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Sökning: WFRF:(Hamm C)

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  • Schiller, D, et al. (författare)
  • The Human Affectome
  • 2024
  • Ingår i: Neuroscience and biobehavioral reviews. - 1873-7528. ; 158, s. 105450-
  • Tidskriftsartikel (refereegranskat)
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  • Forstner, A. J., et al. (författare)
  • Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression
  • 2021
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 4179-4190
  • Tidskriftsartikel (refereegranskat)abstract
    • Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10−4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
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  • Rayner, C, et al. (författare)
  • A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders
  • 2019
  • Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 150-
  • Tidskriftsartikel (refereegranskat)abstract
    • Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
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  • Pajola, M., et al. (författare)
  • The Agilkia boulders/pebbles size-frequency distributions : OSIRIS and ROLIS joint observations of 67P surface
  • 2016
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S242-S252
  • Tidskriftsartikel (refereegranskat)abstract
    • By using the images acquired by the OSIRIS (Optical, Spectroscopic and Infrared Remote Imaging System) and ROLIS (ROsetta Lander Imaging System) cameras, we derive the size-frequency distribution (SFD) of cometary pebbles and boulders covering the size range 0.05-30.0 m on the Agilkia landing site. The global SFD measured on OSIRIS images, reflects the different properties of the multiple morphological units present on Agilkia, combined with selection effects related to lifting, transport and redeposition. Contrarily, the different ROLIS SFD derived on the smooth and rough units may be related to their different regolith thickness present on Agilkia. In the thicker, smoother layer, ROLIS mainly measures the SFD of the airfall population which almost completely obliterates the signature of underlying boulders up to a size of the order of 1 m. This is well matched by the power-law index derived analysing coma particles identified by the grain analyser Grain Impact Analyser and Dust Accumulator. This result confirms the important blanketing dynamism of Agilkia. The steeper SFD observed in rough terrains from 0.4 to 2 m could point out intrinsic differences between northern and southern dust size distributions, or it may suggest that the underlying boulders 'peek through' the thinner airfall layer in the rough terrain, thereby producing the observed excess in the decimetre size range. Eventually, the OSIRIS SFD performed on the Philae landing unit may be due to water sublimation from a static population of boulders, affecting smaller boulders before the bigger ones, thus shallowing the original SFD.
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  • Bonaca, M. P., et al. (författare)
  • Reduction in subtypes and sizes of myocardial infarction with ticagrelor in PEGASUS-TIMI 54
  • 2018
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-—Ticagrelor reduced cardiovascular death, myocardial infarction (MI), or stroke in patients with prior MI in PEGASUSTIMI 54 (Prevention of Cardiovascular Events [eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin). MI can occur in diverse settings and with varying severity; therefore, understanding the types and sizes of MI events prevented is of clinical importance. Methods and Results-—MIs were adjudicated by a blinded clinical events committee and categorized by subtype and fold elevation of peak cardiac troponin over the upper limit of normal. A total of 1042 MIs occurred in 898 of the 21 162 randomized patients over a median follow-up of 33 months. The majority of the MIs (76%) were spontaneous (Type 1), with demand MI (Type 2) and stent thrombosis (Type 4b) accounting for 13% and 9%, respectively; sudden death (Type 3), percutaneous coronary intervention–related (Type 4a) and coronary artery bypass graft–related (Type 5) each accounted for <1%. Half of MIs (520, 50%) had a peak troponin ≥10x upper limit of normal and 21% of MIs (220) had a peak troponin ≥1009 upper limit of normal. A total of 21% (224) were ST-segment–elevation MI STEMI. Overall ticagrelor reduced MI (4.47% versus 5.25%, hazard ratio 0.83, 95% confidence interval 0.72–0.95, P=0.0055). The benefit was consistent among the subtypes, including a 31% reduction in MIs with a peak troponin ≥1009 upper limit of normal (hazard ratio 0.69, 95% confidence interval 0.53–0.92, P=0.0096) and a 40% reduction in ST-segment elevation MI (hazard ratio 0.60, 95% confidence interval 0.46–0.78, P=0.0002). Conclusions-—In stable outpatients with prior MI, the majority of recurrent MIs are spontaneous and associated with a high biomarker elevation. Ticagrelor reduces the MI consistently among subtypes and sizes including large MIs and ST-segment elevation MI. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01225562. © 2018 The Authors.
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  • Neumann, J. T., et al. (författare)
  • Application of High-Sensitivity Troponin in Suspected Myocardial Infarction
  • 2019
  • Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 380:26, s. 2529-2540
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundData regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. MethodsIn 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. ResultsAmong 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. ConclusionsA risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes.
