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1.
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2.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • 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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3.
  • Forouzanfar, Mohammad H, et al. (författare)
  • 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
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
  • 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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4.
  • Wang, Haidong, et al. (författare)
  • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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5.
  • 2021
  • swepub:Mat__t
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6.
  • 2021
  • swepub:Mat__t
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7.
  • Vos, Theo, et al. (författare)
  • Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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8.
  • Weinstein, John N., et al. (författare)
  • The cancer genome atlas pan-cancer analysis project
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
  • Forskningsöversikt (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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12.
  • Gross, Sean M., et al. (författare)
  • A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
  • 2022
  • Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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13.
  • Kato, Norihiro, et al. (författare)
  • Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
  • 2015
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
  • Tidskriftsartikel (refereegranskat)abstract
    • We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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14.
  • Naghavi, Mohsen, et al. (författare)
  • Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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15.
  • Ried, Janina S., et al. (författare)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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16.
  • Glasbey, JC, et al. (författare)
  • 2021
  • swepub:Mat__t
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17.
  • Abel, I, et al. (författare)
  • Overview of the JET results with the ITER-like wall
  • 2013
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
  • Tidskriftsartikel (refereegranskat)abstract
    • Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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18.
  • Barber, R. M., et al. (författare)
  • Healthcare access and quality index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990-2015 : A novel analysis from the global burden of disease study 2015
  • 2017
  • Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 390:10091, s. 231-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Background National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). Previous analyses of mortality amenable to health care only focused on high-income countries and faced several methodological challenges. In the present analysis, we use the highly standardised cause of death and risk factor estimates generated through the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015. Methods We mapped the most widely used list of causes amenable to personal health care developed by Nolte and McKee to 32 GBD causes. We accounted for variations in cause of death certification and misclassifications through the extensive data standardisation processes and redistribution algorithms developed for GBD. To isolate the effects of personal health-care access and quality, we risk-standardised cause-specific mortality rates for each geography-year by removing the joint effects of local environmental and behavioural risks, and adding back the global levels of risk exposure as estimated for GBD 2015. We employed principal component analysis to create a single, interpretable summary measure-the Healthcare Quality and Access (HAQ) Index-on a scale of 0 to 100. The HAQ Index showed strong convergence validity as compared with other health-system indicators, including health expenditure per capita (r=0·88), an index of 11 universal health coverage interventions (r=0·83), and human resources for health per 1000 (r=0·77). We used free disposal hull analysis with bootstrapping to produce a frontier based on the relationship between the HAQ Index and the Socio-demographic Index (SDI), a measure of overall development consisting of income per capita, average years of education, and total fertility rates. This frontier allowed us to better quantify the maximum levels of personal health-care access and quality achieved across the development spectrum, and pinpoint geographies where gaps between observed and potential levels have narrowed or widened over time. Findings Between 1990 and 2015, nearly all countries and territories saw their HAQ Index values improve; nonetheless, the difference between the highest and lowest observed HAQ Index was larger in 2015 than in 1990, ranging from 28·6 to 94·6. Of 195 geographies, 167 had statistically significant increases in HAQ Index levels since 1990, with South Korea, Turkey, Peru, China, and the Maldives recording among the largest gains by 2015. Performance on the HAQ Index and individual causes showed distinct patterns by region and level of development, yet substantial heterogeneities emerged for several causes, including cancers in highest-SDI countries; chronic kidney disease, diabetes, diarrhoeal diseases, and lower respiratory infections among middle-SDI countries; and measles and tetanus among lowest-SDI countries. While the global HAQ Index average rose from 40·7 (95% uncertainty interval, 39·0-42·8) in 1990 to 53·7 (52·2-55·4) in 2015, far less progress occurred in narrowing the gap between observed HAQ Index values and maximum levels achieved; at the global level, the difference between the observed and frontier HAQ Index only decreased from 21·2 in 1990 to 20·1 in 2015. If every country and territory had achieved the highest observed HAQ Index by their corresponding level of SDI, the global average would have been 73·8 in 2015. Several countries, particularly in eastern and western sub-Saharan Africa, reached HAQ Index values similar to or beyond their development levels, whereas others, namely in southern sub-Saharan Africa, the Middle East, and south Asia, lagged behind what geographies of similar development attained between 1990 and 2015. Interpretation This novel extension of the GBD Study shows the untapped potential for personal health-care access and quality improvement across the development spectrum. Amid substantive advances in personal health care at the national level, heterogeneous patterns for individual causes in given countries or territories suggest that few places have consistently achieved optimal health-care access and quality across health-system functions and therapeutic areas. This is especially evident in middle-SDI countries, many of which have recently undergone or are currently experiencing epidemiological transitions. The HAQ Index, if paired with other measures of health-system characteristics such as intervention coverage, could provide a robust avenue for tracking progress on universal health coverage and identifying local priorities for strengthening personal health-care quality and access throughout the world. Copyright © The Author(s). Published by Elsevier Ltd.
