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1.
  • 2017
  • swepub:Mat__t
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2.
  • Aad, G, et al. (författare)
  • 2015
  • swepub:Mat__t
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4.
  • Achberger, Christine, 1968, et al. (författare)
  • State of the Climate in 2011
  • 2012
  • Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 93:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large-scale climate patterns influenced temperature and weather patterns around the globe in 2011. In particular, a moderate-to-strong La Nina at the beginning of the year dissipated during boreal spring but reemerged during fall. The phenomenon contributed to historical droughts in East Africa, the southern United States, and northern Mexico, as well the wettest two-year period (2010-11) on record for Australia, particularly remarkable as this follows a decade-long dry period. Precipitation patterns in South America were also influenced by La Nina. Heavy rain in Rio de Janeiro in January triggered the country's worst floods and landslides in Brazil's history. The 2011 combined average temperature across global land and ocean surfaces was the coolest since 2008, but was also among the 15 warmest years on record and above the 1981-2010 average. The global sea surface temperature cooled by 0.1 degrees C from 2010 to 2011, associated with cooling influences of La Nina. Global integrals of upper ocean heat content for 2011 were higher than for all prior years, demonstrating the Earth's dominant role of the oceans in the Earth's energy budget. In the upper atmosphere, tropical stratospheric temperatures were anomalously warm, while polar temperatures were anomalously cold. This led to large springtime stratospheric ozone reductions in polar latitudes in both hemispheres. Ozone concentrations in the Arctic stratosphere during March were the lowest for that period since satellite records began in 1979. An extensive, deep, and persistent ozone hole over the Antarctic in September indicates that the recovery to pre-1980 conditions is proceeding very slowly. Atmospheric carbon dioxide concentrations increased by 2.10 ppm in 2011, and exceeded 390 ppm for the first time since instrumental records began. Other greenhouse gases also continued to rise in concentration and the combined effect now represents a 30% increase in radiative forcing over a 1990 baseline. Most ozone depleting substances continued to fall. The global net ocean carbon dioxide uptake for the 2010 transition period from El Nino to La Nina, the most recent period for which analyzed data are available, was estimated to be 1.30 Pg C yr(-1), almost 12% below the 29-year long-term average. Relative to the long-term trend, global sea level dropped noticeably in mid-2010 and reached a local minimum in 2011. The drop has been linked to the La Nina conditions that prevailed throughout much of 2010-11. Global sea level increased sharply during the second half of 2011. Global tropical cyclone activity during 2011 was well-below average, with a total of 74 storms compared with the 1981-2010 average of 89. Similar to 2010, the North Atlantic was the only basin that experienced above-normal activity. For the first year since the widespread introduction of the Dvorak intensity-estimation method in the 1980s, only three tropical cyclones reached Category 5 intensity level-all in the Northwest Pacific basin. The Arctic continued to warm at about twice the rate compared with lower latitudes. Below-normal summer snowfall, a decreasing trend in surface albedo, and above-average surface and upper air temperatures resulted in a continued pattern of extreme surface melting, and net snow and ice loss on the Greenland ice sheet. Warmer-than-normal temperatures over the Eurasian Arctic in spring resulted in a new record-low June snow cover extent and spring snow cover duration in this region. In the Canadian Arctic, the mass loss from glaciers and ice caps was the greatest since GRACE measurements began in 2002, continuing a negative trend that began in 1987. New record high temperatures occurred at 20 m below the land surface at all permafrost observatories on the North Slope of Alaska, where measurements began in the late 1970s. Arctic sea ice extent in September 2011 was the second-lowest on record, while the extent of old ice (four and five years) reached a new record minimum that was just 19% of normal. On the opposite pole, austral winter and spring temperatures were more than 3 degrees C above normal over much of the Antarctic continent. However, winter temperatures were below normal in the northern Antarctic Peninsula, which continued the downward trend there during the last 15 years. In summer, an all-time record high temperature of -12.3 degrees C was set at the South Pole station on 25 December, exceeding the previous record by more than a full degree. Antarctic sea ice extent anomalies increased steadily through much of the year, from briefly setting a record low in April, to well above average in December. The latter trend reflects the dispersive effects of low pressure on sea ice and the generally cool conditions around the Antarctic perimeter.
