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Background: Limited understanding exists regarding the influences of engagement, persistence and adherence on the efficacy of cognitive training for age-related cognitive decline and neurodegenerative cognitive impairment., Methods: This study conducted a meta-analysis of randomised controlled trials (RCTs). We systematically searched MEDLINE, PubMed, Web of Science, Embase and CINAHL databases from 1 January 2012 to 13 June 2023, and included RCTs assessing the effects of cognitive training in older adults, both with and without cognitive impairment. Hedges' g with a 95% confidence interval (CI) was used to synthesise cognitive training effect sizes on various neuropsychological tests. Subgroup analyses were conducted based on variables including engagement, persistence, adherence and cognitive conditions of normal cognition, mild cognitive impairment (MCI) or neurodegenerative dementia., Results: This meta-analysis included 55 RCTs with 4,455 participants with cognitive conditions spanning normal cognition, MCI and neurodegenerative dementia. The mean age of participants was 73.9 (range: 65.7-84.5) years. Overall, cognitive training showed a significant cross-domain effect (Hedges' g = 0.286, 95% CI: 0.224-0.348). Training effects are significant when engagement or persistence rates exceed 60% or when adherence rates exceed 80%. Higher levels of persistence are required to achieve significant training effects in memory, visuospatial ability and reasoning than in executive function and attention and language. Higher persistence is also required for older adults with normal cognition to achieve significant training gains compared to those with cognitive impairment., Conclusions: This systematic review highlights the critical roles of engagement, persistence and adherence in augmenting the efficacy of cognitive training., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Biosocial surveys increasingly use interviewers to collect objective physical health measures (or "biomeasures") in respondents' homes. While interviewers play an important role, their high involvement can lead to unintended interviewer effects on the collected measurements. Such interviewer effects add uncertainty to population estimates and have the potential to lead to erroneous inferences. This study examines interviewer effects on the measurement of physical performance in a cross-national and longitudinal setting using data from the Survey of Health, Ageing and Retirement in Europe. The analyzed biomeasures exhibited moderate-to-large interviewer effects on the measurements, which varied across biomeasure types and across countries. Our findings demonstrate the necessity to better understand the origin of interviewer-related measurement errors in biomeasure collection and account for these errors in statistical analyses of biomeasure data., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Association for Public Opinion Research.)

Survey participants' mouse movements provide a rich, unobtrusive source of paradata, offering insight into the response process beyond the observed answers. However, the use of mouse tracking may require participants' explicit consent for their movements to be recorded and analyzed. Thus, the question arises of how its presence affects the willingness of participants to take part in a survey at all-if prospective respondents are reluctant to complete a survey if additional measures are recorded, collecting paradata may do more harm than good. Previous research has found that other paradata collection modes reduce the willingness to participate, and that this decrease may be influenced by the specific motivation provided to participants for collecting the data. However, the effects of mouse movement collection on survey consent and participation have not been addressed so far. In a vignette experiment, we show that reported willingness to participate in a survey decreased when mouse tracking was part of the overall consent. However, a larger proportion of the sample indicated willingness to both take part and provide mouse-tracking data when these decisions were combined, compared to an independent opt-in to paradata collection, separated from the decision to complete the study. This suggests that survey practitioners may face a trade-off between maximizing their overall participation rate and maximizing the number of participants who also provide mouse-tracking data. Explaining motivations for paradata collection did not have a positive effect and, in some cases, even reduced participants' reported willingness to take part in the survey., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Association for Public Opinion Research.)

Cognitive control involves evidence accumulation and response thresholding, but the neural underpinnings of these 2 processes are poorly understood. Based on recent findings that midfrontal theta phase coordinates the correlation between theta power and reaction time during cognitive control, this study investigated whether and how theta phase would modulate the relationships between theta power and evidence accumulation and response thresholding in human participants when they performed a flanker task. Our results confirmed the modulation of theta phase on the correlations between ongoing midfrontal theta power and reaction time under both conditions. Using hierarchical drift-diffusion regression modeling, we found that in both conditions, theta power was positively associated with boundary separation in phase bins with optimal power-reaction time correlations, whereas the power-boundary correlation decreased to nonsignificance in phase bins with reduced power-reaction time correlations. In contrast, the power-drift rate correlation was not modulated by theta phase, but by cognitive conflict. Drift rate was positively correlated with theta power for the bottom-up processing in the non-conflict condition, whereas it was negatively correlated with theta power for the top-down control to address conflict. These findings suggest that evidence accumulation is likely to be a phase-coordinated continuous process, whereas thresholding may be a phase-specific transient process., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To study human behavior, social scientists are increasingly collecting data from mobile apps and sensors embedded in smartphones. A major challenge of studies implemented on general population samples, however, is that participation rates are rather low. While previous research has started to investigate the factors affecting individuals' decision to participate in such studies, less is known about features of the study design which are under the researcher's control and can increase the acceptance of smartphone-based data collection methods. Guided by the Technology Acceptance Model, we varied study characteristics in a vignette experiment to examine their effect on individuals' willingness to download a research app on their smartphone. Data were collected from 1,876 members of the NORC AmeriSpeak Panel, a probability-based panel of the general population aged 18+ in the United States. Respondents were randomly assigned to eight vignettes and, after each vignette, were asked to rate their willingness to participate in the described hypothetical study. The results show that individuals are more willing to participate in smartphone-based studies where they have some control over the data collection process, by having the option either to temporarily switch off the data collection or to review the data before submission. Furthermore, they are more willing to participate in research to which they are invited via postal letter rather than receiving a postal letter plus a phone call from an interviewer who walks them through the app installation. Finally, unconditional incentives increase their willingness to engage with smartphone-based data collection over conditional incentives., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Association for Public Opinion Research.)

