Search

Background: The recent wave of clinical trials of psychedelic substances among patients with life-limiting illness has largely focused on individual healing. This most often translates to a single patient receiving an intervention with researchers guiding them. As social isolation and lack of connection are major drivers of current mental health crises and group work is expected to be an important aspect of psychedelic assisted psychotherapy, it is essential that we understand the role of community in psychedelic healing., Objectives: To explore how psychedelic guides in the United States discuss the role of "community" in naturalistic psychedelic groups., Methods: This is a secondary qualitative data study of data from a larger modified ethnographic study of psychedelic plant medicine use in the US. Fifteen facilitators of naturalistic psychedelic groups were recruited via snowball sampling. Content analysis was used to identify themes., Results: Participants viewed the concept of community as essential to every aspect of psychedelic work, from the motivation to use psychedelics, to the psychedelic dosing experience and the integration of lessons learned during psychedelic experiences into everyday life. Themes and subthemes were identified. Theme 1 : The arc of healing through community ( Subthemes : Community as intention, the group psychedelic journey experience, community and integration); Theme 2 : Naturally occurring psychedelic communities as group therapy ( Subthemes [as described in Table 2] : Belonging, authenticity, corrective experience, trust, touch)., Significance: Results suggest that existing knowledge about therapeutic group processes may be helpful in structuring and optimizing group psychedelic work. More research is needed on how to leverage the benefit of community connection in the therapeutic psychedelic context, including size and composition of groups, selection and dosing of psychedelic substances in group settings, facilitator training, and role of community integration. Psychedelic groups may provide benefits that individual work does not support.

As the demand for lithium-ion batteries (LIBs) continues to increase, there is a growing focus on recycling these battery wastes. Among the existing recycling methods, direct recycling is considered a promising approach, because it allows waste to be returned directly to production. One crucial step in this process is the pretreatment, which involves separating the active materials from the current collector. Thermal treatment provides a feasible and effective approach for achieving this separation. Nonetheless, concerns persist regarding the potential impacts of this process on the structure. This study aims to examine the effects of thermal treatment on the separation efficiency and crystal structure of fresh and cycled NMC (LiNi 0.6 Co 0.2 Mn 0.2 O 2 ) cathodes and graphitic anodes, under various atmospheres and temperatures. The results reveal that an air/oxygen atmosphere facilitates complete separation of cathode materials from aluminum with minimal structural degradation and at lower temperatures compared to other atmospheres. For graphite, thermal treatment under argon, nitrogen and hydrogen demonstrates good structural stability. However, for cycled anodes, the desired separation is not achieved due to the possible interface adhesion that occurs during cycling and heating. Additionally, compared to fresh materials, cycled materials experience more pronounced structural degradation during thermal treatment., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Introduction: The cognitive side-effects of medication are common, but often overlooked in practice, and not routinely considered in interventional trials or post-market surveillance. The cognitive footprint of a medication seeks to quantify the impact of its cognitive effects based on magnitude, duration, and interaction with other factors, evaluated across the exposed population., Methods: Bayesian multivariable regression analysis of retrospective population-based cross-sectional cohorts., Results: We replicate positive and negative cognitive effects of commonly used medications in UK Biobank, and extend observed associations to two additional cohorts, the EPIC Norfolk, and the Caerphilly Prospective Cohort. We quantify the resultant cumulative impact at the population level given known patterns of prescribing and compare it with exemplar common diseases., Conclusion: The cognitive side-effects of commonly used drugs may have significant impact at the population level. Consideration should be given to a routine structured assessment of cognition in interventional trials and post-market surveillance., (© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Anaplastic lymphoma kinase (ALK)-positive histiocytosis has emerged as a clinically relevant diagnosis featuring a wide span of clinical presentations, which are unified by the presence of ALK-positive histiocytes on histopathology and molecular drivers involving the ALK kinase gene. This report presents an adult case of multisystem ALK-positive histiocytosis with xanthogranuloma-like features on histopathology that was responsive to ALK inhibition, and includes a review of ALK-positive histiocytoses with cutaneous involvement reported in the literature. A 56-year-old male developed a widespread eruption of red-brown papules on the face, trunk, and upper extremities. Histopathological evaluation revealed a well-circumscribed, nodular dermal infiltrate of epithelioid histiocytes with Touton giant cells, rare bizarre multinucleated cells, and focal emperipolesis. The lesional cells were positive for CD68 and ALK1 immunohistochemical stains, and negative for CD1a. Next-generation sequencing identified a DCTN1::ALK fusion. On imaging, he was found to have bone, lung, soft tissue, and salivary gland involvement. ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow-up. This case adds to the spectrum of ALK-positive histiocytoses and further demonstrates the positive response with targeted therapy., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Endurance exercise training (ET) is an effective treatment in heart failure with preserved ejection fraction (HFpEF), but the efficacy of resistance training in this patient population has been only scarcely evaluated. In this multicenter, randomized trial, we evaluated the effects of combined endurance and resistance training over 12 months in patients with HFpEF. The primary endpoint was a modified Packer score, including all-cause mortality, hospitalizations classified as potentially related to heart failure or exercise and changes in peak oxygen consumption ( V ̇ O 2 ), diastolic function (E/e'), New York Heart Association (NYHA) class and global self-assessment (GSA). In total, 322 patients (mean age, 70 years; 192 females (59.6%) and 130 males (40.4%)) were randomized (1:1) to ET or usual care (UC). At 12 months, the modified Packer score showed an improvement in 33 ET patients (20.5%) and in 13 UC patients (8.1%) and showed a worsening in 69 ET patients (42.9%) and in 71 UC patients (44.1%) (Kendall's tau-b = -0.073, P = 0.17). Although the primary endpoint was not met, clinically relevant differences favoring the ET group as compared to the UC group were observed for the following secondary endpoints: changes in peak V ̇ O 2 (mean difference, 1.3 ml kg -1  min -1 (95% confidence interval (CI): 0.4-2.1)) and NYHA class (odds ratio = 7.77 (95% CI: 3.73-16.21)). No significant between-group differences were observed for other secondary endpoints, including change in E/e', change in GSA, time to cardiovascular hospitalization or all-cause mortality. In conclusion, 1 year of combined endurance and resistance ET did not result in a significantly better modified Packer score, but it did result in improvements in important clinical parameters, such as peak V ̇ O 2 and NYHA class, as compared to UC. ISRCTN registration: ISRCTN86879094 ., Competing Interests: Competing interests: F.E. reports personal fees from AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, CVRx, Medtronic, Merck, Merck Sharp & Dohme, Novartis, Pfizer, PharmaCosmos, Resmed, Servier and Vifor Pharma; non-financial support from Novartis; and grants from AstraZeneca, Boehringer Ingelheim, Servier and Thermo Fisher Scientific, outside the submitted work. R.W. reports receiving personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, CVRx, Daiichi Sankyo, Medtronic, Novartis, Pfizer, Pharmacosmos and Servier and research support from Boehringer Ingelheim, Bundesministerium für Bildung und Forschung, Deutsche Forschungsgemeinschaft, the European Union and Medtronic, outside the submitted work. S.M. reports personal fees from Bristol Myers Squibb (consulting services), outside the submitted work. E.P.-K. holds minor shares in ICTS GmbH (Imaging in Clinical Trials Services) and is a part-time employee of this company and reports receiving minor personal fees from AstraZeneca. H.-D.D. reports receiving personal fees from Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Merck, Merck Sharp & Dohme, Novartis and Servier, outside the submitted work. H.-D.D. also holds shares in SCIRENT GmbH and d.o.o. (Clinical Trials Services). C.H.-L. reports a personal fee from Novartis; royalties from Hogrefe Publishing Group; and research grants from the German Ministry of Education and Research, the German Research Foundation and the EU Commission. K.E. reports personal fees from Bristol Myers Squibb and Boehringer Ingelheim (honoraria for lectures), outside the submitted work. A.H. reports personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimensions, Daiichi Sankyo, GE Healthcare and Novartis. G.H. reports personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Corvia, Impulse Dynamics, Novartis, Servier and Vifor Pharma; being a co-principal investigator for Impulse Dynamics; and business ownership of Avocet Bio GmbH. B.P. reports institutional grants from AstraZeneca, Bayer Healthcare and Boston Scientific and personal fees for steering committee, consulting and speaker services from Bayer Healthcare, Merck Sharp & Dohme, AstraZeneca, Boehringer Ingelheim, Novartis, Boston Scientific and Abbott, outside the submitted work. B.P. also holds minor shares in ICTS GmbH (Imaging in Clinical Trials Services). M.H. reports receiving personal fees from Abbott, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Sanofi-Aventis, Novartis and Medical Park (consulting fees and honoraria for lectures) and being the past president of the European Association of Preventive Cardiology (2020–2022), outside the submitted work. No other potential conflicts of interest were reported. Additional collaborators: Stephan Gielen, Stephan von Haehling, Stefan Störk, Tobias D. Trippel, Stefan Anker, Hugo Saner, Mitja Lainscak, Andrea Berghold, Daniel Morris, Evgeny Belyavski, Martin Kropf and Aravind Kumar Radhakrishnan., (© 2025. The Author(s).)

