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Dientamoeba fragilis (D. fragilis) is an intestinal protozoan parasite with uncertain pathogenic potential. In the United States, data on D. fragilis in the era of molecular detection are limited. The aim of this retrospective chart review was to evaluate the epidemiology and clinical characteristics of D. fragilis cases identified using polymerase chain reaction assays between 2016 and 2024 at our academic medical centre located in Utah. We identified 28 unique cases with varying gastrointestinal symptomatology including diarrhoea, abdominal pain, nausea, vomiting, and bloating. Approximately half (52%) of patients with follow-up data demonstrated improvement in symptoms following initial treatment for D. fragilis. The overall prevalence of D. fragilis was low among those tested (0.6% positivity). Additional research, including case-control studies, is needed to better describe the etiologic role of D. fragilis.
Wetlands in hypersaline environments are especially vulnerable to loss and degradation, as increasing coastal urbanization and climate change rapidly exacerbate freshwater supply stressors. Hypersaline wetlands pose unique management challenges that require innovative restoration perspectives and approaches that consider complex local and regional socioecological dynamics. In part, this challenge stems from multiple co-occurring stressors and anthropogenic alterations, including estuary mouth closure and freshwater diversions at the catchment scale. In this article, we discuss challenges and opportunities in the restoration of hypersaline coastal wetland systems, including management of freshwater inflow, shoreline modification, the occurrence of concurrent or sequential stressors, and the knowledge and values of stakeholders and Indigenous peoples. Areas needing additional research and integration into practice are described, and paths forward in adaptive management are discussed. There is a broad need for actionable research on adaptively managing hypersaline wetlands, where outputs will enhance the sustainability and effectiveness of future restoration efforts. Applying a collaborative approach that integrates best practices across a diversity of socio-ecological settings will have global benefits for the effective management of hypersaline coastal wetlands.
Coastal wetlands are hotspots of carbon sequestration, and their conservation and restoration can help to mitigate climate change. However, there remains uncertainty on when and where coastal wetland restoration can most effectively act as natural climate solutions (NCS). Here, we synthesize current understanding to illustrate the requirements for coastal wetland restoration to benefit climate, and discuss potential paths forward that address key uncertainties impeding implementation. To be effective as NCS, coastal wetland restoration projects will accrue climate cooling benefits that would not occur without management action (additionality), will be implementable (feasibility) and will persist over management-relevant timeframes (permanence). Several issues add uncertainty to understanding if these minimum requirements are met. First, coastal wetlands serve as both a landscape source and sink of carbon for other habitats, increasing uncertainty in additionality. Second, coastal wetlands can potentially migrate outside of project footprints as they respond to sea-level rise, increasing uncertainty in permanence. To address these first two issues, a system-wide approach may be necessary, rather than basing cooling benefits only on changes that occur within project boundaries. Third, the need for NCS to function over management-relevant decadal timescales means methane responses may be necessary to include in coastal wetland restoration planning and monitoring. Finally, there is uncertainty on how much data are required to justify restoration action. We summarize the minimum data required to make a binary decision on whether there is a net cooling benefit from a management action, noting that these data are more readily available than the data required to quantify the magnitude of cooling benefits for carbon crediting purposes. By reducing uncertainty, coastal wetland restoration can be implemented at the scale required to significantly contribute to addressing the current climate crisis.
Despite the growing availability of sensing and data in general, we remain unable to fully characterize many in-service engineering systems and structures from a purely data-driven approach. The vast data and resources available to capture human activity are unmatched in our engineered world, and, even in cases where data could be referred to as “big,” they will rarely hold information across operational windows or life spans. This paper pursues the combination of machine learning technology and physics-based reasoning to enhance our ability to make predictive models with limited data. By explicitly linking the physics-based view of stochastic processes with a data-based regression approach, a derivation path for a spectrum of possible Gaussian process models is introduced and used to highlight how and where different levels of expert knowledge of a system is likely best exploited. Each of the models highlighted in the spectrum have been explored in different ways across communities; novel examples in a structural assessment context here demonstrate how these approaches can significantly reduce reliance on expensive data collection. The increased interpretability of the models shown is another important consideration and benefit in this context.
