología común y cuáles herramientas y marcos de trabajo aplicar; y la impresión errónea de que la aplicación de estas ciencias consume tiempo y debe ser costosa y compleja. Para asistir en la navegación de la literatura extensa y dispar de las ciencias de la decisión, aclaramos el significado de varios términos comunes: ciencias de la decisión, teoría de la decisión, análisis de decisiones, toma estructurada de decisiones y herramientas de apoyo para las decisiones. La aplicación de las ciencias de la decisión no tiene que ser compleja ni debe llevar mucho tiempo; de hecho, todo comienza con saber cómo pensar detenidamente en los componentes de una decisión mediante el análisis de decisiones (es decir, definir el problema, producir objetivos, desarrollar alternativas, estimar consecuencias y realizar compensaciones). Lo anterior se logra de mejor manera mediante la aplicación de una estrategia prototipos rápidos. En cada paso, las herramientas de apoyo para las decisiones pueden proporcionar visión y claridad adicionales, mientras que los marcos de apoyo para las decisiones (p.ej.: gestión de amenazas prioritarias y planeación sistemática de la conservación) pueden asistir en la navegación de los diferentes pasos de un análisis de decisiones para contextos particulares. Resumimos los marcos de trabajo y las herramientas más importantes de apoyo para las decisiones y describimos el paso, y el contexto, del análisis de decisiones para el que es más útil aplicarlos. Nuestra introducción a las ciencias de la decisión apoyará en la contextualización de las estrategias actuales y los nuevos desarrollos, y ayudarán al órgano decisorio a comenzar a aplicar estas ciencias en los problemas de conservación.

A framework for allocating conservation resources among multiple threats and actions.

Land managers decide how to allocate resources among multiple threats that can be addressed through multiple possible actions. Additionally, these actions vary in feasibility, effectiveness, and cost. We sought to provide a way to optimize resource allocation to address multiple threats when multiple management options are available, including mutually exclusive options. Formulating the decision as a combinatorial optimization problem, our framework takes as inputs the expected impact and cost of each threat for each action (including do nothing) and for each overall budget identifies the optimal action to take for each threat. We compared the optimal solution to an easy to calculate greedy algorithm approximation and a variety of plausible ranking schemes. We applied the framework to management of multiple introduced plant species in Australian alpine areas. We developed a model of invasion to predict the expected impact in 50 years for each species-action combination that accounted for each species' current invasion state (absent, localized, widespread); arrival probability; spread rate; impact, if present, of each species; and management effectiveness of each species-action combination. We found that the recommended action for a threat changed with budget; there was no single optimal management action for each species; and considering more than one candidate action can substantially increase the management plan's overall efficiency. The approximate solution (solution ranked by marginal cost-effectiveness) performed well when the budget matched the cost of the prioritized actions, indicating that this approach would be effective if the budget was set as part of the prioritization process. The ranking schemes varied in performance, and achieving a close to optimal solution was not guaranteed. Global sensitivity analysis revealed a threat's expected impact and, to a lesser extent, management effectiveness were the most influential parameters, emphasizing the need to focus research and monitoring efforts on their quantification.