Background and aims: Lower Extremity Artery Disease (LEAD) is a predictor of atherosclerotic plaques in other locations and significantly increases the risk of death from cardiovascular events. This study aimed to identify cardiology patient subpopulations that should undergo Ankle-Brachial Index (ABI) measurement. Methods: A total of 800 patients hospitalized in the Department of Cardiology were included. Inclusion criteria were age over 40 years for men and over 45 years for women, with the ability to measure ABI. Results: The study group was divided into two subgroups based on ABI values, with LEAD (ABI ≤ 0.9) detected in 61 patients (7.6%). Among these, 45% exhibited symptoms of intermittent claudication. LEAD was significantly more common in patients with a lower ejection fraction, a history of myocardial infarction, coronary artery disease, coronary atherosclerosis, heart failure, hypercholesterolemia, diabetes, and in those with a past diagnosis of atherosclerosis. There was no statistical association with the incidence of ischemic stroke, renal failure, hypertension or a family history of cardiovascular disease. Average living conditions and financial status increased LEAD likelihood ( p = 0.029; p = 0.018), while physical activity reduced it ( p < 0.001). LEAD occurred more often in both current and former smokers. Patients with LEAD were more likely to be on statin therapy ( p = 0.002). Higher hemoglobin A1c levels significantly increased the risk of LEAD. Conclusions: Identifying patients with risk factors for LEAD suggests that ABI measurement should be performed to detect LEAD early and implement appropriate diagnostic and therapeutic strategies.

Background and Objectives: Older people with memory problems living in temporary hostel accommodation have longer stays and higher care needs than those without memory problems. In this ethnographic study, we aimed to elucidate how staff currently support older hostel residents with memory problems, what contextual factors determine support given and, what facilitates positive and meaningful outcomes for staff and residents., Research Design and Methods: We conducted interviews and participant observations with older people (≥50 years) experiencing memory problems and homelessness (interviews n=17, observations n=13), hostel staff and managers (interviews n=15, observations n=20) from seven residential facilities (six hostels and one care home), and health and social care practitioners (interviews n=17, observations n=7), from September 2021-December 2022 in London, England. We analyzed thematically from a critical realist position., Results: We identified four overarching themes: (1) Compensatory strategies and routines, (2) hostels are not homes, (3) meeting challenging interactions with compassion, and (4) facilitating opportunities for meaningful interactions. Social interactions for people with memory problems were restricted and, although sheltered by living in hostels, this did not equate to safety or provide opportunities for positive interactions., Discussion and Implications: Staff worked hard to connect with older residents with memory problems, in resource and time-poor contexts, often left to provide care beyond their roles in contexts of unmet need. Our ethnographic account has informed co-design of a support intervention for hostel staff working with older people with memory problems, alongside recommendations for policy and practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Gerontological Society of America.)

Introduction: Depression and anxiety are common in dementia, with a devastating impact. However, there remains a lack of evidence-based psychological therapies for this clinical group. Compassion-focused therapy (CFT), a talking therapy which addresses feelings of shame and stigma, has shown benefits in other clinical populations. This study is a mixed-methods feasibility randomised controlled trial (RCT) of group CFT for people with dementia and symptoms of anxiety and/or depression, to determine if a future definitive RCT is feasible., Methods and Analysis: 50 people with mild-to-moderate dementia and symptoms of anxiety and/or depression will be randomised to either the intervention arm (12 sessions of group CFT plus treatment as usual (TAU)) or the control arm (TAU). Primary outcome measures include the feasibility of conducting an RCT in terms of recruitment, acceptability, suitability of secondary outcome measures and fidelity. Blind assessments will be conducted at baseline, approximately 16 weeks and 6 months follow-up, to collect data on depression, anxiety, quality of life, quality of the carer-patient relationship, cognition, self-compassion and carer burden. Qualitative interviews will be used to gather participant, carer/supporter and clinician perspectives on the value, acceptability and feasibility of the intervention., Ethics and Dissemination: This study has been approved by the London Riverside REC (Ref: 23/LO/0535) and the Health Research Authority (HRA) ethical approval process through the Integrated Research Application System (IRAS ID: 327086). We plan to publish the results in open-access peer-reviewed journals, present data at conferences and provide feedback to the study participants, sponsors and funders., Trial Registration Number: ISRCTN20868432., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Early childhood socioeconomic disadvantage and mental health problems are both important determinants of adult social and economic experiences, but little is known about how they interact in this respect. We aimed to assess whether poor mental health in adolescence exacerbates labour market inequalities originating from low socioeconomic status (SES) in childhood. We use a birth cohort of individuals born in 1958 in England and follow their employment experiences and cumulative earnings up to age 55. We proxy low SES in childhood with father's occupational class at the time the respondent was aged 11, and use caregiver (usually, parent) ratings of the Rutter inventory at age 16 to identify mental health problems in adolescence. We fit ordinary least squares (OLS) models to estimate the effect of growing up in a low-SES family and experiencing mental health problems (conduct or emotional problems) in adolescence on cumulative earnings (log-transformed). We use an interaction term to test whether the association between mental health problems (conduct and emotional separately) and earnings differed by socioeconomic group. Individuals who experienced conduct problems in adolescence had lower cumulative earnings and employment levels up to age of 55. Moreover, the association between mental health problems and cumulative earnings was higher among individuals who also experienced low SES in childhood. Families from a higher socioeconomic group may have more effective means to counteract the adverse impacts of adolescent mental health problems, likely due to broader access to resources, support systems and opportunities. This underscores the role of structural supports in addressing socioeconomic inequalities in mental health outcomes and their long-terms implications., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Early detection of dementia enables more effective planning and can enable access to treatment and support. The Mini-Cog is a widely used screening instrument in Indonesia; however, this instrument has never undergone a translation and cultural adaptation process. Currently, there is no data on how accurate the tool is against diagnostic criteria, particularly in low-education., Methods: Embedded within the community-based dementia prevalence study was the Strengthening Responses to Dementia in Developing Countries (STRiDE) project; older adults (aged ≥ 65 years) were randomly recruited from sites in Jakarta and North Sumatra, Indonesia. All participants were asked to complete the Mini-Cog and the 10/66 short dementia diagnostic schedule. The accuracy of three Mini-Cog algorithms (Mini-Cog1, Mini-Cog2, and Mini-Cog3) were compared against and the 10/66 short dementia diagnostic schedule. Additional analysis explored its performance accuracy at different educational levels., Results: The Mini-Cog test performance assessment was conducted on 2098 older adults The area under the curve (AUC) of Mini-Cog1, Mini-Cog2, and Mini-Cog3 receiver operator characteristic (ROC) curves were 0.66, 0.62, and 0.64, respectively. All algorithms demonstrated high sensitivity (Sv) but low specificity (Sp). (Mini-Cog1: Sv 83.2%; Sp 49.2%, Mini-Cog2: Sv 87.1%; Sp 37.8% and Mini-Cog3: Sv 72.5%; Sp 56%). All algorithms showed no affected by education. Only 59.1% of people without dementia could do the CDT., Conclusions: The high sensitivity of the Mini-Cog1 algorithm lends itself to screening purposes. Given that the specificity is still low, and less than 60% of patients without dementia can complete the CDT. Further research is needed, as is the development of screening instruments with high accuracy values in low- and middle-income countries, particularly in Indonesia., (© 2024 John Wiley & Sons Ltd.)

Background: While medical costs of chickenpox have been researched, little is known about indirect costs. Understanding total costs is important for decisions about vaccination. This study estimated the value of lost productivity of adults missing work to care for children with chickenpox., Research Design and Methods: It comprised an international literature review, an online survey of 1,526 parents of children aged 1-11 years, and computation of indirect costs of chickenpox in the UK. The survey covered chickenpox episodes amongst respondents' children, time children took off school/nursery, and work absenteeism by parents/caregivers caring for them., Results: Respondents reported on 2,283 children, of whom 52% (1185/2283) experienced chickenpox. Almost half (591/1185) missed days of school/nursery, averaging 5.6 days missed. In 260 cases of 542 adults providing data with such a child, an adult missed work to care for the child. The daily value of this lost productivity was £170. There were approximately 200,000 GP consultations for chickenpox and 625,000 births annually, suggesting the annual chickenpox incidence lies between these figures. The estimated annual UK productivity loss due to chickenpox is £20-£70 million ($25-$90 million)., Conclusions: Annual value of lost productivity due to chickenpox is in range £20 to £70 million.