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19.
  • Barber, R. M., et al. (författare)
  • Healthcare Access and Quality Index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990-2015: a novel analysis from the Global Burden of Disease Study 2015
  • 2017
  • Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 390:10091, s. 231-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Background National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). Previous analyses of mortality amenable to health care only focused on high-income countries and faced several methodological challenges. In the present analysis, we use the highly standardised cause of death and risk factor estimates generated through the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015. Methods We mapped the most widely used list of causes amenable to personal health care developed by Nolte and McKee to 32 GBD causes. We accounted for variations in cause of death certification and misclassifications through the extensive data standardisation processes and redistribution algorithms developed for GBD. To isolate the effects of personal health-care access and quality, we risk-standardised cause-specific mortality rates for each geography-year by removing the joint effects of local environmental and behavioural risks, and adding back the global levels of risk exposure as estimated for GBD 2015. We employed principal component analysis to create a single, interpretable summary measure-the Healthcare Quality and Access (HAQ) Index-on a scale of 0 to 100. The HAQ Index showed strong convergence validity as compared with other health-system indicators, including health expenditure per capita (r= 0.88), an index of 11 universal health coverage interventions (r= 0.83), and human resources for health per 1000 (r= 0.77). We used free disposal hull analysis with bootstrapping to produce a frontier based on the relationship between the HAQ Index and the Socio-demographic Index (SDI), a measure of overall development consisting of income per capita, average years of education, and total fertility rates. This frontier allowed us to better quantify the maximum levels of personal health-care access and quality achieved across the development spectrum, and pinpoint geographies where gaps between observed and potential levels have narrowed or widened over time. Findings Between 1990 and 2015, nearly all countries and territories saw their HAQ Index values improve; nonetheless, the difference between the highest and lowest observed HAQ Index was larger in 2015 than in 1990, ranging from 28.6 to 94.6. Of 195 geographies, 167 had statistically significant increases in HAQ Index levels since 1990, with South Korea, Turkey, Peru, China, and the Maldives recording among the largest gains by 2015. Performance on the HAQ Index and individual causes showed distinct patterns by region and level of development, yet substantial heterogeneities emerged for several causes, including cancers in highest-SDI countries; chronic kidney disease, diabetes, diarrhoeal diseases, and lower respiratory infections among middle-SDI countries; and measles and tetanus among lowest-SDI countries. While the global HAQ Index average rose from 40.7 (95% uncertainty interval, 39.0-42.8) in 1990 to 53.7 (52.2-55.4) in 2015, far less progress occurred in narrowing the gap between observed HAQ Index values and maximum levels achieved; at the global level, the difference between the observed and frontier HAQ Index only decreased from 21.2 in 1990 to 20.1 in 2015. If every country and territory had achieved the highest observed HAQ Index by their corresponding level of SDI, the global average would have been 73.8 in 2015. Several countries, particularly in eastern and western sub-Saharan Africa, reached HAQ Index values similar to or beyond their development levels, whereas others, namely in southern sub-Saharan Africa, the Middle East, and south Asia, lagged behind what geographies of similar development attained between 1990 and 2015. Interpretation This novel extension of the GBD Study shows the untapped potential for personal health-care access and quality improvement across the development spectrum. Amid substantive advances in personal health care at the national level, heterogeneous patterns for individual causes in given countries or territories suggest that few places have consistently achieved optimal health-care access and quality across health-system functions and therapeutic areas. This is especially evident in middle-SDI countries, many of which have recently undergone or are currently experiencing epidemiological transitions. The HAQ Index, if paired with other measures of health-systemcharacteristics such as intervention coverage, could provide a robust avenue for tracking progress on universal health coverage and identifying local priorities for strengthening personal health-care quality and access throughout the world. Copyright (C) The Author(s). Published by Elsevier Ltd.
