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Background: Observed associations of high-protein diets with changes in insulin resistance are inconclusive.Objectives: We aimed to assess associations of changes in both reported and estimated protein (PRep; PEst) and energy intake (EIRep; EIEst) with changes in HOMA-IR, glycated hemoglobin (HbA1c), and BMI (in kg/m2), in 1822 decreasing to 833 adults (week 156) with overweight and prediabetes, during the 3-y PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study on weight-loss maintenance. Eating behavior and measurement errors (MEs) of dietary intake were assessed. Thus, observational post hoc analyses were applied.Methods: Associations of changes in EIEst, EIRep, PEst, and PRep with changes in HOMA-IR, HbA1c, and BMI were determined by linear mixed-model analysis in 2 arms [high-protein-low-glycemic-index (GI) diet and moderate-protein-moderate-GI diet] of the PREVIEW study. EIEst was derived from energy requirement: total energy expenditure = basal metabolic rate × physical activity level; PEst from urinary nitrogen, and urea. MEs were calculated as [(EIEst - EIRep)/EIEst] × 100% and [(PRep - PEst)/PEst] × 100%. Eating behavior was determined using the Three Factor Eating Questionnaire, examining cognitive dietary restraint, disinhibition, and hunger.Results: Increases in PEst and PRep and decreases in EIEst and EIRep were associated with decreases in BMI, but not independently with decreases in HOMA-IR. Increases in PEst and PRep were associated with decreases in HbA1c. PRep and EIRep showed larger changes and stronger associations than PEst and EIEst. Mean ± SD MEs of EIRep and PRep were 38% ± 9% and 14% ± 4%, respectively; ME changes in EIRep and En% PRep were positively associated with changes in BMI and cognitive dietary restraint and inversely with disinhibition and hunger.Conclusions: During weight-loss maintenance in adults with prediabetes, increase in protein intake and decrease in energy intake were not associated with decrease in HOMA-IR beyond associations with decrease in BMI. Increases in PEst and PRep were associated with decrease in HbA1c.This trial was registered at clinicaltrials.gov as NCT01777893.

Background The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches. Objective We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT). Design/setting/participants Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible. Interventions All patients underwent [18F]DCFPyL PET-MR/CT. Patients with molecularly-defined oligorecurrent-PCa had MDT (stereotactic ablative body radiotherapy [SABR] or surgery) without HT. Outcome measurements/statistical analysis Primary endpoint was biochemical response (complete, i.e. biochemical ‘no evidence of disease’ [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon’s two-stage design was employed (null and alternate hypotheses 20% response rate, respectively), with α and β of 0.1. Results Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed. Conclusions PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/− systemic agents can expand the curative therapeutic armamentarium for PCa. Patient summary We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.

Funding Information: The PREVIEW project was funded by the following institutions: EU framework programme 7 (Grant number 312057); The Glycemic Index Foundation Australia through royalties to The University of Sydney; The NZ Health Research Council (14/191) and University of Auckland Faculty Research Development Fund; The Danish Agriculture & Food Council; The Danish Meat and Research Institute; National Institute for Health Research Biomedical Research Centre (NIHR BRC) (UK); Engineering and Physical Sciences Research Council (EPSRC) (UK); Juho Vainio Foundation (FIN); Academy of Finland (grant numbers: 272376, 314383, 266286); Finnish Medical Foundation; Gyllenberg Foundation; Novo Nordisk Foundation; Finnish Diabetes Research Foundation; University of Helsinki; Government Research Funds for Helsinki University Hospital (FIN). The Cambridge Weight Plan© donated all products for the 8-weeks low-energy diet period. Nutritics (Dublin) donated all dietary analyses software used by UNOTT. EJ has received personal grants for the preparation of this manuscript from Jenny and Antti Wihuri Foundation (FIN) and Emil Aaltonen Foundation (FIN). Preparation of this manuscript has also been funded by the Academy of Finland (grants 314135 and 309157 to HK). Open access publication was funded by Helsinki University Library. The funding sources had no role in study design, data collection and analysis, interpretation of the data, preparation of the manuscript or decision to publish the results. Publisher Copyright: © 2022, The Author(s). Background: To better support participants to achieve long-lasting results within interventions aiming for weight loss and maintenance, more information is needed about the maintenance of behavioral changes. Therefore, we examined whether perceived stress predicts the maintenance of changes in eating behavior (flexible and rigid restraint of eating, disinhibition, and hunger). Methods: The present study was a secondary analysis of the PREVIEW intervention including participants with overweight (BMI ≥ 25 kg/m2) at baseline and high risk of type 2 diabetes (n = 1311). Intervention included a 2-month low-energy diet phase and a 34-month subsequent weight maintenance phase. The first 6 months were considered an active behavior change stage and the remaining 2.5 years were considered a behavior maintenance stage. Eating behavior was measured using the Three Factor Eating Questionnaire and stress using the Perceived Stress Scale. The associations between stress and eating behavior were analyzed using linear mixed effects models for repeated measurements. Results: Perceived stress measured after the active behavior change stage (at 6 months) did not predict changes in eating behavior during the behavior maintenance stage. However, frequent high stress during this period was associated with greater lapse of improved flexible restraint (p = 0.026). The mean (SD) change in flexible restraint from 6 to 36 months was −1.1 (2.1) in participants with frequent stress and −0.7 (1.8) in participants without frequent stress (Cohen’s ds (95% CI) = 0.24 (0.04–0.43)). Higher perceived stress at 6 months was associated with less flexible restraint and more disinhibition and hunger throughout the behavior maintenance stage (all p < 0.001). Conclusions: Perceived stress was associated with features of eating behavior that may impair successful weight loss maintenance. Future interventions should investigate, whether incorporating stress reduction techniques results in more effective treatment, particularly for participants experiencing a high stress level. publishersversion published

Aims/hypothesis Lifestyle interventions are the first-line treatment option for body weight and cardiometabolic health management. However, whether age groups or women and men respond differently to lifestyle interventions is under debate. We aimed to examine age- and sex-specific effects of a low-energy diet (LED) followed by a long-term lifestyle intervention on body weight, body composition and cardiometabolic health markers in adults with prediabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). Methods This observational study used longitudinal data from 2223 overweight participants with prediabetes in the multicentre diabetes prevention study PREVIEW. The participants underwent a LED-induced rapid weight loss (WL) period followed by a 3 year lifestyle-based weight maintenance (WM) intervention. Changes in outcomes of interest in prespecified age (younger: 25–45 years; middle-aged: 46–54 years; older: 55–70 years) or sex (women and men) groups were compared. Results In total, 783 younger, 319 middle-aged and 1121 older adults and 1503 women and 720 men were included in the analysis. In the available case and complete case analyses, multivariable-adjusted linear mixed models showed that younger and older adults had similar weight loss after the LED, whereas older adults had greater sustained weight loss after the WM intervention (adjusted difference for older vs younger adults −1.25% [95% CI −1.92, −0.58], ppp1c and systolic blood pressure after the WM intervention than middle-aged adults. In the complete case analysis, the above-mentioned differences between middle-aged and older adults disappeared, but the direction of the effect size did not change. After the WL period, compared with men, women had less weight loss (adjusted difference for women vs men 1.78% [95% CI 1.12, 2.43], p1c, LDL-cholesterol and diastolic blood pressure. After the WM intervention, women had greater fat-free mass and bone mass loss and smaller improvements in HbA1c and LDL-cholesterol, while they had greater improvements in fasting glucose, triacylglycerol (adjusted difference for women vs men −0.08 mmol/l [−0.11, −0.04], p Conclusions/interpretation Older adults benefited less from a lifestyle intervention in relation to body composition and cardiometabolic health markers than younger adults, despite greater sustained weight loss. Women benefited less from a LED followed by a lifestyle intervention in relation to body weight and body composition than men. Future interventions targeting older adults or women should take prevention of fat-free mass and bone mass loss into consideration. Clinical trial registration number ClinicalTrials.gov NCT01777893. Graphical abstract