Chlorophyll (Chl) is one of Nature's most complex pigments to biosynthesize and derivatize. This pigment is vital for survival and also paradoxically toxic if overproduced or released from a protective protein scaffold. Therefore, along with the mass production of Chl, organisms also invest in mechanisms to control its degradation and recycling. One important enzyme that is involved in these latter processes is chlorophyllase. This enzyme is employed by numerous photosynthetic organisms to hydrolyze the phytol tail of Chl. Although traditionally thought to catalyze the first step of Chl degradation, recent work suggests that chlorophyllase is instead employed during times of abiotic stress or conditions that produce reactive oxygen species. However, the molecular details regarding how chlorophyllases are regulated to function under such conditions remain enigmatic. Here, we investigate the Arabidopsis thaliana chlorophyllase isoform At CLH2 using site-directed mutagenesis, mass spectrometry, dynamic light scattering, size-exclusion multiangle light scattering, and both steady-state enzyme kinetic and thermal stability measurements. Through these experiments, we show that At CLH2 exists as a monomer in solution and contains two disulfide bonds. One disulfide bond putatively maps to the active site, whereas the other links two N-terminal Cys residues together. These disulfide bonds are cleaved by chemical or chemical and protein-based reductants, respectively, and are integral to maintaining the activity, stability, and substrate scope of the enzyme. This work suggests that Cys residue oxidation in chlorophyllases is an emerging regulatory strategy for controlling the hydrolysis of Chl pigments., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The high-voltage oxygen redox activity of Li-rich layered oxides enables additional capacity beyond conventional transition metal (TM) redox contributions and drives the development of positive electrode active materials in secondary Li-based batteries. However, Li-rich layered oxides often face voltage decay during battery operation. In particular, although Li-rich positive electrode active materials with a high nickel content demonstrate improved voltage stability, they suffer from poor discharge capacity. Here, via physicochemical and electrochemical measurements, we investigate the correlation between oxygen redox activity and superstructure units in Li-rich layered oxides, specifically the fractions of LiMn 6 and Ni 4+ -stabilized LiNiMn 5 within the TM layer. We prove that an excess of LiNiMn 5 hinders the extraction/insertion of lithium ions during Li metal coin cell charging/discharging, resulting in incomplete oxygen redox activity at a cell potential of about 3.3 V. We also demonstrate that lithium content adjustment could be a beneficial approach to tailor the superstructure units. Indeed, we report an improved oxygen redox reversibility for an optimized Li-rich layered oxide with fewer LiNiMn 5 units., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Lynch syndrome (LS; HNPCC) patients carry heterozygous pathogenic germline variants in mismatch repair (MMR) genes, which have also been shown to play an important role in meiosis. Therefore, it was hypothesized, that LS might be associated with a higher risk for premature ovarian failure (POF) or earlier menopause. Data on medical gynaecological history, cancer diagnoses and therapy were collected from 167 female LS patients and compared to a population-based control cohort. There was no difference between the age of menopause in patients compared to controls and no evidence for a higher risk of POF in LS patients. However, around one third (35%) of the probands have already had premenopausal cancer and mostly cancer-related treatment affecting fertility before the age of 45 years. Therefore, childbearing time might still be limited in these patients, especially due to the premenopausal cancer risk. LS patients should be informed in time about the elevated premenopausal cancer risks and the possible impact on family planning. This is particularly relevant since the average childbearing age has increased during the last decades., (© 2024. The Author(s).)

Reactivation of BK polyomavirus (BKPyV) can cause significant kidney and bladder disease in immunocompromised patients. There are currently no effective, BKPyV-specific therapies. MAU868 is a novel, human immunoglobulin (Ig) G1 monoclonal antibody that binds the major capsid protein, VP1, of BKPyV with picomolar affinity, neutralizes infection by the 4 major BKPyV genotypes (EC 50 ranging from 0.009-0.093 μg/mL; EC 90 ranging from 0.102-4.160 μg/mL), and has comparable activity against variants with highly prevalent VP1 polymorphisms. No resistance-associated variants were identified in long-term selection studies, indicating a high in vitro barrier-to-resistance. The high-resolution crystal structure of MAU868 in complex with VP1 pentamer identified 3 key contact residues in VP1 (Y169, R170, and K172). A first-in-human study was conducted to assess the safety, tolerability, and pharmacokinetics of MAU868 following intravenous and subcutaneous administration to healthy adults in a randomized, placebo-controlled, double-blinded, single ascending dose design. MAU868 was safe and well-tolerated. All adverse events were grade 1 and resolved. The pharmacokinetics of MAU868 was typical of a human IgG, with dose-proportional systemic exposure and an elimination half-life ranging between 23 and 30 days. These results demonstrate the potential of MAU868 as a first-in-class therapeutic agent for the treatment or prevention of BKPyV disease., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. J. R. Abend, A. Sathe, M. B. Wrobel, M. Knapp, L. Xu, L. Zhao, P. Kim, S. Desai, A. Nguyen, X.-C. Leber, A. Hein, M. Scharenberg, J. Shaul, E. Ornelas, K. Wong, T. Pietzonka, P. Pertel, E. Traggiai, and S. J. Kovacs are or were employees of Novartis and shareholders of Novartis stock when the study was performed. L. M. Sterling was an employee of Celerion when the study was performed. MAU868 was discovered at Novartis Institutes for BioMedical Research and was then acquired by Amplyx Pharmaceuticals, Inc, which became a wholly owned subsidiary of Pfizer. MAU868 was most recently acquired and continues to be held by Vera Therapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Diarrhoeal disease caused by Cryptosporidium is a major cause of morbidity and mortality in young and malnourished children from low- and middle-income countries, with no vaccine or effective treatment. Here we describe the discovery of EDI048, a Cryptosporidium PI(4)K inhibitor, designed to be active at the infection site in the gastrointestinal tract and undergo rapid metabolism in the liver. By using mutational analysis and crystal structure, we show that EDI048 binds to highly conserved amino acid residues in the ATP-binding site. EDI048 is orally efficacious in an immunocompromised mouse model despite negligible circulating concentrations, thus demonstrating that gastrointestinal exposure is necessary and sufficient for efficacy. In neonatal calves, a clinical model of cryptosporidiosis, EDI048 treatment resulted in rapid resolution of diarrhoea and significant reduction in faecal oocyst shedding. Safety and pharmacological studies demonstrated predictable metabolism and low systemic exposure of EDI048, providing a substantial safety margin required for a paediatric indication. EDI048 is a promising clinical candidate for the treatment of life-threatening paediatric cryptosporidiosis., (© 2024. The Author(s).)

Objectives: To compare the experiences of people with dementia living alone or with others and how these may change over two years., Design: We analysed longitudinal data from three assessment waves, one year apart, in the British IDEAL cohort., Setting: Participants with mild-to-moderate dementia were recruited through National Health Service providers, where possible with a family caregiver, and interviewed at home., Participants: The current analyses include 281 people with dementia living alone and 1,244 living with others at baseline; follow-up data were available for 200 and 965 respectively at time 2 and 144 and 696 respectively at time 3. For those living alone, 140 nonresident caregivers contributed at baseline, 102 at time 2 and 81 at time 3. For those living with others, 1,127 family caregivers contributed at baseline, 876 at time 2 and 670 at time 3., Measurements: Assessments covered: cognitive and functional ability; self-reported perceptions of health, mood, social engagement, quality of life, satisfaction with life and well-being; use of in-home and community care; and transitions into residential care., Results: People living alone tended to have better cognitive and functional ability and were more frequent users of in-home care. However, they experienced poorer physical, social, and psychological health and reduced quality of life, satisfaction with life, and well-being. These differences persisted over time and rates of transition into residential care were higher., Conclusions: To facilitate continuing in place for people with dementia living alone, a dual focus on supporting functional ability and add ressing psychosocial needs is essential in the context of an enabling policy framework., Competing Interests: DISCLOSURES The authors declare no conflicts of interest. ‘Improving the experience of Dementia and Enhancing Active Life: living well with dementia. The IDEAL study’ was funded jointly by theEconomic and Social Research Council (ESRC)and theNational Institute for Health and Care Research (NIHR)through grantES/L001853/2. Investigators: L. Clare, I.R. Jones, C. Victor, J.V. Hindle, R.W. Jones, M. Knapp, M. Kopelman, R. Litherland, A. Martyr, F.E. Matthews, R.G. Morris, S.M. Nelis, J.A. Pickett, C. Quinn, J. Rusted, J. Thom. ESRC is part of UK Research and Innovation (UKRI). ‘Improving the experience of Dementia and Enhancing Active Life: a longitudinal perspective on living well with dementia. The IDEAL-2 study’ is funded by Alzheimer's Society, grant number 348, AS-PR2-16-001. Investigators: L. Clare, I.R. Jones, C. Victor, C. Ballard, A. Hillman, J.V. Hindle, J. Hughes, R.W. Jones, M. Knapp, R. Litherland, A. Martyr, F.E. Matthews, R.G. Morris, S.M. Nelis, C. Quinn, J. Rusted. This report is independent research supported by the National Institute for Health and Care Research Applied Research Collaboration South-West Peninsula. The views expressed in this publication are those of the authors and not necessarily those of the ESRC, UKRI, NIHR, the Department of Health and Social Care, the National Health Service, or Alzheimer's Society. The support of ESRC, NIHR and Alzheimer's Society is gratefully acknowledged., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

