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1.
  • Lind, Lars, et al. (författare)
  • Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
  • 2021
  • Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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  • Bixby, H., et al. (författare)
  • Rising rural body-mass index is the main driver of the global obesity epidemic in adults
  • 2019
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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3.
  • Mishra, A, et al. (författare)
  • Diminishing benefits of urban living for children and adolescents' growth and development
  • 2023
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
  • Tidskriftsartikel (refereegranskat)abstract
    • Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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  • Taddei, C, et al. (författare)
  • Repositioning of the global epicentre of non-optimal cholesterol
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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15.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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16.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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18.
  • Andrés, E. C., et al. (författare)
  • The AMANDA neutrino telescope
  • 1999
  • Ingår i: Nuclear physics B, Proceedings supplements. - 0920-5632 .- 1873-3832. ; 77:1-3, s. 474-485
  • Tidskriftsartikel (refereegranskat)abstract
    • With an effective telescope area of order 104 m2 for TeV neutrinos, a threshold near ∼50 GeV and a pointing accuracy of 2.5 degrees per muon track, the AMANDA detector represents the first of a new generation of high energy neutrino telescopes, reaching a scale envisaged over 25 years ago. We describe early results on the calibration of natural deep ice as a particle detector as well as on AMANDA's performance as a neutrino telescope.
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19.
  • Andrés, E., et al. (författare)
  • Observation of high-energy neutrinos using Čerenkov detectors embedded deep in Antarctic ice
  • 2001
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 410:6827, s. 441-443
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova2, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water3,4 or ice5. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations1.
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20.
  • Andrés, E., et al. (författare)
  • Recent results from AMANDA
  • 2001
  • Ingår i: International Journal of Modern Physics A. - 0217-751X .- 1793-656X. ; 16:1C, s. 1013-1015
  • Tidskriftsartikel (refereegranskat)abstract
    • We present results based on data taken in 1997 with the 302-PMT Antarctic Muon and Neutrino Detector Array-B10 ("AMANDA-B10") array. Atmospheric neutrinos created in the northern hemisphere are observed indirectly through their charged current interactions which produce relativistic, Cherenkov-light-emitting upgoing muons in the South Pole ice cap. The reconstructed angular distribution of these events is in good agreement with expectation and demonstrates the viability of this ice-based device as a neutrino telescope.
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21.
  • Andres, E., et al. (författare)
  • Results from the AMANDA high energy neutrino detector
  • 2000
  • Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 91:1-3, s. 423-430
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper briefly summarizes the search for astronomical sources of high-energy neutrinos using the AMANDA-B10 detector. The complete data set from 1997 was analyzed. For Eμ > 10 TeV, the detector exceeds 10,000 m2 in effective area between declinations of 25 and 90 degrees. Neutrinos generated in the atmosphere by cosmic ray interactions were used to verify the overall sensitivity of the detector. The absolute pointing accuracy and angular resolution has been confirmed by the analysis of coincident events between the SPASE air shower array and the AMANDA detector. Preliminary flux limits from point source candidates are presented. For declinations larger than +45 degrees, our results compare favorably to existing limits for sources in the Southern sky. We also present the current status of the searches for high energy neutrino emission from diffusely distributed sources, GRBs, and WIMPs from the center of the earth.
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22.
  • Andres, E., et al. (författare)
  • Selected recent results from AMANDA
  • 2001
  • Ingår i: ICHEP 2000. Proceedings of the 30th International Conference on High Energy Physics. - : World Scientific. ; , s. 965-968
  • Konferensbidrag (refereegranskat)abstract
    • We present a selection of results based on data taken in 1997 with the 302-PMT Antarctic Muon and Neutrino Detector Array-B10 ("AMANDA-B10") array. Atmospheric neutrinos created in the northern hemisphere are observed indirectly through their charged current interactions which produce relativistic, Cherenkov-light-emitting upgoing muons in the South Pole ice cap. The reconstructed angular distribution of these events is in good agreement with expectation and demonstrates the viability of this ice-based device as a neutrino telescope. Studies of nearly vertical upgoing muons limit the available parameter space for WIMP dark matter under the assumption that WIMPS are trapped in the earth's gravitational potential well and annihilate with one another near the earth's center.