Previous studies investigated the age-related positivity effect in terms of emotion perception and management, whereas little is known about whether the positivity effect is shown in emotion utilization (EU). If yes, the EU-related intrinsic functional connectivity and its age-associated alterations remain to be elucidated. In this study, we collected resting-state functional magnetic resonance imaging data from 62 healthy older adults and 72 undergraduates as well as their self-ratings of EU. By using the connectome-based predictive modeling (CPM) method, we constructed a predictive model of the positive relationship between EU self-ratings and resting-state functional connectivity. Lesion simulation analyses revealed that the medial-frontal network, default mode network, frontoparietal network, and subcortical regions played key roles in the EU-related CPM. Older subjects showed significantly higher EU self-ratings than undergraduates, which was associated with strengthened connectivity between the left dorsolateral prefrontal cortex and bilateral frontal poles, and between the left frontal pole and thalamus. A mediation analysis indicated that the age-related EU network mediated the age effect on EU self-ratings. Our findings extend previous research on the age-related "positivity effect" to the EU domain, suggesting that the positivity effect on the self-evaluation of EU is probably associated with emotion knowledge which accumulates with age., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Few tract-based spatial statistics (TBSS) studies have investigated the relations between intelligence and white matter microstructure in healthy (young) adults, and those have yielded mixed observations, yet white matter is fundamental for efficient and accurate information transfer throughout the human brain. We used a multicenter approach to identify white matter regions that show replicable structure-function associations, employing data from 4 independent samples comprising over 2000 healthy participants. TBSS indicated 188 voxels exhibited significant positive associations between g factor scores and fractional anisotropy (FA) in all 4 data sets. Replicable voxels formed 3 clusters, located around the left-hemispheric forceps minor, superior longitudinal fasciculus, and cingulum-cingulate gyrus with extensions into their surrounding areas (anterior thalamic radiation, inferior fronto-occipital fasciculus). Our results suggested that individual differences in general intelligence are robustly associated with white matter FA in specific fiber bundles distributed across the brain, consistent with the Parieto-Frontal Integration Theory of intelligence. Three possible reasons higher FA values might create links with higher g are faster information processing due to greater myelination, more direct information processing due to parallel, homogenous fiber orientation distributions, or more parallel information processing due to greater axon density., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The social representation theory states that individual differences in reciprocity decisions are composed of a stable central core (i.e., reciprocity propensity, RP) and a contextual-dependent periphery (i.e., sensitivity to the framing effect; SFE, the effect by how the decision is presented). However, the neural underpinnings that explain RP and SFE are still unknown., Method: Here, we employed prediction and lesion models to decode resting-state functional connectivity (RSFC) of RP and SFE for reciprocity decisions of healthy volunteers who underwent RS functional magnetic resonance imaging and completed one-shot trust (give frame) and distrust (take frame) games as trustees., Results: Regarding the central core, reciprocity rates were positively associated between the give and take frame. Neuroimaging results showed that inter-network RSFC between the default-mode network (DMN; associated with mentalizing) and cingulo-opercular network (associated with cognitive control) contributed to the prediction of reciprocity under both frames. Regarding the periphery, behavioral results demonstrated a significant framing effect-people reciprocated more in the give than in the take frame. Our neuroimaging results revealed that intra-network RSFC of DMN (associated with mentalizing) contributed dominantly to the prediction of SFE., Conclusion: Our findings provide evidence for distinct neural mechanisms of RP and SFE in reciprocity decisions., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Apathy is a quantitative reduction in motivation and goal-directed behaviors, not only observed in neuropsychiatric disorders, but also present in healthy populations. Although brain abnormalities associated with apathy in clinical disorders have been studied, the organization of brain networks in healthy individuals has yet to be identified., Method: We examined properties of intrinsic brain networks in healthy individuals with varied levels of apathy. By using functional magnetic resonance imaging in combination with graph theory analysis and dynamic causal modeling analysis, we tested communications among nodes and modules as well as effective connectivity among brain networks., Results: We found that the average participation coefficient of the subcortical network, especially the amygdala, was lower in individuals with high than low apathy. Importantly, we observed weaker effective connectivity fromthe hippocampus and parahippocampal gyrus to the amygdala, and from the amygdala to the parahippocampal gyrus and medial frontal cortex in individuals with apathy., Conclusion: These findings suggest that individuals with high apathy exhibit aberrant communication within the cortical-to-subcortical network, characterized by differences in amygdala-related effective connectivity. Our work sheds light on the neural basis of apathy in subclinical populations and may have implications for understanding the development of clinical conditions that feature apathy., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Images might provide richer and more objective information than text answers to open-ended survey questions. Little is known, nonetheless, about the consequences for data quality of asking participants to answer open-ended questions with images. Therefore, this paper addresses three research questions: (1) What is the effect of answering web survey questions with images instead of text on breakoff, noncompliance with the task, completion time and question evaluation? (2) What is the effect of including a motivational message on these four aspects? (3) Does the impact of asking to answer with images instead of text vary across device types? To answer these questions, we implemented a 2 × 3 between-subject web survey experiment ( N  = 3043) in Germany. Half of the sample was required to answer using PCs and the other half with smartphones. Within each device group, respondents were randomly assigned to (1) a control group answering open-ended questions with text; (2) a treatment group answering open-ended questions with images; and (3) another treatment group answering open-ended questions with images but prompted with a motivational message. Results show that asking participants to answer with images significantly increases participants' likelihood of noncompliance as well as their completion times, while worsening their overall survey experience. Including motivational messages, moreover, moderately reduces the likelihood of noncompliance. Finally, the likelihood of noncompliance is similar across devices., (© 2022 The Authors. Journal of the Royal Statistical Society: Series A (Statistics in Society) published by John Wiley & Sons Ltd on behalf of Royal Statistical Society.)

