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Sökning: WFRF:(Major John E)

  • Resultat 1-7 av 7
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  • Tidskriftsartikel (refereegranskat)
  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
  • Barretina, Jordi, et al. (författare)
  • Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy.
  • 2010
  • Ingår i: Nature genetics. - 1546-1718. ; 42:8, s. 715-21
  • Tidskriftsartikel (refereegranskat)abstract
    • Soft-tissue sarcomas, which result in approximately 10,700 diagnoses and 3,800 deaths per year in the United States, show remarkable histologic diversity, with more than 50 recognized subtypes. However, knowledge of their genomic alterations is limited. We describe an integrative analysis of DNA sequence, copy number and mRNA expression in 207 samples encompassing seven major subtypes. Frequently mutated genes included TP53 (17% of pleomorphic liposarcomas), NF1 (10.5% of myxofibrosarcomas and 8% of pleomorphic liposarcomas) and PIK3CA (18% of myxoid/round-cell liposarcomas, or MRCs). PIK3CA mutations in MRCs were associated with Akt activation and poor clinical outcomes. In myxofibrosarcomas and pleomorphic liposarcomas, we found both point mutations and genomic deletions affecting the tumor suppressor NF1. Finally, we found that short hairpin RNA (shRNA)-based knockdown of several genes amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields a detailed map of molecular alterations across diverse sarcoma subtypes and suggests potential subtype-specific targets for therapy.
  • Major, Triin, et al. (författare)
  • Pro-IL-1β Is an Early Prognostic Indicator of Severe Donor Lung Injury During Ex Vivo Lung Perfusion
  • 2021
  • Ingår i: Transplantation. - : Lippincott Williams & Wilkins. - 1534-6080. ; 105:4, s. 768-774
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Ex vivo lung perfusion (EVLP) is used to evaluate and recondition extended criteria donor lungs for transplantation. Interleukin-1β (IL-1β) has been identified as a prognostic indicator of nonrecovery during EVLP. This may be an effect of inflammasome activation or cellular necrosis following donation and graft preservation. Delineating the mechanism of IL-1β release is required. METHODS: The inactive intracellular precursor molecule, pro-IL-1β, was characterized along with the pro-IL-1β processing enzyme, caspase-1, in the perfusate of n = 20 human lungs that had undergone EVLP (n = 10 lungs that failed to recover and were discarded versus n = 10 lungs that reconditioned and were transplanted). In an experimental porcine model, n = 8 lungs underwent EVLP and were randomized to receive either a specific NLRP3 inflammasome inhibitor or control. RESULTS: Significant increases in pro-IL-1β and caspase-1 were observed in the perfusate from human lungs that did not recondition during EVLP compared with those that successfully reconditioned and were used for transplantation. Within the porcine EVLP, NLRP3 inflammasome inhibition reduced IL-1β within the perfusate compared with controls, but this had no impact on lung function, hemodynamics, or inflammation. CONCLUSIONS: Our data suggest that pro-IL-1β is passively released following cellular necrosis of the donor lung.
  • Morales, Hernan E., et al. (författare)
  • Neutral and selective drivers of colour evolution in a widespread Australian passerine
  • 2017
  • Ingår i: Journal of Biogeography. - : WILEY-BLACKWELL. - 0305-0270 .- 1365-2699. ; 44:3, s. 522-536
  • Tidskriftsartikel (refereegranskat)abstract
    • AimRump plumage coloration of the Eastern Yellow Robin (Eopsaltria australis), a widespread Australian songbird, varies from bright yellow in the tropical north to olive-green in the temperate south. Here, we test whether colour variation: (1) correlates most strongly with neutral genetic variation and so is best explained by historical processes, (2) reflects selection associated with different visual environments (dense versus open habitats) and/or (3) reflects selection associated with climatic variation. LocationEastern Australia. MethodsWe quantified colour variation using reflectance spectrometry and visual models. We performed geographical cline analysis of colour and neutral genetic variation (genome-wide single nucleotide polymorphisms). We tested for correlations of colour variation with climate, vegetation density, geographical location and genetic variation. We accounted for covariation and spatial autocorrelation, and conducted analyses at continental and regional spatial scales. ResultsClinal variation of colour traits and neutral genetic markers were largely concordant. At the continental scale, colour variation was strongly associated with neutral genetic structure and geography, and to a lesser extent with environment. At the regional scale, environmental variation was a better predictor of colour variation than it was at the larger scale. Main conclusionAt the continental scale, colour variation is strongly associated with large-scale population history. In contrast, at the regional scale, where the influence of history and geography is weaker, environmental variation has a role in facilitating the maintenance of colour variation. Our results highlight the need to assess selective and neutral alternatives at multiple spatial scales when studying geographical variation.
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  • Resultat 1-7 av 7

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