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Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
An experiment addressing electron capture (EC) decay of hydrogen-like 142Pm60+ions has been conducted at the experimental storage ring (ESR) at GSI. The decay appears to be purely exponential and no modulations were observed. Decay times for about 9000 individual EC decays have been measured by applying the single-ion decay spectroscopy method. Both visually and automatically analysed data can be described by a single exponential decay with decay constants of 0.0126(7)s−1 for automatic analysis and 0.0141(7)s−1 for manual analysis. If a modulation superimposed on the exponential decay curve is assumed, the best fit gives a modulation amplitude of merely 0.019(15), which is compatible with zero and by 4.9 standard deviations smaller than in the original observation which had an amplitude of 0.23(4).
We report on a polarization measurement of inclusive J/ψ mesons in the di-electron decay channel at mid-rapidity at 2 < pT < 6 GeV/c in p + p collisions at √s = 200 GeV. Data were taken with the STAR detector at RHIC. The J/ψ polarization measurement should help to distinguish between different models of the J/ψ production mechanism since they predict different pT dependences of the J/ψ polarization. In this analysis, J/ψ polarization is studied in the helicity frame. The polarization parameter λθ measured at RHIC becomes smaller towards high pT , indicating more longitudinal J/ψ polarization as pT increases. The result is compared with predictions of presently available models.
Hypomethylating agents decitabine and azacytidine are regarded as interchangeable in the treatment of acute myeloid leukemia (AML). However, their mechanisms of action remain incompletely understood, and predictive biomarkers for HMA efficacy are lacking. Here, we show that the bioactive metabolite decitabine triphosphate, but not azacytidine triphosphate, functions as activator and substrate of the triphosphohydrolase SAMHD1 and is subject to SAMHD1-mediated inactivation. Retrospective immunohistochemical analysis of bone marrow specimens from AML patients at diagnosis revealed that SAMHD1 expression in leukemic cells inversely correlates with clinical response to decitabine, but not to azacytidine. SAMHD1 ablation increases the antileukemic activity of decitabine in AML cell lines, primary leukemic blasts, and xenograft models. AML cells acquire resistance to decitabine partly by SAMHD1 up-regulation. Together, our data suggest that SAMHD1 is a biomarker for the stratified use of hypomethylating agents in AML patients and a potential target for the treatment of decitabine-resistant leukemia.
The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers (‘average reader’) was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI.
Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.
Background: Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine.
Methods: Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m2 bid (d1-14, d22-35) and oxaliplatin 50 mg/m2 (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate.
Results: 70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection. 47 patients (68.1%) underwent sphincter preserving surgery.
Conclusions: The addition of bevacizumab and oxaliplatin to RCT with capecitabine was well tolerated and did not increase perioperative morbidity or mortality. However, the pCR rate was not improved in comparison to other trials that used capecitabine or capecitabine/oxaliplatin in preoperative radiochemotherapy.
We present a measurement of e+e− pair production in central PbAu collisions at 158A GeV/c. As reported earlier, a significant excess of the e+e− pair yield over the expectation from hadron decays is observed. The improved mass resolution of the present data set, recorded with the upgraded CERES experiment at the CERN-SPS, allows for a comparison of the data with different theoretical approaches. The data clearly favor a substantial in-medium broadening of the ρ spectral function over a density-dependent shift of the ρ pole mass. The in-medium broadening model implies that baryon induced interactions are the key mechanism to the observed modifications of the ρ meson at SPS energy.
