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Depression is a highly prevalent, multifactorial, complex disorder, its etiology is assumed to involve both genetic and environmental factors. Genetic factors, including biological clock genes such as CLOCK and SIRT1, have been linked to depression, particularly its symptom related sleep disturbances. Environmental factors also play a crucial role in the background of depression, particularly in interaction with genetic factors. Known environmental stress factors include stress caused negative life events or childhood adversities.
Objectives
This study aims to delve into the chronotype-specific impacts of genes previously correlated with circadian functionality on the pathomechanism of depression in interaction with environmental stress factors.
Methods
A genome-wide association study on the ‘morning chronotype’ phenotype was conducted with Plink2, utilizing data from the UK Biobank discovery sample (N = 139135). Using LDPred2we derived a polygenic risk score (PRS) for the NewMood Hungarian dataset (N = 1820). We performed pathway-specific analyses including genes implicated within the genetic pathway, drawing on prior research findings. Specifically, we selected the top genes (with a false discovery rate-corrected p-value < 0.05) from the “responders vs. non-responders” analysis conducted by Jerome C. Foo et al.Transl Psychiatry 2019; 9 343). We performed a main effect analysis investigating the pathway specific PRS’s effect on BSI depression scores and interaction analyses using life course (number of negative life events in the past life) and recent (number of negative life events in the past year) stress scores to investigate how the interaction term predicts depression in our target sample.
Results
Our primary analysis revealed a nominally significant protective effect (beta = -20.90938, p = 0.070218). Subsequently, in the context of our interaction analysis, we identified significant risk associations, both with lifetime stress (beta = 13.7416, p = 0.0171) and recent stress (beta = 24.6034, p = 0.0038)
Conclusions
Our study unveiled a protective role in our primary analysis, juxtaposed with risk associations in our interaction analyses. This intriguing dichotomy underscores that this genetic pathway, associated with circadian dysregulation, exerts a protective influence in association with the morning chronotype. However, it transitions into a predisposing factor for depression when influenced by environmental stress factors.
Considering these findings, our study substantiates the hypothesis that both circadian genes and chronotype contribute to the pathogenesis and clinical manifestation of depression. Additionally, it underscores the pivotal role of stress as a contributing factor in the intricate pathogenesis of depression.
Diagnosis of acute ischemia typically relies on evidence of ischemic lesions on magnetic resonance imaging (MRI), a limited diagnostic resource. We aimed to determine associations of clinical variables and acute infarcts on MRI in patients with suspected low-risk transient ischemic attack (TIA) and minor stroke and to assess their predictive ability.
Methods:
We conducted a post-hoc analysis of the Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms (DOUBT) study, a prospective, multicenter cohort study investigating the frequency of acute infarcts in patients with low-risk neurological symptoms. Primary outcome parameter was defined as diffusion-weighted imaging (DWI)-positive lesions on MRI. Logistic regression analysis was performed to evaluate associations of clinical characteristics with MRI-DWI-positivity. Model performance was evaluated by Harrel’s c-statistic.
Results:
In 1028 patients, age (Odds Ratio (OR) 1.03, 95% Confidence Interval (CI) 1.01–1.05), motor (OR 2.18, 95%CI 1.27–3.65) or speech symptoms (OR 2.53, 95%CI 1.28–4.80), and no previous identical event (OR 1.75, 95%CI 1.07–2.99) were positively associated with MRI-DWI-positivity. Female sex (OR 0.47, 95%CI 0.32–0.68), dizziness and gait instability (OR 0.34, 95%CI 0.14–0.69), normal exam (OR 0.55, 95%CI 0.35–0.85) and resolved symptoms (OR 0.49, 95%CI 0.30–0.78) were negatively associated. Symptom duration and any additional symptoms/symptom combinations were not associated. Predictive ability of the model was moderate (c-statistic 0.72, 95%CI 0.69–0.77).