IntroductionThe aim of this randomised controlled trial (RCT) is to investigate whether prolonged consumption of sweeteners and sweetness enhancers (S&SEs) within a healthy diet will improve weight loss maintenance and obesity-related risk factors and affect safety markers compared with sugar.Methods and analysisSWEET (S&SEs: prolonged effects on health, obesity and safety) is a 1-year multicentre RCT including at least 330 adults with overweight (18–65 years, body mass index (BMI) >25 kg/m2) and 40 children (6–12 years, BMI-for-age >85th percentile). In an initial 2-month period, adults will consume a low-energy diet with the aim to achieve ≥5% weight loss. Children are advised to consume a generally healthy diet to maintain body weight, thus reducing their BMI-for-age z-score. In the following 10 months, participants will be randomised to follow a healthy ad libitum diet with or without S&SE products. Clinical investigations are scheduled at baseline, after 2, 6 and 12 months. The primary outcomes are body weight for efficacy and gut microbiota composition (in relation to metabolic health) for safety, both in adults. Secondary outcomes include anthropometry, risk markers for type-2 diabetes and cardiovascular diseases, questionnaires including, for example, food preferences, craving and appetite and tests for allergenicity.Ethics and disseminationThe trial protocol has been approved by the following national ethical committees; The research ethics committees of the capital region (Denmark), approval code: H-19040679, The medical ethics committee of the University Hospital Maastricht and Maastricht University (the Netherlands), approval code: NL70977.068.19/METC19-056s, Research Ethics Committee of the University of Navarra (Spain), approval code: 2019.146 mod1, Research Ethics Committee of Harokopio University (Greece), approval code: 1810/18-06-2019. The trial will be conducted in accordance with the Declaration of Helsinki. Results will be published in international peer-reviewed scientific journals regardless of whether the findings are positive, negative or inconclusive.Trial registration numberNCT04226911(Clinicaltrials.gov)

Background & aims: The association of quantity and quality of carbohydrate sources with appetite during long-term weight-loss maintenance (WLM) after intentional weight loss (WL) is unclear. We aimed to investigate longitudinal associations of quantity and quality of carbohydrate sources with changes in subjective appetite sensations during WLM.Methods: This secondary analysis evaluated longitudinal data from the 3-year WLM phase of the PREVIEW study, a 2 × 2 factorial (diet-physical activity arms), multi-center, randomized trial. 1279 individuals with overweight or obesity and prediabetes (25-70 years; BMI≥25 kg m-2) were included. Individuals were merged into 1 group to assess longitudinal associations of yearly changes in appetite sensations. Quantity and quality of carbohydrate sources including total carbohydrate, glycemic index (GI), glycemic load (GL), and total dietary fiber were assessed via 4-day food diaries at 4 timepoints (26, 52, 104, and 156 weeks) during WLM. Visual analog scales were used to assess appetite sensations in the previous week.Results: During WLM, participants consumed on average 160.6 (25th, 75th percentiles 131.1, 195.8) g·day-1 of total carbohydrate, with GI 53.8 (48.7, 58.8) and GL 85.3 (67.2, 108.9) g day-1, and 22.3 (17.6, 27.3) g·day-1 of dietary fiber. In the available-case analysis, multivariable-adjusted linear mixed models with repeated measures showed that each 30-g increment in total carbohydrate was associated with increases in hunger (1.36 mm year-1, 95% CI 0.77, 1.95, P < 0.001), desire to eat (1.10 mm year-1, 0.59, 1.60, P < 0.001), desire to eat something sweet (0.99 mm year-1, 0.30, 1.68, P = 0.005), and weight regain (0.20%·year-1, 0.03, 0.36, P = 0.022). Increasing GI was associated with weight regain, but not associated with increases in appetite sensations. Each 20-unit increment in GL was associated with increases in hunger (0.92 mm year-1, 0.33, 1.51, P = 0.002), desire to eat (1.12 mm year-1, 0.62, 1.62, P < 0.001), desire to eat something sweet (1.13 mm year-1, 0.44, 1.81, P < 0.001), and weight regain (0.35%·year-1, 0.18, 0.52, P < 0.001). Surprisingly, dietary fiber was also associated with increases in desire to eat, after adjustment for carbohydrate or GL.Conclusions: In participants with moderate carbohydrate and dietary fiber intake, and low to moderate GI, we found that higher total carbohydrate, GL, and total fiber, but not GI, were associated with increases in subjective desire to eat or hunger over 3 years. This study was registered as ClinicalTrials.gov, NCT01777893.

Background: Individuals with pre-diabetes are commonly overweight and benefit from dietary and physical activity strategies aimed at decreasing body weight and hyperglycemia. Early insulin resistance can be estimated via the triglyceride glucose index {TyG = Ln [TG (mg/dl) × fasting plasma glucose (FPG) (mg/dl)/2]} and the hypertriglyceridemic-high waist phenotype (TyG-waist), based on TyG x waist circumference (WC) measurements. Both indices may be useful for implementing personalized metabolic management. In this secondary analysis of a randomized controlled trial (RCT), we aimed to determine whether the differences in baseline TyG values and TyG-waist phenotype predicted individual responses to type-2 diabetes (T2D) prevention programs.Methods: The present post-hoc analyses were conducted within the Prevention of Diabetes through Lifestyle intervention and population studies in Europe and around the world (PREVIEW) study completers (n = 899), a multi-center RCT conducted in eight countries (NCT01777893). The study aimed to reduce the incidence of T2D in a population with pre-diabetes during a 3-year randomized intervention with two sequential phases. The first phase was a 2-month weight loss intervention to achieve ≥8% weight loss. The second phase was a 34-month weight loss maintenance intervention with two diets providing different amounts of protein and different glycemic indices, and two physical activity programs with different exercise intensities in a 2 x 2 factorial design. On investigation days, we assessed anthropometrics, glucose/lipid metabolism markers, and diet and exercise questionnaires under standardized procedures.Results: Diabetes-related markers improved during all four lifestyle interventions. Higher baseline TyG index (p < 0.001) was associated with greater reductions in body weight, fasting glucose, and triglyceride (TG), while a high TyG-waist phenotype predicted better TG responses, particularly in those randomized to physical activity (PA) of moderate intensity.Conclusions: Two novel indices of insulin resistance (TyG and TyG-waist) may allow for a more personalized approach to avoiding progression to T2D.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT01777893 reference, identifier: NCT01777893.