For people experiencing mental health problems, timely access to high-quality healthcare is imperative for improving outcomes. However, limited availability of services, high out-of-pocket costs, insufficient health literacy and stigmatizing attitudes may mean people do not receive the necessary treatment. We analyze Australian longitudinal data to document the extent and predictors of horizontal inequity in mental healthcare use among people with a newly developed mild or moderate mental disorder. Importantly, we compare people with similar health, residing in the same area, thus controlling for differences in healthcare needs and availability of services. Results suggest that mental healthcare use is not significantly associated with household income or financial hardship. In contrast, we find significant inequities by educational attainment, with university graduates around 50% more likely to receive mental healthcare than high-school dropouts. These findings are robust across subsamples and alternative modeling approaches, including panel data models with individual fixed-effects. Additional explorations of the education gradient suggest a potential pathway through mental health-specific knowledge and attitudes., (© 2024 John Wiley & Sons Ltd.)

Background: The delivery of high-quality services in chronically underfunded social or long-term care systems is a major challenge internationally. National guidelines, developed by the National Institute for Health and Care Excellence, set out how local authorities in England and Wales should fund and provide care based on best available evidence. Theoretical and participatory approaches can usefully inform the design and evaluation of implementation strategies for guidelines. The aim of the study is to develop a Theory-of-Change for how the implementation of these guidelines is expected to lead to impacts from a local authority perspective., Methods: As part of a comparative case study (The 'Valuing Care Guidelines' study; February 2022 to April 2024) with three local authority sites in England and Wales, we involved altogether 17 participants in two Theory-of-Change online workshops per site, each of 2 hours. Additional data gathered from the same participants as part of the overall study were used to conceptualise and enrich information from the workshops., Results: Participants described the Theory-of-Change map as follows: A wide range of activities (categorised in stages of 'pre-implementation', 'implementation', 'sustainment and scaling') and skills were required to implement guidelines, and achieve long-term organisational sustainability and service delivery outcomes, leading to final impacts for service users and carers. Participants described a co-creation implementation model, led by 'Implementation Support Practitioners', who utilised relational skills to achieve motivation, trust, and confidence at different organisational levels, addressing contextual barriers such as inadequate staffing, lack of resources and of organisational support systems. Consistent use of guidelines by frontline staff could only be achieved if the value of guideline implementation was promoted widely, and if consideration was given to the roles of stakeholders, such as the inspection body, local health care providers, users and carers., Conclusions: Our study is the first to investigate the implementation of national social care guidelines by local authorities in England and Wales. It generates insights that can guide implementation practice as well as inform the evaluation of future implementation strategies., (© 2024. The Author(s).)

Purpose. This study identified restaurant manager/owner factors that may contribute to adoption of a restaurant-based healthy eating program, Eat Fit. Findings may be used to engage restaurants in efforts to increase access to and availability of healthy foods, promote healthy food choices, and work toward improving diet and lowering obesity and chronic disease risk in the community. Methods . Cross-sectional survey data were collected from restaurant managers/owners interested in partnering with Eat Fit. Variables included restaurant manager/owner beliefs, perceived staff knowledge/skills, support, self-efficacy, outcome expectancies, and barriers and facilitators to implementation. Results . Forty-nine managers/owners participated. Most managers/owners held positive beliefs about offering healthy food items in restaurants (83.7%). Most agreed that restaurants could influence eating behaviors (83.7%) and that restaurants have a responsibility to offer healthy options (77.6%). Most managers/owners perceived high levels of support (83.7%) and were confident in their ability (95.9%) to implement the Eat Fit program. The most cited barriers were customer preference, ingredient availability, staff knowledge, and operational challenges. The most common reasons for involvement in the program were a desire to increase access to healthy food, to entice customers looking for healthier food, a belief that restaurants should offer healthy food, and opportunities to market through Eat Fit. Conclusions . This research contributes to knowledge about beliefs and perceptions of restaurant manager/owners. Efforts to engage restaurants should focus on benefits of offering healthy food and the role restaurants can play in promoting health. Furthermore, programs may benefit from enhanced restaurant staff training, customer-targeted marketing, and educational efforts.

The COVID-19 pandemic highlights the ongoing risk of zoonotic transmission of coronaviruses to global health. To prepare for future pandemics, it is essential to develop effective antivirals targeting a broad range of coronaviruses. Targeting the essential and clinically validated coronavirus main protease (M pro ), we constructed a structurally diverse M pro panel by clustering all known coronavirus sequences by M pro active site sequence similarity. Through screening, we identified a potent covalent inhibitor that engaged the catalytic cysteine of SARS-CoV-2 Mpro and used structure-based medicinal chemistry to develop compounds in the pyrazolopyrimidine sulfone series that exhibit submicromolar activity against multiple M pro homologues. Additionally, we solved the first X-ray cocrystal structure of M pro from the human-infecting OC43 coronavirus, providing insights into potency differences among compound-target pairs. Overall, the chemical compounds described in this study serve as starting points for the development of antivirals with broad-spectrum activity, enhancing our preparedness for emerging human-infecting coronaviruses.

