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4.
  • Aaltonen, T., et al. (author)
  • Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode
  • 2010
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:6, s. 061802-
  • Journal article (peer-reviewed)abstract
    • We combine searches by the CDF and D0 Collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb(-1) of p (p) over bar collisions at root s = 1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L.
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5.
  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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6.
  • Griffin, M. J., et al. (author)
  • The Herschel-SPIRE instrument and its in-flight performance
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L3-
  • Journal article (peer-reviewed)abstract
    • The Spectral and Photometric Imaging REceiver (SPIRE), is the Herschel Space Observatory`s submillimetre camera and spectrometer. It contains a three-band imaging photometer operating at 250, 350 and 500 mu m, and an imaging Fourier-transform spectrometer (FTS) which covers simultaneously its whole operating range of 194-671 mu m (447-1550 GHz). The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 0.3 K. The photometer has a field of view of 4' x 8', observed simultaneously in the three spectral bands. Its main operating mode is scan-mapping, whereby the field of view is scanned across the sky to achieve full spatial sampling and to cover large areas if desired. The spectrometer has an approximately circular field of view with a diameter of 2.6'. The spectral resolution can be adjusted between 1.2 and 25 GHz by changing the stroke length of the FTS scan mirror. Its main operating mode involves a fixed telescope pointing with multiple scans of the FTS mirror to acquire spectral data. For extended source measurements, multiple position offsets are implemented by means of an internal beam steering mirror to achieve the desired spatial sampling and by rastering of the telescope pointing to map areas larger than the field of view. The SPIRE instrument consists of a cold focal plane unit located inside the Herschel cryostat and warm electronics units, located on the spacecraft Service Module, for instrument control and data handling. Science data are transmitted to Earth with no on-board data compression, and processed by automatic pipelines to produce calibrated science products. The in-flight performance of the instrument matches or exceeds predictions based on pre-launch testing and modelling: the photometer sensitivity is comparable to or slightly better than estimated pre-launch, and the spectrometer sensitivity is also better by a factor of 1.5-2.
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  • Ahmed, M., et al. (author)
  • Search for the lepton-family-number nonconserving decay μ +→e +γ
  • 2002
  • In: Physical Review D. - : American Physical Society. - 1550-7998 .- 1550-2368. ; 65:11
  • Journal article (peer-reviewed)abstract
    • The MEGA experiment, which searched for the muon- and electron-number violating decay μ +→e + γ, is described. The spectrometer system, the calibrations, the data taking procedures, the data analysis, and the sensitivity of the experiment are discussed. The most stringent upper limit on the branching ratio, B(μ + →e + γ)<1.2×10 -11 with 90% confidence, is derived from a likelihood analysis.
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  • Stoffel, M. A., et al. (author)
  • Demographic histories and genetic diversity across pinnipeds are shaped by human exploitation, ecology and life-history
  • 2018
  • In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
  • Journal article (peer-reviewed)abstract
    • A central paradigm in conservation biology is that population bottlenecks reduce genetic diversity and population viability. In an era of biodiversity loss and climate change, understanding the determinants and consequences of bottlenecks is therefore an important challenge. However, as most studies focus on single species, the multitude of potential drivers and the consequences of bottlenecks remain elusive. Here, we combined genetic data from over 11,000 individuals of 30 pinniped species with demographic, ecological and life history data to evaluate the consequences of commercial exploitation by 18th and 19th century sealers. We show that around one third of these species exhibit strong signatures of recent population declines. Bottleneck strength is associated with breeding habitat and mating system variation, and together with global abundance explains much of the variation in genetic diversity across species. Overall, bottleneck intensity is unrelated to IUCN status, although the three most heavily bottlenecked species are endangered. Our study reveals an unforeseen interplay between human exploitation, animal biology, demographic declines and genetic diversity.
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  • Szymanski, J. J., et al. (author)
  • MEGA : A search for the decay mu –> e gamma
  • 1994
  • In: Intersections between particle and nuclear physics. Proceedings, 5th Conference, St. Petersburg, USA, May 31-June 6, 1994. ; , s. 789-792
  • Conference paper (peer-reviewed)
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13.
  • Adam, A, et al. (author)
  • Abstracts from Hydrocephalus 2016.
  • 2017
  • In: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
  • Journal article (peer-reviewed)
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14.
  • Amann, F., et al. (author)
  • A search for murarregamma at the level of 10-13
  • 1991
  • In: Proceedings of the 25th International Conference on High Energy Physics. - 9810024347 ; , s. 1070-1071
  • Conference paper (peer-reviewed)abstract
    • The MEGA experiment, which is a search for the decay murarregamma with a branching ratio sensitivity of about 10-13, employs highly modular, fast detectors, state-of-the-art electronics, and a staged trigger with on-line filters. The detectors are contained in a 1.5-T solenoidal field produced by a superconducting magnet. Positrons are confined to the central region and are measured by a set of thin MWPCs. Photons are measured by one of four layers of pair spectrometers in the outer region. Most aspects of the design have been validated in engineering runs; data taking will begin in 1990 with much of the electron arm and one pair spectrometer layer installed.
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  • Middeldorp, Christel M., et al. (author)
  • The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
  • 2019
  • In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
  • Journal article (peer-reviewed)abstract
    • The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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17.