Un Marco de Referencia para Asignar Recursos para la Conservación entre Múltiples Amenazas y Acciones Resumen Los administradores de tierras deciden cómo asignar recursos entre múltiples amenazas que pueden abordarse por medio de múltiples acciones. Adicionalmente, estas acciones varían en viabilidad, efectividad y costo. Buscamos proporcionar una manera para optimizar la asignación de recursos para abordar varias amenazas cuando están disponibles muchas opciones de manejo, incluyendo opciones mutuamente excluyentes. Con una formulación de la decisión como un problema combinatorio de optimización, nuestro marco de referencia toma como entradas el impacto esperado y el costo de cada amenaza para cada acción (incluyendo hacer nada) y para cada presupuesto generalizado identifica la acción óptima a realizar ante cada amenaza. Comparamos la solución óptima con una aproximación de un algoritmo avaricioso fácil de calcular y una variedad de esquemas plausibles de clasificación. Aplicamos el marco de trabajo al manejo de múltiples especies de plantas introducidas en las áreas alpinas de Australia. Desarrollamos un modelo de invasión para predecir el impacto esperado en 50 años para cada combinación de especie-acción que consideró el estado actual de invasión para cada especie (ausente, localizada, ampliamente distribuida), la probabilidad de invasión, la tasa de esparcimiento, el impacto, cuando abundante, de cada especie y la efectividad de manejo de cada combinación especie-acción. Descubrimos que la acción recomendada para una amenaza cambia con el presupuesto, que no existe una acción única de manejo óptimo para cada especie y que considerar más de una acción candidata puede incrementar sustancialmente la eficiencia general del plan de manejo. La solución aproximada (solución clasificada por rentabilidad) tuvo un buen desempeño cuando el presupuesto fue igual al costo de las acciones prioritarias, lo que indica que esta estrategia sería efectiva si el presupuesto está fijado como parte del proceso de priorización. Los esquemas de clasificación variaron en cuanto a desempeño, y lograr una solución cercana a lo óptimo no estuvo garantizado. El análisis de sensibilidad global reveló que el impacto esperado de una amenaza y, a menor grado, la efectividad del manejo no fueron los parámetros con mayor influencia, lo que enfatiza la necesidad de enfocar la investigación y los esfuerzos de monitoreo en la cuantificación del impacto esperado y la efectividad del manejo.

General practitioners' perceptions of compassionate communities: a qualitative study.

BACKGROUND: General Practitioners (GPs) face challenges when providing palliative care, including an ageing, multimorbid population, and falling GP numbers. A 'public health palliative care' approach, defined as "working with communities to improve people's experience of death, dying and bereavement", is gaining momentum. 'Compassionate communities' is one example, with a focus on linking professional health carers with supportive community networks. Primary care is central to the approach, which has been incorporated into United Kingdom GP palliative care guidance. No research to date, however, has investigated GP perspectives of these approaches. Our aim, therefore, was to explore GP perceptions of a public health approach to palliative care, and compassionate communities. METHODS: GPs working in the United Kingdom were recruited through university teaching and research networks using snowball sampling. Purposive sampling ensured wide representation of gender, level of experience and practice populations. Semi-structured, digitally audio-recorded interviews were conducted with nine GPs. Interviews were transcribed verbatim, and thematic analysis was undertaken, informed by a qualitative descriptive methodology. Interviews continued until data saturation was reached. RESULTS: Most participants were unfamiliar with the term 'compassionate communities', but recognised examples within their practice. Three major themes with seven subthemes were identified: 1) Perceived potential of compassionate communities, including: 'maximising use of existing community services'; 'influencing health outside of healthcare'; and 'combatting taboo', 2) Perceived challenges of compassionate communities, including: 'patient safety'; 'limited capacity of the community'; 'limited capacity of general practice', and 'applicability of public health to palliative care', and 3) The role of the GP in compassionate communities. CONCLUSIONS: GPs recognised the importance of the wider community in caring for palliative care patients, however most were unfamiliar with the compassionate community approach. Participants held differing views regarding the application of the model, and the position of general practice within this. Further research into the approach's practical implementation, and exploring the views of other key stakeholders, would help establish the feasibility of compassionate communities in practice, and guide its future application.

Simultaneous choice bioassays accompanied by physiological changes identify civetone and decanoic acid as pheromone candidates for giant pandas.

Chemicals present in urine are thought to play an important role in mate identification in the solitary giant panda (Ailuropoda melanoleuca). During the breeding season, females will deposit chemical signals to advertise sexual receptivity to potential mates. The goal of this study was to determine if specific volatile compounds found in female urine could be considered as pheromones that elicit behavioral and physiological responses in males. Experimental simultaneous choice trials were conducted with captive male giant pandas (n = 3) housed at Memphis Zoo, San Diego Zoo, and Zoo Atlanta. Octanoic acid, 1H-pyrrole-2-carboxaldehyde, decanoic acid, and civetone were selected as stimuli because previous studies reported their elevation in urine during the breeding season. Male interest was determined by a behavioral preference toward these volatile compounds diluted in synthetic urine compared with nontreated synthetic urine. Male urine samples were collected 1 week prior, during, and 1 week after the experimental period to assess changes in urinary semiochemical composition and urinary androgen concentrations. No significant differences in investigation response (p = .395) or flehmen response (p = .600) were found when stimuli were compared; however, decanoic acid and civetone elicited a behavioral preference over the control (response ratio > 0.5). The relative abundance of 16 compounds identified in male urine was significantly elevated (p < .05) above baseline values after the males were exposed to the stimuli. Androgen levels were significantly elevated (p < .05) in one male after exposure to 1H-pyrrole-2-carboxaldehyde, decanoic acid, and civetone. These data suggested that civetone and decanoic acid in female urine may motivate sexual responses in males.