Marine sponges have recently emerged as efficient natural environmental DNA (eDNA) samplers. The ability of sponges to accumulate eDNA provides an exciting opportunity to reconstruct contemporary communities and ecosystems with high temporal and spatial precision. However, the use of historical eDNA, trapped within the vast number of specimens stored in scientific collections, opens up the opportunity to begin to reconstruct the communities and ecosystems of the past. Here, we define the term 'heDNA' to denote the historical environmental DNA that can be obtained from the recent past with high spatial and temporal accuracy. Using a variety of Antarctic sponge specimens stored in an extensive marine invertebrate collection, we were able to recover information on Antarctic fish biodiversity from specimens up to 20 years old. We successfully recovered 64 fish heDNA signals from 27 sponge specimens. Alpha diversity measures did not differ among preservation methods, but sponges stored frozen had a significantly different fish community composition compared to those stored dry or in ethanol. Our results show that we were consistently and reliably able to extract the heDNA trapped within marine sponge specimens, thereby enabling the reconstruction and investigation of communities and ecosystems of the recent past with a spatial and temporal resolution previously unattainable. Future research into heDNA extraction from other preservation methods, as well as the impact of specimen age and collection method, will strengthen and expand the opportunities for this novel resource to access new knowledge on ecological change during the last century., (© 2024 The Author(s). Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Purpose: Inflammation plays a crucial role in the development of atherosclerotic plaques. Pentraxin 3 (PTX3) is produced at the site of inflammation and has been identified as a specific marker of atherosclerosis, vascular inflammation, and progression of the coronary artery disease (CAD). The aim of the study was to establish if PTX3 has potential relations with classical markers of cardiovascular risk, and if PTX3 may act as an independent risk factor of CAD occurrence and advancement., Materials and Methods: The study included 98 patients with stable CAD confirmed in coronary angiography (CAD group) (median age 65 interquartile range [IQR] 61-72 years; 72 ​% men). The control group consisted of 40 patients without CAD., Results: The CAD group had significantly higher PTX3 concentration compared to the control group. There was a correlation with age, male gender, lipid profile and intima-media thickness. There was no correlation between PTX3 concentration and the number of coronary vessels with significant atherosclerotic lesions and the advancement of atherosclerotic lesions on the Gensini scoring scale. The cut-off point was determined for 0.89 ​ng/ml for the exclusion of angiographically significant atherosclerotic lesions., Conclusions: Patients with CAD have significantly higher concentration of PTX3. There was no correlation between PTX3 and the advancement of angiographically significant atherosclerotic lesions in coronary arteries. Low PTX3 concentration may serve as an indicator for the absence of atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Individual-level interventions for dementia risk factors could reduce costs associated with dementia and some are cost-effective. We aimed to estimate the cost-effectiveness of population-level interventions for tackling dementia risk factors., Methods: In this economic modelling study, we included recommended population-based interventions from a previously published review article for which there was consistent and robust evidence of effectiveness in tackling a dementia risk factor (tobacco smoking, excess alcohol use, hypertension, obesity, air pollution, and head injury). We only included interventions if they had not been introduced in England or were in place but could be extended. The interventions studied were increases in tobacco pricing, minimum pricing for alcohol, raising alcohol price, salt reduction policies, sugar reduction policies, low emission zones, and compulsory helmet use for cycling by children (aged 5-18 years). We used published intervention effect sizes and relative risks for each risk factor and a Markov model to estimate progression to dementia in populations with and without the intervention, looking at lifetime risk, in the population of England., Findings: We estimated that reductions in excess alcohol use through minimum unit pricing would lead to cost-savings of £280 million and 4767 quality-adjusted life-years (QALYs) gained over an indefinite succession of age cohorts. Reformulation of food products to reduce salt would lead to cost-savings of £2·4 billion and 39 433 QALYs gained and reformulation to reduce sugar would lead to cost-savings of £1·046 billion and 17 985 QALYs gained. Reducing dementia risk from air pollution by introducing low emission zones in English cities with a population of 100 000 or more (that do not already impose restrictions) would lead to £260 million cost-savings and 5119 QALYs gained. Raising cigarette prices by 10% to reduce dementia risk from smoking would lead to 2277 QALYs gained and cost-savings of £157 million. Making bicycle helmets compulsory for children (aged 5-18 years) to reduce dementia risk from head injury would lead to cost-savings of £91 million and 1554 QALYs gained., Interpretation: Population-level interventions could help tackle life course dementia risk and save costs., Funding: UK National Institute for Health and Care Research Three Schools dementia research programme., Competing Interests: Declaration of interests GL is supported by grants from the UK National Institute for Health and Care Research (NIHR) Applied Research Collaborations, NIHR Biomedical Research Centre, NIHR Health Technology Assessment, NIHR programme grants, North Thames Applied Research Collaborations, Alzheimer’s Association, Norwegian Research Council, and Wellcome Trust. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Teacher well-being and experiences of violence have become issues of national concern, and teacher shortages have increased since the onset of COVID-19. In this national study, we examined verbal and physical violence against teachers from multiple aggressors and the role of anxiety and stress in predicting intentions to transfer positions or quit the profession. The majority of the sample of 9,370 pre-Kindergarten-12th grade teachers was White (79%) and female (79%). Descriptive analyses revealed that 25% of teachers reported intentions to transfer schools and 43% of teachers reported intentions to quit teaching. Structural equation model results indicated pre-COVID-19 verbal and threatening violence from students, parents, colleagues, and administrators predicted teacher anxiety and stress and intentions to transfer schools ( R ² ranged from .18 to .23) and quit the profession during COVID-19 ( R ² ranged from .34 to .36). Anxiety and stress significantly mediated the relation between verbal and threatening violence across all aggressors and teacher intentions to transfer schools and quit the profession. Physical violence from certain aggressors predicted anxiety and stress and intention to transfer schools ( R ² ranged from .15 to .18) and quit the profession ( R ² ranged from .32 to .34). Further, teacher and school characteristics, such as identifying as a person of color and teaching at the middle and high school levels, were associated with greater intentions to transfer schools and quit the profession. Implications for school-based research, practice, and policy are discussed to address violence and promote positive work and learning environments for all school stakeholders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Lithium thiophosphates are a promising class of solid electrolyte (SE) materials for all-solid-state batteries (ASSBs) due to their high Li-ion conductivity. Yet, the practical application of lithium thiophosphates is hindered by their chemical instability, which remains a prevalent challenge in the field. Oxygen substitution has been discussed in the literature as a promising strategy to enhance stability. Nevertheless, the lack of understanding of the role of synthesis strategy on the resulting structure-property relationship makes it difficult to predict and control the material's behaviour, limiting our ability to fully utilize oxygen substitution as a viable solution. Here, we show that not only the total oxygen content but also the oxygen distribution within the material affects the ion conductivity. By carefully analysing the local structure of oxy-sulfide glasses, we find that few highly oxygenated structural units like [PO 4 ] 3- and [PO 3 S] 3- are more detrimental to the ionic conductivity than a larger amount of less substituted units like [POS 3 ] 3- . Further, we demonstrate how the oxygen distribution is connected to the synthesis in high-energy ball milling by comparing two different sets of precursor materials. The results may explain the deviations in the past literature. The findings should be transferable to other Li-thiophosphate materials and enable more directed design of new materials.

This study sought to develop a user-friendly decision-making tool to explore country-specific estimates for costs and economic consequences of different options for scaling screening and psychosocial interventions for women with common perinatal mental health problems in Malawi. We developed a simple simulation model using a structure and parameter estimates that were established iteratively with experts, based on published trials, international databases and resources, statistical data, best practice guidance and intervention manuals. The model projects annual costs and returns to investment from 2022 to 2026. The study perspective is societal, including health expenditure and productivity losses. Outcomes in the form of health-related quality of life are measured in Disability Adjusted Life Years, which were converted into monetary values. Economic consequences include those that occur in the year in which the intervention takes place. Results suggest that the net benefit is relatively small at the beginning but increases over time as learning effects lead to a higher number of women being identified and receiving (cost‑)effective treatment. For a scenario in which screening is first provided by health professionals (such as midwives) and a second screening and the intervention are provided by trained and supervised volunteers to equal proportions in group and individual sessions, as well as in clinic versus community setting, total costs in 2022 amount to US$ 0.66 million and health benefits to US$ 0.36 million. Costs increase to US$ 1.03 million and health benefits to US$ 0.93 million in 2026. Net benefits increase from US$ 35,000 in 2022 to US$ 0.52 million in 2026, and return-on-investment ratios from 1.05 to 1.45. Results from sensitivity analysis suggest that positive net benefit results are highly sensitive to an increase in staff salaries. This study demonstrates the feasibility of developing an economic decision-making tool that can be used by local policy makers and influencers to inform investments in maternal mental health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bauer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Exposure to cold temperatures is known to be associated with deterioration of physical and mental health as well as poorer well-being in many countries. The Winter Fuel Payment, an unconditional direct cash transfer of value between £250-£300, was designed to help older people in England cover heating costs during the winter months, to counteract the particular vulnerability of older people to the effects of cold weather., Aims: We evaluated the impact of the Winter Fuel Payment scheme on subsequent prevalence of care needs such as being unable to eat or shower independently, quality of life and the likelihood of having cold-related housing conditions. We also explored the potential effects of the Winter Fuel Payment across different sub-samples (poorer/richer individuals, those living in newer/older properties, and in the North/South of England) to explore whether its benefits (if any) are spread equally across the eligible population., Data and Methods: We used a regression discontinuity design approach with age as running variable to analyse seven waves of a nationally representative sample, the English Longitudinal Study of Ageing, covering the period 2002/2003 to 2016/2017, and consisting of 24,651 observations., Results: The Winter Fuel Payment had no overall effect on the outcomes of interest (care needs, quality of life, and cold-related housing problems). However, the Payment increased quality of life for poorer individuals, for those living in Northern regions of England, and for those living in newer dwellings. The likelihood of living in a property with at least one cold-related housing problem also decreased for those living in newer properties., Conclusions: Findings from this research provide important insights into the effectiveness of a winter cash transfer among the older population in England, and they are potentially relevant for other nations looking for strategies to deal with cold seasons and poorly insulated homes. In particular, this evaluation contributes to the 'universality versus targeting' policy debate and has implications for the development of energy-efficient policies., Competing Interests: Declaration of competing interest We have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chronic HCV infection leads to a complex interplay with adaptive immune cells that may result in B cell dyscrasias like cryoglobulinemia or lymphoma. While direct-acting antiviral therapy has decreased the incidence of severe liver damage, its effect on extrahepatic HCV manifestations such as B cell dyscrasias is still unclear., Methods: We sequenced B cell receptor (BCR) repertoires in patients with chronic HCV mono-infection and patients with HCV with a sustained virological response (SVR) after direct-acting antiviral therapy. This data set was mined for highly neutralizing HCV antibodies and compared to a diffuse large B cell lymphoma data set. The TKO model was used to test the signaling strength of selected B-BCRs in vitro. Single-cell RNA sequencing of chronic HCV and HCV SVR samples was performed to analyze the transcriptome of B cells with HCV-neutralizing antigen receptors., Results: We identified a B cell fingerprint with high richness and somatic hypermutation in patients with chronic HCV and SVR. Convergence to specific immunoglobulin genes produced high-connectivity complementarity-determining region 3 networks. In addition, we observed that IGHV1-69 CDR1 and FR3 mutations characterizing highly neutralizing HCV antibodies corresponded to recurrent point mutations found in clonotypic BCRs of high-grade lymphomas. These BCRs did not show autonomous signaling but a lower activation threshold in an in vitro cell model for the assessment of BCR signaling strength. Single-cell RNA sequencing revealed that B cells carrying these point mutations showed a persisting oncogenic transcriptome signature with dysregulation in signaling nodes such as CARD11, MALT1, RelB, MAPK, and NFAT., Conclusions: We provide evidence that lymphoma-like cells derive from the anti-HCV immune response. In many patients, these cells persist for years after SVR and can be interpreted as a mechanistic basis for HCV-related B cell dyscrasias and increased lymphoma risk even beyond viral elimination., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Understanding how reaction heterogeneity impacts cathode materials during Li-ion battery (LIB) electrochemical cycling is pivotal for unraveling their electrochemical performance. Yet, experimentally verifying these reactions has proven to be a challenge. To address this, we employed scanning μ-XRD computed tomography to scrutinize Ni-rich layered LiNi 0.6 Co 0.2 Mn 0.2 O 2 (NCM622) and Li-rich layered Li[Li 0.2 Ni 0.2 Mn 0.6 ]O 2 (LLNMO). By harnessing machine learning (ML) techniques, we scrutinized an extensive dataset of μ-XRD patterns, about 100,000 patterns per slice, to unveil the spatial distribution of crystalline structure and microstrain. Our experimental findings unequivocally reveal the distinct behavior of these materials. NCM622 exhibits structural degradation and lattice strain intricately linked to the size of secondary particles. Smaller particles and the surface of larger particles in contact with the carbon/binder matrix experience intensified structural fatigue after long-term cycling. Conversely, both the surface and bulk of LLNMO particles endure severe strain-induced structural degradation during high-voltage cycling, resulting in significant voltage decay and capacity fade. This work holds the potential to fine-tune the microstructure of advanced layered materials and manipulate composite electrode construction in order to enhance the performance of LIBs and beyond., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Women's mental health during the perinatal period is a major public health problem in Pakistan. Many challenges and competing priorities prevent progress to address the large treatment gap. Aim To quantify the long-term impacts of untreated perinatal depression and anxiety in economic terms, thus highlighting its overall burden based on country-specific evidence., Methods: Cost estimates were generated for a hypothetical cohort of women giving birth in 2017, and their children. Women and children experiencing adverse events linked to perinatal mental health problems were modelled over 40 years. Costs assigned to adverse events included were those linked to losses in quantity and quality-of-life, productivity, and healthcare-related expenditure. Present values were derived using a discount rate of 3 %. Data were taken from published cohort studies, as well as from sources of population, economic and health indicators., Results: The total costs were $16.5 billion for the cohort and $2680 per woman giving birth. The by far largest proportion referred to quality-of-life losses ($15.8 billion). Productivity losses and out-of-pocket expenditure made up only a small proportion of the costs, due to low wages and market prices. When the costs of maternal suicide were included, total costs increased to $16.6 billion., Limitations: Important evidence gaps prevented the inclusion of all cost consequences linked to perinatal mental health problems., Conclusions: Total national costs are much higher compared with those in other, higher middle-income countries, reflecting the excessive disease burden. This study is an important first step to inform resource allocations., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract: Simulation-enhanced interprofessional education is widely viewed as an effective teaching pedagogy to foster effective communication and teamwork for healthcare students. Pharmacists and registered nurses must learn to work collaboratively during their educational programs in order to be prepared for the complexities of modern healthcare. This study evaluated prelicensure pharmacy and prelicensure nursing students' perceptions of professional collaboration before and after caring for a standardized patient exhibiting opioid dependence secondary to inappropriate use of an opioid analgesic. Statistically significant gains in communication, collaboration, roles and responsibilities, patient-centered care, conflict management, and team functioning were measured for both pharmacy and nursing students after the interprofessional simulation. This study adds to the existing evidence that suggests simulation-enhanced interprofessional education is an effective teaching strategy; however, this study demonstrates its usefulness for students learning about safer opioid analgesic practices., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (Copyright © 2024 International Nurses Society on Addictions.)

