Brief Consultation to Families of Treatment Refusers with Symptoms of Obsessive Compulsive Disorder: Does It Impact Family Accommodation and Quality of Life?

Family members are often directly and significantly impacted by the restrictive demands of OCD, a frequently disabling disorder. Family accommodation behaviors (i.e., doing things for or because of the OCD sufferer that a person would not normally do) are associated with dysfunction, including poorer treatment responses in OCD sufferers and greater distress in family members. Although evidence suggests family-based intervention can reduce symptoms in OCD sufferers who participate in treatment, there is a lack of research documenting the impact of interventions designed for the families of OCD treatment refusers (TR). Brief Family Consultation (BFC) was developed by our clinical team to help families refocus their efforts on the things that they can realistically control and change (e.g., participation in compulsions). In this crossover study, twenty families related to an individual who exhibited OCD symptoms but had refused treatment were assigned to five phone sessions of either BFC or a psychoeducation condition. Compared to this credible, attention-placebo control group (Brief Educational Support; BES), BFC (but not BES) resulted in reductions in family accommodation behavior, yet neither BFC nor BES resulted in improved quality of life for family members of treatment refusers. BFC is one of the first interventions to be evaluated for its ability to help families when their loved ones with obsessive compulsive symptoms refuse treatment. This pilot study provides new insights for clinicians and researchers to better address the needs of these neglected families

Optimistic Planning for Markov Decision Processes

International audienceThe reinforcement learning community has recently intensified its interest in online planning methods, due to their relative independence on the state space size. However, tight near-optimality guarantees are not yet available for the general case of stochastic Markov decision processes and closed-loop, state-dependent planning policies. We therefore consider an algorithm related to AO* that optimistically explores a tree representation of the space of closed-loop policies, and we analyze the near-optimality of the action it returns after n tree node expansions. While this optimistic planning requires a finite number of actions and possible next states for each transition, its asymptotic performance does not depend directly on these numbers, but only on the subset of nodes that significantly impact near-optimal policies. We characterize this set by introducing a novel measure of problem complexity, called the near-optimality exponent. Specializing the exponent and performance bound for some interesting classes of MDPs illustrates the algorithm works better when there are fewer near-optimal policies and less uniform transition probabilities

Multicentre RCT and economic evaluation of a psychological intervention together with a leaflet to reduce risk behaviour amongst men who have sex with men (MSM) prescribed post-exposure prophylaxis for HIV following sexual exposure (PEPSE): A protocol

Background: Post-exposure prophylaxis (PEP) following sexual exposure to HIV has been recommended as a method of preventing HIV infection in the UK. Men who have sex with men (MSM) are the group most affected by HIV in the UK and their sexual risk taking behaviour is reported to be increasing. One-to-one behavioural interventions, such as motivational interviewing (MI) have been recommended to reduce HIV in high risk groups. The Information, Motivation and Behavioral skills (IMB) model has been shown to provide a good basis for understanding and predicting HIV-relevant health behaviour and health behaviour change, however the IMB has yet to be applied to PEP after risky sexual exposure. The primary aim of this trial is to examine the impact of MI augmented with information provision and behavioural skills building (informed by the IMB Model), over and above usual care, on risky sexual behaviour in MSM prescribed PEP after potential sexual exposure. A secondary aim of this research is to examine the impact of the intervention on adherence to PEP. This study will also provide estimates of the cost-effectiveness of the intervention. Methods: A manualised parallel group randomised controlled trial with economic evaluation will be conducted. The primary outcome is the proportion of risky sexual practices. Secondary outcomes include: i) Levels of adherence to PEP treatment; ii) Number of subsequent courses of PEP; iii) Levels of motivation to avoid risky sexual behaviours; iv) Levels of HIV risk-reduction information/knowledge; v) Levels of risk reduction behavioural skills; vi) Diagnosis of anal gonorrhoea, Chlamydia and/or HIV. 250 participants will be asked to self-complete a questionnaire at four time points during the study (at 0,3,6,12 months). The intervention will consist of a two-session, fixed duration, telephone administered augmented MI intervention based on the IMB model. A newly developed treatment manual will guide the selection of persuasive communication strategies as appropriate for each participant and will be based on underlying change mechanisms specified by the IMB theoretical framework. Information provision and skills building will also be included in the intervention package through the use of information leaflets and tailored action plans. Fidelity of intervention delivery will be assessed. Discussion: The results from this NIHR funded study will identify whether it is appropriate and cost-effective to intervene using one-to-one telephone calls with MSM seeking PEP. If the intervention is effective, further work will be needed on training staff to deliver the intervention competently

Expanded encyclopaedias of DNA elements in the human and mouse genomes

All data are available on the ENCODE data portal: www.encodeproject. org. All code is available on GitHub from the links provided in the methods section. Code related to the Registry of cCREs can be found at https:// github.com/weng-lab/ENCODE-cCREs. Code related to SCREEN can be found at https://github.com/weng-lab/SCREEN.© The Author(s) 2020. The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.This work was supported by grants from the NIH under U01HG007019, U01HG007033, U01HG007036, U01HG007037, U41HG006992, U41HG006993, U41HG006994, U41HG006995, U41HG006996, U41HG006997, U41HG006998, U41HG006999, U41HG007000, U41HG007001, U41HG007002, U41HG007003, U54HG006991, U54HG006997, U54HG006998, U54HG007004, U54HG007005, U54HG007010 and UM1HG009442

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Cognitive-behavioral treatment of older adults with obsessive-compulsive disorder

Despite substantial evidence supporting the general efficacy of cognitive behavioral treatment for obsessive-compulsive disorder (OCD), little has been written to guide practitioners treating older adults with this potentially disabling condition. The present article reviews the research literature on the cognitive behavioral treatment of elders with OCD and discusses adaptations of treatment that may be required to respond effectively to clinical issues and challenges associated with this disorder in later life. Though more research is clearly needed, preliminary findings suggest exposure and response prevention is effective with older adults. However, practitioners may need to adjust clinical procedure to address medical comorbidity and physical and cognitive limitations associated with aging, cultural issues and attitudes that may promote treatment resistance and nonadherence, the influence of family members and other caretakers, and complications presented by stressors and fears common in older adults