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20.
  • Kassebaum, Nicholas J., et al. (författare)
  • Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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21.
  • Mills, James A., et al. (författare)
  • Archiving Primary Data : Solutions for Long-Term Studies
  • 2015
  • Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 30:10, s. 581-589
  • Tidskriftsartikel (refereegranskat)abstract
    • The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (PIs) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers.
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22.
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23.
  • Shungin, Dmitry, et al. (författare)
  • New genetic loci link adipose and insulin biology to body fat distribution.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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24.
  • Wang, Haidong, et al. (författare)
  • Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015.
  • 2016
  • Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
  •  
25.
  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
  •  
26.
  • Tabiri, S, et al. (författare)
  • 2021
  • swepub:Mat__t
  •  
27.
  • Aaltonen, T., et al. (författare)
  • Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode
  • 2010
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:6, s. 061802-
  • Tidskriftsartikel (refereegranskat)abstract
    • We combine searches by the CDF and D0 Collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb(-1) of p (p) over bar collisions at root s = 1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L.
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28.
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29.
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30.
  • Charchar, Fadi J., et al. (författare)
  • Lifestyle management of hypertension : International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension
  • 2024
  • Ingår i: Journal of Hypertension. - : Wolters Kluwer. - 0263-6352 .- 1473-5598. ; 42:1, s. 23-49
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.
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31.
  • Cnattingius, Sven, et al. (författare)
  • The paradoxical effect of smoking in preeclamptic pregnancies : smoking reduces the incidence but increases the rates of perinatal mortality, abruptio placentae, and intrauterine growth restriction
  • 1997
  • Ingår i: American Journal of Obstetrics and Gynecology. - 0002-9378 .- 1097-6868. ; 177:1, s. 156-61
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Smoking is associated with a reduced risk of preeclampsia, but what is the outcome of pregnancy when preeclampsia develops in women who smoke? STUDY DESIGN: Single births in Sweden from 1987 through 1993 to nulliparous women aged 15 to 34 years (N = 317,652) were included. Poisson regression analyses were used to calculate adjusted relative risks and rates of adverse pregnancy outcomes. RESULTS: Maternal smoking was associated with significantly reduced risks of mild and severe preeclampsia (relative risks = 0.6 and 0.5, respectively). In pregnancies with severe preeclampsia, smoking at least 10 cigarettes per day was associated with increased rates of perinatal mortality (from 24 to 36 per 1000), abruptio placentae (from 31 to 67 per 1000), and being small for gestational age (from 28% to 68%), whereas the corresponding smoking-related increases in rates in nonhypertensive pregnancies were considerably less. CONCLUSIONS: Smokers in whom preeclampsia develops have very high risks of perinatal mortality, abruptio placentae, and small-for-gestational-age infants.
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32.
  • Commins, Scott P, et al. (författare)
  • Galactose-α-1,3-galactose-specific IgE is associated with anaphylaxis but not asthma.
  • 2012
  • Ingår i: American journal of respiratory and critical care medicine. - 1535-4970 .- 1073-449X. ; 185:7, s. 723-30
  • Tidskriftsartikel (refereegranskat)abstract
    • IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract.
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33.
  • Commins, Scott P., et al. (författare)
  • The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose
  • 2011
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 127:5, s. 1286-1293.e6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In 2009, we reported a novel form of delayed anaphylaxis to red meat that is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives: We sought to investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur.Methods: Serum assays were carried out with biotinylated proteins and extracts bound to a streptavidin ImmunoCAP.Results: Prospective studies on IgE antibodies in 3 subjects after tick bites showed an increase in levels of IgE to alpha-gal of 20fold or greater. Other evidence included (1) a strong correlation between histories of tick bites and levels of IgE to alpha-gal (chi(2) = 26.8, P < .001), (2) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and (3) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A americanum (r(s) = 0.75, P < .001).Conclusion: The results presented here provide evidence that tick bites are a cause, possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.
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34.
