Optimizing prediction of binge eating episodes : a comparison approach to test alternative conceptualizations of the affect regulation model

Background : Although a wealth of studies have tested the link between negative mood states and likelihood of a subsequent binge eating episode, the assumption that this relationship follows a typical linear dose&ndash;response pattern (i.e., that risk of a binge episode increases in proportion to level of negative mood) has not been challenged. The present study demonstrates the applicability of an alternative, non-linear conceptualization of this relationship, in which the strength of association between negative mood and probability of a binge episode increases above a threshold value for the mood variable relative to the slope below this threshold value (threshold dose response model). Methods : A sample of 93 women aged 18 to 40 completed an online survey at random intervals seven times per day for a period of one week. Participants self-reported their current mood state and whether they had recently engaged in an eating episode symptomatic of a binge. Results : As hypothesized, the threshold approach was a better predictor than the linear dose&ndash;response modeling of likelihood of a binge episode. The superiority of the threshold approach was found even at low levels of negative mood (3 out of 10, with higher scores reflecting more&nbsp; negative mood). Additionally, severity of negative mood beyond this threshold value appears to be useful for predicting time to onset of a binge episode. Conclusions : Present findings suggest that simple dose&ndash;response formulations for the association between&nbsp; negative mood and onset of binge episodes miss vital aspects of this relationship. Most&nbsp; notably, the impact of mood on binge eating appears to depend on whether a threshold value&nbsp; of negative mood has been breached, and elevation in mood beyond this point may be useful&nbsp; for clinicians and researchers to identify time to onset. <br /

The pharmacological effect of BGC20-1531, a novel prostanoid EP4 receptor antagonist, in the Prostaglandin E2 human model of headache

Using a human Prostaglandin E2 (PGE2) model of headache, we examined whether a novel potent and selective EP4 receptor antagonist, BGC20-1531, may prevent headache and dilatation of the middle cerebral (MCA) and superficial temporal artery (STA). In a three-way cross-over trial, eight healthy volunteers were randomly allocated to receive 200 and 400 mg BGC20-1531 and placebo, followed by a 25-min infusion of PGE2. We recorded headache intensity on a verbal rating scale, MCA blood flow velocity and STA diameter. There was no difference in headache response or prevention of the dilation of the MCA or the STA (P > 0.05) with either dose of BGC20-1531 relative to placebo, although putative therapeutic exposures were not reached in all volunteers. In conclusion, these data suggest that the other EP receptors may be involved in PGE2 induced headache and dilatation in normal subjects

Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration

BACKGROUND: HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: OBJECTIVES: To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes. DESIGN: A proof of concept double-masked randomized controlled study. PARTICIPANTS: 114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA ≥ 20/60 in at least one eye, and a normal lipid profile. INTERVENTION: Simvastatin 40 mg/day or placebo, allocated 1:1. MAIN OUTCOME MEASURES: Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18-0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27-3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07-0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02-0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected. CONCLUSION/SIGNIFICANCE: Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065

A mathematical model of the metabolic and perfusion effects on cortical spreading depression

Cortical spreading depression (CSD) is a slow-moving ionic and metabolic disturbance that propagates in cortical brain tissue. In addition to massive cellular depolarization, CSD also involves significant changes in perfusion and metabolism -- aspects of CSD that had not been modeled and are important to traumatic brain injury, subarachnoid hemorrhage, stroke, and migraine. In this study, we develop a mathematical model for CSD where we focus on modeling the features essential to understanding the implications of neurovascular coupling during CSD. In our model, the sodium-potassium--ATPase, mainly responsible for ionic homeostasis and active during CSD, operates at a rate that is dependent on the supply of oxygen. The supply of oxygen is determined by modeling blood flow through a lumped vascular tree with an effective local vessel radius that is controlled by the extracellular potassium concentration. We show that during CSD, the metabolic demands of the cortex exceed the physiological limits placed on oxygen delivery, regardless of vascular constriction or dilation. However, vasoconstriction and vasodilation play important roles in the propagation of CSD and its recovery. Our model replicates the qualitative and quantitative behavior of CSD -- vasoconstriction, oxygen depletion, extracellular potassium elevation, prolonged depolarization -- found in experimental studies. We predict faster, longer duration CSD in vivo than in vitro due to the contribution of the vasculature. Our results also help explain some of the variability of CSD between species and even within the same animal. These results have clinical and translational implications, as they allow for more precise in vitro, in vivo, and in silico exploration of a phenomenon broadly relevant to neurological disease.Comment: 17 pages including 9 figures, accepted by PLoS On

