| 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. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 3. |
- Downey, Harriet, et al.
(författare)
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Training future generations to deliver evidence-based conservation and ecosystem management
- 2021
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Ingår i: Ecological Solutions and Evidence. - : Wiley. - 2688-8319. ; 2:1
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Forskningsöversikt (refereegranskat)abstract
- 1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis.2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice.3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses.4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.
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| 4. |
- Pirkis, Jane, et al.
(författare)
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Suicide numbers during the first 9-15 months of the COVID-19 pandemic compared with pre-existing trends : An interrupted time series analysis in 33 countries
- 2022
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 51
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Tidskriftsartikel (refereegranskat)abstract
- Background Predicted increases in suicide were not generally observed in the early months of the COVID-19 pandemic. However, the picture may be changing and patterns might vary across demographic groups. We aimed to provide a timely, granular picture of the pandemic's impact on suicides globally. Methods We identified suicide data from official public-sector sources for countries/areas-within-countries, searching websites and academic literature and contacting data custodians and authors as necessary. We sent our first data request on 22nd June 2021 and stopped collecting data on 31st October 2021. We used interrupted time series (ITS) analyses to model the association between the pandemic's emergence and total suicides and suicides by sex-, age-and sex-by-age in each country/area-within-country. We compared the observed and expected numbers of suicides in the pandemic's first nine and first 10-15 months and used meta-regression to explore sources of variation. Findings We sourced data from 33 countries (24 high-income, six upper-middle-income, three lower-middle-income; 25 with whole-country data, 12 with data for area(s)-within-the-country, four with both). There was no evidence of greater-than-expected numbers of suicides in the majority of countries/areas-within-countries in any analysis; more commonly, there was evidence of lower-than-expected numbers. Certain sex, age and sex-by-age groups stood out as potentially concerning, but these were not consistent across countries/areas-within-countries. In the meta-regression, different patterns were not explained by countries' COVID-19 mortality rate, stringency of public health response, economic support level, or presence of a national suicide prevention strategy. Nor were they explained by countries' income level, although the meta-regression only included data from high-income and upper-middle-income countries, and there were suggestions from the ITS analyses that lower-middle-income countries fared less well. Interpretation Although there are some countries/areas-within-countries where overall suicide numbers and numbers for certain sex- and age-based groups are greater-than-expected, these countries/areas-within-countries are in the minority. Any upward movement in suicide numbers in any place or group is concerning, and we need to remain alert to and respond to changes as the pandemic and its mental health and economic consequences continue. Copyright (C) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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| 5. |
- Appleton, Katherine Marie, et al.
(författare)
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A mobile phone app for the provision of personalized food-based information in an eating-out situation : development and initial evaluation
- 2019
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Ingår i: JMIR Formative Research. - : JMIR Publications Inc.. - 2561-326X. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increasing pressure from governments, public health bodies, and consumers is driving a need for increased food-based information provision in eating-out situations. Meals eaten outside the home are known to be less healthy than meals eaten at home, and consumers can complain of poor information on the health impact and allergen content of meals eaten out.Objective: This paper aimed to describe the development and early assessment of a mobile phone app that allows the provision of accurate personalized food-based information while considering individual characteristics (allergies, diet type, and preferences) to enable informed consumer choice when eating out.Methods: An app was designed and developed to address these requirements using an agile approach. The developed app was then evaluated at 8 public engagement events using the System Usability Scale (SUS) questionnaire and qualitative feedback.Results: Consideration of the literature and consultation with consumers revealed a need for information provision for consumers in the eating-out situation, including the ability to limit the information provided to that which was personally relevant or interesting. The app was designed to provide information to consumers on the dishes available in a workplace canteen and to allow consumers the freedom to personalize the app and choose the information that they received. Evaluation using the SUS questionnaire revealed positive responses to the app from a range of potential users, and qualitative comments demonstrated broad interest in its use.Conclusions: This paper details the successful development and early assessment of a novel mobile phone app designed to provide food-based information in an eating-out situation in a personalized manner.
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| 6. |
- Baigent, Colin, et al.