Cardiovascular diseases are the main cause of sudden cardiac death (SCD) in developed and developing countries. Inherited cardiac channelopathies are linked to 5-10% of SCDs, mainly in the young. Short QT syndrome (SQTS) is a rare inherited channelopathy, which leads to both atrial and ventricular tachyarrhythmias, syncope, and even SCD. International European Society of Cardiology guidelines include as diagnostic criteria: (i) QTc ≤ 340 ms on electrocardiogram, (ii) QTc ≤ 360 ms plus one of the follwing, an affected short QT syndrome pathogenic gene mutation, or family history of SQTS, or aborted cardiac arrest, or family history of cardiac arrest in the young. However, further evaluation of the QTc ranges seems to be required, which might be possible by assembling large short QT cohorts and considering genetic screening of the newly described pathogenic mutations. Since the mechanisms underlying the arrhythmogenesis of SQTS is unclear, optimal therapy for SQTS is still lacking. The disease is rare, unclear genotype-phenotype correlations exist in a bevy of cases and the absence of an international short QT registry limit studies on the pathophysiological mechanisms of arrhythmogenesis and therapy of SQTS. This leads to the necessity of experimental models or platforms for studying SQTS. Here, we focus on reviewing preclinical SQTS models and platforms such as animal models, heterologous expression systems, human-induced pluripotent stem cell-derived cardiomyocyte models and computer models as well as three-dimensional engineered heart tissues. We discuss their usefulness for SQTS studies to examine genotype-phenotype associations, uncover disease mechanisms and test drugs. These models might be helpful for providing novel insights into the exact pathophysiological mechanisms of this channelopathy and may offer opportunities to improve the diagnosis and treatment of patients with SQT syndrome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Deviant interviewer behavior is a potential hazard of interviewer-administered surveys, with interviewers fabricating entire interviews as the most severe form. Various statistical methods (e.g., cluster analysis) have been proposed to detect falsifiers. These methods often rely on falsification indicators aiming to measure differences between real and falsified data. However, due to a lack of real-world data, empirical evaluations and comparisons of different statistical methods and falsification indicators are scarce. Using a large-scale nationally representative refugee survey in Germany with known fraudulent interviews, this study tests, evaluates, and compares statistical methods for identifying falsified data. We investigate the use of new and existing falsification indicators as well as multivariate detection methods for combining them. Additionally, we introduce a new and easy-to-use multivariate detection method that overcomes practical limitations of previous methods. We find that the vast majority of used falsification indicators successfully measure differences between falsifiers and nonfalsifiers, with the newly proposed falsification indicators outperforming some existing indicators. Furthermore, different multivariate detection methods perform similarly well in detecting the falsifiers., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Association for Public Opinion Research.)

We examine how the life courses of couples in East and West Germany are linked to women's income in later life using multichannel sequence analysis. By applying a couple perspective, we overcome the individualistic approach in most previous research analysing women's old-age income. Detailed monthly information on spouses' employment and earnings trajectories from age 20 to 50 for the birth cohorts 1925-1965 ( N  = 2020) stems from SHARE-RV, a data linkage of the administrative records of the German public pension insurance with the Survey of Health, Ageing and Retirement in Europe (SHARE). We identify seven clusters of couples' life courses and link them to women's absolute individual and relative household income in later life using a cohort comparison to identify trends over time. While in older cohorts, women in male-breadwinner type clusters achieve the lowest, and those in dual-earner type couples have the highest incomes, this relationship does no longer prevail in younger cohorts. Here, we identify a polarization in dual-earner and male-breadwinner type clusters. The former increasingly diverge into successful female-breadwinner constellations and those with both partners in marginalized careers. The latter polarize between persistent male-breadwinner constellations and those in which women increase their labor market engagement., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Carcinoma associated with perianal fistula in Crohn's disease is a pending threat for patients. This study aimed to improve understanding and facilitate development of diagnostic and therapeutic strategies., Methods: A retrospective case-control study was conducted at four German hospitals. The analysis included 40 patients with proven malignancy associated with perianal Crohn's fistulas and 40 randomly selected controls with fistulizing perianal Crohn's disease. Differences between groups were analysed and multivariate calculations were performed to describe risk factors for oncological outcomes., Results: Histology revealed adenocarcinoma in 33/40 patients and squamous cell carcinoma in 7/40 patients. Compared to fistula patients without carcinoma, patients with malignancies associated with fistula had a diagnosis of Crohn's disease at younger age. Crohn's disease lasted longer in patients with malignancy [25.8 ± 9.0 vs 19.6 ± 10.4; p = 0.006]. Fistula-related findings differed significantly between the two groups. Signs of complicated and severe fistulation including complex anatomy and chronic activity occurred significantly more often in patients with malignancy associated with fistula. Significant multivariate hazard ratios for overall mortality and progression-free survival were shown for histological type of cancer, metastatic disease and R1 resection. Overall survival was 45.1 ± 28.6 months and the 5-year survival rate was 65%., Conclusions: In patients with adenocarcinoma or squamous cell carcinoma associated with perianal fistula in Crohn's disease, fistula characteristics determine the risk of malignancy. Early diagnosis influences outcomes, while treatment of chronic fistula activity may be key to preventing malignancy. Expert multimodal therapy is paramount for successful treatment of perianal fistula-associated malignancies., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The present study combined a novel hypothetical investment game with functional magnetic resonance imaging to examine how moral conflict biases our real decision preference when it is not obvious or explicitly presented. Investment projects were chosen based on their prior subjective morality ratings to fit into 2 categories: a high level of moral conflict (HMC) or a low level of moral conflict (LMC). Participants were instructed to invest high or low amounts of capital into different projects. Behavioral and neural responses during decision making were recorded and compared. Behaviorally, we observed a significant decision bias such that investments were lower for HMC projects than for LMC projects. At the neural level, we found that moral conflict-related activity in the anterior cingulate cortex (ACC) was higher in the HMC condition than in the LMC condition and that reward-related activity in bilateral striatum was lower. Dynamic causal modeling further suggested that the moral conflict detected in the ACC influenced final decisions by modulating the representation of subjective value through the ACC's connection to the reward system., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study investigates how married mothers' relative bargaining power before the birth of their first child affects their subsequent accumulation of pension entitlements in East versus West Germany. I use a novel data linkage between the German sample of the "Survey of Health, Ageing and Retirement in Europe" and administrative records from the German pension insurance (SHARE-RV) to analyze monthly life-course data on married mothers from East ( N = 226) and West Germany ( N = 586) who were born between 1925 and 1967. Applying random effects growth curve models and mediation analyses, I find that women's relative bargaining power before parenthood is linked to their subsequent accumulation of pension entitlements in West (but not East) Germany. The results support the notion that bargaining power early in couples' linked lives has long-term consequences for women's pension income. Moreover, the results indicate that negotiations within the couple are constricted by the extent to which the institutional context supports or hinders the reconciliation of women's work-family conflict., (© The Author(s) 2021. Published by Oxford University Press. For permissions please e-mail: journals.permissions@oup.com.)

