| 1. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Naghavi, Mohsen, et al.
(författare)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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| 3. |
- Adger, W. Neil, et al.
(författare)
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Resilience implications of policy responses to climate change
- 2011
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Ingår i: Wiley Interdisciplinary Reviews. - : Wiley. - 1757-7780 .- 1757-7799. ; 2:5, s. 757-766
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Tidskriftsartikel (refereegranskat)abstract
- This article examines whether some response strategies to climate variability and change have the potential to undermine long-term resilience of social-ecological systems. We define the parameters of a resilience approach, suggesting that resilience is characterized by the ability to absorb perturbations without changing overall system function, the ability to adapt within the resources of the system itself, and the ability to learn, innovate, and change. We evaluate nine current regional climate change policy responses and examine governance, sensitivity to feedbacks, and problem framing to evaluate impacts on characteristics of a resilient system. We find that some responses, such as the increase in harvest rates to deal with pine beetle infestations in Canada and expansion of biofuels globally, have the potential to undermine long-term resilience of resource systems. Other responses, such as decentralized water planning in Brazil and tropical storm disaster management in Caribbean islands, have the potential to increase long-term resilience. We argue that there are multiple sources of resilience in most systems and hence policy should identify such sources and strengthen capacities to adapt and learn.
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| 4. |
- Ay, Hakan, et al.
(författare)
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Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network
- 2014
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Ingår i: Stroke. - 0039-2499. ; 45:12, s. 3589-3596
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.
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| 5. |
- Blythe, Jessica, et al.
(författare)
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The Dark Side of Transformation : Latent Risks in Contemporary Sustainability Discourse
- 2018
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Ingår i: Antipode. - : Wiley. - 0066-4812 .- 1467-8330. ; 50:5, s. 1206-1223
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Tidskriftsartikel (refereegranskat)abstract
- The notion of transformation is gaining traction in contemporary sustainability debates. New ways of theorising and supporting transformations are emerging and, so the argument goes, opening exciting spaces to (re)imagine and (re)structure radically different futures. Yet, questions remain about how the term is being translated from an academic concept into an assemblage of normative policies and practices, and how this process might shape social, political, and environmental change. Motivated by these questions, we identify five latent risks associated with discourse that frames transformation as apolitical and/or inevitable. We refer to these risks as the dark side of transformation. While we cannot predict the future of radical transformations towards sustainability, we suggest that scientists, policymakers, and practitioners need to consider such change in more inherently plural and political ways.
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| 6. |
- Bousquet, Francois, et al.
(författare)
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Resilience and development : mobilizing for transformation
- 2016
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Ingår i: Ecology and Society. - 1708-3087. ; 21:3
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Tidskriftsartikel (refereegranskat)abstract
- In 2014, the Third International Conference on the resilience of social-ecological systems chose the theme resilience and development: mobilizing for transformation. The conference aimed specifically at fostering an encounter between the experiences and thinking focused on the issue of resilience through a social and ecological system perspective, and the experiences focused on the issue of resilience through a development perspective. In this perspectives piece, we reflect on the outcomes of the meeting and document the differences and similarities between the two perspectives as discussed during the conference, and identify bridging questions designed to guide future interactions. After the conference, we read the documents (abstracts, PowerPoints) that were prepared and left in the conference database by the participants (about 600 contributions), and searched the web for associated items, such as videos, blogs, and tweets from the conference participants. All of these documents were assessed through one lens: what do they say about resilience and development? Once the perspectives were established, we examined different themes that were significantly addressed during the conference. Our analysis paves the way for new collective developments on a set of issues: (1) Who declares/assign/cares for the resilience of what, of whom? (2) What are the models of transformations and how do they combine the respective role of agency and structure? (3) What are the combinations of measurement and assessment processes? (4) At what scale should resilience be studied? Social transformations and scientific approaches are coconstructed. For the last decades, development has been conceived as a modernization process supported by scientific rationality and technical expertise. The definition of a new perspective on development goes with a negotiation on a new scientific approach. Resilience is presently at the center of this negotiation on a new science for development.
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| 7. |
- Chaigneau, Tomas, et al.