  • Underwood, J, et al. (author)
  • Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
  • 2019
  • In: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
  • Journal article (peer-reviewed)abstract
    • BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P &lt; .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P &lt; .05), as well as smaller brain volumes (P &lt; .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
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  • Garcia, Victor B., et al. (author)
  • The Neoarchean GT-34 Ni deposit, Carajás mineral Province, Brazil : An atypical IOCG-related Ni sulfide mineralization
  • 2020
  • In: Ore Geology Reviews. - 0169-1368 .- 1872-7360. ; 127
  • Journal article (peer-reviewed)abstract
    • The GT-34 deposit, located 12 km to the SW of the Sossego copper–gold mine in the Carajás Province, northern Brazil, represents an unusual Ni sulfide mineralization. The deposit occurs along a NE-SW-trending sub-vertical shear zone marked by progressive Mg-alkalic alteration zones, predominantly hosted in granitic and locally in granodioritic to tonalitic orthogneisses. Initial alteration zones result in unique scapolite-orthopyroxene assemblage, which is partially preserved within pervasive hornblende-chlorapatite ± plagioclase replacement zones. Nickel mineralization occurs mainly as matrix-supported breccias characterized by a pentlandite-pyrrhotite-rich matrix and rounded fragments chiefly of hornblende and chlorapatite. Irregular stockworks and net textured veins containing chalcopyrite-pentlandite are less common. Phlogopite ± talc ± actinolite alteration and late-stage veinlets crosscut the previous alteration zones and the mineralization. The phlogopite ± talc ± actinolite alteration occurs as irregular veins and chalcopyrite-pyrrhotite-magnetite are commonly observed where such alteration intersects the Ni mineralization. Late-stage veinlets are represented by K feldspar-epidote-chlorite-calcite and quartz-albite-chlorite-calcite-epidote veins, both containing minor amounts of millerite, pyrite and F-OH-apatite. High-resolution SIMS U-Pb zircon geochronology obtained for the GT-34 deposit revealed an age of 2828 ± 4 Ma for zircon grains inherited from the host orthogneisses. The timing of the mineralization altered zircon grains from the scapolite-orthopyroxene and phlogopite ± talc ± actinolite alteration zones, is attributed to an age interval between 2751 and 2720 Ma. Although poorly constrained, the geochronological data corroborate a Neoarchean age for the GT-34 Ni mineralization, similar to that of other IOCG deposits in the Carajás Province and coeval with the bimodal magmatism in the area. The atypical orthopyroxene-marialite mineral chemistry support a metasomatic crystallization at high temperatures (>700 °C), low aH2O (<0.5) and pressures between 5 and 7 kbar. Hypersaline fluids, as the ones described for the IOCG deposits in Carajás at such PxT conditions, would enable the orthopyroxene-marialite crystallization, as supported by experimental studies available in the literature. Mineralogical and geochemical considerations on the nature of the Ni sulfide mineralization points toward a metasomatic origin, feasible with the predicted P-T-fluid scenario for the hydrothermal alteration. Such conditions raise the initial temperature and pressure estimates of the IOCG metasomatic alteration by at least 200 °C and pressure up to 7 kbar, making it the hottest and probably deepest IOCG-related metasomatic alteration known to date for Carajás.
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  • Gauthier, S, et al. (author)
  • Mild cognitive impairment
  • 2006
  • In: Lancet (London, England). - 1474-547X. ; 367:9518, s. 1262-1270
  • Journal article (peer-reviewed)
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  • Hayden-Evans, M, et al. (author)
  • An Evaluation of the Overall Utility of Measures of Functioning Suitable for School-Aged Children on the Autism Spectrum: A Scoping Review
  • 2022
  • In: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 19:21
  • Journal article (peer-reviewed)abstract
    • A diagnosis of an autism spectrum condition (autism) provides limited information regarding an individual’s level of functioning, information key in determining support and funding needs. Using the framework introduced by Arksey and O’Malley, this scoping review aimed to identify measures of functioning suitable for school-aged children on the autism spectrum and evaluate their overall utility, including content validity against the International Classification of Functioning, Disability and Health (ICF) and the ICF Core Sets for Autism. The overall utility of the 13 included tools was determined using the Outcome Measures Rating Form (OMRF), with the Adaptive Behavior Assessment System (ABAS-3) receiving the highest overall utility rating. Content validity of the tools in relation to the ICF and ICF Core Sets for Autism varied, with few assessment tools including any items linking to Environmental Factors of the ICF. The ABAS-3 had the greatest total number of codes linking to the Comprehensive ICF Core Set for Autism while the Vineland Adaptive Behavior Scales (Vineland-3) had the greatest number of unique codes linking to both the Comprehensive ICF Core Set for Autism and the Brief ICF Core Set for Autism (6–16 years). Measuring functioning of school-aged children on the spectrum can be challenging, however, it is important to accurately capture their abilities to ensure equitable and individualised access to funding and supports.
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  • Ip, H. F., et al. (author)
  • Genetic association study of childhood aggression across raters, instruments, and age
  • 2021
  • In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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  • Middeldorp, C. M., et al. (author)
  • A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts
  • 2016
  • In: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567. ; 55:10
  • Journal article (peer-reviewed)abstract
    • Objective The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46× 10−6 and 2.66× 10−6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. Conclusion The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants. © 2016 American Academy of Child and Adolescent Psychiatry
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  • Neumann, A, et al. (author)
  • A genome-wide association study of total child psychiatric problems scores
  • 2022
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:8, s. e0273116-
  • Journal article (peer-reviewed)abstract
    • Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.
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