| 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. |
- Daneshjou, Roxana, et al.
(författare)
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Working toward precision medicine : Predicting phenotypes from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges
- 2017
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 38:9, s. 1182-1192
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Tidskriftsartikel (refereegranskat)abstract
- Precision medicine aims to predict a patient's disease risk and best therapeutic options by using that individual's genetic sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. For CAGI 4, three challenges involved using exome-sequencing data: Crohn's disease, bipolar disorder, and warfarin dosing. Previous CAGI challenges included prior versions of the Crohn's disease challenge. Here, we discuss the range of techniques used for phenotype prediction as well as the methods used for assessing predictive models. Additionally, we outline some of the difficulties associated with making predictions and evaluating them. The lessons learned from the exome challenges can be applied to both research and clinical efforts to improve phenotype prediction from genotype. In addition, these challenges serve as a vehicle for sharing clinical and research exome data in a secure manner with scientists who have a broad range of expertise, contributing to a collaborative effort to advance our understanding of genotype-phenotype relationships.
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| 3. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 4. |
- Fuso-Nerini, Francesco, et al.
(författare)
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Estimating the cost of energy access : The case of the village of Suro Craic in Timor Leste
- 2015
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Ingår i: Energy. - : Elsevier BV. - 0360-5442 .- 1873-6785. ; 79, s. 385-397
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Tidskriftsartikel (refereegranskat)abstract
- Energy access targets at national, sub-national, and local levels, are often not specified in great detail - and tend to focus on supply. Another approach to better inform policy and investment might benefit from an indicator that focuses on the services derived from electricity access. To provide support for decision-making, this research investigates the costs of reaching different levels of energy access in rural areas, with a case study of a village in the Ainaro district of Timor Leste. Utilizing the multi-tier definition of energy access proposed in the World Bank's "Global Tracking Framework" for Sustainable Energy for All, we present results both on the cost difference of achieving different tiers of energy access, and on the comparison among selected electrification and cooking options. Results show that in the period 2010-2030 achieving the highest tier of electricity access could be as much as seventy-five times more costly than achieving the lowest one. In addition moving across tiers, least cost solutions shift from stand-alone to mini-grid and finally grid connected options as electricity access increases. Regarding cooking, moving from open fires to some of the more modern solutions has the potential to reduce overall costs over the same period.
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| 5. |
- Inker, Lesley A., et al.
(författare)
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New creatinine- and cystatin C-based equations to estimate GFR without race
- 2021
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 385:19, s. 1737-1749
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Tidskriftsartikel (refereegranskat)abstract
- Background: Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct.Methods: We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations.Results: In the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m2; 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m2; 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m2; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m2; 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks.Conclusions: New eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone.
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| 8. |
- Martínez-Sánchez, Noelia, et al.
(författare)
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Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
- 2017
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Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12
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Tidskriftsartikel (refereegranskat)abstract
- Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
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| 9. |
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| 10. |
- Rockström, Johan, et al.
(författare)
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Climate change : The necessary, the possible and the desirable Earth League climate statement on the implications for climate policy from the 5th IPCC Assessment
- 2014
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Ingår i: Earth’s Future. - 2328-4277. ; 2:12, s. 606-611
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Tidskriftsartikel (refereegranskat)abstract
- The development of human civilisations has occurred at a time of stable climate. This climate stability is now threatened by human activity. The rising global climate risk occurs at a decisive moment for world development. World nations are currently discussing a global development agenda consequent to the Millennium Development Goals (MDGs), which ends in 2015. It is increasingly possible to envisage a world where absolute poverty is largely eradicated within one generation and where ambitious goals on universal access and equal opportunities for dignified lives are adopted. These grand aspirations for a world population approaching or even exceeding nine billion in 2050 is threatened by substantial global environmental risks and by rising inequality. Research shows that development gains, in both rich and poor nations, can be undermined by social, economic and ecological problems caused by human-induced global environmental change. Climate risks, and associated changes in marine and terrestrial ecosystems that regulate the resilience of the climate system, are at the forefront of these global risks. We, as citizens with a strong engagement in Earth system science and socio-ecological dynamics, share the vision of a more equitable and prosperous future for the world, yet we also see threats to this future from shifts in climate and environmental processes. Without collaborative action now, our shared Earth system may not be able to sustainably support a large proportion of humanity in the decades ahead.
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| 11. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 12. |
- Schaefer, Bettina, et al.
(författare)
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Microbial life in the nascent Chicxulub crater
- 2020
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Ingår i: Geology. - Boulder : Geological Society of America. - 0091-7613 .- 1943-2682. ; 48, s. 328-332
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Tidskriftsartikel (refereegranskat)abstract
- The Chicxulub crater was formed by an asteroid impact at ca. 66 Ma. The impact is considered to have contributed to the end-Cretaceous mass extinction and reduced productivity in the world’s oceans due to a transient cessation of photosynthesis. Here, biomarker profiles extracted from crater core material reveal exceptional insights into the post-impact upheaval and rapid recovery of microbial life. In the immediate hours to days after the impact, ocean resurge flooded the crater and a subsequent tsunami delivered debris from the surrounding carbonate ramp. Deposited material, including biomarkers diagnostic for land plants, cyanobacteria, and photosynthetic sulfur bacteria, appears to have been mobilized by wave energy from coastal microbial mats. As that energy subsided, days to months later, blooms of unicellular cyanobacteria were fueled by terrigenous nutrients. Approximately 200 k.y. later, the nutrient supply waned and the basin returned to oligotrophic conditions, as evident from N2-fixing cyanobacteria biomarkers. At 1 m.y. after impact, the abundance of photosynthetic sulfur bacteria supported the development of water-column photic zone euxinia within the crater.
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| 13. |
- Unterkalmsteiner, Michael, et al.
(författare)
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Software startups-A research agenda
- 2016
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Ingår i: e-Informatica Software Engineering Journal. - : Politechnika Wroclawska. - 1897-7979 .- 2084-4840. ; 10:1, s. 89-123
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Tidskriftsartikel (refereegranskat)abstract
- Software startup companies develop innovative, software-intensive products within limited time frames and with few resources, searching for sustainable and scalable business models. Software startups are quite distinct from traditional mature software companies, but also from micro-, small-, and medium-sized enterprises, introducing new challenges relevant for software engineering research. This paper's research agenda focuses on software engineering in startups, identifying, in particular, 70+ research questions in the areas of supporting startup engineering activities, startup evolution models and patterns, ecosystems and innovation hubs, human aspects in software startups, applying startup concepts in non-startup environments, and methodologies and theories for startup research. We connect and motivate this research agenda with past studies in software startup research, while pointing out possible future directions. While all authors of this research agenda have their main background in Software Engineering or Computer Science, their interest in software startups broadens the perspective to the challenges, but also to the opportunities that emerge from multi-disciplinary research. Our audience is therefore primarily software engineering researchers, even though we aim at stimulating collaborations and research that crosses disciplinary boundaries. We believe that with this research agenda we cover a wide spectrum of the software startup industry current needs.
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| 14. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
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Tidskriftsartikel (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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