Psychological androgyny has long been associated with greater cognitive flexibility, adaptive behavior, and better mental health, but whether a similar concept can be defined using neural features remains unknown. Using the neuroimaging data from 9620 participants, we found that global functional connectivity was stronger in the male brain before middle age but became weaker after that, when compared with the female brain, after systematic testing of potentially confounding effects. We defined a brain gender continuum by estimating the likelihood of an observed functional connectivity matrix to represent a male brain. We found that participants mapped at the center of this continuum had fewer internalizing symptoms compared with those at the 2 extreme ends. These findings suggest a novel hypothesis proposing that there exists a neuroimaging concept of androgyny using the brain gender continuum, which may be associated with better mental health in a similar way to psychological androgyny., (© The Author(s) 2021. Published by Oxford University Press.)

Derailment of inhibitory control (IC) underlies numerous psychiatric and behavioral disorders, many of which emerge during adolescence. Identifying reliable predictive biomarkers that place the adolescents at elevated risk for future IC deficits can help guide early interventions, yet the scarcity of longitudinal research has hindered the progress. Here, using a large-scale longitudinal dataset in which the same subjects performed a stop signal task during functional magnetic resonance imaging at ages 14 and 19, we tracked their IC development individually and tried to find the brain features predicting their development by constructing prediction models using 14-year-olds' functional connections within a network or between a pair of networks. The participants had distinct between-subject trajectories in their IC development. Of the candidate connections used for prediction, ventral attention-subcortical network interconnections could predict the individual development of IC and formed a prediction model that generalized to previously unseen individuals. Furthermore, we found that connectivity between these two networks was related to substance abuse problems, an IC-deficit related problematic behavior, within 5 years. Our study reveals individual differences in IC development from mid- to late-adolescence and highlights the importance of ventral attention-subcortical network interconnections in predicting future IC development and substance abuse in adolescents., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cross-sectional studies have found that the coronavirus disease 2019 (COVID-19) pandemic has negatively affected population-level mental health. Longitudinal studies are necessary to examine trajectories of change in mental health over time and identify sociodemographic groups at risk for persistent distress., Purpose: To examine the trajectories of mental distress between March 10 and August 4, 2020, a key period during the COVID-19 pandemic., Methods: Participants included 6,901 adults from the nationally representative Understanding America Study, surveyed at baseline between March 10 and 31, 2020, with nine follow-up assessments between April 1 and August 4, 2020. Mixed-effects logistic regression was used to examine the association between date and self-reported mental distress (measured with the four-item Patient Health Questionnaire) among U.S. adults overall and among sociodemographic subgroups defined by sex, age, race/ethnicity, household structure, federal poverty line, and census region., Results: Compared to March 11, the odds of mental distress among U.S. adults overall were 1.84 (95% confidence interval [CI] = 1.65-2.07) times higher on April 1 and 1.92 (95% CI = 1.62-2.28) times higher on May 1; by August 1, the odds of mental distress had returned to levels comparable to March 11 (odds ratio [OR] = 0.80, 95% CI = 0.66-0.96). Females experienced a sharper increase in mental distress between March and May compared to males (females: OR = 2.29, 95% CI = 1.85-2.82; males: OR = 1.53, 95% CI = 1.15-2.02)., Conclusions: These findings highlight the trajectory of mental health symptoms during an unprecedented pandemic, including the identification of populations at risk for sustained mental distress., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Voice modulation is important when navigating social interactions-tone of voice in a business negotiation is very different from that used to comfort an upset child. While voluntary vocal behavior relies on a cortical vocomotor network, social voice modulation may require additional social cognitive processing. Using functional magnetic resonance imaging, we investigated the neural basis for social vocal control and whether it involves an interplay of vocal control and social processing networks. Twenty-four healthy adult participants modulated their voice to express social traits along the dimensions of the social trait space (affiliation and competence) or to express body size (control for vocal flexibility). Naïve listener ratings showed that vocal modulations were effective in evoking social trait ratings along the two primary dimensions of the social trait space. Whereas basic vocal modulation engaged the vocomotor network, social voice modulation specifically engaged social processing regions including the medial prefrontal cortex, superior temporal sulcus, and precuneus. Moreover, these regions showed task-relevant modulations in functional connectivity to the left inferior frontal gyrus, a core vocomotor control network area. These findings highlight the impact of the integration of vocal motor control and social information processing for socially meaningful voice modulation., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Vancomycin is an extensively used anti-infective drug in neonatal ICUs. However, exposure-toxicity relationships have not been clearly defined., Objectives: To evaluate the risk profile for hearing deficits in vancomycin-exposed very-low-birthweight infants (VLBWI)., Methods: In a large cohort study of the German Neonatal Network (GNN; n = 16 967 VLBWI) we assessed the association of vancomycin treatment and pathological hearing tests at discharge and at 5 year follow-up. We performed audits on vancomycin exposure, drug levels, dose adjustments and exposure to other ototoxic drugs in a subgroup of 1042 vancomycin-treated VLBWI., Results: In the GNN cohort, 28% (n = 4739) were exposed to IV vancomycin therapy. In multivariable logistic regression analysis, vancomycin exposure proved to be independently associated with pathological hearing test at discharge (OR 1.18, 95% CI 1.03-1.34, P = 0.016). Among vancomycin-treated infants, a cumulative vancomycin dose above the upper quartile (>314 mg/kg bodyweight) was associated with pathological hearing test at discharge (OR 2.1, 95% CI 1.21-3.64, P = 0.009), whereas a vancomycin cumulative dose below the upper quartile was associated with a reduced risk of pathological tone audiometry results at 5 years of age (OR 0.29, 95% CI 0.1-0.8, P = 0.02, n = 147)., Conclusions: Vancomycin exposure in VLBWI is associated with an increased, dose-dependent risk of pathological hearing test results at discharge and at 5 years of age. Prospective studies on long-term hearing impairment are needed., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The R-package MoBPS provides a computationally efficient and flexible framework to simulate complex breeding programs and compare their economic and genetic impact. Simulations are performed on the base of individuals. MoBPS utilizes a highly efficient implementation with bit-wise data storage and matrix multiplications from the associated R-package miraculix allowing to handle large scale populations. Individual haplotypes are not stored but instead automatically derived based on points of recombination and mutations. The modular structure of MoBPS allows to combine rather coarse simulations, as needed to generate founder populations, with a very detailed modeling of todays' complex breeding programs, making use of all available biotechnologies. MoBPS provides pre-implemented functions for common breeding practices such as optimum genetic contributions and single-step GBLUP but also allows the user to replace certain steps with personalized and/or self-written solutions., (Copyright © 2020 Pook et al.)