  • Fadista, João, et al. (författare)
  • Genome-wide meta-analysis identifies BARX1 and EML4-MTA3 as new loci associated with infantile hypertrophic pyloric stenosis.
  • 2019
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 28:2, s. 332-340
  • Tidskriftsartikel (refereegranskat)abstract
    • Infantile hypertrophic pyloric stenosis (IHPS) is a disorder of young infants with a population incidence of ∼2/1000 live births, caused by hypertrophy of the pyloric sphincter smooth muscle. Reported genetic loci associated with IHPS explain only a minor proportion of IHPS risk. To identify new risk loci, we carried out a genome-wide meta-analysis on 1395 surgery-confirmed cases and 4438 controls, with replication in a set of 2427 cases and 2524 controls. We identified and replicated six independent genomic loci associated with IHPS risk at genome wide significance (P < 5 × 10-8), including novel associations with two single nucleotide polymorphisms (SNPs). One of these SNPs, rs6736913 [odds ratio (OR) = 2.32; P = 3.0 × 10-15], is a low frequency missense variant in EML4 at 2p21. The second SNP, rs1933683 (OR = 1.34; P = 3.1 × 10-9) is 1 kb downstream of BARX1 at 9q22.32, an essential gene for stomach formation in embryogenesis. Using the genome-wide complex trait analysis method, we estimated the IHPS SNP heritability to be 30%, and using the linkage disequilibrium score regression method, we found support for a previously reported genetic correlation of IHPS with lipid metabolism. By combining the largest collection of IHPS cases to date (3822 cases), with results generalized across populations of different ancestry, we elucidate novel mechanistic avenues of IHPS disease architecture.
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35.
  • Fitzmauric, C., et al. (författare)
  • Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017 : A Systematic Analysis for the Global Burden of Disease Study
  • 2019
  • Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 5:12, s. 1749-1768
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs).Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. 
  •  
36.
  • Frayling, Timothy M., et al. (författare)
  • A Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young: Evidence for Further Genetic Heterogeneity.
  • 2003
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 52:3, s. 872-881
  • Tidskriftsartikel (refereegranskat)abstract
    • Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non–insulin-dependent diabetes, an early onset and autosomal dominant inheritance. Mutations in six genes have been shown to cause MODY. Approximately 15–20% of families fitting MODY criteria do not have mutations in any of the known genes. These families provide a rich resource for the identification of new MODY genes. This will potentially enable further dissection of clinical heterogeneity and bring new insights into mechanisms of β-cell dysfunction. To facilitate the identification of novel MODY loci, we combined the results from three genome-wide scans on a total of 23 families fitting MODY criteria. We used both a strict parametric model of inheritance with heterogeneity and a model-free analysis. We did not identify any single novel locus but provided putative evidence for linkage to chromosomes 6 (nonparametric linkage [NPL]score 2.12 at 71 cM) and 10 (NPL score 1.88 at 169–175 cM), and to chromosomes 3 (heterogeneity LOD [HLOD] score 1.27 at 124 cM) and 5 (HLOD score 1.22 at 175 cM) in 14 more strictly defined families. Our results provide evidence for further heterogeneity in MODY.
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37.
  • Frazier-Wood, Alexis C., et al. (författare)
  • Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
  • 2016
  • Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
  • Tidskriftsartikel (refereegranskat)abstract
    • Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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38.
  • Gregoromichelaki, Eleni, et al. (författare)
  • Completability vs (In)completeness
  • 2020
  • Ingår i: Acta Linguistica Hafniensia. - : Informa UK Limited. - 0374-0463 .- 1949-0763. ; 52:2, s. 260-284
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2020 The Linguistic Circle of Copenhagen. In everyday conversation, no notion of “complete sentence” is required for syntactic licensing. However, so-called “fragmentary”, “incomplete”, and abandoned utterances are problematic for standard formalisms. When contextualised, such data show that (a) non-sentential utterances are adequate to underpin agent coordination, while (b) all linguistic dependencies can be systematically distributed across participants and turns. Standard models have problems accounting for such data because their notions of ‘constituency’ and ‘syntactic domain’ are independent of performance considerations. Concomitantly, we argue that no notion of “full proposition” or encoded speech act is necessary for successful interaction: strings, contents, and joint actions emerge in conversation without any single participant having envisaged in advance the outcome of their own or their interlocutors’ actions. Nonetheless, morphosyntactic and semantic licensing mechanisms need to apply incrementally and subsententially. We argue that, while a representational level of abstract syntax, divorced from conceptual structure and physical action, impedes natural accounts of subsentential coordination phenomena, a view of grammar as a “skill” employing domain-general mechanisms, rather than fixed form-meaning mappings, is needed instead. We provide a sketch of a predictive and incremental architecture (Dynamic Syntax) within which underspecification and time-relative update of meanings and utterances constitute the sole concept of “syntax”.
