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1.
  • Niemi, MEK, et al. (author)
  • 2021
  • swepub:Mat__t
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2.
  • Kanai, M, et al. (author)
  • 2023
  • swepub:Mat__t
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3.
  • Schael, S, et al. (author)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • Research review (peer-reviewed)abstract
    • We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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4.
  • Wang, H. D., et al. (author)
  • Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016
  • 2017
  • In: Lancet. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1084-1150
  • Journal article (peer-reviewed)abstract
    • Background Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. Methods We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0.5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Sociodemographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. Findings Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86.9 years (95% UI 86.7-87.2), and for men in Singapore, at 81.3 years (78.8-83.7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. Interpretation Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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  • 2017
  • In: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
  • Journal article (peer-reviewed)
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  • Fullman, N., et al. (author)
  • Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016
  • 2017
  • In: Lancet. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1423-1459
  • Journal article (peer-reviewed)abstract
    • Background The UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of "leaving no one behind". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030. Methods We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2.5th percentile estimated between 1990 and 2030, and 100 as the 97.5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. Findings Globally, the median health-related SDG index was 56.7 (IQR 31.9-66.8) in 2016 and country-level performance markedly varied, with Singapore (86.8, 95% uncertainty interval 84.6-88.9), Iceland (86.0, 84.1-87.6), and Sweden (85.6, 81.8-87.8) having the highest levels in 2016 and Afghanistan (10.9, 9.6-11.9), the Central African Republic (11.0, 8.8-13.8), and Somalia (11.3, 9.5-13.1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past. Interpretation GBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations. Copyright The Authors. Published by Elsevier Ltd. This is an Open Access article published under the CC BY 4.0 license.
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8.
  • Blokland, G. A. M., et al. (author)
  • Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
  • 2022
  • In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
  • Journal article (peer-reviewed)abstract
    • Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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  • Campbell, PJ, et al. (author)
  • Pan-cancer analysis of whole genomes
  • 2020
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
  • Journal article (peer-reviewed)abstract
    • Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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  • Jiang, X., et al. (author)
  • Shared heritability and functional enrichment across six solid cancers
  • 2019
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
  • Journal article (peer-reviewed)abstract
    • Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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  • Aartsen, M. G., et al. (author)
  • Very high-energy gamma-ray follow-up program using neutrino triggers from IceCube
  • 2016
  • In: Journal of Instrumentation. - 1748-0221. ; 11
  • Journal article (peer-reviewed)abstract
    • We describe and report the status of a neutrino-triggered program in IceCube that generates real-time alerts for gamma-ray follow-up observations by atmospheric-Cherenkov telescopes (MAGIC and VERITAS). While IceCube is capable of monitoring the whole sky continuously, high-energy gamma-ray telescopes have restricted fields of view and in general are unlikely to be observing a potential neutrino-flaring source at the time such neutrinos are recorded. The use of neutrino-triggered alerts thus aims at increasing the availability of simultaneous multi-messenger data during potential neutrino flaring activity, which can increase the discovery potential and constrain the phenomenological interpretation of the high-energy emission of selected source classes (e. g. blazars). The requirements of a fast and stable online analysis of potential neutrino signals and its operation are presented, along with first results of the program operating between 14 March 2012 and 31 December 2015.
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  • Aartsen, M. G., et al. (author)
  • Multiwavelength follow-up of a rare IceCube neutrino multiplet
  • 2017
  • In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 607
  • Journal article (peer-reviewed)abstract
    • On February 17, 2016, the IceCube real-time neutrino search identified, for the first time, three muon neutrino candidates arriving within 100 s of one another, consistent with coming from the same point in the sky. Such a triplet is expected once every 13.7 years as a random coincidence of background events. However, considering the lifetime of the follow-up program the probability of detecting at least one triplet from atmospheric background is 32%. Follow-up observatories were notified in order to search for an electromagnetic counterpart. Observations were obtained by Swift's X-ray telescope, by ASAS-SN, LCO and MASTER at optical wavelengths, and by VERITAS in the very-high-energy gamma-ray regime. Moreover, the Swift BAT serendipitously observed the location 100 s after the first neutrino was detected, and data from the Fermi LAT and HAWC observatory were analyzed. We present details of the neutrino triplet and the follow-up observations. No likely electromagnetic counterpart was detected, and we discuss the implications of these constraints on candidate neutrino sources such as gamma-ray bursts, core-collapse supernovae and active galactic nucleus flares. This study illustrates the potential of and challenges for future follow-up campaigns.
