Effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified: study protocol of a randomized controlled trial

Background: Disordered eating behavior and body dissatisfaction affect a large proportion of the Dutch population and account for severe psychological, physical and social morbidity. Yet, the threshold for seeking professional care is still high. In the Netherlands, only 7.5% of patients with bulimia nervosa and 33% of patients with anorexia nervosa are treated within the mental health care system. Easily accessible and low-threshold interventions, therefore, are needed urgently. The internet has great potential to offer such interventions. The aim of this study is to determine whether a web-based treatment program for patients with eating disorders can improve eating disorder psychopathology among female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified. Methods/design: This randomized controlled trial will compare the outcomes of an experimental treatment group to a waiting list control group. In the web-based treatment program, participants will communicate personally and asynchronously with their therapists exclusively via the internet. The first part of the program will focus on analyzing eating attitudes and behaviors. In the second part of the program participants will learn how to change their attitudes and behaviors. Participants assigned to the waiting list control group will receive no-reply email messages once every two weeks during the waiting period of 15 weeks, after which they can start the program. The primary outcome measure is an improvement in eating disorder psychopathology as determined by the Eating Disorder Examination Questionnaire. Secondary outcomes include improvements in body image, physical and mental health, body weight, self-esteem, quality of life, and social contacts. In addition, the participants’ motivation for treatment and their acceptability of the program and the therapeutic alliance will be measured. The study will follow the recommendations in the CONSORT statement relating to designing and reporting on RCTs. Discussion: This study protocol presents the design of a RCT for evaluating the effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified

Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression

Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges

Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148

Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele

Shared and Disorder-Specific Event-Related Brain Oscillatory Markers of Attentional Dysfunction in ADHD and Bipolar Disorder.

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) often present with overlapping symptoms and cognitive impairments, such as increased fluctuations in attentional performance measured by increased reaction-time variability (RTV). We previously provided initial evidence of shared and distinct event-related potential (ERP) impairments in ADHD and BD in a direct electrophysiological comparison, but no study to date has compared neural mechanisms underlying attentional impairments with finer-grained brain oscillatory markers. Here, we aimed to compare the neural underpinnings of impaired attentional processes in ADHD and BD, by examining event-related brain oscillations during a reaction-time task under slow-unrewarded baseline and fast-incentive conditions. We measured cognitive performance, ERPs and brain-oscillatory modulations of power and phase variability in 20 women with ADHD, 20 women with BD (currently euthymic) and 20 control women. Compared to controls, both ADHD and BD groups showed increased RTV in the baseline condition and increased RTV, theta phase variability and lower contingent negative variation in the fast-incentive condition. Unlike controls, neither clinical group showed an improvement from the slow-unrewarded baseline to the fast-incentive condition in attentional P3 amplitude or alpha power suppression. Most impairments did not differ between the disorders, as only an adjustment in beta suppression between conditions (lower in the ADHD group) distinguished between the clinical groups. These findings suggest shared impairments in women with ADHD and BD in cognitive and neural variability, preparatory activity and inability to adjust attention allocation and activation. These overlapping impairments may represent shared neurobiological mechanisms of attentional dysfunction in ADHD and BD, and potentially underlie common symptoms in both disorders.We thank all who made this research possible: The National Adult ADHD Clinic at the South London and Maudsley Hospital, Dr Helen Costello, Prof Sophia Frangou, Prof Anne Farmer, Jessica Deadman, Hannah Collyer, Sarah-Jane Gregori, and all participants who contributed their time to the study. Dr Giorgia Michelini was supported by a 1+3 PhD studentship awarded by the MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London (G9817803). This project was supported by an Economic and Social Research Council studentship to Dr Viryanaga Kitsune (ES/100971X/1). Dr Giorgia Michelini and Prof Philip Asherson are supported by generous grants from the National Institute for Health Research Biomedical Research Centre for Mental Health at King’s College London, Institute of Psychiatry, Psychology and Neuroscience and South London and Maudsley National Health Service (NHS) Foundation Trust. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication

THz resonances with infinite lifetime in array of gold resonators

\u3cp\u3eMetasurfaces consisting of two metallic rods per unit-cell in a lattice can support resonances at THz frequencies with infinitely long lifetime. These resonances are known as bound states in the continuum (BICs). We investigate theoretically and experimentally the conditions leading to the formation of these resonances in gold particle arrays.\u3c/p\u3

Ocular melanoma is not associated with CDKN2A or MC1R variants--a population-based study

Germline variants in the melanocortin 1 receptor gene (MC1R) and the p16 gene (CDKN2A) are associated with an increased risk of cutaneous melanoma. The frequency of these germline variants was examined in a population-based, incident series of 62 ocular melanoma cases and ethnicity-matched population controls. In both cases and controls, 59% of individuals carried at least one MC1R variant and there were no significant differences in the frequency of any of the five most common variants of MC1R. We also found no significant differences between cases and controls in the frequency of any of the four most common variants of CDKN2A, and no melanoma case carried a deleterious germline CDKN2A mutation. Our findings argue against an important predisposing effect of the MC1R and CDKN2A genes for ocular melanom