Individual-based Modeling of Genome Evolution in Haplodiploid Organisms

Ants, bees, wasps, bark beetles, and other species have haploid males and diploid females. Although such haplodiploid species play key ecological roles and are threatened by environmental changes, no general framework exists for simulating their genetic evolution. Here, we use the SLiM simulation environment to build a novel model for individual-based forward simulation of genetic evolution in haplodiploids. We compare the fates of adaptive and deleterious mutations and find that selection on recessive mutations is more effective in haplodiploids than in diploids. Our open-source model will foster an understanding of the evolution of sociality and how ecologically important haplodiploid species may respond to changing environments

Acute and Chronic Effects of Exercise on Appetite, Energy Intake, and Appetite-Related Hormones: The Modulating Effect of Adiposity, Sex, and Habitual Physical Activity.

Exercise facilitates weight control, partly through effects on appetite regulation. Single bouts of exercise induce a short-term energy deficit without stimulating compensatory effects on appetite, whilst limited evidence suggests that exercise training may modify subjective and homeostatic mediators of appetite in directions associated with enhanced meal-induced satiety. However, a large variability in responses exists between individuals. This article reviews the evidence relating to how adiposity, sex, and habitual physical activity modulate exercise-induced appetite, energy intake, and appetite-related hormone responses. The balance of evidence suggests that adiposity and sex do not modify appetite or energy intake responses to acute or chronic exercise interventions, but individuals with higher habitual physical activity levels may better adjust energy intake in response to energy balance perturbations. The effect of these individual characteristics and behaviours on appetite-related hormone responses to exercise remains equivocal. These findings support the continued promotion of exercise as a strategy for inducing short-term energy deficits irrespective of adiposity and sex, as well as the ability of exercise to positively influence energy balance over the longer term. Future well-controlled studies are required to further ascertain the potential mediators of appetite responses to exercise

The virtual haptic back: A simulation for training in palpatory diagnosis

<p>Abstract</p> <p>Background</p> <p>Models and simulations are finding increased roles in medical education. The Virtual Haptic Back (VHB) is a virtual reality simulation of the mechanical properties of the human back designed as an aid to teaching clinical palpatory diagnosis.</p> <p>Methods</p> <p>Eighty-nine first year medical students of the Ohio University College of Osteopathic Medicine carried out six, 15-minute practice sessions with the VHB, plus tests before and after the sessions in order to monitor progress in identifying regions of simulated abnormal tissue compliance. Students palpated with two digits, fingers or thumbs, by placing them in gimbaled thimbles at the ends of PHANToM 3.0^®haptic interface arms. The interface simulated the contours and compliance of the back surface by the action of electric motors. The motors limited the compression of the virtual tissues induced by the palpating fingers, by generating counterforces. Users could see the position of their fingers with respect to the back on a video monitor just behind the plane of the haptic back. The abnormal region varied randomly among 12 locations between trials. During the practice sessions student users received immediate feedback following each trial, indicating either a correct choice or the actual location of the abnormality if an incorrect choice had been made. This allowed the user to feel the actual abnormality before going on to the next trial. Changes in accuracy, speed and Weber fraction across practice sessions were analyzed using a repeated measures analysis of variance.</p> <p>Results</p> <p>Students improved in accuracy and speed of diagnosis with practice. The smallest difference in simulated tissue compliance users were able to detect improved from 28% (SD = 9.5%) to 14% (SD = 4.4%) during the practice sessions while average detection time decreased from 39 (SD = 19.8) to 17 (SD = 11.7) seconds. When asked in anonymous evaluation questionnaires if they judged the VHB practice to be helpful to them in the clinical palpation and manual medicine laboratory, 41% said yes, 51% said maybe, and 8% said no.</p> <p>Conclusion</p> <p>The VHB has potential value as a teaching aid for students in the initial phases of learning palpatory diagnosis.</p

Do acute elevations of serum creatinine in primary care engender an increased mortality risk?

