Universität Mannheim
  • Mannheim, Germany
Recent publications
Background: A dissociative subtype of posttraumatic stress disorder (D-PTSD) was introduced into the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) but latent profiles and clinical correlates of D-PTSD remain controversial. Objective: The aims of our study were to identify subgroups of individuals with distinct patterns of PTSD symptoms, including dissociative symptoms, by means of latent class analyses (LCA), to compare these results with the categorization of D-PTSD vs. PTSD without dissociative features according to the CAPS-5 interview, and to explore whether D-PTSD is associated with higher PTSD severity, difficulties in emotion regulation, and depressive symptoms. Method: A German sample of treatment-seeking individuals was investigated (N = 352). We conducted an LCA on the basis of symptoms of PTSD and dissociation as assessed by the CAPS-5. Moreover, severity of PTSD (PCL-5), difficulties in emotion regulation (DERS), and depressive symptoms (BDI-II) were compared between patients with D-PTSD according to the CAPS-5 interview and patients without dissociative symptoms. Results: LCA results suggested a 5-class model with one subgroup showing the highest probability to fulfill criteria for the dissociative subtype and high scores on both BDI and DERS. Significantly higher scores on the DERS, BDI and PCL-5 were found in the D-PTSD group diagnosed with the CAPS-5 (n = 75; 35.7%). Sexual trauma was also reported more often by this subgroup. When comparing the dissociative subtype to the LCA results, only a partial overlap could be found. Conclusions: Our findings suggest that patients with D-PTSD have significantly more problems with emotion regulation, more depressive symptoms, and more severe PTSD-symptoms. Given the results of our LCA, we conclude that the dissociative subtype seems to be more complex than D-PTSD as diagnosed by means of the CAPS-5.
The transcription factor p53 exerts its tumour suppressive effect through transcriptional activation of numerous target genes controlling cell cycle arrest, apoptosis, cellular senescence and DNA repair. In addition, there is evidence that p53 influences the translation of specific mRNAs, including translational inhibition of ribosomal protein synthesis and translational activation of MDM2. A challenge in the analysis of translational control is that changes in mRNA abundance exert a kinetic (passive) effect on ribosome densities. In order to separate these passive effects from active regulation of translation efficiency in response to p53 activation, we conducted a comprehensive analysis of translational regulation by comparative analysis of mRNA levels and ribosome densities upon DNA damage induced by neocarzinostatin in wild-type and TP53-/- HCT116 colorectal carcinoma cells. Thereby, we identified a specific group of mRNAs that are preferentially translated in response to p53 activation, many of which correspond to p53 target genes including MDM2, SESN1 and CDKN1A. By subsequent polysome profile analysis of SESN1 and CDKN1A mRNA, we could demonstrate that p53-dependent translational activation relies on a combination of inducing the expression of translationally advantageous isoforms and trans-acting mechanisms that further enhance the translation of these mRNAs.
Despite high drop-out rates from vocational education and training (VET) throughout most countries and a long research tradition on potential drop-out reasons, little is known about the effects exerted on drop-out intentions by the quality of training. Furthermore, only rarely do scholars distinguish between different drop-out directions, and systematic insights on possibly differing causes are scarce. This study explores the factors influencing four directions of drop-out intention (‘upwards’, ‘downwards’, ‘company change’, ‘occupation change’). Linear regression modelling is used to analyse survey data on the motivation, socio-demographic aspects and competency of 562 trainees as industrial management assistants in Germany and on how they perceived the training quality. The results show that different directions of drop-out intention stem from various factors, with training quality in general having the largest effect. Additionally, the findings indicate a two-tier-scheme of influence factors, ‘core’ and ‘direction-typical’ factors.
The outbreak of the COVID-19 pandemic has led to a vast increase in the demand for fast, frequent, and multi-faceted data to study the impact of the pandemic on people’s lives. Existing data collection infrastructures had to be adapted quickly during the early phase of the pandemic to meet this data demand. Our research group contributed to this by conducting the Mannheim Corona Study (MCS), a longitudinal probability-based online survey, in a daily rotating panel design that took place from March 20 through July 10, 2020. The fast-and-frequent panel data collection design of the MCS had numerous consequences for designing its questionnaires and choosing its measurement instruments. This included designing new instruments on the fly in the ever-changing pandemic environment, making efficient use of limited questionnaire space, and deciding on measurement frequencies in a structured manner under uncertain external conditions. In this report, we document the MCS approach to choosing measurement instruments fit for the purpose of fast and frequent data collection during the early phase of COVID-19 in Germany. We particularly highlight three examples of measurement instruments in the MCS and reflect on their measurement properties.