Redirecting research efforts on the diversification-performance linkage: The search for synergy

We review the literature on the diversification-performance (D-P) relationship to a) propose that the time is ripe for a renewed attack on understanding the relationship between diversification and firm performance, and b) outline a new approach to attacking the question. Our paper makes four main contributions. First, through a review of the literature we establish the inherent complexities in the D-P relationship and the methodological challenges confronted by the literature in reaching its current conclusion of a non-linear relationship between diversification and performance. Second, we argue that to better guide managers the literature needs to develop along a complementary path – whereas past research has often focused on answering the big question of does diversification affect firm performance, this second path would focus more on identifying the precise micro-mechanisms through which diversification adds or subtracts value. Third, we outline a new approach to the investigation of this topic, based on (a) identifying the precise underlying mechanisms through which diversification affects performance; (b) identifying performance outcomes that are “proximate” to the mechanism that the researcher is studying, and (c) identifying an appropriate research design that can enable a causal claim. Finally, we outline a set of directions for future research

Validation of the western ontario rotator cuff index in patients with arthroscopic rotator cuff repair: A study protocol

<p>Abstract</p> <p>Background</p> <p>Arthroscopic rotator cuff repair is described as being a successful procedure. These results are often derived from clinical general shoulder examinations, which are then classified as 'excellent', 'good', 'fair' or 'poor'. However, the cut-off points for these classifications vary and sometimes modified scores are used.</p> <p>Arthroscopic rotator cuff repair is performed to improve quality of life. Therefore, disease specific health-related quality of life patient-administered questionnaires are needed. The WORC is a quality of life questionnaire designed for patients with disorders of the rotator cuff. The score is validated for rotator cuff disease, but not for rotator cuff repair specifically.</p> <p>The aim of this study is to investigate reliability, validity and responsiveness of WORC in patients undergoing arthroscopic rotator cuff repair.</p> <p>Methods/Design</p> <p>An approved translation of the WORC into Dutch is used. In this prospective study three groups of patients are used: 1. Arthroscopic rotator cuff repair; 2. Disorders of the rotator cuff without rupture; 3. Shoulder instability.</p> <p>The WORC, SF-36 and the Constant Score are obtained twice before therapy is started to measure reliability and validity. Responsiveness is tested by obtaining the same tests after therapy.</p

Effectiveness of dual-task functional power training for preventing falls in older people: Study protocol for a cluster randomised controlled trial

Background: Falls are a major public health concern with at least one third of people aged 65 years and over falling at least once per year, and half of these will fall repeatedly, which can lead to injury, pain, loss of function and independence, reduced quality of life and even death. Although the causes of falls are varied and complex, the age-related loss in muscle power has emerged as a useful predictor of disability and falls in older people. In this population, the requirements to produce explosive and rapid movements often occurs whilst simultaneously performing other attention-demanding cognitive or motor tasks, such as walking while talking or carrying an object. The primary aim of this study is to determine whether dual-task functional power training (DT-FPT) can reduce the rate of falls in community-dwelling older people. Methods/Design: The study design is an 18-month cluster randomised controlled trial in which 280 adults aged =65 years residing in retirement villages, who are at increased risk of falling, will be randomly allocated to: 1) an exercise programme involving DT-FPT, or 2) a usual care control group. The intervention is divided into 3 distinct phases: 6 months of supervised DT-FPT, a 6-month 'step down' maintenance programme, and a 6-month follow-up. The primary outcome will be the number of falls after 6, 12 and 18 months. Secondary outcomes will include: lower extremity muscle power and strength, grip strength, functional assessments of gait, reaction time and dynamic balance under single- and dual-task conditions, activities of daily living, quality of life, cognitive function and falls-related self-efficacy. We will also evaluate the cost-effectiveness of the programme for preventing falls. Discussion: The study offers a novel approach that may guide the development and implementation of future community-based falls prevention programmes that specifically focus on optimising muscle power and dual-task performance to reduce falls risk under 'real life' conditions in older adults. In addition, the 'step down' programme will provide new information about the efficacy of a less intensive maintenance programme for reducing the risk of falls over an extended period. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12613001161718. Date registered 23 October 2013