(författare)
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Incorporating basic needs to reconcile poverty and ecosystem services
- 2019
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Ingår i: Conservation Biology. - : Wiley. - 0888-8892 .- 1523-1739. ; 33:3, s. 655-664
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Tidskriftsartikel (refereegranskat)abstract
- Conservation managers frequently face the challenge of protecting and sustaining biodiversity without producing detrimental outcomes for (often poor) human populations that depend on ecosystem services for their well-being. However, mutually beneficial solutions are often elusive and can mask trade-offs and negative outcomes for people. To deal with such trade-offs, ecological and social thresholds need to be identified to determine the acceptable solution space for conservation. Although human well-being as a concept has recently gained prominence, conservationists still lack tools to evaluate how their actions affect it in a given context. We applied the theory of human needs to conservation by building on an extensive historical application of need approaches in international development. In an innovative participatory method that included focus groups and household surveys, we evaluated how human needs are met based on locally relevant thresholds. We then established connections between human needs and ecosystem services through key-informant focus groups. We applied our method in coastal East Africa to identify households that would not be able to meet their basic needs and to uncover the role of ecosystem services in meeting these. This enabled us to identify how benefits derived from the environment were contributing to meeting basic needs and to consider potential repercussions that could arise through changes to ecosystem service provision. We suggest our approach can help conservationists and planners balance poverty alleviation and biodiversity protection and ensure conservation measures do not, at the very least, cause serious harm to individuals. We further argue it can be used as a basis for monitoring the impacts of conservation on multidimensional poverty.
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| 8. |
- Chaigneau, Tomas, et al.
(författare)
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Money, use and experience : Identifying the mechanisms through which ecosystem services contribute to wellbeing in coastal Kenya and Mozambique
- 2019
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Ingår i: Ecosystem Services. - : Elsevier BV. - 2212-0416 .- 2212-0416. ; 38
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Tidskriftsartikel (refereegranskat)abstract
- Despite extensive recent research elucidating the complex relationship between ecosystem services and human wellbeing, little work has sought to understand how ecosystem services contribute to wellbeing and poverty alleviation. This paper adopts concepts from the Theory of Human Need and the Capability Approach to both identify the multitude of links occurring between ecosystem services and wellbeing domains, and to understand the mechanisms through which ecosystem services contribute to wellbeing. Focus Group Discussions (N = 40) were carried out at 8 sites in Mozambique and Kenya to elicit how, why, and to what extent benefits derived from ecosystem services contribute to different wellbeing domains. Our results highlight three types of mechanisms through which ecosystem services contribute to wellbeing, monetary, use and experience. The consideration of these mechanisms can inform the development of interventions that aim to protect or improve flows of benefits to people. Firstly, interventions that support multiple types of mechanisms will likely support multiple domains of wellbeing. Secondly, overemphasising certain types of mechanism over others could lead to negative social feedbacks, threatening the future flows of ecosystem services. Finally, the three mechanism types are interlinked and can act synergistically to enhance the capacities of individuals to convert ecosystem services to wellbeing.
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| 9. |
- Chaigneau, Tomas, et al.
(författare)
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Reconciling well-being and resilience for sustainable development
- 2022
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 5:April 2022, s. 287-293
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Tidskriftsartikel (refereegranskat)abstract
- Securing well-being and building resilience in response to shocks are often viewed as key goals of sustainable development. Here, we present an overview of the latest published evidence, as well as the consensus of a diverse group of scientists and practitioners drawn from a structured analytical review and deliberative workshop process. We argue that resilience and well-being are related in complex ways, but in their applications in practice they are often assumed to be synergistic. Although theoretically compatible, evidence we present here shows that they may in fact work against each other. This has important implications for policy.
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| 10. |
- Daw, Tim, et al.
(författare)
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Applying the ecosystem services concept to poverty alleviation : the need to disaggregate human well-being
- 2011
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Ingår i: Environmental Conservation. - 0376-8929 .- 1469-4387. ; 38:04, s. 370-379
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Tidskriftsartikel (refereegranskat)abstract
- The concept of ecosystem services (ES), the benefits humans derive from ecosystems, is increasingly applied to environmental conservation, human well-being and poverty alleviation, and to inform the development of interventions. Payments for ecosystem services (PES) implicitly recognize the unequal distribution of the costs and benefits of maintaining ES, through monetary compensation from ‘winners’ to ‘losers’. Some research into PES has examined how such schemes affect poverty, while other literature addresses trade-offs between different ES. However, much evolving ES literature adopts an aggregated perspective of humans and their well-being, which can disregard critical issues for poverty alleviation. This paper identifies four issues with examples from coastal ES in developing countries. First, different groups derive well-being benefits from different ES, creating winners and losers as ES, change. Second, dynamic mechanisms of access determine who can benefit. Third, individuals' contexts and needs determine how ES contribute to well-being. Fourth, aggregated analyses may neglect crucial poverty alleviation mechanisms such as cash-based livelihoods. To inform the development of ES interventions that contribute to poverty alleviation, disaggregated analysis is needed that focuses on who derives which benefits from ecosystems, and how such benefits contribute to the well-being of the poor. These issues present challenges in data availability and selection of how and at which scales to disaggregate. Disaggregation can be applied spatially, but should also include social groupings, such as gender, age and ethnicity, and is most important where inequality is greatest. Existing tools, such as stakeholder analysis and equity weights, can improve the relevance of ES research to poverty alleviation.
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