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Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

BackgroundThe gender gap in time use and its impact on health and well-being are still prevalent. Women work longer hours than men when considering both paid and unpaid (eg, childcare and chores) work, and this gender disparity is particularly visible among parents. Less is known about factors that could potentially mediate or moderate this relationship (eg, work-family conflict and gender role beliefs). Ecological momentary assessment (EMA) allows for the documentation of changes in momentary internal states, such as time use, stress, or mood. It has shown particular validity to measure shorter-term activities (eg, unpaid work) and is thus useful to address gender differences. ObjectiveThe feasibility of the daily EMA surveys in a parent sample will be examined. The associations between time use, well-being, and stress will be examined, along with potential moderating and mediating factors such as gender, gender role beliefs, and work-family conflict. Finally, the act of monitoring one’s own time use, well-being, and stress will be examined in relation to, for example, the quality of life. MethodsWe conducted a quasi-experimental, nonrandomized controlled trial with 3 data collection methods, namely, online questionnaires, EMA surveys, and qualitative interviews. The intervention group (n=64) will participate in the online questionnaires and EMA surveys, and a subsample of the intervention group (n=6-17) will also be invited to participate in qualitative interviews. Over a period of 1 week, participants in the intervention group will answer daily EMA surveys (4 times per day). In contrast, the control group (n=17) will only participate in the online questionnaires at baseline and after 1 week. The following constructs were surveyed: sociodemographic background (eg, age, gender, and household composition; baseline questionnaire); mediators and moderators (eg, gender role beliefs and work-family conflict; baseline and follow-up questionnaires); well-being, quality of life, and trait mindfulness (baseline and follow-up questionnaires); momentary activity and well-being, as well as state mindfulness (EMA); and feasibility (baseline and follow-up questionnaires as well as interviews). We anticipate that participants will regard the daily EMA as feasible. Particular daily time-use patterns (eg, high paid and unpaid workload) are expected to be related to lower well-being, higher stress, and health-related quality of life. These associations are expected to be moderated and mediated by factors such as gender, gender role beliefs, work-family conflict, and social support. Participants in the intervention group are expected to show higher values of mindfulness, well-being, health-related quality of life, and lower stress. ResultsPatient recruitment started in November 2023 and ended in mid April 2024. Data analysis commenced in mid April 2024. ConclusionsThis study aims to provide valuable insights into the feasibility of using EMAs and the potential benefits of activity tracking in various aspects of daily life. Trial RegistrationOpen Science Framework 8qj3d; https://osf.io/8qj3d International Registered Report Identifier (IRRID)PRR1-10.2196/54728

Abstract To identify und support particular target groups for mental health prevention, we explore the links between shame and help-seeking intentions concerning mental health in different lifestyles (based on socioeconomic status as well as health-related behaviors). Lifestyles were operationalized by nine confirmatory, homogenous clusters of the sample. These clusters are based on individuals’ similarities in sociodemographic aspects and health behavior. Analyses included t tests, Chi-square, ANOVA, regressions investigating in sociodemographic characteristics. Hierarchical linear models examining cross-sectional associations of shame and willingness to seek help for different lifestyles of participants of the Study of Health in Pomerania (SHIP-START-1 and SHIP-START-3, data collected 2002–2006 and 2014–2016; n = 1630). Hierarchical linear models showed small context effects for lifestyle-related associations of shame and willingness to seek help. For younger as well as male participants, lifestyles indicated different associations of shame and help-seeking intentions: Especially the lifestyles with unhealthy behaviors and high as well as low socioeconomic status resulted in higher shame being associated with low help-seeking intentions in case of mental illness. Lifestyle clusters might be a useful tool to identify marginalized groups with unhealthy behaviors, which should be addressed by interventions and prevention programs.

Background: Despite available professional healthcare, people often delay or avoid help-seeking. Understanding the underlying reasons is crucial and research has explored the role of self-efficacy in this context. Additionally, studies have highlighted the significance of culturally influenced self-construals in individuals' health behaviour. There seems to be a relationship between self-efficacy and self-construal.The aim of the study is to explore the influence of self-efficacy on help-seeking, considering self-construal as a moderator. Differential experiences of self-efficacy and varying associations among help-seeking variables based on self-construal are posited. Methods: A quasi-experimental online study is conducted with a baseline assessment, including self-efficacy interventions, and follow-ups at three and six months. Self-construal groups are compared, i.e., independent vs. interdependent individuals. A series of multi-group path analyses are conducted to examine potential variations in the interventional effects and among the help-seeking variables respective of help-seeking instance, i.e. professional mental health care or informal care. Self-construal functions as the global moderator. Results: The study included N = 1′368 participants, 65.6 % identifying as female and an average age of 42.38 (SD = 15.22). More independent compared to more interdependent individuals were older, more frequently identified as male, had higher socioeconomic status, fewer depressive symptoms, and greater self-efficacy. Multi-group path analyses for professional mental health care (CFI = 0.992, RMSEA = 0.018, SRMR = 0.004) and informal help (CFI = 0.999, RMSEA = 0.004, SRMR = 0.006) demonstrated excellent model fits. The analysis for informal help was interpretable, as the unconstrained model had a significantly better fit than the constrained model. There were varying associations among help-seeking variables based on self-construals. The intervention effect was differential, with independent participants benefiting significantly (β = 0.203), while the effect was non-significant for interdependent participants. Discussion: The study's findings, strengths, and limitations are discussed in relation to current research. Results indicate differential experiences of self-efficacy interventions based on individuals' self-construal. Moreover, varying associations among help-seeking variables suggest self-construal-based differences in their interrelationships. These findings highlight the importance of considering self-construal in health related research.

