Impact of Right Ventricular Performance in Patients Undergoing Extracorporeal Membrane Oxygenation Following Cardiac Surgery

Background: Extracorporeal membrane oxygenation following cardiac surgery safeguards end‐organ oxygenation but unfavorably alters cardiac hemodynamics. Along with the detrimental effects of cardiac surgery to the right heart, this might impact outcome, particularly in patients with preexisting right ventricular (RV) dysfunction. We sought to determine the prognostic impact of RV function and to improve established risk‐prediction models in this vulnerable patient cohort. Methods and Results: Of 240 patients undergoing extracorporeal membrane oxygenation support following cardiac surgery, 111 had echocardiographic examinations at our institution before implantation of extracorporeal membrane oxygenation and were thus included. Median age was 67 years (interquartile range 60‐74), and 74 patients were male. During a median follow‐up of 27 months (interquartile range 16‐63), 75 patients died. Fifty‐one patients died within 30 days, 75 during long‐term follow‐up (median follow‐up 27 months, minimum 5 months, maximum 125 months). Metrics of RV function were the strongest predictors of outcome, even stronger than left ventricular function (P<0.001 for receiver operating characteristics comparisons). Specifically, RV free‐wall strain was a powerful predictor univariately and after adjustment for clinical variables, Simplified Acute Physiology Score‐3, tricuspid regurgitation, surgery type and duration with adjusted hazard ratios of 0.41 (95%CI 0.24‐0.68; P=0.001) for 30‐day mortality and 0.48 (95%CI 0.33‐0.71; P<0.001) for long‐term mortality for a 1‐SD (SD=−6%) change in RV free‐wall strain. Combined assessment of the additive EuroSCORE and RV free‐wall strain improved risk classification by a net reclassification improvement of 57% for 30‐day mortality (P=0.01) and 56% for long‐term mortality (P=0.02) compared with the additive EuroSCORE alone. Conclusions: RV function is strongly linked to mortality, even after adjustment for baseline variables and clinical risk scores. RV performance improves established risk prediction models for short‐ and long‐term mortality

In-situ estimation of ice crystal properties at the South Pole using LED calibration data from the IceCube Neutrino Observatory

The IceCube Neutrino Observatory instruments about 1 km3 of deep, glacial ice at the geographic South Pole using 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. A unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. Birefringent light propagation has been examined as a possible explanation for this effect. The predictions of a first-principles birefringence model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties do not only include the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube LED calibration data, the theory and parametrization of the birefringence effect, the fitting procedures of these parameterizations to experimental data as well as the inferred crystal properties.</p

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

Evidence for Increased Genetic Risk Load for Major Depression in Patients Assigned to Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant depression; disorder severity and unfavorable treatment outcomes are shown to be influenced by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment and response/nonresponse are associated with an increased genetic burden for major depression (MD) using polygenic risk score (PRS), which summarize the contribution of diseaserelated common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive episode underwent ECT. MD-PRS were calculated for these inpatients and a separate population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary statistics from the Psychiatric Genomics Consortium MDD-working group (Cases: n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate that ECT cohorts show an increased genetic burden for MD and are consistent with the hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic risk for MD. Larger samples are needed to better substantiate these findings

Similarities and Differences of Mental Health in Women and Men: A Systematic Review of Findings in Three Large German Cohorts

In Germany, large, population-based cohort studies have been implemented in order to identify risk and protective factors for maintaining health across the life span. The purpose of this systematic review is to analyse findings from three large ongoing cohorts and to identify sex-specific prevalence rates, risk and protective factors for mental health. Published studies from the Cooperative Health Research in the Region Augsburg (KORA), the Study of Health in Pomerania (SHIP) and the Gutenberg Health Study (GHS)), representing the southern, north-eastern and middle parts of Germany, were identified through searches of the databases PubMed and Web of Science. A total of 52 articles was identified from the start of each cohort until June 2019. Articles reporting prevalence rates of mental health [N = 22], explanatory factors for mental health [N = 25], or both [N = 5] were identified. Consistent across cohorts, higher prevalence rates of internalizing disorders were found for women and more externalizing disorders for men. Risk and protective factors for mental health included social factors, lifestyle, physical health, body mass index (BMI), diabetes, genetic and biological factors. In all areas, differences and similarities were found between women and men. The most evident were the sex-specific risk profiles for depression with mostly external risk factors for men and internal risk factors for women. Gender was not assessed directly, therefore we examined whether socioeconomic and family-related factors reflecting gender roles or institutionalized gender could be used as a proxy for gender. Overall, this systematic review shows differences and similarities in prevalence rates and determinants of mental health indicators between women and men. They underline the importance of focussing on sex specific approaches in mental health research and in the development of prevention measures. Current research on mental health still lacks focus on gender aspects. Therefore, an increased focus on sex and gender in mental health research is of great importance

Do We Need to Rethink the Epidemiology and Healthcare Utilization of Parkinson's Disease in Germany?

Epidemiological aspects of Parkinson's disease (PD), co-occurring diseases and medical healthcare utilization of PD patients are still largely elusive. Based on claims data of 3.7 million statutory insurance members in Germany in 2015 the prevalence and incidence of PD was determined. PD cases had at least one main hospital discharge diagnosis of PD, or one physician diagnosis confirmed by a subsequent or independent diagnosis or by PD medication in 2015. Prevalence of (co-)occurring diseases, mortality, and healthcare measures in PD cases and matched controls were compared. In 2015, 21,714 prevalent PD cases (standardized prevalence: 511.4/100,000 persons) and 3,541 incident PD cases (standardized incidence: 84.1/100,000 persons) were identified. Prevalence of several (co-)occurring diseases/complications, e.g., dementia (PD/controls: 39/13%), depression (45/22%), bladder dysfunction (46/22%), and diabetes (35/31%), as well as mortality (10.7/5.8%) differed between PD cases and controls. The annual healthcare utilization was increased in PD cases compared to controls, e.g., regarding mean ± SD physician contacts (15.2 ± 7.6/12.2 ± 7.3), hospitalizations (1.3 ± 1.8/0.7 ± 1.4), drug prescriptions (overall: 37.7 ± 24.2/21.7 ± 19.6; anti-PD medication: 7.4 ± 7.4/0.1 ± 0.7), assistive/therapeutic devices (47/30%), and therapeutic remedies (57/16%). The standardized prevalence and incidence of PD in Germany as well as mortality in PD may be substantially higher than reported previously. While frequently diagnosed with co-occurring diseases/complications, such as dementia, depression, bladder dysfunction and diabetes, the degree of healthcare utilization shows large variability between PD patients. These findings encourage a rethinking of the epidemiology and healthcare utilization in PD, at least in Germany. Longitudinal studies of insurance claims data should further investigate the individual and epidemiological progression and healthcare demands in PD