Excessive alcohol consumption is one of the most important lifestyle factors affecting the disease burden in the Western world. The results of treatment in daily practice are modest at best. The aim of the RESCueH programme is to develop and evaluate methods, which are as practice-near as possible, and therefore can be implemented quickly and easily in everyday clinical practice. It is the first clinical alcohol programme to be transatlantic in scope, with implementation in treatment centers located in Denmark, Germany and the US. The RESCueH programme comprises 5 randomized controlled trials, and the studies can be expected to result in (1) more patients starting treatment in specialized outpatient clinics, (2) a greater number of elderly patients being treated, (3) increased patient motivation for treatment and thus improved adherence, (4) more patients with stable positive outcomes after treatment and (5) fewer patients relapsing into harmful drinking. The aim of this paper is to discuss the rationale for the RESCueH programme, to present the studies and expected results.

Alcohol use disorders (AUDs), and alcohol dependence (AD) in particular, are prevalent and associated with a large burden of disability and mortality. The aim of this study was to estimate prevalence of AD in the European Union (EU), Iceland, Norway, and Switzerland for the year 2010, and to investigate potential influencing factors. The 1-year prevalence of AD in the EU was estimated at 3.4% among people 18–64 years of age in Europe (women 1.7%, men 5.2%), resulting in close to 11 million affected people. Taking into account all people of all ages, AD, abuse and harmful use resulted in an estimate of 23 million affected people. Prevalence of AD varied widely between European countries, and was significantly impacted by drinking cultures and social norms. Correlations with level of drinking and other drinking variables and with major known outcomes of heavy drinking, such as liver cirrhosis or injury, were moderate. These results suggest a need to rethink the definition of AUDs.

Background: Effective interventions for maltreated children are impeded by gaps in our knowledge of the etiopathogenic mechanisms leading from maltreatment to mental disorders. Although some studies have already identified individual risk factors, there is a lack of large-scale multilevel research on how psychosocial, neurobiological, and genetic factors act in concert to modulate risk of internalizing psychopathology in childhood following maltreatment. To help close this gap, we aim to delineate gender-specific pathways from maltreatment to psychological disorder/resilience. To this end, we examine the interplay of specific maltreatment characteristics and psychological, endocrine, metabolomic, and (epi-)genomic stress response patterns as well as cognitive-emotional/social processes as determinants of developmental outcome. Specifically, we will explore endocrine, metabolomic, and epigenetic mechanisms leading from maltreatment to a higher risk of depression and anxiety disorders.

In the early 20th century, there were few therapeutic options for mental illness and asylum numbers were rising. This pessimistic outlook favoured the rise of the eugenics movement. Heredity was assumed to be the principal cause of mental illness. Politicians, scientists and clinicians in North America and Europe called for compulsory sterilisation of the mentally ill. Psychiatric genetic research aimed to prove a Mendelian mode of inheritance as a scientific justification for these measures. Ernst Rüdin’s seminal 1916 epidemiological study on inheritance of dementia praecox featured large, systematically ascertained samples and statistical analyses. Rüdin’s 1922–1925 study on the inheritance of “manic-depressive insanity” was completed in manuscript form, but never published. It failed to prove a pattern of Mendelian inheritance, counter to the tenets of eugenics of which Rüdin was a prominent proponent. It appears he withheld the study from publication, unable to reconcile this contradiction, thus subordinating his carefully derived scientific findings to his ideological preoccupations. Instead, Rüdin continued to promote prevention of assumed hereditary mental illnesses by prohibition of marriage or sterilisation and was influential in the introduction by the National Socialist regime of the 1933 “Law for the Prevention of Hereditarily Diseased Offspring” (Gesetz zur Verhütung erbkranken Nachwuchses).

