Developing tools for making inferences from genomic data

The central question that the King lab seeks to answer is, "What happens on the genomic level when phenotypes evolve?" To this end, the core focus of my work has been on developing software and analytical methods that facilitate the ability of other researchers working in this space to answer their questions of interest. ... In the second chapter, we describe the problem of inferring ancestral haplotype frequencies from pooled sequence data. We discuss five approaches to this problem that have already been developed, and we discuss a new genetic algorithm based approach that we designed. We perform a benchmarking test on a method developed by Burke et al. and we compare that method to the genetic algorithm by evaluating the performance of each on a simulated dataset. We find that the new method outperforms the existing one.by Paul PetrowskiIncludes bibliographical reference

Massively Parallel Video Networks

We introduce a class of causal video understanding models that aims to improve efficiency of video processing by maximising throughput, minimising latency, and reducing the number of clock cycles. Leveraging operation pipelining and multi-rate clocks, these models perform a minimal amount of computation (e.g. as few as four convolutional layers) for each frame per timestep to produce an output. The models are still very deep, with dozens of such operations being performed but in a pipelined fashion that enables depth-parallel computation. We illustrate the proposed principles by applying them to existing image architectures and analyse their behaviour on two video tasks: action recognition and human keypoint localisation. The results show that a significant degree of parallelism, and implicitly speedup, can be achieved with little loss in performance.Comment: Fixed typos in densenet model definition in appendi

Cortisol stress reactivity to the trier social stress test in obese adults

Approximately 600 million adults worldwide suffer from obesity. In addition to individual’s eating behavior and lack of physical activity in the development of obesity and overweight, psychosocial stress as well as hormonal stress reactivity must also be considered as important contributing factors. In the current study we compared the cortisol stress response pathway in a psychosocial stress induction (Trier Social Stress Test; TSST) with obese individuals and normal-weight controls. 32 obese individuals (17 females; mean age = 33.94 years, SD = 11.31 years) and 32 normal-weight controls (17 females; mean age = 29.09 years, SD = 10.46 years) underwent the TSST. The salivary cortisol responses and three appraisal questionnaires (Primary Appraisal Secondary Appraisal, Visual Analogue Scale, Trier Inventory for Chronic Stress) were measured. After stress induction, there was a significant main group difference between the obese individuals and the normal-weight controls for cortisol, with lower baseline and post-stress cortisol levels in the obese individuals. Nevertheless, the obese individuals as well as the normal-weight controls showed no significant difference in the self reported assessment of the stress condition but some significant differences in the cognitive appraisal of the TSST. In conclusion, the induction of psychosocial stress showed differences in the cortisol patterns between the obese individuals and the normal-weight controls. Furthermore, the present data suggest that obesity leads to lower cortisol activity, which may indicate alterations in the Hypothalamic-pituitary-adrencortical (HPA) axis

Factor structure and psychometric properties of the trier inventory for chronic stress (TICS) in a representative german sample

<p>Abstract</p> <p>Background</p> <p>Chronic stress results from an imbalance of personal traits, resources and the demands placed upon an individual by social and occupational situations. This chronic stress can be measured using the Trier Inventory for Chronic Stress (TICS). Aims of the present study are to test the factorial structure of the TICS, report its psychometric properties, and evaluate the influence of gender and age on chronic stress.</p> <p>Methods</p> <p>The TICS was answered by <it>N </it>= 2,339 healthy participants aged 14 to 99. The sample was selected by random-route sampling. Exploratory factor analyses with Oblimin-rotated Principal Axis extraction were calculated. Confirmatory factor analyses applying Robust Maximum Likelihood estimations (MLM) tested model fit and configural invariance as well as the measurement invariance for gender and age. Reliability estimations and effect sizes are reported.</p> <p>Results</p> <p>In the exploratory factor analyses, both a two-factor and a nine-factor model emerged. Confirmatory factor analyses resulted in acceptable model fit (RMSEA), with model comparison fit statistics corroborating the superiority of the nine-factor model. Most factors were moderately to highly intercorrelated. Reliabilities were good to very good. Measurement invariance tests gave evidence for differential effects of gender and age on the factor structure. Furthermore, women and younger individuals, especially those aged 35 to 44, tended to report more chronic stress than men and older individuals.</p> <p>Conclusions</p> <p>The proposed nine-factor structure could be factorially validated, results in good scale reliability, and heuristically can be grouped by two higher-order factors: "High Demands" and "Lack of Satisfaction". Age and gender represent differentiable and meaningful contributors to the perception of chronic stress.</p

Type-D Personality in Unemployed Subjects: Prevalence, Self-Efficacy and Heart Rate Variability/Autonomic Response