BackgroundYoung people with chronic health conditions and disabilities rely on the healthcare system to maintain their best possible health. The appropriate delivery and utilization of healthcare services are key to improve their autonomy, self-efficacy and employment outcomes. The research question of our study is directed toward investigating if poor availability and accessibility of healthcare services in general, as identified by unmet needs in healthcare, are associated with dissatisfaction with healthcare.MethodsWithin a European multicenter observational study, 357 young adults with cerebral palsy aged 19–28 were included. We assessed special healthcare needs, utilization of healthcare services, and satisfaction with healthcare applying the short-form of the YHC-SUN-SF, environmental and social variables (EAEQ) as well as indicators for severity of condition and functionality (e.g., GMFCS) of these participants based on a self-, assisted self- or proxy-reports. We used correlation analyses to explore associations between satisfaction with healthcare and respective indicators related to availability and accessibility of healthcare services as well as severity of the condition. In addition, we included reference values for satisfaction with heath care from young adults with various chronic conditions assessed within population-based surveys from some of the European countries included in the study.ResultsWe identified several unmet healthcare needs, especially for widely used and established services (e.g., physical therapy). Satisfaction with healthcare (YHC-SUN-SF general and subscale scores) was moderate to high and almost consistently better for the sample of young adults with cerebral palsy as compared to reference values for young adults with various chronic conditions assessed within general population surveys). Correlation coefficients between satisfaction with healthcare and utilization of services and (unmet) healthcare needs were low, also with different indicators for severity of the condition or functionality.ConclusionYoung adults with cerebral palsy reports of unmet healthcare needs varied largely but showed substantial deficits in some aspects. This seems to have no impact on the satisfaction with healthcare those patients currently receive. We conclude that these are two different constructs and somewhat independent indicators to evaluate the quality of healthcare. Clinicians and other practitioners should consider this distinction when monitoring patient needs in their daily practice.

Abstract Background Pregnancy and the postpartum period are times when women are at increased risk for depression and mental problems. This may also negatively affect the foetus. Thus, there is a need for interventions with low-threshold access and care. Telemedicine interventions are a promising approach to address these issues. This systematic literature review examined the efficacy of telemedicine interventions for pregnant women and/or new mothers to address mental health-related outcomes. The primary objective was to analyse whether telemedicine interventions can reduce mental health problems in pregnant women and new mothers. The secondary aim was to clarify the impact of type of interventions, their frequency and their targets. Methods Inclusion criteria: randomized controlled trials, with participants being pregnant women and/or new mothers (with infants up to twelve months), involving telemedicine interventions of any kind (e.g. websites, apps, chats, telephone), and addressing any mental health-related outcomes like depression, postnatal depression, anxiety, stress and others. Search terms were pregnant women, new mothers, telemedicine, RCT (randomised controlled trials), mental stress as well as numerous synonyms including medical subject headings. The literature search was conducted within the databases PubMed, Cochrane Library, Web of Science and PsycINFO. Screening, inclusion of records and data extraction were performed by two researchers according to the PRISMA guidelines, using the online tool CADIMA. Results Forty four articles were included. A majority (62%) reported significantly improved mental health-related outcomes for participants receiving telemedicine interventions compared to control. In particular (internet-delivered) Cognitive Behavioural Therapy was successful for depression and stress, and peer support improved outcomes for postnatal depression and anxiety. Interventions with preventive approaches and interventions aimed at symptom reduction were largely successful. For the most part there was no significant improvement in the symptoms of anxiety. Conclusion Telemedicine interventions evaluated within RCTs were mostly successful. However, they need to be designed to specifically target a certain mental health issue because there is no one-size-fits-all approach. Further research should focus on which specific interventions are appropriate for which mental health outcomes in terms of intervention delivery modes, content, target approaches, etc. Further investigation is needed, in particular with regard to anxiety.

IntroductionStigma is an individual and societal process based on attitudes and power and relates to both spatial disparities and social distinction. In this study, we examined differences in desire for social distance toward people with mental illness within a city using social and spatial information.MethodsANOVAs and Scheffé post-hoc tests analyzed varying desires for social distance toward people with mental illness within Leipzig (East Germany). Joint Correspondence Analyses (JCA) explored correspondences between desire for social distance, socio-economic status, age, life orientation, social support, duration of living in Leipzig, and shame toward having a mental illness in five city districts of Leipzig in LIFE study participants (by Leipzig Research Center for Civilization Disease, data collected 2011–2014 and 2018–2021, n = 521).ResultsStigma varied among Leipzig’s districts (F(df = 4) = 4.52, p = 0.001). JCAs showed that a higher desired social distance toward people with mental illness corresponded with spatial differences, high levels of pessimism, high shame of being mentally ill, low social support, low socio-economic status, and older age (75.74 and 81.22% explained variances).ConclusionIn terms of stigma, where people with mental illness live matters. The results identified target groups that should be addressed by appropriate intervention and prevention strategies for mental health care.

BackgroundOnly approximately a third of people with depressive symptoms seek professional health care. Furthermore, people labelled as mentally ill may experience stigmatisation, which can impede help-seeking behaviour.AimTo examine the effects of three vignette-based interventions endorsing biopsychosocial causal beliefs and strengthening self-efficacy on help-seeking intention and behaviour, as well as the predictive values of these variables and previous treatment experience.MethodA quasi-experimental online study utilising a fractioned factorial design was carried out. People were screened for depressive symptoms and their current treatment status. After baseline assessment, they were randomly allocated into one of 24 groups receiving a combination of interventional messages. Actual help-seeking behaviour was measured at follow-ups 3 and 6 months after baseline.ResultsAltogether, N = 1,368 participants were included in the final analyses and N = 983 provided data on their help-seeking behaviour within 3 to 6 months after the baseline assessment. The intention to seek help from a general practitioner or a mental health professional was significantly influenced by the interventions. However, help-seeking behaviour was not influenced by the interventions. On a conceptual level, biopsychosocial causal beliefs (β = 0.09–0.23) and self-efficacy to seek help (β = 0.16–0.25) predicted help-seeking intention. There was a negative interaction effect of both self-efficacy beliefs on intention and behaviour, which changed depending on depression severity. In all models, the intention was the main predictor of actual behaviour. Treatment experience predicted both help-seeking intention and behaviour.ConclusionBiopsychosocial causal beliefs and self-efficacy have a direct effect on help-seeking intention. Interventions should include information on how to actually seek help as a means to strengthen self-efficacy beliefs and simulate previous treatment experience. Further research is needed to investigate the respective interaction effects on intention and behaviour.Clinical Trial Registrationhttps://drks.de/search/de/trial/DRKS00023557, German Clinical Trials Register: DRKS00023557. Registered 11 December 2020. World Health Organization, Universal Trial Number: U1111–1264-9954. Registered 16 February 2021.

