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Importance: UV-induced mutagenesis leads to a higher tumor mutational burden (TMB) in cutaneous melanoma relative to other cancer types. TMB is an important prognostic marker in advanced melanoma; higher TMB is associated with greater clinical response to immune checkpoint inhibition and improved survival., Objective: To evaluate the association between cutaneous melanoma TMB and indoor tanning exposure, as well as other demographic, dermatologic, and tumor characteristics., Design, Setting, and Participants: This retrospective cohort study took place at Dana-Farber Cancer Institute, a tertiary-care cancer treatment center in Boston, Massachusetts, between 2013 and 2022. Patients with a diagnosis of cutaneous melanoma for whom next-generation sequencing data and tanning bed exposure history were available were included., Exposures: Indoor tanning exposure history, tumor characteristics, demographics, and dermatologic history were collected via retrospective medical record review., Main Outcomes and Measures: The association of tanning bed use with TMB was modeled using inverse probability of treatment weighted, multivariable modeling., Results: Among 617 patients (median [IQR] age at diagnosis, 61 [50-71] years; 337 [62.9%] male), there was no association between indoor tanning exposure and TMB after adjustment for demographic, tumor, and dermatologic characteristics (yes vs no: log2 TMB [SE], 4.07 [0.44] vs 3.97 [0.45]; P = .39). However, there was a statistically significant association between higher TMB and older age at diagnosis, history of nonmelanoma skin cancer, and head and neck tumors relative to other primary sites. Average TMB was statistically significantly lower in patients with a history of abnormal nevi (yes vs no: log2 TMB [SE], 3.89 [0.44] vs 4.15 [0.44]; P = .01)., Conclusions and Relevance: This cohort study suggests that indoor tanning exposure, while known to increase risk of melanoma, may not be meaningfully associated with melanoma TMB. Additional characteristics were associated with higher TMB and, thus, potentially improved immune checkpoint inhibitor response.

Background: Birthing on Country principles in Australia have seen a revitalisation in midwifery care over the last decade with it being seen as a metaphor for the best start to life for First Nations peoples. This scoping review aimed to explore the extent of evidence of Australian First Nations women's experiences of out-of-hospital childbirth and the alignment with Birthing on Country principles to inform paramedic practice., Methods: Four databases were searched including MEDLINE, CINAHL, EBSCOhost Health and Scopus utilising the Joanna Briggs Institute (JBI) methodology for Scoping Reviews. Inclusion and exclusion criteria were identified. All articles were reviewed in a two stage process., Results: Fifty two papers were yielded with 6 meeting the inclusion criteria. Using reflective thematic analysis four key themes were generated; Birthing on Country and identity, inequitable access to healthcare, trusting relationships and medicalisation of birth., Conclusions: There is a large gap in the literature surrounding delivery of care by paramedics to First Nations women birthing out-of-hospital in Australia. This review proposes supports and actions required to implement Birthing on Country principles into paramedicine. Further, standard maternity care has been found to be insufficient for First Nations women due to a lack of culturally safe care., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest. The authors affiliations with Charles Sturt University and University of Southern Queensland have had no impact on the article as to influence the outcome. All authors meet the authorship criteria, and the manuscript has been read and approved for submission to Australian Emergency Care by all named authors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: To assess the effectiveness of intravesical gentamicin in managing recurrent urinary tract infections (rUTIs) refractory to first- and second-line treatments., Methods and Materials: This single-centre prospective cohort study included 41 patients treated with intravesical gentamicin over a 24-month period from 2021 to 2023. A multidisciplinary team comprising functional urologists, microbiologists, and specialist nurses was involved in the decision-making process and in designing the treatment protocol. Patients self-administered gentamicin instillations into the bladder according to a 6-month instillation schedule. Patients were followed up during and after the treatment period to assess the treatment response., Results: A total of 41 patients with rUTIs were treated using the 6-month intravesical gentamicin regimen. Of these, 10 were male and 31 were female, with a mean age of 53 years. E. coli was isolated from urine cultures in 19 patients (46%), while 19 patients had multiple organisms. Serum gentamicin levels were undetectable in all patients 1 week after treatment initiation. The mean follow-up period was 15 months with minimum follow up of 6 months for all patients. Following gentamicin administration, hospital admission rates due to urosepsis decreased from 46% to 5%, and the prevalence of multidrug-resistant organisms in urine cultures decreased from 44% to 10%. A significant reduction in UTI frequency was observed in 80.5% of patients, with 71% reporting good to excellent Patient Global Impression of Improvement (PGI-I) scores. Additionally, 76% of patients reported a significant improvement in Quality of Life (QoL)., Conclusion: In our cohort of patients with recurrent and refractory UTIs, intravesical gentamicin instillations has shown to be both safe and effective, leading to notable improvements in patients' symptoms and QoL., (© 2024 Wiley Periodicals LLC.)

A flexible electrochemical sensor with high sensitivity and specificity is developed using gold nanoparticles (AuNPs) and a reduced graphene oxide/molybdenum disulfide (rGo-MoS 2 ) composite modified screen printed carbon electrode (SPCE), with L-cysteine (L-Cys) as a probe for Cu 2+ target recognition. Owing to the AuNPs/rGo-MoS 2 , the electron transference ability is improved by increasing the specific surface area of the working electrode, and a high sensitivity is achieved. Meanwhile, the bidentate chelation of L-Cys to Cu 2+ contributes to a good selectivity. Using differential pulse voltammetry (DPV) for spiked standard Cu 2+ , the test results show a dynamic range from 0.1 μM to 100 μM, a detection limit of 0.020 μM, and a high sensitivity of 1.190 μA μM -1 . Furthermore, detection in both environmental water and human plasma samples demonstrates a wide applicability of this sensor in various matrices, and an excellent feasibility for environmental and clinical applications.

Background: The frequency and significance of IDH mutations in glioma across age groups are incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes., Methods: Clinical, histologic, and sequencing data from patients with IDH-mutant, grades 2-4 gliomas, were collected from collaborating institutions between 2013 and 2019. Patients were categorized as pediatric (<19 years), young adult (YA; 19-39 years), or older adult (≥40 years). Clinical presentation, treatment, histologic, and molecular features were compared across age categories using Fisher's exact test or analysis-of-variance. Cox proportional-hazards regression was used to determine the association of age and other covariates with overall (OS) and progression-free survival (PFS)., Results: We identified a cohort of 379 patients (204 YA) with IDH-mutant glioma with clinical data. There were 155 (41%) oligodendrogliomas and 224 (59%) astrocytomas. YA showed significantly shorter PFS and shorter median time-to-malignant transformation (MT) compared to pediatric and adult groups, but no significant OS difference. Adjusting for pathology type, extent of resection, and upfront therapy in multivariable analysis, the YA group was independently prognostic of shorter PFS than pediatric and adult groups. Among astrocytomas, CDK4/6 copy number amplifications were associated with both shorter PFS and shorter OS. Among oligodendrogliomas, PIK3CA and CDKN2A/2B alterations were associated with shorter OS., Conclusions: IDH-mutant glioma YA patients had significantly shorter PFS and time to MT but did not differ in OS compared to pediatric and adult groups. Treatment approaches varied significantly by patient age and warrant further study as addressable age-associated outcome drivers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Competing interests: JK is an Associate Editor for BMJ Sexual & Reproductive Health.

Competing Interests: Disclosure of interest: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author) and disclose no relevant interest.