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5.
  • Mullins, N., et al. (författare)
  • Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
  • 2021
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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  • Fomalont, E. B., et al. (författare)
  • THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
  • 2015
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
  • Tidskriftsartikel (refereegranskat)abstract
    • A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
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8.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • Tidskriftsartikel (refereegranskat)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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  • Jonsson, Lina, 1982, et al. (författare)
  • Characterisation of age and polarity at onset in bipolar disorder
  • 2021
  • Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 219:6, s. 659-669
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (beta = -0.34 years, s.e. = 0.08), major depression (beta = -0.34 years, s.e. = 0.08), schizophrenia (beta = -0.39 years, s.e. = 0.08), and educational attainment (beta = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
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  • Arndt, D. S., et al. (författare)
  • State of the Climate in 2016
  • 2017
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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12.
  • Bethlehem, RAI, et al. (författare)
  • Brain charts for the human lifespan
  • 2022
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:7906, s. 525-
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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15.
  • Blunden, Jessica, et al. (författare)
  • State of the Climate in 2012
  • 2013
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
  • Tidskriftsartikel (refereegranskat)abstract
    • For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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16.
  • Ekelund, U., et al. (författare)
  • Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women : the EPIC-InterAct Study
  • 2012
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 55:7, s. 1944-1952
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined the independent and combined associations of physical activity and obesity with incident type 2 diabetes in men and women. The InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a randomly selected subcohort of 16,154 individuals, drawn from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Physical activity was assessed by a four-category index. Obesity was measured by BMI and waist circumference (WC). Associations between physical activity, obesity and case-ascertained incident type 2 diabetes were analysed by Cox regression after adjusting for educational level, smoking status, alcohol consumption and energy intake. In combined analyses, individuals were stratified according to physical activity level, BMI and WC. A one-category difference in physical activity (equivalent to approximately 460 and 365 kJ/day in men and women, respectively) was independently associated with a 13% (HR 0.87, 95% CI 0.80, 0.94) and 7% (HR 0.93, 95% CI 0.89, 0.98) relative reduction in the risk of type 2 diabetes in men and women, respectively. Lower levels of physical activity were associated with an increased risk of diabetes across all strata of BMI. Comparing inactive with active individuals, the HRs were 1.44 (95% CI 1.11, 1.87) and 1.38 (95% CI 1.17, 1.62) in abdominally lean and obese inactive men, respectively, and 1.57 (95% CI 1.19, 2.07) and 1.19 (95% CI 1.01, 1.39) in abdominally lean and obese inactive women, respectively. Physical activity is associated with a reduction in the risk of developing type 2 diabetes across BMI categories in men and women, as well as in abdominally lean and obese men and women.
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  • Besson, H., et al. (författare)
  • A cross-sectional analysis of physical activity and obesity indicators in European participants of the EPIC-PANACEA study
  • 2009
  • Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 33:4, s. 497-506
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Cross-sectional data suggest a strong association between low levels of physical activity and obesity. The EPIC-PANACEA ( European Prospective Investigation into Cancer-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of home And obesity) project was designed to investigate the associations between physical activity and body mass index (BMI) and waist circumference based on individual data collected across nine European countries. Methods: In the European Prospective Investigation into Cancer and Nutrition ( EPIC), 519 931 volunteers were recruited between 1992 and 2000, of whom 405 819 had data on main variables of interest. Height, body weight and waist circumference were measured using standardized procedures. Physical activity was assessed using a validated four-category index reflecting a self-reported usual activity during work and leisure time. The associations between physical activity and BMI and waist circumference were estimated using multilevel mixed effects linear regression models, adjusted for age, total energy intake, smoking status, alcohol consumption and educational level. Results: A total of 125 629 men and 280 190 women with a mean age of 52.9 (s.d. 9.7) and 51.5 (s.d. 10.0) years, respectively were included. The mean BMI was 26.6 kg/m(2) (s.d. 3.6) in men and 25.0 kg/m(2) (s.d. 4.5) in women. Fifty percent of men and 30% of women were categorized as being active or moderately active. A one-category difference in the physical activity index was inversely associated with a difference of 0.18 kg/m(2) in the mean BMI (95% confidence interval, CI, 0.11, 0.24) and 1.04-cm (95% CI 0.82, 1.26) difference in waist circumference in men. The equivalent figures for women were 0.31 kg/m(2) (95% CI 0.23, 0.38) and 0.90 cm ( 95% CI 0.71, 1.08), respectively. Conclusions: Physical activity is inversely associated with both BMI and waist circumference across nine European countries. Although we cannot interpret the association causally, our results were observed in a large and diverse cohort independently from many potential confounders.