Background: The significant impact Acute Kidney Injury (AKI) has on patient morbidity and mortality emphasizes the need for early recognition and effective treatment. AKI presenting to or occurring during hospitalisation has been widely studied but little is known about the incidence and outcomes of patients experiencing acute elevations in serum creatinine in the primary care setting where people are not subsequently admitted to hospital. The aim of this study was to define this incidence and explore its impact on mortality. Methods: The study cohort was identified by using hospital data bases over a six month period. Inclusion criteria: People with a serum creatinine request during the study period, 18 or over and not on renal replacement therapy. The patients were stratified by a rise in serum creatinine corresponding to the Acute Kidney Injury Network (AKIN) criteria for comparison purposes. Descriptive and survival data were then analysed. Ethical approval was granted from National Research Ethics Service (NRES) Committee South East Coast and from the National Information Governance Board. Results: The total study population was 61,432. 57,300 subjects with ‘no AKI’, mean age 64.The number (mean age) of acute serum creatinine rises overall were, ‘AKI 1’ 3,798 (72), ‘AKI 2’ 232 (73), and ‘AKI 3’ 102 (68) which equates to an overall incidence of 14,192 pmp/year (adult). Unadjusted 30 day survival was 99.9% in subjects with ‘no AKI’, compared to 98.6%, 90.1% and 82.3% in those with ‘AKI 1’, ‘AKI 2’ and ‘AKI 3’ respectively. After multivariable analysis adjusting for age, gender, baseline kidney function and co-morbidity the odds ratio of 30 day mortality was 5.3 (95% CI 3.6, 7.7), 36.8 (95% CI 21.6, 62.7) and 123 (95% CI 64.8, 235) respectively, compared to those without acute serum creatinine rises as defined. Conclusions: People who develop acute elevations of serum creatinine in primary care without being admitted to hospital have significantly worse outcomes than those with stable kidney function

Meta-analysis of non-tumour doses for radiation-induced cancer on the basis of dose-rate

Purpose: Quantitative analysis of cancer risk of ionising radiation as a function of dose-rate

The hemodynamic tolerability and feasibility of sustained low efficiency dialysis in the management of critically ill patients with acute kidney injury

<p>Abstract</p> <p>Background</p> <p>Minimization of hemodynamic instability during renal replacement therapy (RRT) in patients with acute kidney injury (AKI) is often challenging. We examined the relative hemodynamic tolerability of sustained low efficiency dialysis (SLED) and continuous renal replacement therapy (CRRT) in critically ill patients with AKI. We also compared the feasibility of SLED administration with that of CRRT and intermittent hemodialysis (IHD).</p> <p>Methods</p> <p>This cohort study encompassed four critical care units within a single university-affiliated medical centre. 77 consecutive critically ill patients with AKI who were treated with CRRT (n = 30), SLED (n = 13) or IHD (n = 34) and completed at least two RRT sessions were included in the study. Overall, 223 RRT sessions were analyzed. Hemodynamic instability during a given session was defined as the composite of a > 20% reduction in mean arterial pressure or any escalation in pressor requirements. Treatment feasibility was evaluated based on the fraction of the prescribed therapy time that was delivered. An interrupted session was designated if < 90% of the prescribed time was administered. Generalized estimating equations were used to compare the hemodynamic tolerability of SLED vs CRRT while accounting for within-patient clustering of repeated sessions and key confounders.</p> <p>Results</p> <p>Hemodynamic instability occurred during 22 (56.4%) SLED and 43 (50.0%) CRRT sessions (p = 0.51). In a multivariable analysis that accounted for clustering of multiple sessions within the same patient, the odds ratio for hemodynamic instability with SLED was 1.20 (95% CI 0.58-2.47), as compared to CRRT. Session interruption occurred in 16 (16.3), 30 (34.9) and 11 (28.2) of IHD, CRRT and SLED therapies, respectively.</p> <p>Conclusions</p> <p>In critically ill patients with AKI, the administration of SLED is feasible and provides comparable hemodynamic control to CRRT.</p