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  • Abbasi, R., et al. (author)
  • A Search for IceCube Sub-TeV Neutrinos Correlated with Gravitational-wave Events Detected By LIGO/Virgo
  • 2023
  • In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 1538-4357 .- 0004-637X. ; 959:2
  • Journal article (peer-reviewed)abstract
    • The LIGO/Virgo collaboration published the catalogs GWTC-1, GWTC-2.1, and GWTC-3 containing candidate gravitational-wave (GW) events detected during its runs O1, O2, and O3. These GW events can be possible sites of neutrino emission. In this paper, we present a search for neutrino counterparts of 90 GW candidates using IceCube DeepCore, the low-energy infill array of the IceCube Neutrino Observatory. The search is conducted using an unbinned maximum likelihood method, within a time window of 1000 s, and uses the spatial and timing information from the GW events. The neutrinos used for the search have energies ranging from a few GeV to several tens of TeV. We do not find any significant emission of neutrinos, and place upper limits on the flux and the isotropic-equivalent energy emitted in low-energy neutrinos. We also conduct a binomial test to search for source populations potentially contributing to neutrino emission. We report a nondetection of a significant neutrino-source population with this test.
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  • Abbasi, R., et al. (author)
  • IceCat-1: The IceCube Event Catalog of Alert Tracks
  • 2023
  • In: Astrophysical Journal, Supplement Series. - : IOP Publishing Ltd. - 1538-4365 .- 0067-0049. ; 269:1
  • Journal article (peer-reviewed)abstract
    • We present a catalog of likely astrophysical neutrino track-like events from the IceCube Neutrino Observatory. IceCube began reporting likely astrophysical neutrinos in 2016, and this system was updated in 2019. The catalog presented here includes events that were reported in real time since 2019, as well as events identified in archival data samples starting from 2011. We report 275 neutrino events from two selection channels as the first entries in the catalog, the IceCube Event Catalog of Alert Tracks, which will see ongoing extensions with additional alerts. The Gold and Bronze alert channels respectively provide neutrino candidates with a 50% and 30% probability of being astrophysical, on average assuming an astrophysical neutrino power-law energy spectral index of 2.19. For each neutrino alert, we provide the reconstructed energy, direction, false-alarm rate, probability of being astrophysical in origin, and likelihood contours describing the spatial uncertainty in the alert's reconstructed location. We also investigate a directional correlation of these neutrino events with gamma-ray and X-ray catalogs, including 4FGL, 3HWC, TeVCat, and Swift-BAT.
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  • Abbasi, R., et al. (author)
  • Limits on Neutrino Emission from GRB 221009A from MeV to PeV Using the IceCube Neutrino Observatory
  • 2023
  • In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 946:1
  • Journal article (peer-reviewed)abstract
    • Gamma-ray bursts (GRBs) have long been considered a possible source of high-energy neutrinos. While no correlations have yet been detected between high-energy neutrinos and GRBs, the recent observation of GRB 221009A-the brightest GRB observed by Fermi-GBM to date and the first one to be observed above an energy of 10 TeV-provides a unique opportunity to test for hadronic emission. In this paper, we leverage the wide energy range of the IceCube Neutrino Observatory to search for neutrinos from GRB 221009A. We find no significant deviation from background expectation across event samples ranging from MeV to PeV energies, placing stringent upper limits on the neutrino emission from this source.
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  • Abbasi, R., et al. (author)
  • Measurement of atmospheric neutrino mixing with improved IceCube DeepCore calibration and data processing
  • 2023
  • In: Physical Review D. - 2470-0010 .- 2470-0029. ; 108:1
  • Journal article (peer-reviewed)abstract
    • We describe a new data sample of IceCube DeepCore and report on the latest measurement of atmospheric neutrino oscillations obtained with data recorded between 2011-2019. The sample includes significant improvements in data calibration, detector simulation, and data processing, and the analysis benefits from a sophisticated treatment of systematic uncertainties, with significantly greater level of detail since our last study. By measuring the relative fluxes of neutrino flavors as a function of their reconstructed energies and arrival directions we constrain the atmospheric neutrino mixing parameters to be sin2θ23=0.51±0.05 and Δm322=2.41±0.07×10-3 eV2, assuming a normal mass ordering. The errors include both statistical and systematic uncertainties. The resulting 40% reduction in the error of both parameters with respect to our previous result makes this the most precise measurement of oscillation parameters using atmospheric neutrinos. Our results are also compatible and complementary to those obtained using neutrino beams from accelerators, which are obtained at lower neutrino energies and are subject to different sources of uncertainties.
