| 1. |
- Cunningham, Virginia, et al.
(author)
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GRB 160625B : Evidence for a Gaussian-shaped Jet
- 2020
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 904:2
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Journal article (peer-reviewed)abstract
- We present multiwavelength modeling of the afterglow from the long gamma-ray burst (GRB) 160625B using Markov Chain Monte Carlo techniques of the afterglowpy Python package. GRB 160625B is an extremely bright burst with a rich set of observations spanning from radio to gamma-ray frequencies. These observations range from similar to 0.1 days to >1000 days, thus making this event extremely well suited to such modeling. In this work we compare top-hat and Gaussian jet structure types in order to find best-fit values for the GRB jet collimation angle, viewing angle, and other physical parameters. We find that a Gaussian-shaped jet is preferred (2.7 sigma-5.3 sigma) over the traditional top-hat model. Our estimate for the opening angle of the burst ranges from 126 to 390, depending on jet-shape model. We also discuss the implications that assumptions on jet shape, viewing angle, and particularly the participation a fraction of electrons have on the final estimation of GRB intrinsic energy release and the resulting energy budget of the relativistic outflow. Most notably, allowing the participation fraction to vary results in an estimated total relativistic energy of similar to 10(53) erg. This is two orders of magnitude higher than when the total fraction is assumed to be unity; thus, this parameter has strong relevance for placing constraints on long GRB central engines, details of the circumburst media, and host environment.
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| 2. |
- Hau, Stephan, 1960-, et al.
(author)
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Die Frankfurter Präventionsstudie. Zur psychischen und psychosozialen Integration von verhaltensauffälligen Kindern (insbesondere von ADHS) im Kindergartenalter - ein Arbeitsbericht.
- 2006
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In: ADHS - Frühprävention statt Medikalisierung. Theorie, Forschung, Kontroversen.. - Göttingen : Vandenhoeck & Ruprecht. - 9783525451786 - 3525451784 ; , s. 238-269
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Book chapter (other academic/artistic)abstract
- Wie soll ADHS behandelt werden? Dieses Buch setzt sich auf fachlich-wissenschaftlicher Ebene sowohl mit der Diagnose als auch mit der Behandlung von ADHS auseinander. Die einen plädieren für einen verstehenden und therapeutischen Umgang mit dem betroffenen Kind, während andere in einer medikamentösen Behandlung das Mittel der Wahl sehen.Das Aufmerksamkeits-Defizit-Hyperaktivitäts-Syndrom (ADHS) ist heutzutage eine weitverbreitete Diagnose, mancherorts für fast alle kindlichen Schwierigkeiten im Vorschul- und Grundschulalter. Die Erklärungen reichen von Störungen des Hirnstoffwechsels, Frühverwahrlosungen, psychischen oder psychosozialen Regulationsstörungen bis hin zu Hochbegabungen. Bei den Präventions- und Therapieangeboten gehen die Empfehlungen weit auseinander. Für die einen ist ein verstehender Zugang zum einzelnen Kind und seiner Lebenssituation der richtige Weg, während andere in einer medikamentösen Behandlung die Lösung des Problems sehen. Diese Sichtweise hat in den letzten zehn Jahren enormen Auftrieb erhalten. Die Autoren dieses Bandes problematisieren und diskutieren eine drohende Medikalisierung sozialer Probleme. Sie greifen aktuelle Kontroversen auf und plädieren für eine sorgfältige Diagnostik sowie für eine professionelle Zusammenarbeit aller beteiligten Experten bei der Therapie der betroffenen Kinder.
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| 3. |
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| 4. |
- Sánchez Van Kammen, Mayte, et al.
(author)
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Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia
- 2021
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In: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 78:11, s. 1314-1323
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Journal article (peer-reviewed)abstract
- Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS.Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination.Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria.Main Outcomes and Measures: Clinical characteristics and mortality rate.Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later.Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination..
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| 5. |
- Scutelnic, Adrian, et al.
(author)
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Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.
- 2022
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In: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 92:4, s. 562-573
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Journal article (peer-reviewed)abstract
- Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p<0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR]=0.43, 95% confidence interval [CI]=0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR=0.19, 95% CI=0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR=0.70, 95% CI=0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR=2.19, 95% CI=0.74-6.54).In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
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| 6. |
- Stys, Patrycja, et al.
(author)
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Brokering between (not so) overt and (not so) covert networks in conflict zones
- 2020
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In: Global crime. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 1744-0572 .- 1744-0580. ; 21:1, s. 74-110
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Journal article (peer-reviewed)abstract
- There is a tendency to consider covert networks as separate from overt networks. Drawing on data from the Democratic Republic of the Congo, we demonstrate that this is not the case and identify how covert and overt networks are mutually constitutive. While most studies of African brokers have relied on network metaphors like Big Men and social membranes, we consider the embeddedness of covert networks in overt networks explicitly. We perform two analyses on a large original dataset encompassing 396 partially overlapping ego-nets obtained from a hybrid link-tracing design. An ego-net analysis reveals a large degree of homophily and a deep embeddedness of the different networks. A multilevel exponential random graph model fitted to the reconstructed network of a 110-node subset shows that demobilised combatants are the actors likely to broker between armed groups, state forces, and civilian blocs, suggesting their capacity to broker peace or foment war.
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| 7. |
- Szulkin, Robert, et al.
(author)
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Prediction of individual genetic risk to prostate cancer using a polygenic score.
- 2015
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In: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 75:13, s. 1467-74
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Journal article (peer-reviewed)abstract
- BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction.METHODS: We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls.RESULTS: The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk.CONCLUSIONS: Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction.
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| 8. |
- Thienel, Manuela, et al.
(author)
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Immobility-associated thromboprotection is conserved across mammalian species from bear to human
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6641, s. 178-187
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Journal article (peer-reviewed)abstract
- Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.
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| 9. |
- Vogelezang, Suzanne, et al.
(author)
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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
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Journal article (peer-reviewed)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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| 10. |
- Wang, Zhaoming, et al.
(author)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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