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  • Pajola, M., et al. (författare)
  • The pebbles/boulders size distributions on Sais : Rosetta's final landing site on comet 67P/Churyumov-Gerasimenko
  • 2017
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 469:Suppl. 2, s. S636-S645
  • Tidskriftsartikel (refereegranskat)abstract
    • By using the imagery acquired by the Optical, Spectroscopic, and Infrared Remote Imaging System Wide-Angle Camera (OSIRISWAC), we prepare a high-resolution morphological map of the Rosetta Sais final landing site, characterized by an outcropping consolidated terrain unit, a coarse boulder deposit and a fine particle deposit. Thanks to the 0.014 m resolution images, we derive the pebbles/boulders size-frequency distribution (SFD) of the area in the size range of 0.07-0.70 m. Sais' SFD is best fitted with a two-segment differential power law: the first segment is in the range 0.07-0.26 m, with an index of -1.7 ± 0.1, while the second is in the range 0.26-0.50 m, with an index of -4.2 +0.4/-0.8. The 'knee' of the SFD, located at 0.26 m, is evident both in the coarse and fine deposits. When compared to the Agilkia Rosetta Lander Imaging System images, Sais surface is almost entirely free of the ubiquitous, cm-sized debris blanket observed by Philae. None the less, a similar SFD behaviour of Agilkia, with a steeper distribution above ~0.3 m, and a flatter trend below that, is observed. The activity evolution of 67P along its orbit provides a coherent scenario of how these deposits were formed. Indeed, different lift pressure values occurring on the two locations and at different heliocentric distances explain the presence of the cm-sized debris blanket on Agilkia observed at 3.0 au inbound. Contrarily, Sais activity after 2.1 au outbound has almost completely eroded the fine deposits fallen during perihelion, resulting in an almost dust-free surface observed at 3.8 au.
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  • Puymirat, E, et al. (författare)
  • Euro Heart Survey 2009 Snapshot : regional variations in presentation and management of patients with AMI in 47 countries
  • 2013
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 2:4, s. 359-370
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS:Detailed data on patients admitted for acute myocardial infarction (AMI) on a European-wide basis are lacking. The Euro Heart Survey 2009 Snapshot was designed to assess characteristics, management, and hospital outcomes of AMI patients throughout European Society of Cardiology (ESC) member countries in a contemporary 'real-world' setting, using a methodology designed to improve the representativeness of the survey.METHODS:Member countries of the ESC were invited to participate in a 1-week survey of all patients admitted for documented AMI in December 2009. Data on baseline characteristics, type of AMI, management, and complications were recorded using a dedicated electronic form. In addition, we used data collected during the same time period in national registries in Sweden, England, and Wales. Data were centralized at the European Heart House.RESULTS:Overall, 4236 patients (mean age 66±13 years; 31% women) were included in the study in 47 countries. Sixty per cent of patients had ST-segment elevation myocardial infarction, with 50% having primary percutaneous coronary intervention and 21% fibrinolysis. Aspirin and thienopyridines were used in >90%. Unfractionated and low-molecular-weight heparins were the most commonly used anticoagulants. Statins, beta-blockers, and angiotensin-converting enzyme inhibitors were used in >80% of the patients. In-hospital mortality was 6.2%. Regional differences were observed, both in terms of population characteristics, management, and outcomes.CONCLUSIONS:In-hospital mortality of patients admitted for AMI in Europe is low. Although regional variations exist in their presentation and management, differences are limited and have only moderate impact on early outcomes.
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  • Sakatani, N., et al. (författare)
  • Anomalously porous boulders on (162173) Ryugu as primordial materials from its parent body
  • 2021
  • Ingår i: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:8, s. 766-774
  • Tidskriftsartikel (refereegranskat)abstract
    • Planetesimals—the initial stage of the planetary formation process—are considered to be initially very porous aggregates of dusts1,2, and subsequent thermal and compaction processes reduce their porosity3. The Hayabusa2 spacecraft found that boulders on the surface of asteroid (162173) Ryugu have an average porosity of 30–50% (refs. 4,5,6), higher than meteorites but lower than cometary nuclei7, which are considered to be remnants of the original planetesimals8. Here, using high-resolution thermal and optical imaging of Ryugu’s surface, we discovered, on the floor of fresh small craters (<20 m in diameter), boulders with reflectance (~0.015) lower than the Ryugu average6 and porosity >70%, which is as high as in cometary bodies. The artificial crater formed by Hayabusa2’s impact experiment9 is similar to these craters in size but does not have such high-porosity boulders. Thus, we argue that the observed high porosity is intrinsic and not created by subsequent impact comminution and/or cracking. We propose that these boulders are the least processed material on Ryugu and represent remnants of porous planetesimals that did not undergo a high degree of heating and compaction3. Our multi-instrumental analysis suggests that fragments of the highly porous boulders are mixed within the surface regolith globally, implying that they might be captured within collected samples by touch-down operations10,11.
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