Relapse rates in high-risk neuroblastoma remain exceedingly high. The malignant cells that are responsible for relapse have not been identified, and mechanisms of therapy resistance remain poorly understood. In this study, we used single-nucleus RNA sequencing and bulk whole-genome sequencing to identify and characterize the residual malignant persister cells that survive chemotherapy from a cohort of 20 matched diagnosis and definitive surgery tumor samples from patients treated with high-risk neuroblastoma induction chemotherapy. We show that persister cells share common mechanisms of chemotherapy escape, including suppression of MYC(N) activity and activation of NFκB signaling, and the latter is further enhanced by cell-cell communication between the malignant cells and the tumor microenvironment. Overall, our work dissects the transcriptional landscape of cellular persistence in high-risk neuroblastoma and paves the way to the development of new therapeutic strategies to prevent disease relapse. Significance: Approximately 50% of patients with high-risk neuroblastoma die of relapsed refractory disease. We identified the malignant cells that likely contribute to relapse and discovered key signaling pathways that mediate cellular persistence. Inhibition of these pathways and their downstream effectors is postulated to eliminate persister cells and prevent relapse. See related commentary by Wolf et al., p. 2308., (©2024 The Authors; Published by the American Association for Cancer Research.)

Low HIV testing among men, particularly highly mobile fishermen, is a persistent challenge. The Owete study (NCT#04772469) used social network-central men (Promoters) to promote testing and linkage to HIV services among social networks of fishermen in western Kenya. The Promoters and fishermen networks were randomised to intervention or control arms. We describe Owete's interactive training approach and Promoters' training experiences for implementation insights. The 146 Promoters trained (balanced across arms) were highly engaged, eager learners, and supportive of targeted health training sessions for men. Promoters felt the knowledge gained improved their understanding of health matters and elevated their social status. Promoters felt empowered knowing how to interpret self-testing results and how to address pre-exposure prophylaxis use questions and correct misconceptions. Offering capacity building for social network-central men to spearhead campaigns on health issues affecting fishermen can leverage established relationships and trust, expand knowledge, and help increase health-seeking practices among underserved, highly mobile men.

Aflatoxin B 1 (AFB 1 ) is a highly toxic substance found in food, necessitating rapid and sensitive detection methods. Combining interfacial capacitive sensing with AC electrothermal (ACET) enrichment, an aptasensor based on a PCB electrode array is developed for real-time detection of trace AFB 1 . Owing to the sensitive solid-liquid capacitance with a pF-level resolution, AFB 1 detection at sub-femtomolar level is achieved. The induced ACET flows enrich AFB 1 molecules towards the electrode surface during capacitance measurement, enabling a one-step detection containing target enrichment, with an overall time of 20 s without any extra concentrating devices or processes. This sensor has a low detection limit of 620 aM, a selectivity of 2262:1 against interferences, and a wide semi-log linear range from 1 fM to 10 pM. It is with a cost below 1 US dollar for disposable detection and a convenient operation for on-site application. The detection of AFB 1 in three types of quality control samples demonstrates a good feasibility for food safety inspection., 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 Elsevier Ltd. All rights reserved.)

Background: The objective of this study was to compare the accuracy of available tests for pyuria, including newer automated tests, and to examine the implications of requiring them for the diagnosis of urinary tract infections (UTIs)., Methods: We included children between 1 and 36 months of age undergoing bladder catheterization for suspected UTIs who presented to 1 of 3 pediatric centers. Using a positive urine culture result as the reference standard, we compared the sensitivity of 5 modalities for assessing pyuria at the cutoffs most often used clinically for detecting children with a positive culture result: leukocyte esterase on a dipstick, white blood cell (WBC) count on manual microscopy with and without using a hemocytometer, automated WBC enumeration using flow cytometry, and automated WBC enumeration using digital imaging with particle recognition., Results: A total of 4188 children were included. Among febrile children, the sensitivity of the 2 most widely available modalities, the leukocyte esterase test and WBC enumeration using digital imaging, had sensitivity values of 84% (95% confidence interval, 0.80-0.87) and 75% (95% confidence interval, 0.66-0.83), respectively., Conclusions: Our findings suggest that for febrile children <36 months of age undergoing bladder catheterization for suspected UTI, pyuria will be absent in ∼20% of children who are eventually shown to have pure growth of a pathogen on a culture. This raises questions about the appropriateness of requiring pyuria for the diagnosis of UTIs., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: We evaluated the results of examining a single faecal sample for gastrointestinal parasites (GIP) using a combination of traditional methods with multiplex qPCR for helminths and protozoa, compared to a reference standard of examining three faecal samples from each person using traditional diagnostic methods alone., Methods: Three faecal samples were collected at weekly intervals from 596 healthy Nepalese men. Each sample underwent formalin-ethyl acetate (FEA) concentration and light microscopy, and charcoal culture. The combined results of these investigations for all three stool samples were designated the reference standard. The first sample was also analysed using a multiplex TaqMan™ qPCR assay, screening for five helminths and three protozoa. We compared sensitivity and specificity of analysing the first faecal sample with qPCR alone, or a hybrid approach combining qPCR with traditional methods, to the reference standard. Additionally, a serum sample was taken from each participant for Strongyloides stercoralis IgG ELISA., Results: The reference standard identified 139 GIP infections in 133 (22.3%) participants. Use of qPCR alone in one stool identified 176 infections in 147 (24.8%) participants, rising to 187 infections in 156 (26.3%) when combined with FEA microscopy and charcoal culture. The sensitivity of this latter hybrid approach was 100% for Strongyloides spp., 90.9% for Trichuris trichiura, 86.8% for hookworm species and 75% for Giardia duodenalis compared to the reference standard. The hybrid approach increased the detected prevalence of G. duodenalis by 4.5% (27 cases) overall, T. trichiura by 2.9% (17 cases), Strongyloides spp. by 1% (6 cases), and hookworm by 0.5% (3 cases), compared to the reference standard., Conclusion: Examination of a single faecal sample using qPCR alone showed superior or equivalent sensitivity to traditional methods for most GIP infections when both were compared to the reference standard. Combining molecular and traditional methods to analyse a single stool improved the detection rate for most studied parasites. This approach has value in settings where repeated sampling and/or faecal culture for helminths is impractical, but molecular diagnostics are available., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We sought to investigate the association between hazardous alcohol use and gaps in care for people living with HIV over a long-term follow-up period. Adults who had participated in our previously published Phase I study of hazardous alcohol use at HIV programs in Kenya and Uganda were eligible at their 42 to 48 month follow-up visit. Those who re-enrolled were followed for an additional ~ 12 months. Hazardous alcohol use behavior was measured using the Alcohol Use Disorders Identification Test (AUDIT) tool. Deidentified clinical data were used to assess gaps in care (defined as failure to return to clinic within 60 days after a missed visit). The proportion of patients experiencing a gap in care at a specific time point was based on a nonparametric moment-based estimator. A semiparametric Cox proportional hazard model was used to determine the association between hazardous alcohol use at enrollment in Phase I (AUDIT score ≥ 8) and gaps in care. Of the 731 study-eligible participants from Phase I, 5.5% had died, 10.1% were lost to follow-up, 39.5% transferred, 7.5% declined/not approached, and 37.3% were enrolled. Phase II participants were older, had less hazardous drinking and had a lower WHO clinical stage than those not re-enrolled. Hazardous drinking in the re-enrolled was associated with a Hazard Ratio (HR) of 1.88 [p-value = 0.016] for a gap in care. Thus, hazardous alcohol use at baseline was associated with an increased risk of experiencing a gap in care and presents an early target for intervention., Competing Interests: Declarations. Conflict of interest: Alexa Monroy, Suzanne Goodrich, Kara Wools-Kaloustian, Giorgos Bakoyannis, Steven Brown, Theofanis Balanos, Lameck Diero, Helen Byakwaga, Winnie Muyindike, Michael Kanyesigye, Maurice Aluda, Jayne Lewis-Kulzer, Constantin Yiannoutsos have not disclosed any competing interests. Ethical Approval: This prospective observational study was approved by the Indiana University Institutional Review Board and the ethical bodies affiliated with each participating site: The Academic Model Providing Access to Healthcare (AMPATH): Moi University College of Health Sciences and MOI Teaching and Referral Hospital’s Institutional Research and Ethics Committee; Family AIDS Care and Education Services (FACES): Kenya Medical Research Institute/National Ethics Review Committee; Mbarara Immune Suppression Syndrome (ISS) Clinic: Mbarara University of Science & Technology Institutional Review Committee and Uganda National Council of Science and Technology (UNCST) Participant written informed consent was obtained at the time of enrollment into study. Consent to Participant (Include Appropriate Consent Statements): Included in text. Consent for Publication (Consent Statement Regarding Publishing an Individual’s Data or Image): N/A, (© 2024. The Author(s).)

