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1.
  • 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.
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2.
  • Beecham, Ashley H, et al. (författare)
  • Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
  • 2013
  • Ingår i: Nature genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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3.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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4.
  • Wood, Andrew R, et al. (författare)
  • Defining the role of common variation in the genomic and biological architecture of adult human height.
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 46:11, s. 1173-1186
  • Tidskriftsartikel (refereegranskat)abstract
    • Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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5.
  • Anderson, Leif G., et al. (författare)
  • The effect of the Siberian tundra on the environment of the shelf seas and the Arctic Ocean
  • 1999
  • Ingår i: Ambio. - : Springer. - 0044-7447. ; 28:3, s. 270-280
  • Tidskriftsartikel (refereegranskat)abstract
    • The Tundra Ecology -94 expedition investigated inflow of inorganic and organic carbon to the shelf seas by river runoff, and its transformation by biochemical processes in seawater and sediment. In addition, anthropogenic radionuclides, 137Cs, 90Sr, and 239,240Pu, were studied in water and sediments. The distribution of dissolved inorganic carbon indicates that the majority of the Ob and Yenisey discharges flow into the Laptev Sea before entering the central Arctic Ocean. The sediment study shows that there is a marked difference in benthic oxygen uptake, efflux of dissolved inorganic carbon and nutrients between localities. 137Cs activity from the Chernobyl accident is 30% in the Barents, Kara, and Laptev Seas. 137Cs increased from 5-8 Bq m-3 in Barents Sea, 5-13 Bq m-3 in the Kara Sea to 8-15 Bq m-3 in the Laptev Sea, but with locally low concentrations at the river mouths. Corresponding values for 90Sr were 2.5, 3, and 4 Bq m-3, respectively.
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6.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 45:5, s. 501-512
  • Tidskriftsartikel (refereegranskat)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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7.
  • Bonaglia, Stefano, et al. (författare)
  • The fate of fixed nitrogen in marine sediments with low organic loading : an in situ study
  • 2017
  • Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 14:2, s. 285-300
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the last decades, the impact of human activities on the global nitrogen (N) cycle has drastically increased. Consequently, benthic N cycling has mainly been studied in anthropogenically impacted estuaries and coasts, while in oligotrophic systems its understanding is still scarce. Here we report on benthic solute fluxes and on rates of denitrification, anammox, and dissimilatory nitrate reduction to ammonium (DNRA) studied by in situ incubations with benthic chamber landers during two cruises to the Gulf of Bothnia (GOB), a cold, oligotrophic basin located in the northern part of the Baltic Sea. Rates of N burial were also inferred to investigate the fate of fixed N in these sediments. Most of the total dissolved fixed nitrogen (TDN) diffusing to the water column was composed of organic N. Average rates of dinitrogen (N-2) production by denitrification and anammox (range: 53-360 mu mol Nm(-2) day(-1)) were comparable to those from Arctic and subarctic sediments worldwide (range: 34-344 mu mol Nm(-2) day(-1)). Anammox accounted for 18-26% of the total N2 production. Absence of free hydrogen sulfide and low concentrations of dissolved iron in sediment pore water suggested that denitrification and DNRA were driven by organic matter oxidation rather than chemolithotrophy. DNRA was as important as denitrification at a shallow, coastal station situated in the northern Bothnian Bay. At this pristine and fully oxygenated site, ammonium regeneration through DNRA contributed more than one-third to the TDN efflux and accounted, on average, for 45% of total nitrate reduction. At the offshore stations, the proportion of DNRA in relation to denitrification was lower (0-16% of total nitrate reduction). Median value and range of benthic DNRA rates from the GOB were comparable to those from the southern and central eutrophic Baltic Sea and other temperate estuaries and coasts in Europe. Therefore, our results contrast with the view that DNRA is negligible in cold and well-oxygenated sediments with low organic carbon loading. However, the mechanisms behind the variability in DNRA rates between our sites were not resolved. The GOB sediments were a major source (237 kt yr(-1), which corresponds to 184% of the external N load) of fixed N to the water column through recycling mechanisms. To our knowledge, our study is the first to document the simultaneous contribution of denitrification, DNRA, anammox, and TDN recycling combined with in situ measurements.
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8.
  • de Boer, Anneloes, et al. (författare)
  • Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI
  • 2020
  • Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool.PURPOSE: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies.STUDY TYPE: Systematic consensus process using a modified Delphi method.POPULATION: Not applicable.SEQUENCE FIELD/STRENGTH: Renal fast gradient echo-based 2D PC-MRI.ASSESSMENT: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4-10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated.STATISTICAL TESTS: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60-74% agreement among the experts.RESULTS: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting.DATA CONCLUSION: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI.LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.
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9.
  • de Jong, Simone, et al. (författare)
  • Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
  • 2018
  • Ingår i: Communications Biology. - : Nature Publishing Group. - 2399-3642. ; 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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10.
  • Deloukas, Panos, et al. (författare)
  • Large-scale association analysis identifies new risk loci for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 45:1, s. 25-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
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