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31.
  • Abbasi, R., et al. (author)
  • Observation of seasonal variations of the flux of high-energy atmospheric neutrinos with IceCube
  • 2023
  • In: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 83:9
  • Journal article (peer-reviewed)abstract
    • Atmospheric muon neutrinos are produced by meson decays in cosmic-ray-induced air showers. The flux depends on meteorological quantities such as the air temperature, which affects the density of air. Competition between decay and re-interaction of those mesons in the first particle production generations gives rise to a higher neutrino flux when the air density in the stratosphere is lower, corresponding to a higher temperature. A measurement of a temperature dependence of the atmospheric νμ flux provides a novel method for constraining hadronic interaction models of air showers. It is particularly sensitive to the production of kaons. Studying this temperature dependence for the first time requires a large sample of high-energy neutrinos as well as a detailed understanding of atmospheric properties. We report the significant (>10σ) observation of a correlation between the rate of more than 260,000 neutrinos, detected by IceCube between 2012 and 2018, and atmospheric temperatures of the stratosphere, measured by the Atmospheric Infrared Sounder (AIRS) instrument aboard NASA’s AQUA satellite. For the observed 10 % seasonal change of effective atmospheric temperature we measure a 3.5(3) % change in the muon neutrino flux. This observed correlation deviates by about 2-3 standard deviations from the expected correlation of 4.3 % as obtained from theoretical predictions under the assumption of various hadronic interaction models.
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  • Abbasi, R., et al. (author)
  • Search for neutrino lines from dark matter annihilation and decay with IceCube
  • 2023
  • In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 108:10
  • Journal article (peer-reviewed)abstract
    • Dark matter particles in the Galactic Center and halo can annihilate or decay into a pair of neutrinos producing a monochromatic flux of neutrinos. The spectral feature of this signal is unique and it is not expected from any astrophysical production mechanism. Its observation would constitute a dark matter smoking gun signal. We performed the first dedicated search with a neutrino telescope for such signal, by looking at both the angular and energy information of the neutrino events. To this end, a total of five years of IceCube's DeepCore data has been used to test dark matter masses ranging from 10 GeV to 40 TeV. No significant neutrino excess was found and upper limits on the annihilation cross section, as well as lower limits on the dark matter lifetime, were set. The limits reached are of the order of 10-24 cm3/s for an annihilation and up to 1027 s for decaying dark matter. Using the same data sample we also derive limits for dark matter annihilation or decay into a pair of Standard Model charged particles.
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  • Antoniou, A. C., et al. (author)
  • Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers
  • 2009
  • In: Human Molecular Genetics. - [Antoniou, Antonis C.; McGuffog, Lesley; Peock, Susan; Cook, Margaret; Frost, Debra; Oliver, Clare; Platte, Radka; Pooley, Karen A.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Cambridge, England. [Sinilnikova, Olga M.; Leone, Melanie] Univ Lyon, CNRS, Hosp Civils Lyon,Ctr Leon Berard,UMR5201, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Healey, Sue; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Simard, Jacques] Univ Quebec, Ctr Hosp, Canada Res Chair Oncogenet, Canc Genom Lab, Quebec City, PQ, Canada. Peter MacCallum Canc Inst, Melbourne, Vic 3002, Australia. [Neuhausen, Susan L.; Ding, Yuan C.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Couch, Fergus J.; Wang, Xianshu; Fredericksen, Zachary] Mayo Clin, Rochester, MN USA. [Peterlongo, Paolo; Peissel, Bernard; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Molecolare, Milan, Italy. [Bonanni, Bernardo; Bernard, Loris] Ist Europeo Oncol, Milan, Italy. [Viel, Alessandra] IRCCS, Ctr Riferimento Oncol, Aviano, Italy. [Bernard, Loris] Cogentech, Consortium Genom Technol, Milan, Italy. [Szabo, Csilla I.