Objective: We aimed to prospectively evaluate the association between leisure-time physical activity and outcomes related to low back pain (LBP), such as pain intensity and daily activity limitation., Methods: We analyzed data from the PAMPA (Prospective Study about Mental and Physical Health) cohort, a longitudinal study with adults residing in Southern Brazil. Participants answered an online-based, self-administered questionnaire. Physical activity was assessed as minutes per week, and those who reported engaging in 150 min/week or more were considered active. We also assessed the types of activities participants engaged. Pain intensity was assessed with a numeric pain rating scale (from 0 to 10), and participants reported whether their pain restricted their daily activities. Generalized linear models were used to investigate the association between physical activity and LBP outcomes., Results: Data from 991 individuals (82.7% women) aged 38.9 ± 13.9 were analyzed. Pain intensity was higher in those inactive in waves one (β: 0.54; 95 % CI 0.23, 0.86), three (β: 0.38; 95% CI 0.02, 0.75), and four (β: 0.48; 95% CI 0.06, 0.90). Also, being physically inactive at wave one was associated with a higher probability of daily activity limitation at waves two (IRR 1.77; 95% CI 1.27; 2.46), three (IRR 1.63; 95% CI 1.17, 2.29), and four (IRR 1.73; 95% CI 1.20, 2.50)., Conclusion: Not practicing at least 150 min/week of physical activity resulted in higher levels of pain and an increased risk of daily activity limitation in individuals with LBP. Moreover, various forms of activities have shown to be advantageous in alleviating pain among this group., Competing Interests: Declarations. Conflict of interest: None to declare., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this project was to examine age-related use of action, metacognitive, and metalinguistic verbs because factors related to verb transparency are thought to impact word learning. Performance on fictional, oral narratives elicited using a single-episode picture was evaluated for 84 children with typical language (TL) and 38 age-matched children with a Developmental Language Disorder (DLD) ranging in age from 5;1 to 14;4 years of age. Narrative samples were transcribed and coded for occurrences of action verbs (AV), metacognitive verbs (MCV), and metalinguistic verbs (MLV). The total number of verbs used and the number of different verbs produced in each category were examined across ages, as was the difference in verb usage patterns across language ability groups. A statistically significant increase in the overall use of action, MCV, and MLV with age was observed. TL children used a wider variety of each verb type as compared to those with DLD. Age-related progression for verb use was observed in the fictional narrative generation task by both groups of children. However, despite similar rates of total verb use, children with DLD produced fewer different verbs in the three categories. These findings indicate the total number of verbs used is similar in children with TL and DLD, but there is a difference in the number of different verbs used in functional tasks such as narratives for children with DLD. These results also indicate a need for ongoing examination of the factors not only impacting verb acquisition but also use in communication tasks.

Purpose : There has been concern that a shift in disability funding to the National Disability Insurance Scheme (NDIS) in Australia may have influenced paediatric speech and language intervention to involve parents less in service delivery. This study aimed to describe paediatric speech-language pathologists' (SLPs) practices and perceptions of parent involvement in NDIS-funded speech and/or language intervention. Method : Seventy-two paediatric SLPs currently practicing in Australia with NDIS-funded speech and/or language clients completed an online survey. The survey assessed SLPs' self-reported practices supporting parent involvement through Likert scale responses and included open-text questions about perceived barriers and facilitators in NDIS-funded intervention services. Results from the survey were analysed using descriptive statistics, significance testing, and thematic analysis. Result : The majority of SLPs indicated commitment to involving parents in intervention. Experienced SLPs used more family-centred practices and Department of Education (DE)-based SLPs used fewer. Barriers arose from SLP, parent, and workplace characteristics. Facilitators included communication and rapport building, utilising a family-centred model of service delivery, and parent characteristics. Conclusion : This self-selected sample of Australian SLPs utilised many techniques to facilitate parent involvement within NDIS-funded paediatric speech and language intervention. Results indicate NDIS-funded SLP services for families are family focused.

Background: Increasing resistance to sulfadoxine-pyrimethamine (SP) threatens the effectiveness of intermittent preventive treatment (IPTp) to prevent malaria in pregnancy. Dihydroartemisinin-piperaquine (DP) is the most promising candidate to emerge from clinical trials, but requires a multi-day regimen. Despite being a single-dose regimen, coverage of IPTp-SP remains low, fuelling concerns about adherence to multi-day drug options. An implementation feasibility trial in routine antenatal care settings in western Kenya demonstrated that adherence to the multi-day DP regimen was improved when IPTp-DP was delivered with a targeted information transfer intervention that comprised healthcare provider training and communication tools to support delivery and uptake. This study explored healthcare provider and pregnant women perspectives to understand (1) how the targeted information transfer improved adherence to IPTp-DP and (2) if improved adherence to IPTp-DP influenced provider perceptions towards implementation feasibility of multi-day drug regimens for IPTp., Methods: In-depth interviews were conducted with 64 healthcare providers and 64 pregnant women, selected using a convenience sampling approach from across the three trial arms: IPTp-DP+ (with intervention), IPTp-DP, and current standard of care IPTp-SP. Transcripts from healthcare providers and pregnant women were coded in Nvivo-12 using separate a priori frameworks that included components of the consolidated framework for implementation research. Thematic analysis was used to understand how the targeted information transfer affected adherence to IPTp-DP and how concerns about adherence might influence provider perceptions towards multi-day drug regimens for IPTp., Results: Adherence to IPTp-DP doses taken at home was compromised when women experienced unpleasant side effects. Pregnant women valued being given information about IPTp-DP, including potential side effects and how to manage them. Among providers in the IPTp-DP + arm, confidence in advising women on how to manage side effects increased, and they believed this guidance improved adherence. When concerns about adherence were reduced, providers in the IPTp-DP + arm were positive about implementation feasibility, whereas providers in the IPTp-SP arm remained focused on the dosing complexities and were less convinced of the feasibility of implementing IPTp-DP., Conclusions: Healthcare provider confidence in advising women on how to minimize side effects was boosted through targeted information transfer, which was perceived to improve adherence to IPTp-DP. Policy makers are encouraged to consider supportive interventions that enhance provider confidence around adherence should they shift to multi-day drug regimens for IPTp., Competing Interests: Declarations. Ethics approval and consent to participate: The Kenya Medical Research Institute’s (KEMRI) Scientific and Ethics Review Unit (SERU) [CGHR/005/3751], Kenya, and the research ethics committees of the Liverpool School of Tropical Medicine [18–073], UK, the London School of Hygiene and Tropical Medicine [17179], UK and the University of Bergen [2018/2112], Norway approved the trial. The study team obtained written informed consent from participants before data collection. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background HIV self-testing (HIVST) can improve HIV testing uptake by offering convenience and privacy. Yet HIVST accessibility and uptake remain limited in Lake Victorias beach communities where HIVST holds promise to address many barriers highly mobile populations of men in fishing communities face. We assessed HIVST knowledge and acceptability among highly mobile fishermen, a high priority population for HIV prevention and treatment, participating in a social network-based study ("Owete"; NCT04772469) to promote HIV testing, prevention, and treatment in Kenya. Methods Sixty-five in-depth baseline interviews (IDIs) and two focus group discussions (FGDs) were conducted at study baseline from December 2021 to June 2022 with fishermen, including 30 who were social network-central men recruited as HIVST "promoters" from three fishing communities along Lake Victoria, Kenya. Fishermen were purposively-sampled based on study arm, community and age (18-34 and 35+) for interviews exploring HIVST knowledge, perceived benefits, and concerns. IDIs and FGDs were audio-recorded, translated/transcribed into English and inductively-coded and analyzed by six researchers using a framework approach. Results Nearly all participants had heard about HIVST and expressed willingness to self-test. Almost half reported learning about HIVST for the first time through the Owete study. Perceived benefits of self-testing included privacy, convenience, and being able to learn one's status with the freedom to choose when and where to test, which minimized stigma and work interruptions. Few participants had used HIVST prior to joining Owete, all of whom reported ease of use. Potential barriers to HIVST included fear of HIV-seropositive results, feeling unsure about how to use HIVSTs, and fear of stigma if a HIVST was discovered. Nearly all Owete promoters indicated willingness to distribute HIVST to help their peers know their status. Promoters stressed the importance of approaching HIVST discussions strategically and thoughtfully to garner trust and engagement, and felt they needed training to answer HIVST questions. Conclusion While few fishermen had ever used HIVST, this study found high awareness, positive perceptions, and substantial willingness to use and distribute HIVST to other men. The "promoter" model, with known peers engaged in disseminating HIVST information and test kits, shows promise for engaging men in testing.

