Adults with autism spectrum condition have atypical perception of ambiguous figures when bottom-up and top-down interactions are incongruous.

We examined the perception of an ambiguous squares stimulus evoking bistable perception in a sample of 31 individuals with autistic spectrum condition and 22 matched typical adults. The perception of the ambiguous figure was manipulated by adaptation to unambiguous figures and/or by placing the ambiguous figure into a context of unambiguous figures. This resulted in four conditions testing the independent and combined (congruent and incongruent) manipulations of adaptation (bottom-up) and spatial context (top-down) effects. The strength of perception, as measured by perception of the first reported orientation of the ambiguous stimulus, was affected comparably between groups. Nevertheless, the strength of perception, as measured by perceptual durations, was affected differently between groups: the perceptual effect was strongest for the autistic spectrum condition group when combined bottom-up and top-down conditions were congruent. In contrast, the strength of the perceptual effect in response to the same condition in the typical adults group was comparable to the adaptation, but stronger than both the context and the incongruent combined bottom-up and top-down conditions. Furthermore, the context condition was stronger than the incongruent combined bottom-up and top-down conditions for the typical adults group. Thus, our findings support the view of stimulus-specific top-down modulation in autistic spectrum condition

Duration and predictors of emergency surgical operations - basis for medical management of mass casualty incidents

<p>Abstract</p> <p>Background</p> <p>Hospitals have a critically important role in the management of mass causality incidents (MCI), yet there is little information to assist emergency planners. A significantly limiting factor of a hospital's capability to treat those affected is its surgical capacity. We therefore intended to provide data about the duration and predictors of life saving operations.</p> <p>Methods</p> <p>The data of 20,815 predominantly blunt trauma patients recorded in the Trauma Registry of the German-Trauma-Society was retrospectively analyzed to calculate the duration of life-saving operations as well as their predictors. Inclusion criteria were an ISS ≥ 16 and the performance of relevant ICPM-coded procedures within 6 h of admission.</p> <p>Results</p> <p>From 1,228 patients fulfilling the inclusion criteria 1,793 operations could be identified as life-saving operations. Acute injuries to the abdomen accounted for 54.1% followed by head injuries (26.3%), pelvic injuries (11.5%), thoracic injuries (5.0%) and major amputations (3.1%). The mean cut to suture time was 130 min (IQR 65-165 min). Logistic regression revealed 8 variables associated with an emergency operation: AIS of abdomen ≥ 3 (OR 4,00), ISS ≥ 35 (OR 2,94), hemoglobin level ≤ 8 mg/dL (OR 1,40), pulse rate on hospital admission < 40 or > 120/min (OR 1,39), blood pressure on hospital admission < 90 mmHg (OR 1,35), prehospital infusion volume ≥ 2000 ml (OR 1,34), GCS ≤ 8 (OR 1,32) and anisocoria (OR 1,28) on-scene.</p> <p>Conclusions</p> <p>The mean operation time of 130 min calculated for emergency life-saving surgical operations provides a realistic guideline for the prospective treatment capacity which can be estimated and projected into an actual incident admission capacity. Knowledge of predictive factors for life-saving emergency operations helps to identify those patients that need most urgent operative treatment in case of blunt MCI.</p

Evolution of Robustness to Noise and Mutation in Gene Expression Dynamics

Phenotype of biological systems needs to be robust against mutation in order to sustain themselves between generations. On the other hand, phenotype of an individual also needs to be robust against fluctuations of both internal and external origins that are encountered during growth and development. Is there a relationship between these two types of robustness, one during a single generation and the other during evolution? Could stochasticity in gene expression have any relevance to the evolution of these robustness? Robustness can be defined by the sharpness of the distribution of phenotype; the variance of phenotype distribution due to genetic variation gives a measure of `genetic robustness' while that of isogenic individuals gives a measure of `developmental robustness'. Through simulations of a simple stochastic gene expression network that undergoes mutation and selection, we show that in order for the network to acquire both types of robustness, the phenotypic variance induced by mutations must be smaller than that observed in an isogenic population. As the latter originates from noise in gene expression, this signifies that the genetic robustness evolves only when the noise strength in gene expression is larger than some threshold. In such a case, the two variances decrease throughout the evolutionary time course, indicating increase in robustness. The results reveal how noise that cells encounter during growth and development shapes networks' robustness to stochasticity in gene expression, which in turn shapes networks' robustness to mutation. The condition for evolution of robustness as well as relationship between genetic and developmental robustness is derived through the variance of phenotypic fluctuations, which are measurable experimentally.Comment: 25 page