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39.
  • Hautmann, Richard E., et al. (författare)
  • Urinary diversion
  • 2007
  • Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 69:1, Supplement 1, s. 17-49
  • Forskningsöversikt (refereegranskat)abstract
    • A consensus conference convened by the World Health Organization (WHO) and the Societe Internationale d'Urologie (SIU) met to critically review reports of urinary diversion. The world literature on urinary diversion was identified through a Medline search. Evidence-based recommendations for urinary diversion were prepared with reference to a 4-point scale. Many level 3 and 4 citations, but very few level 2 and no level 1, were noted. This outcome supported the clinical practice pattern. Findings of > 300 reviewed citations are Summarized. Published reports on urinary diversion rely heavily on expert opinion and single-institution retrospective case series: (1) The frequency distribution of urinary diversions performed by the authors of this report in > 7000 patients with cystectomy reflects the current status of urinary diversion after cystectomy for bladder cancer: ncobladder, 47%; conduit, 33%; anal diversion, 10%; continent cutaneous diversion, 8%; incontinent cutaneous diversion, 2%; and others, 0.1%. (2) No randomized controlled studies have investigated quality of life (QOL) after radical cystectomy. Such studies are desirable but are probably difficult to conduct. Published evidence does not Support an advantage of one type of reconstruction over the others with regard to QOL. An important proposed reason for this is that patients are subjected preoperatively to method-to-patient matching, and thus are prepared for disadvantages associated with different methods. (3) Simple end-to-side, freely refluxing ureterointestinal anastomosis to an afferent limb of a low-pressure orthotopic reconstruction, in combination with regular voiding and close follow-up, is the procedure that results in the lowest overall complication rate. The potential benefit of "conventional" antireflux procedures in combination with orthotopic reconstruction seems outweighed by the higher complication and reoperation rates. The need to prevent reflux in a continent cutaneous reservoir is not significantly debated, and this should be done. (4) Most reconstructive surgeons have abandoned the continent Kock ileal reservoir largely because of the significant complication rate associated with the intussuscepted nipple valve.
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40.
  • Heslop, James A., et al. (författare)
  • Concise Review : Workshop Review: Understanding and Assessing the Risks of Stem Cell-Based Therapies
  • 2015
  • Ingår i: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 4:4, s. 389-400
  • Forskningsöversikt (refereegranskat)abstract
    • The field of stem cell therapeutics is moving ever closer to widespread application in the clinic. However, despite the undoubted potential held by these therapies, the balance between risk and benefit remains difficult to predict. As in any new field, a lack of previous application in man and gaps in the underlying science mean that regulators and investigators continue to look for a balance between minimizing potential risk and ensuring therapies are not needlessly kept from patients. Here, we attempt to identify the important safety issues, assessing the current advances in scientific knowledge and how they may translate to clinical therapeutic strategies in the identification and management of these risks. We also investigate the tools and techniques currently available to researchers during preclinical and clinical development of stem cell products, their utility and limitations, and how these tools may be strategically used in the development of these therapies. We conclude that ensuring safety through cutting-edge science and robust assays, coupled with regular and open discussions between regulators and academic/industrial investigators, is likely to prove the most fruitful route to ensuring the safest possible development of new products.
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41.
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42.