Introduction: The purpose of this study was to investigate the relationship between sleep and pain in military personnel and to determine if metrics of sleep and pain intensity differ between the injured and uninjured in this population., Methods: Active-duty US Army Soldiers (n=308; 26.8±6.5 years, 82% male) from the 2nd Infantry Division, Joint Base Lewis-McChord, Washington, and 101st Airborne Division, Fort Campbell, Kentucky, completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and questionnaires about current musculoskeletal injuries and pain intensity (0=no pain to 10=worst imaginable pain). Pearson correlation coefficients were used to assess the association between pain and sleep. Differences in sleep and pain between injured and uninjured participants were determined using an analysis of covariance., Results: Pain intensity was positively correlated with sleep quality (global PSQI score, r=0.337, p<0.001) and daytime sleepiness (ESS score, r=0.163, p=0.005), and negatively associated with sleep duration (r=-0.118, p=0.039). Injured participants accounted for 37.7% (n=116) of the study population. Injured participants reported greater pain intensity (3.7±2.5 vs 1.3±1.9, p<0.001), were older (28.5±7.4 years vs 25.8±5.7 years, p=0.001) and in the service longer (6.3±6.3 years vs 4.6±4.7 years, p=0.013) than uninjured participants. Injured participants had higher global PSQI scores (9.0±4.1 vs 6.4±3.4, p<0.001), including each of the seven PSQI components (all p<0.050), and reported sleeping less per night than uninjured participants (5.7±1.3 hours vs 6.1±1.2 hours, p=0.026)., Conclusion: These data demonstrate that pain intensity is associated with sleep in active-duty US Army Soldiers and that those who report a musculoskeletal injury, regardless of age and time in service, report poorer sleep quality, shorter sleep durations, and greater levels of pain than uninjured Soldiers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Simulation-based hospital design testing (SbHDT) applied during the design of a healthcare facility ensures that the architectural design supports safe, high-quality, and efficient care delivery beyond applicable building code compliance. This prospective investigation assesses the financial impact of SbHDT in the form of cost avoidance., Methods: In designing a new free-standing 400+ bed children's hospital, SbHDT identified latent conditions early in the planning process to mitigate safety concerns related to the proposed design of 15 clinical areas. Architectural modifications were made to address concerns and resolve latent conditions before construction. The estimated cost of materials and labor to make an architectural change was documented for each architectural modification. Unit cost multiplied by unit count for each design element changed was summed together as total cost avoidance., Results: The cost to conduct the simulation was $1.6M (0.01% of overall project cost). Seven hundred twenty-two latent conditions were identified, and 57% of those latent conditions were mitigated by design changes. Ninety million dollars in costs were avoided by making design modifications before construction. Twenty-eight percent of latent conditions (n = 117) would have been cost-prohibitive to modify after construction., Conclusions: SbHDT harnessed evidence-based design to improve clinical care, optimize safety, and maximize investment. SbHDT was financially practical and had a significant impact on cost avoidance. Implementing SbHDT is associated with upfront costs, but long-term savings will accumulate over time through expenses avoided through mitigation of safety threats and operational savings., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Eosinophilia is a common finding in returning travellers, migrants and other travelling groups. In this setting it often indicates an underlying helminth infection. Infections associated with eosinophilia are frequently either asymptomatic or associated with non-specific symptoms but some can cause severe disease. Here the British Infection Association guidelines group has comprehensively reviewed and updated the UK recommendations for the investigation and management of eosinophilia in returning travellers, migrants and other relevant groups, first published in 2010. 1 Literature reviews have been undertaken to update the evidence on the prevalence and causes of eosinophilia in these groups and on the treatment of relevant pathogens and clinical conditions. Diagnostic tests available to UK-based clinicians are summarised. Changes made to the updated guidelines include in sections on the investigation and empirical treatment of asymptomatic eosinophilia and on the treatment of trichuriasis, lymphatic filariasis, onchocerciasis, hookworm, fascioliasis, taeniasis. Pathogens which are rarely encountered in UK practice have been removed from the guidelines and others added, including an expanded section on fungal infection. A section on off-license and rarely used drugs has been included., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Short 'programmes' of professional development can have limited impact on clinical supervisors' practices. This paper reports on an innovative programme of professional development, implemented in a tertiary teaching hospital, that was designed to build clinical supervision capacity, improve the educational practice of frontline clinical supervisors and cultivate future educational leaders., Approach: The programme was a partnership venture between St. Vincent's Hospital Melbourne and the University of Melbourne. It has a three-tiered tapered design: a foundational self-paced online course; online, interprofessional learning communities; and a Graduate Certificate in Clinical Education. Participants progressed from one tier to the next, with the largest number of employees participating in the primary tier (N = 112)., Evaluation: We adopted a utilisation-focused approach to evaluation, collecting multiple data sets across the tiers. Participants reported greater consciousness of their teaching practices, made changes to their practice, and the interprofessional learning communities allowed better integration of practical knowledge with the formal knowledge from the foundational course. Systemic outcomes included the creation of informal educator networks and the diffusion of ideas and practices within the hospital., Implications: Managers and clinical education leaders at the hospital concluded that funding this programme of professional development provided significant benefits, with a high return on investment, which may be transferable to other health care settings that place value on clinical education. For the outcomes to be sustainable, an ongoing programme of professional development needs to be built into the institution's fabric so that the resultant supervisory practices become strongly embedded in the organisational culture., (© 2024 Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Introduction. Strongyloides stercoralis , the human threadworm, is a parasitic nematode with global distribution, estimated to infect over 600 million people. Chronic infection is often asymptomatic, but hyperinfection and dissemination syndromes can occur in the immunosuppressed with high case fatality rates. Whilst strongyloidiasis is endemic in Fiji, its prevalence in Fijian migrant groups in the UK is unknown. Gap Statement. No previous studies have been conducted on the prevalence of Strongyloides and other gastrointestinal parasites (GIPs) in Fijian migrants to the UK. Aim. We conducted a cross-sectional study of the prevalence of GIPs in a Fijian migrant population. Methodology. Participants completed a questionnaire on residence, travel and clinical symptoms and were asked to provide a serum sample for S. stercoralis IgG ELISA, venous blood samples for eosinophil count and a faecal sample for charcoal culture, multiplex real-time PCR (rtPCR) and microscopy after formalin-ethyl acetate concentration. Sequencing was performed on pooled Strongyloides larvae for nuclear 18S rRNA hyper-variable regions (HVRs) I and IV. Results. A total of 250 participants (94% male) with median (range) age 37 (20-51) years entered the study, 15 (1-24) years since leaving Fiji. S. stercoralis IgG ELISA was positive in 87/248 (35.1 %) and 14/74 (18.9 %) had a GIP detected in faeces. This included 7/74 (9.5 %) with Strongyloides and 5/74 (6.8 %) with hookworms. Dermatological symptoms were more common in those with Strongyloides, and eosinophilia (>0.5×10 9 cells per litre) was present in 55.6% of those with positive S. stercoralis IgG. rtPCR was the most sensitive faecal diagnostic test for Strongyloides and hookworms in faeces. Sequences of nuclear 18S rRNA for HVRs I and IV confirmed the presence of S. stercoralis . Conclusion. This first cross-sectional study in Fijian migrants found a high rate of chronic infection with GIPs, particularly S. stercoralis . Faecal microscopy was insensitive compared to charcoal culture, rtPCR or serology, demonstrating the importance of specialist parasitological tests when investigating people with a suspected chronic infection. Our study highlights an overlooked burden of strongyloidiasis in the UK and has implications for screening and treatment programmes in Fiji and for migrants from Fiji.

