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    Treatment as usual psychological therapy for complex post‐traumatic stress disorder in National Health Services in Scotland

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    Objectives: With Complex Post Traumatic Stress Disorder (CPTSD) as a new diagnostic category, there is a diversity of interventions and influences on clinical practice, it is prudent that we gather information about current ‘treatment as usual’. This study aims to address this need by describing the current clinical landscape of CPTSD treatments offered in NHS services in Scotland. Methods: An online survey was distributed via heads of service managers to clinicians working with adults. The survey posed questions about psychological therapy models, professional experience and, for the clinicians' latest 3 discharged cases, the length of therapy and perceived patient outcomes. Results: Forty‐nine clinicians, most of whom were clinical psychologists, took part and provided data about 139 clinical cases. Twenty‐three different therapeutic models were cited by clinicians, with phase‐based approaches described by 64% of clinicians. The modal number of sessions was 21–30. Most cases were described as completed, with 28% ending before therapy was completed, and a further 7% dropped out. Of those who completed therapy, 86% were judged to have improved after therapy, with 11% judged to have deteriorated. Conclusions: There is a wide variety of treatments available for complex PTSD, and innovative interventions and trials are required to support future clinical decision‐making about the optimal treatment components and therapy length

    Delphi consensus guidelines for the use of striatal dopaminergic imaging and cardiac metaiodobenzylguanidine (MIBG) scintigraphy for the diagnosis of dementia and mild cognitive impairment with Lewy bodies

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    INTRODUCTION The aim of this Delphi process was to develop consensus guidelines to support the effective use of striatal dopaminergic imaging and cardiac metaiodobenzylguanidine (MIBG) scintigraphy in the diagnosis of dementia with Lewy bodies and mild cognitive impairment with Lewy bodies. METHODS A Delphi consensus panel of 37 international experts independently indicated their agreement or disagreement with statements on indications for the use of these biomarkers and clinical situations in which each biomarker should and should not be used. Statements were accepted if they reached > 80% agreement. RESULTS Overall, 36/70 statements (51%) were accepted in Round 1, and 19/37 (51%) were accepted in Round 2. DISCUSSION The Delphi consensus process has developed freely available guidelines outlining clinical situations in which striatal dopaminergic imaging and cardiac MIBG scintigraphy may be useful and considerations for their use, including the effect of specific comorbidities and medications on each of the biomarkers

    Dynamic real-time control for a multi-energy prosumer with electricity and heat

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    Multi-energy prosumers have emerged as a promising avenue for curtailing energy consumption by integrating diverse energy vectors in a synchronised operation. Prevailing investigations have predominantly focused on static analyses directed at optimising cost functions for power dispatch problems, often overlooking the dynamic facets of the system. This paper introduces a dynamic real-time control scheme for a multi-energy prosumer encompassing electricity and heat as energy vectors. A novel state-based energy management system (EMS) is designed, with the goal of ensuring energy balance (electrical and thermal), while prioritising the utilization of renewable energy and diminishing reliance on local electrical distribution networks. To this end, three different operating modes are defined regarding the real-time renewable capacity. The EMS and multi-energy prosumer are subjected to evaluation across several weather conditions in a 4-h variable load profile. A sensibility analysis considering 250 simulations of 1-h duration, with a wide range of irradiance, water demand, underfloor heating load, and state-of-charge conditions were used to validate the control response, demonstrating the lack of use of the local grid. Moreover, a real-time experiment employing hardware-in-the-loop testing with an OPAL-RT4512 unit and a dSPACE MicroLabBox control prototype confirms the adequate response in a practical scenario. Comparative validation against a fuzzy-logic benchmark throughout a 24-h dynamic horizon revealed that the proposed state-based EMS reduced grid dependency by 36.61% and auxiliary gas boiler by 2.23%. Furthermore, the architecture achieved a 30-fold reduction in computational time while maintaining negligible control errors, establishing its superior suitability for real-time implementation in prosumers environments

    What big eyes you have! Well, until 500 m, that is

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    Reevaluating the nutrient timeline: Francevillian basin geochemistry reveals early permissive conditions for eukaryotic life