[This corrects the article DOI: 10.3389/fnut.2021.685648.].Copyright © 2021 Zhu, Fogelholm, Larsen, Poppitt, Silvestre, Vestentoft, Jalo, Navas-Carretero, Huttunen-Lenz, Taylor, Stratton, Swindell, Kaartinen, Lam, Handjieva-Darlenska, Handjiev, Schlicht, Martinez, Seimon, Sainsbury, Macdonald, Westerterp-Plantenga, Brand-Miller and Raben.

Background: Individuals with pre-diabetes are commonly overweight and benefit from dietary and physical activity strategies aimed at decreasing body weight and hyperglycemia. Early insulin resistance can be estimated via the triglyceride glucose index {TyG = Ln [TG (mg/dl) × fasting plasma glucose (FPG) (mg/dl)/2]} and the hypertriglyceridemic-high waist phenotype (TyG-waist), based on TyG x waist circumference (WC) measurements. Both indices may be useful for implementing personalized metabolic management. In this secondary analysis of a randomized controlled trial (RCT), we aimed to determine whether the differences in baseline TyG values and TyG-waist phenotype predicted individual responses to type-2 diabetes (T2D) prevention programs. Methods: The present post-hoc analyses were conducted within the Prevention of Diabetes through Lifestyle intervention and population studies in Europe and around the world (PREVIEW) study completers (n = 899), a multi-center RCT conducted in eight countries (NCT01777893). The study aimed to reduce the incidence of T2D in a population with pre-diabetes during a 3-year randomized intervention with two sequential phases. The first phase was a 2-month weight loss intervention to achieve ≥8% weight loss. The second phase was a 34-month weight loss maintenance intervention with two diets providing different amounts of protein and different glycemic indices, and two physical activity programs with different exercise intensities in a 2 x 2 factorial design. On investigation days, we assessed anthropometrics, glucose/lipid metabolism markers, and diet and exercise questionnaires under standardized procedures. Results: Diabetes-related markers improved during all four lifestyle interventions. Higher baseline TyG index (p < 0.001) was associated with greater reductions in body weight, fasting glucose, and triglyceride (TG), while a high TyG-waist phenotype predicted better TG responses, particularly in those randomized to physical activity (PA) of moderate intensity. Conclusions: Two novel indices of insulin resistance (TyG and TyG-waist) may allow for a more personalized approach to avoiding progression to T2D. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01777893 reference, identifier: NCT01777893.

Background: Previous studies have shown an increase in hunger during weight-loss maintenance (WLM) after diet-induced weight loss. Whether a combination of a higher protein, lower glycemic index (GI) diet and physical activity (PA) can counteract this change remains unclear.Aim: To compare the long-term effects of two diets [high protein (HP)-low GI vs. moderate protein (MP)-moderate GI] and two PA programs [high intensity (HI) vs. moderate intensity (MI)] on subjective appetite sensations during WLM after ≥8% weight loss (WL).Methods: Data derived from the 3-years PREVIEW randomized intervention study. An 8-weeks WL phase using a low-energy diet was followed by a 148-weeks randomized WLM phase. For the WLM phase, participants were assigned to one of the four groups: HP-MI, HP-HI, MP-MI, and MP-HI. Available data from 2,223 participants with overweight or obesity (68% women; BMI ≥ 25 kg/m2). Appetite sensations including satiety, hunger, desire to eat, and desire to eat something sweet during the two phases (at 0, 8 weeks and 26, 52, 104, and 156 weeks) were assessed based on the recall of feelings during the previous week using visual analogue scales. Differences in changes in appetite sensations from baseline between the groups were determined using linear mixed models with repeated measures.Results: There was no significant diet × PA interaction. From 52 weeks onwards, decreases in hunger were significantly greater in HP-low GI than MP-moderate GI (Ptime × diet = 0.018, Pdietgroup = 0.021). Although there was no difference in weight regain between the diet groups (Ptime × diet = 0.630), hunger and satiety ratings correlated with changes in body weight at most timepoints. There were no significant differences in appetite sensations between the two PA groups. Decreases in hunger ratings were greater at 52 and 104 weeks in HP-HI vs. MP-HI, and greater at 104 and 156 weeks in HP-HI vs. MP-MI.Conclusions: This is the first long-term, large-scale randomized intervention to report that a HP-low GI diet was superior in preventing an increase in hunger, but not weight regain, during 3-years WLM compared with a MP-moderate GI diet. Similarly, HP-HI outperformed MP-HI in suppressing hunger. The role of exercise intensity requires further investigation.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT01777893.

Machine learning (ML) holds great promise for impacting healthcare delivery; however, to date most methods are tested in 'simulated' environments that cannot recapitulate factors influencing real-world clinical practice. We prospectively deployed and evaluated a random forest algorithm for therapeutic curative-intent radiation therapy (RT) treatment planning for prostate cancer in a blinded, head-to-head study with full integration into the clinical workflow. ML- and human-generated RT treatment plans were directly compared in a retrospective simulation with retesting (n = 50) and a prospective clinical deployment (n = 50) phase. Consistently throughout the study phases, treating physicians assessed ML- and human-generated RT treatment plans in a blinded manner following a priori defined standardized criteria and peer review processes, with the selected RT plan in the prospective phase delivered for patient treatment. Overall, 89% of ML-generated RT plans were considered clinically acceptable and 72% were selected over human-generated RT plans in head-to-head comparisons. RT planning using ML reduced the median time required for the entire RT planning process by 60.1% (118 to 47 h). While ML RT plan acceptability remained stable between the simulation and deployment phases (92 versus 86%), the number of ML RT plans selected for treatment was significantly reduced (83 versus 61%, respectively). These findings highlight that retrospective or simulated evaluation of ML methods, even under expert blinded review, may not be representative of algorithm acceptance in a real-world clinical setting when patient care is at stake.

QUOKKA is a 40 m pinhole small-angle neutron scattering instrument in routine user operation at the OPAL research reactor at the Australian Nuclear Science and Technology Organisation. Operating with a neutron velocity selector enabling variable wavelength, QUOKKA has an adjustable collimation system providing source–sample distances of up to 20 m. Following the large-area sample position, a two-dimensional 1 m2 position-sensitive detector measures neutrons scattered from the sample over a secondary flight path of up to 20 m. Also offering incident beam polarization and analysis capability as well as lens focusing optics, QUOKKA has been designed as a general purpose SANS instrument to conduct research across a broad range of scientific disciplines, from structural biology to magnetism. As it has recently generated its first 100 publications through serving the needs of the domestic and international user communities, it is timely to detail a description of its as-built design, performance and operation as well as its scientific highlights. Scientific examples presented here reflect the Australian context, as do the industrial applications, many combined with innovative and unique sample environments.