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18.
  • Cooper, A. J., et al. (författare)
  • Fruit and vegetable intake and type 2 diabetes : EPIC-InterAct prospective study and meta-analysis
  • 2012
  • Ingår i: European Journal of Clinical Nutrition. - London : Nature Publishing Group. - 0954-3007 .- 1476-5640. ; 66:10, s. 1082-1092
  • Forskningsöversikt (refereegranskat)abstract
    • Fruit and vegetable intake (FVI) may reduce the risk of type 2 diabetes (T2D), but the epidemiological evidence is inconclusive. The aim of this study is to examine the prospective association of FVI with T2D and conduct an updated meta-analysis. In the European Prospective Investigation into Cancer-InterAct (EPIC-InterAct) prospective case-cohort study nested within eight European countries, a representative sample of 16 154 participants and 12 403 incident cases of T2D were identified from 340 234 individuals with 3.99 million person-years of follow-up. For the meta-analysis we identified prospective studies on FVI and T2D risk by systematic searches of MEDLINE and EMBASE until April 2011. In EPIC-InterAct, estimated FVI by dietary questionnaires varied more than twofold between countries. In adjusted analyses the hazard ratio (95% confidence interval) comparing the highest with lowest quartile of reported intake was 0.90 (0.80-1.01) for FVI; 0.89 (0.76-1.04) for fruit and 0.94 (0.84-1.05) for vegetables. Among FV subtypes, only root vegetables were inversely associated with diabetes 0.87 (0.77-0.99). In meta-analysis using pooled data from five studies including EPIC-InterAct, comparing the highest with lowest category for FVI was associated with a lower relative risk of diabetes (0.93 (0.87-1.00)). Fruit or vegetables separately were not associated with diabetes. Among FV subtypes, only green leafy vegetable (GLV) intake (relative risk: 0.84 (0.74-0.94)) was inversely associated with diabetes. Subtypes of vegetables, such as root vegetables or GLVs may be beneficial for the prevention of diabetes, while total FVI may exert a weaker overall effect.
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22.
  • Langenberg, C., et al. (författare)
  • Design and cohort description of the InterAct Project : an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC Study
  • 2011
  • Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 54:9, s. 2272-2282
  • Tidskriftsartikel (refereegranskat)abstract
    • Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This case-cohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prentice-weighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n = 778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age. InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.
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  • Tedersoo, L., et al. (författare)
  • The Global Soil Mycobiome consortium dataset for boosting fungal diversity research
  • 2021
  • Ingår i: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 111, s. 573-588
  • Tidskriftsartikel (refereegranskat)abstract
    • Fungi are highly important biotic components of terrestrial ecosystems, but we still have a very limited understanding about their diversity and distribution. This data article releases a global soil fungal dataset of the Global Soil Mycobiome consortium (GSMc) to boost further research in fungal diversity, biogeography and macroecology. The dataset comprises 722,682 fungal operational taxonomic units (OTUs) derived from PacBio sequencing of full-length ITS and 18S-V9 variable regions from 3200 plots in 108 countries on all continents. The plots are supplied with geographical and edaphic metadata. The OTUs are taxonomically and functionally assigned to guilds and other functional groups. The entire dataset has been corrected by excluding chimeras, index-switch artefacts and potential contamination. The dataset is more inclusive in terms of geographical breadth and phylogenetic diversity of fungi than previously published data. The GSMc dataset is available over the PlutoF repository.
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26.