Background: In heart failure with reduced left ventricular ejection fraction (HFrEF) patients the effects of exercise-based cardiac rehabilitation on top of state-of-the-art pharmacological and device therapy on mortality, hospitalization, exercise capacity and quality-of-life are not well established., Design: The design of this study involved a structured review and meta-analysis., Methods: Evaluation of randomised controlled trials of exercise-based cardiac rehabilitation in HFrEF-patients with left ventricular ejection fraction ≤40% of any aetiology with a follow-up of ≥6 months published in 1999 or later., Results: Out of 12,229 abstracts, 25 randomised controlled trials including 4481 HFrEF-patients were included in the final evaluation. Heterogeneity in study population, study design and exercise-based cardiac rehabilitation-intervention was evident. No significant difference in the effect of exercise-based cardiac rehabilitation on mortality compared to control-group was found (hazard ratio 0.75, 95% confidence interval 0.39-1.41, four studies; 12-months follow-up: relative risk 1.29, 95% confidence interval 0.66-2.49, eight studies; six-months follow-up: relative risk 0.91, 95% confidence interval 0.26-3.16, seven studies). In addition there was no significant difference between the groups with respect to 'hospitalization-for-any-reason' (12-months follow-up: relative risk 0.79, 95% confidence interval 0.41-1.53, four studies), or 'hospitalization-due-to-heart-failure' (12-months follow-up: relative risk 0.59, 95% confidence interval 0.12-2.91, four studies; six-months follow-up: relative risk 0.84, 95% confidence interval 0.07-9.71, three studies). All studies show improvement of exercise capacity. Participation in exercise-based cardiac rehabilitation significantly improved quality-of-life as evaluated with the Kansas City Cardiomyopathy Questionnaire: (six-months follow-up: mean difference 1.94, 95% confidence interval 0.35-3.56, two studies), but no significant results emerged for quality-of-life measured by the Minnesota Living with Heart Failure Questionnaire (nine-months or more follow-up: mean difference -4.19, 95% confidence interval -10.51-2.12, seven studies; six-months follow-up: mean difference -5.97, 95% confidence interval -16.17-4.23, four studies)., Conclusion: No association between exercise-based cardiac rehabilitation and mortality or hospitalisation could be observed in HFrEF patients but exercise-based cardiac rehabilitation is likely to improve exercise capacity and quality of life.

Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2-94.3; P < 0.005), and up to 3.0% in IntegraMooDS (F1,725 = 10.0-21.0; P < 0.005). The association between polygenic scores and g-factor was partially mediated by SA and CT in prefrontal, anterior cingulate, insula, and medial temporal cortices in both samples (PFWER-corrected < 0.005). The variance explained by mediation was up to 0.75% in IMAGEN and 0.77% in IntegraMooDS. Our results provide evidence that cumulative genetic load influences g-factor via cortical structure. The consistency of our results across samples suggests that cortex morphology could be a novel potential biomarker for neurocognitive dysfunction that is among the most intractable psychiatric symptoms., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The additive genomic variance in linear models with random marker effects can be defined as a random variable that is in accordance with classical quantitative genetics theory. Common approaches to estimate the genomic variance in random-effects linear models based on genomic marker data can be regarded as estimating the unconditional (or prior) expectation of this random additive genomic variance, and result in a negligence of the contribution of linkage disequilibrium (LD). We introduce a novel best prediction (BP) approach for the additive genomic variance in both the current and the base population in the framework of genomic prediction using the genomic best linear unbiased prediction (gBLUP) method. The resulting best predictor is the conditional (or posterior) expectation of the additive genomic variance when using the additional information given by the phenotypic data, and is structurally in accordance with the genomic equivalent of the classical additive genetic variance in random-effects models. In particular, the best predictor includes the contribution of (marker) LD to the additive genomic variance and possibly fully eliminates the missing contribution of LD that is caused by the assumptions of statistical frameworks such as the random-effects model. We derive an empirical best predictor (eBP) and compare its performance with common approaches to estimate the additive genomic variance in random-effects models on commonly used genomic datasets., (Copyright © 2019 Schreck et al.)

The concept of haplotype blocks has been shown to be useful in genetics. Fields of application range from the detection of regions under positive selection to statistical methods that make use of dimension reduction. We propose a novel approach ("HaploBlocker") for defining and inferring haplotype blocks that focuses on linkage instead of the commonly used population-wide measures of linkage disequilibrium. We define a haplotype block as a sequence of genetic markers that has a predefined minimum frequency in the population, and only haplotypes with a similar sequence of markers are considered to carry that block, effectively screening a dataset for group-wise identity-by-descent. From these haplotype blocks, we construct a haplotype library that represents a large proportion of genetic variability with a limited number of blocks. Our method is implemented in the associated R-package HaploBlocker, and provides flexibility not only to optimize the structure of the obtained haplotype library for subsequent analyses, but also to handle datasets of different marker density and genetic diversity. By using haplotype blocks instead of single nucleotide polymorphisms (SNPs), local epistatic interactions can be naturally modeled, and the reduced number of parameters enables a wide variety of new methods for further genomic analyses such as genomic prediction and the detection of selection signatures. We illustrate our methodology with a dataset comprising 501 doubled haploid lines in a European maize landrace genotyped at 501,124 SNPs. With the suggested approach, we identified 2991 haplotype blocks with an average length of 2685 SNPs that together represent 94% of the dataset., (Copyright © 2019 by the Genetics Society of America.)

The rising penetration of smartphones now gives researchers the chance to collect data from smartphone users through passive mobile data collection via apps. Examples of passively collected data include geolocation, physical movements, online behavior and browser history, and app usage. However, to passively collect data from smartphones, participants need to agree to download a research app to their smartphone. This leads to concerns about nonconsent and nonparticipation. In the current study, we assess the circumstances under which smartphone users are willing to participate in passive mobile data collection. We surveyed 1,947 members of a German nonprobability online panel who own a smartphone using vignettes that described hypothetical studies where data are automatically collected by a research app on a participant's smartphone. The vignettes varied the levels of several dimensions of the hypothetical study, and respondents were asked to rate their willingness to participate in such a study. Willingness to participate in passive mobile data collection is strongly influenced by the incentive promised for study participation but also by other study characteristics (sponsor, duration of data collection period, option to switch off the app) as well as respondent characteristics (privacy and security concerns, smartphone experience).

Background: Exercise-based cardiac rehabilitation (ebCR) often includes various psychological interventions for lifestyle change or distress management. However, the additional benefit of specific psychological interventions on depression, anxiety, quality of life, cardiac morbidity and cardiovascular or total mortality is not well investigated., Design: Systematic review and meta-analysis., Methods: Randomized controlled trials and controlled cohort trials published between January 1995 and October 2017 comparing ebCR with or without pre-specified psychosocial interventions were selected and evaluated on the basis of predefined inclusion and outcome criteria., Results: Out of 15,373 records, 20 studies were identified, including 4450 patients with coronary artery disease (88.5%) or congestive heart failure (11.5%), respectively. Studies were of low to moderate quality and methodological heterogeneity was high. As compared with ebCR alone, additional psychological interventions for lifestyle change or distress management showed a trend to reduce depressive symptoms (standardized mean difference -0.13, 95% confidence interval (CI) -0.30; 0.05). Furthermore, during a follow-up of five years, distress management was associated with a trend to reduce cardiac morbidity (risk ratio 0.74, 95% CI 0.51; 1.07). There was no evidence for an additional impact of either psychological lifestyle change interventions or distress management on anxiety, quality of life, cardiovascular or total mortality., Conclusions: Specific psychological interventions offered during ebCR may contribute to a reduction of depressive symptoms and cardiac morbidity, but there remains considerable uncertainty under which conditions these interventions exert their optimal effects. (CRD42015025920).

Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-κB activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 × 10-19) and regional methylation (P = 5.90 × 10-25). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-κB. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior., (© The Author(s) 2019. Published by Oxford University Press.)

Studies of classical musicians have demonstrated that expertise modulates neural responses during auditory perception. However, it remains unclear whether such expertise-dependent plasticity is modulated by the instrument that a musician plays. To examine whether the recruitment of sensorimotor regions during music perception is modulated by instrument-specific experience, we studied nonclassical musicians-beatboxers, who predominantly use their vocal apparatus to produce sound, and guitarists, who use their hands. We contrast fMRI activity in 20 beatboxers, 20 guitarists, and 20 nonmusicians as they listen to novel beatboxing and guitar pieces. All musicians show enhanced activity in sensorimotor regions (IFG, IPC, and SMA), but only when listening to the musical instrument they can play. Using independent component analysis, we find expertise-selective enhancement in sensorimotor networks, which are distinct from changes in attentional networks. These findings suggest that long-term sensorimotor experience facilitates access to the posterodorsal "how" pathway during auditory processing.