(författare)
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The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection) : a randomised placebo-controlled trial
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 377:9784, s. 2181-2192
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Tidskriftsartikel (refereegranskat)abstract
- Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and I SRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0.85 mmol/L (SE 0.02; with about two-thirds compliance) during a median follow-up of 4.9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11.3%] simvastatin plus ezetimibe vs 619 [13.4%] placebo; rate ratio [RR] 0.83, 95% CI 0.74-0.94; log-rank p=0.0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4.6%] vs 230 [5.0%]; RR 0.92,95% CI 0.76-1.11; p=0.37) and there were significant reductions in non-haemorrhagic stroke (131 [2.8%] vs 174 [3.8%]; RR 0.75,95% CI 0.60-0.94; p=0.01) and arterial revascularisation procedures (284 [6.1%] vs 352 [7.6%]; RR 0.79, 95% CI 0.68-0.93; p=0.0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0.2%] vs 5 [0.1%]). There was no evidence of excess risks of hepatitis (21 [0.5%] vs 18 [0.4%]), gallstones (106 [2.3%] vs 106 [2.3%]), or cancer (438 [9.4%] vs 439 [9.5%], p=0.89) and there was no significant excess of death from any non-vascular cause (668 [14.4%] vs 612 [13.2%], p=0.13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease.
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| 7. |
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| 8. |
- Narasimha, Maithreyi, et al.
(författare)
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Grainy head promotes expression of septate junction proteins and influences epithelial morphogenesis
- 2008
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 121:6, s. 747-752
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Tidskriftsartikel (refereegranskat)abstract
- Transcription factors of the Grainy head (Grh) family are required in epithelia to generate the impermeable apical layer that protects against the external environment. This function is conserved in vertebrates and invertebrates, despite the differing molecular composition of the protective barrier. Epithelial cells also have junctions that create a paracellular diffusion barrier (tight or septate junctions). To examine whether Grh has a role in regulating such characteristics, we used an epidermal layer in the Drosophila embryo that has no endogenous Grh and lacks septate junctions, the amnioserosa. Expression of Grh in the amnioserosa caused severe defects in dorsal closure, a process similar to wound closure, and induced robust expression of the septate junction proteins Coracle, Fasciclin 3 and Sinuous. Grh-binding sites are present within the genes encoding these proteins, consistent with them being direct targets. Removal of Grh from imaginal disc cells caused a reduction in Fasciclin 3 and Coracle levels, suggesting that Grh normally fine tunes their epithelial expression and hence contributes to barrier properties. The fact that ectopic Grh arrests dorsal closure also suggests that this dynamic process relies on epithelia having distinct adhesive properties conferred by differential deployment of Grh.
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| 9. |
- Vallejo-Vaz, Antonio J, et al.
(författare)
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Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study FromDA VINCI.
- 2022
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Ingår i: Cardiovascular drugs and therapy. - : Springer Science and Business Media LLC. - 1573-7241 .- 0920-3206.
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Tidskriftsartikel (refereegranskat)abstract
- Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (<70 vs.<55mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated.DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy(LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C≥70mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of<70 or<55mg/dl (LDL-C of 69 or 54mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs andARRs) were simulated.Of the 2039 patients, 61% did not achieve LDL-C<70mg/dl. For patients with LDL-C≥70mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively.In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10years versusthe ACC/AHA approach.
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| 10. |
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| 11. |
- Yao, Liqun, et al.
(författare)
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Genome-wide identification of Grainy head targets in Drosophila reveals regulatory interactions with the POU domain transcription factor Vvl
- 2017
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Ingår i: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 144:17, s. 3145-3155
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Tidskriftsartikel (refereegranskat)abstract
- Grainy head (Grh) is a conserved transcription factor (TF) controlling epithelial differentiation and regeneration. To elucidate Grh functions we identified embryonic Grh targets by ChIP-seq and gene expression analysis. We show that Grh controls hundreds of target genes. Repression or activation correlates with the distance of Grh-binding sites to the transcription start sites of its targets. Analysis of 54 Grh-responsive enhancers during development and upon wounding suggests cooperation with distinct TFs in different contexts. In the airways, Grh-repressed genes encode key TFs involved in branching and cell differentiation. Reduction of the POU domain TF Ventral veins lacking (Vvl) largely ameliorates the airway morphogenesis defects of grh mutants. Vvl and Grh proteins additionally interact with each other and regulate a set of common enhancers during epithelial morphogenesis. We conclude that Grh and Vvl participate in a regulatory network controlling epithelial maturation.
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