We examine the cost-effectiveness of treating epilepsy with anti-epileptic medicines in autistic children, looking at impacts on healthcare providers (in England, Ireland, Italy and Spain) and children's families (in Ireland). We find carbamazepine to be the most cost-effective drug to try first in children with newly diagnosed focal seizures. For England and Spain, oxcarbazepine is the most cost-effective treatment when taken as additional treatment for those children whose response to monotherapy is suboptimal. In Ireland and Italy, gabapentin is the most cost-effective option. Our additional scenario analysis presents the aggregate cost to families with autistic children who are being treated for epilepsy: this cost is considerably higher than healthcare provider expenditure., (© 2023. The Author(s).)

Background: Dementia is a leading cause of death globally. However, end-of-life care is often poor or non-existent. People with dementia from ethnic minorities or socioeconomically deprived communities are even less likely to receive good palliative care. Despite this, research into end-of-life care often fails to include people from these populations., Aim: To find out what research is required to improve end-of-life care for everyone with dementia and how to facilitate inclusivity., Method: A scoping review of the academic literature (Medline, CINAHL, EMBASE, PsycInfo and Scopus databases) published between Jan 2000 and April 2023 was conducted. Findings were shared with diverse key stakeholders through a series of workshops. Conclusions were subsequently used to provide evidence-based recommendations for inclusive end-of-life care and future research., Results: Themes from the literature were evident in the personal and professional experiences of key stakeholders. Palliative care providers are often ignorant of the needs of those dying in the margins. Support services are scarce and unequal geographically. There is a lack of personalised and culturally appropriate care for those with dementia and their families. Themes from the stakeholder groups included a need for better communication between services, and more investment into dementia as a palliative condition, with avenues created to increase trust and facilitate engagement with services., Conclusion: Future research should focus on educational strategies, including how optimal end-of-life care differs for those with dementia compared to other life-limiting conditions, with appropriate models of inclusive, appropriately funded care needed., (© British Journal of General Practice 2024.)

Background: Globally, guidance recommends the integration of mental health into maternal and child healthcare to address common maternal mental health problems during the perinatal period. However, implementing this in the real-world requires substantial resource allocations., Objective: The aim of this study was to estimate the likely costs and consequences linked to scaling the delivery of treatment (in the form of psychosocial interventions) during the perinatal period., Design: Simulation modelling., Setting(s): England., Methods: Costs and consequences were modelled for three scenarios of assumed provision of services, whereby one referred to the projected provision under current government plans, with no additional scaling up of treatment. The other two scenarios referred to additional scaling of treatment: in one scenario, this referred to the provision of treatment by midwives and health visitors trained in the routine enquiry about mental health and delivery of psychosocial interventions; in the other scenario this referred to an expanded provision by primary mental health services. For each scenario and in yearly intervals (covering a ten-year period, 2015 to 2024), unit cots and outcomes were assigned to the activities women were assumed to receive (routine enquiry, assessment, treatment, care coordination). All costs were in 2020 pounds sterling. Data sources for the modelling included: published findings from randomised controlled trials; national unit cost source; national statistics; and expert consultation., Results: If the projected treatment gap was to be addressed, an estimated additional 111,154 (50,031) women would be accessing treatment in 2015 (2024). Estimated total costs (including cost offsets) in the scenario of projected provision under current government plans would be £73.5 million in 2015 and £95.2 million in 2024, whilst quality-adjusted life years gained would be 901 and 928 respectively. Addressing the treatment gap through provision by trained midwives and health visitors could mean additional costs of £7.3 million in 2015 but lower costs of £18.4 million in 2024. The additional quality-adjusted life years gained are estimated at 2096 in 2015 and 1418 in 2024. A scenario in which the treatment gap would be met by primary mental health services was likely to be more costly and delivered less health gains., Conclusions: Findings from this modelling study suggest that scaling the integration of mental health care into routinely delivered care for women during the perinatal period might be economically viable., Registration: N/A., Tweetable Abstract: Integrating mental health into maternal and child healthcare might generate economic benefits new study by @a&#95;annettemaria and @knappem @CPEC&#95;LSE finds #increasing access to treatment for women with perinatal mental health problems., Competing Interests: Declaration of Competing Interest Dr Alain Gregoire is founder and honorary president of the Maternal Mental Health Alliance, which funded the research. He was not involved in decisions concerning the funding of the research. The other authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study examines the association between mental health problems in adolescence and general practice (GP) costs during adulthood up to age 50 in the UK., Methods: We conducted secondary analyses of three British birth cohorts (individuals born in single weeks in 1946, 1958 and 1970). Data for the three cohorts were analysed separately. All respondents who participated in the cohort studies were included. Adolescent mental health status was assessed in each cohort using the Rutter scale (or, for one cohort, a forerunner of that scale) completed in interviews with parents and teachers when cohort members were aged around 16. Presence and severity of conduct and emotional problems were modelled as independent variables in two-part regression models in which the dependent variable was costs of GP services from data collection sweeps up to mid-adulthood. All analyses were adjusted for covariates (cognitive ability, mother's education, housing tenure, father's social class and childhood physical disability)., Results: Adolescent conduct and emotional problems, particularly when coexisting, were associated with relatively high GP costs in adulthood up to age 50. Associations were generally stronger in females than males., Conclusion: Associations between adolescent mental health problems and annual GP cost were evident decades later, to age 50, suggesting that there could be significant future savings to healthcare budgets if rates of adolescent conduct and emotional problems could be reduced., Trial Registration: Not applicable., (© 2023. The Author(s).)