Purpose Limited data exist on testicular dose measurements using modern radiation treatment techniques and volumes for testicular seminoma. The aim of this study was to report the testicular dose using in vivo measurements in men with testicular seminoma receiving abdominopelvic radiation therapy (APRT) and a modified dog-leg field with and without gonadal shielding. Methods and materials Men with histologically confirmed testicular seminoma, either newly diagnosed stage II disease or isolated retroperitoneal relapse on surveillance for stage I disease, treated with APRT had testicular dose measurements recorded using MOSFET dosimeters. Those patients wishing to preserve fertility underwent radiation treatment with daily gonadal shielding. Factors that may influence testicular dose including field size, distance of the remaining testis from the radiation field, and patient separation, were also measured. Results Measurements were performed for 16 men; 10 with gonadal shielding and 6 without. The mean measured dose to the testis in the patients with gonadal shielding was 2.6 cGy (standard error, 0.75; range, 0-13) compared with 28.6 cGy (standard error, 12.6; range, 0-86) in the unshielded group for a 20-fraction treatment. Conclusions The use of gonadal shielding during APRT with a modified dog-leg technique results in a low testicular dose that is below the likely threshold for impaired spermatogenesis. In those men wishing to preserve fertility, we recommend the use of gonadal shielding, even with the use of modern radiation therapy techniques.

Objective To determine the cost-effectiveness of individual face-to-face cognitive behavioral therapy (CBT) compared to therapist guided Internet-based self-help (GSH-I) in overweight or obese adults with binge-eating disorder (BED). Method Analysis was conducted alongside the multicenter randomized controlled INTERBED trial. CBT (n = 76) consisted of up to 20 individual therapy sessions over 4 months. GSH-I (n = 71) consisted of 11 modules combining behavioral interventions, exercises including a self-monitoring food diary, psychoeducation, and 2 face-to-face coaching sessions over 4 months. Assessments at baseline, after 4 months (post-treatment), as well as 6 and 18 months after the end of treatment included health care utilization and sick leave days to calculate direct and indirect costs. Binge-free days (BFD) were calculated as effect measure based on the German version of the Eating Disorder Examination. The incremental cost-effectiveness ratio (ICER) was determined, and net benefit regressions, adjusted for comorbidities and baseline differences, were used to derive cost-effectiveness acceptability curves. Results After controlling for baseline differences, CBT was associated with non-significantly more costs (+€2,539) and BFDs (+40.1) compared with GSH-I during the 22-month observation period, resulting in an adjusted ICER of €63 per additional BFD. CBTs probability of being cost-effective increased above 80% only if societal willingness to pay (WTP) was ≥€250 per BFD. Discussion We did not find clear evidence for one of the treatments being more cost-effective. CBT tends to be more effective but also more costly. If the societal WTP for an additional BFD is low, then our results suggest that GSH-I should rather be adopted.

Objective Internet-based guided self-help (GSH-I) is an efficacious treatment for adults with binge-eating disorder (BED) and overweight or obesity. Although broadly accessible, high dropout from GSH-I has been reported. However, little is known about the factors explaining dropout from GSH-I, including patients' adherence to treatment. Method Within a randomized trial on the treatment of BED, adherence to 4-month GSH-I was objectively assessed in N = 89 patients with BED and overweight or obesity. Objective adherence and subjective treatment evaluation were evaluated as predictors of dropout from GSH-I, defined as having accessed 5 or less of 11 modules. Cutoffs with optimal sensitivity and specificity were derived using Receiver Operating Characteristics curves analysis, and baseline sociodemographic and clinical correlates were determined. Results According to our definition, n = 22 (24.7%) patients were defined as dropouts. Results of the full logistic regression model accounted for 72% of the variance in dropout and all objective adherence parameters (i.e., number of messages exchanged, days with a completed food diary, and days spent per module), but not patients' subjective GSH-I evaluation significantly predicted dropout. Specifically, not completing the food diary in week 7 had maximized sensitivity and specificity in predicting dropout. Patients' body mass index was positively associated with the number of messages exchanged between patients and coaches. No other associations between baseline variables and objective adherence were found. Discussion Patients at risk for dropout from GSH-I can be reliably identified via monitoring of objective adherence and may be provided with additional interventions to prevent dropout.

The paper is a review paper based on lit search and authors' research experiences.

We describe the initial experience using a hydrogel spacer (SpaceOAR) to separate the prostate-rectum interspace in patients planned to undergo radical hypofractionated image-guided intensity-modulated radiotherapy (IG-IMRT). We depict and discuss the impact of SpaceOAR in the context of hypofractionated IG-IMRT, and the particular considerations for its applications in the Canadian setting.

At the age of digital era, supervised / unsupervised machine learning, sharp data analysis and neuron network are some of many ways to formulate optimization problems with millions or billions of variables. Classical building system and environmental optimization algorithms are not designed to scale to instances of this size; new approaches are needed. The Digital Platform developed by Arup – Neuron is an innovative console which embodies 5G, IoT, Big Data, Cloud Computing and AI technology for smart building with advanced data analytic capabilities. It can fully integrate with the existing Building Management System as well as various data sources generated from the IoT sensors, enabling prompt and adaptive response to dynamic environment, serving as a foundation for buildings to consolidate and connect data from disparate equipment and devices to provide customised insight and machine learning models for built environmental management and improvement, new building design, operation and asset management, energy monitoring and optimisation. One significant success achieved with our integrated digital platform is that it has been adopted by multiple clients in the East Asia region in managing their building. With full implementation and other appropriate energy saving and/or retro-commissioning practices, Neuron is expected to save up to 30% total HVAC energy consumption for a typical existing commercial building. Apart from energy saving, Neuron also focuses on creating a better indoor environment, which could significantly improve employees’ productivity. Neuron, as a smart building console, is set to have a momentous impact on Hong Kong, not only for a better built environment, but also a game changer for the East Asia region to excel in the era of digital economy. This paper elaborates how Neuron could help in digital transformation of new and existing buildings in the new era. The challenges and experiences of projects will also be discussed.Start your abstract here…