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Zikan, Michal] Charles Univ Prague, Dept Biochem & Expt Oncol, Fac Med 1, Prague, Czech Republic. [Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. [Greene, Mark H.; Mai, Phuong L.] US Natl Canc Inst, Clin Genet Branch, Rockville, MD USA. [Rennert, Gad; Lejbkowicz, Flavio] CHS Natl Canc Control Ctr, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] B Rappaport Fac Med, Haifa, Israel. [Andrulis, Irene L.; Glendon, Gord] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON M5G 2L7, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Gerdes, Anne-Marie; Thomassen, Mads] Odense Univ Hosp, Dept Biochem Pharmacol & Genet, DK-5000 Odense, Denmark. [Sunde, Lone] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Caligo, Maria A.] Univ Pisa, Div Surg Mol & Ultrastructural Pathol, Dept Oncol, Pisa, Italy. [Caligo, Maria A.] Pisa Univ Hosp, Pisa, Italy. [Laitman, Yael; Kontorovich, Tair; Cohen, Shimrit; Friedman, Eitan] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella; Friedman, Eitan] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Dagan, Efrat; Baruch, Ruth Gershoni] Rambam Med Ctr, Genet Inst, Haifa, Israel. [Harbst, Katja] Lund Univ, Dept Oncol, S-22100 Lund, Sweden. [Barbany-Bustinza, Gisela; Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Ehrencrona, Hans] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden. [Karlsson, Per] Sahlgrenska Univ, Dept Oncol, Gothenburg, Sweden. [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Philadelphia, PA 19104 USA. [Osorio, Ana; Benitez, Javier] Ctr Invest Biomed Red Enfermedades Raras CIBERERE, Inst Salud Carlos III, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Blanco, Ignacio] Catalan Inst Oncol ICO, Canc Genet Counseling Program, Barcelona, Spain. [Lasa, Adriana] Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Spain. [Hamann, Ute] Deutsch Krebsforschungszentrum, Neuenheimer Feld 580 69120, D-6900 Heidelberg, Germany. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Dept Pathol, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Collee, J. Margriet] Erasmus Univ, Dept Clin Genet, Rotterdam Family Canc Clin, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Devilee, Peter] Dept Genet Epidemiol, Leiden, Netherlands. [Wijnen, Juul] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands. [Ligtenberg, Marjolijn J.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [van der Luijt, Rob B.] Univ Utrecht, Med Ctr, Dept Clin Mol Genet, NL-3508 TC Utrecht, Netherlands. [Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Waisfisz, Quinten] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [van Roozendaal, Cornelis E. P.] Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp, NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, Rosalind] Inst Canc Res, Translat Canc Genet Team, London SW3 6JB, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London, England. [Izatt, Louise] Guys Hosp, Clin Genet, London SE1 9RT, England. [Davidson, Rosemarie] Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Cole, Trevor] Birmingham Womens Hosp Healthcare, NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Hodgson, Shirley] Univ London, Dept Canc Genet, St Georges Hosp, London, England. [Godwin, Andrew K.; Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM U509, Serv Genet Oncol, Paris, France. [Buecher, Bruno] Inst Curie, Dept Genet, Paris, France. [Bressac-de Paillerets, Brigitte; Remenieras, Audrey; Lenoir, Gilbert M.] Inst Cancrol Gustave Roussy, Dept Genet, Villejuif, France. [Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, INSERM U946, Villejuif, France. [Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France. [Lenoir, Gilbert M.] Inst Cancerol Gustave Roussy, CNRS FRE2939, Villejuif, France. [Sevenet, Nicolas; Longy, Michel] Inst Bergonie, Lab Genet Constitutionnelle, Bordeaux, France. [Longy, Michel] Inst Bergonie, INSERM U916, Bordeaux, France. [Ferrer, Sandra Fert] Hop Hotel Dieu, Ctr Hosp, Lab Genet Chromosom, Chambery, France. [Prieur, Fabienne] CHU St Etienne, Serv Genet Clin Chromosom, St Etienne, France. [Goldgar, David] Univ Utah, Dept Dermatol, Salt Lake City, UT 84112 USA. [Miron, Alexander; Yassin, Yosuf] Dana Farber Canc Inst, Boston, MA 02115 USA. [John, Esther M.] No Calif Canc Ctr, Fremont, CA USA. [John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA. [Hopper, John L.] Univ Melbourne, Melbourne, Australia. [Terry, Mary Beth] Columbia Univ, New York, NY USA. [Singer, Christian; Gschwantler-Kaulich, Daphne; Staudigl, Christine] Med Univ Vienna, Div Special Gynecol, Dept OB GYN, Vienna, Austria. [Hansen, Thomas V. O.] Univ Copenhagen, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark. [Barkardottir, Rosa Bjork] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Kirchhoff, Tomas; Pal, Prodipto; Kosarin, Kristi; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Piedmonte, Marion] Roswell Pk Canc Inst, GOG Stat & Data Ctr, Buffalo, NY 14263 USA. [Rodriguez, Gustavo C.] Evanston NW Healthcare, NorthShore Univ Hlth Syst, Evanston, IL 60201 USA. [Wakeley, Katie] Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. [Boggess, John F.