Let us consider the singularly perturbed model problem Lu := -epsilon laplace u-bu_x+cu = f with homogeneous Dirichlet boundary conditions on the unit-square (0,1)^2. Assuming that b > 0 is of order one, the small perturbation parameter 0 < epsilon << 1 causes boundary layers in the solution. In order to solve above problem numerically, it is beneficial to resolve these layers. On properly layer-adapted meshes we can apply finite element methods and observe convergence. We will consider standard Galerkin and stabilised FEM applied to above problem. Therein the polynomial order p will be usually greater then two, i.e. we will consider higher-order methods. Most of the analysis presented here is done in the standard energy norm. Nevertheless, the question arises: Is this the right norm for this kind of problem, especially if characteristic layers occur? We will address this question by looking into a balanced norm. Finally, a-posteriori error analysis is an important tool to construct adapted meshes iteratively by solving discrete problems, estimating the error and adjusting the mesh accordingly. We will present estimates on the Green’s function associated with L, that can be used to derive pointwise error estimators.

Background: When assessing the association between a factor X and a subsequent outcome Y in observational studies, the question that arises is what are the variables to adjust for to reduce bias due to confounding for causal inference on the effect of X on Y. Disregarding such factors is often a source of overestimation because these variables may affect both X and Y. On the other hand, adjustment for such variables can also be a source of underestimation because such variables may be the causal consequence of X and part of the mechanism that leads from X to Y. Methods: In this paper, we present a simple method to compute control variables in the presence of age at onset data on both X and a set of other variables. Using these age at onset data, control variables are computed that adjust only for conditions that occur prior to X. This strategy can be used in prospective as well as in survival analysis. Our method is motivated by an argument based on the counterfactual model of a causal effect. Results: The procedure is exemplified by examining of the relation between panic attack and the subsequent incidence of MDD. Conclusions: The results reveal that the adjustment for all other variables, irrespective of their temporal relation to X, can yield a false negative result (despite unconsidered confounders and other sources of bias).

Hintergrund Ziel der vorliegenden Untersuchung war die Erfassung der Lebensqualität von älteren Menschen mit leichten kognitiven Störungen im Vergleich zu kognitiv gesunden älteren Menschen. Die Prävalenz von leichten kognitiven Störungen in der Bevölkerung wird in epidemiologischen Studien mit 3 bis 19 % der über 65-Jährigen angegeben (Ritchie, 2004). Methode Es handelt sich um eine 2012 bundesweit durchgeführte bevölkerungsrepräsentative Befragung zur subjektiven Lebensqualität von 997 Probanden (60 Jahre und älter). Die Erfassung erfolgte mittels der Messinstrumente WHOQOL-BREF und dem speziell für ältere Menschen entwickelten WHOQOL-OLD. Zudem wurden die ermittelten Werte für die Lebensqualität in den soziodemografischen Kontext gesetzt, um eventuelle Faktoren zu ermitteln, die die unterschiedlichen Bereiche der Lebensqualität beeinflussen. Zur Identifikation kognitiver Störungen wurde der DemTect eingesetzt. Bei Verdacht auf Demenz fand das Interview nicht statt. Probanden mit leichten kognitiven Beeinträchtigungen wurden interviewt. Das Ergebnis des DemTects bestimmte die Zuteilung der Probanden in die jeweilige Gruppe (leichte kognitive Störungen vs. kognitiv gesund). Die Kriterien für die Gruppe der Probanden mit leichten kognitiven Störungen erfüllten 267 Probanden, für 730 Teilnehmer fanden sich keine Anzeichen einer kognitiven Beeinträchtigung. Ergebnis Die befragten Probanden im Alter ab 60 Jahre mit leichten kognitiven Störungen schätzten ihre Lebensqualität in allen Bereichen des WHOQOL-BREF und WHOQOL-OLD (außer im Bereich Ängste und Befürchtungen hinsichtlich Tod und Sterben) geringer ein als kognitiv gesunde Probanden. Schlussfolgerung Es konnte gezeigt werden, dass bereits leichte kognitive Störungen mit einer erheblichen Reduktion der subjektiven Lebensqualität einhergehen.:Bibliografische Zusammenfassung 3 Abkürzungsverzeichnis 4 Abbildungs- und Tabellenverzeichnis 6 1 Einleitung 7 1.1 Lebensqualität und ihre Erfassungsinstrumente 8 1.2 Leichte kognitive Störungen und ihre Diagnostik 13 2 Theorie und Stand der Forschung 17 2.1 Theoretischer Ansatz 17 2.2 Stand der Forschung 18 3 Fragestellungen und Ziele der Studie 39 4 Methodisches Vorgehen 41 4.1 Auswahl der Probanden 41 4.2 Datenerhebung 41 4.3 Beschreibung der Erhebungsinstrumente 42 4.4 Statistische Auswertung 44 5 Ergebnisse 45 5.1 Soziodemografische Merkmale der Studienteilnehmer 45 5.2 Mittelwerte WHOQOL-BREF 48 5.3 Mittelwerte WHOQOL-OLD 49 5.4 Einfluss von soziodemografischen und gesundheitsbezogenen Determinanten auf die Lebensqualität 50 5.4.1 Lebensqualitätsbereiche des WHOQOL-BREF 51 5.4.2 Lebensqualitätsbereiche des WHOQOL-OLD 54 6 Diskussion 57 7 Schlussfolgerungen und Ausblick 69 8 Zusammenfassung der Arbeit 70 9 Literaturverzeichnis 72 Erklärung über die eigenständige Abfassung der Arbeit 89 Lebenslauf 90 Publikationen 91 Danksagung 92

