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Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom non-remission in first-episode psychosis.
Our development cohort consisted of 1027 patients with first-episode psychosis recruited between 2005 to 2010 from 14 early intervention services across the National Health Service in England. Our validation cohort consisted of 399 patients with first-episode psychosis recruited between 2006 to 2009 from a further 11 English early intervention services. The one-year non-remission rate was 52% and 54% in the development and validation cohorts, respectively. Multivariable logistic regression was used to develop a risk prediction model for non-remission, which was externally validated.
The prediction model showed good discrimination (C-statistic of 0.74 (0.72, 0.76) and adequate calibration with intercept alpha of 0.13 (0.03, 0.23) and slope beta of 0.99 (0.87, 1.12). Our model improved the net-benefit by 16% at a risk threshold of 50%, equivalent to 16 more detected non-remitted first-episode psychosis individuals per 100 without incorrectly classifying remitted cases.
Once prospectively validated, our first episode psychosis prediction model could help identify patients at increased risk of non-remission at initial clinical contact.
Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver disease that accompanies obesity and the metabolic syndrome. Excess fructose consumption can initiate or exacerbate NAFLD in part due to a consequence of impaired hepatic fructose metabolism. Preclinical data emphasized that fructose-induced altered gut microbiome, increased gut permeability, and endotoxemia play an important role in NAFLD, but human studies are sparse. The present study aimed to determine if two weeks of excess fructose consumption significantly alters gut microbiota or permeability in humans.
We performed a pilot double-blind, cross-over, metabolic unit study in 10 subjects with obesity (body mass index [BMI] 30–40 mg/kg/m2). Each arm provided 75 grams of either fructose or glucose added to subjects’ individual diets for 14 days, substituted isocalorically for complex carbohydrates, with a 19-day wash-out period between arms. Total fructose intake provided in the fructose arm of the study totaled a mean of 20.1% of calories. Outcome measures included fecal microbiota distribution, fecal metabolites, intestinal permeability, markers of endotoxemia, and plasma metabolites.
Routine blood, uric acid, liver function, and lipid measurements were unaffected by the fructose intervention. The fecal microbiome (including Akkermansia muciniphilia), fecal metabolites, gut permeability, indices of endotoxemia, gut damage or inflammation, and plasma metabolites were essentially unchanged by either intervention.
In contrast to rodent preclinical findings, excess fructose did not cause changes in the gut microbiome, metabolome, and permeability as well as endotoxemia in humans with obesity fed fructose for 14 days in amounts known to enhance NAFLD.
The Kilmaluag Formation on the Isle of Skye, Scotland, provides one of the richest Mesozoic vertebrate fossil assemblages in the UK, and is among the richest globally for Middle Jurassic tetrapods. Since its discovery in 1971, this assemblage has predominantly yielded small-bodied tetrapods, including salamanders, choristoderes, lepidosaurs, turtles, crocodylomorphs, pterosaurs, dinosaurs, non-mammalian cynodonts and mammals, alongside abundant fish and invertebrates. It is protected as a Site of Special Scientific Interest and by Nature Conservancy Order. Unlike contemporaneous localities from England, this assemblage yields associated partial skeletons, providing unprecedented new data. We present a comprehensive updated overview of the Kilmaluag Formation, including its geology and the fossil collections made to date, with evidence of several species occurrences presented here for the first time. We place the vertebrate faunal assemblage in an international context through comparisons with relevant contemporaneous localities from the UK, Europe, Africa, Asia and the US. This wealth of material reveals the Kilmaluag Formation as a vertebrate fossil assemblage of global significance, both in terms of understanding Middle Jurassic faunal composition and the completeness of specimens, with implications for the early evolutionary histories of mammals, squamates and amphibians.