Assessment of strategies for switching patients from olanzapine to risperidone: A randomized, open-label, rater-blinded study

<p>Abstract</p> <p>Background</p> <p>In clinical practice, physicians often need to change the antipsychotic medications they give to patients because of an inadequate response or the presence of unacceptable or unsafe side effects. However, there is a lack of consensus in the field as to the optimal switching strategy for antipsychotics, especially with regards to the speed at which the dose of the previous antipsychotic should be reduced. This paper assesses the short-term results of strategies for the discontinuation of olanzapine when initiating risperidone.</p> <p>Methods</p> <p>In a 6-week, randomized, open-label, rater-blinded study, patients with schizophrenia or schizoaffective disorder, on a stable drug dose for more than 30 days at entry, who were intolerant of or exhibiting a suboptimal symptom response to more than 30 days of olanzapine treatment, were randomly assigned to the following switch strategies (common risperidone initiation scheme; varying olanzapine discontinuation): (i) abrupt strategy, where olanzapine was discontinued at risperidone initiation; (ii) gradual 1 strategy, where olanzapine was given at 50% entry dose for 1 week after risperidone initiation and then discontinued; or (iii) gradual 2 strategy, where olanzapine was given at 100% entry dose for 1 week, then at 50% in the second week, and then discontinued.</p> <p>Results</p> <p>The study enrolled 123 patients on stable doses of olanzapine. Their mean age was 40.3 years and mean (± standard deviation (SD)) baseline Positive and Negative Syndrome Scale (PANSS) total score of 75.6 ± 11.5. All-cause treatment discontinuation was lowest (12%) in the group with the slowest olanzapine dose reduction (gradual 2) and occurred at half the discontinuation rate in the other two groups (25% in abrupt and 28% in gradual 1). The relative risk of early discontinuation was 0.77 (confidence interval 0.61–0.99) for the slowest dose reduction compared with the other two strategies. After the medication was changed, improvements at endpoint were seen in PANSS total score (-7.3; <it>p </it>< 0.0001) and in PANSS positive (-3.0; <it>p </it>< 0.0001), negative (-0.9; <it>p </it>= 0.171) and anxiety/depression (-1.4; <it>p </it>= 0.0005) subscale scores. Severity of movement disorders and weight changes were minimal.</p> <p>Conclusion</p> <p>When switching patients from olanzapine to risperidone, a gradual reduction in the dose of olanzapine over 2 weeks was associated with higher rates of retention compared with abrupt or less gradual discontinuation. Switching via any strategy was associated with significant improvements in positive and anxiety symptoms and was generally well tolerated.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00378183</p

Boundaries of Semantic Distraction: Dominance and Lexicality Act at Retrieval

Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category-exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1) and occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech is discussed

Absence of Inhibin Alpha and Retinoblastoma Protein Leads to Early Sertoli Cell Dysfunction

Sertoli cells, the support cells of mammalian spermatogenesis, are regulated by a number of nuclear factors and express retinoblastoma (RB) tumor suppressor protein. We hypothesized that RB is an important mediator of Sertoli cell tumorigenesis in inhibin α knockout (Inha KO) mice. In our previous mouse studies, we found that conditional knockout (cKO) of Rb in Sertoli cells caused progressive Sertoli cell dysfunction. Initially, loss of RB had no gross effect on Sertoli cell function as the mice were fertile with normal testis weights at 6 weeks of age, but by 10–14 weeks of age, mutant mice demonstrated severe Sertoli cell dysfunction and infertility. Although double knockout (dKO) of Rb and Inha did not result in exacerbation of the tumorigenic phenotype of Inha-null mice, we found that the dKO mice demonstrate an acceleration of Sertoli cell dysfunction compared to Rb cKO mice. Specifically, in contrast to Rb cKO mice, Inha/Rb dKO mice showed signs of Sertoli cell dysfunction as early as 4 weeks of age. These results demonstrate that RB is not essential for Sertoli cell tumorigenesis in Inha KO mice but that loss of Inha accelerates the infertility phenotype of Rb cKO mice