Estimates of the current and future burden of cancer attributable to alcohol consumption in Canada.

Alcohol consumption is associated with elevated risk of oropharyngeal, laryngeal, esophageal, colon, rectal, breast, liver, pancreatic and stomach cancers. The purpose of this analysis was to provide national and provincial estimates of the number and proportion of cancers attributable to alcohol consumption in Canada and to project the numbers of potentially avoidable cancers using possible intervention scenarios. We estimated the population attributable risk (PAR) for cancers associated with alcohol consumption levels (drinks/day) using: i) relative risks obtained from the World Cancer Research Fund/(WCRF) reports or meta-analyses, ii) alcohol consumption (prevalence) data from the 2003 Canadian Community Health Survey, and iii) cancer incidence data from the 2015 Canadian Cancer Registry. We used potential impact fractions (PIFs) to estimate the future avoidable cancer burden under four counterfactual scenarios: (1) lowering alcohol consumption to meet the WCRF low risk guidelines, (2) meeting the Canada's Low-Risk Drinking Guidelines, (3) reducing daily intake by one drink/day, and (4) decreasing consumption to 50% of the 2003 levels by 2032. We estimated that 3282 incident cancer cases (5.2% of alcohol-associated cancers and 1.8% of all cancers) diagnosed in Canada in 2015 were attributable to alcohol consumption. At the current consumption levels, alcohol-attributable cancers are expected to increase to 10,122 (8.8% of cases among alcohol-associated cancers) by 2042. Under the best case scenario, reducing alcohol consumption to 50% of 2003 levels by 2032, could prevent 70,261 cases by 2042. Strategies that effectively reduce alcohol consumption at a population level can have a meaningful impact on reducing the cancer burden in Canada.

Estimates of the current and future burden of cancer attributable to active and passive tobacco smoking in Canada.

Although previous studies have examined the burden of cancer attributable to tobacco smoking, updated estimates are needed given the dramatic changes in smoking behaviours over the last 20 years. In this study, we estimate the proportion of cancer cases in 2015 attributable to past tobacco smoking and passive exposure in Canada and the proportion of cancers in the future that could be prevented through the implementation of interventions targeted at reducing tobacco use. Data from the Canadian Community Health Survey (2003) were used to estimate the prevalence of active tobacco smoking and passive exposure. Population attributable risk estimates were employed to estimate the proportion of cancers attributable to tobacco in 2015. The prevalence of active tobacco smoking and passive exposure was projected to 2032 and cancer incidence was projected from 2016 to 2042 to estimate the future burden of cancer attributable to tobacco. In 2003, 30% and 24% of Canadians were former and current smoker, respectively and 24% had been exposed to tobacco smoke in the past. We estimated that 17.5% (32,655 cases; 95% CI: 31,253-34,034) of cancers were attributable to active tobacco smoking and 0.8% (1408 cases; 95% CI: 1048-1781) to passive tobacco exposure in never smokers. Between 41,191 and 50,696 cases of cancer could be prevented by 2042 under various prevention scenarios. By decreasing passive tobacco exposure by 10-50%, between 730 and 3650 cancer cases could be prevented by 2042. Strategies focused on reducing the prevalence of tobacco smoking are crucial for cancer control in Canada.

The current and future burden of cancer attributable to modifiable risk factors in Canada: Summary of results.