Summary: Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014–2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12–26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p

Abstract Background Only about half the people with depression seek professional health care services. To constitute the different predictors and associating variables of health care utilisation, we model the process and aim to test our hypothesised Seeking Mental Health Care Model. The model includes empirical influences on the help-seeking process to predict actual behaviour and incorporates superordinate (stigma, treatment experiences) as well as intermediate attitudinal variables (continuum and causal beliefs, depression literacy and self-efficacy). Method All variables are examined in an online study (baseline, three- and six-month follow-up). The sample consisted of adults with depressive symptoms (PHQ-9 sum score ≥ 8), currently not receiving mental health care treatment. To examine the prediction of variables explaining help-seeking behaviour, a path model analysis was carried out (lavaan package, software R). Results Altogether, 1368 participants (M age = 42.38, SD age = 15.22, 65.6% female) were included, 983 participating in at least one follow-up. Model fit was excellent (i.e., RMSEA = 0.059, CFI = 0.989), and the model confirmed most of the hypothesised predictions. Intermediary variables were significantly associated with stigma and experiences. Depression literacy (ß = .28), continuum beliefs (ß = .11) and openness to a balanced biopsychosocial causal model (ß = .21) significantly influenced self-identification (R 2 = .35), which among the causal beliefs and self-efficacy influenced help-seeking intention (R 2 = .10). Intention (ß = .40) prospectively predicted help-seeking behaviour (R 2 = .16). Conclusion The Seeking Mental Health Care Model provides an empirically validated conceptualisation of the help-seeking process of people with untreated depressive symptoms as a comprehensive approach considering internal influences. Implications and open questions are discussed, e.g., regarding differentiated assessment of self-efficacy, usefulness of continuum beliefs and causal beliefs in anti-stigma work, and replication of the model for other mental illnesses. Trial registration German Clinical Trials Register: DRKS00023557. Registered 11 December 2020. World Health Organization, Universal Trial Number: U1111–1264-9954. Registered 16 February 2021.

Abstract Background Self-reported time-use in relation to health-related quality of life (HRQoL) has been widely studied, yet less is known about the directionality of the association and how it compares across genders when controlling for sociodemographic confounders. Methods This study focused on the working population of the most recent waves (2013–2018) of the Core-Study of the German Socio-Economic Panel (N = 30,518, 46.70% female, M = 39.24 years). It examined the relationship between three time-use categories (contracted, committed, & leisure time) and HRQoL (self-rated health & life satisfaction) in men and women via multigroup fixed effects cross-lagged panel models. The models controlled for sociodemographic background (age, household income, number of children living in household, employment status, education, & marital status), which was associated with time-use and psychosocial health in previous research. Results Contracted time showed consistent positive relationships with HRQoL across genders while associations with the other types of time use differed significantly between men and women and across indicators of HRQoL. Conclusions The way we spend our time directly predicts our health perceptions, but in the same vein our health also predicts how we can spend our time. Contracted time in particular was associated with positive HRQoL, across genders, and beyond sociodemographic predictors, highlighting the important role of employment in health, for men and women alike. The impact of commitments beyond contracted time-use—like household chores and childcare—however, continues to affect mainly women, which ultimately reflects in poorer health outcomes.

Abstract Background While evidence concerning Quality of Life (QoL) in youth with cerebral palsy (CP) in comparison to the general population has been accumulating, there is a lack of studies exploring differences on a wider range of positive and negative mental health outcomes in emerging adults. Methods This binational case control study is part of the SPARCLE cohort study on QoL and participation of youth with CP. QoL (WHOQOL-BREF), depression (PHQ-9), anxiety (GAD-7) and self-efficacy (GSE) were assessed in 198 emerging adults with CP and 593 emerging adults from the general population, matched for country of residence, age and gender. ANCOVAs with impairment and pain as covariates were run. Results Similar levels of QoL were found in both samples, except for the environmental domain, with better QoL for emerging adults with CP compared to the general population. There were significant descriptive differences regarding depression with worse levels in the CP sample, however, also worse levels of self-efficacy. Pain as a covariate had a significant negative impact on all measures, leading to poorer self-efficacy while worsening depression and anxiety; impairment had a significant worsening impact on physical QoL and self-efficacy only. Conclusion Similar expressions of mental health outcomes in emerging adults with CP and the general population indicate the high adaptive capability of emerging adults with CP.

Abstract Background Epidemiological studies show that even in highly developed countries many people with depression do not seek help for their mental health issues, despite promising prevention approaches encouraging people to seek help and reduce self-stigma. Therefore, an anti-stigma intervention study to support help-seeking behaviour will be developed on the basis of the newly explicated “Seeking Mental Health Care Model”. Methods A quasi-experimental online study will be carried out to assess the effect of different intervention variables relevant for the help-seeking process. The study is conceived as a fractional factorial design. Participants will be screened for depressive complaints (PHQ-9 sum score ≥ 8) and current psychiatric/psychotherapeutic treatment. After baseline assessment the participants will be randomly allocated into one of the 24 study groups receiving different combinations of the vignette-based intervention aiming to reduce stigma and support help-seeking. Next, relevant outcome measures will be administered a second time. In a 3- and 6-month follow-up help-seeking behaviour will be measured. Gamified elements and avatar-choice techniques will be used to heighten study immersion and adherence. Discussion On the basis of the project results, promising research and intervention perspectives can be developed. Results, firstly, allow for a more detailed empirical investigation and conceptualisation of the stages of mental health care utilisation, as well as an examination of theoretical approaches to stigmatisation. Secondly, our online study could provide insights for an evidence-based design and evaluation of online interventions for people with a mental illness. Trial registration German Clinical Trials Register: DRKS00023557 . Registered 11 December 2020. World Health Organization, Universal Trial Number: U1111–1264-9954. Registered 16 February 2021.

Abstract Background Time-use surveys can closely monitor daily activities, times of stress and relaxation, and examine predictors and trajectories with regard to health. However, previous studies have often neglected the complex interaction of daily activities when looking at health outcomes. Methods Using latent profile analysis, this study examined patterns of self-reported daily time use (0–12h hours) for nine types of behaviour (work, errands, housework, childcare, care of persons in need, education, repairs and gardening, physical activity, and hobbies/leisure-time activities) in the 2018 wave of the German Socio-Economic Panel (N = 30,152; 51.9% female; M = 46.87 years). Sociodemographic variables, affective wellbeing, general and domain-specific life satisfaction, and self-rated health were inspected as predictors via multinomial logistic regression models. Results Six latent profiles emerged: full-time work (47.2%), leisure (33.8%), childcare (8.9%), education (7.0%), part-time work & care (2.6%), and care (0.5%). Overall, the care and part-time work & care profiles showed the lowest wellbeing scores, lower subjective health, and life satisfaction. Women were more likely to be members of the care and childcare profiles. Men were more likely to belong to the full-time work profile, and they reported significantly higher wellbeing than women. Conclusions The analysis revealed distinct patterns of time use and a burden on women, given their investment in care and childcare. Part-time work, and care seemed particularly demanding, and thus, are important areas for prevention, for instance, regarding mental health problems. However, time use was assessed via self-reports, therefore future studies could implement objective measures like digital trackers to validate findings.