Conclusion:
Detailed clinical information is helpful in assessing the risk of ischemia in patients with low-risk neurological events, but a predictive model had only moderate discriminative ability. Patients with clinically suspected low-risk TIA or minor stroke require MRI to confirm the diagnosis of cerebral ischemia.
Odd Radio Circles (ORCs) are a class of low surface brightness, circular objects approximately one arcminute in diameter. ORCs were recently discovered in the Australian Square Kilometre Array Pathfinder (ASKAP) data and subsequently confirmed with follow-up observations on other instruments, yet their origins remain uncertain. In this paper, we suggest that ORCs could be remnant lobes of powerful radio galaxies, re-energised by the passage of a shock. Using relativistic hydrodynamic simulations with synchrotron emission calculated in post-processing, we show that buoyant evolution of remnant radio lobes is alone too slow to produce the observed ORC morphology. However, the passage of a shock can produce both filled and edge-brightnened ORC-like morphologies for a wide variety of shock and observing orientations. Circular ORCs are predicted to have host galaxies near the geometric centre of the radio emission, consistent with observations of these objects. Significantly offset hosts are possible for elliptical ORCs, potentially causing challenges for accurate host galaxy identification. Observed ORC number counts are broadly consistent with a paradigm in which moderately powerful radio galaxies are their progenitors.
Geriatric depression (GD) is associated with cognitive impairment and brain atrophy. Tai-Chi-Chih (TCC) is a promising adjunct treatment to antidepressants. We previously found beneficial effects of TCC on resting state connectivity in GD. We now tested the effect of TCC on gray matter volume (GMV) change and the association between baseline GMV and clinical outcome.
Participants completed 3 months of TCC (N = 26) or health and wellness education control (HEW; N = 23).
Measurements:
Depression and anxiety symptoms and MRI scans were acquired at baseline and 3-month follow-up. General linear models (GLMs) tested group-by-time interactions on clinical scores. Freesurfer 6.0 was used to process T1-weighted images and to perform voxel-wise whole-brain GLMs of group on symmetrized percent GMV change, and on the baseline GMV and symptom change association, controlling for baseline symptom severity. Age and sex served as covariates in all models.
Results:
There were no group differences in baseline demographics or clinical scores, symptom change from baseline to follow-up, or treatment-related GMV change. However, whole-brain analysis revealed that lower baseline GMV in several clusters in the TCC, but not the HEW group, was associated with larger improvements in anxiety. This was similar for right precuneus GMV and depressive symptoms.
Conclusions:
While we observed no effect on GMV due to the interventions, baseline regional GMV predicted symptom improvements with TCC but not HEW. Longer trials are needed to investigate the long-term effects of TCC on clinical symptoms and neuroplasticity.
Maternal perinatal depression (PND) and partnership problems have been identified to influence the development of later child adjustment difficulties. However, PND and partnership problems are closely linked which makes it difficult to draw conclusions about the exact transmission pathways. The aim of the present study was to investigate to what extent PND symptoms and partnership problems influence each other longitudinally and to examine the influence of their trajectories on child adjustment difficulties at the age of three. Analyses were based on publicly available data from the German family panel “pairfam”. N = 354 mothers were surveyed on depressive symptoms and partnership problems annually from pregnancy (T0) until child age three (T4). Child adjustment difficulties were assessed at age three. Results of latent change score modeling showed that partnership problems predicted change in PND symptoms at T0 and T3 while PND symptoms did not predict change in partnership problems. Child adjustment difficulties at age three were predicted by PND symptoms, but not by partnership problems. Partnership problems predicted externalizing, but not internalizing symptoms. Results underline the effects of family factors for the development of child adjustment difficulties and emphasize the importance of early interventions from pregnancy onwards
Cigarette smoking prevalence is significantly higher among people with mental health problems than among the general population. Smoking accounts for much of the reduction in life expectancy associated with mental illness, why the high co-occurrence of smoking and mental health illness is a major public health concern. Persons belonging to socioeconomical disadvantaged groups have higher risk of mental health conditions and also higher smoking rates.