Nearly one in two Canadians are expected to be diagnosed with cancer in their lifetime. However, there are opportunities to reduce the impact of modifiable cancer risk factors through well-informed interventions and policies. Since no comprehensive Canadian estimates have been available previously, we estimated the proportion of cancer diagnosed in 2015 and the future burden in 2042 attributable to lifestyle and environmental factors, and infections. Population-based historical estimates of exposure prevalence and their associated risks for each exposure-cancer site pair were obtained to estimate population attributable risks, assuming the exposures were distributed independently and that the risk estimates were multiplicative. We estimated that between 33 and 37% (up to 70,000 cases) of incident cancer cases among adults aged 30 years and over in 2015 were attributable to preventable risk factors. Similar proportions of cancer cases in males (34%) and females (33%) were attributable to these risk factors. Tobacco smoking and a lack of physical activity were associated with the highest proportions of cancer cases. Cancers with the highest number of preventable cases were lung (20,100), colorectal (9800) and female breast (5300) cancer. If current trends in the prevalence of preventable risk factors continue into the future, we project that by 2042 approximately 102,000 incident cancer cases are expected to be attributable to these risk factors per year, which would account for roughly one-third of all incident cancers. Through various risk reduction interventions, policies and public health campaigns, an estimated 10,600 to 39,700 cancer cases per year could be prevented by 2042.

Estimates of the current and future burden of cancer attributable to low fruit and vegetable consumption in Canada.

Low fruit and vegetable consumption is associated with colorectal cancer and may be associated with lung, breast, bladder, pancreatic, ovarian, liver, stomach, esophageal, head and neck cancers. We estimated the current attributable and future avoidable burden of cancer associated with low fruit and vegetable consumption in Canada. Using data on cancer incidence, exposure prevalence and risk effects, we estimated the population attributable risk (PAR) for cancers associated with low fruit and vegetable consumption as well as the future avoidable burden. The prevalence of fruit and vegetable consumption was projected to 2032 and cancer incidence was projected to 2042 to estimate the future potential impact fraction of cancer attributable to low fruit and vegetable consumption. Based on estimates from the Canadian Community Health Survey, the prevalence of low fruit (<4 servings/day) and vegetable (<4 servings/day) consumption in the Canadian population was 80.5% and 86.6%, respectively. The PARs for colorectal cancer associated with low fruit and vegetable consumption were 6.1% (1, 371 cases) and 2.2% (487 cases), respectively. For all incident cancers in 2015, 0.7% and 0.3% were attributable to low fruit and vegetable consumption, respectively. An increase of one serving/week of fruit could prevent 20,710 colorectal cancer cases cumulatively by 2042, and the same increase in vegetable consumption could prevent 10,185 cases. Although more research on the association between fruit and vegetable consumption and cancer risk is needed, our results demonstrate that with reasonable increases in current fruit and vegetable consumption by Canadians, over 30,000 colorectal cancer cases could be prevented by 2042.

Estimates of the current and future burden of cancer attributable to red and processed meat consumption in Canada.

Red meat and processed meat have been consistently associated with an increased risk of colorectal, stomach, pancreatic cancer and esophageal cancer (processed meat only). The purpose of this analysis was to estimate the current attributable and future avoidable burden of cancer related to red and processed meat consumption in Canada. We estimated the population attributable risk of cancer separately for red meat consumption (beef, lamb, and pork, excluding processed meat) and processed meat consumption (sausage and bacon) incorporating current cancer incidence data, relative risks, and exposure prevalence. We also estimated the future avoidable burden of cancer from 2015 to 2042 for Canada and by province using the potential impact fraction associated with various potential intervention scenarios intended to reduce consumption, ranging from a decrease of 0.2 servings/week to 2.0 servings/week among the adult Canadian population aged 20 and over. The estimated mean red meat consumption in the Canadian population in 2007 to 2011 was approximately 3.2 times per week. In addition, Canadians consume an average of 1.2 times of processed meat per week. In 2015, an estimated 5.9% of associated cancers and 0.9% of all cancers were attributable to red meat consumption. An estimated 4.5% of associated cancers and 0.7% of all cancers were attributable to processed meat consumption. A mean decrease of 0.5 servings/week of red meat or processed meat could prevent about 8700 or 16,600 cancer cases, respectively, between 2015 and 2042. In conclusion, a small but meaningful cancer burden is associated with red and processed meat consumption. Interventions aimed at reducing consumption at the population level have the potential in the prevention of many cancers in Canada.