This study explored the evidence of validity of internal structure of the 12-item Functional Assessment of Chronic Illness Therapy—Spiritual Wellbeing Scale (FACIT-Sp-12) in Brazilian adolescents with chronic health conditions. The study involved 301 Brazilian adolescents with cancer, type 1 diabetes mellitus, or cystic fibrosis. Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA), and Item Response Theory (IRT) were used to test the internal structure. Reliability was determined with Cronbach’s Alpha and McDonald’s Omega. The EFA suggested a one-dimensional scale structure in contrast to the original 2-factor model or the 3-factor model which were not reproduced in the current CFA. All quality indicators for the EFA one-factor exceeded the required criteria (FDI = 0.97, EAP = 0.97, SR = 3.96 and EPTD = 0.96, latent GH = 0.90. and the observed GH = 0.85). The FACIT-Sp-12 for adolescents yielded strong evidence for a 1-factor model and with good reliability.

Abstract Background Although telemedical applications are increasingly used in the area of both mental and physical illness, there is no quality of life (QoL) instrument that takes into account the specific context of the healthcare setting. Therefore, the aim of this study was to determine a concept of quality of life in telemedical care to inform the development of a setting-sensitive patient-reported outcome measure. Methods Overall, 63 semi-structured single interviews and 15 focus groups with 68 participants have been conducted to determine the impact of telemedical care on QoL. Participants were patients with chronic physical or mental illnesses, with or without telemedicine supported healthcare as well as telemedical professionals. Mayring's content analysis approach was used to encode the qualitative data using MAXQDA software. Results The majority of aspects that influence the QoL of patients dealing with chronic conditions or mental illnesses could be assigned to an established working model of QoL. However, some aspects that were considered important (e. g. perceived safety) were not covered by the pre-existing domains. For that reason, we re-conceptualized the working model of QoL and added a sixth domain, referred to as healthcare-related domain. Conclusion Interviewing patients and healthcare professionals brought forth specific aspects of QoL evolving in telemedical contexts. These results reinforce the assumption that existing QoL measurements lack sensitivity to assess the intended outcomes of telemedical applications. We will address this deficiency by a telemedicine-related re-conceptualization of the assessment of QoL and the development of a suitable add-on instrument based on the resulting category system of this study.

Abstract Background Effective inclusion in society for young people with disabilities is increasingly seen as generating opportunities for self-development, and improving well-being. However, significant barriers remain in the vast majority of activities meaningful for young adults. Research argues that various personal (disabilities, health) and environmental (access to the resources needed, accessible environment, discrimination, lack of personal economic independence) factors contribute to limited participation. However, previous studies conducted in young people with cerebral palsy (CP) mainly investigated the transition period to adulthood, and did not fully consider the whole range of impairment severity profiles or environmental barriers. In this study, we will use the follow-up of the SPARCLE cohort and a comparison group from the general population (1) to investigate the impact of the environment on participation and quality of life of young adults with CP, (2) to determine predictors of a successful young adulthood in educational, professional, health and social fields, (3) to compare quality of life and frequency of participation in social, work and recreational activities with the general population, (4) to document on participation and quality of life in those with severe disabilities. Methods The SPARCLE3 study has a combined longitudinal and cross-sectional design. Young adults with CP aged 22 to 27 years in 6 European regions previously enrolled in the SPARCLE cohort or newly recruited will be invited to self-complete a comprehensive set of questionnaires exploring participation (daily life and discretionary activities), health-related quality of life, body function, personal factors (health, personal resources), and contextual factors (availability of needed environmental items, family environment, services provision) during home visits supervised by trained researchers. Proxy-reports or adapted questionnaires will be used for those with the most severe impairments. The recruitment of a large group from the general population (online survey) will enable to identify life areas where the discrepancies between young people with CP and their able-bodied peers are the most significant. Discussion This study will help identify to what extent disabilities and barriers in environment negatively affect participation and quality of life, and how previous valued experiences during childhood or adolescence might modulate these effects.

ObjectiveSpine injury is highly prevalent in patients with poly-trauma, but data on the co-occurrence of spine trauma in patients with traumatic brain injury (TBI) are scarce. In this study, we used the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) database to assess the prevalence, characteristics, and outcomes of patients with TBI and a concurrent traumatic spinal injury (TSI).MethodsData from the European multi-center CENTER-TBI study were analyzed. Adult patients with TBI (≥18 years) presenting with a concomitant, isolated TSI of at least serious severity (Abbreviated Injury Scale; AIS ≥3) were included. For outcome analysis, comparison groups of TBI patients with TSI and systemic injuries (non-isolated TSI) and without TSI were created using propensity score matching. Rates of mortality, unfavorable outcomes (Glasgow Outcome Scale Extended; GOSe < 5), and full recovery (GOSe 7–8) of all patients and separately for patients with only mild TBI (mTBI) were compared between groups at 6-month follow-up.ResultsA total of 164 (4%) of the 4,254 CENTER-TBI core study patients suffered from a concomitant isolated TSI. The median age was 53 [interquartile range (IQR): 37–66] years and 71% of patients were men. mTBI was documented in 62% of cases, followed by severe TBI (26%), and spine injuries were mostly cervical (63%) or thoracic (31%). Surgical spine stabilization was performed in 19% of cases and 57% of patients were admitted to the ICU. Mortality at 6 months was 11% and only 36% of patients regained full recovery. There were no significant differences in the 6-month rates of mortality, unfavorable outcomes, or full recovery between TBI patients with and without concomitant isolated TSI. However, concomitant non-isolated TSI was associated with an unfavorable outcome and a higher mortality. In patients with mTBI, a negative association with full recovery could be observed for both concomitant isolated and non-isolated TSI.ConclusionRates of mortality, unfavorable outcomes, and full recovery in TBI patients with and without concomitant, isolated TSIs were comparable after 6 months. However, in patients with mTBI, concomitant TSI was a negative predictor for a full recovery. These findings might indicate that patients with moderate to severe TBI do not necessarily exhibit worse outcomes when having a concomitant TSI, whereas patients with mTBI might be more affected.