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23.
  • Bai, X., et al. (författare)
  • Status of the Neutrino Telescope AMANDA : Monopoles and WIMPS
  • 2001
  • Ingår i: Dark Matter in Astro- and Particle Physics. - Berlin, Heidelberg : Springer. - 9783642626081 ; , s. 699-706
  • Konferensbidrag (refereegranskat)abstract
    • The neutrino telescope AMANDA has been set up at the geographical South Pole as first step to a neutrino telescope of the scale of one cubic kilometer, which is the canonical size for a detector sensitive to neutrinos from Active Galactic Nuclei (AGN), Gamma Ray Bursts (GRB) and Topological Defects (TD). The location and depth in which the detector is installed is given by the requirement to detect neutrinos by the Cherenkov light produced by their reaction products and to keep the background due to atmospheric muons as small as possible. However, a detector optimized for this purpose is also capable to detect the bright Cherenkov light from relativistic Monopoles and neutrino signals from regions with high gravitational potential, where WIMPS are accumulated and possibly annihilate. Both hypothetical particles might contribute to the amount of dark matter. Therefore here a report about the status of the experiment (autumn 2000) and about the status of the search for these particles with the AMANDA B10 sub-detector is given.
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27.
  • Edsjö, Joakim, et al. (författare)
  • WIMP searches with AMANDA-B10
  • 2001
  • Ingår i: The Identification Of Dark Matter. - : World Scientific. - 9789810246020 ; , s. 499-505
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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28.
  • Gaudet, Mia M., et al. (författare)
  • Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
  • 2010
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
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29.
  • Horvath, I., et al. (författare)
  • Exhaled breath condensate: methodological recommendations and unresolved questions
  • 2005
  • Ingår i: Eur Respir J. ; 26:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.
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30.
  • Karle, A., et al. (författare)
  • Observation of high energy atmospheric neutrinos with AMANDA
  • 2000
  • Ingår i: AIP Conference Proceedings. - : American Institute of Physics (AIP). ; , s. 823-827
  • Konferensbidrag (refereegranskat)abstract
    • In 1997 the Antarctic Muon and Neutrino Detector Array (AMANDA) started operating with 10 strings. In an analysis of data taken during the first year of operation 188 atmospheric neutrino candidates were found. Their zenith angle distribution agrees with expectations based on Monte Carlo simulations. A preliminary upper limit is given on a diffuse flux of high energy neutrinos of astrophysical origin.
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  • Rubinstein, TA, et al. (författare)
  • A Transgenic Model Reveals the Role of Klotho in Pancreatic Cancer Development and Paves the Way for New Klotho-Based Therapy
  • 2021
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Klotho is an anti-aging transmembrane protein, which can be shed and can function as a hormone. Accumulating data indicate that klotho is a tumor suppressor in a wide array of malignancies, and designate the subdomain KL1 as the active region of the protein towards this activity. We aimed to study the role of klotho as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Bioinformatics analyses of The Cancer Genome Atlas (TCGA) datasets revealed a correlation between the survival of PDAC patients, levels of klotho expression, and DNA methylation, and demonstrated a unique hypermethylation pattern of klotho in pancreatic tumors. The in vivo effects of klotho and KL1 were examined using three mouse models. Employing a novel genetic model, combining pancreatic klotho knockdown with a mutation in Kras, the lack of klotho contributed to PDAC generation and decreased mousece survival. In a xenograft model, administration of viral particles carrying sKL, a spliced klotho isoform containing the KL1 domain, inhibited pancreatic tumors. Lastly, treatment with soluble sKL prolonged survival of Pdx1-Cre; KrasG12D/+;Trp53R172H/+ (KPC) mice, a model known to recapitulate human PDAC. In conclusion, this study provides evidence that klotho is a tumor suppressor in PDAC. Furthermore, these data suggest that the levels of klotho expression and DNA methylation could have prognostic value in PDAC patients, and that administration of exogenous sKL may serve as a novel therapeutic strategy to treat PDAC.