Estimates of the current and future burden of cancer attributable to excess body weight and abdominal adiposity in Canada.

The increasing prevalence of obesity among Canadians has important implications for newly diagnosed cases of cancer given that excess body weight and abdominal adiposity are known to increase the risk of several cancers. The purpose of this analysis was to estimate the current attributable and future avoidable burden of cancer related to excess body weight and abdominal adiposity among Canadian adults. We estimated the population attributable risk (PAR) for all cancers associated with excess body weight and abdominal adiposity using contemporary cancer incidence, relative risk and exposure prevalence data for body mass index (BMI), waist circumference and waist-to-hip-ratio. Using the partial impact fraction (PIF), we also estimated the future avoidable burden of cancer from 2015 to 2042 in Canada, and by province, through various hypothetical intervention scenarios. In 2003, approximately half (50.5%) of the Canadian population was estimated to be overweight (BMI 25.0-29.9) or obese (BMI ≥30.0), 56.5% to have excess abdominal adiposity and 56.8% with a high waist-to-hip ratio. In 2015, the estimated PARs of all incident cancers associated with excess body weight, excess abdominal adiposity and high waist-to-hip ratio were 7.2%, 8.9% and 10.0%, respectively. If the population BMI could revert to its 1994 distribution, 72,157 associated cancer cases could be prevented cumulatively by 2042. A reduction in excess body weight and abdominal adiposity has the potential to decrease the future cancer burden in Canada substantially, and hence efforts to reverse increasing trends in obesity should be prioritized.

Estimates of the current and future burden of cancer attributable to lack of physical activity in Canada.

Physical activity reduces the risk of many cancers, yet the prevalence of inadequate physical activity among Canadians remains high. Here we estimated the current attributable and future avoidable burden of cancer related to inadequate physical activity among Canadian adults. Population attributable risk (PAR) for all cancers associated with inadequate physical activity were estimated using relative risks obtained from comprehensive reports, meta-analyses and pooled analyses. Cancer incidence data were acquired from the Canadian Cancer Registry. Physical activity data were taken from Canadian Community Health Survey (Cycle 2.1, 2003), in which respondents were classified as "physically inactive" (<1.5 kcal/kg/day), "moderately active" (1.5-2.9 kcal/kg/day) or "physically active (≥3.0 kcal/kg/day). We defined "inadequate physical activity" as being either "physically inactive" or "moderately active" to determine the PAR of cancer due to inadequate physical activity. We estimated the future burden of inadequate physical activity using potential impact fractions and a series of intervention scenarios, including 10% to 50% reductions in inadequate physical activity from 2015 to 2042. For 2015, the total attributable burden due to inadequate physical activity for associated cancers was 10.6% and 4.9% for all cancers. A 50% reduction in inadequate physical activity could avoid 39,877 cumulative cases of cancer by 2042. Over 9000 cancer cases in 2015 were estimated to be attributable to inadequate physical activity and 5170 incident cases of cancer could be prevented with increases in physical activity levels by 2042. Policies aimed at increasing physical activity among Canadian could have a meaningful impact for cancer prevention.

Estimates of the current and future burden of cancer attributable to sedentary behavior in Canada.

Leisure-time sedentary behavior is an emerging modifiable risk factor for cancer. We estimated the proportion of cancers attributed to leisure-time sedentary behavior as a separate risk factor from physical activity in Canada for 2015. We projected numbers of future avoidable cancers by 2042 using various assumed levels of reduced leisure-time sedentary behavior in the population. We calculated population attributable risks (PAR) for associated cancers and all-cancers associated with leisure-time sedentary behavior. Our analysis used pooled data on leisure-time sedentary behavior from the Canadian Community Health Survey (CCHS), and incident cancer data from the Canadian Cancer Registry (CCR). Survey respondents were categorized into three levels of leisure-time sedentary behavior, "<3 h/day", "≥3-<6 h/day", and "≥6 h/day". Estimates for the future burden of leisure-time sedentary behavior were calculated using the potential impact fractions framework (PIF) and counterfactual scenarios, from 10% to 50% decreases in leisure-time sedentary behavior. The estimated prevalence of leisure-time sedentary behavior at the highest level (≥6 h/day) in Canada during the 2000s was 9.9% among both sexes combined across age-groups. The total attributable burden due to leisure-time sedentary behavior was estimated to be 10.3% for associated cancers and 6.5% for all-cancers in 2015. A 50% reduction in leisure-time sedentary behavior across the Canadian population could avoid 4054 cancers by 2042. We estimated that over 3000 cancer cases in Canada were attributable to leisure-time sedentary behavior in 2015, and that that 4054 incident cancer cases could be prevented by 2042 with meaningful reductions in leisure-time sedentary behavior.