OBJECTIVES/GOALS: Innovations with positive health impact are a high priority for NCATS and CTSAs. Program design that uses the Causal Pathway approach incorporates performance indicators that assess impact. We applied Causal Pathway thinking to an ongoing national program to enhance the evaluation of program impact. We report Lessons Learned. METHODS/STUDY POPULATION: We conducted a day-long onsite workshop to introduce the model to the project team, build capacity, and map the existing program elements to Logic Models representing program Specific Aims. A local Causal Pathway (CP) champion was identified. Alignment of the Logic Models with the CP approach (input→activities→ outputs→effects/impact) developed iteratively through biweekly, then monthly conferral among stakeholders. Key tasks included distinguishing among activities, outputs, and effects (impacts), and identification of performance indicators for each stage of the Causal Pathway. Visualization tools and an additional late stage half-day workshop were used to foster consensus. Implementation of the CP model tested the feasibility of collecting specific indicators and prompted model revisions. RESULTS/ANTICIPATED RESULTS: Program leadership and team members (n = 30) participated in the kick-off workshop. Four Specific Aims were mapped to Logic Models. Multiple Causal Pathway (CP) diagrams, one for each project in the program, were developed and mapped to Aims. Alignment of CP threads to Aims and identification of performance indicators required iteration. CP threads converged onto common final Impacts, sometimes crossing to another Aim. Performance indicators for operations were readily accessible to team members, and less so for impacts. Assumptions about program effects were subjected to specific indicators. Over time, Leadership noticed more expression of CP thinking in daily activities. New projects developed during this period incorporated the CP approach. Teams were able to streamline and simplify Logic/CP models. DISCUSSION/SIGNIFICANCE OF IMPACT: Through capacity-building and mentored exercises, an innovation team was able to infuse CP thinking into the evaluation of their ongoing program. The CP approach to design and evaluation maps progress and indicators across the life of a program from initial activities to its ultimate impact.
Devolution presented an opportunity for the Welsh Government to introduce changes to housing and homelessness policy, and the subsequent homelessness reforms are seen as one of the best examples to date of the Welsh Government using its powers. However, devolved governments in small countries face a number of challenges in terms of realising their housing policy ambitions. In this article we argue that there is inevitable dissonance between the policy behind the Welsh Government legislation (prevention) and practice (implementation) associated with structural challenges (for example, austerity and budget restrictions, Welfare Reform and the availability of affordable accommodation). In response we propose a number of actions the Welsh Government might undertake to attempt to mitigate such structural challenges which also resonate in the English context where welfare retrenchment and homelessness prevention policies operate simultaneously.
Homelessness is largely understood as an urban issue and so rural homelessness is to a large extent invisible in both academic literature and in policy and practice discussions, just as it is often invisible in discourses of everyday rural life. This article draws on extensive interviews with homeless service users and providers in three rural authorities in Wales to give a clearer sense of the nature and challenges of rural homelessness. The article documents and explores the very different strategies employed by those facing homelessness in the rural context, as well as those of rural local authorities providing them preventative and person-centred support. Analysis of the struggle of many rural households to remain in place, often at the cost of homelessness and lowered ability to access services, will have resonance in a range of contexts and have implications for policy makers and practitioners in rural contexts beyond Wales.
Part 2 of the Housing Act (Wales) 2014 and its implementation has been keenly observed by governments outside of Wales, as they continue to search for policy solutions to help address the homelessness crisis. This article examines the extent to which there has been policy transfer from Wales to other national contexts and the potential for such transfer to occur in the future. It is identified that some transfer has already taken place within the UK and there is the potential for future policy transfer both within the UK and internationally. Adaptation to each of the new contexts is necessary to underpin successful transfer of provisions of the Act; however, outside of the UK this will need to be more extensive and include the introduction of a right to housing.
Alongside an increasing focus on ‘prevention’, moving homeless adults into work is frequently considered an important part of helping them overcome homelessness and sustain an ‘independent’ life. However, a growing evidence base shows that work does not always offer the means to escape poverty, and many in employment face housing insecurity. Relatedly, there is increasing concern about the phenomenon of ‘in-work homelessness’. Drawing on new data from a study of people’s experience of homelessness in Wales, this article considers the hitherto underexplored topic of being both in work and homeless. The article provides a critical examination of how homelessness policy operates in practice, through presenting evidence of the experiences of a marginalised group (namely, working homeless people as users of homelessness services). It also considers how policy and practice could be modified to improve outcomes for homeless people and how prevention could play out in other contexts and welfare regimes.