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34.
  • Wischnewski, R., et al. (författare)
  • The AMANDA neutrino detector : Status report
  • 2000
  • Ingår i: Nuclear physics B, Proceedings supplements. - 0920-5632 .- 1873-3832. ; 85:1-3, s. 141-145
  • Tidskriftsartikel (refereegranskat)abstract
    • The first stage of the AMANDA High Energy Neutrino Detector at the South Pole, the 302 PMT array AMANDA-B10, is taking data since 1997. We describe results on atmospheric neutrinos, limits on indirect WIMP detection, seasonal muon flux variation, relativistic monopole flux limits, a search for gravitational collapse neutrinos, and a depth scan of the optical ice properties. The next stage 19-string detector AMANDA-II with ∼650 PMTs will be completed in spring 2000.
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35.
  • Akimov, D., et al. (författare)
  • Physics with WASA and PROMICE
  • 1994
  • Ingår i: Physics with GeV-particle beams, Juelich 1994. ; , s. 519-530
  • Konferensbidrag (refereegranskat)
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36.
  • Andrés, E., et al. (författare)
  • Status of the AMANDA experiment
  • 1999
  • Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 70:1-3, s. 448-452
  • Tidskriftsartikel (refereegranskat)abstract
    • The AMANDA high energy neutrino telescope has successfully been increased in size from four detector strings to ten detector strings during the 1996/1997 season. The first upward going muon-neutrino candidates have been reconstructed from the 1996 year's four-string data. Three new detector strings will be deployed during 1997/1998 to 2350 metres depth.
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37.
  • Andres, E., et al. (författare)
  • The AMANDA neutrino telescope : Principle of operation and first results
  • 2000
  • Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 13:1, s. 1-20
  • Tidskriftsartikel (refereegranskat)abstract
    • AMANDA is a high-energy neutrino telescope presently under construction at the geographical South Pole. In the Antarctic summer 1995/96, an array of 80 optical modules (OMs) arranged on 4 strings (AMANDA-B4) was deployed at depths between 1.5 and 2 km. In this paper we describe the design and performance of the AMANDA-B4 prototype, based on data collected between February and November 1996. Monte Carlo simulations of the detector response to down-going atmospheric muon tracks show that the global behavior of the detector is understood. We describe the data analysis method and present first results on atmospheric muon reconstruction and separation of neutrino candidates. The AMANDA array was upgraded with 216 OMs on 6 new strings in 1996/97 (AMANDA-B10), and 122 additional OMs on 3 strings in 1997/98.
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38.
  • Antoniou, Antonis C., et al. (författare)
  • A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
  • Tidskriftsartikel (refereegranskat)abstract
    • Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
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39.
  • Askebjer, P., et al. (författare)
  • AMANDA : status report from the 1993-94 campaign and optical properties of the South Pole ice
  • 1995
  • Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 38:1-3, s. 287-292
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the first results of the AMANDA detector. During the antarctic summer 1993-94 four strings were deployed between 0.8 an 1 km depth, each equipped with 20 photomultiplier tubes (PMTs). A laser source was used to investigate the optical properties of the ice in situ. We find that the ice is intrinsically extremely transparent. The measured absorption length is 59 ± 3 m, i.e. comparable with the quality of the ultra-pure water used in the IMB and Kamiokande proton-decay and neutrino experiments [1,2] and more than two times longer than the best value reported for laboratory ice [3]. Due to a residual density of air bubbles at these depths, the motion of photons in the medium is randomized. For spherical, smooth bubbles we find that, at 1 km depth, the average distance between collisions is about 25 cm. The measured inverse scattering length on bubbles decreases linearly with increasing depth in the volume of ice investigated. © 1995 Elsevier Science B.V. All rights reserved.