The burden of cancer attributable to modifiable risk factors in Canada: Methods overview.

Up-to-date estimates of current and projected future cancer burden attributable to various exposures are essential for planning and implementing cancer prevention initiatives. The Canadian Population Attributable Risk of Cancer (ComPARe) study was conducted to: i) estimate the number and proportion of cancers diagnosed among adults in Canada in 2015 that are attributable to modifiable risk factors and ii) project the future avoidable cancers by 2042 under various intervention targets. We estimated the population attributable risk (with 95% confidence intervals) and the potential impact fraction of cancers associated with selected lifestyle, environmental, and infectious factors. Exposure-specific sensitivity analyses were also completed where appropriate. Several exposures of interest included active and passive smoking, obesity and abdominal adiposity, leisure-time physical inactivity, sedentary behaviour, alcohol consumption, insufficient fruit and vegetable intake, red and processed meat consumption, air pollution (PM2.5, NO2), indoor radon gas, ultraviolet radiation (UVR), hepatitis B and C virus, Helicobacter pylori, Epstein-Barr virus, human papillomavirus, human herpesvirus type 8 and human T-cell lymphotropic virus type 1. We used the 2015 cancer incidence data for 35 cancer sites from the Canadian Cancer Registry and projected cancer incidence to 2042 using historical data from 1983 to 2012. Here, we provide an overview of the data sources and methods used in estimating the current and future cancer burden in Canada. Specific methodologic details for each exposure are included in the individual articles included as part of this special issue.

Age-standardized cancer-incidence trends in Canada, 1971-2015.

BACKGROUND: Although cancer incidence over time is well documented in Canada, trends by birth cohort and age group are less well known. We analyzed age- and sex-standardized incidence trends in Canada for 16 major cancer sites and all cancers combined. METHODS: We obtained nationally representative population-based cancer incidence data in Canada between 1971 and 2015 from the National Cancer Incidence Reporting System (1969-1992) and the Canadian Cancer Registry (1992-2015). We analyzed cancer-incidence trends, reported as annual percent change (APC) for each 10-year group from age 20 to 89 years. We also estimated age-adjusted incidence rate ratios from fitted birth cohort models. RESULTS: Across most age categories, the most recent trends show significant decreases in the incidence of cervical (APC -8.8% to -0.33%), lung (men: -7.42% to -0.36%; women: -6.27% to 1.07%), bladder (women: -4.12% to -0.07%; men: -5.13% to -0.38%) and prostate cancer (-11.11% to -1.11%). Significant increasing trends were observed for kidney, thyroid and uterine cancers. Overall incidence has increased among both sexes younger than 50 years of age, with recent increases in pancreatic cancer among men, breast cancer among women and colorectal cancer among both sexes. From the birth cohort analysis, we observed increasing trends in colorectal, liver and prostate cancers among men; kidney cancer and melanoma among women; and thyroid cancer among both sexes. We observed decreasing trends in cervical and ovarian cancers, and in bladder and lung cancers among men. INTERPRETATION: Cancer incidence is decreasing at many sites targeted by primary-prevention efforts, such as smoking cessation and screening programs. Substantial increases in incidence among younger populations are driven by cancers possibly associated with obesity.

Measures of excess body weight and anthropometry among adult Albertans: cross-sectional results from Alberta's tomorrow project cohort.

