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| 25. |
- Orpana, Heather M., et al.
(author)
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Global, regional, and national burden of suicide mortality 1990 to 2016 : Systematic analysis for the Global Burden of Disease Study 2016
- 2019
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In: BMJ (Online). - : BMJ. - 1756-1833 .- 0959-8138. ; 364
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Journal article (peer-reviewed)abstract
- Objectives To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Design Systematic analysis. Main outcome measures Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). Results The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Conclusions Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
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| 26. |
- Yang, W., et al.
(author)
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Immunogenic neoantigens derived from gene fusions stimulate T cell responses
- 2019
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:5
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Journal article (peer-reviewed)abstract
- Anti-tumor immunity is driven by self versus non-self discrimination. Many immunotherapeutic approaches to cancer have taken advantage of tumor neoantigens derived from somatic mutations. Here, we demonstrate that gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy. We identified an exceptional responder with metastatic head and neck cancer who experienced a complete response to immune checkpoint inhibitor therapy, despite a low mutational load and minimal pre-treatment immune infiltration in the tumor. Using whole-genome sequencing and RNA sequencing, we identified a novel gene fusion and demonstrated that it produces a neoantigen that can specifically elicit a host cytotoxic T cell response. In a cohort of head and neck tumors with low mutation burden, minimal immune infiltration and prevalent gene fusions, we also identified gene fusion-derived neoantigens that generate cytotoxic T cell responses. Finally, analyzing additional datasets of fusion-positive cancers, including checkpoint-inhibitor-treated tumors, we found evidence of immune surveillance resulting in negative selective pressure against gene fusion-derived neoantigens. These findings highlight an important class of tumor-specific antigens and have implications for targeting gene fusion events in cancers that would otherwise be less poised for response to immunotherapy, including cancers with low mutational load and minimal immune infiltration.
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| 27. |
- Zhang, P, et al.
(author)
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Tackling the Complexity of the Exposome: Considerations from the Gunma University Initiative for Advanced Research (GIAR) Exposome Symposium
- 2019
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In: Metabolites. - : MDPI AG. - 2218-1989. ; 9:6
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Journal article (other academic/artistic)abstract
- The attempt to describe complex diseases by solely genetic determination has not been successful. There is increasing recognition that the development of disease is often a consequence of interactions between multiple genetic and environmental factors. To date, much of the research on environmental determinants of disease has focused on single exposures generally measured at a single time point. In order to address this limitation, the concept of the exposome has been introduced as a comprehensive approach, studying the full complement of environmental exposures from conception onwards. However, exposures are vast, dynamic, and diverse, and only a small proportion can be reasonably measured due to limitations in technology and feasibility. In addition, the interplay between genes and exposure as well as between different exposures is complicated and multifaceted, which leads to difficulties in linking disease or health outcomes with exposures. The large numbers of collected samples require well-designed logistics. Furthermore, the immense data sets generated from exposome studies require a significant computational investment for both data analysis and data storage. This report summarizes discussions during an international exposome symposium held at Gunma University in Japan regarding the concept of the exposome, challenges in exposome research, and future perspectives in the field.
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- Arai, Sally, et al.
(author)
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Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation : a report from the Center for International Blood and Marrow Transplant Research.
- 2015
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In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:2, s. 266-74
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Journal article (peer-reviewed)abstract
- Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research.
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