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    Environmental thresholds of oxygen and nutrients have played a pivotal role in shaping the timing and nature of major biological transitions throughout Earth’s history. Limited marine phosphate availability is thought to have constrained the tempo and trajectory of early eukaryotic evolution. A sustained global rise in marine P and trace metal nutrient availability, reaching near-modern levels, coincided with the Neoproterozoic Oxidation Event (NOE) and the emergence and radiation of Ediacaran and Cambrian animal lineages. Here, we present new geochemical evidence from the 2.1-billion-year-old (Ga) Francevillian Basin that reveals a striking exception to this timeline. Our data indicate that Paleoproterozoic seawater in the Francevillian Basin episodically reached nutrient and oxygen levels comparable to, and in the case of phosphate and zinc, potentially exceeded concentrations associated with the seawater in which the Cambrian biota of Burgess Shale emerged. The data suggest that permissible key chemical conditions for complex life existed in the Francevillian sea long before the Ediacaran–Cambrian nutrient surge. The coincidence of this anomalous Paleoproterozoic nutrient-rich window with the earliest known marine experimentation at macrobiological complexity, represented by the much-debated 2.1 Ga Francevillian macrobiota, challenges established timelines of biological innovation and environmental prerequisites

    Nucleoside analogue with thymidine nucleobase inhibits Leishmania infantum and depolarizes the plasma membrane potential in vitro

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    Visceral leishmaniasis, caused by the protozoan parasites Leishmania infantum or L. donovani, remains a lethal neglected tropical disease without effective therapy. Current drugs available are toxic, leading to severe side effects, treatment abandonment, and resistance, underscoring the urgent need for new therapeutic options. As Leishmania spp. are auxotrophic for purines, they rely on the purine salvage pathway for their nucleotide biosynthesis. Consequently, nucleoside analogues (NAs) represent a promising class of compounds for the design of antiparasitic agents. This study aimed to investigate the in vitro antileishmanial activity of NA compounds and the cellular alterations induced by treatment. Twelve NA compounds were screened for antileishmanial activity against promastigote and amastigote forms of L. infantum and cytotoxic effects in mammalian cells. Among all compounds evaluated, six of them demonstrated antipromastigote activity, exhibiting 50% effective concentration (EC50) values ranging from 9.29 to 76.74 μM. As for amastigote activity, two compounds, 5 and 10, were effective, with values of EC50 of 8.02 and 31.95 μM, respectively. Only compound 1 maintained cellular viability at the maximum concentration tested (>200 μM). The selective index for the derivatives investigated ranges from 0.5 to 4.2. Compound 5, a tritylated thymidine NA, the most active, was further subjected to analysis of cellular alterations using fluorescent-based approaches. This analogue demonstrated a lack of cytotoxicity against murine peritoneal macrophages up to 50 μM and nonhemolytic activity up to 100 μM. When applied at EC50, it did not cause damage to plasma membrane permeability, the integrity of the genetic material, acidocalcisomes, intracellular Ca2+, and ROS levels of treated Leishmania parasites. However, it caused depolarization of the plasma membrane potential, leading to cell death. Further studies are also necessary to understand the enzymatic action of this most active compound, and optimization is required to develop more effective and safer antileishmanial lead compounds. In conclusion, compound 5 might be a suitable candidate for the development of antileishmanial agents

    From mountain range to flat plateau in the Qiangtang Block (western China): Insights from low-temperature thermochronology

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    The Tibetan Plateau is currently undergoing lateral extrusion and expansion, but it remains unclear whether such orogen-parallel growth occurred during the plateau’s early uplift. Additionally, it is uncertain how this process developed after the formation of the proto-Tibetan Plateau. Constraining both these processes will help improve our understanding of the plateau’s uplift history and mechanisms of formation. This study focuses on the Qiangtang terrane of western China, the core of the proto-Tibetan Plateau, and integrates new low-temperature thermochronological data from Eocene granites with published datasets to reconstruct the uplift history from the perspective of spatiotemporal exhumation patterns. Results reveal that prior to 40−35 Ma, the Qiangtang Plateau experienced not only orogen-perpendicular growth but also east−west-trending expansion. Following establishment of this proto-Tibetan Plateau, localized exhumation persisted in northern Qiangtang. Based on the correlation between apparent exhumation rates and fault activity, geomorphic indices, precipitation, and magmatism, we suggest that compressive thickening was the primary mechanism governing the initial uplift, while crustal channel flow drove the northeastward expansion of the Qiangtang Plateau. Conversely, extensional lithospheric thinning and climate-related erosion processes may have only played a role in localized regions. This study reconstructs the uplift history of the Qiangtang Plateau, from its initial formation as a mountain range to a flat plateau. The findings confirm that lateral growth was likely prevalent during the early stage of uplift and provide thermochronological evidence supporting the topographic transition driven by crustal melting