Abstract Background While a strong negative impact of unemployment on health has been established, the present research examined the lesser studied interplay of gender, social context and job loss on health trajectories. Methods Data from the German Socio-Economic Panel was used, which provided a representative sample of 6838 participants. Using latent growth modelling the effects of gender, social context (East vs. West Germans), unemployment (none, short-term or long-term), and their interactions were examined on health (single item measures of self-rated health and life satisfaction respectively). Results Social context in general significantly predicted the trajectories of self-rated health and life satisfaction. Most notably, data analysis revealed that West German women reported significantly lower baseline values of self-rated health following unemployment and did not recover to the levels of their East German counterparts. Only long-term, not short-term unemployment was related to lower baseline values of self-rated health, whereas, in relation to baseline values of life satisfaction, both types of unemployment had a similar negative effect. Conclusions In an economic crisis, individuals who already carry a higher burden, and not only those most directly affected economically, may show the greatest health effects.

Introduction: Neurocognitive problems associated with posttraumatic stress disorder (PTSD) can interact with impairment resulting from traumatic brain injury (TBI). Research question: We aimed to identify neurocognitive problems associated with probable PTSD following TBI in a civilian sample. Material and methods: The study is part of the CENTER-TBI project (Collaborative European Neurotrauma Effectiveness Research) that aims to better characterize TBI. For this cross-sectional study, we included patients of all severities aged over 15, and a Glasgow Outcome Score Extended (GOSE) above 3. Participants were assessed at six months post-injury on the PTSD Checklist-5 (PCL-5), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT) and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Primary analysis was a complete case analysis. Regression analyses were performed to investigate the association between the PCL-5 and cognition. Results: Of the 1134 participants included in the complete case analysis, 13.5% screened positive for PTSD. Probable PTSD was significantly associated with higher TMT-(B-A) (OR ​= ​1.35, 95% CI: 1.14–1.60, p ​

Legionella pneumophila, the causative agent of Legionnaires’ disease, a severe pneumonia, injects via a type 4 secretion system (T4SS) more than 300 proteins into macrophages, its main host cell in humans. Certain of these proteins are implicated in reprogramming the metabolism of infected cells by reducing mitochondrial oxidative phosphorylation (OXPHOS) early after infection. Here. we show that despite reduced OXPHOS, the mitochondrial membrane potential (Δψm) is maintained during infection of primary human monocyte-derived macrophages (hMDMs). We reveal that L. pneumophila reverses the ATP-synthase activity of the mitochondrial FOF1-ATPase to ATP-hydrolase activity in a T4SS-dependent manner, which leads to a conservation of the Δψm, preserves mitochondrial polarization, and prevents macrophage cell death. Analyses of T4SS effectors known to target mitochondrial functions revealed that LpSpl is partially involved in conserving the Δψm, but not LncP and MitF. The inhibition of the L. pneumophila-induced ‘reverse mode’ of the FOF1-ATPase collapsed the Δψm and caused cell death in infected cells. Single-cell analyses suggested that bacterial replication occurs preferentially in hMDMs that conserved the Δψm and showed delayed cell death. This direct manipulation of the mode of activity of the FOF1-ATPase is a newly identified feature of L. pneumophila allowing to delay host cell death and thereby to preserve the bacterial replication niche during infection.

Introduction: While most people with cerebral palsy (CP) will have a life expectancy similar to that of the general population, international research has primarily focused on childhood and adolescence; and knowledge about the quality of life (QoL) of young adults with CP, its trajectories, and associated factors remains scarce.Methods: This longitudinal study included young adults with CP living in five European regions and who had previously participated in the SPARCLE cohort as children and/or adolescents. Their QoL in the psychological well-being and social relationships domains was estimated using age-appropriate validated instruments (KIDSCREEN-52 in childhood/adolescence and WHOQOL-Bref in young adulthood). We used generalized linear mixed-effect models with random intercept to estimate long-term trajectories of QoL in both domains and to investigate whether severity of impairment, pain, and seizure influenced these trajectories. We sought to identify potentially different trajectories of QoL from childhood to adulthood using a shape-based clustering method.Results: In total, 164 young adults with CP aged 22–27 years participated in the study. Psychological well-being linearly decreased by 0.78 points (scale 0–100) per year (95% confidence interval (CI) −0.99 to −0.56) from childhood to young adulthood, whereas QoL in the social relationships domain increased (β coefficient 1.24, 95% CI 0.92–1.55). Severity of impairment was associated with reduced QoL in all life periods of the study (childhood, adolescence, and young adulthood): motor impairment with social relationships, and more nuancedly intellectual disability with psychological well-being and social relationships. At all periods, frequent pain significantly reduced psychological well-being, and seizures were associated with lower QoL in the social relationships domain. In both domains, we identified a group of individuals with CP who presented a reverse trajectory compared with the general QoL trajectory.Conclusion: Identification of QoL trajectories and their associated factors yields improved knowledge about the experience of individuals with CP until young adulthood. Further studies are needed to better understand the determinants that have the greatest influence on the different shapes of long-term trajectories of QoL.

BackgroundIn crisis communication, warning messages are key to informing and galvanizing the public to prevent or mitigate damage. Therefore, this study examines how risk appraisal and individual characteristics influence the intention to comply with behavioral recommendations of a warning message regarding three hazard types: the COVID-19 pandemic, violent acts, and severe weather.MethodsA cross-sectional survey examined 403 German participants from 18 to 89 years (M = 29.24; 72% female). Participants were allocated to one of three hazard types (COVID-19 pandemic, violent acts, severe weather) and presented with warning messages that were previously issued via an official warning app. Four components of risk appraisal—perceived severity (PS), anticipated negative emotions (AE), anticipatory worry (AW), and risk perception (RP)—were assessed before and after presenting the warning message. Path models were calculated to predict the intention to comply with the warning message, controlling for age, gender, and previous hazard experience.ResultsFor the COVID-19 pandemic, higher age (β = 0.18) predicted warning compliance (R2 = 0.05). AE (β = 0.20) predicted compliance in the case of violent acts (R2 = 0.09). For severe weather, PS (β = 0.28), age (β = 0.29), and female gender (β = 0.34) lead to higher compliance (R2 = 0.27). Changes across risk appraisal components were not consistent, as some facets decreased after the receipt of a warning message.DiscussionRisk appraisal has shown a marginal yet differential influence on warning message compliance in different types of hazards. Regarding the COVID-19 pandemic, the impact of sociodemographic factors on compliance should be studied more intensively. Moreover, integrating intermediary variables, such as self-efficacy, is necessary.