Objectives
In this study we aim to examine smoking trajectories among adult smokers between 2012 and 2020. Furthermore, we aim to investigate differences in smoking trajectories by adult depression by taking into consideration participants intergenerational socioeconomic mobility (ISEM).
Methods
Analyses were based on data from CONSTANCES, a French general population cohort conducted from 2012 to 2020. In total were 107,734 participants included after exclusion of never smokers. Depression was measured by the CES-D scale, and depression was classified with a score ≥16. ISEM is based on childhood (maternal and parental occupational grade) and adult socioeconomic position (SEP), and low ISEM includes those with low SEP as child and adult and high ISEM those with consistent high SEP. Group-based trajectories modelling (GBTM) was used to determine smoking status trajectories. To address the association between ISEM and smoking trajectory class we used multinomial logistic regression with former smokers as reference class adjusted for depression, household income, sex and age.
Results
We identified five smoking trajectories 1) Former smokers (56.6%), 2) Long-term smokers (26.4%), 3) Intermediate smokers (3.3%), 4) Early quitters (5.0%) and 5) Late quitters (8.7%). Preliminary results from multinomial logistic regression showed that persons with low ISEM had higher odds of depression (OR [95%CI]=1.91 [1.77;2.06]) than those with high ISEM. Participants with low ISEM had higher odds of being long-term smoking than former smokers compared to those with high ISEM (ORa [95%CI]=1.55 [1.43;1.67]). Furthermore, those with low ISEM had lower odds of being in any of the other smoking trajectory groups vs. former smokers compared to those with high ISEM (ORa [95%CI]=0.82 [0.69;0.97]) for intermediate smokers, ORa [95%CI]=0.75 [0.66;0.85]) for early quitters, and ORa [95%CI]=0.78 [0.70;0.87]) for late quitters).
Conclusions
Preliminary results showed an association between ISEM and smoking trajectories in our study. Persons with low ISEM are more likely to be long-term smokers. Future analysis should consider the effect of depression as a mediating factor on the association between ISEM and smoking trajectories.
Geriatric depression (GD) is associated with significant medical comorbidity, cognitive impairment, brain atrophy, premature mortality, and suboptimal treatment response. While apathy and anxiety are common comorbidities, resilience is a protective factor. Understanding the relationships between brain morphometry, depression, and resilience in GD could inform clinical treatment. Only few studies have addressed gray matter volume (GMV) associations with mood and resilience.
Participants:
Forty-nine adults aged >60 years (38 women) with major depressive disorder undergoing concurrent antidepressant treatment participated in the study.
Measurements:
Anatomical T1-weighted scans, apathy, anxiety, and resilience data were collected. Freesurfer 6.0 was used to preprocess T1-weighted images and qdec to perform voxel-wise whole-brain analyses. Partial Spearman correlations controlling for age and sex tested the associations between clinical scores, and general linear models identified clusters of associations between GMV and clinical scores, with age and sex as covariates. Cluster correction and Monte-Carlo simulations were applied (corrected alpha = 0.05).
Results:
Greater depression severity was associated with greater anxiety (r = 0.53, p = 0.0001), lower resilience (r = −0.33, p = 0.03), and greater apathy (r = 0.39, p = 0.01). Greater GMV in widespread, partially overlapping clusters across the brain was associated with reduced anxiety and apathy, as well as increased resilience.
Conclusion:
Our results suggest that greater GMV in extended brain regions is a potential marker for resilience in GD, while GMV in more focal and overlapping regions may be markers for depression and anxiety. Interventions focused on improving symptoms in GD may seek to examine their effects on these brain regions.
Focusing on the so-called “romances of adventure” (romans d’aventure) which made up the largest and most popular category of romances, this chapter provides representative glimpses of how complicated, and fluid, the presentation of gender is in romance. It primarily examines romances written in French because they were the earliest to be written and served as the model for most of those we find in other western European languages, as it explores how binaries such as passive/active and male/female were complicated by deliberate strategies on the part of authors (and patrons).