Background: Unemployment may impair mental and physical health. The influencing factors causing such negative effects are relevant from an individual and public health perspective. The personality as one possible influencing factor was discussed. This study investigated the prevalence of the type-D personality in an unemployed population and its connections to socio-demographic, psychological and heart rate variability (HRV) parameters. Methods: A questionnaire set including socio-demographics, type-D scale (DS14), Complaint list (BL), Beck-Depression-Inventory II (BDI-II) and the General Self-Efficacy Scale (GSE) was handed out to 203 unemployed individuals [126 females, mean age ± SD: 42.36 ± 11.08]. For HRV assessment (RMSSD), a subsample of 83 participants [50 females, median age ± IQR: 47.00 ± 17.00] passed the “stress-tests” (timed breathing, d2-attention-stress-test, math test) while heart frequency (HF) was acquired via the Stressball software (BioSign GmbH, Ottenhofen, Germany). Results: 53% of the unemployed had a type-D personality. Compared to non-type-D individuals, type-D individuals had rarely children and by trend a lower educational level; they showed significantly higher scores in the BDI-II and lower scores in the GSE and BL. No differences were observed in mean HF or RMSSD during all the stress-tests. Conclusion: The HRV of individuals with a type-D personality is no worse than that of individuals without a type-D personality. Type-D personality was significantly associated with negative health effects regarding depressiveness, self-efficacy and physical complaints. Our main findings implicate that the DS14 could serve as a short and reliable screening instrument to select concerned unemployed individuals who might be at risk for negative health effects for adequate intervention

Stress hormone response to the DEX-CRH test and its relation to psychotherapy outcome in panic disorder patients with and without agoraphobia

This study tested whether the hormonal stress response to the DEX-CRH test may be predictive of the psychotherapy success for panic disorder (PD). Thirty-four patients diagnosed either with agoraphobia with PD or PD without agoraphobia were subjected to cognitive behavioural therapy (CBT). Patients (pre-therapy) and healthy volunteers were exposed to the DEX-CRH test. Blood samples were taken for cortisol and adrenocorticotropic hormone (ACTH) assessment. Established panic-specific questionnaires were handed out for the pre-therapy and post-therapy evaluation of disease severity (with reference to panic beliefs and agoraphobic cognitions, fear of bodily sensations, agoraphobic avoidance behaviour). Repeated measures ANCOVA were conducted for the analysis of the pre-therapy hormonal response, and Pearson's correlation analysis to test for associations with the psychotherapy outcome. Data analyses revealed large effect sizes for CBT in the clinical measures (η2 ≥ 0.321), main effects of time for cortisol and ACTH with no differences between both groups, and significant associations between cortisol release and agoraphobic cognitions for the patients. PD diagnosis had no impact on the hormonal response. However, those patients with higher cortisol release showed less improvement after CBT (significantly for agoraphobic cognitions). Clinical implications of these findings are the prediction of the therapy success from a potential endocrine correlate whose persistency (if assessed repeatedly) during the treatment may predict (non-)response to the current treatment, possibly representing a decision support for a change in treatment to avoid the continuation of an inefficient treatment

Factor structure and convergent validity of the short version of the Bielefeld partnership expectations questionnaire in patients with anxiety disorder and Healthy Controls

The short version of the Bielefeld Partnership Expectations Questionnaire (BPEQ-12) assesses the partner-related attachment dimensions fear of rejection, readiness for self-disclosure, and conscious need for care. The presented study investigated the factor structure in two samples and evaluated the convergent validity of scales. The sample included N = 175 patients with panic disorder and/or agoraphobia and N = 143 healthy controls. Besides, the BPEQ, the Experiences in Close Relationships Questionnaire (ECR), and the Brief Symptom Inventory (BSI) were assessed as well, and the Adult Attachment Prototype Rating (AAPR) was conducted. A confirmatory factor analysis of the three factor model (using a WLSMV estimator) revealed an acceptable model fit for the entire sample, patients and controls in terms of low RMSEA and SRMR ( 0.95). We found metric, scalar, and strict measurement invariance for the presence of anxiety disorder (ΔCFI ≤ –0.01 and ΔRMSEA ≥ 0.01). However, only for fear of rejection and readiness for self-disclosure the reliability was acceptable (Cronbach’s α > 0.7), and convergent validity in terms of large correlations ( r > 0.7) with the ECR scales was found in both samples. The scale conscious need for care had a questionable reliability (Cronbach’s α > 0.6) and correlated only slightly with ECR-R scales. We conclude that fear of rejection and readiness for self-disclosure of the BPEQ-12 are reliable and valid scales for measuring partner-related attachment in healthy and clinical samples

High/low cortisol reactivity and food intake in people with obesity and healthy weight

Increased food intake, termed “comfort eating”, is a pathologic coping mechanism in chronic stress. Cortisol reactivity under stress is a potent predictor of stress-induced eating behavior affecting the body mass index (BMI). However, cortisol reactivity and food intake under stress in people with obesity has not been evaluated. The aim of this study was to investigate the effect of high/low cortisol reactivity on food intake in people with obesity and healthy weight test controls, following standardized stress induction and a resting condition. Thirty-six men and women with obesity (BMI: 33.00 ± 3.23 kg/m²), as well as 36 age- and gender-matched healthy weight controls (BMI: 21.98 ± 1.81 kg/m²) were categorized into high cortisol reactors (HCR) and low cortisol reactors (LCR) in the Trier Social Stress Test (TSST). Following the TSST and a resting condition, the food intake of all participants was recorded in a standardized laboratory meal. Obese HCR demonstrated a significantly higher food intake than LCR (t (34) = −2.046, p ≤ 0.05). However, there were no significant differences between HCR and LCR in the healthy weight controls (p = 0.26). In addition, HCR of the people with obesity showed lower values in the emotion coping strategy of cognitive reappraisal than obese LCR (t (32) = 2.087, p ≤ 0.05). In conclusion, the magnitude of the cortisol reactivity to stress predicts stress-induced food intake in people with obesity, but not in the healthy weight controls. Limited use of cognitive reappraisal in emotion regulation in the obese HCR may be a marker of vulnerability to stress-induced eating