| 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. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 3. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 4. |
- Shetrone, Matthew, et al.
(författare)
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Constraining Metallicity-dependent Mixing and Extra Mixing Using [C/N] in Alpha-rich Field Giants
- 2019
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 872:2
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Tidskriftsartikel (refereegranskat)abstract
- Internal mixing on the giant branch is an important process which affects the evolution of stars and the chemical evolution of the galaxy. While several mechanisms have been proposed to explain this mixing, better empirical constraints are necessary. Here, we use [C/N] abundances in 26,097 evolved stars from the SDSS-IV/APOGEE-2 Data Release 14 to trace mixing and extra mixing in old field giants with -1.7 < [Fe/H] < 0.1. We show that the APOGEE [C/N] ratios before any dredge-up occurs are metallicity dependent, but that the change in [C/N] at the first dredge-up is metallicity independent for stars above [Fe/H] similar to -1. We identify the position of the red giant branch (RGB) bump as a function of metallicity, note that a metallicity-dependent extra mixing episode takes place for low-metallicity stars ([Fe/H] < -0.4) 0.14 dex in log g above the bump, and confirm that this extra mixing is stronger at low metallicity, reaching Delta[C/N] = 0.58 dex at [Fe/H] = -1.4. We show evidence for further extra mixing on the upper giant branch, well above the bump, among the stars with [Fe/H] < -1.0. This upper giant branch mixing is stronger in the more metal-poor stars, reaching 0.38 dex in [C/N] for each 1.0 dex in log g. The APOGEE [C/N] ratios for red clump (RC) stars are significantly higher than for stars at the tip of the RGB, suggesting additional mixing processes occur during the helium flash or that unknown abundance zero points for C and N may exist among the RC sample. Finally, because of extra mixing, we note that current empirical calibrations between [C/N] ratios and ages cannot be naively extrapolated for use in low-metallicity stars specifically for those above the bump in the luminosity function.
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| 5. |
- Johnson, Toby, et al.
(författare)
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Blood Pressure Loci Identified with a Gene-Centric Array.
- 2011
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 89:6, s. 688-700
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Tidskriftsartikel (refereegranskat)abstract
- Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56× 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56× 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
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| 6. |
- Jönsson, Henrik, et al.
(författare)
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APOGEE Data Releases 13 and 14 : Stellar Parameter and Abundance Comparisons with Independent Analyses
- 2018
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Ingår i: Astronomical Journal. - : Institute of Physics Publishing (IOPP). - 0004-6256 .- 1538-3881. ; 156:3
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Tidskriftsartikel (refereegranskat)abstract
- Data from the SDSS-IV/Apache Point Observatory Galactic Evolution Experiment (APOGEE-2) have been released as part of SDSS Data Releases 13 (DR13) and 14 (DR14). These include high-resolution H-band spectra, radial velocities, and derived stellar parameters and abundances. DR13, released in 2016 August, contained APOGEE data for roughly 150,000 stars, and DR14, released in 2017 August, added about 110,000 more. Stellar parameters and abundances have been derived with an automated pipeline, the APOGEE Stellar Parameter and Chemical Abundance Pipeline (ASPCAP). We evaluate the performance of this pipeline by comparing the derived stellar parameters and abundances to those inferred from optical spectra and analysis for several hundred stars. For most elements-C, Na, Mg, Al, Si, S, Ca, Cr, Mn, Ni-the DR14 ASPCAP analyses have systematic differences with the comparisons samples of less than 0.05 dex (median), and random differences of less than 0.15 dex (standard deviation). These differences are a combination of the uncertainties in both the comparison samples as well as the ASPCAP analysis. Compared to the references, magnesium is the most accurate alpha-element derived by ASPCAP, and shows a very clear thin/thick disk separation, while nickel is the most accurate iron-peak element (besides iron itself).
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| 7. |
- Kunder, Andrea, et al.
(författare)
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THE RADIAL VELOCITY EXPERIMENT (RAVE) : FIFTH DATA RELEASE
- 2017
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Ingår i: The Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 153:2
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Tidskriftsartikel (refereegranskat)abstract
- Data Release 5 (DR5) of the Radial Velocity Experiment (RAVE) is the fifth data release from a magnitude-limited (9 < I < 12) survey of stars randomly selected in the Southern Hemisphere. The RAVE medium-resolution spectra (R ∼ 7500) covering the Ca-triplet region (8410-8795 A) span the complete time frame from the start of RAVE observations in 2003 to their completion in 2013. Radial velocities from 520,781 spectra of 457,588 unique stars are presented, of which 255,922 stellar observations have parallaxes and proper motions from the Tycho-Gaia astrometric solution in Gaia DR1. For our main DR5 catalog, stellar parameters (effective temperature, surface gravity, and overall metallicity) are computed using the RAVE DR4 stellar pipeline, but calibrated using recent K2 Campaign 1 seismic gravities and Gaia benchmark stars, as well as results obtained from high-resolution studies. Also included are temperatures from the Infrared Flux Method, and we provide a catalog of red giant stars in the dereddened color - (J Ks) 0 interval (0.50, 0.85) for which the gravities were calibrated based only on seismology. Further data products for subsamples of the RAVE stars include individual abundances for Mg, Al, Si, Ca, Ti, Fe, and Ni, and distances found using isochrones. Each RAVE spectrum is complemented by an error spectrum, which has been used to determine uncertainties on the parameters. The data can be accessed via the RAVE Web site or the VizieR database.