  • James, Hayley R, et al. (författare)
  • IgE Antibodies to Mammalian Allergens Are a Major Risk Factor for Prevalence, Severity, and Persistence of Asthma in Northern Sweden
  • 2015
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 135:2, s. AB22-AB22
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • IgE to mammalian allergens can contribute significantly to asthma risk. Studying the details of the relationship between animal sensitization and asthma is simpler in an environment where mite, fungal, and cockroach allergens make little or no contribution to asthma risk. Methods: Quantitative assays for IgE to eight allergens were carried out on 963 sera from 19-year-olds in a population-based cohort in northern Sweden, and associations with questionnaire data from ages 7, 12, and 19 on asthma symptoms, diagnosis, and treatment were tested. Results: Overall, 79 (53%) of the students with a physician diagnosis of asthma were positive to one or more of the mammalian allergens (cat, dog, or horse danders) tested. Of the allergens assessed, only mammalian allergens, birch, and timothy grass pollen showed a significant relationship with asthma diagnosis. Multivariate analysis showed that high titer (>17.5 IU/ml) IgE to any mammalian allergen had the strongest relationship with asthma at age 19 (odds ratio 5.1 [3.0-8.6]). Furthermore, IgE to mammalian allergens gave an odds ratio of 8.5 [4.9-15] for asthma that started before age 12 and was still present at age 19. Sensitization to Fel d 1 and Fel d 4 was strongly associated with asthma and significantly reduced in cat owners. Conclusions: Sensitization to cat and dog related allergens, and specifically to the components Fel d 1 and Fel d 4, is a major risk factor for the persistence and severity of asthma in an area where these are the only significant perennial allergens.
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43.
  • Khalil, Ibrahim, et al. (författare)
  • Burden of Diarrhea in the Eastern Mediterranean Region, 1990-2013 : Findings from the Global Burden of Disease Study 2013
  • 2016
  • Ingår i: American Journal of Tropical Medicine and Hygiene. - : American Society of Tropical Medicine and Hygiene. - 1476-1645 .- 0002-9637. ; 95:6, s. 1319-1329
  • Tidskriftsartikel (refereegranskat)abstract
    • Diarrheal diseases (DD) are leading causes of disease burden, death, and disability, especially in children in low-income settings. DD can also impact a child's potential livelihood through stunted physical growth, cognitive impairment, and other sequelae. As part of the Global Burden of Disease Study, we estimated DD burden, and the burden attributable to specific risk factors and particular etiologies, in the Eastern Mediterranean Region (EMR) between 1990 and 2013. For both sexes and all ages, we calculated disability-adjusted life years (DALYs), which are the sum of years of life lost and years lived with disability. We estimate that over 125,000 deaths (3.6% of total deaths) were due to DD in the EMR in 2013, with a greater burden of DD in low- and middle-income countries. Diarrhea deaths per 100,000 children under 5 years of age ranged from one (95% uncertainty interval [UI] = 0-1) in Bahrain and Oman to 471 (95% UI = 245-763) in Somalia. The pattern for diarrhea DALYs among those under 5 years of age closely followed that for diarrheal deaths. DALYs per 100,000 ranged from 739 (95% UI = 520-989) in Syria to 40,869 (95% UI = 21,540-65,823) in Somalia. Our results highlighted a highly inequitable burden of DD in EMR, mainly driven by the lack of access to proper resources such as water and sanitation. Our findings will guide preventive and treatment interventions which are based on evidence and which follow the ultimate goal of reducing the DD burden.
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44.
  • Khan, Muhammad Shahzeb, et al. (författare)
  • Leveraging electronic health records to streamline the conduct of cardiovascular clinical trials
  • 2023
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1890-1909
  • Forskningsöversikt (refereegranskat)abstract
    • Conventional randomized controlled trials (RCTs) can be expensive, time intensive, and complex to conduct. Trial recruitment, participation, and data collection can burden participants and research personnel. In the past two decades, there have been rapid technological advances and an exponential growth in digitized healthcare data. Embedding RCTs, including cardiovascular outcome trials, into electronic health record systems or registries may streamline screening, consent, randomization, follow-up visits, and outcome adjudication. Moreover, wearable sensors (i.e. health and fitness trackers) provide an opportunity to collect data on cardiovascular health and risk factors in unprecedented detail and scale, while growing internet connectivity supports the collection of patient-reported outcomes. There is a pressing need to develop robust mechanisms that facilitate data capture from diverse databases and guidance to standardize data definitions. Importantly, the data collection infrastructure should be reusable to support multiple cardiovascular RCTs over time. Systems, processes, and policies will need to have sufficient flexibility to allow interoperability between different sources of data acquisition. Clinical research guidelines, ethics oversight, and regulatory requirements also need to evolve. This review highlights recent progress towards the use of routinely generated data to conduct RCTs and discusses potential solutions for ongoing barriers. There is a particular focus on methods to utilize routinely generated data for trials while complying with regional data protection laws. The discussion is supported with examples of cardiovascular outcome trials that have successfully leveraged the electronic health record, web-enabled devices or administrative databases to conduct randomized trials.