Rezensionen [2018]
(2018)
Verzeichnis
Einzelrezensionen
154 Beauvais, Clémentine: The Mighty Child. Time and Power in Children’s Literature (Thomas Kullmann)
155 Dean-Ruzicka, Rachel: Tolerance Discourse and Young Adult Holocaust Literature. Engaging Difference and Identity (Susanne Blumesberger)
157 Dolle-Weinkauff, Bernd (Hrsg.): Geschichte im Comic. Befunde – Theorien – Erzählweisen (Caroline Wittig)
159 Ewers, Hans-Heino (Hrsg.): Erster Weltkrieg: Kindheit, Jugend und Literatur. Deutschland, Österreich, Osteuropa, England, Belgien und Frankreich (Kurt Franz)
161 Franz, Kurt / Lange, Günter (Hrsg.): Der Stoff, aus dem Geschichten sind. Intertextualität im Werk Otfried Preußlers (sabine fuchs)
163 Glasenapp, Gabriele von/Kagelmann, Andre/Giesa, Felix (Hrsg.): Die Zeitalter werden besichtigt. Aktuelle Tendenzen der Kinder- und Jugendliteraturforschung. Festschrift für Otto Brunken (Karin Richter)
165 Josting, Petra/Schmideler, Sebastian (Hrsg.): Bonsels’ Tierleben. Insekten und Kriechtiere in Kinder- und Jugendmedien (Kurt Franz)
167 Kriegleder, Wynfrid/ Lexe, Heidi / Loidl, Sonja/ Seibert, Ernst (Hrsg.): Jugendliteratur im Kontext von Jugendkultur (Lena Hoffmann)
169 Kurwinkel, Tobias: Bilderbuchanalyse. Narrativik – Ästhetik – Didaktik (Annette Kliewer)
171 Langenhorst, Georg/Naurath, Elisabeth (Hrsg.): Kindertora – Kinderbibel – Kinderkoran. Neue Chancen für (inter-)religiöses Lernen (Renate Grubert)
172 Lathey, Gillian: Translating Children’s Literature (heike Elisabeth Jüngst)
174 Mairbäurl, Gunda/Seibert, Ernst (Hrsg.): Kulturelle Austauschprozesse in der Kinder- und Jugendliteratur. Zur genrespezifischen Transformation von Themen, Stoffen und Motiven im medialen Kontext (Sarah Terhorst)
176 Maiwald, Klaus /Meyer, Anna-Maria/Pecher, Claudia Maria (Hrsg.): »Klassiker« des Kinderund Jugendfilms (Michael Stierstorfer)
177 Mills, Claudia (Hrsg.): Ethics in Children’s Literature (Thomas Kullmann)
179 Nast, Mirjam: »Perry Rhodan« lesen. Zur Serialität der Lektürepraktiken einer Heftromanserie (Wolfgang Biesterfeld)
181 O’Sullivan, Emer / Immel, Andrea (Hrsg.): Imagining Sameness and Difference in Children’s Literature. From the Enlightenment to the Present Day (Iris Schäfer)
182 Oetken, Mareile: Wie Bilderbücher erzählen. Analysen multimodaler Strukturen und bimedialen Erzählens im Bilderbuch (Katharina Egerer)
184 Schmideler, Sebastian (Hrsg.): Wissensvermittlung in der Kinder- und Jugendliteratur der DDR. Themen, Formen, Strukturen, Illustrationen (Sabine Planka)
186 Standke, Jan (Hrsg.): Wolfgang Herrndorf lesen. Beiträge zur Didaktik der deutschsprachigen Gegenwartsliteratur (Sabine Planka)
187 Viel, Bernhard: Der Honigsammler. Waldemar Bonsels, Vater der Biene Maja. Eine Biografie (Renate Grubert)
189 Zellerhoff, Rita: Komplexe sprachliche Strukturen in der Jugendliteratur. Aufgezeigt an Beispielen preisgekrönter Werke der Jugendjury des Deutschen Jugendliteraturpreises (Susanne Riegler)
Sammelrezensionen
191 Anker, Martin u.a. (Hrsg.): Grimms Märchenwelten im Bilderbuch. Beiträge zur Entwicklung des Märchenbilderbuches seit Mitte des 20. Jahrhunderts. – Brinker-von der Heyde, Claudia u. a. (Hrsg.): Märchen, Mythen und Moderne. 200 Jahre Kinder- und Hausmärchen der Brüder Grimm. – Joosen, Vanessa/ Lathey, Gillian (Hrsg.): Grimms’ Tales around the Globe. The Dynamics of their International Reception (Thomas Bitterlich)
194 Böhm, Kerstin: Archaisierung und Pinkifizierung. Mythen von Weiblichkeit und Männlichkeit in der Kinder- und Jugendliteratur. – Dangendorf, Sarah: Kleine Mädchen in High Heels. Über die visuelle Sexualisierung frühadoleszenter Mädchen (Annette Kliewer)
197 Gordon, Ian: Kid Comic Strips. A Genre Across Four Countries. – Kupczynska, Kalina/Renata Makarska (Hrsg.): Comic in Polen. Polen im Comic. – Kutch, Lynn Marie (Hrsg.): Novel Perspectives on German-Language Comics Studies. History, Pedagogy, Theory. – Reddition. Zeitschrift für Graphische Literatur (66) 2017: Ein halbes Jahrhundert Carlsen Comics. – Rosenfeldt, Reginald: ComicPioniere. Die deutschen Comic-Künstler der 1950er Jahre (Felix Giesa)