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Basil, Jack] St Elizabeth Hosp, Edgewood, KY 41017 USA. [Schwartz, Peter E.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Blank, Stephanie V.] New York Univ, Sch Med, New York, NY 10016 USA. [Toland, Amanda E.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Div Human Canc Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Montagna, Marco; Casella, Cinzia] IRCCS, Ist Oncologico Veneto, Immunol & Mol Oncol Unit, Padua, Italy. [Imyanitov, Evgeny N.] NN Petrov Inst Res Inst, St Petersburg, Russia. [Allavena, Anna] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. [Schmutzler, Rita K.; Versmold, Beatrix; Arnold, Norbert] Univ Cologne, Dept Obstet & Gynaecol, Div Mol Gynaeco Oncol, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Obstet & Gynecol, Munich, Germany. Univ Schleswig Holstein, Dept Obstet & Gynaecol, Campus Kiel, Germany. [Niederacher, Dieter] Univ Duesseldorf, Dept Obstet & Gynaecol, Mol Genet Lab, Dusseldorf, Germany. [Deissler, Helmut] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Fiebig, Britta] Univ Regensburg, Inst Human Genet, Regensburg, Germany. [Suttner, Christian] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Schoenbuchner, Ines] Univ Wurzburg, Inst Human Genet, D-8700 Wurzburg, Germany. [Gadzicki, Dorothea] Med Univ, Inst Cellular & Mol Pathol, Hannover, Germany. [Caldes, Trinidad; de la Hoya, Miguel] Hosp Clinico San Carlos 28040, Madrid, Spain. : Oxford University Press. - 0964-6906 .- 1460-2083. ; 18:22, s. 4442-4456
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 × 10-4]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not. 
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34.
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35.
  • Figlioli, G, et al. (author)
  • The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
  • 2019
  • In: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
  • Journal article (peer-reviewed)abstract
    • Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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36.
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37.
  • Aartsen, M. G., et al. (author)
  • Neutrino emission from the direction of the blazar TXS 0506+056 prior to the IceCube-170922A alert
  • 2018
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 361:6398, s. 147-151
  • Journal article (peer-reviewed)abstract
    • A high-energy neutrino event detected by IceCube on 22 September 2017 was coincident in direction and time with a gamma-ray flare from the blazar TXS 0506+056. Prompted by this association, we investigated 9.5 years of IceCube neutrino observations to search for excess emission at the position of the blazar. We found an excess of high-energy neutrino events, with respect to atmospheric backgrounds, at that position between September 2014 and March 2015. Allowing for time-variable flux, this constitutes 3.5 sigma evidence for neutrino emission from the direction of TXS 0506+056, independent of and prior to the 2017 flaring episode. This suggests that blazars are identifiable sources of the high-energy astrophysical neutrino flux.
  •  
38.
  • Wang, Haidong, et al. (author)
  • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
  •  
39.
  • Aartsen, M. G., et al. (author)
  • Constraints on Minute-Scale Transient Astrophysical Neutrino Sources
  • 2019
  • In: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 122:5
  • Journal article (peer-reviewed)abstract
    • High-energy neutrino emission has been predicted for several short-lived astrophysical transients including gamma-ray bursts (GRBs), core-collapse supernovae with choked jets, and neutron star mergers. IceCube's optical and x-ray follow-up program searches for such transient sources by looking for two or more muon neutrino candidates in directional coincidence and arriving within 100 s. The measured rate of neutrino alerts is consistent with the expected rate of chance coincidences of atmospheric background events and no likely electromagnetic counterparts have been identified in Swift follow-up observations. Here, we calculate generic bounds on the neutrino flux of short-lived transient sources. Assuming an E-2.5 neutrino spectrum, we find that the neutrino flux of rare sources, like long gamma-ray bursts, is constrained to < 5% of the detected astrophysical flux and the energy released in neutrinos (100 GeV to 10 PeV) by a median bright GRB-like source is < 10(52.5) erg. For a harder E-2.13 neutrino spectrum up to 30% of the flux could be produced by GRBs and the allowed median source energy is < 10(52) erg. A hypothetical population of transient sources has to be more common than 10(-5) Mpc(-3) yr(-1) (5 x 10(-8) Mpc(-3) yr(-1) for the E-2.13 spectrum) to account for the complete astrophysical neutrino flux.