Compositing different crystal structures of layered transition metal oxides (LTMOs) is an emerging strategy to improve the electrochemical performance of LTMOs in sodium-ion batteries. Herein, a cobalt-free P2/P3-layered spinel composite, P2/P3-LS-Na 1/2 Mn 2/3 Ni 1/6 Fe 1/6 O 2 (LS-NMNF), is synthesized, and the synergistic effects from the P2/P3 and spinel phases were investigated. The material delivers an initial discharge capacity of 143 mAh g -1 in the voltage range of 1.5-4.0 V and displays a capacity retention of 73% at the 50 th cycle. The material shows a discharge capacity of 72 mAh g -1 at 5C. This superior rate performance by the material could be by virtue of the increased electronic conductivity contribution of the incorporated spinel phase. The charge compensation mechanism of the material is investigated by in operando X-ray absorption spectroscopy (in a voltage range of 1.5-4.5 V vs Na + /Na), which revealed the contribution of all transition metals toward the generated capacity. The crystal structure evolution of each phase during electrochemical cycling was analyzed by in operando X-ray diffraction. Unlike in the case of many reported P2/P3 composite cathode materials and spinel-incorporated cobalt-containing P2/P3 composites, the formation of a P'2 phase at the end of discharge is absent here.

The ARID1A and ARID1B subunits are mutually exclusive components of the BAF variant of SWI/SNF chromatin remodeling complexes. Loss of function mutations in ARID1A are frequently observed in various cancers, resulting in a dependency on the paralog ARID1B for cancer cell proliferation. However, ARID1B has never been targeted directly, and the high degree of sequence similarity to ARID1A poses a challenge for the development of selective binders. In this study, we used mRNA display to identify peptidic ligands that bind with nanomolar affinities to ARID1B and showed high selectivity over ARID1A. Using orthogonal biochemical, biophysical, and chemical biology tools, we demonstrate that the peptides engage two different binding pockets, one of which directly involves an ARID1B-exclusive cysteine that could allow covalent targeting by small molecules. Our findings impart the first evidence of the ligandability of ARID1B, provide valuable tools for drug discovery, and suggest opportunities for the development of selective molecules to exploit the synthetic lethal relationship between ARID1A and ARID1B in cancer.

Background: Getting a diagnosis of dementia does not equate to equitable access to care. People with dementia and unpaid carers face many barriers to care, which can vary within, and across, different countries and cultures. With little evidence across different countries, the aim of this scoping exercise was to identify the different and similar types of inequalities in dementia across Europe, and provide recommendations for addressing these., Methods: We conducted a brief online survey with INTERDEM and INTERDEM Academy members across Europe, and with members of Alzheimer Europe's European Working Group of People with Dementia and Carers in February and March 2023. Members were asked about whether inequalities in dementia care existed within their country; if yes, to highlight three key inequalities. Responses on barriers were coded into groups, and frequencies of inequalities were calculated. Highlighted inequalities were discussed and prioritised at face-to-face and virtual consensus meetings in England, Ireland, Italy, and Poland, involving people with dementia, unpaid carers, health and social care providers, and non-profit organisations., Results: Forty-nine academics, PhD students, people with dementia and unpaid carers from 10 countries (Belgium, Denmark, Germany, Greece, Ireland, Italy, Poland, Malta, Netherlands, UK) completed the survey. The most frequently identified inequalities focused on unawareness and lack of information, higher level system issues (i.e. lack of communication among care professionals), lack of service suitability, and stigma. Other barriers included workforce training and knowledge, financial costs, culture and language, lack of single-point-of-contact person, age, and living location/postcode lottery. There was general consensus among people living dementia and care providers of unawareness as a key barrier in different European countries, with varied priorities in Ireland depending on geographical location., Conclusions: These findings provide a first insight on dementia inequalities across Europe, generate cross-country learnings on how to address these inequalities in dementia, and can underpin further solution-focused research that informs policy and key decision makers to implement changes., (© 2024 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Background: Most studies on the impact of the COVID-19 pandemic on depression burden focused on the earlier pandemic phase specific to lockdowns, but the longer-term impact of the pandemic is less well-studied. In this population-based cohort study, we examined the short-term and long-term impacts of COVID-19 on depression incidence and healthcare service use among patients with depression., Methods: Using the territory-wide electronic medical records in Hong Kong, we identified all patients aged ≥ 10 years with new diagnoses of depression from 2014 to 2022. We performed an interrupted time-series (ITS) analysis to examine changes in incidence of medically attended depression before and during the pandemic. We then divided all patients into nine cohorts based on year of depression incidence and studied their initial and ongoing service use patterns until the end of 2022. We applied generalized linear modeling to compare the rates of healthcare service use in the year of diagnosis between patients newly diagnosed before and during the pandemic. A separate ITS analysis explored the pandemic impact on the ongoing service use among prevalent patients with depression., Results: We found an immediate increase in depression incidence (RR = 1.21, 95% CI: 1.10-1.33, p < 0.001) in the population after the pandemic began with non-significant slope change, suggesting a sustained effect until the end of 2022. Subgroup analysis showed that the increases in incidence were significant among adults and the older population, but not adolescents. Depression patients newly diagnosed during the pandemic used 11% fewer resources than the pre-pandemic patients in the first diagnosis year. Pre-existing depression patients also had an immediate decrease of 16% in overall all-cause service use since the pandemic, with a positive slope change indicating a gradual rebound over a 3-year period., Conclusions: During the pandemic, service provision for depression was suboptimal in the face of increased demand generated by the increasing depression incidence during the COVID-19 pandemic. Our findings indicate the need to improve mental health resource planning preparedness for future public health crises., (© 2024. The Author(s).)

Background: By combining theory-driven and data-driven methods, this study aimed to develop dementia predictive algorithms among Chinese older adults guided by the cognitive footprint theory., Methods: Electronic medical records from the Clinical Data Analysis and Reporting System in Hong Kong were employed. We included patients with dementia diagnosed at 65+ between 2010 and 2018, and 1:1 matched dementia-free controls. We identified 51 features, comprising exposures to established modifiable factors and other factors before and after 65 years old. The performances of four machine learning models, including LASSO, Multilayer perceptron (MLP), XGBoost, and LightGBM, were compared with logistic regression models, for all patients and subgroups by age., Findings: A total of 159,920 individuals (40.5% male; mean age [SD]: 83.97 [7.38]) were included. Compared with the model included established modifiable factors only (area under the curve [AUC] 0.689, 95% CI [0.684, 0.694]), the predictive accuracy substantially improved for models with all factors (0.774, [0.770, 0.778]). Machine learning and logistic regression models performed similarly, with AUC ranged between 0.773 (0.768, 0.777) for LASSO and 0.780 (0.776, 0.784) for MLP. Antipsychotics, education, antidepressants, head injury, and stroke were identified as the most important predictors in the total sample. Age-specific models identified different important features, with cardiovascular and infectious diseases becoming prominent in older ages., Interpretation: The models showed satisfactory performances in identifying dementia. These algorithms can be used in clinical practice to assist decision making and allow timely interventions cost-effectively., Funding: The Research Grants Council of Hong Kong under the Early Career Scheme 27110519., Competing Interests: ICK Wong received research funding from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, Takeda, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, and the European Union’s Seventh Framework Programme for research and technological development, unrelated to this work. He has also received consulting fees from IQVIA, the WHO and expert testimony for Appeal Court in Hong Kong over the past three years. He is an advisory member of Pharmacy and Poisons Board, Expert Committee on Clinical Events Assessment Following COVID-19 Immunization, and the Advisory Panel on COVID-19 Vaccines of the Hong Kong Government. He is also a non-executive director of Jacobson Medical Hong Kong, founder and director of the Therakind Limited (United Kingdom), Adanced Data Analytics for Medical Science (ADAMS) Limited and OCUS Innovation Limited (Hong Kong, Ireland and United Kingdom). WC Chan received consulting fees from Eisai (Hong Kong). All other authors declare no financial or non-financial competing interests., (© 2024 The Author(s).)

