Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016

Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING: Bill & Melinda Gates Foundation

Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.

BACKGROUND: Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. FINDINGS: Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9-3·0) for men and 3·5 years (3·4-3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78-0·92) and 1·2 years (1·1-1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. INTERPRETATION: Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum. FUNDING: Bill & Melinda Gates Foundation

Commercial Change in Toronto’s West-Central Neighbourhoods

The literature on gentrification has focused predominantly on housing dynamics. To the extent that it has addressed the commercial dimension of gentrification, the emphasis has generally been on the characteristics of consumers as gentrifiers. With a few exceptions, what is absent from the literature on commercial change is an analysis of the types, motivations, and experiences of commercial establishments in gentrifying neighbourhoods—especially those at risk of displacement—or strategies for retaining those businesses serving the needs of low-income and ethnically mixed residents. A fundamental premise of this research is that retaining such businesses is crucial to preserving the affordability of neighbourhoods and creating urban spaces where people can encounter one another and recognize common interests across social differences. This study of commercial change in Toronto’s downtown West-Central neighbourhoods explores how commercial change contributes to wider processes of exclusion and gentrification, as well as the strategies and resources available to counter this pervasive trend. Specifically, the study has the following objectives: to document patterns of commercial change in West Downtown, concentrating specifically on the characteristics of three commercial strips in different “stages” of commercial gentrification; to identify challenges and opportunities that businesses face, particularly those serving lowincome residents, for the purpose of identifying key themes in commercial gentrification; to recommend ways to support long-time businesses in the study area through policy change and community organizing. “Commercial gentrification” refers to the processes by which long-established businesses providing products and services affordable to low-income people are leaving downtown Toronto neighbourhoods and being replaced by establishments catering to more affluent consumers. While we adopted the politically neutral language of “commercial change” in our interview questions, we use the term “gentrification” explicitly in this report to underscore our analytical emphasis on the exclusions, struggles, and displacements associated with the production of commercial space for progressively more affluent users. We selected three commercial strips to represent different characteristics and stages of commercial gentrification, based on a combination of anecdotal evidence and data on rates of land value change. We conducted semi-structured interviews with 10 business owners or managers on each strip and a representative of the local Business Improvement Area. The businesses were selected to represent both a range of ownership structures and a combination of businesses that serve low-income residents and those that reflect the changing character of gentrifying neighbourhoods. Finally, we assessed patterns of commercial change over time in the context of the commercial structure on the three strips by examining the “activity code” assigned by the City of Toronto to each individual business on the strips. We conducted statistical tests to identify whether changes in activity codes on the strips between the years 2000 and 2005 were statistically significant, and compared this information with qualitative interview data on the changes taking place. Our findings and analysis are presented in two subsections. The first presents key characteristics of the commercial strips that we have identified as “rapidly gentrifying,” “gentrifying,” and “not-gentrified.” What is clear from these descriptions is that gentrification is not a straightforward process in which the three commercial strips represent fixed positions along a stable and predictable trajectory. Understanding gentrification requires an appreciation of local social histories, and how those social histories articulate wider-scale capital flows and shape the opportunities and constraints faced by businesses in any given location. Our classifications are useful in comparing types and states of neighbourhood change, but the goal is not to generalize about commercial strips. Rather we want to identify themes for discussion that might inform a critical understanding of the complexity of commercial gentrification processes and potential areas of policy intervention and advocacy to support long-time local businesses serving the needs of low-income and ethnoculturally diverse residents. The second section is devoted to exploring those themes. It takes up the issues of ownership structure in relation to local investment and perceptions of community; transnationality in relation to the commodification of ethnocultural difference, the politics of strip “branding,” and the role of immigrant-owned businesses in building social cohesion; the role of BIAs in both promoting local development and fragmenting the urban landscape; networks of local retailers, consumers and labour that form clusters of agglomeration; the multiple forms and actors in the community economy; and the challenges and opportunities for business finance. The report concludes with some recommendations for policy and community organizing in the areas of providing education about the social costs of commercial gentrification, developing strategies to retain businesses that provide affordable goods and services, supporting BIAs in local asset building and inclusionary practices, and countering fragmentation through comprehensive planning measures

Community BIAs as practices of assemblage: contingent politics in the neoliberal city

Business Improvement Areas (BIAs) are a domain of urban governance that has been aptly characterized as a form of neoliberal urbanization aimed at improving the business climate of downtowns. This paper engages with a growing body of literature on contingent neoliberal urbanisms to consider BIAs as an assemblage of coevolving projects and actors. It focuses specifically on two ‘community’ BIAs in Toronto’s downtown West, where recent actions of differently positioned stakeholders effectively reveal how multiple agendas can inform BIA practices. Our objective is twofold: (a) to draw attention to the practices of smaller, community-based BIAs that predominate in North America; and (b) to explore the analytical and political openings that arise when institutions commonly identified as neoliberal are investigated as an assemblage of related but distinctive and sometimes disjunctive projects.

The State of Business in Mount Dennis: Disinvestment and Gentrification in Toronto's Inner-Suburbs

No abstract available