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| 8. |
- Leonard, Jennifer A., et al.
(författare)
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Phylogeography of vertebrates on the Sunda Shelf : a multi-species comparison
- 2015
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 42:5, s. 871-879
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Tidskriftsartikel (refereegranskat)abstract
- Aim Pleistocene environmental fluctuations had well-characterized impacts on the patterns of within-species divergences and diversity in temperate habitats. Here we examine the impact the Pleistocene had on widely distributed forest vertebrates in a tropical system where the distribution of the habitat was affected by those fluctuations. LocationSundaland, tropical Southeast Asia. Methods We conducted a comparative phylogeographical analysis of 28 non-migratory, forest-dependent vertebrates, for which we constructed rooted, intraspecifc phylogenies based on mitochondrial DNA sequences of individuals from at least the three major landmasses in the area (Borneo, Sumatra and the Malay Peninsula) and compared them to hypothetical phylogenies based on independent geological data and climate models regarding connections and relationships between the major landmasses of Sundaland. Java was included where possible. We dated the phylogenies to determine whether patterns of differentiation were concordant across species. Results In most species, populations on the Malay Peninsula and Sumatra were most closely related, and sister to those from Borneo. The dates of these divergences, however, varied extensively between species. Borneo harbours multiple deeply divergent lineages of many species compared to the diversity within those species. Javan populations of several birds were most divergent relative to those from the rest of the Sunda Shelf. Main conclusions These results suggest a dynamic history, including recurrent population extinctions and replacements and a strong priority effect for local populations. The close relationship between populations in Sumatra and the Malay Peninsula supports the existence of forest on the exposed shelf during the Pleistocene at many different times, and suggests that proximity was more important than the presence of palaeorivers for dispersal of forest taxa between landmasses.
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| 9. |
- Nidever, David L., et al.
(författare)
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The Lazy Giants : APOGEE Abundances Reveal Low Star Formation Efficiencies in the Magellanic Clouds
- 2020
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Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 895:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the first APOGEE metallicities and alpha-element abundances measured for 3600 red giant stars spanning a large radial range of both the Large (LMC) and Small Magellanic Clouds, the largest Milky Way (MW) dwarf galaxies. Our sample is an order of magnitude larger than that of previous studies and extends to much larger radial distances. These are the first results presented that make use of the newly installed southern APOGEE instrument on the du Pont telescope at Las Campanas Observatory. Our unbiased sample of the LMC spans a large range in metallicity, from [Fe/H] = -0.2 to very metal-poor stars with [Fe/H] -2.5, the most metal-poor Magellanic Cloud (MC) stars detected to date. The LMC [alpha/Fe]-[Fe/H] distribution is very flat over a large metallicity range but rises by similar to 0.1 dex at -1.0 < [Fe/H] less than or similar to -0.5. We interpret this as a sign of the known recent increase in MC star formation activity and are able to reproduce the pattern with a chemical evolution model that includes a recent "starburst." At the metal-poor end, we capture the increase of [alpha/Fe] with decreasing [Fe/H] and constrain the "alpha-knee" to [Fe/H] less than or similar to -2.2 in both MCs, implying a low star formation efficiency of similar to 0.01 Gyr(-1). The MC knees are more metal-poor than those of less massive MW dwarf galaxies such as Fornax, Sculptor, or Sagittarius. One possible interpretation is that the MCs formed in a lower-density environment than the MW, a hypothesis that is consistent with the paradigm that the MCs fell into the MW's gravitational potential only recently.
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| 10. |
- Ryan, Amy L, et al.
(författare)
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Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases 2017 : An Official American Thoracic Society Workshop Report
- 2019. - 4
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The University of Vermont Larner College of Medicine, in collaboration with the National Heart, Lung, and Blood Institute (NHLBI), the Alpha-1 Foundation, the American Thoracic Society, the Cystic Fibrosis Foundation, the European Respiratory Society, the International Society for Cell & Gene Therapy, and the Pulmonary Fibrosis Foundation, convened a workshop titled "Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases" from July 24 through 27, 2017, at the University of Vermont, Burlington, Vermont. The conference objectives were to review and discuss current understanding of the following topics: 1) stem and progenitor cell biology and the role that they play in endogenous repair or as cell therapies after lung injury, 2) the emerging role of extracellular vesicles as potential therapies, 3) ex vivo bioengineering of lung and airway tissue, and 4) progress in induced pluripotent stem cell protocols for deriving lung cell types and applications in disease modeling. All of these topics are research areas in which significant and exciting progress has been made over the past few years. In addition, issues surrounding the ethics and regulation of cell therapies worldwide were discussed, with a special emphasis on combating the growing problem of unproven cell interventions being administered to patients with lung diseases. Finally, future research directions were discussed, and opportunities for both basic and translational research were identified.
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