Background: In daily practice, there are problems with adequately diagnosing the cause of dyspnea in patients with heart failure with preserved and mildly reduced ejection fractions (HFpEF and HFmrEF). This study aimed to assess the usefulness of lung ultrasound in diagnosing HFpEF and HFmrEF and determine its correlation with IGFBP7 (insulin-like growth factor binding protein 7), NTproBNP (N-terminal pro-B-type natriuretic peptide), and echocardiographic markers. Methods: The research was conducted on 143 patients hospitalized between 2018 and 2020, admitted due to dyspnea, and diagnosed with HFpEF and HFmrEF. Venous blood was collected from all participants to obtain basic biochemical parameters, NTproBNP, and IGFBP7. Moreover, all participants underwent echocardiography and transthoracic lung ultrasound. Two years after hospitalization a follow-up telephone visit was performed. Results: The number of B-lines in the LUS ≥ 16 was determined with a sensitivity of-73% and specificity of-62%, indicating exacerbation of heart failure symptoms on admission. The number of B-lines ≥ 14 on admission was determined as a cut-off point, indicating an increased risk of death during the 2-year follow-up period. The factors that significantly impacted mortality in the study patient population were age and the difference between the number of B-lines on ultrasound at admission and at hospital discharge. IGFBP7 levels had no significant effect on the duration of hospitalization, risk of rehospitalization, or mortality during follow-up. Conclusions: Lung ultrasonography provides additional diagnostic value in patients with HFpEF or HFmrEF and exacerbation of heart failure symptoms. The number of B-lines ≥ 14 may indicate an increased risk of death.

Background: The Dementia Severity Rating Scale (DSRS) is an informant report, dementia staging tool that is quick to administer and has previous been shown to differentiate between people with dementia and healthy controls. However, it is not clear how accurate the tool is screening against diagnostic criteria in middle-income settings., Methods: Embedded within the STRiDE programme, older adults (aged ≥65 years) and their informants were randomly recruited from four sites across Indonesia and South Africa. All informants were asked to complete DSRS. We report the tool's psychometric properties and accuracy against the 10/66 short diagnostic algorithm., Results: Between September and December 2021, data was collected from 2110 older adults in Indonesia and 408 in South Africa. Overall, the DSRS scores significantly differed between those with and without dementia, as identified on the 10/66 short algorithm ( p < .05). The difference between groups remained significant after controlling for key factors related to older adult and informant demographics. A score >2 on the DSRS had the greatest agreement with the 10/66 short algorithm and had excellent discriminative properties in both Indonesia (Area Under Curve (AUC) = .75, 95% CIs = .72-.77) and South Africa (AUC = .82, 95% CIs = .76-.88)., Conclusions: The DSRS has potential as a screening tool for dementia in middle-income countries, with high sensitivity and specificity against a standardized diagnostic algorithm., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Economics and dementia are interconnected in many ways. There is, for example, accumulating evidence of the ways in which dementia impacts on the economic status of individuals and families, on health and social care system budgets, and on national economies. An individual's economic status can affect their risk of dementia and their ability to respond to it. Governments and other strategic decision-makers are aware of the (growing, indeed urgent) need to take action - whether that is prevention, treatment or care - but also very aware of the limited resources available to them and to the general population. Research evidence can potentially inform the difficult decisions that government and others need to take. We briefly summarise some economic evaluation studies in the dementia area as a basis for identifying the main challenges of moving from evidence to better policy and practice. We then discuss some possible responses (from a range of stakeholders) to these challenges, and how the STRiDE study has sought to contribute to this fast-moving field., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Evidence on the healthcare utilization associated with comorbidity in people with dementia is lacking in Chinese societies. This study aimed to quantify healthcare utilization associated with comorbidity that is common in people living with dementia. We conducted a cohort study using population-based data from Hong Kong public hospitals. Individuals aged 35+ with a dementia diagnosis between 2010 and 2019 were included. Among 88,151 participants, people with at least two comorbidities accounted for 81.2%. Estimates from negative binomial regressions showed that compared to those with one or no comorbid condition other than dementia, adjusted rate ratios of hospitalizations among individuals with six or seven and eight or more conditions were 1.97 [98.75% CI, 1.89-2.05] and 2.74 [2.63-2.86], respectively; adjusted rate ratios of Accident and Emergency department visits among individuals with six or seven and eight or more conditions were 1.53 [1.44-1.63] and 1.92 [1.80-2.05], respectively. Comorbid chronic kidney diseases were associated with the highest adjusted rate ratios of hospitalizations (1.81 [1.74-1.89]), whereas comorbid chronic ulcer of the skin was associated with the highest adjusted rate ratios of Accident and Emergency department visits (1.73 [1.61-1.85]). Healthcare utilization for individuals with dementia differed substantially by both the number of comorbid chronic conditions and the presence of some specific comorbid conditions. These findings further highlight the importance of taking account of multiple long-term conditions in tailoring the care approach and developing healthcare plans for people with dementia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

STRiDE was an ambitious four-year project in seven countries aiming to build capacity around generating and using research to support the development of policies to improve quality of life of people with dementia and their carers. The project's innovative approach combined rigorous academic research and hands-on civil society advocacy. This paper explores the project's unique strategy for policy change and compiles case-studies from several of the STRiDE countries. Finally, we share lessons learned and next steps to keep momentum for policy change going in each of these countries - and beyond., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There is a need in South Africa to understand the status of available care and support to strengthen responses to dementia. This study provides a situational analysis of the current provisions of health, care and support for older persons, people living with dementia and their families in South Africa. It is a first step towards describing the landscape of needs and services available, and provides an evidence base to inform priority-setting for strengthening responses to dementia in South Africa. This situational analysis was conducted in three phases: (1) a desk review guided by a comprehensive topic guide which includes the WHO's Global Dementia Observatory indicators; (2) multi-sectoral stakeholder interviews to verify the secondary sources used in the desk review, and to identify gaps and opportunities in policy and service provisions; and (3) a SWOT-analysis examining the strengths, weaknesses, opportunities and threats in current care and support provisions in South Africa. Our findings highlight the gaps and opportunities with current service provision and show how structural factors create barriers to diagnosis, support, and care. There is an urgent need for intersectoral policy responses to support and strengthen current health, social care, and long-term support systems so that people living with dementia and their families can live and age well. This paper forms part of a larger study on strengthening responses to dementia (The STRIDE project)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Numerous studies have previously estimated the dementia prevalence in India. However, as these estimates use different methodologies and sampling strategies, generating definitive prevalence estimates can be difficult., Methods: A Delphi process involving eight clinical and academic experts provided prevalence estimates of dementia within India, split by sex and age. The experts were also asked to estimate the number of people potentially living at different stages of the condition. A priori criteria were used to ascertain the point in which consensus was achieved., Results: Our consensus estimates generated a dementia prevalence of 2.8% (95% CI = 1.9 to 3.6) for those aged 60 years and above in India. Consensus was achieved across age and sex prevalence estimates, with the exception of one (females aged 60-64). Our experts estimated that 42.9% of people living with dementia in India had a mild severity., Conclusions: The findings indicate that there could be approximately 3.9 million people living with dementia in India, of which 1.7 million could be living with dementia of mild severity. Such estimates can better help researchers and policy makers to estimate the true cost and impact of dementia in India and can inform resource allocation decisions., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Longitudinal evidence documenting health conditions in spousal caregivers of people with dementia and whether these influence caregivers' outcomes is scarce. This study explores type and number of health conditions over two years in caregivers of people with dementia and subgroups based on age, sex, education, hours of care, informant-rated functional ability, neuropsychiatric symptoms, cognition of the person with dementia, and length of diagnosis in the person with dementia. It also explores whether over time the number of health conditions is associated with caregivers' stress, positive experiences of caregiving, and social networks METHODS: Longitudinal data from the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort were used. Participants comprised spousal caregivers (n = 977) of people with dementia. Self-reported health conditions using the Charlson Comorbidity Index, stress, positive experiences of caregiving, and social network were assessed over two years. Mixed effect models were used RESULTS: On average participants had 1.5 health conditions at baseline; increasing to 2.1 conditions over two years. More health conditions were reported by caregivers who were older, had no formal education, provided 10 + hours of care per day, and/or cared for a person with more neuropsychiatric symptoms at baseline. More baseline health conditions were associated with greater stress at baseline but not with stress over time. Over two years, when caregivers' health conditions increased, their stress increased whereas their social network diminished DISCUSSION: Findings highlight that most caregivers have their own health problems which require management to avoid increased stress and shrinking of social networks., (© 2024. The Author(s).)