Background: Research suggests that a low omega-3 index may contribute to the low heart rate variability and the increased risk of cardiovascular morbidity and mortality in bipolar disorders. However, so far, no intervention trial with EPA and DHA has been conducted in bipolar patients attempting to increase their heart rate variability. - Methods: 119 patients with bipolar disorder according to DSM-IV were screened, with 55 euthymic bipolar patients—owing to inclusion criteria (e.g. low omega-3 index (< 6%), SDNN < 60 ms.)—being enrolled in a randomized, double-blind, 12-week parallel study design with omega-3 fatty acids (4 capsules of 530 mg EPA, 150 mg DHA) or corn oil as a placebo, in addition to usual treatment. Heart rate variability as well as the omega-3 index were measured at baseline and at the endpoint of the study. - Results: A total of 42 patients (omega-3: n = 23, corn oil: n = 19) successfully completed the study after 12 weeks. There was a significant increase in the omega-3 index (value at endpoint minus value at baseline) in the omega-3 group compared to the corn oil group (p < 0.0001). However, there was no significant difference in the change of the SDNN (value at endpoint minus value at baseline) between the treatment groups (p = 0.22). In addition, no correlation between changes in SDNN and change in the omega-3 index could be detected in the omega-3 group (correlation coefficient = 0.02, p = 0.94) or the corn oil group (correlation coefficient = − 0.11, p = 0.91). Similarly, no significant differences between corn oil and omega-3 group regarding the change of LF (p = 0.19), HF (p = 0.34) and LF/HF ratio (p = 0.84) could be demonstrated. - Conclusions: In our randomized, controlled intervention trial in euthymic bipolar patients with a low omega-3 index and reduced heart rate variability no significant effect of omega-3 fatty acids on SDNN or frequency-domain measures HF, LF and LF/HF ratio could be detected. Possible reasons include, among others, the effect of psychotropic medication present in our trial and/or the genetics of bipolar disorder itself. Further research is needed to test these hypotheses.