Background: Overweight and obesity are among the leading risk factors for death worldwide. Scientists believe that the increase in obesity is primarily due to environmental changes and thus favor obesity prevention measures targeting the environment. However, it is less clear what lay people perceive as causes of obesity, and which measures they deem acceptable and promising in fighting it., Purpose: This article compares lay beliefs about obesity with beliefs about other major health risks sharing certain similarities with obesity (alcohol and tobacco dependence, depression) in three countries with high obesity rates., Methods: Computer-assisted face-to-face interviews with representative samples in the UK (N = 1,216) and Germany (N = 973) and an online survey in the USA (N = 982) tapping beliefs about locus of responsibility, liability for treatment costs, and effectiveness of policy measures., Results: In each country, respondents attributed responsibility for obesity primarily to the individual; the same pattern emerged for alcohol and tobacco dependence, but not for depression (ps < .01). The higher the attribution of personal responsibility, the more strongly respondents endorsed individual liability for treatment costs (ps < .01). Respondents judged information and fiscal policies as most and least effective, respectively, in obesity prevention., Conclusions: Respondents' views about obesity are similar to those about addictions; however, they regard fiscal and regulatory policies as less effective for obesity than for addictions. Raising awareness about environmental drivers of obesity and framing policy measures by reference to the fight against tobacco and alcohol could increase public support of obesity-targeted policies.

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF.

Background: Current treatment of bullous pemphigoid (BP) is based on the long-term use of topical and/or systemic corticosteroids, which are associated with a high rate of adverse events and increased mortality., Objectives: To study the corticosteroid-sparing potential of azathioprine and dapsone., Methods: This was a prospective, multicentre, randomized, nonblinded clinical trial that compared the efficacy and safety of two parallel groups of patients with BP treated with oral methylprednisolone 0·5 mg kg -1 per day in combination with either azathioprine 1·5-2·5 mg kg -1 per day or dapsone 1·5 mg kg -1 per day. Nine German and Austrian departments of dermatology included 54 patients based on clinical lesions, positive direct immunofluorescence (IF) microscopy and detection of serum autoantibodies by indirect IF microscopy, immunoblotting or enzyme-linked immunosorbent assay. The primary end point was the time until complete tapering of methylprednisolone, and the most important secondary end point was the cumulative corticosteroid dose., Results: In eight patients (five azathioprine, three dapsone), methylprednisolone could be discontinued after a median time of 251 days in the azathioprine group and 81 days in the dapsone group. The median cumulative corticosteroid dose was 2·65 g for azathioprine compared with 1·92 g for dapsone (P = 0·06). The median numbers of days when corticosteroids were applied were 148 and 51, respectively (P = 0·24). No significant difference in the number of adverse events was seen between the treatment arms. Four patients (8%) died within the observation period of 12 months., Conclusions: Due to the lower than intended number of patients, the results of the primary and secondary end points were not or only barely significant. Dapsone appeared to have a moderately higher corticosteroid-sparing potential than azathioprine. The combination regimen of either drug with oral methylprednisolone is associated with a relatively low 1-year mortality in this vulnerable patient population., (© 2017 British Association of Dermatologists.)

Aims: Data mining is the computational process to obtain information from a data set and transform it for further use. Herein, through data mining with supportive statistical analyses, we identified and consolidated variables of the Flecainide Short-Long (Flec-SL-AFNET 3) trial dataset that are associated with the primary outcome of the trial, recurrence of persistent atrial fibrillation (AF) or death., Methods and Results: The 'Ranking Instances by Maximizing the Area under the ROC Curve' (RIMARC) algorithm was applied to build a classifier that can predict the primary outcome by using variables in the Flec-SL dataset. The primary outcome was time to persistent AF or death. The RIMARC algorithm calculated the predictive weights of each variable in the Flec-SL dataset for the primary outcome. Among the initial 21 parameters, 6 variables were identified by the RIMARC algorithm. In univariate Cox regression analysis of these variables, increased heart rate during AF and successful pharmacological conversion (PC) to sinus rhythm (SR) were found to be significant predictors. Multivariate Cox regression analysis revealed successful PC as the single relevant predictor of SR maintenance. The primary outcome risk was 3.14 times (95% CI:1.7-5.81) lower in those who had successful PC to SR than those who needed electrical cardioversion., Conclusions: Pharmacological conversion of persistent AF with flecainide without the need for electrical cardioversion is a powerful and independent predictor of maintenance of SR. A strategy of flecainide pretreatment for 48 h prior to planned electrical cardioversion may be a useful planning of a strategy of long-term rhythm control., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Cross-national data production in social science research has increased dramatically in recent decades. Assessing the comparability of data is necessary before drawing substantive conclusions that are based on cross-national data. Researchers assessing data comparability typically use either quantitative methods such as multigroup confirmatory factor analysis or qualitative methods such as online probing. Because both methods have complementary strengths and weaknesses, this study applies both multigroup confirmatory factor analysis and online probing in a mixed-methods approach to assess the comparability of constructive patriotism and nationalism, two important concepts in the study of national identity. Previous measurement invariance tests failed to achieve scalar measurement invariance, which prohibits a cross-national comparison of latent means (Davidov 2009). The arrival of the 2013 ISSP Module on National Identity has encouraged a reassessment of both constructs and a push to understand why scalar invariance cannot be achieved. Using the example of constructive patriotism and nationalism, this study demonstrates how the combination of multigroup confirmatory factor analysis and online probing can uncover and explain issues related to cross-national comparability.

