| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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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.
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| 2. |
- Bellucci, Jeremy, et al.
(författare)
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Terrestrial-like zircon in an Apollo 14 breccia.
- 2019
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Ingår i: Earth and Planetary Science Letters. - Netherlands : Elsevier. - 0012-821X .- 1385-013X. ; 510, s. 173-185
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Carville, N. Craig, et al.
(författare)
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Biocompatibility of ferroelectric lithium niobate and the influence of polarization charge on osteoblast proliferation and function
- 2015
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Ingår i: Journal of Biomedical Materials Research. Part A. - : John Wiley and Sons. - 1549-3296 .- 1552-4965. ; 103:8, s. 2540-2548
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Tidskriftsartikel (refereegranskat)abstract
- In this work, the influence of substrate surface charge on in vitro osteoblast cell proliferation on ferroelectric lithium niobate (LN) crystal surfaces is investigated. LN has a spontaneous polarization along the z-axis and is thus characterized by positive and negative bound polarization charge at the +z and -z surfaces. Biocompatibility of LN was demonstrated via culturing and fluorescence imaging of MC3T3 osteoblast cells for up to 11 days. The cells showed enhanced proliferation rates and improved osteoblast function through mineral formation on the positively and negatively charged LN surfaces compared to electrostatically neutral x-cut LN and a glass cover slip control. These results highlight the potential of LN as a template for investigating the role of charge on cellular processes.
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| 4. |
- Freitag, Daniel F., et al.
(författare)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Tidskriftsartikel (refereegranskat)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 5. |
- Green, Jonathan M. H., et al.
(författare)
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Research priorities for managing the impacts and dependencies of business upon food, energy, water and the environment
- 2017
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Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 12:2, s. 319-331
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Tidskriftsartikel (refereegranskat)abstract
- Delivering access to sufficient food, energy and water resources to ensure human wellbeing is a major concern for governments worldwide. However, it is crucial to account for the 'nexus' of interactions between these natural resources and the consequent implications for human wellbeing. The private sector has a critical role in driving positive change towards more sustainable nexus management and could reap considerable benefits from collaboration with researchers to devise solutions to some of the foremost sustainability challenges of today. Yet opportunities are missed because the private sector is rarely involved in the formulation of deliverable research priorities. We convened senior research scientists and influential business leaders to collaboratively identify the top forty questions that, if answered, would best help companies understand and manage their food-energy-water-environment nexus dependencies and impacts. Codification of the top order nexus themes highlighted research priorities around development of pragmatic yet credible tools that allow businesses to incorporate nexus interactions into their decision-making; demonstration of the business case for more sustainable nexus management; identification of the most effective levers for behaviour change; and understanding incentives or circumstances that allow individuals and businesses to take a leadership stance. Greater investment in the complex but productive relations between the private sector and research community will create deeper and more meaningful collaboration and cooperation.
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| 6. |
- Murray, Elizabeth, et al.
(författare)
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Evaluating Digital Health Interventions Key Questions and Approaches
- 2016
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Ingår i: American Journal of Preventive Medicine. - : ELSEVIER SCIENCE INC. - 0749-3797 .- 1873-2607. ; 51:5, s. 843-851
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Tidskriftsartikel (refereegranskat)abstract
- Digital health interventions have enormous potential as scalable tools to improve health and healthcare delivery by improving effectiveness, efficiency, accessibility, safety, and personalization. Achieving these improvements requires a cumulative knowledge base to inform development and deployment of digital health interventions. However, evaluations of digital health interventions present special challenges. This paper aims to examine these challenges and outline an evaluation strategy in terms of the research questions needed to appraise such interventions. As they are at the intersection of biomedical, behavioral, computing, and engineering research, methods drawn from all of these disciplines are required. Relevant research questions include defining the problem and the likely benefit of the digital health intervention, which in turn requires establishing the likely reach and uptake of the intervention, the causal model describing how the intervention will achieve its intended benefit, key components, and how they interact with one another, and estimating overall benefit in terms of effectiveness, cost effectiveness, and harms. Although RCTs are important for evaluation of effectiveness and cost effectiveness, they are best undertaken only when: (1) the intervention and its delivery package are stable; (2) these can be implemented with high fidelity; and (3) there is a reasonable likelihood that the overall benefits will be clinically meaningful (improved outcomes or equivalent outcomes at lower cost). Broadening the portfolio of research questions and evaluation methods will help with developing the necessary knowledge base to inform decisions on policy, practice, and research. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
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| 7. |
- Xiang, Jinbao, et al.
(författare)
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Hindered dialkyl ether synthesis with electrogenerated carbocations
- 2019
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 573:7774, s. 398-
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Tidskriftsartikel (refereegranskat)abstract
- Hindered ethers are of high value for various applications; however, they remain an underexplored area of chemical space because they are difficult to synthesize via conventional reactions(1,2). Such motifs are highly coveted in medicinal chemistry, because extensive substitution about the ether bond prevents unwanted metabolic processes that can lead to rapid degradation in vivo. Here we report a simple route towards the synthesis of hindered ethers, in which electrochemical oxidation is used to liberate high-energy carbocations from simple carboxylic acids. These reactive carbocation intermediates, which are generated with low electrochemical potentials, capture an alcohol donor under non-acidic conditions; this enables the formation of a range of ethers (more than 80 have been prepared here) that would otherwise be difficult to access. The carbocations can also be intercepted by simple nucleophiles, leading to the formation of hindered alcohols and even alkyl fluorides. This method was evaluated for its ability to circumvent the synthetic bottlenecks encountered in the preparation of 12 chemical scaffolds, leading to higher yields of the required products, in addition to substantial reductions in the number of steps and the amount of labour required to prepare them. The use of molecular probes and the results of kinetic studies support the proposed mechanism and the role of additives under the conditions examined. The reaction manifold that we report here demonstrates the power of electrochemistry to access highly reactive intermediates under mild conditions and, in turn, the substantial improvements in efficiency that can be achieved with these otherwise-inaccessible intermediates.
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