  • Abbas, S., et al. (författare)
  • Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study
  • 2014
  • Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 68:2, s. 196-202
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/OBJECTIVES: Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation. SUBJECTS/METHODS: Using a case-cohort design, 11 245 incident cases of type 2 diabetes and a representative subcohort (N = 15 798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N = 2347) were used to calibrate habitual intake data derived from dietary questionnaires. RESULTS: Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (P-trend = 0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 mg/day dietary vitamin D. CONCLUSIONS: This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.
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27.
  • Andreoni, I., et al. (författare)
  • Follow Up of GW170817 and Its Electromagnetic Counterpart by Australian-Led Observing Programmes
  • 2017
  • Ingår i: Publications Astronomical Society of Australia. - : Cambridge University Press (CUP). - 1323-3580 .- 1448-6083. ; 34
  • Forskningsöversikt (refereegranskat)abstract
    • The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (similar to 2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
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28.
  • Arndt, D. S., et al. (författare)
  • STATE OF THE CLIMATE IN 2017
  • 2018
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
  • Forskningsöversikt (refereegranskat)
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29.
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30.
  • Bendinelli, B., et al. (författare)
  • Association between dietary meat consumption and incident type 2 diabetes : the EPIC-InterAct study
  • 2013
  • Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 56:1, s. 47-59
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption.Results: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants.Conclusions/interpretation: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.
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31.
  • Beulens, J. W. J., et al. (författare)
  • Alcohol consumption and risk of type 2 diabetes in European men and women : influence of beverage type and body size The EPIC-InterAct study
  • 2012
  • Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 272:4, s. 358-370
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type. Design: Multicentre prospective casecohort study. Setting: Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort. Subjects: A representative baseline sample of 16 154 participants and 12 403 incident cases of type 2 diabetes. Interventions: Alcohol consumption assessed using validated dietary questionnaires. Main outcome measures: Occurrence of type 2 diabetes based on multiple sources (mainly self-reports), verified against medical information. Results: Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.781.05) for 6.112.0 versus 0.16.0 g day-1, adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.196.0 g day-1 with an HR of 0.86 (95% CI: 0.750.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.720.92) for 6.112.0 g day-1 (P interaction gender <0.01). The inverse association between alcohol consumption and diabetes was more pronounced amongst overweight (BMI = 25 kg m-2) than normal-weight men and women (P interaction < 0.05). Adjusting for waist and hip circumference did not alter the results for men, but attenuated the association for women (HR=0.90, 95% CI: 0.791.03 for 6.112.0 g day-1). Wine consumption for men and fortified wine  consumption for women were most strongly associated with a reduced risk of diabetes. Conclusions: The results of this study show that moderate alcohol consumption is associated with a lower risk of type 2 diabetes amongst women only. However, this risk reduction is in part explained by fat distribution. The relation between alcohol consumption and type 2 diabetes was stronger for overweight than normal-weight women and men.
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32.
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33.
  • Graham, N. S. N., et al. (författare)
  • Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury
  • 2021
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:613
  • Tidskriftsartikel (refereegranskat)abstract
    • Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication.
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34.
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35.
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36.
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37.
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38.
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39.
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40.
  • Pfaller, M.A., et al. (författare)
  • Twelve years of fluconazole in clinical practice : Global-trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida
  • 2004
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 10:SUPPL. 1, s. 11-23
  • Tidskriftsartikel (refereegranskat)abstract
    • We determined the species distribution and in-vitro susceptibility of 6082 bloodstream infection (BSI) isolates of Candida spp. collected from 250 medical centres in 32 nations over a 10-year period from 1992 through 2001. The species included 3401 C. albicans, 984 C. glabrata, 796 C. parapsilosis, 585 C. tropicalis, 153 C. krusei, 67 C. lusitaniae, 48 C. guilliermondii, 10 C. famata, 10 C. kefyr, six C. pelliculosa, five C. rugosa, four C. lipolytica, three C. dubliniensis, three C. inconspicua, two C. sake and one isolate each of C. lambica, C. norvegensis and C. zeylanoides. Minimum inhibitory concentration determinations were made using the National Committee for Clinical Laboratory Standards reference broth microdilution method. Variation in the rank order and frequency of the different species of Candida was observed over time and by geographic area. The proportion of BSI due to C. albicans and C. glabrata increased and C. parapsilosis decreased over time in Canada, the USA and Europe. C. glabrata was an infrequent cause of BSI in Latin America and the Asia-Pacific region. Very little variation in fluconazole susceptibility was observed among isolates of C. albicans, C. tropicalis and C. parapsilosis. These species accounted for 78% of all BSI and remained highly susceptible (91-100% susceptible) to fluconazole from 1992 to 2001 irrespective of geographic origin. The prevalence of fluconazole resistance among C. glabrata isolates was variable both over time and among the various countries and regions. Resistance to fluconazole among C. glabrata isolates was greatest in the USA and varied by US census region (range 0-23%). These observations are generally encouraging relative to the sustained usefulness of fluconazole as a systemically active antifungal agent for the treatment of candida BSI. © 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases.