A popular focus in affective neuroscience research has been to map the relationships between individual differences (e.g. personality and environmental experiences) and psychophysiological responses, in order to further understand the effect of individual differences upon neurobehavioral systems that support affect and arousal. Despite this trend, there have been a lack of practical examples demonstrating how the quantification of individual differences (e.g. categorical or continuous) impacts the observed relationships between different units of analysis (e.g. self-report > psychophysiological responses). To address this gap, we conducted a two-stage aggregated meta-analysis of self-reported intolerance of uncertainty (IU) and skin conductance responses during threat extinction (k = 18, n = 1006) using different quantification choices for individual differences in self-reported intolerance of uncertainty (continuous, categorical via median split, and categorical via extremes - one standard deviation above/below). Results from the meta-analyses revealed that the different quantification techniques produced some consistent (e.g. higher IU was significantly associated with skin conductance responding during late extinction training) and inconsistent IU-related effects. Furthermore, the number of statistically significant effects and effect sizes varied based on the quantification of individual differences in IU (e.g. categorical, compared to continuous was associated with more statistically significant effects, and larger effect sizes). The current study highlights how conducting different quantification methods for individual differences may help researchers understand the individual difference construct of interest (e.g. characterisation, measurement), as well as examine the stability and reliability of individual difference-based effects and correspondence between various units of analysis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The neurocognitive aspects of DMD have received less attention than the physiological sequalae. This study conducted a systematic review and meta-analysis of available literature on the neurocognitive profile of children and young people with DMD. Method: Five databases (EMBASE, Medline, PsycInfo, Scopus and Web of Science) and the grey literature was searched on 27 th January 2023. Eligible articles were available in English and reported neurocognitive outcomes. Neurocognitive domains reported in a comparable way across a minimum of three studies were included. The neurocognitive domains of Full-Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ) and Working memory (WMI) derived from Wechsler scales and receptive vocabulary ability derived from the Peabody Picture Verbal Test (PPVT) were included. A single mean meta-analysis was completed. Results: Relevant data was extracted and presented for 38 eligible studies; 2 of which are from grey literature. Results suggest children with DMD perform around 1SD below non-clinical norms for FSIQ, PIQ, VIQ and WMI. Unlike VIQ, scores derived from the PPVT were within the non-clinical norms. Studies were of moderate - high quality, there was significant heterogeneity and no publication bias. Conclusion: A systematic review of working memory has not previously been completed, it appears that children with DMD perform around 1SD below the mean, like FSIQ, PIQVIQ and WMI. The PPVT is a measure of receptive verbal ability and caution is recommended around the interchangeability of PPVT scores and the wider construct of verbal intelligence.

Objective: To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS)., Methods: All patients fulfilled International League Against Epilepsy (ILAE) DEE-SWAS or EE-SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed. We compared the phenotypic features of individuals with DEE-SWAS and EE-SWAS. Brain-specific gene co-expression analysis was performed for D/EE-SWAS genes., Results: We identified the etiology in 42/91 (46%) patients in our Core cohort, including 29/44 (66%) with DEE-SWAS and 13/47 (28%) with EE-SWAS. A genetic etiology was identified in 31/91 (34%). D/EE-SWAS genes were highly co-expressed in brain, highlighting the importance of channelopathies and transcriptional regulators. Structural etiologies were found in 12/91 (13%) individuals. We identified 10 novel D/EE-SWAS genes with a range of functions: ATP1A2, CACNA1A, FOXP1, GRIN1, KCNMA1, KCNQ3, PPFIA3, PUF60, SETD1B, and ZBTB18, and 2 novel copy number variants, 17p11.2 duplication and 5q22 deletion. Although developmental regression patterns were similar in both syndromes, DEE-SWAS was associated with a longer duration of epilepsy and poorer intellectual outcome than EE-SWAS., Interpretation: DEE-SWAS and EE-SWAS have highly heterogeneous genetic and structural etiologies. Phenotypic analysis highlights valuable clinical differences between DEE-SWAS and EE-SWAS which inform clinical care and prognostic counseling. Our etiological findings pave the way for the development of precision therapies. ANN NEUROL 2024;96:932-943., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Hospital-acquired pneumonia (HAP) also known as non-ventilator associated pneumonia, is one of the most common infections acquired in hospitalised patients. Improving oral hygiene appears to reduce the incidence of HAP. This study aimed to describe current practices, barriers and facilitators, knowledge and educational preferences of registered nurses performing oral health care in the Australian hospital setting, with a focus on the prevention of HAP. We present this as a short research report., Methods: We undertook a cross sectional online anonymous survey of Australian registered nurses. Participants were recruited via electronic distribution through existing professional networks and social media. The survey used was modified from an existing survey on oral care practice., Results: The survey was completed by 179 participants. Hand hygiene was considered a very important strategy to prevent pneumonia (n = 90, 58%), while 45% (n = 71) felt that oral care was very important. The most highly reported barriers for providing oral care included: an uncooperative patient; inadequate staffing; and a lack of oral hygiene requisite. Patients' reminders, prompts and the provision of toothbrushes were common ways believed to help facilitate improvements in oral care., Conclusion: Findings from this survey will be used in conjunction with consumer feedback, to help inform a planned multi-centre randomised trial, the Hospital Acquired Pneumonia PrEveNtion (HAPPEN) study, aimed at reducing the incidence of HAP. Findings may also be useful for informing studies and quality improvement initiatives aimed at improving oral care to reduce the incidence of HAP., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: There is a dearth of information on cultural perceptions of children's language development for ethnic minorities in New Zealand to guide service provision. The current study explored differences across ethnicities in mothers' report of language concern and child language scores within a complex cultural, social, educational, and political context., Method: Data from the antenatal and 54-month waves of Growing Up in New Zealand were utilized. At the 54-month wave interviews, 5,053 mothers were asked if language concerns had been raised and to rate their child's main language proficiency along with other measures., Results: Logistic regression models (including influencing variables) indicated Chinese, Indian, and other Asian mothers were less likely to report language concern, whereas Māori, Pacific, other Asian, and Middle Eastern, Latin American, and African children were more likely to score low on the language measure. Higher maternal education was associated with higher child main language scores, but not with language concerns. Child multilingualism was not associated with low language scores, and these mothers were less likely to raise concern., Conclusions: This study demonstrated differences by ethnicity in mothers' language concern and child main language scores, which are likely to affect access to speech-language pathology services, as these typically rely on parent concern being expressed. Cultural bias in the language measure may also be present. Further research is needed to ask ethnic communities their views on culturally appropriate ways to identify children with communication needs and to develop culturally safe services.