Importance Although cognitive behavioral therapy (CBT) represents the criterion standard for treatment of binge eating disorder (BED), most individuals do not have access to this specialized treatment. Objective To evaluate the efficacy of internet-based guided self-help (GSH-I) compared with traditional, individual face-to-face CBT. Design, Setting, and Participants The Internet and Binge Eating Disorder (INTERBED) study is a prospective, multicenter, randomized, noninferiority clinical trial (treatment duration, 4 months; follow-ups, 6 months and 1.5 years). A volunteer sample of 178 adult outpatients with full or subsyndromal BED were recruited from 7 university-based outpatient clinics from August 1, 2010, through December 31, 2011; final follow-up assessment was in April 2014. Data analysis was performed from November 30, 2014, to May 27, 2015. Interventions Participants received 20 individual face-to-face CBT sessions of 50 minutes each or sequentially completed 11 internet modules and had weekly email contacts. Main Outcomes and Measures The primary outcome was the difference in the number of days with objective binge eating episodes (OBEs) during the previous 28 days between baseline and end of treatment. Secondary outcomes included OBEs at follow-ups, eating disorder and general psychopathologic findings, body mass index, and quality of life. Results A total of 586 patients were screened, 178 were randomized, and 169 had at least one postbaseline assessment and constituted the modified intention-to-treat analysis group (mean [SD] age, 43.2 [12.3] years; 148 [87.6%] female); the 1.5-year follow-up was available in 116 patients. The confirmatory analysis using the per-protocol sample (n = 153) failed to show noninferiority of GSH-I (adjusted effect, 1.47; 95% CI, −0.01 to 2.91; P = .05). Using the modified intention-to-treat sample, GSH-I was inferior to CBT in reducing OBE days at the end of treatment (adjusted effect, 1.63; 95% CI, 0.17-3.05; P = .03). Exploratory longitudinal analyses also showed the superiority of CBT over GSH-I by the 6-month (adjusted effect, 0.36; 95% CI, 0.23-0.55; P P = .70). Reductions in eating disorder psychopathologic findings were significantly higher in the CBT group than in the GSH-I group at 6-month follow-up (adjusted effect, −0.4; 95% CI, −0.68 to −0.13; P = .005). No group differences were found for body mass index, general psychopathologic findings, and quality of life. Conclusions and Relevance Face-to-face CBT leads to quicker and greater reductions in the number of OBE days, abstinence rates, and eating disorder psychopathologic findings and may be a better initial treatment option than GSH-I. Internet-based guided self-help remains a viable, slower-acting, low-threshold treatment alternative compared with CBT for adults with BED. Trial Registration isrctn.org Identifier:ISRCTN40484777and germanctr.de Identifier:DRKS00000409

Type-2 diabetes (T2D) is one of the fastest growing chronic diseases worldwide. The PREVIEW project has been initiated to find the most effective lifestyle (diet and physical activity) for the prevention of T2D, in overweight and obese participants with increased risk for T2D. The study is a three-year multi-centre, 2 × 2 factorial, randomised controlled trial. The impact of a high-protein, low-glycaemic index (GI) vs. moderate protein, moderate-GI diet in combination with moderate or high-intensity physical activity on the incidence of T2D and the related clinical end-points are investigated. The intervention started with a two-month weight reduction using a low-calorie diet, followed by a randomised 34-month weight maintenance phase comprising four treatment arms. Eight intervention centres are participating (Denmark, Finland, United Kingdom, The Netherlands, Spain, Bulgaria, Australia, and New Zealand). Data from blood specimens, urine, faeces, questionnaires, diaries, body composition assessments, and accelerometers are collected at months 0, 2, 6, 12, 18, 24, and 36. In total, 2326 adults were recruited. The mean age was 51.6 (SD 11.6) years, 67% were women. PREVIEW is, to date, the largest multinational trial to address the prevention of T2D in pre-diabetic adults through diet and exercise intervention. Participants will complete the final intervention in March, 2018.

282 Background: Coordinating lung cancer screening requires risk assessment for patient selection. Optimal selection can reduce costs and improve efficiency of low dose computed tomography (LDCT) screening of lung cancer. This study evaluated clinic-based spirometry as a tool to improve patient selection for lung cancer screening. Methods: Eligibility criteria for three large LDCT screening studies were retrospectively applied to the highest risk patients enrolled in the Princess Margaret Lung Cancer Screening Program who had received clinic-based research spirometry. The three studies were: Danish Lung Cancer Screening Trial (DLST), National Lung Screening Trial (NLST), and the Ontario Lung Cancer Screening Program (OLCS). Lung cancer incidence was compared between those who would were included by the screening study eligibility criteria (Group I), those who were excluded by the eligibility criteria but demonstrated obstruction on spirometry (defined as a Forced Expiratory Volume in 1 Second % Predicted (FEV1%) < 90%) (Group II), and those who did not meet eligibility criteria and had no obstruction (FEV1% ≥90) (Group III). Results: The 321 highest risk participants of the screening program had a mean age of 65 years and were 39% male. The median number of pack years in this group was 39. After undergoing spirometry, this cohort was screened using LDCT for a median of 3.3 years (range 1–8.1 years). Under DLST criteria, Groups I and II had virtually identical lung cancer incidences detected by screening at 13.1% and 13.6% of the individuals screened, respectively; Group III had a substantially lower incidence at 6.3%. Results were similar by NLST criteria where the incidence of screen-detected lung cancer were 13.7% for Groups I, 11.1% for Group II, and 8.6% for Group III. Under OLCS criteria, these values were 13.4% (Group I), 13.5% (Group II), and 8.2% (Group III). Conclusions: Individuals who were excluded from LDCT screening because they lacked other clinical eligibility criteria, but had a FEV1 < 90%, had similar lung cancer incidence as patients who had met screening study eligibility criteria. Coordinating care for screening of at-risk individuals could be improved by incorporating spirometric tools.

Although standard psychological treatments have been successful in treating several core features in eating disorders (ED), other characteristics such as emotional regulation or impulsivity appear to be more resistant to change. There is a growing body of evidence to support the efficacy of cognitive remediation for cognitive and emotional difficulties in ED. Playmancer/ Islands is a video game (VG) designed to specifically treat mental disorders, characterized by problems in impulse control. The objective of the game is to increase self-control over emotions, decision making and behaviours. The aim of this study is to describe the results from a consecutive series of nine bulimia nervosa patients who were treated with the VG in addition to cognitive behaviour therapy (CBT). The outcomes included clinical and psychopathological questionnaires, and physiological measures were obtained during the VG. Emotional regulation improved, heart rate variability increased, and respiratory rate and impulsivity measures reduced after the treatment. These findings suggest that VG training may enhance treatment for ED.

Several aspects of social and emotional functioning are abnormal in people with eating disorders. The aim of the present study was to measure facial emotional expression in patients with eating disorders and healthy controls whilst playing a therapeutic video game (Playmancer) designed to train individuals in emotional regulation. Participants were 23 ED patients (11 AN, 12 BN) and 11 HCs. ED patients self reported more anger at baseline but expressed less facial expression of anger during the Playmancer game. The discrepancy between self-report and non-verbal expression may lead to problems in social communication.