Background Research on spatiotemporal gene landscape can provide insights into the spatial characteristics of human kidney development and facilitate kidney organoid cultivation. Here, we profiled the spatiotemporal gene programs of the human embryonic kidneys at 9 and 18 post-conception weeks (PCW) by integrating the application of microarray-based spatial transcriptomics and single-cell transcriptomics. Results We mapped transcriptomic signatures of scRNA-seq cell types upon the 9 and 18 PCW kidney sections based on cell-type deconvolution and multimodal intersection analyses, depicting a spatial landscape of developing cell subpopulations. We established the gene characteristics in the medullary regions and revealed a strong mitochondrial oxidative phosphorylation and glycolysis activity in the deeper medullary region. We also built a regulatory network centered on GDNF-ETV4 for nephrogenic niche development based on the weighted gene co-expression network analysis and highlighted the key roles of Wnt , FGF , and JAG1-Notch2 signaling in maintaining renal branching morphogenesis. Conclusions Our findings obtained by this spatiotemporal gene program are expected to improve the current understanding of kidney development.
In 1980, a few years after its democratization process, Spain raised the minimum working age from 14 to 16, while the compulsory education age remained at 14. This reform changed the within-cohort incentives to remain in the educational system. We use a difference-in-differences approach, where our treated and control individuals only differ in their month of birth, to analyze the gender asymmetries in mortality generated by this change. The reform decreased mortality at ages 14–29 among men by 6.4% and women by 8.9%, mainly from a reduction in deaths due to traffic accidents. However, the reform also increased mortality for women ages 30–45 by 7%. This is driven by increases in HIV mortality, as well as by diseases related to the nervous and circulatory systems. We show that women’s health habits deteriorated as a consequence of the reform, while this was not the case for men. The gender differences in the impact of the reform on smoking and drinking should be understood in the context of the gender equalization process that affected women were experiencing when the reform took place. All in all, these patterns help explain the narrowing age gap in life expectancy between women and men in many developed countries while, at the same time, they provide important policy implications for middle-income countries that are undergoing those gender equalization processes right now.
Competing power generation sources have experienced considerable shifts in both their revenue potential and their costs in recent years. Here we introduce the concept of Levelized Profit Margins (LPM) to capture the changing unit economics of both intermittent and dispatchable generation technologies. We apply this framework in the context of the California and Texas wholesale power markets. Our LPM estimates indicate that solar photovoltaic and wind power have both substantially improved their competitive position during the years 2012–2019, primarily due to falling life-cycle costs of production. In California, these gains far outweigh an emerging “cannibalization” effect that results from substantial additions of solar power having made energy less valuable in the middle of the day. As such, intermittent renewables in both states have been approaching or exceeding the break-even value of zero for the estimated LPMs. We also find the competitiveness of natural gas power plants to have either improved in Texas or held steady at negative LPMs in California. For these plants, declining capacity utilization rates have effectively been counterbalanced by a “dispatchability price premium” that reflects the growing market share of intermittent renewables.
Introduction Activation of the plasmatic coagulation system is a major contributor to acute myocardial infarction (AMI). Markers of plasmatic coagulation and thrombin activation are correlated with clinical, laboratory and outcome parameters. In this study, we sought to evaluate if the catalytically active coagulation factors thrombin and activated protein C (APC) can be measured in patients with AMI and whether there are associations with laboratory or clinical parameters. Methods Thrombin and APC was quantified using oligonucleotide-enzyme-capture assays (OECAs) in 132 patients presenting with AMI immediately before and 24 h after percutaneous coronary intervention (PCI). Results APC was measured above the lower limit of quantification (LLOQ) in 43 (32.6%) patients before PCI (day 0) and in 55 (41.7%) patients on the following day (day 1). Thrombin was measured in 62 (47.0%) patients on day 0 and 60 (45.5%) on day 1. Both APC and thrombin were correlated with markers of thrombin generation including F1 + 2 and TAT. Additionally, APC values correlated with CK and CK-MB while thrombin correlated with CK and troponin I after PCI. APC levels above a cutoff of 0.141 ng/ml after PCI, but not thrombin, predicted 30 day major adverse cerebrovascular events. Conclusion Both thrombin and APC were elevated above the LLOQ in a subset of patients with AMI before and after PCI and correlated with surrogate markers of myocardial injury. Our results indicate that enzymatically active APC and thrombin are present in the circulation of patients with AMI.
Security of supply concerns are at the forefront of the public debate. The pandemic and post-pandemic times have demonstrated that preparing for global shocks requires the quick availability of some essential goods and services, including energy. Private incentives are typically insufficient for an economy to be prepared for rare events with large negative impacts. Instead, governments and preferably supranational institutions should implement mechanisms that make sure that prevention, detection and mitigation measures are taken. The economics of electricity capacity mechanisms provides valuable lessons for the provision of essential goods in such events, which need to be complemented with other elements aimed at mitigating the causes and impacts of potential crises.