BACKGROUND: Excess body weight during adulthood has been consistently associated with all-cause mortality, cardiovascular disease, and cancer at multiple sites among other chronic diseases. We describe the prevalence of excess body weight and abdominal obesity reported by participants enrolled in Alberta's Tomorrow Project (ATP). METHODS: ATP is a geographically-based cohort study conducted among adults aged 35-69 years from across the province of Alberta. Participants completed anthropometric measures and health and lifestyle questionnaires at enrolment. Overweight and obese were categorized as a body mass index (BMI) of 25.0-29.9 kg/m2 and ≥30 kg/m2, respectively. Abdominal obesity was categorized using cut-offs of waist circumference of >94 cm for men and >80 cm for women and waist-tp-hip ratio cut-offs of >0.90 for men and >0.85 for women. RESULTS: BMI and hip and waist circumference data were obtained from 12,062 men and 18,853 women enrolled between 2001 and 2009. Overall, 76.8% of men and 59.5% of women reported a BMI ≥25 kg/m2. The proportions of overweight and obese were significantly higher in older age groups (p < 0.001). In addition, the proportion of participants reporting being overweight and obese was higher among lower education (p < 0.001) and lower income groups (p < 0.001). Overall, approximately two thirds of men and women in ATP cohort reported abdominal obesity. Overweight, obesity and abdominal obesity were all associated with a history of several cardiometabolic chronic conditions including hypertension, heart attack, angina, high cholesterol, stroke and diabetes. CONCLUSION: A large majority of ATP participants were overweight and carried excess abdominal fat. Strategies to improve energy balance among Albertans are encouraged and may have a notable impact on future chronic disease burden.

Current practices in the identification of critical habitat for threatened species.

The term critical habitat is used to describe the subset of habitat that is essential to the survival and recovery of species. Some countries legally require that critical habitat of listed threatened and endangered species be identified and protected. However, there is little evidence to suggest that the identification of critical habitat has had much impact on species recovery. We hypothesized that this may be due at least partly to a mismatch between the intent of critical habitat identification, which is to protect sufficient habitat for species persistence and recovery, and its practice. We used content analysis to systematically review critical habitat documents from the United States, Canada, and Australia. In particular, we identified the major trends in type of information used to identify critical habitat and in occupancy of habitat identified as critical. Information about population viability was used to identify critical habitat for only 1% of the species reviewed, and for most species, designated critical habitat did not include unoccupied habitat. Without reference to population viability, it is difficult to determine how much of a species' occupied and unoccupied habitat will be required for persistence. We therefore conclude that the identification of critical habitat remains inconsistent with the goal of protecting sufficient habitat to support persistence and recovery of the species. Ensuring that critical habitat identification aligns more closely with its intent will improve the accuracy of the designations and may therefore help improve the benefits to species recovery when combined with adequate implementation and enforcement of legal protections.

The transport of DDT from chylomicrons to adipocytes does not mimic triacylglycerol transport.

Despite being banned in the U.S., organochlorine toxins such as DDT are frequently detected in human adipose tissue. The main route of exposure is through the consumption of contaminated foods and subsequent intestinal packaging of DDT into chylomicrons. These chylomicrons, which also contain dietary triacylglycerol (TG), are delivered directly to peripheral tissues without first being metabolized by the liver. The physiological process by which these compounds are delivered from chylomicrons to adipose is not well understood, but is clinically relevant since it bypasses first-pass metabolism. Based on its highly lipophilic nature, it has been assumed that DDT is transferred to peripheral tissues similar to TG; however, this has not been measured. Here, we use the lymph fistula rat to isolate chylomicrons containing both DDT and TG. These chylomicrons are the in vivo DDT delivery vehicle. Using 3T3-L1 adipocytes, we investigated the rate at which DDT transfers from chylomicrons to adipocytes, and mediators of this process. This novel approach closely approximates the in vivo DDT exposure route. We show that: 1) DDT repartitions from chylomicrons to adipocytes, 2) this transport does not require hydrolysis of TG within the chylomicron, and is stimulated by the inhibition of LPL, 3) albumin does not inhibit DDT uptake, 4) DDT dissolved in DMSO does not appropriately mimic in vivo DDT transport; and most importantly, 5) DDT uptake from chylomicrons does not mimic the uptake of TG from the same particles. Understanding these factors is important for designing interventions for human populations exposed to DDT.