Ultrasound (US) is a non-invasive method used to study the kinematics of the swallowing function. Kinematic measurements are reported in studies evaluating swallowing using US, but there is no standardization. The aim of this scoping review was to identify and characterize the kinematic measurements of swallowing obtained by ultrasound. We followed the methodological recommendations of the Joanna Briggs Institute (JBI) and the reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-extension for scoping reviews (PRISMA-ScR). The research question followed the acronym PCC (population, concept, and context). Seven databases and gray literature were searched. Studies were selected using a blind, paired, and independent method. Data were extracted using a standardized tool. There were 2591 studies and 42 were eligible. Most studies had samples of less than 30 participants and mostly included healthy young adults and older people. The swallowing tasks during the assessments were not standardized. The most commonly studied measures were hyoid displacement and tongue movement during swallowing. However, there is no consensus between studies on the definition of the measures and the procedures for ultrasound assessment, including image acquisition and analysis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Intolerance of uncertainty, the tendency to interpret and react negatively to uncertainty, is a transdiagnostic risk factor for anxiety, depression and eating-related disorders. Given the high comorbidity between anxiety, depression and schizophrenia-spectrum diagnoses (SSDs), there is potential for intolerance of uncertainty to play a role in modulating psychosis symptoms. To address this gap in our understanding, we conducted the first prospectively registered systematic review on intolerance of uncertainty and psychotic symptoms in both people with SSDs and in the general population., Methods: Four databases were searched (PsycINFO, Medline, Web of Science and PubMed), which identified ten studies with a total of 1503 participants that measured intolerance of uncertainty and psychosis symptoms., Results: Key findings suggest the following: (1) Intolerance of uncertainty was associated with total negative psychotic symptoms with small-medium effect sizes; (2) intolerance of uncertainty was higher in individuals with an 'at-risk' mental state for psychosis compared to controls; (3) higher intolerance of uncertainty was associated with more individual psychotic symptoms related to delusions and paranoia within clinical and nonclinical samples; and (4) there was mixed evidence for a relationship between intolerance of uncertainty and auditory hallucinations and intolerance of uncertainty and total positive symptoms in clinical samples., Conclusions: Overall, these findings highlight that intolerance of uncertainty may be an important transdiagnostic dimension and potential treatment target for psychotic symptoms such as delusions and paranoia in people with SSDs., (© 2024 The Author(s). British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Children's hospices are central to specialist palliative care provision for the increasing number of children and young people with life-limiting conditions and their families. These hospices provide holistic care through a range of services, including ongoing care from the point of diagnosis, at the end of life and into bereavement. This article outlines the services provided by children's hospices, while dispelling misconceptions that they exclusively provide care at the end of life. It also explains how these services have developed and evolved as a result of technological advances. It is useful for nurses to be aware of the role of children's hospices, so that they can support the effective care of children and young people with life-limiting conditions and their families., Competing Interests: None declared, (© 2024 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Purpose: To evaluate the use, acceptability, and experience of a seven-item palliative care referral screening tool in an outpatient oncology setting., Methods: A two-phase convergent parallel mixed-methods study. Patient participants who met any of the "Royal Marsden Triggers Tool" criteria were compared with those who did not in terms of demographic data, palliative care needs (Integrated Palliative Outcome Scale, IPOS) and quality of life indicators (EORTC-QLQ-C30). In-depth interviews were carried out with patients and oncology staff about their views and experience of the "Royal Marsden Triggers Tool". Qualitative and quantitative data were triangulated at data interpretation., Results: Three hundred forty-eight patients were recruited to the quantitative phase of the study of whom 53% met at least one of the Triggers tool palliative care referral criteria. When compared with patients who were negative using the Triggers tool, "Royal Marsden Triggers Tool" positive patients had a lower quality of life (EORTC QLQ-C30 Global Health Status scale (p < 0.01)) and a higher proportion had severe or overwhelming physical needs on IPOS (38% versus 20%, p < 0.001). Median survival of "Royal Marsden Triggers Tool" positive patients was 11.7 months. Sixteen staff and 19 patients participated in qualitative interviews. The use of the tool normalised palliative care involvement, supporting individualised care and access to appropriate expertise., Conclusion: The use of a palliative care referral tool streamlines palliative care within oncology outpatient services and supports teams working together to provide an early holistic patient-centred service. Further research is needed to evaluate the effectiveness and feasibility of this approach., (© 2024. The Author(s).)

Twenty-five chimera compounds of Pitstop 1 and 2 were synthesised and screened for their ability to block the clathrin terminal domain-amphiphysin protein-protein interaction (NTD-PPI using an ELISA) and clathrin mediated endocytosis (CME) in cells. Library 1 was based on Pitstop 2, but no notable clathrin PPI or in-cell activity was observed. With the Pitstop 1, 16 analogues were produced with 1,8-naphthalic imide core as a foundation. Analogues with methylene spaced linkers and simple amides showed a modest to good range of PPI inhibition (7.6-42.5 μM, naphthyl 39 and 4-nitrophenyl 40 respectively) activity. These data reveal the importance of the naphthalene sulfonate moiety, with no des-SO 3 analogue displaying PPI inhibition. This was consistent with the observed analogue docked poses within the clathrin terminal domain Site 1 binding pocket. Further modifications targeted the naphthalene imide moiety, with the installation of 5-Br (45 a), 5-OH (45 c) and 5-propyl ether (45 d) moieties. Among them, the OH 45 c and propyl ether 45 d retained PPI inhibition, with propyl ether 45 d being the most active with a PPI inhibition IC 50 =7.3 μM. This is 2x more potent than Pitstop 2 and 3x more potent than Pitstop 1., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

MYCN amplification predicts poor prognosis in childhood neuroblastoma. To identify MYCN oncogenic signal dependencies we performed N-ethyl-N-nitrosourea (ENU) mutagenesis on the germline of neuroblastoma-prone TH-MYCN transgenic mice to generate founders which had lost tumorigenesis. Sequencing of the mutant mouse genomes identified the Ring Finger Protein 121 (RNF121 WT ) gene mutated to RNF M158R associated with heritable loss of tumorigenicity. While the RNF121 WT protein localised predominantly to the cis-Golgi Complex, the RNF121 M158R mutation in Helix 4 of its transmembrane domain caused reduced RNF121 protein stability and absent Golgi localisation. RNF121 WT expression markedly increased during TH-MYCN tumorigenesis, whereas hemizygous RNF121 WT gene deletion reduced TH-MYCN tumorigenicity. The RNF121 WT -enhanced growth of MYCN-amplified neuroblastoma cells depended on RNF121 WT transmembrane Helix 5. RNF121 WT directly bound MYCN protein and enhanced its stability. High RNF121 mRNA expression associated with poor prognosis in human neuroblastoma tissues and another MYC-driven malignancy, laryngeal cancer. RNF121 is thus an essential oncogenic cofactor for MYCN and a target for drug development., (© 2024. The Author(s).)

Background and Objectives: Reproductive-aged women are at an increased risk of developing iron deficiency (ID). We aimed to develop a non-invasive screening tool to identify ID in women and assess the acceptability of screening., Study Design and Methods: We screened women (age 18-49 years) in the community of Western Australia., Primary Outcome: acceptability of screening, assessed by the feasibility of recruiting the required sample size (n = 323)., Secondary Outcomes: Hand grip strength, finger prick haemoglobin concentration (Hb), prevalence of heavy menstrual bleeding (HMB), diet, pregnancy history, blood donation, symptoms of ID and history of ID or anaemia (Hb < 120 g/L). Those with Hb <130 g/L and no history of iron therapy in the past 2 years were given referrals for venous full blood count and ferritin sampling., Results: Across 5 days, we recruited 640 eligible women. Of which, 178 (28%) had HMB and 79 (12%) were anaemic. Mean age was 33.5 ± 9.2 years, and mean Hb was 132.4 ± 11.9 g/L. In the past 2 years: 335 (52%) were diagnosed with ID or anaemia; 322 (50%) had taken oral iron; and 210 (33%) had an intravenous iron infusion. Vegetarian diets were followed by 89 (14%); 40 (6%) were regular blood donors; 290 (45%) had a previous pregnancy. HMB increased the risk of symptoms of ID and having prior ID/anaemia diagnosis (67% vs. 47%) or treatment (p < 0.022). Hand grip strength showed a positive relationship with both Hb (adjusted R 2  = 0.012, p = 0.004) and ferritin (adjusted R 2  = 0.135, p = 0.005)., Conclusion: ID screening was well accepted by women in the community, with high recruitment rates over a short period. Future screening tool development may consider incorporating hand grip strength and HMB assessment., (© 2024 The Author(s). Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