Purpose: Regular sports activities are associated with multiple physical and psychological health benefits. However, sports also may lead to injuries and the development of osteoarthritis (OA). This systematic review investigated the association between sports activity, sports type, and the risk of developing OA. Methods: A systematic review was performed by assessing studies that have investigated the risk of OA development in sports. Data extracted included general information, study design, number of participants, related body mass index, sports type, and assessment of OA. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. Results: A total of 63 studies were included in this systematic review. The overall Newcastle-Ottawa Scale score was 6.46±1.44 demonstrating a good methodological quality of the articles included in the present study. A total of 628,036 participants were included, with a mean follow-up of 8.0±8.4 years. The mean age of the included athletes was 45.6±15.8, with a mean body mass index of 24.9±2.3 kg/m2. Conclusion: Football and soccer players seem to be at higher risk for the development of OA, although the injury status of the joint should be considered when assessing the risk of OA. High equipment weight and increased injury risk also put military personnel at a higher risk of OA, although elite dancing leads to more hip labral tears. Femoroacetabular impingement was also often diagnosed in ice-hockey players and ballet dancers.
Testing for genetic alterations in tumor tissue allows clinicians to identify patients who most likely will benefit from molecular targeted treatment. EXLIQUID – exploiting liquid biopsies to advance cancer precision medicine – investigates the potential of additional non-invasive tools for guiding therapy decisions and monitoring of advanced cancer patients. The term “liquid biopsy” (LB) refers to non-invasive analysis of tumor-derived circulating material such as cell-free DNA in blood samples from cancer patients. Although recent technological advances allow sensitive and specific detection of LB biomarkers, only few LB assays have entered clinical routine to date. EXLIQUID is a German Cancer Consortium (DKTK)-wide joint funding project that aims at establishing LBs as a minimally-invasive tool to analyze molecular changes in circulating tumor DNA (ctDNA). Here, we present the structure, clinical aim, and methodical approach of the new DKTK EXLIQUID consortium. Within EXLIQUID, we will set up a multicenter repository of high-quality LB samples from patients participating in DKTK MASTER and local molecular tumor boards, which use molecular profiles of tumor tissues to guide targeted therapies. We will develop LB assays for monitoring of therapy efficacy by the analysis of tumor mutant variants and tumor-specific DNA methylation patterns in ctDNA from these patients. By bringing together LB experts from all DKTK partner sites and exploiting the diversity of their particular expertise, complementary skills and technologies, the EXLIQUID consortium addresses the challenges of translating LBs into the clinic. The DKTK structure provides EXLIQUID a unique position for the identification of liquid biomarkers even in less common tumor types, thereby extending the group of patients benefitting from non-invasive LB testing. Besides its scientific aims, EXLIQUID is building a valuable precision oncology cohort and LB platform which will be available for future collaborative research studies within the DKTK and beyond.
Conduct problems (CP) in patients with disruptive behavior disorders have been linked to impaired prefrontal processing of negative facial affect compared to controls. However, it is unknown whether associations with prefrontal activity during affective face processing hold along the CP dimension in a healthy population sample, and how subcortical processing is affected. We measured functional brain responses during negative affective face processing in 1444 healthy adolescents [ M = 14.39 years (SD = 0.40), 51.5% female] from the European IMAGEN multicenter study. To determine the effects of CP, we applied a two-step approach: (a) testing matched subgroups of low versus high CP, extending into the clinical range [ N = 182 per group, M = 14.44 years, (SD = 0.41), 47.3% female] using analysis of variance, and (b) considering (non)linear effects along the CP dimension in the full sample and in the high CP group using multiple regression. We observed no significant cortical or subcortical effect of CP group on brain responses to negative facial affect. In the full sample, regression analyses revealed a significant linear increase of left orbitofrontal cortex (OFC) activity with increasing CP up to the clinical range. In the high CP group, a significant inverted u-shaped effect indicated that left OFC responses decreased again in individuals with high CP. Left OFC activity during negative affective processing which is increasing with CP and decreasing in the highest CP range may reflect on the importance of frontal control mechanisms that counteract the consequences of severe CP by facilitating higher social engagement and better evaluation of social content in adolescents.