Our objective was to investigate whether the direct bilateral infusion of the monounsaturated fatty acid (MUFA) oleic acid (OA) within the mediobasal hypothalamus (MBH) is sufficient to reproduce the effect of administration of OA (30 nmol) in the third cerebral ventricle, which inhibits glucose production (GP) in rats. We used the pancreatic basal insulin clamp technique (plasma insulin ∼20 mU/ml) in combination with tracer dilution methodology to compare the effect of MBH OA on GP to that of a saturated fatty acid (SFA), palmitic acid (PA), and a polyunsaturated fatty acid (PUFA), linoleic acid (LA). The MBH infusion of 200 but not 40 pmol of OA was sufficient to markedly inhibit GP (by 61% from 12.6 ± 0.6 to 5.1 ± 1.6 mg·kg−1·min−1) such that exogenous glucose had to be infused at the rate of 6.0 ± 1.2 mg·kg−1·min−1 to prevent hypoglycemia. MBH infusion of PA also caused a significant decrease in GP, but only at a total dose of 4 nmol (GP 5.8 ± 1.6 mg·kg−1·min−1). Finally, MBH LA at a total dose of 0.2 and 4 nmol failed to modify GP compared with rats receiving MBH vehicle. Increased availability of OA within the MBH is sufficient to markedly inhibit GP. LA does not share the effect of OA, whereas PA can reproduce the potent effect of OA on GP, but only at a higher dose. It remains to be determined whether SFAs need to be converted to MUFAs to exert this effect or whether they activate a separate signaling pathway to inhibit GP.

Although cognitive behavioral therapy (CBT) has been demonstrated to be the most effective approach for the treatment of bulimia nervosa (BN), there is lack of studies showing whether a combination with a serious video game (SVG) might be useful to enhance patients' emotional regulation capacities and general outcome. The aims of this study were (a) to analyze whether outpatient CBT + SVG, when compared with outpatient CBT - SVG, shows better short-term outcome; (b) to examine whether the CBT + SVG group is more effective in reducing emotional expression and levels of anxiety than CBT - SVG. Thirty-eight patients diagnosed as having BN according to DSM-5 criteria were consecutively assigned to two outpatient group therapy conditions (that lasted for 16 weekly sessions): 20 CBT + SVG versus 18 CBT - SVG. Patients were assessed before and after treatment using not only a food and binging/purging diary and clinical questionnaires in the field of eating disorders but also additional indexes for measuring anger expression and anxiety. Regarding the post-treatment psychometric measures, most of the mean differences (Eating Disorder Inventory-2, Symptom Checklist-Revised, State-Trait Anxiety Index, and partially State-Trait Anger Expression Inventory) achieved moderate to high effect size (d > 0.5), in the sense that CBT + SVG obtained the best results compared with the CBT - SVG group. Regarding therapy outcome (dropout, partial remission, and total remission), CBT + SVG showed better results and a moderate effect size emerged for the comparison of the risk of dropout during the treatment, being higher for CBT - SVG compared with CBT + SVG (44.1 percent versus 20.0 percent, d = 0.54). Although the sample size in our study was low, and consequently results should be considered with caution, we have obtained promising findings suggesting that in the short-term CBT + SVG might be a good option not only for improving emotional dysregulation and approaching the current limitations of CBT - SVG in BN but also for enhancing the therapy adherence of patients.

Background: PlayMancer is a video game designed to increase emotional regulation and reduce general impulsive behaviors, by training to decrease arousal and improve decision-making and planning. We have previously demonstrated the usefulness of PlayMancer in reducing impulsivity and improving emotional regulation in bulimia nervosa (BN) patients. However, whether these improvements are actually translated into brain changes remains unclear. Objective: The aim of this case study was to report on a 28-year-old Spanish woman with BN, and to examine changes in physiological variables and brain activity after a combined treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT). Methods: Ten VGT sessions were carried out on a weekly basis. Anxiety, physiological, and impulsivity measurements were recorded. The patient was scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching task, and (2) a multi-source interference task (MSIT). Results: Upon completing the treatment, a decrease in average heart rate was observed. The functional magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in reaction time along with high accuracy. The patient engaged areas typically active in healthy controls, although the cluster extension of the active areas decreased after the combined treatment. Conclusions: These results suggest a global improvement in emotional regulation and impulsivity control after the VGT therapy in BN, demonstrated by both physiological and neural changes. These promising results suggest that a combined treatment of CBT and VGT might lead to functional cerebral changes that ultimately translate into better cognitive and emotional performances. [J Med Internet Res 2014;16(8):e183]

Expression of emotional state is considered to be a core facet of an individual's emotional competence. Emotional processing in BN has not been often studied and has not been considered from a broad perspective. This study aimed at examining the implicit and explicit emotional expression in BN patients, in the acute state and after recovery. Sixty-three female participants were included: 22 BN, 22 recovered BN (R-BN), and 19 healthy controls (HC). The clinical cases were drawn from consecutive admissions and diagnosed according to DSM-IV-TR diagnostic criteria. Self reported (explicit) emotional expression was measured with State-Trait Anger Expression Inventory-2, State-Trait Anxiety Inventory, and Symptom Check List-90 items-Revised. Emotional facial expression (implicit) was recorded by means of an integrated camera (by detecting Facial Feature Tracking), during a 20 minutes therapeutic video game. In the acute illness explicit emotional expression [anxiety (p

A novel peptolide antibiotic, serratiomycin, 1 , was isolated from the culture broth of a eubacterium by solvent extraction and column chromatography. The structure of 1 was determined to be cyclo( d -β-hydroxydecanoyl- l -leucyl- l -seryl- l - allo threonyl- d -phenylalanyl- d -isoleucyl). 1 exhibited a weak and mostly Gram-positive antibacterial spectrum in vitro .

Access to software tools for interactive data reduction, visualisation and analysis during a neutron scattering experiment enables instrument users to make informed decisions regarding the direction and success of their experiment. ANSTO aims to enhance the experiment experience of its facility's users by integrating these data reduction tools with the instrument control interface for immediate feedback. GumTree is a software framework and application designed to support an Integrated Scientific Experimental Environment, for concurrent access to instrument control, data acquisition, visualisation and analysis software. The Data Reduction and Analysis (DRA) module is a component of the GumTree framework that allows users to perform data reduction, correction and basic analysis within GumTree while an experiment is running. It is highly integrated with GumTree, able to pull experiment data and metadata directly from the instrument control and data acquisition components. The DRA itself uses components common to all instruments at the facility, providing a consistent interface. It features familiar ISAW-based 1D and 2D plotting, an OpenGL-based 3D plotter and peak fitting performed by fityk. This paper covers the benefits of integration, the flexibility of the DRA module, ease of use for the interface and audit trail generation.

GumTree is an open source and multi-platform graphical user interface for performing neutron scattering and X-ray experiments. It handles the complete experiment life cycle from instrument calibration, data acquisition, and real time data analysis to results publication. The aim of the GumTree Project is to create a highly Integrated Scientific Experiment Environment (ISEE), allowing interconnectivity and data sharing between different distributed components such as motors, detectors, user proposal database and data analysis server. GumTree is being adapted to several instrument control server systems such as TANGO, EPICS and SICS, providing an easy-to-use front-end for users and simple-to-extend model for software developers. The design of GumTree is aimed to be reusable and configurable for any scientific instrument. GumTree will be adapted to six neutron beam instruments for the OPAL reactor at ANSTO. Other European institutes including ESRF, ILL and PSI have shown interest in using GumTree as their workbench for instrument control and data analysis.