The rising prevalence of dementia calls for a competent workforce capable of delivering quality dementia care. A standard for assessing dementia-care-specific competencies is necessary to guide curriculum development and implementation in a competency-based educational framework during academic training. This study evaluated the psychometric properties of the Dementia Care Competency Model (DCCM) among students enrolled in physical (PT) and occupational therapist (OT) programs. Eighty PT and OT students completed the DCCM by rating the 11 sub-competencies using the National Institute of Health Proficiency Likert Scale. The Exploratory Factor Analysis yielded a Kaiser-Meyer-Olkin of 0.878 and Bartlett's test significance value of < 0.001, which indicates that the data were very good for factor analysis. The Eigenvalues and scree plot derived two factors with an excellent internal consistency (Cronbach's alpha = 0.936). When examining the grouping of sub-competencies, the two factors that emerged were patient-centered and interprofessional collaborative care. The DCCM version 2.0 can guide educators in designing learning experiences that target the essential competencies in dementia care, ensuring that PT and OT graduates are well-prepared to work with individuals living with dementia. Future research should refine the model by exploring additional sub-competencies within each domain and expanding the model's applicability across multiple healthcare disciplines.

The phytohormone gibberellic acid (GA) is critical for environmentally sensitive plant development including germination, skotomorphogenesis, and flowering. The Förster resonance energy transfer biosensor GIBBERELLIN PERCEPTION SENSOR1, which permits single-cell GA measurements in vivo, has been used to observe a GA gradient correlated with cell length in dark-grown, but not light-grown, hypocotyls. We sought to understand how light signaling integrates into cellular GA regulation. Here, we show how the E3 ligase CONSTITUTIVE PHOTOMORPHOGENESIS1 (COP1) and transcription factor ELONGATED HYPOCOTYL 5 (HY5) play central roles in directing cellular GA distribution in skoto- and photomorphogenic hypocotyls, respectively. We demonstrate that the expression pattern of the GA biosynthetic enzyme gene GA20ox1 is the key determinant of the GA gradient in dark-grown hypocotyls and is a target of COP1 signaling. We engineered a second generation GPS2 biosensor with improved orthogonality and reversibility. GPS2 revealed a previously undetectable cellular pattern of GA depletion during the transition to growth in the light. This GA depletion partly explains the resetting of hypocotyl growth dynamics during photomorphogenesis. Achieving cell-level resolution has revealed how GA distributions link environmental conditions with morphology and morphological plasticity. The GPS2 biosensor is an ideal tool for GA studies in many conditions, organs, and plant species., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Background: In nearly all jurisdictions where it is permitted, Medical Assistance in Dying is situated in a healthcare system. Currently, limited evidence demonstrates how supply and demand factors influence access to Medical Assistance in Dying., Objective: The aim of this study is to synthesise empirical research from jurisdictions where Medical Assistance in Dying is legal to identify how supply and demand factors influence access for eligible adults., Method: An integrative review was conducted. CINAHL Complete, PubMed, ProQuest, PsycINFO and Embase databases were systematically searched for studies published between January 1998 and January 2024. Records were independently assessed against inclusion and exclusion criteria. Additional studies were identified by forward and backward citation searching. All studies were assessed for quality. Findings were analysed deductively using an established conceptual framework, and a secondary narrative synthesis was undertaken., Results: Fifty-eight studies met the inclusion criteria. Most studies (n = 32) reported results related to the supply side, 16 reported on the demand side and 10 reported on both supply and demand dimensions of access. Studies about supply showed that health service policies may obstruct access to Medical Assistance in Dying. For healthcare professionals, the practice entails an additional workload and can create tensions with colleagues. Studies of the demand for Medical Assistance in Dying focused on supporting time-critical decisions, adequate planning and caregiver support., Conclusion: Access to Medical Assistance in Dying requires the participation of health services and healthcare professionals but is hindered by policies that obstruct access and direct financial and indirect emotional labour costs. Innovative and inclusive models to promote high-quality, compassionate care at the end of life and access to Medical Assistance in Dying should be considered., Patient or Public Contribution: Patients, caregivers and service users were involved in many of the studies included in this review, and their experiences and perspectives contributed to the analysis and synthesis in this review., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Background: High-level resistance to sulfadoxine-pyrimethamine threatens the efficacy of WHO-recommended intermittent preventive treatment in pregnancy (IPTp) with single-dose sulfadoxine-pyrimethamine to prevent malaria. Monthly IPTp with dihydroartemisinin-piperaquine, a 3-day regimen, is an emerging alternative, but this regimen poses potential implementation and adherence challenges. We aimed to assess adherence to a multiday IPTp with dihydroartemisinin-piperaquine regimen and its delivery effectiveness in routine antenatal care settings in western Kenya., Methods: We conducted a pragmatic, three-armed, open-label, cluster-randomised trial in antenatal clinics in 18 health-care facilities (six facilities per group) in Kisumu County and Homa Bay County in western Kenya. Clusters were facilities offering routine antenatal care services provided by trained Ministry of Health staff with 100 or more antenatal clinic attendances per month between July, 2018, and June, 2019. Private or mission hospitals, dispensaries, referral hospitals, and trial sites were excluded. Individuals in their first trimester, living with HIV, or who were not attending a scheduled antenatal clinic visit were excluded. The 18 antenatal clinics were grouped into matched triplets stratified by location and clinics in each matched triplet were randomly assigned to one of the three study groups (1:1:1). Masking was not possible. Two groups were given IPTp with dihydroartemisinin-piperaquine (one group with a targeted information transfer intervention and one group without any additional interventions) and one group was given the standard of care (ie, IPTp with sulfadoxine-pyrimethamine). The primary endpoint, adherence, was defined as the proportion of participants completing their most recent 3-day IPTp with dihydroartemisinin-piperaquine regimen. This completion was verified by pill counts during home visits no more than 2 days after participants' 3-day regimens ended. The secondary endpoint, delivery effectiveness, was defined as the proportion of participants who received the correct number of IPTp tablets and correctly repeated dosing instructions (ie, correctly recalled the instructions they received about self-administered dihydroartemisinin-piperaquine doses and the number of sulfadoxine-pyrimethamine tablets they had received) at their exit from the antenatal clinic. Individuals receiving treatment for malaria, visiting a clinic for registration only, or interviewed during IPTp drug stock-outs were excluded from analyses. We used generalised linear mixed models to compare endpoints among the IPTp with dihydroartemisinin-piperaquine groups. This trial was registered with ClinicalTrials.gov, NCT04160026, and is complete., Findings: 15 facilities (five per group) completed the trial, with 1189 participants having exit interviews (377 in the IPTp with sulfadoxine-pyrimethamine group, 408 in the IPTp with dihydroartemisinin-piperaquine only group, and 404 in the IPTp with dihydroartemisinin-piperaquine plus targeted information transfer intervention group) and 586 participants having home visits (267 in the IPTp with dihydroartemisinin-piperaquine only group and 319 in the IPTp with dihydroartemisinin-piperaquine plus targeted information transfer intervention group) from Sept 8 to Dec 10, 2020. Relative to the IPTp with dihydroartemisinin-piperaquine only group, adherence was 16% higher in the IPTp with dihydroartemisinin-piperaquine plus targeted information transfer intervention group (266 [83%] of 319 participants vs 196 [73%] of 267 participants; adjusted relative risk [RR] 1·16, 95% CI 1·03-1·31; p=0·0140). Delivery effectiveness in the IPTp with dihydroartemisinin-piperaquine plus targeted information transfer intervention group was not significantly different from that in the IPTp with sulfadoxine-pyrimethamine group (352 [87%] of 403 participants vs 335 [89%] of 375 participants; adjusted RR 0·97, 95% CI 0·90-1·05; p=0·4810). However, delivery effectiveness in the IPTp with dihydroartemisinin-piperaquine only group was significantly lower than in the IPTp with sulfadoxine-pyrimethamine group (300 [74%] of 404 participants vs 335 [89%] of 375 participants; 0·84, 0·75-0·95; p=0·0030)., Interpretation: Targeted information transfer interventions to health-care providers and pregnant individuals boost antenatal care delivery adherence to a multiday regimen with dihydroartemisinin-piperaquine., Funding: European and Developing Countries Clinical Trials Partnership 2, UK Joint Global Health Trials Scheme of the Foreign, Commonwealth and Development Office, Medical Research Council, National Institute for Health and Care Research, and Wellcome Trust; and Swedish International Development Cooperation Agency., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: This survey study aimed to (1) identify patient/family research priorities in pediatric-onset multiple sclerosis (POMS), and (2) delineate optimized methods for research study/clinical trials design, engagement, and implementation., Methods: Participants were as follows: (1) parents of a child (<18 years) with POMS enrolled in a national registry, (2) adolescents (13-17 years) with POMS in the registry, and (3) adults (18-40 years) with POMS receiving care at a registry affiliated clinic. Of 293 eligible participants, 192 completed surveys., Results: Experiences with health care and medications were generally positive but there remain areas of priority improvement. Incentives to participate in clinical trials included medications previously tested and in pill form, bloodwork/study visits required ⩾ every 3 months, cognitive testing ⩽1 hour, compensation for travel and time, ability to continue current multiple sclerosis (MS) medication, option to take study medication if on placebo, and individualized study feedback. Priorities for clinical research were (1) psychosocial impact, (2) cognitive/academic impact, (3) environmental risk, and (4) nutrition., Conclusions: Results highlighted the importance of a holistic approach to study design and a focus on the impact of disease on daily life to best engage patients and families in POMS clinical trials and research., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.C. has received compensation for consulting from Banner Life Sciences*, Biogen, Bristol Myers Squibb, Janssen, Genentech, Novartis Pharmaceuticals, Octave Bioscience, Sandoz, Siemens, TG Therapeutics*, UCB Biopharma, and Vida Ventures*. He has received compensation for speaking engagements from Prime Education, LLC*. He has received research support from the National Institutes of Health, National MS Society, US Department of Defense, Sumaira Foundation, Brainstorm Cell Therapeutics, Bristol Myers Squibb, Genentech, EMD Serono, I-Mab Biopharma, Mallinckrodt ARD, Massachusetts Life Sciences Center, Novartis Pharmaceuticals, Octave Bioscience, Sanofi Genzyme, Tiziana Life Sciences, and Wesley Clover International. All activities and funding have occurred within the past 24 months (*relationship has since ended), and disclosures do not conflict with the work being presented.