We present the Cosmological Double Radio Active Galactic Nuclei (CosmoDRAGoN) project: a large suite of simulated AGN jets in cosmological environments. These environments sample the intra-cluster media of galaxy clusters that form in cosmological smooth particle hydrodynamics (SPH) simulations, which we then use as inputs for grid-based hydrodynamic simulations of radio jets. Initially conical jets are injected with a range of jet powers, speeds (both relativistic and non-relativistic), and opening angles; we follow their collimation and propagation on scales of tens to hundreds of kiloparsecs, and calculate spatially resolved synthetic radio spectra in post-processing. In this paper, we present a technical overview of the project, and key early science results from six representative simulations which produce radio sources with both core- (Fanaroff-Riley Type I) and edge-brightened (Fanaroff-Riley Type II) radio morphologies. Our simulations highlight the importance of accurate representation of both jets and environments for radio morphology, radio spectra, and feedback the jets provide to their surroundings.
The COVID-19 pandemic and associated preventive measures have an impact on the persons’ mental health, including increasing risk of symptoms of anxiety and depression in particular. Individual experiencing mental health difficulties in the past could be especially vulnerable during lockdown, however, few studies have tested this empirically considering preexisting mental health difficulties using longitudinal data.
Objectives
The objective of this study is to examine the longitudinal association between preexisting symptoms of anxiety/depression and symptoms of anxiety/depression during lockdown due to the COVID-19 pandemic in a community sample.
Methods
Seven waves of data collection were implemented from March-May 2020. Generalized estimation equations models were used to estimate the association between preexisting symptoms of anxiety/depression and symptoms of anxiety/depression during lockdown among 662 mid-aged individuals from the French TEMPO cohort.
Results
We found an elevated odds ratio of symptoms of anxiety/depression (OR=6.73 95% [CI=4.45–10.17]) among individuals experiencing such symptoms prior lockdown. Furthermore, the odds of symptoms of anxiety/depression during lockdown was elevated among women (OR=2.07 [95% CI=1.32–3.25]), subjects with low household income (OR=2.28 [1.29–4.01]) and persons who reported loneliness (OR=3.94 [2.47–6.28]).
Conclusions
This study demonstrates a strong relationship between preexisting symptoms of anxiety/depression and anxiety/depression during the COVID-19 outbreak among mid-aged French adults. The findings underline the role of preexisting symptoms of anxiety/depression as a vulnerability factor of anxiety/depression during lockdown. Furthermore, the study shows that loneliness is independently associated with symptoms of anxious/depression, when controlling for prior anxiety/depression symptoms.
The new development of cyber-physical product families currently lacks a methodically supported modularisation approach. This paper provides an approach for module-based mechatronic development, which provides design for future product variety. The state of the art in terms of mechatronic system design and modular product architecture design is presented. A modified V-model is then shown that integrates initial product architecture design and life phase modularisation. The method is applied and evaluated for the development of product family generations of robot units in a teaching course.
The modular lightweight design attempts to reconcile the partially conflicting goals between modularization and lightweight design in order to establish a harmonized modular hybrid design. This requires a close exchange of the resulting development data between the two areas. In this contribution a concept for an interface for the data exchange between system models and FEM models is presented and successfully implemented in the Cameo Systems Modeler and applied to examples from the aircraft cabin. With the interface the homogenization step of modular lightweight design can be performed.
This paper analyzes the potential of crossdisciplinary collaboration in the methodical development of Modular Design by harmonization asynchronous mechatronic system structures. Subsystem boundaries in multidisciplinary development processes are set disciplinespecific, resulting in inconsistencies in module fitting. Based on a case study, harmonization of disciplines is elaborated as a solution. This aligns discipline structures and reduces effects on the variety in system structures.This implementation shows support for modular design and enables an integrated view as a systems-in-system.