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40.
  • Askebjer, P., et al. (författare)
  • On the age vs depth and optical clarity of deep ice at South Pole
  • 1995
  • Ingår i: Journal of Glaciology. - 0022-1430 .- 1727-5652. ; 41:139, s. 445-454
  • Tidskriftsartikel (refereegranskat)abstract
    • The first four strings of phototubes for the AMANDA high-energy neutrino observatory are now frozen in place at a depth of 800 to 1000 m in ice at the South Pole. During the 1995-96 season an additional six strings will be deployed at greater depths. Provided absorption, scattering, and refraction of visible light are sufficiently small, the trajectory of a muon into which a neutrino converts can be determined by using the array of phototubes to measure the arrival times of \v{C}erenkov light emitted by the muon. To help in deciding on the depth for implantation of the six new strings, we discuss models of age vs depth for South Pole ice, we estimate mean free paths for scattering from bubbles and dust as a function of depth, and we assess distortion of light paths due to refraction at crystal boundaries and interfaces between air-hydrate inclusions and normal ice. We conclude that the depth interval 1600 to 1800 m will be suitably transparent for the next six AMANDA strings and, moreover, that the interval 1600 to 2100 m will be suitably transparent for a future 1-km 3   observatory except possibly in a region a few tens of meters thick at a depth corresponding to a peak in the dust concentration at 60 kyr BP.
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41.
  • Askebjer, P., et al. (författare)
  • Optical properties of deep ice at the South Pole : Absorption
  • 1997
  • Ingår i: Applied Optics. - : Optical Society of America. - 0003-6935 .- 1539-4522. ; 36:18, s. 4168-4180
  • Tidskriftsartikel (refereegranskat)abstract
    • We discuss recent measurements of the wavelength-dependent absorption coefficients in deep South Pole ice. The method uses transit-time distributions of pulses from a variable-frequency laser sent between emitters and receivers embedded in the ice. At depths of 800-1000 m scattering is dominated by residual air bubbles, whereas absorption occurs both in ice itself and in insoluble impurities. The absorption coefficient increases approximately exponentially with wavelength in the measured interval 410-610 nm. At the shortest wavelength our value is approximately a factor 20 below previous values obtained for laboratory ice and lake ice; with increasing wavelength the discrepancy with previous measurements decreases. At ∼415 to ∼500 nm the experimental uncertainties are small enough for us to resolve an extrinsic contribution to absorption in ice: submicrometer dust particles contribute by an amount that increases with depth and corresponds well with the expected increase seen near the Last Glacial Maximum in Vostok and Dome C ice cores. The laser pulse method allows remote mapping of gross structure in dust concentration as a function of depth in glacial ice.
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42.
  • Askebjer, P., et al. (författare)
  • Optical properties of the South Pole ice at depths between 0.8 and 1 kilometer
  • 1995
  • Ingår i: Science. - 0036-8075 .- 1095-9203. ; 267:5201, s. 1147-1150
  • Tidskriftsartikel (refereegranskat)abstract
    • The optical properties of the ice at the geographical South Pole have been investigated at depths between 0.8 and 1 kilometer. The absorption and scattering lengths of visible light (∼515 nanometers) have been measured in situ with the use of the laser calibration setup of the Antarctic Muon and Neutrino Detector Array (AMANDA) neutrino detector. The ice is intrinsically extremely transparent. The measured absorption length is 59 ± 3 meters, comparable with the quality of the ultrapure water used in the Irvine-Michigan-Brookhaven and Kamiokande proton-decay and neutrino experiments and more than twice as long as the best value reported for laboratory ice. Because of a residual density of air bubbles at these depths, the trajectories of photons in the medium are randomized. If the bubbles are assumed to be smooth and spherical, the average distance between collisions at a depth of 1 kilometer is about 25 centimeters. The measured inverse scattering length on bubbles decreases linearly with increasing depth in the volume of ice investigated.