  •  
40.
  • Aartsen, M. G., et al. (author)
  • Detection of the Temporal Variation of the Sun's Cosmic Ray Shadow with the IceCube Detector
  • 2019
  • In: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 872:2
  • Journal article (peer-reviewed)abstract
    • We report on the observation of a deficit in the cosmic ray flux from the directions of the Moon and Sun with five years of data taken by the IceCube Neutrino Observatory. Between 2010 May and 2011 May the IceCube detector operated with 79 strings deployed in the glacial ice at the South Pole, and with 86 strings between 2011 May and 2015 May. A binned analysis is used to measure the relative deficit and significance of the cosmic ray shadows. Both the cosmic ray Moon and Sun shadows are detected with high statistical significance (>10σ) for each year. The results for the Moon shadow are consistent with previous analyses and verify the stability of the IceCube detector over time. This work represents the first observation of the Sun shadow with the IceCube detector. We show that the cosmic ray shadow of the Sun varies with time. These results make it possible to study cosmic ray transport near the Sun with future data from IceCube.
  •  
41.
  • Aartsen, M. G., et al. (author)
  • Development of an analysis to probe the neutrino mass ordering with atmospheric neutrinos using three years of IceCube DeepCore data IceCube Collaboration
  • 2020
  • In: European Physical Journal C. - : SPRINGER. - 1434-6044 .- 1434-6052. ; 80:1
  • Journal article (peer-reviewed)abstract
    • The Neutrino Mass Ordering (NMO) remains one of the outstanding questions in the field of neutrino physics. One strategy to measure the NMO is to observe matter effects in the oscillation pattern of atmospheric neutrinos above similar to 1GeV, as proposed for several next-generation neutrino experiments. Moreover, the existing IceCube DeepCore detector can already explore this type of measurement. We present the development and application of two independent analyses to search for the signature of the NMO with three years of DeepCore data. These analyses include a full treatment of systematic uncertainties and a statistically-rigorous method to determine the significance for the NMO from a fit to the data. Both analyses show that the dataset is fully compatible with both mass orderings. For the more sensitive analysis, we observe a preference for normal ordering with a p-value of pIO=15.3% and CLs=53.3% for the inverted ordering hypothesis, while the experimental results from both analyses are consistent within their uncertainties. Since the result is independent of the value of delta CP and obtained from energies E nu greater than or similar to 5GeV, it is complementary to recent results from long-baseline experiments. These analyses set the groundwork for the future of this measurement with more capable detectors, such as the IceCube Upgrade and the proposed PINGU detector.
  •  
42.
  • Aartsen, M. G., et al. (author)
  • Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
  • 2018
  • In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 98:6
  • Journal article (peer-reviewed)abstract
    • We report a quasidifferential upper limit on the extremely-high-energy (EHE) neutrino flux above 5 x 10(6) GeV based on an analysis of nine years of IceCube data. The astrophysical neutrino flux measured by IceCube extends to PeV energies, and it is a background flux when searching for an independent signal flux at higher energies, such as the cosmogenic neutrino signal. We have developed a new method to place robust limits on the EHE neutrino flux in the presence of an astrophysical background, whose spectrum has yet to be understood with high precision at PeV energies. A distinct event with a deposited energy above 10(6) GeV was found in the new two-year sample, in addition to the one event previously found in the seven-year EHE neutrino search. These two events represent a neutrino flux that is incompatible with predictions for a cosmogenic neutrino flux and are considered to be an astrophysical background in the current study. The obtained limit is the most stringent to date in the energy range between 5 x 10(6) and 2 x 10(10) GeV. This result constrains neutrino models predicting a three-flavor neutrino flux of E-nu(2)phi(nu e+nu mu+nu tau) similar or equal to 2 x 10(-8) GeV/cm(2) sec sr at 10(9) GeV. A significant part of the parameter space for EHE neutrino production scenarios assuming a proton-dominated composition of ultra-high-energy cosmic rays is disfavored independently of uncertain models of the extragalactic background light which previous IceCube constraints partially relied on.
  •  
43.