Aircraft cabin monuments must be optimized in terms of lightweight design, cost structure and variance. Model-based approaches support the aircraft data and help to modify them consistently during further development. In this paper, a holistic methodological approach for product families of aircraft cabin development is shown, which integrates lightweight and cost-efficient aspects, in addition to the variance focus. For this purpose, the development of cost-efficient and ligthweight optimized cabin modules is supported in a model-based way.
The coronavirus disease 2019 (COVID-19) pandemic might affect mental health. Data from population-representative panel surveys with multiple waves including pre-COVID data investigating risk and protective factors are still rare.
Methods
In a stratified random sample of the German household population (n = 6684), we conducted survey-weighted multiple linear regressions to determine the association of various psychological risk and protective factors assessed between 2015 and 2020 with changes in psychological distress [(PD; measured via Patient Health Questionnaire for Depression and Anxiety (PHQ-4)] from pre-pandemic (average of 2016 and 2019) to peri-pandemic (both 2020 and 2021) time points. Control analyses on PD change between two pre-pandemic time points (2016 and 2019) were conducted. Regularized regressions were computed to inform on which factors were statistically most influential in the multicollinear setting.
Results
PHQ-4 scores in 2020 (M = 2.45) and 2021 (M = 2.21) were elevated compared to 2019 (M = 1.79). Several risk factors (catastrophizing, neuroticism, and asking for instrumental support) and protective factors (perceived stress recovery, positive reappraisal, and optimism) were identified for the peri-pandemic outcomes. Control analyses revealed that in pre-pandemic times, neuroticism and optimism were predominantly related to PD changes. Regularized regression mostly confirmed the results and highlighted perceived stress recovery as most consistent influential protective factor across peri-pandemic outcomes.
Conclusions
We identified several psychological risk and protective factors related to PD outcomes during the COVID-19 pandemic. A comparison of pre-pandemic data stresses the relevance of longitudinal assessments to potentially reconcile contradictory findings. Implications and suggestions for targeted prevention and intervention programs during highly stressful times such as pandemics are discussed.
The cosmic evolution of the chemical elements from the Big Bang to the present time is driven by nuclear fusion reactions inside stars and stellar explosions. A cycle of matter recurrently re-processes metal-enriched stellar ejecta into the next generation of stars. The study of cosmic nucleosynthesis and this matter cycle requires the understanding of the physics of nuclear reactions, of the conditions at which the nuclear reactions are activated inside the stars and stellar explosions, of the stellar ejection mechanisms through winds and explosions, and of the transport of the ejecta towards the next cycle, from hot plasma to cold, star-forming gas. Due to the long timescales of stellar evolution, and because of the infrequent occurrence of stellar explosions, observational studies are challenging, as they have biases in time and space as well as different sensitivities related to the various astronomical methods. Here, we describe in detail the astrophysical and nuclear-physical processes involved in creating two radioactive isotopes useful in such studies, $^{26}\mathrm{Al}$ and $^{60}\mathrm{Fe}$. Due to their radioactive lifetime of the order of a million years, these isotopes are suitable to characterise simultaneously the processes of nuclear fusion reactions and of interstellar transport. We describe and discuss the nuclear reactions involved in the production and destruction of $^{26}\mathrm{Al}$ and $^{60}\mathrm{Fe}$, the key characteristics of the stellar sites of their nucleosynthesis and their interstellar journey after ejection from the nucleosynthesis sites. This allows us to connect the theoretical astrophysical aspects to the variety of astronomical messengers presented here, from stardust and cosmic-ray composition measurements, through observation of $\gamma$ rays produced by radioactivity, to material deposited in deep-sea ocean crusts and to the inferred composition of the first solids that have formed in the Solar System. We show that considering measurements of the isotopic ratio of $^{26}\mathrm{Al}$ to $^{60}\mathrm{Fe}$ eliminate some of the unknowns when interpreting astronomical results, and discuss the lessons learned from these two isotopes on cosmic chemical evolution. This review paper has emerged from an ISSI-BJ Team project in 2017–2019, bringing together nuclear physicists, astronomers, and astrophysicists in this inter-disciplinary discussion.