Rates of homelessness and poor mental health present significant challenges across the globe. In this article, we explore how these intersecting issues have been addressed in Wales through Part 2 of the Housing (Wales) Act 2014 through a paradigm shift towards a prevention model. This article reports findings from a study (conducted between 2016 and 2018) which evaluated the processes and impacts of the Act against the backdrop of welfare reform and systemic changes taking place in Wales and the UK. Using new evidence, we offer a critical examination of how homelessness prevention policy operates in practice and how social values and power affect policy implementation. We offer new evidence of the translation of policy into practice through the experiences of two stakeholder groups: people with mental health needs and service providers. In doing so, we offer a critique of how policy and practice could be modified to improve outcomes for homeless people with implications for prevention policy in Wales and in other contexts and different welfare regimes.
More than 68 million people worldwide have been forcibly displaced and one-third of these are refugees. This article offers an overview of the current literature and reviews the epidemiology and evidence-based psychological and pharmacological management of post-traumatic stress disorder (PTSD), sleep disturbance and pain in refugees and asylum seekers. It also considers the relationship between sleep disturbance and PTSD and explores concepts of pain in relation to physical and psychological trauma and distress. During diagnosis, clinicians must be aware of ethnic variation in the somatic expression of distress. Treatments for PTSD, pain and sleep disturbance among refugees and asylum seekers are essentially the same as those used in the general population, but treatment strategies must allow for cultural and contextual factors, including language barriers, loss of freedom and threat of repatriation.
After reading this article you will be able to:
• recognise the challenges faced by the large number of refugees worldwide
• understand the relationship between PTSD, sleep disturbance and pain in refugees
• broadly understand the evidence for psychological and pharmacological therapy for treating PTSD, sleep disturbance and pain in refugees.
Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode.
Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning.
Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders.
Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP.
Although school-based programmes for the identification of children and young people (CYP) with mental health difficulties (MHD) have the potential to improve short- and long-term outcomes across a range of mental disorders, the evidence-base on the effectiveness of these programmes is underdeveloped. In this systematic review, we sought to identify and synthesise evidence on the effectiveness and cost-effectiveness of school-based methods to identify students experiencing MHD, as measured by accurate identification, referral rates, and service uptake.
Electronic bibliographic databases: MEDLINE, Embase, PsycINFO, ERIC, British Education Index and ASSIA were searched. Comparative studies were included if they assessed the effectiveness or cost-effectiveness of strategies to identify students in formal education aged 3–18 years with MHD, presenting symptoms of mental ill health, or exposed to psychosocial risks that increase the likelihood of developing a MHD.
We identified 27 studies describing 44 unique identification programmes. Only one study was a randomised controlled trial. Most studies evaluated the utility of universal screening programmes; where comparison of identification rates was made, the comparator test varied across studies. The heterogeneity of studies, the absence of randomised studies and poor outcome reporting make for a weak evidence-base that only generate tentative conclusions about the effectiveness of school-based identification programmes.
Well-designed pragmatic trials that include the evaluation of cost-effectiveness and detailed process evaluations are necessary to establish the accuracy of different identification models, as well as their effectiveness in connecting students to appropriate support in real-world settings.
Most planetary nebulae (PNe) show beautiful, axisymmetric morphologies despite their progenitor stars being essentially spherical. Angular momentum provided by a close binary companion is widely invoked as the main agent that would help eject an axisymmetric nebula, after a brief phase of engulfment of the secondary within the envelope of the Asymptotic Giant Branch (AGB) star, known as a common envelope (CE). The evolution on the AGB would thus be interrupted abruptly, its (still quite) massive envelope fully ejected to form the PN, which should be more massive than a PN coming from the same star were it single. We test this hypothesis by deriving the ionised+molecular masses of a pilot sample of post-CE PNe and comparing them to a regular PNe sample. We find the mass of post-CE PNe to be actually lower, on average, than their regular counterparts, raising some doubts on our understanding of these intriguing objects.
Transient Ischaemic Attack (TIA) is a neurologic event with symptom resolution within 24 hours. Early specialist assessment of TIA reduces risk of stroke and death. National United Kingdom (UK) guidelines recommend patients with TIA are seen in specialist clinics within 24 hours (high risk) or seven days (low risk).