Effective supply chain management is a critical pillar of well-functioning health systems ensuring that medical commodities reach those in need. In Liberia, the national neglected tropical disease (NTD) programme supports health systems strengthening for case management of NTDs. Integration of NTD commodities into the national health system supply chain is central to the integrated approach; however, there is minimal evidence on enablers and barriers. Drawing on qualitative evaluation data, we illustrate that perceived benefits and strengths to integrating NTD commodities into the supply chain include leveraged storage and management capacities capitalized at lower system levels; the political will to integrate based on cost-saving and capacity strengthening potential and positive progress integrating paper-based reporting tools. Challenges remain, specifically the risk of reliance on donor funding; difficulty in accessing commodities due to bureaucratic bottlenecks; lack of inclusion of NTD commodities within electronic data tools and poor coordination leading to an inability to meet demand. Collectively, the negative consequences of ineffective integration of NTD commodities into the supply chain has a detrimental impact on health workers (including community health workers) unable to deliver the quality of care to patients. Trust between affected populations and the health system is compromised when treatments are unavailable.
Treatments for MDD that can improve both overall depressive and anhedonic symptoms are urgently needed.
AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity being developed for MDD. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.
Objective
To evaluate the effect of AXS-05 in improving anhedonic symptoms in MDD.
Methods
GEMINI (N=327) was a randomized, double-blind, placebo-controlled, 6-week study, which randomized adults with MDD to AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) or placebo, twice daily. The primary endpoint was change from baseline in the MADRS total score at Week 6. A post-hoc analysis was conducted to determine the impact of AXS-05 versus placebo on the 5-item MADRS anhedonia subscale (MAS).
Results
Baseline MAS scores were 19.8 and 19.6 in the AXS-05 and placebo group, respectively. At Week 1, AXS-05 treatment resulted in a significant mean reduction from baseline in the MAS score of 4.44 versus 2.69 points for placebo (p< 0.001). At Week 6, the mean reduction from baseline in the MAS was 9.70 for AXS-05 compared to 7.22 for placebo (p=0.001). Response rates (≥ 50% MAS improvement) were significantly greater for AXS-05 compared to placebo at Week 1 (p< 0.001) and at every time point thereafter.
Treatment with AXS-05 was generally safe and well tolerated. The most common adverse events being dizziness, nausea, headache, diarrhea, somnolence, and dry mouth.
Conclusions
Treatment with AXS-05 rapidly and significantly reduced anhedonic symptoms as well as overall depressive symptoms.
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.
Method
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.
Result
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.
Conclusion
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Close binary evolution is widely invoked to explain the formation of axisymmetric planetary nebulae, after a brief common envelope phase. The evolution of the primary would be interrupted abruptly, its still quite massive envelope being fully ejected to form the PN, which should be more massive than a planetary nebula coming from the same star, were it single. We test this hypothesis by investigating the ionised and molecular masses of a sample consisting of 21 post-common-envelope planetary nebulae, roughly one fifth of their known total population, and comparing them to a large sample of regular planetary nebulae (not known to host close-binaries). We find that post-common-envelope planetary nebulae arising from single-degenerate systems are, on average, neither more nor less massive than regular planetary nebulae, whereas post-common-envelope planetary nebulae arising from double-degenerate systems are considerably more massive, and show substantially larger linear momenta and kinetic energy than the rest. Reconstruction of the common envelope of four objects further suggests that the mass of single-degenerate nebulae actually amounts to a very small fraction of the envelope of their progenitor stars. This leads to the uncomfortable question of where the rest of the envelope is, raising serious doubts on our understanding of these intriguing objects.
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.
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.
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.
LEARNING OBJECTIVES
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.
Method
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.
Results
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.
Conclusions
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.
Method
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.
Results
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.
Conclusions
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.