ANZAED eating disorder treatment principles and general clinical practice and training standards

Introduction: Eating disorders are complex to manage, and there is limited guidance around the depth and breadth of knowledge, skills and experience required by treatment providers. The Australia & New Zealand Academy for Eating Disorders (ANZAED) convened an expert group of eating disorder researchers and clinicians to define the clinical practice and training standards recommended for mental health professionals and dietitians providing treatment for individuals with an eating disorder. General principles and clinical practice standards were first developed, after which separate mental health professional and dietitian standards were drafted and collated by the appropriate members of the expert group. The subsequent review process included four stages of consultation and document revision: (1) expert reviewers; (2) a face-to-face consultation workshop attended by approximately 100 health professionals working within the sector; (3) an extensive open access online consultation process; and (4) consultation with key professional and consumer/carer stakeholder organisations. Recommendations: The resulting paper outlines and describes the following eight eating disorder treatment principles: (1) early intervention is essential; (2) co-ordination of services is fundamental to all service models; (3) services must be evidence-based; (4) involvement of significant others in service provision is highly desirable; (5) a personalised treatment approach is required for all patients; (6) education and/or psychoeducation is included in all interventions; (7) multidisciplinary care is required and (8) a skilled workforce is necessary. Seven general clinical practice standards are also discussed, including: (1) diagnosis and assessment; (2) the multidisciplinary care team; (3) a positive therapeutic alliance; (4) knowledge of evidence-based treatment; (5) knowledge of levels of care; (6) relapse prevention; and (7) professional responsibility. Conclusions: These principles and standards provide guidance to professional training programs and service providers on the development of knowledge required as a foundation on which to build competent practice in the eating disorder field. Implementing these standards aims to bring treatment closer to best practice, and consequently improve treatment outcomes, reduce financial cost to patients and services and improve patient quality of life

SOCS3 Is a Critical Physiological Negative Regulator of G-CSF Signaling and Emergency Granulopoiesis

AbstractTo determine the importance of suppressor of cytokine signaling-3 (SOCS3) in the regulation of hematopoietic growth factor signaling generally, and of G-CSF-induced cellular responses specifically, we created mice in which the Socs3 gene was deleted in all hematopoietic cells. Although normal until young adulthood, these mice then developed neutrophilia and a spectrum of inflammatory pathologies. When stimulated with G-CSF in vitro, SOCS3-deficient cells of the neutrophilic granulocyte lineage exhibited prolonged STAT3 activation and enhanced cellular responses to G-CSF, including an increase in cloning frequency, survival, and proliferative capacity. Consistent with the in vitro findings, mutant mice injected with G-CSF displayed enhanced neutrophilia, progenitor cell mobilization, and splenomegaly, but unexpectedly also developed inflammatory neutrophil infiltration into multiple tissues and consequent hind-leg paresis. We conclude that SOCS3 is a key negative regulator of G-CSF signaling in myeloid cells and that this is of particular significance during G-CSF-driven emergency granulopoiesis

A new mathematical model for nucleation of spherical agglomerates by the immersion mechanism

Initial wetting of crystals by binder droplets is a key rate process in spherical agglomeration, however there are no models to predict the kinetics and formation of agglomerate nuclei. Two new mathematical models are introduced for agglomerate nucleation by an immersion mechanism; immersion rate limited model and collision rate limited model. The agglomerate nucleation number developed in this work predicts different regimes; immersion rate limited, collision rate limited and intermediate. In an immersion rate limited regime, agglomerate size increases with square root of time. In a collision rate limited regime, size increases linearly with time if the bulk crystal volume fraction, φPb, is constant, or with an exponential decay rate for batch crystallisation with decreasing φPb. The timescale for nucleation is less than ten minutes for a broad range of conditions, significantly less than most crystallisation timescales. These models have great promise for population balance modelling and spherical agglomeration optimisation

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747

A pragmatic cluster randomised trial evaluating three implementation interventions

Background Implementation research is concerned with bridging the gap between evidence and practice through the study of methods to promote the uptake of research into routine practice. Good quality evidence has been summarised into guideline recommendations to show that peri-operative fasting times could be considerably shorter than patients currently experience. The objective of this trial was to evaluate the effectiveness of three strategies for the implementation of recommendations about peri-operative fasting. Methods A pragmatic cluster randomised trial underpinned by the PARIHS framework was conducted during 2006 to 2009 with a national sample of UK hospitals using time series with mixed methods process evaluation and cost analysis. Hospitals were randomised to one of three interventions: standard dissemination (SD) of a guideline package, SD plus a web-based resource championed by an opinion leader, and SD plus plan-do-study-act (PDSA). The primary outcome was duration of fluid fast prior to induction of anaesthesia. Secondary outcomes included duration of food fast, patients' experiences, and stakeholders' experiences of implementation, including influences. ANOVA was used to test differences over time and interventions. Results Nineteen acute NHS hospitals participated. Across timepoints, 3,505 duration of fasting observations were recorded. No significant effect of the interventions was observed for either fluid or food fasting times. The effect size was 0.33 for the web-based intervention compared to SD alone for the change in fluid fasting and was 0.12 for PDSA compared to SD alone. The process evaluation showed different types of impact, including changes to practices, policies, and attitudes. A rich picture of the implementation challenges emerged, including inter-professional tensions and a lack of clarity for decision-making authority and responsibility. Conclusions This was a large, complex study and one of the first national randomised controlled trials conducted within acute care in implementation research. The evidence base for fasting practice was accepted by those participating in this study and the messages from it simple; however, implementation and practical challenges influenced the interventions' impact. A set of conditions for implementation emerges from the findings of this study, which are presented as theoretically transferable propositions that have international relevance. Trial registration ISRCTN18046709 - Peri-operative Implementation Study Evaluation (POISE

An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.

Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP), promoting evasion of T cell-mediated immunity. MHC-I APP gene promoters in MHC-I low cancers harbor bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine-induced upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological MHC-I silencing highlights a conserved mechanism by which cancers arising from these primitive tissues exploit PRC2 activity to enable immune evasion.Cancer Research UK Clinician Scientist Fellowship C53779/A20097 (M.L.B), Leukaemia Foundation Australia Senior Fellowship and Howard Hughes Medical Institute International Research Scholarship 55008729 (M.A.D), Peter and Julie Alston Centenary fellowship (K.D.S.), Wellcome Trust Principal Research Fellowship 101835/Z/13/Z (P.J.L), Peter MacCallum Postgraduate Scholarship (C.E.S), NHMRC Postgraduate Scholarship (K.L.C.), Maddie Riewoldt's Vision 064728 (Y-C.C), Victorian Cancer Agency (E.Y.N.L), CSL Centenary fellowship (S-J.D), National Breast Cancer Foundation Fellowship ECF-17-005 (P.A.B.), Addenbrooke’s Charitable Trust and NIHR Cambridge BRC (M.L.B., P.J.L), NHMRC grant 1085015, 1106444 (M.A.D) and 1128984 (M.A.D, S-J.D)

Evaluating Promotional Approaches for Citizen Science Biological Recording: Bumblebees as a Group Versus Harmonia axyridis as a Flagship for Ladybirds

Over the past decade, the number of biological records submitted by members of the public have increased dramatically. However, this may result in reduced record quality, depending on how species are promoted in the media. Here we examined the two main promotional approaches for citizen science recording schemes: flagship-species, using one charismatic species as an umbrella for the entire group (here, Harmonia axyridis (Pallas) for Coleoptera: Coccinellidae), and general-group, where the group is promoted as a whole and no particular prominence is given to any one species (here, bumblebees, genus Bombus (Hymenoptera: Apidae)). Of the two approaches, the general-group approach produced data that was not biased towards any one species, but far fewer records per year overall. In contrast, the flagship-species approach generated a much larger annual dataset, but heavily biased towards the flagship itself. Therefore, we recommend that the approach for species promotion is fitted to the result desired

The vaccination of 35,000 dogs in 20 working days using combined static point and door-to-door methods in Blantyre, Malawi

An estimated 60,000 people die of rabies annually. The vast majority of cases of human rabies develop following a bite from an infected dog. Rabies can be controlled in both human and canine populations through widespread vaccination of dogs. Rabies is particularly problematic in Malawi, costing the country an estimated 13 million USD and 484 human deaths annually, with an increasing paediatric incidence in Blantyre City. Consequently, the aim of this study was to vaccinate a minimum of 75% of all the dogs within Blantyre city during a one month period. Blantyre's 25 administrative wards were divided into 204 working zones. For initial planning, a mean human:dog ratio from the literature enabled estimation of dog population size and dog surveys were then performed in 29 working zones in order to assess dog distribution by land type. Vaccination was conducted at static point stations at weekends, at a total of 44 sites, with each operating for an average of 1.3 days. On Monday to Wednesday, door-to-door vaccination sessions were undertaken in the areas surrounding the preceding static point stations. 23,442 dogs were vaccinated at static point stations and 11,774 dogs were vaccinated during door-to-door vaccinations. At the end of the 20 day vaccination programme, an assessment of vaccination coverage through door-to-door surveys found that of 10,919 dogs observed, 8,661 were vaccinated resulting in a vaccination coverage of 79.3% (95%CI 78.6-80.1%). The estimated human:dog ratio for Blantyre city was 18.1:1. Mobile technology facilitated the collection of data as well as efficient direction and coordination of vaccination teams in near real time. This study demonstrates the feasibility of vaccinating large numbers of dogs at a high vaccination coverage, over a short time period in a large African city

Post COVID‐19: a solution scan of options for preventing future zoonotic epidemics

The crisis generated by the emergence and pandemic spread of COVID-19 has thrown into the global spotlight the dangers associated with novel diseases, as well as the key role of animals, especially wild animals, as potential sources of pathogens to humans. There is a widespread demand for a new relationship with wild and domestic animals, including suggested bans on hunting, wildlife trade, wet markets or consumption of wild animals. However, such policies risk ignoring essential elements of the problem as well as alienating and increasing hardship for local communities across the world, and might be unachievable at scale. There is thus a need for a more complex package of policy and practical responses. We undertook a solution scan to identify and collate 161 possible options for reducing the risks of further epidemic disease transmission from animals to humans, including potential further SARS-CoV-2 transmission (original or variants). We include all categories of animals in our responses (i.e. wildlife, captive, unmanaged/feral and domestic livestock and pets) and focus on pathogens (especially viruses) that, once transmitted from animals to humans, could acquire epidemic potential through high rates of human-to-human transmission. This excludes measures to prevent well-known zoonotic diseases, such as rabies, that cannot readily transmit between humans. We focused solutions on societal measures, excluding the development of vaccines and other preventive therapeutic medicine and veterinary medicine options that are discussed elsewhere. We derived our solutions through reading the scientific literature, NGO position papers, and industry guidelines, collating our own experiences, and consulting experts in different fields. Herein, we review the major zoonotic transmission pathways and present an extensive list of options. The potential solutions are organised according to the key stages of the trade chain and encompass solutions that can be applied at the local, regional and international scales. This is a set of options targeted at practitioners and policy makers to encourage careful examination of possible courses of action, validating their impact and documenting outcomes