  • Aartsen, M. G., et al. (author)
  • Measurements using the inelasticity distribution of multi-TeV neutrino interactions in IceCube
  • 2019
  • In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 99:3
  • Journal article (peer-reviewed)abstract
    • Inelasticity, the fraction of a neutrino's energy transferred to hadrons, is a quantity of interest in the study of astrophysical and atmospheric neutrino interactions at multi-TeV energies with IceCube. In this work, a sample of contained neutrino interactions in IceCube is obtained from five years of data and classified as 2650 tracks and 965 cascades. Tracks arise predominantly from charged-current nu(mu) interactions, and we demonstrate that we can reconstruct their energy and inelasticity. The inelasticity distribution is found to be consistent with the calculation of Cooper-Sarkar et al. across the energy range from similar to 1 to similar to 100 TeV. Along with cascades from neutrinos of all flavors, we also perform a fit over the energy, zenith angle, and inelasticity distribution to characterize the flux of astrophysical and atmospheric neutrinos. The energy spectrum of diffuse astrophysical neutrinos is described well by a power law in both track and cascade samples, and a best-fit index gamma = 2.62 +/- 0.07 is found in the energy range from 3.5 TeV to 2.6 PeV. Limits are set on the astrophysical flavor composition and are compatible with a ratio of (1/3 : 1/3 : 1/3)(circle plus). Exploiting the distinct inelasticity distribution of nu(mu) and (nu) over bar (mu) interactions, the atmospheric nu(mu) to (nu) over bar (mu) flux ratio in the energy range from 770 GeV to 21 TeV is found to be 0.77(-0.25)(+0.44) times the calculation by Honda et al. Lastly, the inelasticity distribution is also sensitive to neutrino charged-current charm production. The data are consistent with a leading-order calculation, with zero charm production excluded at 91% confidence level. Future analyses of inelasticity distributions may probe new physics that affects neutrino interactions both in and beyond the Standard Model.
  •  
44.
  • Aartsen, M. G., et al. (author)
  • PINGU : a vision for neutrino and particle physics at the South Pole
  • 2017
  • In: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 44:5
  • Journal article (peer-reviewed)abstract
    • The Precision IceCube Next Generation Upgrade (PINGU) is a proposed low-energy in-fill extension to the IceCube Neutrino Observatory. With detection technology modeled closely on the successful IceCube example, PINGU will provide a 6 Mton effective mass for neutrino detection with an energy threshold of a few GeV. With an unprecedented sample of over 60 000 atmospheric neutrinos per year in this energy range, PINGU will make highly competitive measurements of neutrino oscillation parameters in an energy range over an order of magnitude higher than long-baseline neutrino beam experiments. PINGU will measure the mixing parameters theta(23) and Delta m(32)(2), including the octant of theta(23) for a wide range of values, and determine the neutrino mass ordering at 3 sigma median significance within five years of operation. PINGU's high precision measurement of the rate of nu(T) appearance will provide essential tests of the unitarity of the 3 x 3 PMNS neutrino mixing matrix. PINGU will also improve the sensitivity of searches for low mass dark matter in the Sun, use neutrino tomography to directly probe the composition of the Earth's core, and improve IceCube's sensitivity to neutrinos from Galactic supernovae. Reoptimization of the PINGU design has permitted substantial reduction in both cost and logistical requirements while delivering performance nearly identical to configurations previously studied.
  •  
45.
  • Aartsen, M. G., et al. (author)
  • Search for Astrophysical Sources of Neutrinos Using Cascade Events in IceCube
  • 2017
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 846:2
  • Journal article (peer-reviewed)abstract
    • The IceCube neutrino observatory has established the existence of a flux of high-energy astrophysical neutrinos, which is inconsistent with the expectation from atmospheric backgrounds at a significance greater than 5 sigma. This flux has been observed in analyses of both track events from muon neutrino interactions and cascade events from interactions of all neutrino flavors. Searches for astrophysical neutrino sources have focused on track events due to the significantly better angular resolution of track reconstructions. To date, no such sources have been confirmed. Here we present the first search for astrophysical neutrino sources using cascades interacting in IceCube with deposited energies as small as 1 TeV. No significant clustering was observed in a selection of 263 cascades collected from 2010 May to 2012 May. We show that compared to the classic approach using tracks, this statistically independent search offers improved sensitivity to sources in the southern sky, especially if the emission is spatially extended or follows a soft energy spectrum. This enhancement is due to the low background from atmospheric neutrinos forming cascade events and the additional veto of atmospheric neutrinos at declinations less than or similar to-30 degrees.
  •  
46.