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41.
  • Pfeffer, W. Tad, et al. (författare)
  • The Randolph Glacier Inventory : a globally complete inventory of glaciers
  • 2014
  • Ingår i: Journal of Glaciology. - 0022-1430 .- 1727-5652. ; 60:221, s. 537-552
  • Tidskriftsartikel (refereegranskat)abstract
    • The Randolph Glacier Inventory (RGI) is a globally complete collection of digital outlines of glaciers, excluding the ice sheets, developed to meet the needs of the Fifth Assessment of the Intergovernmental Panel on Climate Change for estimates of past and future mass balance. The RGI was created with limited resources in a short period. Priority was given to completeness of coverage, but a limited, uniform set of attributes is attached to each of the similar to 198 000 glaciers in its latest version, 3.2. Satellite imagery from 1999-2010 provided most of the outlines. Their total extent is estimated as 726 800 +/- 34 000 km(2). The uncertainty, about +/- 5%, is derived from careful single-glacier and basin-scale uncertainty estimates and comparisons with inventories that were not sources for the RGI. The main contributors to uncertainty are probably misinterpretation of seasonal snow cover and debris cover. These errors appear not to be normally distributed, and quantifying them reliably is an unsolved problem. Combined with digital elevation models, the RGI glacier outlines yield hypsometries that can be combined with atmospheric data or model outputs for analysis of the impacts of climatic change on glaciers. The RGI has already proved its value in the generation of significantly improved aggregate estimates of glacier mass changes and total volume, and thus actual and potential contributions to sea-level rise.
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42.
  • Romaguera, D., et al. (författare)
  • Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct
  • 2013
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 56:7, s. 1520-1530
  • Tidskriftsartikel (refereegranskat)abstract
    • Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults. We established a case-cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case-cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence. In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence. This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults.
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43.
  • Saxena, Richa, et al. (författare)
  • Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 142-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18).
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44.
  • Threlfell, S., et al. (författare)
  • Striatal Dopamine Transporter Function Is Facilitated by Converging Biology of alpha-Synuclein and Cholesterol
  • 2021
  • Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Striatal dopamine transporters (DAT) powerfully regulate dopamine signaling, and can contribute risk to degeneration in Parkinson's disease (PD). DATs can interact with the neuronal protein alpha-synuclein, which is associated with the etiology and molecular pathology of idiopathic and familial PD. Here, we tested whether DAT function in governing dopamine (DA) uptake and release is modified in a human-alpha-synuclein-overexpressing (SNCA-OVX) transgenic mouse model of early PD. Using fast-scan cyclic voltammetry (FCV) in ex vivo acute striatal slices to detect DA release, and biochemical assays, we show that several aspects of DAT function are promoted in SNCA-OVX mice. Compared to background control alpha-synuclein-null mice (Snca-null), the SNCA-OVX mice have elevated DA uptake rates, and more pronounced effects of DAT inhibitors on evoked extracellular DA concentrations ([DA](o)) and on short-term plasticity (STP) in DA release, indicating DATs play a greater role in limiting DA release and in driving STP. We found that DAT membrane levels and radioligand binding sites correlated with alpha-synuclein level. Furthermore, DAT function in Snca-null and SNCA-OVX mice could also be promoted by applying cholesterol, and using Tof-SIMS we found genotype-differences in striatal lipids, with lower striatal cholesterol in SNCA-OVX mice. An inhibitor of cholesterol efflux transporter ABCA1 or a cholesterol chelator in SNCA-OVX mice reduced the effects of DAT-inhibitors on evoked [DA](o). Together these data indicate that human alpha-synuclein in a mouse model of PD promotes striatal DAT function, in a manner supported by extracellular cholesterol, suggesting converging biology of alpha-synuclein and cholesterol that regulates DAT function and could impact DA function and PD pathophysiology.
