GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation: the 8th AFNET/EHRA consensus conference

Aims Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy.Methods and results This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework.Conclusions Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.</p

Sulfine-based synthesis of four-, five- and six-membered heterocycles

Contains fulltext : 19352_sulfsyoff.pdf (publisher's version ) (Open Access)109 p

Vorurteile und Rassismus - sozialpsychologische Einblicke

Zick A. Vorurteile und Rassismus - sozialpsychologische Einblicke. In: Cropley AJ, Ruddat H, Dehn D, Lucassen S, eds. Theorien, Modelle und Befunde der Weiterbildung. Probleme der Zuwanderung, 2. Hogrefe: Verlag für Angewandte Psychologie; 1995: 46-70

Progress in Fixed-Photon-Energy Time-Efficient Double Imaging Photoelectron/Photoion Coincidence Measurements in Quantitative Flame Analysis

Felsmann D, Lucassen A, Krüger J, et al. Progress in Fixed-Photon-Energy Time-Efficient Double Imaging Photoelectron/Photoion Coincidence Measurements in Quantitative Flame Analysis. ZEITSCHRIFT FÜR PHYSIKALISCHE CHEMIE. 2016;230(8):1067-1097

Isomer identification in flames with double-imaging photoelectron/photoion coincidence spectroscopy (i²PEPICO) using measured and calculated reference photoelectron spectra

Pieper J, Schmitt S, Hemken C, et al. Isomer identification in flames with double-imaging photoelectron/photoion coincidence spectroscopy (i²PEPICO) using measured and calculated reference photoelectron spectra. Zeitschrift für Physikalische Chemie. 2018;232(2):153–187

Electron ionization, photoionization and photoelectron/photoion coincidence spectroscopy in mass-spectrometric investigations of a low-pressure ethylene/oxygen flame

Felsmann D, Moshammer K, Krüger J, et al. Electron ionization, photoionization and photoelectron/photoion coincidence spectroscopy in mass-spectrometric investigations of a low-pressure ethylene/oxygen flame. PROCEEDINGS OF THE COMBUSTION INSTITUTE. 2015;35(1):779-786