  • Aartsen, M. G., et al. (author)
  • Search for neutrinos from dark matter self-annihilations in the center of the Milky Way with 3 years of IceCube/DeepCore
  • 2017
  • In: European Physical Journal C. - : SPRINGER. - 1434-6044 .- 1434-6052. ; 77:9
  • Journal article (peer-reviewed)abstract
    • We present a search for a neutrino signal from dark matter self-annihilations in the Milky Way using the Ice-Cube Neutrino Observatory (IceCube). In 1005 days of data we found no significant excess of neutrinos over the background of neutrinos produced in atmospheric air showers from cosmic ray interactions. We derive upper limits on the velocity averaged product of the darkmatter self-annihilation cross section and the relative velocity of the dark matter particles . Upper limits are set for darkmatter particle candidate masses ranging from 10GeV up to 1TeV while considering annihilation through multiple channels. This work sets the most stringent limit on a neutrino signal from dark matter with mass between 10 and 100GeV, with a limit of 1.18 . 10-23 cm(3)s(-1) for 100GeV dark matter particles self-annihilating via iota(+)iota(-) t-to neutrinos (assuming the Navarro-Frenk-White dark matter halo profile).
  •  
47.
  • Aartsen, M. G., et al. (author)
  • Search for steady point-like sources in the astrophysical muon neutrino flux with 8 years of IceCube data
  • 2019
  • In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 79:3
  • Journal article (peer-reviewed)abstract
    • The IceCube Collaboration has observed a high-energy astrophysical neutrino flux and recently found evidence for neutrino emission from the blazar TXS 0506+056. These results open a new window into the high-energy universe. However, the source or sources of most of the observed flux of astrophysical neutrinos remains uncertain. Here, a search for steady point-like neutrino sources is performed using an unbinned likelihood analysis. The method searches for a spatial accumulation of muon-neutrino events using the very high-statistics sample of about 497,000 neutrinos recorded by IceCube between 2009 and 2017. The median angular resolution is approximate to 1 degrees at 1 TeV and improves to approximate to 0.3 degrees for neutrinos with an energy of 1 PeV. Compared to previous analyses, this search is optimized for point-like neutrino emission with the same flux-characteristics as the observed astrophysical muon-neutrino flux and introduces an improved event-reconstruction and parametrization of the background. The result is an improvement in sensitivity to the muon-neutrino flux compared to the previous analysis of approximate to 35% assuming an E-2 spectrum. The sensitivity on the muon-neutrino flux is at a level of E2dN/dE=310-13s-1. No new evidence for neutrino sources is found in a full sky scan and in an a priori candidate source list that is motivated by gamma-ray observations. Furthermore, no significant excesses above background are found from populations of sub-threshold sources. The implications of the non-observation for potential source classes are discussed.
  •  
48.
  • Antoniou, A. C., et al. (author)
  • Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers : Implications for risk prediction
  • 2010
  • In: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:23, s. 9742-9754
  • Journal article (peer-reviewed)abstract
    • The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10-11 - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.
  •  
49.
  •  
50.
  • Garrappa, S., et al. (author)
  • Investigation of Two Fermi-LAT Gamma-Ray Blazars Coincident with High-energy Neutrinos Detected by IceCube
  • 2019
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 880:2
  • Journal article (peer-reviewed)abstract
    • After the identification of the gamma-ray blazar TXS 0506+056 as the first compelling IceCube neutrino source candidate, we perform a systematic analysis of all high-energy neutrino events satisfying the IceCube realtime trigger criteria. We find one additional known gamma-ray source, the blazar GB6 J1040+0617, in spatial coincidence with a neutrino in this sample. The chance probability of this coincidence is 30% after trial correction. For the first time, we present a systematic study of the gamma-ray flux, spectral and optical variability, and multiwavelength behavior of GB6 J1040+0617 and compare it to TXS 0506+056. We find that TXS 0506+056 shows strong flux variability in the Fermi-Large Area Telescope gamma-ray band, being in an active state around the arrival of IceCube-170922A, but in a low state during the archival IceCube neutrino flare in 2014/15. In both cases the spectral shape is statistically compatible (<= 2 sigma) with the average spectrum showing no indication of a significant relative increase of a high-energy component. While the association of GB6 J1040+0617 with the neutrino is consistent with background expectations, the source appears to be a plausible neutrino source candidate based on its energetics and multiwavelength features, namely a bright optical flare and modestly increased gamma-ray activity. Finding one or two neutrinos originating from gamma-ray blazars in the given sample of high-energy neutrinos is consistent with previously derived limits of neutrino emission from gamma-ray blazars, indicating the sources of the majority of cosmic high-energy neutrinos remain unknown.
  •  
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