Human Retinal Gene Therapy for Leber Congential Amaurosis Shows Advancing Retinal Degeneration Despite Enduring Visual Improvement

Leber congenital amaurosis (LCA) associated with retinal pigment epithelium-specific protein 65 kDa (RPE65) mutations is a severe hereditary blindness resulting from both dysfunction and degeneration of photoreceptors. Clinical trials with gene augmentation therapy have shown partial reversal of the dysfunction, but the effects on the degeneration are not known. We evaluated the consequences of gene therapy on retinal degeneration in patients with RPE65-LCA and its canine model. In untreated RPE65-LCA patients, there was dysfunction and degeneration of photoreceptors, even at the earliest ages. Examined serially over years, the outer photoreceptor nuclear layer showed progressive thinning. Treated RPE65-LCA showed substantial visual improvement in the short term and no detectable decline from this new level over the long term. However, retinal degeneration continued to progress unabated. In RPE65-mutant dogs, the first one-quarter of their lifespan showed only dysfunction, and there was normal outer photoreceptor nuclear layer thickness retina-wide. Dogs treated during the earlier dysfunction-only stage showed improved visual function and dramatic protection of treated photoreceptors from degeneration when measured 5–11 y later. Dogs treated later during the combined dysfunction and degeneration stage also showed visual function improvement, but photoreceptor loss continued unabated, the same as in human RPE65-LCA. The results suggest that, in RPE65 disease treatment, protection from visual function deterioration cannot be assumed to imply protection from degeneration. The effects of gene augmentation therapy are complex and suggest a need for a combinatorial strategy in RPE65-LCA to not only improve function in the short term but also slow retinal degeneration in the long term

Genetic susceptibility to burnout in a Swedish twin cohort

Most previous studies of burnout have focused on work environmental stressors, while familial factors so far mainly have been overlooked. The aim of the study was to estimate the relative importance of genetic influences on burnout (measured with Pines Burnout Measure) in a sample of monozygotic (MZ) and dizygotic (DZ) Swedish twins. The study sample consisted of 20,286 individuals, born 1959–1986 from the Swedish twin registry who participated in the cross-sectional study of twin adults: genes and environment. Probandwise concordance rates (the risk for one twin to be affected given that his/her twin partner is affected by burnout) and within pair correlations were calculated for MZ and DZ same—and opposite sexed twin pairs. Heritability coefficients i.e. the proportion of the total variance attributable to genetic factors were calculated using standard biometrical model fitting procedures. The results showed that genetic factors explained 33% of the individual differences in burnout symptoms in women and men. Environmental factors explained a substantial part of the variation as well and are thus important to address in rehabilitation and prevention efforts to combat burnout

Teaching Mindfulness to Teachers: a Systematic Review and Narrative Synthesis

School teachers report high levels of stress which impact on their engagement with pupils and effectiveness as a teacher. Early intervention or prevention approaches may support teachers to develop positive coping and reduce the experience and impact of stress. This article reviews research on one such approach: mindfulness-based interventions (MBIs) for school teachers. A systematic review and narrative synthesis were conducted for quantitative and qualitative studies that report the effects of MBIs for teachers of children aged 5– 18 years on symptoms of stress and emotion regulation and self-efficacy. Twelve independent publications were identified meeting the inclusion criteria and these gave a total of 13 samples. Quality appraisal of the identified articles was carried out. The effect sizes and proportion of significant findings are reported for relevant outcomes. The quality of the literature varied, with main strengths in reporting study details, and weaknesses including sample size considerations. A range of MBIs were employed across the literature, ranging in contact hours and aims. MBIs showed strongest promise for intermediary effects on teacher emotion regulation. The results of the review are discussed in the context of a model of teacher stress. Teacher social and emotional competence has implications for pupil wellbeing through teacher–pupil relationships and effective management of the classroom. The implications for practice and research are considered

Stress Processes: An Essential Ingredient in the Entrepreneurial Process

The entrepreneurial process is associated with high uncertainty. Uncertainty is also a major source of stress. Therefore, a core aim of entrepreneurs is to reduce uncertainty to an extent that allows the entrepreneurial process to unfold. However, entrepreneurship scholars have insufficiently addressed stress processes that may be associated with this uncertainty. We argue that uncertainty is the concept connecting both the entrepreneurial and stress processes. We discuss the link between the two processes regarding: (1) opportunity recognition, (2) opportunity exploitation, and (3) associated outcomes. We then illustrate how future research should incorporate the interaction between the two processes using a morphological box and discuss how such research would change the way we specify entrepreneurial process models and study entrepreneurial behavior

Untersuchungen zu Eigenspannungen in hochtemperaturgelöteten Cr-CrNi-Stahl-Mischverbindungen und Entwicklung löttechnischer Fertigungsstrategien zu deren Minimierung

Bei der Fertigung von komplexen Stahlblechbauteilen kommen vielfach löttechnische Fertigungsprozesse zum Einsatz, bei denen hochlegierte Stahlkomponenten in Vakuum- oder Schutzgasöfen bei Temperaturen über 1000 °C gefügt werden. Zunehmend ist da-bei das Verbinden von ferritischen mit austenitischen Stahlkomponenten gefragt. Auf-grund unterschiedlicher thermomechanischer Eigenschaften der Werkstoffe können da-bei hohe Eigenspannungen auftreten, die im Vergleich zu Lötbaugruppen aus artglei-chen Stahlsorten zu Bauteilverzug und Reduktion der Verbindungsfestigkeit führen. Zur Untersuchung dieser Problematik wurden Bauteilmodelle aus gelöteten Stahlblechkom-ponenten verwendet, an denen mittels Röntgendiffraktometrie und inkrementellen DMS-Bohrlochmessungen die Eigenspannungszustände im Bereich der Fügezonen in Abhängigkeit von Werkstoffkombinationen, Fügegeometrie und Prozessparametern beim Ofenlöten analysiert wurden. Durch die experimentellen Daten wurden FEM-Si-mulationen, in die eigene Messungen zum temperaturabhängigen Spannungs-Deh-nungs-Verhalten der Stahlbleche implementiert wurden, verifiziert. Die FEM-Simula-tion zur Analyse der Eigenspannungsverteilung in Lötbauteilen ließ sich auf andere Fü-gegeometrien übertragen. Folglich sind entsprechende FEM-Simulationen geeignet, löt-prozessbedingte Eigenspannungen und Deformationen von Blechbaugruppen in Stahl-mischbauweise zu erfassen und somit etwaige konstruktive Optimierungsmaßnahmen vorab zu bewerten