Objectives: Examine family safety-reporting after implementing a parent-nurse-physician-leader coproduced, health literacy-informed, family safety-reporting intervention for hospitalized families of children with medical complexity., Methods: We implemented an English and Spanish mobile family-safety-reporting tool, staff and family education, and process for sharing comments with unit leaders on a dedicated inpatient complex care service at a pediatric hospital. Families shared safety concerns via predischarge surveys (baseline and intervention) and mobile tool (intervention). Three physicians with patient safety expertise classified events. We compared safety-reporting baseline (via survey) versus intervention (via survey and/or mobile tool) with generalized estimating equations and sub-analyzed data by COVID-19-era and educational attainment. We also compared mobile tool-detected event rates with hospital voluntary incident reporting., Results: 232 baseline and 208 intervention parents participated (78.2% consented); 29.5% of baseline families versus 38.2% of intervention families reported safety concerns (P = .09). Adjusted odds ratio (95% CI) of families reporting safety concerns intervention versus baseline was 1.6 (1.0-2.6) overall, 2.6 (1.3-5.4) for those with < college education, and 3.1 (1.3-7.3) in the COVID-19-era subgroup. Safety concerns reported via mobile tool (34.6% of enrolled parents) included 42 medical errors, 43 nonsafety-related quality issues, 11 hazards, and 4 other. 15% of mobile tool concerns were also detected with voluntary incident reporting., Conclusions: Family safety-reporting was unchanged overall after implementing a mobile reporting tool, though reporting increased among families with lower educational attainment and during the COVID-19 pandemic. The tool identified many events not otherwise captured by staff-only voluntary incident reporting. Hospitals should proactively engage families in reporting to improve safety, quality, and equity., (Copyright © 2024 by the American Academy of Pediatrics.)

Purpose: To determine the feasibility of modified constraint-induced movement therapy (mCIMT) paired with neuromuscular electrical stimulation (NMES) for infants with asymmetrical hand function (AHF)., Methods: Five infants received an experimental ABA design: (A1) 3 weeks of our Standard AHF Care, (B) 3 weeks mCIMT-NMES, and (A2) 3 weeks of our Standard AHF Care. Parents tracked key data in a daily log, and infants were assessed 4 times using the Hand Assessment for Infants and Peabody Developmental Motor Scale-2., Results: There was a high level of participant enrollment, visit frequency adherence, and compliance with the treatment protocol. No adverse events were reported. Mean Hand Assessment for Infants Both Hands measure scores changed more after mCIMT-NMES than after our Standard AHF Care., Conclusions: mCIMT-NMES is a feasible early intervention for infants with AHF at risk for unilateral cerebral palsy. A future study in a larger sample should examine the efficacy of mCIMT-NMES in this population., Competing Interests: K.G. received payment for lecturing at Concordia University, and the remaining authors declare no conflict of interest., (Copyright © 2024 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)

Background: Assisted dying, also commonly known as euthanasia and physician-assisted suicide, is legal in many countries. Interest in assisted dying is growing due to evolving societal understandings of a good death and a desire for choice. Ethico-legal perspectives are well-known, but as societies become more heterogenous, a greater understanding of the perspectives of people from diverse racial, ethnic, and cultural backgrounds is needed., Aim: To explore perspectives of people from diverse racial, ethnic and cultural backgrounds about assisted dying., Design: Scoping review with narrative synthesis. The protocol was registered with Open Science Framework., Data Sources: Medline, CINAHL Complete, PsycINFO and ProQuest Dissertations & Theses Global were searched from inception to May 2023. Citations were independently assessed against inclusion and exclusion criteria., Results: Of the 17 included studies, perspectives of assisted dying were presented according to religion, religiosity, spirituality, race, ethnicity and ancestry. Perspectives were diverse, presenting more as a spectrum, with multiple intersections and interconnections. Support and/or opposition for assisted dying differed according to cultural attributes, but even amongst those with similar cultural attributes, perspectives differed according to life experiences and notions of suffering., Conclusion: Perspectives on assisted dying are dynamic and evolving. Even where assisted dying is legalised, individual's cultural attributes contribute to unique perspectives of assisted dying as an end-of-life option. Thus, understanding a person's culture, beliefs, expectations and choices in illness, treatment goals and care is fundamental, extending beyond what may be already considered as part of clinician-patient care relationships and routine advance care planning., 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.

Monkeypox virus (MPXV) is zoonotic and capable of infecting many mammal species. However, whether common companion animals are susceptible to MPXV infection is unclear. During July 2022-March 2023, we collected animal and environmental swab samples within homes of confirmed human mpox case-patients and tested for MPXV and human DNA by PCR. We also used ELISA for orthopoxvirus antibody detection. Overall, 12% (22/191) of animal and 25% (14/56) of environmental swab samples from 4 households, including samples from 4 dogs and 1 cat, were positive for MPXV DNA, but we did not detect viable MPXV or orthopoxvirus antibodies. Among MPXV PCR-positive swab samples, 82% from animals and 93% from environment amplified human DNA with a statistically significant correlation in observed cycle threshold values. Our findings demonstrate likely DNA contamination from the human mpox cases. Despite the high likelihood for exposure, we found no indications that companion animals were infected with MPXV.