| 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. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 3. |
- Su, Zhan, et al.
(författare)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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| 4. |
- Wang, Thomas J, et al.
(författare)
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Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
- 2010
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Ingår i: Lancet. - 1474-547X. ; 376:9736, s. 180-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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| 5. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 6. |
- Gallego-Sala, Angela V., et al.
(författare)
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Latitudinal limits to the predicted increase of the peatland carbon sink with warming
- 2018
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 8:10, s. 907-
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Tidskriftsartikel (refereegranskat)abstract
- The carbon sink potential of peatlands depends on the balance of carbon uptake by plants and microbial decomposition. The rates of both these processes will increase with warming but it remains unclear which will dominate the global peatland response. Here we examine the global relationship between peatland carbon accumulation rates during the last millennium and planetary-scale climate space. A positive relationship is found between carbon accumulation and cumulative photosynthetically active radiation during the growing season for mid- to high-latitude peatlands in both hemispheres. However, this relationship reverses at lower latitudes, suggesting that carbon accumulation is lower under the warmest climate regimes. Projections under Representative Concentration Pathway (RCP)2.6 and RCP8.5 scenarios indicate that the present-day global sink will increase slightly until around AD 2100 but decline thereafter. Peatlands will remain a carbon sink in the future, but their response to warming switches from a negative to a positive climate feedback (decreased carbon sink with warming) at the end of the twenty-first century.
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| 7. |
- McGuigan, Fiona, et al.
(författare)
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Large-scale population-based study shows no association between common polymorphisms of the TGFB1 gene and BMD in women
- 2007
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 22:2, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The gene encoding TGFBI is a strong functional candidate for genetic susceptibility to osteoporosis. Several polymorphisms have been identified in TGFB1, and previous work has suggested that allelic variants of TGFBI. may regulate BMD and susceptibility to osteoporotic fracture. Materials and Methods: We studied the relationship between common polymorphisms of TGFBI and several osteoporosis-related phenotypes including BMD at the lumbar spine and femoral neck, measured by DXA; bone loss over a 6-year period; biochemical markers of bone turnover (urinary free deoxypyridinoline and free pyridinoline/creatinine ratio and serum N-terminal propeptide of type 1 collagen), and fractures in a population-based study of 2975 women from the United Kingdom. Participants were genotyped for single nucleotide polymorphisms (SNPs) in the TGFB1 promoter(G-800A; rs1800468; C-509T; rs1800469), exon 1 (T29C; rs1982073 and G74C; rs1982073); and exon 5 (C788T; rs1800471) on PCR-generated fragments of genomic DNA. Haplotypes were constructed from genotype data using the PHASE software program, and genotypes and haplotypes were related to the phenotypes of interest using general linear model ANOVA, with correction for confounding factors including age, height, weight, menopausal status, hormone replacement therapy (HRT) use, physical activity score, and dietary calcium intake. Results: The polymorphisms were in strong linkage disequilibrium, and four common haplotypes accounted for > 95% of alleles at the locus. There was no association between individual SNPs and BMD, bone loss, or biochemical markers of bone turnover. Haplotype analysis showed a nominally significant association with femoral neck BMD (p = 0.042) and with incident osteoporotic fracture (p = 0.013), but these were not significant after correcting for multiple testing. Conclusions: Common polymorphic variants of the TGFBI gene did not influence BMD or bone loss in this population.
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| 8. |
- Siemieniuk, Reed A.C., et al.
(författare)
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Arthroscopic surgery for degenerative knee arthritis and meniscal tears : A clinical practice guideline
- 2017
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Ingår i: British Medical Journal. - : BMJ. - 0959-8146. ; 357
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Tidskriftsartikel (refereegranskat)abstract
- What is the role of arthroscopic surgery in degenerative knee disease? An expert panel produced these recommendations based on a linked systematic review triggered by a randomised trial published in The BMJ in June 2016, which found that, among patients with a degenerative medial meniscus tear, knee arthroscopy was no better than exercise therapy. The panel make a strong recommendation against arthroscopy for degenerative knee disease. Box 1 shows all of the articles and evidence linked in this Rapid Recommendation package. The infographic provides an overview of the absolute benefits and harms of arthroscopy in standard GRADE format. Table 2 below shows any evidence that has emerged since the publication of this article.
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