Plain English Summary It is often argued that failure is a particularly rich source of learning. It is reasonable to expect, therefore, that entrepreneurs who have failed once will do better the second time than those who try for the first time. In this paper, we compare the survival chances of businesses of entrepreneurs who failed with their ventures in the past with those of first-time entrepreneurs (novices). We find that entrepreneurs whose previous business has failed keep new businesses running for less time than novices do. This result remains even after a series of robustness checks in which we look at different subgroups of entrepreneurs. Thus, we cannot find evidence for the assumption that previous entrepreneurial failure is particularly valuable for entrepreneurs. To explain our result, we point to the selection process that takes place before we see failed entrepreneurs another time in business. Some of the failed entrepreneurs decide to start again, while others do not, and it is likely that this process is not random. A potential driver of this process is entrepreneurial talent and our results are consistent with the hypothesis that failed entrepreneurs are those with below-average entrepreneurial talent. Although this does not imply that all entrepreneurs who failed have poor talent, a general second-chance policy cannot be easily justified. A targeted search and support of high-profile entrepreneurs among the failed might be more sensible.
Purpose Displaced femoral neck fractures (FNF) usually require surgical treatment with either a total hip arthroplasty (THA), unipolar hemiarthroplasty (U-HHA), or bipolar hemiarthroplasty (B-HHA). However, there is still controversy regarding the optimal implant. This network meta-analysis compared the outcomes and complication rates of THA versus B-HHA and versus U-HHA in elderly patients with FNF. Material and methods This study was conducted according to the PRISMA extension statement for reporting of systematic reviews, and incorporated network meta-analyses of health care interventions. The literature search was performed in September 2020. All randomized clinical trials comparing two or more of the index surgical interventions for displaced FNF in the elderly were eligible for inclusion. For the Bayesian network meta-analysis, the standardized mean difference (SMD) and Log Odd Ratio (LOR) were used. Results Data from 24 RCTs (2808 procedures) were analysed. The mean follow-up was 33.8 months. The THA group had the longest surgical time (SMD 85.74) and the greatest Harris Hip Score (SMD − 17.31). THA scored similarly in terms of mortality (LOR 3.89), but had lower rates of revision surgeries (LOR 2.24), higher rates of dislocations (LOR 2.60), and lower rates of acetabular erosion (LOR − 0.02). Cementless implants required a shorter surgical duration (− 18.05 min; P = 0.03). Mortality was positively associated with acetabular erosion ( P = 0.006), female gender ( P = 0.007), revision ( P < 0.0001). Conclusion THA led to the highest Harris Hip scores and lowest rate of revision surgery compared to B-HHA and U-HHA. However, B-HHA had the lowest dislocation rate when compared with U-HHA and THA. No significant differences in functional outcomes and complication rates were found between cemented and uncemented implants; however, a tendency for lower mortality, revision and dislocation rates in cemented implants was evidenced. Level of evidence I, Bayesian network meta-analysis of RCTs.
Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm associated with poor overall survival (OS). This study (NCT04695431) compared clinical outcomes between patients with AdvSM treated with avapritinib in the Phase 1 EXPLORER (NCT0256198) and Phase 2 PATHFINDER (NCT03580655) trials (N = 176) and patients treated with best available therapy (BAT; N = 141). A multi-center, observational, retrospective chart review study was conducted at six study sites (four European, two American) to collect data from patients with AdvSM who received BAT; these data were pooled with data from EXPLORER and PATHFINDER. Comparisons between outcomes of OS, duration of treatment (DOT), and maximum reduction in serum tryptase were conducted between the treatment cohorts, with adjustment for key covariates. The results indicated that the avapritinib cohort had significantly better survival (adjusted hazard ratio (HR) (95% confidence interval (CI)): 0.48 (0.29, 0.79); p = 0.004) and significantly longer DOT (HR: 0.36 (0.26, 0.51); p < 0.001) compared to the BAT cohort. Additionally, the mean difference in percentage maximum reduction in serum tryptase levels was 60.3% greater in the avapritinib cohort (95% CI: −72.8, −47.9; p < 0.001). With no randomized controlled trials comparing avapritinib to BAT, these data offer crucial insights into the improved efficacy of avapritinib for the treatment of AdvSM.
In an artefactual field experiment with a large and heterogeneous population sample, we test the implications of social norms for market interactions associated with negative real-world externalities. We run large stylized markets in which sellers and buyers decide whether to enter the market and how much to bid for experimental coupons. Trading leads to profits for sellers and buyers but at the same time destroys donations for a good cause. Calculated over all our treatments, we observe that two-thirds of the participants refuse to trade. Eliciting a controlled measure for conditional moral behavior in one treatment, we find that roughly a quarter of potential traders make their decisions contingent on the decisions of others, indicating that the desire to conform to social norms affects trading decisions in markets with negative externalities. If observers can sanction traders, we find that more than 80% of them are willing to incur personal costs to sanction trading, thus enforcing a social norm for moral behavior.
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5,397 members
Teresa Naab
  • Institut für Medien- und Kommunikationswissenschaft
Jennifer Shore
  • Mannheimer Zentrum für Europäische Sozialforschung
Jochen Streb
  • Department of Economics
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Mannheim, Germany