Time-of-Flight (ToF)-Kameras erzeugen Tiefenbilder (3D-Bilder), indem sie Infrarotlicht aussenden und die Zeit messen, bis die Reflexion des Lichtes wieder empfangen wird. Durch den Einsatz mehrerer ToF-Kameras können ihre vergleichsweise geringere Auflösungen überwunden, das Sichtfeld vergrößert und Verdeckungen reduziert werden. Der gleichzeitige Betrieb birgt jedoch die Möglichkeit von Störungen, die zu fehlerhaften Tiefenmessungen führen. Das Problem der gegenseitigen Störungen tritt nicht nur bei Mehrkamerasystemen auf, sondern auch wenn mehrere unabhängige ToF-Kameras eingesetzt werden. In dieser Arbeit wird eine neue optische Synchronisation vorgestellt, die keine zusätzliche Hardware oder Infrastruktur erfordert, um ein Zeitmultiplexverfahren (engl. Time-Division Multiple Access, TDMA) für die Anwendung mit ToF-Kameras zu nutzen, um so die Störungen zu vermeiden. Dies ermöglicht es einer Kamera, den Aufnahmeprozess anderer ToF-Kameras zu erkennen und ihre Aufnahmezeiten schnell zu synchronisieren, um störungsfrei zu arbeiten. Anstatt Kabel zur Synchronisation zu benötigen, wird nur die vorhandene Hardware genutzt, um eine optische Synchronisation zu erreichen. Dazu wird die Firmware der Kamera um das Synchronisationsverfahren erweitert. Die optische Synchronisation wurde konzipiert, implementiert und in einem Versuchsaufbau mit drei ToF-Kameras verifiziert. Die Messungen zeigen die Wirksamkeit der vorgeschlagenen optischen Synchronisation. Während der Experimente wurde die Bildrate durch das zusätzliche Synchronisationsverfahren lediglich um etwa 1 Prozent reduziert. / Time-of-Flight (ToF) cameras produce depth images (three-dimensional images) by measuring the time between the emission of infrared light and the reception of its reflection. A setup of multiple ToF cameras may be used to overcome their comparatively low resolution, increase the field of view, and reduce occlusion. However, the simultaneous operation of multiple ToF cameras introduces the possibility of interference resulting in erroneous depth measurements. The problem of interference is not only related to a collaborative multicamera setup but also to multiple ToF cameras operating independently. In this work, a new optical synchronization for ToF cameras is presented, requiring no additional hardware or infrastructure to utilize a time-division multiple access (TDMA) scheme to mitigate interference. It effectively enables a camera to sense the acquisition process of other ToF cameras and rapidly synchronizes its acquisition times to operate without interference. Instead of requiring cables to synchronize, only the existing hardware is utilized to enable an optical synchronization. To achieve this, the camera’s firmware is extended with the synchronization procedure. The optical synchronization has been conceptualized, implemented, and verified with an experimental setup deploying three ToF cameras. The measurements show the efficacy of the proposed optical synchronization. During the experiments, the frame rate was reduced by only about 1% due to the synchronization procedure.

Objective: Although autism spectrum disorder (ASD) is a relatively common, well-known but heterogeneous neuropsychiatric disorder, specific knowledge about characteristics of this heterogeneity is scarce. There is consensus that IQ contributes to this heterogeneity as well as complicates diagnostics and treatment planning. In this study, we assessed the accuracy of the Autism Diagnostic Observation Schedule (ADOS/2) in the whole and IQ-defined subsamples, and analyzed if the ADOS/2 accuracy may be increased by the application of machine learning (ML) algorithms that processed additional information including the IQ level. Methods: The study included 1,084 individuals: 440 individuals with ASD (with a mean IQ level of 3.3 ± 1.5) and 644 individuals without ASD (with a mean IQ level of 3.2 ± 1.2). We applied and analyzed Random Forest (RF) and Decision Tree (DT) to the ADOS/2 data, compared their accuracy to ADOS/2 cutoff algorithms, and examined most relevant items to distinguish between ASD and Non-ASD. In sum, we included 49 individual features, independently of the applied ADOS module. Results: In DT analyses, we observed that for the decision ASD/Non-ASD, solely one to four items are sufficient to differentiate between groups with high accuracy. In addition, in sub-cohorts of individuals with (a) below (IQ level ≥4)/ID and (b) above average intelligence (IQ level ≤ 2), the ADOS/2 cutoff showed reduced accuracy. This reduced accuracy results in (a) a three times higher risk of false-positive diagnoses or (b) a 1.7 higher risk for false-negative diagnoses; both errors could be significantly decreased by the application of the alternative ML algorithms. Conclusions: Using ML algorithms showed that a small set of ADOS/2 items could help clinicians to more accurately detect ASD in clinical practice across all IQ levels and to increase diagnostic accuracy especially in individuals with below and above average IQ level.