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45.
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46.
  • Luces, Mario, et al. (författare)
  • An Emulator-Based Prediction of Dynamic Stiffness for Redundant Parallel Kinematic Mechanisms
  • 2016
  • Ingår i: Journal of Mechanisms and Robotics. - : ASME International. - 1942-4310 .- 1942-4302. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The accuracy of a parallel kinematic mechanism (PKM) is directly related to its dynamic stiffness, which in turn is configuration dependent. For PKMs with kinematic redundancy, configurations with higher stiffness can be chosen during motion-trajectory planning for optimal performance. Herein, dynamic stiffness refers to the deformation of the mechanism structure, subject to dynamic loads of changing frequency. The stiffness-optimization problem has two computational constraints: (i) calculation of the dynamic stiffness of any considered PKM configuration, at a given task-space location, and (ii) searching for the PKM configuration with the highest stiffness at this location. Due to the lack of available analytical models, herein, the former subproblem is addressed via a novel effective emulator to provide a computationally efficient approximation of the high-dimensional dynamic-stiffness function suitable for optimization. The proposed method for emulator development identifies the mechanism's structural modes in order to breakdown the high-dimensional stiffness function into multiple functions of lower dimension. Despite their computational efficiency, however, emulators approximating high-dimensional functions are often difficult to develop and implement due to the large amount of data required to train the emulator. Reducing the dimensionality of the approximation function would, thus, result in a smaller training data set. In turn, the smaller training data set can be obtained accurately via finite-element analysis (FEA). Moving least-squares (MLS) approximation is proposed herein to compute the low-dimensional functions for stiffness approximation. Via extensive simulations, some of which are described herein, it is demonstrated that the proposed emulator can predict the dynamic stiffness of a PKM at any given configuration with high accuracy and low computational expense, making it quite suitable for most high-precision applications. For example, our results show that the proposed methodology can choose configurations along given trajectories within a few percentage points of the optimal ones.
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47.
  • Lum, Jarrad A. G., et al. (författare)
  • Transcranial direct current stimulation enhances retention of a second (but not first) order conditional visuo-motor sequence
  • 2018
  • Ingår i: Brain and Cognition. - : Elsevier. - 0278-2626 .- 1090-2147. ; 127, s. 34-41
  • Tidskriftsartikel (refereegranskat)abstract
    • This study examined the role of the left inferior frontal gyrus in the implicit learning and retention of a ‘simple’ first order conditional (FOC) sequence and a relatively ‘complex’ second order conditional (SOC) sequence, using anodal transcranial direct current stimulation (a-tDCS). Groups of healthy adults received either a-tDCS (n = 18) over the left inferior frontal gyrus or sham/placebo (n = 18) stimulation. On separate days, participants completed a serial reaction time (SRT) task whilst receiving stimulation. On one of the days, participants were presented with a FOC sequence and in another, a SOC sequence. Both the learning and short-term retention of the sequences were measured. Results showed a-tDCS enhanced the short-term retention of the SOC sequence but not the FOC sequence. There was no effect of a-tDCS on the learning of either FOC or SOC sequences. The results provide evidence of prefrontal involvement in the retention of a motor sequence. However, its role appears to be influenced by the complexity of the sequence’s structure. Additionally, the results show a-tDCS can enhance retention of an implicitly learnt motor sequence.
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48.