Purpose: To investigate the dynamics of volunteering in the population aged 50 years or older across 11 Continental European countries., Design and Methods: Using longitudinal data from the first 2 waves of the Survey of Health, Ageing and Retirement in Europe, we run multivariate regressions on a set of binary-dependent variables indicating transitions from active volunteering to inactivity and vice versa., Results: Volunteer transitions were affected by both time-invariant individual resources and changes in individuals' resources. Moreover, we found that the societal context in which older persons live not only has a significant impact on the prevalence of volunteering at a given point in time but that the dynamics of volunteering also vary by country., Implications: Our study supports the notion of volunteering as an important productive aging activity and underlines the importance of both life-course and social context factors as determinants of volunteer dynamics at older ages.

Interindividual differences of endothelial cells in response to endotoxins might contribute to the diversity in clinical outcome among septic patients. The present study was conducted to test the hypothesis that endothelial cells (EC) with high and low proinflammatory potential exist and to dissect the molecular basis underlying this phenomenon. Thirty human umbilical vein endothelial cell (HUVEC) lines were stimulated for 24 h with lipopolysaccharide (LPS) and screened for interleukin (IL)-8 production. Based on IL-8 production five low and five high producers, tentatively called types I and II responders, respectively, were selected for genome-wide gene expression profiling. From the 74 genes that were modulated by LPS in all type II responders, 33 genes were not influenced in type I responders. Among the 41 genes that were increased in both responders, 17 were expressed significantly stronger in type II responders. Apart from IL-8, significant differences in the expression of proinflammatory related genes between types I and II responders were found for adhesion molecules [intercellular adhesion molecule (ICAM-1), E-selectin)], chemokines [monocyte chemoattractant protein (MCP-1), granulocyte chemotactic protein (GCP-2)], cytokines (IL-6) and the transcription factor CCAAT/enhancer binding protein-delta (C/EBP-delta). Type I responders also displayed a low response towards tumour necrosis factor (TNF)-alpha. In general, maximal activation of nuclear factor (NF)-kappaB was achieved in type I responders at higher concentrations of LPS compared to type II responders. In the present study we demonstrate that LPS-mediated gene expression differs quantitatively and qualitatively in types I and II responders. Our results suggest a pivotal role for common transcription factors as a low inflammatory response was also observed after TNF-alpha stimulation. Further studies are required to elucidate the relevance of these findings in terms of clinical outcome in septic patients.

We investigated tree water relations in a lower tropical montane rain forest at 1950-1975 m a.s.l. in southern Ecuador. During two field campaigns, sap flow measurements (Granier-type) were carried out on 16 trees (14 species) differing in size and position within the forest stand. Stomatal conductance (g(s)) and leaf transpiration (E(l)) were measured on five canopy trees and 10 understory plants. Atmospheric coupling of stomatal transpiration was good (decoupling coefficient Omega = 0.25-0.43), but the response of g(s) and E(l) to the atmospheric environment appeared to be weak as a result of the offsetting effects of vapor pressure deficit (VPD) and photosynthetic photon flux (PPF) on g(s). In contrast, sap flow (F) followed these atmospheric parameters more precisely. Daily F depended chiefly on PPF sums, whereas on short time scales, VPD impeded transpiration when it exceeded a value of 1-1.2 kPa. This indicates an upper limit to transpiration in the investigated trees, even when soil water supply was not limiting. Mean g(s) was 165 mmol m(-2) s(-1) for the canopy trees and about 90 mmol m(-2) s(-1) for the understory species, but leaf-to-leaf as well as tree-to-tree variation was large. Considering whole-plant water use, variation in the daily course of F was more pronounced among trees differing in size and crown status than among species. Daily F increased sharply with stem diameter and tree height, and ranged between 80 and 120 kg day(-1) for dominant canopy trees, but was typically well below 10 kg day(-1) for intermediate and suppressed trees of the forest interior.

We present a protein fold recognition method, MANIFOLD, which uses the similarity between target and template proteins in predicted secondary structure, sequence and enzyme code to predict the fold of the target protein. We developed a non-linear ranking scheme in order to combine the scores of the three different similarity measures used. For a difficult test set of proteins with very little sequence similarity, the program predicts the fold class correctly in 34% of cases. This is an over twofold increase in accuracy compared with sequence-based methods such as PSI-BLAST or GenTHREADER, which score 13-14% correct first hits for the same test set. The functional similarity term increases the prediction accuracy by up to 3% compared with using the combination of secondary structure similarity and PSI-BLAST alone. We argue that using functional and secondary structure information can increase the fold recognition beyond sequence similarity.

Age-related changes in functional subsets of lymphocytes may influence the potential to build up immune responses. In particular, the capacity of tonsillar lymphocytes to counter infections may be altered during ageing. In order to address this question we investigated the proportional distribution of several subsets of tonsillar T and B cells with regard to ageing. Tonsils were derived from 119 patients between 2 and 65 years of age. Lymphocyte subsets were monitored by three-colour fluorescence of relevant CD markers in flow cytometry. As a general tendency the percentage of CD3+ T cells steadily increased whereas that of CD19+ B cells decreased at the same time. No significant differences were observed between lymphocytes of patients with and without inflammatory history of the tonsils. The percentage of CD8+ T cells declined whereas that of CD4+ T cells increased during the same time span. CD45RA+ T cells increased during the first two decades of life and gradually decreased thereafter. In contrast, CD45RO+ T cells showed an opposite trend. No differences were seen in the population of CD3-/CD56+ natural killer (NK) cells. The mature B cell marker CD40 showed no significant changes during ageing. However, CD38+ B cells, representing B cells of late maturation stages, dramatically declined up to the age of 65. In a similar manner the CD5+ subpopulation of B cells decreased during ageing. Substantial changes in major tonsillar T and B cell populations as shown in this study may have an impact on the ageing process of the immune system.