13 research outputs found

    Genomic investigations of unexplained acute hepatitis in children

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    Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

    Characterization factors to assess land use impacts on pollinator abundance in life cycle assessment

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    While wild pollinators play a key role in global food production, their assessment is currently missing from the most commonly used environmental impact assessment method, Life Cycle Assessment (LCA). This is mainly due to constraints in data availability and compatibility with LCA inventories. To target this gap, relative pollinator abundance estimates were obtained with the use of a Delphi assessment, during which 25 experts, covering 16 nationalities and 45 countries of expertise, provided scores for low, typical, and high expected abundance associated with 24 land use categories. Based on these estimates, this study presents a set of globally generic characterization factors (CFs) that allows translating land use into relative impacts to wild pollinator abundance. The associated uncertainty of the CFs is presented along with an illustrative case to demonstrate the applicability in LCA studies. The CFs based on estimates that reached consensus during the Delphi assessment are recommended as readily applicable and allow key differences among land use types to be distinguished. The resulting CFs are proposed as the first step for incorporating pollinator impacts in LCA studies, exemplifying the use of expert elicitation methods as a useful tool to fill data gaps that constrain the characterization of key environmental impacts

    Characterization factors to assess land use impacts on pollinator abundance in life cycle assessment

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    While wild pollinators play a key role in global food production, their assessment is currently missing from the most commonly used environmental impact assessment method, Life Cycle Assessment (LCA). This is mainly due to constraints in data availability and compatibility with LCA inventories. To target this gap, relative pollinator abundance estimates were obtained with the use of a Delphi assessment, during which 25 experts, covering 16 nationalities and 45 countries of expertise, provided scores for low, typical, and high expected abundance associated with 24 land use categories. Based on these estimates, this study presents a set of globally generic characterization factors (CFs) that allows translating land use into relative impacts to wild pollinator abundance. The associated uncertainty of the CFs is presented along with an illustrative case to demonstrate the applicability in LCA studies. The CFs based on estimates that reached consensus during the Delphi assessment are recommended as readily applicable and allow key differences among land use types to be distinguished. The resulting CFs are proposed as the first step for incorporating pollinator impacts in LCA studies, exemplifying the use of expert elicitation methods as a useful tool to fill data gaps that constrain the characterization of key environmental impacts

    Characterization Factors to Assess Land Use Impacts on Pollinator Abundance in Life Cycle Assessment

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    While wild pollinators play a key role in global food production, their assessment is currently missing from the most commonly used environmental impact assessment method, Life Cycle Assessment (LCA). This is mainly due to constraints in data availability and compatibility with LCA inventories. To target this gap, relative pollinator abundance estimates were obtained with the use of a Delphi assessment, during which 25 experts, covering 16 nationalities and 45 countries of expertise, provided scores for low, typical, and high expected abundance associated with 24 land use categories. Based on these estimates, this study presents a set of globally generic characterization factors (CFs) that allows translating land use into relative impacts to wild pollinator abundance. The associated uncertainty of the CFs is presented along with an illustrative case to demonstrate the applicability in LCA studies. The CFs based on estimates that reached consensus during the Delphi assessment are recommended as readily applicable and allow key differences among land use types to be distinguished. The resulting CFs are proposed as the first step for incorporating pollinator impacts in LCA studies, exemplifying the use of expert elicitation methods as a useful tool to fill data gaps that constrain the characterization of key environmental impacts

    The "Woundosome" Concept and Its Impact on Procedural Outcomes in Patients With Chronic Limb-Threatening Ischemia

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    This editorial assembles endovascular specialists from diverse clinical backgrounds and nationalities with a global call to address key challenges to enhance revascularization in chronic limb-threatening ischemia (CLTI) patients.- Dedicated below-the-ankle (BTA) angiography and revascularization is underutilized in ischemic foot treatment. Existing guidelines do not address comprehensive BTA vessel analysis. CLTI trials also often lack data on in-line arterial flow to the ischemic lesion and BTA vessel evaluation, hindering outcome assessment.- Dedicated multi-planar angiographic evaluation of the distal microcirculation is key: Direct arterial flow or good-quality collaterals are crucial in influencing wound healing and need to be assessed diligently to the level of the distal ischemic wound territory, termed “woundosome.”- An important primary emphasis of future trials should be on validating technologies and strategies for assessing tissue perfusion before, during, and after revascularization undertaken to heal tissue loss in CLTI patients. This will allow determination of a potentially significant delta in tissue perfusion prior to and following intervention at the “woundosome” level. Once changes in arterial perfusion have been identified as positively correlated to wound healing, these could serve as a much-needed novel primary technical outcome measure for patients with tissue loss undergoing surgical, hybrid, or endovascular revascularization
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