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45.
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46.
  • Underwood, J, et al. (författare)
  • Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
  • 2019
  • Ingår i: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P &lt; .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P &lt; .05), as well as smaller brain volumes (P &lt; .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
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47.
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48.
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49.
  • Buijsse, B, et al. (författare)
  • Consumption of fatty foods and incident type 2 diabetes in populations from eight European countries.
  • 2015
  • Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 69:4, s. 455-461
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Objectives:Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes (T2D) risk, but studies on foods high in fat per unit weight are sparse. We assessed whether the intake of vegetable oil, butter, margarine, nuts and seeds and cakes and cookies is related to incident T2D.Subjects/Methods:A case-cohort study was conducted, nested within eight countries of the European Prospective Investigation into Cancer (EPIC), with 12 403 incident T2D cases and a subcohort of 16 835 people, identified from a cohort of 340 234 people. Diet was assessed at baseline (1991-1999) by country-specific questionnaires. Country-specific hazard ratios (HRs) across four categories of fatty foods (nonconsumers and tertiles among consumers) were combined with random-effects meta-analysis.Results:After adjustment not including body mass index (BMI), nonconsumers of butter, nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption. Among consumers, cakes and cookies were inversely related to T2D (HRs across increasing tertiles 1.14, 1.00 and 0.92, respectively; P-trend <0.0001). All these associations attenuated upon adjustment for BMI, except the higher risk of nonconsumers of cakes and cookies (HR 1.57). Higher consumption of margarine became positively associated after BMI adjustment (HRs across increasing consumption tertiles: 0.93, 1.00 and 1.12; P-trend 0.03). Within consumers, vegetable oil, butter and nuts and seeds were unrelated to T2D.Conclusions:Fatty foods were generally not associated with T2D, apart from weak positive association for margarine. The higher risk among nonconsumers of cakes and cookies needs further explanation.European Journal of Clinical Nutrition advance online publication, 26 November 2014; doi:10.1038/ejcn.2014.249.
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50.
  • Gorgoraptis, N., et al. (författare)
  • In vivo detection of cerebral tau pathology in long-term survivors of traumatic brain injury
  • 2019
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 11:508
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic brain injury (TBI) can trigger progressive neurodegeneration, with tau pathology seen years after a single moderate-severe TBI. Identifying this type of posttraumatic pathology in vivo might help to understand the role of tau pathology in TBI pathophysiology. We used flortaucipir positron emission tomography (PET) to investigate whether tau pathology is present many years after a single TBI in humans. We examined PET data in relation to markers of neurodegeneration in the cerebrospinal fluid (CSF), structural magnetic resonance imaging measures, and cognitive performance. Cerebral flortaucipir binding was variable, with many participants with TBI showing increases in cortical and white matter regions. At the group level, flortaucipir binding was increased in the right occipital cortex in TBI when compared to healthy controls. Flortaucipir binding was associated with increased total tau, phosphorylated tau, and ubiquitin carboxyl-terminal hydrolase L1 CSF concentrations, as well as with reduced fractional anisotropy and white matter tissue density in TBI. Apolipoprotein E (APOE) epsilon 4 genotype affected the relationship between flortaucipir binding and time since injury, CSF beta amyloid 1-42 (A beta 42) concentration, white matter tissue density, and longitudinal Mini-Mental State Examination scores in TBI. The results demonstrate that tau PET is a promising approach to investigating progressive neurodegeneration associated with tauopathy after TBI.
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