| 1. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 2. |
- Andersson, Urban, 1965, et al.
(författare)
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Research.chalmers.se : building the next generation research information infrastructure at Chalmers University of Technology
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- research.chalmers.se is the new research infrastructure - repository platform and CRIS - that is currently being developed by the library at Chalmers University of Technology, Sweden.With the aim of eventually becoming the place for all relevant research information at the university, and built in accordance with the principles of UX (User eXperience) and agile development (SCRUM) and with a steady focus on value and continuous deliveries, research.chalmers.se is set to replace most of the current research information infrastructure at the university. It will provide new services for collecting, curating and providing quality data, as well as tools for analysis, sharing and promotion of research output by new and up-to-date means.research.chalmers.se is (or will be)- creating and preserving values - research output and data repository with qualitativedata, researcher profiles, open access.- promoting open access publishing, by proving the value of knowledge sharing, visibilityand impact as a researcher.- collecting and curating all kinds of research information, including publications,research data and information about research projects and other research activities.- built with responsive design that is adapted to current user needs. - using current standards for validity and sustainability, such as ORCID, DOI andFundRef IDs.- providing new ways of exploring and analyzing data, such as altmetrics, open APIs andvisualization tools.In the first phase (starting in 2014) a complete system for handling research project and grant information has been developed, together with integration of the local HR system for persistent and structured data about staff and organisation.In the current phase (2016-) repository services are being developed, such as a new publication database and a new digital repository, along with services for sharing and collecting data.The next phase(s) will include handling of research data, research activities, learning objects and tools for bibliometric analysis.This poster will show some of the current and future features and the principles of UX and agile development, as well as the experiences of moving out of the comfort zone and dealing with new, non-publication related data, while sustaining and enhancing existing data and current services. It will discuss the challenges and possible solutions, when handling different kinds of research information for use and re-use, in the long run enabling the comprehension of the big picture of research at Chalmers University of Technology.
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| 3. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 5. |
- Forouzanfar, Mohammad H, et al.
(författare)
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Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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| 8. |
- Jackson, Victoria E, et al.
(författare)
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Meta-analysis of exome array data identifies six novel genetic loci for lung function.
- 2018
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
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| 9. |
- Jensen, Hanne Irene, et al.
(författare)
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Practice Recommendations for End-of-Life Care in the Intensive Care Unit.
- 2020
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Ingår i: Critical care nurse. - : AACN Publishing. - 1940-8250 .- 0279-5442. ; 40:3, s. 14-22
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Tidskriftsartikel (refereegranskat)abstract
- TOPIC: A substantial number of patients die in the intensive care unit, so high-quality end-of-life care is an important part of intensive care unit work. However, end-of-life care varies because of lack of knowledge of best practices.CLINICAL RELEVANCE: Research shows that high-quality end-of-life care is possible in an intensive care unit. This article encourages nurses to be imaginative and take an individual approach to provide the best possible end-of-life care for patients and their family members.PURPOSE OF PAPER: To provide recommendations for high-quality end-of-life care for patients and family members.CONTENT COVERED: This article touches on the following domains: end-of-life decision-making, place to die, patient comfort, family presence in the intensive care unit, visiting children, family needs, preparing the family, staff presence, when the patient dies, after-death care of the family, and caring for staff.
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| 10. |
- Jensen, Kristin, et al.
(författare)
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Comparing five different iterative reconstruction algorithms for computed tomography in an ROC study
- 2014
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 24:12, s. 2989-3002
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate lesion conspicuity achieved with five different iterative reconstruction techniques from four CT vendors at three different dose levels. Comparisons were made of iterative algorithm and filtered back projection (FBP) among and within systems. An anthropomorphic liver phantom was examined with four CT systems, each from a different vendor. CTDIvol levels of 5 mGy, 10 mGy and 15 mGy were chosen. Images were reconstructed with FBP and the iterative algorithm on the system. Images were interpreted independently by four observers, and the areas under the ROC curve (AUCs) were calculated. Noise and contrast-to-noise ratios (CNR) were measured. One iterative algorithm increased AUC (0.79, 0.95, and 0.97) compared to FBP (0.70, 0.86, and 0.93) at all dose levels (p < 0.001 and p = 0.047). Another algorithm increased AUC from 0.78 with FBP to 0.84 (p = 0.007) at 5 mGy. Differences at 10 and 15 mGy were not significant (p-values: 0.084-0.883). Three algorithms showed no difference in AUC compared to FBP (p-values: 0.008-1.000). All of the algorithms decreased noise (10-71 %) and improved CNR. Only two algorithms improved lesion detection, even though noise reduction was shown with all algorithms. aEuro cent Iterative reconstruction algorithms affected lesion detection differently at different dose levels. aEuro cent One iterative algorithm improved lesion detectability compared to filtered back projection. aEuro cent Three algorithms did not significantly improve lesion detectability. aEuro cent One algorithm improved lesion detectability at the lowest dose level.
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