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43.
  • Askebjer, P., et al. (författare)
  • UV and optical light transmission properties in deep ice at the South Pole
  • 1997
  • Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 24:11, s. 1355-1358
  • Tidskriftsartikel (refereegranskat)abstract
    • Both absorption and scattering of light at wavelengths 410 to 610 nanometers were measured in the South Pole ice at depths 0.8 to 1 kilometer with the laser calibration system of the Antarctic Muon And Neutrino Detector Array (AMANDA). At the shortest wavelengths the absorption lengths exceeded 200 meters - an order of magnitude longer than has been reported for laboratory ice. The absorption shows a strong wavelength dependence while the scattering length is found to be independent of the wavelength, consistent with the hypothesis of a residual density of air bubbles in the ice. The observed linear decrease of the inverse scattering length with depth is compatible with an earlier measurement by the AMANDA collaboration (at ∼515 nanometers).
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44.
  •  
45.
  • Bay, R. C., et al. (författare)
  • The AMANDA neutrino telescope and the indirect search for dark matter : AMANDA Colaboration
  • 1998
  • Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 307:1-4, s. 243-252
  • Tidskriftsartikel (refereegranskat)abstract
    • With an effective telescope area of order 104m2, a threshold of ~50GeV and a pointing accuracy of 2.5°, the AMANDA detector represents the first of a new generation of high energy neutrino telescopes, reaching a scale envisaged over 25 years ago. We describe its performance, focussing on the capability to detect halo dark matter particles via their annihilation into neutrinos.
  •  
46.
  • Calen, H., et al. (författare)
  • Status of the CELSIUS and WASA projects
  • 1990
  • Ingår i: Gif-sur-Yvette 1990, Proceedings, Rare decays of light mesons. ; , s. 187-197
  • Konferensbidrag (refereegranskat)
  •  
47.
  • Danaei, Goodarz, et al. (författare)
  • Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
  • 2015
  • Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
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48.
  •  
49.
  • Di Trani, Justin M., et al. (författare)
  • Structural basis of mammalian complex IV inhibition by steroids
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
  • Tidskriftsartikel (refereegranskat)abstract
    • The mitochondrial electron transport chain maintains the proton motive force that powers adenosine triphosphate (ATP) synthesis. The energy for this process comes from oxidation of reduced nicotinamide adenine dinucleotide (NADH) and succinate, with the electrons from this oxidation passed via intermediate carriers to oxygen. Complex IV (CIV), the terminal oxidase, transfers electrons from the intermediate electron carrier cytochrome c to oxygen, contributing to the proton motive force in the process. Within CIV, protons move through the K and D pathways during turnover. The former is responsible for transferring two protons to the enzyme’s catalytic site upon its reduction, where they eventually combine with oxygen and electrons to form water. CIV is the main site for respiratory regulation, and although previous studies showed that steroid binding can regulate CIV activity, little is known about how this regulation occurs. Here, we characterize the interaction between CIV and steroids using a combination of kinetic experiments, structure determination, and molecular simulations. We show that molecules with a sterol moiety, such as glyco-diosgenin and cholesteryl hemisuccinate, reversibly inhibit CIV. Flash photolysis experiments probing the rapid equilibration of electrons within CIV demonstrate that binding of these molecules inhibits proton uptake through the K pathway. Single particle cryogenic electron microscopy (cryo-EM) of CIV with glyco-diosgenin reveals a previously undescribed steroid binding site adjacent to the K pathway, and molecular simulations suggest that the steroid binding modulates the conformational dynamics of key residues and proton transfer kinetics within this pathway. The binding pose of the sterol group sheds light on possible structural gating mechanisms in the CIV catalytic cycle.
  •  
50.
  • Ding, Yuan C, et al. (författare)
  • A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
  • 2012
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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