Background: Forced displacement has been suggested as a potential cause for depression and anxiety in later life. Little research has been done on the influence of the host country's socio-political system. Here we examine whether the later-life effects of displacement on mental health (i.e. depressive symptoms and anxiety attacks) differ between socio-political contexts. We hypothesized that between-group differences (displaced vs. nondisplaced) in self-rated depression scores and frequencies of anxiety attacks are more pronounced in East versus West German populations. Methods: Datasets from three representative nationwide surveys (2002, 2003, 2007) were analyzed; study participants born 1946 and earlier were included. The final sample comprised 2239 participants, including 1235 women. The depression and anxiety modules of the Patient Health Questionnaire (PHQ-D) were used to assess current anxiety and depression. Results: Of the total sample, 15.4% reported WW2 displacement, 18.9% (n = 129) in the East and 13.9% (n = 216) in the West German sample. Concerning depression, we found significant between-group differences (displaced vs. nondisplaced) in the East (but not West) German sample. Concerning anxiety, both displaced East and West Germans reported a significantly higher frequency of anxiety attacks, as compared to nondisplaced individuals. Differences between effect sizes (East vs. West) were significant for depression, and anxiety after controlling for age and sex. Limitations: Limitations include the self-rated assessment, not controlling for the confounding impact of the German reunification, and the cross-sectional study design. Conclusion: Results corroborate the assumption of an unsupportive socio-political context as a potential predisposing factor for later-life anxiety or depression after forced displacement.

BackgroundPediatric traumatic brain injury (TBI) may cause a wide range of symptoms, which can negatively affect the quality of life of patients and their entire families. No internationally and simultaneously developed disease-specific instrument exists for assessing pediatric health-related quality of life (HRQoL) after TBI. The aim of the current project is to provide original material from small group interviews with individuals after TBI concerning what they state is relevant for their HRQoL. This material is required for a further study to generate items for age-adapted questionnaires assessing the TBI-specific HRQoL of children and adolescents (C&A): the QOLIBRI-Kiddy/Kid/Ado and proxy versions (Quality of Life after Brain Injury-Kiddy/Kids/Adolescents/Proxy) for individuals aged 6-17 and their parents.MethodsThe semi-structured interviews were conducted with separate small groups of C&A (n = 19), divided into three age groups (5-7y, 8-12y, 13-17y), after mild, moderate, and severe TBI, and with groups of the corresponding parents (n = 26). All interviews lasted for about 60 minutes, were recorded and transcribed verbatim. The statements were investigated by qualitative analyses and sorted into categories relevant to the HRQoL of C&A after TBI. Only descriptive group comparisons but no pairwise comparisons between children and corresponding parents were performed.ResultsThe analyses led to 32 subcategories, which were assigned to six main theoretically based HRQoL categories. Many agreements exist between the C&A's and parents' perspectives within the main categories, however their focus on HRQoL differs, especially concerning age-related contents. Parents of the youngest participant group already focus on topics such as autonomy, whereas this only becomes relevant for C&A from the age of eight years on. Interestingly, even 5-year-old children were able to discuss their HRQoL, which indicates the importance of a self-report instrument.ConclusionsResults obtained from this qualitative study identify the content of the HRQoL dimensions important for C&A after TBI and their parents. Both, differences and similarities in the children's and the parents' views were investigated, to get a first insight in valid dimensions for the prospective questionnaires to be developed. In a future study, items for the questionnaires will be deducted from the small group interview material and psychometrically tested in C&A after TBI from Germany. This study will address whether all statements were assigned to the suitable dimensions and whether differences between C&A and parents persist.

ABSTRACT Through coevolution with host cells, microorganisms have acquired mechanisms to avoid the detection by the host surveillance system and to use the cell’s supplies to establish themselves. Indeed, certain pathogens have evolved proteins that imitate specific eukaryotic cell proteins, allowing them to manipulate host pathways, a phenomenon termed molecular mimicry. Bacterial “eukaryotic-like proteins” are a remarkable example of molecular mimicry. They are defined as proteins that strongly resemble eukaryotic proteins or that carry domains that are predominantly present in eukaryotes and that are generally absent from prokaryotes. The widest diversity of eukaryotic-like proteins known to date can be found in members of the bacterial genus Legionella, some of which cause a severe pneumonia in humans. The characterization of a number of these proteins shed light on their importance during infection. The subsequent identification of eukaryotic-like genes in the genomes of other amoeba-associated bacteria and bacterial symbionts suggested that eukaryotic-like proteins are a common means of bacterial evasion and communication, shaped by the continuous interactions between bacteria and their protozoan hosts. In this review, we discuss the concept of molecular mimicry using Legionella as an example and show that eukaryotic-like proteins effectively manipulate host cell pathways. The study of the function and evolution of such proteins is an exciting field of research that is leading us toward a better understanding of the complex world of bacterium-host interactions. Ultimately, this knowledge will teach us how host pathways are manipulated and how infections may possibly be tackled.

Introduction: Following behavioral recommendations is key to successful containment of the COVID-19 pandemic. Therefore, it is important to identify causes and patterns of non-compliance in the population to further optimize risk and health communication.Methods: A total of 157 participants [80% female; mean age = 27.82 years (SD = 11.01)] were surveyed regarding their intention to comply with behavioral recommendations issued by the German government. Latent class analysis examined patterns of compliance, and subsequent multinomial logistic regression models tested sociodemographic (age, gender, country of origin, level of education, region, and number of persons per household) and psychosocial (knowledge about preventive behaviors, risk perception, stigmatizing attitudes) predictors.Results: Three latent classes were identified: high compliance (25%) with all recommendations; public compliance (51%), with high compliance regarding public but not personal behaviors; and low compliance (24%) with most recommendations. Compared to high compliance, low compliance was associated with male gender [relative risk ratio (RRR) = 0.08 (0.01; 0.85)], younger age [RRR = 0.72 (0.57; 0.93)], and lower public stigma [RRR = 0.21 (0.05; 0.88)]. Low compliers were also younger than public compliers [RRR = 0.76 (0.59; 0.98)].Discussion: With 25% of the sample reporting full compliance, and 51% differing in terms of public and personal compliance, these findings challenge the sustainability of strict regulatory measures. Moreover, young males were most likely to express low compliance, stressing the need for selective health promotion efforts. Finally, the positive association between public stigma and compliance points to potential othering effects of stigma during a pandemic, but further longitudinal research is required to examine its impact on health and social processes throughout the pandemic.