Scaling properties of protein family phylogenies

One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of balance) of a large set of protein phylogenies with a set of species phylogenies. The comparative analysis shows that both sets of phylogenies share remarkably similar scaling behavior, suggesting the universality of branching rules and of the evolutionary processes that drive biological diversification from gene to species level. In order to explain such generality, we propose a simple model which allows us to estimate the proportion of evolvability/robustness needed to approximate the scaling behavior observed in the phylogenies, highlighting the relevance of the robustness of a biological system (species or protein) in the scaling properties of the phylogenetic trees. Thus, the rules that govern the incapability of a biological system to diversify are equally relevant both at the gene and at the species level.Comment: Replaced with final published versio

DNA damage signalling prevents deleterious telomere addition at DNA breaks

The response to DNA damage involves regulation of multiple essential processes to maximize the accuracy of DNA damage repair and cell survival 1. Telomerase has the potential to interfere with repair by inappropriately adding telomeres to DNA breaks. It was unknown whether cells modulate telomerase in response to DNA damage, to increase the accuracy of repair. Here we report that telomerase action is regulated as a part of the cellular response to a DNA double-strand break (DSB). Using yeast, we show that the major ATR/Mec1 DNA damage signalling pathway regulates telomerase action at DSBs. Upon DNA damage, MEC1-RAD53-DUN1-dependent phosphorylation of the telomerase inhibitor Pif1 occurs. Utilizing a separation of function PIF1 mutation, we show that this phosphorylation is required for the Pif1-mediated telomerase inhibition that takes place specifically at DNA breaks, but not telomeres. Hence DNA damage signalling down-modulates telomerase action at a DNA break via Pif1 phosphorylation, thus preventing aberrant healing of broken DNA ends by telomerase. These findings uncover a novel regulatory mechanism that coordinates competing DNA end-processing activities and thereby promotes DNA repair accuracy and genome integrity

The working alliance in a randomized controlled trial comparing online with face-to-face cognitive-behavioral therapy for depression

Background: Although numerous efficacy studies in recent years have found internet-based interventions for depression to be effective, there has been scant consideration of therapeutic process factors in the online setting. In face-to face therapy, the quality of the working alliance explains variance in treatment outcome. However, little is yet known about the impact of the working alliance in internet-based interventions, particularly as compared with face-to-face therapy. Methods: This study explored the working alliance between client and therapist in the middle and at the end of a cognitive-behavioral intervention for depression. The participants were randomized to an internet-based treatment group (n = 25) or face-to-face group (n = 28). Both groups received the same cognitive behavioral therapy over an 8-week timeframe. Participants completed the Beck Depression Inventory (BDI) post-treatment and the Working Alliance Inventory at mid- and post- treatment. Therapists completed the therapist version of the Working Alliance Inventory at post-treatment. Results: With the exception of therapists' ratings of the tasks subscale, which were significantly higher in the online group, the two groups' ratings of the working alliance did not differ significantly. Further, significant correlations were found between clients' ratings of the working alliance and therapy outcome at post-treatment in the online group and at both mid- and post-treatment in the face-to-face group. Correlation analysis revealed that the working alliance ratings did not significantly predict the BDI residual gain score in either group. Conclusions: Contrary to what might have been expected, the working alliance in the online group was comparable to that in the face-to-face group. However, the results showed no significant relations between the BDI residual gain score and the working alliance ratings in either group

Internet-based treatment for PTSD reduces distress and facilitates the development of a strong therapeutic alliance: a randomized controlled clinical trial

BACKGROUND: The present study was designed to evaluate the efficacy of an internet-based therapy (Interapy) for Posttraumatic Stress Disorder (PTSD) in a German speaking population. Also, the quality of the online therapeutic relationship, its development and its relevance as potential moderator of the treatment effects was investigated. METHOD: Ninety-six patients with posttraumatic stress reactions were allocated at random to ten sessions of Internet-based cognitive behavioural therapy (CBT) conducted over a 5-week period or a waiting list control group. Severity of PTSD was the primary outcome. Secondary outcome variables were depression, anxiety, dissociation and physical health. Follow-up assessments were conducted at the end of treatment and 3 months after treatment. RESULTS: From baseline to post-treatment assessment, PTSD severity and other psychopathological symptoms were significantly improved for the treatment group (intent-to-treat group x time interaction effect size d = 1.40). Additionally, patients of the treatment condition showed significantly greater reduction of co-morbid depression and anxiety as compared to the waiting list condition. These effects were sustained during the 3-months follow-up period. High ratings of the therapeutic alliance and low drop-out rates indicated that a positive and stable therapeutic relationship could be established online. Significant improvement of the online working alliance in the course of treatment and a substantial correlation between the quality of the online relationship at the end of treatment and treatment outcome emerged. CONCLUSION: Interapy proved to be a viable treatment alternative for PTSD with large effect sizes and sustained treatment effects. A stable and positive online therapeutic relationship can be established through the Internet which improved during the treatment process. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN012606000401550