Although standard psychological treatments have been successful in treating several core features in eating disorders (ED), other characteristics such as emotional regulation or impulsivity appear to be more resistant to change. There is a growing body of evidence to support the efficacy of cognitive remediation for cognitive and emotional difficulties in ED. Playmancer/ Islands is a video game (VG) designed to specifically treat mental disorders, characterized by problems in impulse control. The objective of the game is to increase self-control over emotions, decision making and behaviours. The aim of this study is to describe the results from a consecutive series of nine bulimia nervosa patients who were treated with the VG in addition to cognitive behaviour therapy (CBT). The outcomes included clinical and psychopathological questionnaires, and physiological measures were obtained during the VG. Emotional regulation improved, heart rate variability increased, and respiratory rate and impulsivity measures reduced after the treatment. These findings suggest that VG training may enhance treatment for ED.

A new metabolite, L-755,807, 1, was isolated from an endophytic Microsphaeropsis sp. in the course of searching for a bradykinin binding inhibitor. The structure of 1, including relative stereochemistry, was determined. 1 showed an IC50 of 71 μM in 3H-bradykinin binding to a cloned human B2 receptor.

194 Background: Patients with cancer have an increased risk of venous thromboembolism (VTE) and frequently require anticoagulation. In addition, many patients with cancer also have comorbidities such as atrial fibrillation (AF) and are on stroke prevention. Rivaroxaban (RV) is an oral (factor Xa inhibitor) used in these scenarios; however, there is little experience utilizing this agent in patients with cancer. Our aim is to describe practice patterns and outcomes of RV usage in patients with cancer. Methods: We conducted a retrospective study of 62 patients with cancer receiving RV for at least 5 days for VTE or non-valvular AF from 1/1/2012 through 10/31/2015. Practice patterns included RV perioperative use and blood and platelet transfusions. Outcomes of interest were recurrent VTE and bleeding. Descriptive statistics were utilized to summarize demographic and clinical variables. Results: Of 62 patients with cancer, the mean age was 62 years (range 31-83), 50% were male, and 77% white. The most common cancer types were gastrointestinal 9 (15%), sarcoma 9 (15%), and breast and hematologic each with 8 (13%). Of those, 49 (79%) had VTE, 9 AF (15%), and 4 (7%) had both. 42 (68%) patients were switched to RV from a prior anticoagulant, the majority from low molecular weight heparin. 22 (36%) had RV withheld temporarily; 15 due to surgical procedure and 5 due to bleeding. 5 (33%) received bridging anticoagulation prior to surgery. RV was held a mean of 2 days prior to surgery and resumed 9 days post-op. 14 (21%) received blood and 2 (3%) received platelet transfusions while on RV. 2 (3%) patients had VTE recurrence while on RV. 18 (29%) discontinued RV due to bleeding, 5 (28%) due to hematuria and only 1 patient due to thrombocytopenia (6%). There were no major bleeds or deaths related to RV. Conclusions: RV was used in solid and hematologic cancers. The majority were transitioned from another anticoagulant. Although VTE recurrence was low, discontinuation of RV due to bleeding was higher. Further study of the use of RV in patients with cancer is needed for continued guidance of appropriate and safe usage.

69 Background: Patient-reported outcomes (PROs) contribute to the assessment and treatment of cancer-related fatigue (CRF). Paper-based symptom assessments are cumbersome and time-consuming. Electronic assessments are an efficient alternative. This study describes CRF Clinic patients at a major cancer Institution, the time they required to complete self-reported CRF symptom assessments via a tablet computer (iPad), and the factors influencing PRO assessment completion time. Methods: From 1/1/2011 to 8/21/2012, 190 newly-referred CRF Clinic patients utilized an iPad to complete standardized CRF symptom assessments for: fatigue, pain, depression, anxiety, stress, sleepiness, and apathy. A web-based assessment module (BrightOutcome) was employed, which recorded assessment start and completion times. Non-Parametric test statistics were utilized for analysis. Results: Of the initial 190 patients, 3 were excluded due to non-cancer diagnoses and 1 was excluded due to an erroneous completion time of 8,903 minutes. Sample size is 186 patients; mean age was 55.49 years (range: 31-89); 69.4% (n = 119) were female. Patient mean fatigue score (Brief Fatigue Inventory) was 6.4. Mean assessment completion time was 16.73 minutes (range: 4-47). Assessments took longer to complete for patients ≥ 65 years (mean: 21.53 minutes; range: 9-43), males (mean of 18.3 vs. 16 minutes for females), patients with severe fatigue (7-10) (mean 18.31 minutes; range: 4-47), greatest apathy (38-72) (mean: 19.5 minutes; range 8-47), those with active cancer (mean: 18.02 minutes vs. 15.15 minutes in cancer survivors), and those with 2 or more comorbidities (mean: 18.41 minutes vs. 15.86 minutes in those with less than 2 comorbidities). Pain severity and interference, anxiety, depression, stress, and sleepiness did not statistically significantly impact assessment completion time. Conclusions: Patients who are older, male, fatigued, apathetic, with active cancer or with 2 or more comorbidities may require longer in-clinic time to complete standard symptom assessments. Further studies exploring these and other patient characteristics potentially impacting the integration of new technologies into patient care and research are warranted.

Background Binge eating disorder (BED) is a prevalent clinical eating disorder associated with increased psychopathology, psychiatric comorbidity, overweight and obesity, and increased health care costs. Since its inclusion in the DSM-IV, a few randomized controlled trials (RCTs) have suggested efficacy of book-based self-help interventions in the treatment of this disorder. However, evidence from larger RCTs is needed. Delivery of self-help through new technologies such as the internet should be investigated in particular, as these approaches have the potential to be more interactive and thus more attractive to patients than book-based approaches. This study will evaluate the efficacy of an internet-based guided self-help program (GSH-I) and cognitive-behavioral therapy (CBT), which has been proven in several studies to be the gold standard treatment for BED, in a prospective multicenter randomized trial. Methods The study assumes the noninferiority of GSH-I compared to CBT. Both treatments lasted 4 months, and maintenance of outcome will be assessed 6 and 18 months after the end of treatment. A total of 175 patients with BED and a body mass index between 27 and 40 kg/m2 were randomized at 7 centers in Germany and Switzerland. A 20% attrition rate was assumed. As in most BED treatment trials, the difference in the number of binge eating days over the past 28 days is the primary outcome variable. Secondary outcome measures include the specific eating disorder psychopathology, general psychopathology, body weight, quality of life, and self-esteem. Predictors and moderators of treatment outcome will be determined, and the cost-effectiveness of both treatment conditions will be evaluated. Results The methodology for the INTERBED study has been detailed. Conclusions Although there is evidence that CBT is the first-line treatment for BED, it is not widely available. As BED is still a recent diagnostic category, many cases likely remain undiagnosed, and a large number of patients either receive delayed treatment or never get adequate treatment. A multicenter efficacy trial will give insight into the efficacy of a new internet-based guided self-help program and will allow a direct comparison to the evidence-based gold standard treatment of CBT in Germany. Trial Registration Current Controlled Trials ISRCTN40484777 German Clinical Trial Register DRKS00000409