ObjectivesThe current study aims to examine the construct of empowerment in the context of a transition education program. Patient education programs strive to empower adolescents with chronic conditions to take responsibility for their own health care to manage their transition from pediatric to adult medicine. Our study aimed to identify the core components of patient empowerment and examined whether its components are responsive to a patient education program.MethodsData was collected in two longitudinal studies involving N = 723 adolescents with chronic conditions. We used Latent Difference Score models (LDSm) of: 1) self-efficacy (GSE), 2) transition competence (TCS), and 3) patient activation (PAM) to quantify the latent variable of patient empowerment (PE). Additionally, the LDSm were extended to analyze the effects of group affiliation (intervention vs. control) and participants' age on empowerment.ResultsPE was identifiable by the three components. The intervention group developed significantly higher scores of PE compared to the control group. Age (13-21 years) did not moderate the relation between group affiliation and PE.ConclusionsWe quantified PE successfully using a psychometric modeling of change. Patient empowerment is measureable and utilizable in the specific context of transition of adolescents with chronic conditions.

Abstract Background The Internet enables an unprecedented opportunity to access a broad range of self-tests (e.g. testing for HIV, cancer, hepatitis B/C), which can be conducted by lay consumers without the help of a health professional. However, there is only little knowledge about the determinants of the use of self-tests. Thus, the aims of this study were (1) to experimentally investigate the impact of situational and application-related characteristics on the intention to use a self-test (ST), compared to being tested by a health professional at home (HPH) or at a doctor’s office (HPD), (2) to examine the applicability of social-cognitive health behaviour theories on self-testing, and (3) to explore the advantages of integrating technological affinity into social-cognitive health behaviour models to predict self-testing. Methods In a factorial survey, 1248 vignettes were rated by 208 students. The core concepts of social-cognitive health behaviour theories, technological affinity, and different situational and application-related characteristics were investigated. Results Intention to ST was only predicted by the medical expertise of the tested person, while HPH and HPD were also associated with the application purpose of the test and the presence of an emotionally supporting person. Perceived severity and outcome-expectancy significantly predicted intention to self-test. Technological enthusiastic people had a higher intention to use a self-test. Conclusions Intention to ST, HPH and HPD were predicted by different situational and application-related characteristics. Social-cognitive health behaviour theories can be applied to predict self-testing and do not need to be extended by technological affinity.

The aim of this study was to focus on the ethical and social issues derived from the implementation of transtelephonic electrocardiography (TTECG) in the public healthcare sector in Chile, studying patients and healthcare providers' acceptance and expectations concerning: (a) TTECG effectiveness and safety; and (b) data protection issues, such as confidentiality, privacy and security. For this purpose, we developed two psychosocial surveys; the first was addressed to patients receiving transtelephonic electrocardiogram (either in the emergency services of hospitals or in distant primary care services) and the second one aimed at healthcare providers involved in either administering and/or interpreting it. Results included: (a) major acceptability of TTECG in terms of safety and security; (b) privacy and confidentiality of the patients were considered to be well protected; and (c) the patient-doctor relationship was not affected by this device.

Military veterans may have higher rates of amyotrophic lateral sclerosis (ALS) mortality than non-veterans. Few studies, with sparse exposure information and mixed results, have studied relationships between military-related factors and ALS survival. We evaluated associations between military-related factors and ALS survival among U.S. military veteran cases.We followed 616 medical record-confirmed cases from enrollment (2005-2010) in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study until death or July 25, 2013, whichever came first. We ascertained vital status information from several sources within the Department of Veterans Affairs. We obtained information regarding military service, deployments, and 39 related exposures via standardized telephone interviews. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals. We adjusted for potential confounding and missing covariate data biases via inverse probability weights. We also used inverse probability weights to adjust for potential selection bias among a case group that included a disproportionate number of long-term survivors at enrollment.We observed 446 deaths during 24,267 person-months of follow-up (median follow-up: 28 months). Survival was shorter for cases who served before 1950, were deployed to World War II, or mixed and applied burning agents, with HRs between 1.58 and 2.57. Longer survival was associated with exposure to: paint, solvents, or petrochemical substances; local food not provided by the Armed Forces; or burning agents or Agent Orange in the field with HRs between 0.56 and 0.73.Although most military-related factors were not associated with survival, associations we observed with shorter survival are potentially important because of the large number of military veterans.

A broad range of self-tests (testing for e.g. HIV, cancer, hepatitis B/C) have become available and can be conducted by lay consumers without the help of a health professional. The aims of this study were to (a) investigate the prevalence of self-testing, (b) identify the most frequently used self-tests, and (c) explore the associations between socio-demographic, health-related and individual factors with self-testing.A face-to-face plus paper-pencil cross-sectional survey was conducted. The sample consisted of 2.527 respondents who were representative of the German population in terms of the age, sex, and residence. Basic descriptive statistics and univariate logistic regression analyses were performed.8.5% of the participants reported having used one or more self-tests in the past, totalling 363 self-tests, with a mean of 1.7 (min. = 1, max. = 6). The three self-tests most frequently indicated were for detecting diabetes, bowel cancer, and allergies. Self-testers were older (Nagelkerke R2 = .006, p < .01), had a higher BMI (Nagelkerke R2 = .013, p < .001) and displayed more physical and mental fatigue (Nagelkerke R2 = .031, p < .001) than non-testers. Self-testers also reported higher global life satisfaction values (Nagelkerke R2 = .008, p < .01) and a higher educational level (Nagelkerke R2 = .015, p < .01).Self-testing is fairly prevalent in Germany Given the current shortage of physicians in Germany, especially in rural areas, and recent studies on the use of self-medication, the topic of self-testing has a great practical and socio-political relevance. Future studies should investigate further predictors of self-testing (e.g. contextual, situational and individual factors) as well as the emotional consequences of testing as a layperson without the attendance of a health professional.

Psychosocial, emotional, and physical problems can emerge after traumatic brain injury (TBI), potentially impacting health-related quality of life (HRQoL). Until now, however, neither the discriminatory power of disease-specific (QOLIBRI) and generic (SF-36) HRQoL nor their correlates have been compared in detail. These aspects as well as some psychometric item characteristics were studied in a sample of 795 TBI survivors. The Shannon H' index absolute informativity, as an indicator of an instrument’s power to differentiate between individuals within a specific group or health state, was investigated. Psychometric performance of the two instruments was predominantly good, generally higher, and more homogenous for the QOLIBRI than for the SF-36 subscales. Notably, the SF-36 “Role Physical,” “Role Emotional,” and “Social Functioning” subscales showed less satisfactory discriminatory power than all other dimensions or the sum scores of both instruments. The absolute informativity of disease-specific as well as generic HRQoL instruments concerning the different groups defined by different correlates differed significantly. When the focus is on how a certain subscale or sum score differentiates between individuals in one specific dimension/health state, the QOLIBRI can be recommended as the preferable instrument.