  • Marabita, Francesco, et al. (författare)
  • Multiomics and digital monitoring during lifestyle changes reveal independent dimensions of human biology and health
  • 2022
  • Ingår i: Cell Systems. - : Cell Press. - 2405-4712 .- 2405-4720. ; 13:3, s. 241-255.e7
  • Tidskriftsartikel (refereegranskat)abstract
    • We explored opportunities for personalized and predictive health care by collecting serial clinical measurements, health surveys, genomics, proteomics, autoantibodies, metabolomics, and gut microbiome data from 96 individuals who participated in a data-driven health coaching program over a 16-month period with continuous digital monitoring of activity and sleep. We generated a resource of >20,000 biological samples from this study and a compendium of >53 million primary data points for 558,032 distinct features. Multiomics factor analysis revealed distinct and independent molecular factors linked to obesity, diabetes, liver function, cardiovascular disease, inflammation, immunity, exercise, diet, and hormonal effects. For example, ethinyl estradiol, a common oral contraceptive, produced characteristic molecular and physiological effects, including increased levels of inflammation and impact on thyroid, cortisol levels, and pulse, that were distinct from other sources of variability observed in our study. In total, this work illustrates the value of combining deep molecular and digital monitoring of human health. A record of this paper's transparent peer review process is included in the supplemental information.
  •  
49.
  • Mills, Bethany, et al. (författare)
  • Molecular detection of Gram-positive bacteria in the human lung through an optical fiber-based endoscope
  • 2021
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Nature. - 1619-7070 .- 1619-7089. ; 48:3, s. 800-807
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose The relentless rise in antimicrobial resistance is a major societal challenge and requires, as part of its solution, a better understanding of bacterial colonization and infection. To facilitate this, we developed a highly efficient no-wash red optical molecular imaging agent that enables the rapid, selective, and specific visualization of Gram-positive bacteria through a bespoke optical fiber-based delivery/imaging endoscopic device. Methods We rationally designed a no-wash, red, Gram-positive-specific molecular imaging agent (Merocy-Van) based on vancomycin and an environmental merocyanine dye. We demonstrated the specificity and utility of the imaging agent in escalating in vitro and ex vivo whole human lung models (n = 3), utilizing a bespoke fiber-based delivery and imaging device, coupled to a wide-field, two-color endomicroscopy system. Results The imaging agent (Merocy-Van) was specific to Gram-positive bacteria and enabled no-wash imaging ofS. aureuswithin the alveolar space of whole ex vivo human lungs within 60 s of delivery into the field-of-view, using the novel imaging/delivery endomicroscopy device. Conclusion This platform enables the rapid and specific detection of Gram-positive bacteria in the human lung.
  •  
50.
  • Murphy, Laurel E., et al. (författare)
  • Folate and vitamin B-12 in idiopathic male infertility
  • 2011
  • Ingår i: Asian Journal of Andrology. - : Medknow. - 1008-682X .- 1745-7262. ; 13:6, s. 856-861
  • Tidskriftsartikel (refereegranskat)abstract
    • Although methylenetetrahydrofolate reductase, a folate enzyme gene, has been associated with idiopathic male infertility, few studies have examined other folate-related metabolites and genes. We investigated whether idiopathic male infertility is associated with variants in folate, vitamin B-12 (B12) and total homocysteine (tHcy)-related genes and measured these metabolites in blood. We conducted a case-control study that included 153 men with idiopathic infertility and 184 fertile male controls recruited at the Fertility Center and Antenatal Care Center, University Hospital, Malmo and Lund, Sweden. Serum folate, red cell folate (RCF), serum B12, plasma tHcy and semen quality were measured. Subjects were genotyped for 20 common variants in 12 genes related to folate/B12/homocysteine metabolism. Metabolite concentrations and genotype distributions were compared between cases and controls using linear and logistic regression with adjustment for covariates. The phosphatidylethanolamine N-methyltransferase (PEMT) M175V and TCblR rs173665 polymorphisms were significantly associated with infertility (P=0.01 and P=0.009, respectively), but not with semen quality. Among non-users of supplements, infertile men had lower serum folate concentrations than fertile men (12.89 vs. 14.73 nmol l(-1); P=0.02), but there were no significant differences in RCF, B12 or tHcy. Folate, B12 and tHcy concentrations were not correlated with any semen parameters. This study provides little support for low folate or B12 status in the pathogenesis of idiopathic male infertility. Although additional data are needed to confirm these initial findings, our results suggest that PEMT and TCblR, genes involved in choline and B12 metabolism, merit further investigation in idiopathic male infertility. Asian Journal of Andrology (2011) 13, 856-861; doi: 10.1038/aja.2011.96; published online 22 August 2011
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