Several aspects of social and emotional functioning are abnormal in people with eating disorders. The aim of the present study was to measure facial emotional expression in patients with eating disorders and healthy controls whilst playing a therapeutic video game (Playmancer) designed to train individuals in emotional regulation. Participants were 23 ED patients (11 AN, 12 BN) and 11 HCs. ED patients self reported more anger at baseline but expressed less facial expression of anger during the Playmancer game. The discrepancy between self-report and non-verbal expression may lead to problems in social communication.

Background: Previous review studies have suggested that computer games can serve as an alternative or additional form of treatment in several areas (schizophrenia, asthma or motor rehabilitation). Although several naturalistic studies have been conducted showing the usefulness of serious video games in the treatment of some abnormal behaviours, there is a lack of serious games specially designed for treating mental disorders. Aim: The purpose of our project was to develop and evaluate a serious video game designed to remediate attitudinal, behavioural and emotional processes of patients with impulse-related disorders. Method and results: The video game was created and developed within the European research project PlayMancer. It aims to prove potential capacity to change underlying attitudinal, behavioural and emotional processes of patients with impulse-related disorders. New interaction modes were provided by newly developed components, such as emotion recognition from speech, face and physiological reactions, while specific impulsive reactions were elicited. The video game uses biofeedback for helping patients to learn relaxation skills, acquire better self-control strategies and develop new emotional regulation strategies. In this article, we present a description of the video game used, rationale, user requirements, usability and preliminary data, in several mental disorders.

The object of this study was to examine the effectiveness of an Internet-based therapy (IBT) for bulimia nervosa (BN) as compared to a waiting list (WL). Sixty-two female BN patients, diagnosed according to DSM-IV criteria, were assigned to either the IBT or a WL. The control participants (WL) were matched to the IBT group in terms of age, duration of the disorder, number of previous treatments, and severity of the disorder. Assessment measures included the EDI, SCL-90-R, BITE, the TCI-R, and other clinical and psychopathological indices, which were administrated before and after the treatment. Considering the IBT, while the mean scores were lower at the end of the treatment for some EDI scales (bulimic, interpersonal distrust, maturity fears, and total score) and the BITE symptomatology subscale, the mean BMI was higher at posttherapy. Predictors of good IBT outcome were higher scores on the EDI perfectionism scale and EAT and a higher minimum BMI. Drop-out (after IBT 35.5% of cases) was related to higher SCL-anxiety scores, a lower hyperactivity, a lower minimum BMI, and lower TCI-reward dependence scores. At the end of the treatment, bingeing and vomiting abstinence rates differed significantly between the two groups. Results suggest that an online self-help approach appears to be a valid treatment option for BN when compared to a WL control group, especially for people who present a lower severity of their eating disorder (ED) symptomatology and some specific personality traits.

The discovery and physico-chemical characterization of three novel and minor virginiamycin M1 analogs as potent gastrin antagonists from a culture of a strain of Streptomyces olivaceus are described. These analogs are L-156,586, L-156,587 and L-156,588. They are, respectively, 15-dihydro-13,14-anhydro-, 13,14-anhydro- and 13-desoxy-analogs of virginiamycin M1. We also chemically converted virginiamycin M1 (via L-156,587) to L-156,586 and its unnatural epimer, L-156,906. These analogs are competitive and selective antagonists of gastrin and brain cholecystokinin binding at nanomolar concentrations. These are the most potent gastrin/brain cholecystokinin antagonists from natural products. The same compounds showed poor Gram-positive antibiotic activity versus virginiamycin M1. Structurally related Gram-positive antibiotics, griseoviridin and madumycin I, were inactive in gastrin and brain cholecystokinin binding at up to 100 microM.

Computer-assisted reconstructions of small parts of the macular neural network show how the nerve terminals and receptive fields are organized in 3-dimensional space. This biological neural network is anatomically organized for parallel distributed processing of information. Processing appears to be more complex than in computer-based neural networks, because spatiotemporal factors figure into synaptic weighting. Serial reconstruction data show anatomical arrangements which suggest that 1) assemblies of cells analyse and distribute information with inbuilt redundancy, to improve reliability; 2) feedforward/feedback loops provide the capacity for presynaptic modulation of output during processing; 3) constrained randomness in connectivities contributes to adaptability; and 4) local variations in network complexity permit differing analyses of incoming signals to take place simultaneously. The last inference suggests that there may be segregation of information flow to central stations subserving particular functions.

Computer-assisted, 3-dimensional reconstructions of macular receptive fields and of their linkages into a neural network have revealed new information about macular functional organization. Both type I and type II hair cells are included in the receptive fields. The fields are rounded, oblong, or elongated, but gradations between categories are common. Cell polarizations are divergent. Morphologically, each calyx of oblong and elongated fields appears to be an information processing site. Intrinsic modulation of information processing is extensive and varies with the kind of field. Each reconstructed field differs in detail from every other, suggesting that an element of randomness is introduced developmentally and contributes to endorgan adaptability.

Cancer patients visiting the emergency center (EC) are seldom assessed or treated for severe fatigue, a common symptom in sick patients due to acute medical conditions arising from cancer and cancer treatment. We provide a profile of cancer-related fatigue within the EC setting. Using a single-item screening tool derived from the Brief Fatigue Inventory, 928 patients (636 with solid tumors, 292 with hematological malignancies) triaged in the EC of a tertiary cancer center rated their fatigue at its worst in the last 24hours. Patient demographic and clinical factors were retrospectively reviewed from medical records. The chief complaints of patients seeking emergency care included fever, pain, gastrointestinal symptoms, dyspnea, fatigue, and bleeding. More than half (54%) reported severe fatigue (seven or higher on a 0–10 scale) upon EC admission. Moderate to severe pain was highly associated with fatigue severity. Patients with severe fatigue were more likely to be unstable and unable to go home after EC care. In multivariate logistic regression analysis for severe fatigue, the significant risk factors for patients with solid tumors included dizziness (odds ratio [OR]=3.59), severe pain (OR=1.98), poor performance status (OR=1.81), and being female (OR=1.56). Dyspnea was significantly associated with severe fatigue in patients with hematological malignancies (OR=4.74). Although fatigue was not the major reason for an ER visit, single-item fatigue-severity screening demonstrated highly prevalent severe fatigue in sicker EC cancer patients and in those patients who also suffered from other symptoms.