To identify dietary self-monitoring implementation strategies in behavioural weight loss interventions.
Design:
We conducted a systematic review of eight databases and examined fifty-nine weight loss intervention studies targeting adults with overweight/obesity that used dietary self-monitoring.
Setting:
NA.
Participants:
NA.
Results:
We identified self-monitoring implementation characteristics, effectiveness of interventions in supporting weight loss and examined weight loss outcomes among higher and lower intensity dietary self-monitoring protocols. Included studies utilised diverse self-monitoring formats (paper, website, mobile app, phone) and intensity levels (recording all intake or only certain aspects of diet). We found the majority of studies using high- and low-intensity self-monitoring strategies demonstrated statistically significant weight loss in intervention groups compared with control groups.
Conclusions:
Based on our findings, lower and higher intensity dietary self-monitoring may support weight loss, but variability in adherence measures and limited analysis of weight loss relative to self-monitoring usage limits our understanding of how these methods compare with each other.
The increased demand for customer-adapted product solutions shows an increasing trend of product variety, leading to an increased internal variety and therefore -costs. The concept of modularization provides apossible solution to this challenge by developing modular kits. Nevertheless, modularization methods to not lead to one individual modular kit, but to several alternatives. The decision of which alternative to implement can be crucial to the applying companys succes. During this decision-making both customer- and company perspectives need to be taken into account. This contribution is to present a simulation-based approach to support the decision making by using a model-based configuration system. Furthermore, as classical decision-making processes are based upon historical data, future aspects are usually not taken into account. In order to counteract this situation, this contribution intends to simulate as well future aspects impacting the modular product architecture. In this case, the simulation is used in order to evaluate the individual performances of a Design-for-Variety product architecture as opposed to a Design-for-Future-Robustness by applying this method to the example of customer-individual laser machines.
(1) To investigate if gut microbiota can be a predictor of remission in geriatric depression and to identify features of the gut microbiota that is associated with remission. (2) To determine if changes in gut microbiota occur with remission in geriatric depression.
Design:
Secondary analysis of a parent randomized placebo-controlled trial (NCT02466958).
Setting:
Los Angeles, CA, USA (2016-2018)
Participants:
Seventeen subjects with major depressive disorder, over 60 years of age, 41.2% female.
Intervention:
Levomilacipran (LVM) or placebo.
Measurements:
Remission was defined by Hamilton Depression Rating Scale score of 6 or less at 12 weeks. 16S-ribosomal RNA sequencing based fecal microbiota composition and diversity were measured at baseline and 12 weeks. Differences in fecal microbiota were evaluated between remitters and non-remitters as well as between baseline and post-treatment samples. LVM and placebo groups were combined in all the analyses.
Results:
Baseline microbiota showed no community level α-diversity or β-diversity differences between remitters and non-remitters. At the individual taxa level, a random forest classifier created with nine genera from the baseline microbiota was highly accurate in predicting remission (AUC = .857). Of these, baseline enrichment of Faecalibacterium, Agathobacter and Roseburia relative to a reference frame was associated with treatment outcome of remission. Differential abundance analysis revealed significant genus level changes from baseline to post-treatment in remitters, but not in non-remitters.
Conclusions:
This is the first study demonstrating fecal microbiota as a potential predictor of treatment response in geriatric depression. Our findings need to be confirmed in larger prospective studies.
The requirements on validity for studies in design research are very high. Therefore, this paper aims at identifying challenges that occur when setting up studies and suggests solution strategies to address them. Three different institutes combining their experience discussed several studies in a workshop. Resulting main challenges are to find a suitable task, to operationalise the variables and to deal with a high analysis effort per participant. Automation in data evaluation and a detailed practical guideline on studies in design research are considered necessary.