We aimed to develop a complex intervention for patients with low risk TIA presenting to the emergency ambulance service. The intervention is being tested in the TIER feasibility trial, in line with Medical Research Council (MRC) guidance on staged development and evaluation of complex interventions.
We conducted three interrelated activities to produce the TIER intervention:
• Survey of UK Ambulance Services (n = 13) to gather information about TIA pathways already in use
• Scoping review of literature describing prehospital care of patients with TIA
• Synthesis of data and definition of intervention by specialist panel of: paramedics; Emergency Department (ED) and stroke consultants; service users; ambulance service managers.
The panel used results to define the TIER intervention, to include:
1. Protocol for paramedics to assess patients presenting with TIA and identify and refer low risk patients for prompt (< 7day) specialist review at TIA clinic
2. Patient Group Directive and information pack to allow paramedic administration of aspirin to patients left at home with referral to TIA clinic
3. Referral process via ambulance control room
4. Training package for paramedics
5. Agreement with TIA clinic service provider including rapid review of referred patients
We followed MRC guidance to develop a clinical intervention for assessment and referral of low risk TIA patients attended by emergency ambulance paramedic. We are testing feasibility of implementing and evaluating this intervention in the TIER feasibility trial which may lead to fully powered multicentre randomized controlled trial (RCT) if predefined progression criteria are met.
The discrepancy between abundances computed using optical recombination lines (ORLs) and collisionally excited lines (CELs) is a major, unresolved problem with significant implications for the determination of chemical abundances throughout the Universe. In planetary nebulae (PNe), the most common explanation for the discrepancy is that two different gas phases coexist: a hot component with standard metallicity, and a much colder plasma enhanced in heavy elements. This dual nature is not predicted by mass loss theories, and direct observational support for it is still weak. In this work, we present our recent findings that demonstrate that the largest abundance discrepancies are associated with close binary central stars. OSIRIS-GTC tunable filter imaging of the faint O ii ORLs and MUSE-VLT deep 2D spectrophotometry confirm that O ii ORL emission is more centrally concentrated than that of [Oiii] CELs and, therefore, that the abundance discrepancy may be closely linked to binary evolution.
A highly accurate multi-point pressure measurement system based on MEMS pressure sensors spliced into a fiber optic cable and suitable for downhole deployment in a CO2 sequestration well was designed, developed and tested in the laboratory. An interrogator system based on a pulsed laser excitation was shown to be capable of multiple (potentially 60+) point sensor measurements on a single fiber. The interrogator was interfaced with the GE PredixTM industrial internet to demonstrate a remote monitoring system. Sensor packages were fabricated and tested at high temperatures and pressures in supercritical CO2. Environmental and stress testing of the sensor components and package indicated areas in which the design of the package should be further improved.
North American studies show bipolar disorder is associated with elevated
rates of problem gambling; however, little is known about rates in the
different presentations of bipolar illness.
To determine the prevalence and distribution of problem gambling in
people with bipolar disorder in the UK.
The Problem Gambling Severity Index was used to measure gambling problems
in 635 participants with bipolar disorder.
Moderate to severe gambling problems were four times higher in people
with bipolar disorder than in the general population, and were associated
with type 2 disorder (OR = 1.74, P = 0.036), history of
suicidal ideation or attempt (OR = 3.44, P = 0.02) and
rapid cycling (OR = 2.63, P = 0.008).
Approximately 1 in 10 patients with bipolar disorder may be at moderate
to severe risk of problem gambling, possibly associated with suicidal
behaviour and a rapid cycling course. Elevated rates of gambling problems
in type 2 disorder highlight the probable significance of modest but
unstable mood disturbance in the development and maintenance of such
C46 was a Commission of the Executive Committee of the IAU under Division XII (Union-Wide Activities), then after 2012 under Division C (Education, Outreach, and Heritage). It was the only commission dealing exclusively with astronomy education; a previous Commission 38 (Exchange of Astronomers), which allocated travel grants to astronomers who needed them, and a Working Group on the Worldwide Development of Astronomy, have been absorbed by Commission 46.