147 research outputs found

    An integrated framework for assessing coastal community vulnerability across cultures, oceans and scales.

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    Coastal communities are some of the most at-risk populations with respect to climate change impacts. It is therefore important to determine the vulnerability of such communities to co-develop viable adaptation options. Global efforts to address this issue include international scientific projects, such as Global Learning for Local Solutions (GULLS), which focuses on five fast warming regions of the southern hemisphere and aims to provide an understanding of the local scale processes influencing community vulnerability that can then be up-scaled to regional, country and global levels. This paper describes the development of a new social and ecological vulnerability framework which integrates exposure, sensitivity and adaptive capacity with the social livelihoods and food security approaches. It also measures community flexibility to understand better the adaptive capacity of different levels of community organization. The translation of the conceptual framework to an implementable method is described and its application in a number of “hotspot” countries, where ocean waters are warming faster than the rest of the world, is presented. Opportunities for cross-cultural comparisons to uncover similarities and differences in vulnerability and adaptation patterns among the study’s coastal communities, which can provide accelerated learning mechanisms to other coastal regions, are highlighted. The social and ecological framework and the associated survey approach allow for future integration of local-level vulnerability data with ecological and oceanographic models

    Patterns of response in patients with advanced melanoma treated with Pembrolizumab (MK-3475) and evaluation of immune-related response criteria (irRC)

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    Unique patterns of response have been observed with immunotherapies. Notably, objective response and prolonged disease stabilization can occur after an initial increase in tumor burden. irRC were developed to better characterize response to immunotherapy based on data for Ipilimumab. We previously showed that patients with melanoma treated with the anti-PD-1 monoclonal antibody Pembrolizumab may also experience unique patterns of response and that conventional response criteria may underestimate the therapeutic benefit of Pembrolizumab [1]. We updated our initial analysis to include an additional 6 months of follow-up

    Impact of financial inclusion in low- and middle-income countries: a systematic review of reviews

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    Financial inclusion programmes seek to increase access to financial services such as credit, savings, insurance and money transfers and so allow poor and low-income households in low- and middle-income countries to enhance their welfare, grasp opportunities, mitigate shocks, and ultimately escape poverty. This systematic review of reviews assesses the evidence on economic, social, behavioural and gender-related outcomes from financial inclusion. It collects and appraises all of the existing meta-studies - that is systematic reviews and meta-analyses - of the impact of financial inclusion. The authors first analyse the strength of the methods used in those meta-studies, then synthesise the findings from those that are of a sufficient quality, and finally, report the implications for policy, programming, practice and further research arising from the evidence. Eleven studies are included in the analysis

    Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma

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    The mitochondrial genome (mtDNA) encodes essential machinery for oxidative phosphorylation and metabolic homeostasis. Tumor mtDNA is among the most somatically mutated regions of the cancer genome, but whether these mutations impact tumor biology is debated. We engineered truncating mutations of the mtDNA-encoded complex I gene, Mt-Nd5, into several murine models of melanoma. These mutations promoted a Warburg-like metabolic shift that reshaped tumor microenvironments in both mice and humans, consistently eliciting an anti-tumor immune response characterized by loss of resident neutrophils. Tumors bearing mtDNA mutations were sensitized to checkpoint blockade in a neutrophil-dependent manner, with induction of redox imbalance being sufficient to induce this effect in mtDNA wild-type tumors. Patient lesions bearing >50% mtDNA mutation heteroplasmy demonstrated a response rate to checkpoint blockade that was improved by ~2.5-fold over mtDNA wild-type cancer. These data nominate mtDNA mutations as functional regulators of cancer metabolism and tumor biology, with potential for therapeutic exploitation and treatment stratification
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