    Discourses of inclusive and exclusionary health communication: Healthcare, language, and inclusivity

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    As the first of two companion volumes, this book provides a comprehensive collection of applied linguistics studies on health inclusivity, showcasing empirical research and methodological insights on different languages such as British Sign Language, Chinese, Danish, English, German, Japanese, and Spanish. The volume presents studies on health inclusivity based on first-hand patient experiences and explores the representation of health and illness across scientific, institutional, and media discourses. It features a wide range of linguistic methodologies and frameworks such as qualitative discourse studies, corpus-based discourse analysis, sociolinguistics, public involvement, narrative analysis, and metaphor analysis, as applied to a variety of contexts and communities. Integrating examples of projects and campaigns that promote inclusive healthcare, the chapters discuss potential practical implications and offer recommendations for applications to Equality, Diversity, and Inclusion (EDI). This is an essential resource for academics working in linguistics and discourse studies applied to healthcare, as well as students seeking deeper insights into how health communication, sociology, and health and social care workers can inform institutional practices and shape policy discussions, and broaden social perspectives of health inclusivity across a global scale

    Hidden threats: exploring biofilm communities in broiler houses and pig nursery units drinking water lines

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    Background Drinking water systems (DWS) are often an overlooked source of microbial contamination of drinking water in broiler and piglet production. Persistent biofilms within water lines can act as reservoirs of contamination, reintroducing microorganisms into the flowing water and potentially compromising animal health. This study investigates the microbial composition of biofilms in the DWS of broiler houses and pig nursery units, their impact on drinking water quality, and the influence of the source water on both water quality and biofilm communities. Results The bacterial load of DWS biofilm swabs, collected at the end of production cycles before cleaning and disinfection was evaluated, and the dominant bacterial taxa were identified. Furthermore, 16S gene metabarcoding was applied to the biofilm samples. No significant differences in microbial load were observed between the two sectors, with a median total aerobic count of 3.6 log CFU/cm2. Enterococci, a faecal indicator, were detected in 80% of all samples. Moreover, Escherichia coli was found more frequently in broiler houses (47%) than in pig nursery units (27%). The two dominant identified genera were Staphylococcus and Pseudomonas. The Staphylococcus saprophyticus species was the most frequently identified isolate, accounting for 10.6% of all isolates across both broiler houses and pig nursery units. In broiler houses, the next most frequently identified species were Pseudomonas aeruginosa (5.6%) and Stenotrophomonas maltophilia (5.3%). In contrast, in pig nursery units, Pseudomonas fluorescens (6.3%) and Psychrobacter faecalis/pulmonis (5.5%) were most frequently identified. Research showed that the drinking water microbial community not only depended on the source water but was also influenced by biofilms in DWS, as similar bacterial taxa were found in both the drinking water at the drinking nipples and in biofilms on water-contact surfaces. Conclusions The presence of faecal indicator bacteria and potential animal pathogens underscores the risks associated with the biofilms. These biofilms can contaminate drinking water to animals, underscoring the need for targeted strategies to monitor and mitigate biofilm formation

    Clinical trial simulation: planning with the OCTAVE framework, implementation and validation principles

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    The adoption of complex innovative clinical trial designs has steadily increased in recent years. These are trial designs that have one or more unconventional features—often resulting in multiple stages—with the goal of improving on conventional single-stage, fixed-setting designs in terms of efficiency, for example, by reducing the required sample size or the time to establish findings about an intervention. The motivation for these designs may not be difficult to follow, but their set-up and implementation is usually more challenging. Statistical properties of these designs can also be difficult to compute. Clinical trial simulation (CTS), which uses software to generate artificial data for learning, can be conducted to identify the (optimal) setting of a clinical trial, evaluate the design's statistical properties under some hypothetical scenarios for sensitivity analysis, and compare different design set-ups and data analysis strategies, all of which contribute to a better understanding of the value of unconventional features before implementing the design in an actual clinical trial. Existing literature on simulation primarily focuses on the evaluation of statistical analysis methods, with less attention on the detailed specification and planning of CTS. This tutorial presents a new framework, called OCTAVE, for outlining the details of CTS, provides practical recommendations for their implementation, and addresses key computational considerations. The target audience is trial statisticians who are involved in designing and analyzing clinical trials. This tutorial covers a range of complex innovative designs, without the expectation that readers are familiar with the mentioned examples

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