Background : Examination of existing research on posttraumatic adjustment after disasters suggests that survivors’ posttraumatic stress levels might be better understood by investigating the influence of the characteristics of the event experienced on how people thought and felt, during the event as well as afterwards. Objective : To compare survivors’ perceived post- and peritraumatic emotional and cognitive reactions across different types of disasters. Additionally, to investigate individual and event characteristics. Design : In a European multi-centre study, 102 survivors of different disasters terror attack, flood, fire and collapse of a building were interviewed about their responses during the event. Survivors’ perceived posttraumatic stress levels were assessed with the Impact of Event Scale-Revised (IES-R). Peritraumatic emotional stress and risk perception were rated retrospectively. Influences of individual characteristics, such as socio-demographic data, and event characteristics, such as time and exposure factors, on post- and peritraumatic outcomes were analyzed. Results : Levels of reported post- and peritraumatic outcomes differed significantly between types of disasters. Type of disaster was a significant predictor of all three outcome variables but the factors gender, education, time since event, injuries and fatalities were only significant for certain outcomes. Conclusion : Results support the hypothesis that there are differences in perceived post- and peritraumatic emotional and cognitive reactions after experiencing different types of disasters. However, it should be noted that these findings were not only explained by the type of disaster itself but also by individual and event characteristics. As the study followed an explorative approach, further research paths are discussed to better understand the relationships between variables.

Synthesis of acetate from carbon dioxide and molecular hydrogen is considered to be the first carbon assimilation pathway on earth. It combines carbon dioxide fixation into acetyl-CoA with the production of ATP via an energized cell membrane. How the pathway is coupled with the net synthesis of ATP has been an enigma. The anaerobic, acetogenic bacterium Acetobacterium woodii uses an ancient version of this pathway without cytochromes and quinones. It generates a sodium ion potential across the cell membrane by the sodium-motive ferredoxin:NAD oxidoreductase (Rnf). The genome sequence of A. woodii solves the enigma: it uncovers Rnf as the only ion-motive enzyme coupled to the pathway and unravels a metabolism designed to produce reduced ferredoxin and overcome energetic barriers by virtue of electron-bifurcating, soluble enzymes.

Following reports of an increased incidence of amyotrophic lateral sclerosis (ALS) in U.S. veterans, we have conducted a high-density genome-wide association study (GWAS) of ALS outcome and survival time in a sample of U.S. veterans. We tested ∼1.3 million single nucleotide polymorphisms (SNPs) for association with ALS outcome in 442 incident Caucasian veteran cases diagnosed with definite or probable ALS and 348 Caucasian veteran controls. To increase power, we also included genotypes from 5909 publicly-available non-veteran controls in the analysis. In the survival analysis, we tested for association between SNPs and post-diagnosis survival time in 639 Caucasian veteran cases with definite or probable ALS. After this discovery phase, we performed follow-up genotyping of 299 SNPs in an independent replication sample of Caucasian veterans and non-veterans (ALS outcome: 183 cases and 961 controls; survival: 118 cases). Although no SNPs reached genome-wide significance in the discovery phase for either phenotype, three SNPs were statistically significant in the replication analysis of ALS outcome: rs6080539 (177 kb from PCSK2), rs7000234 (4 kb from ZNF704), and rs3113494 (13 kb from LOC100506746). Two SNPs located in genes that were implicated by previous GWA studies of ALS were marginally significant in the pooled analysis of discovery and replication samples: rs17174381 in DPP6 (p = 4.4×10(-4)) and rs6985069 near ELP3 (p = 4.8×10(-4)). Our results underscore the difficulty of identifying and convincingly replicating genetic associations with a rare and genetically heterogeneous disorder such as ALS, and suggest that common SNPs are unlikely to account for a substantial proportion of patients affected by this devastating disorder.

Primary open-angle glaucoma (POAG) is the most common form of glaucoma and one of the leading causes of vision loss worldwide. The genetic etiology of POAG is complex and poorly understood. The purpose of this work is to identify genomic regions of interest linked to POAG. This study is the largest genetic linkage study of POAG performed to date: genomic DNA samples from 786 subjects (538 Caucasian ancestry, 248 African ancestry) were genotyped using either the Illumina GoldenGate Linkage 4 Panel or the Illumina Infinium Human Linkage-12 Panel. A total of 5233 SNPs was analyzed in 134 multiplex POAG families (89 Caucasian ancestry, 45 African ancestry). Parametric and non-parametric linkage analyses were performed on the overall dataset and within race-specific datasets (Caucasian ancestry and African ancestry). Ordered subset analysis was used to stratify the data on the basis of age of glaucoma diagnosis. Novel linkage regions were identified on chromosomes 1 and 20, and two previously described loci-GLC1D on chromosome 8 and GLC1I on chromosome 15--were replicated. These data will prove valuable in the context of interpreting results from genome-wide association studies for POAG.

The objective of this study was to determine if MTND2*LHON4917G (4917G), a specific non-synonymous polymorphism in the mitochondrial genome previously associated with neurodegenerative phenotypes, is associated with increased risk for age-related macular degeneration (AMD). A preliminary study of 393 individuals (293 cases and 100 controls) ascertained at Vanderbilt revealed an increased occurrence of 4917G in cases compared to controls (15.4% vs.9.0%, p = 0.11). Since there was a significant age difference between cases and controls in this initial analysis, we extended the study by selecting Caucasian pairs matched at the exact age at examination. From the 1547 individuals in the Vanderbilt/Duke AMD population association study (including 157 in the preliminary study), we were able to match 560 (280 cases and 280 unaffected) on exact age at examination. This study population was genotyped for 4917G plus specific AMD-associated nuclear genome polymorphisms in CFH, LOC387715 and ApoE. Following adjustment for the listed nuclear genome polymorphisms, 4917G independently predicts the presence of AMD (OR = 2.16, 95%CI 1.20-3.91, p = 0.01). In conclusion, a specific mitochondrial polymorphism previously implicated in other neurodegenerative phenotypes (4917G) appears to convey risk for AMD independent of recently discovered nuclear DNA polymorphisms.