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Abstract This phase 3 trial compared safety, tolerability, immunogenicity and efficacy of the self-amplifying mRNA COVID-19 vaccine, ARCT-154, with ChAdOx1-S adenovirus-vector vaccine. In four centers in Vietnam adult participants aged 18‒85 years were randomly assigned to receive two doses, 28 days apart, of either ARCT-154 (n = 1186) or ChAdOx1-S (n = 1180). Both vaccines were well tolerated with similar safety and reactogenicity profiles consisting of mainly mild-to-moderate solicited adverse events and few related serious adverse events. Higher neutralizing antibody responses persisting to one-year post-vaccination after ARCT-154 compared with ChAdOx1-S were associated with a generally higher efficacy against COVID-19. In an exploratory analysis relative vaccine efficacy of ARCT-154 vs. ChAdOx1-S against any COVID-19 from Day 36 to Day 394 was 19.8% (95% CI: 4.0–33.0). Self-amplifying mRNA vaccine offers potential immunological advantages in terms of immunogenicity and efficacy over adenovirus-vector vaccine without compromising safety.

Abstract The COVID-19 pandemic and ensuing lockdowns led to sweeping changes in the everyday lives of children and families, including school closures, remote work and learning, and social distancing. To date no study has examined whether these profound changes in young children’s day to day social interactions impacted the development of social cognition skills in early childhood. To address this question, we compared the performance of two cohorts of 3.5- to 5.5-year-old children tested before and after the COVID-19 lockdowns on several measures of false-belief understanding, a critical social cognition skill that undergoes important developments in this age range. Controlling for age and language skills, children tested after the pandemic demonstrated significantly worse false-belief understanding than those tested before the pandemic, and this difference was larger for children from lower socioeconomic status (SES) backgrounds. These results suggest that the pandemic negatively impacted the development of social cognition skills in early childhood, especially for lower SES children.

Abstract Liquid biopsies have the potential to revolutionize cancer care through non-invasive early detection of tumors. Developing a robust liquid biopsy test requires collecting high-dimensional data from a large number of blood samples across heterogeneous groups of patients. We propose that the generative capability of variational auto-encoders enables learning a robust and generalizable signature of blood-based biomarkers. In this study, we analyze orphan non-coding RNAs (oncRNAs) from serum samples of 1050 individuals diagnosed with non-small cell lung cancer (NSCLC) at various stages, as well as sex-, age-, and BMI-matched controls. We demonstrate that our multi-task generative AI model, Orion, surpasses commonly used methods in both overall performance and generalizability to held-out datasets. Orion achieves an overall sensitivity of 94% (95% CI: 87%–98%) at 87% (95% CI: 81%–93%) specificity for cancer detection across all stages, outperforming the sensitivity of other methods on held-out validation datasets by more than ~ 30%.

Abstract Background Women from areas of social deprivation and minority ethnic groups are more likely to experience poor physical health and have higher rates of mental health problems relative to women from less socially disadvantaged groups. However, very little research has examined this in relation to perinatal anxiety. The current study aims to determine prevalence, risk factors and desire for treatment for perinatal anxiety in three regions of the UK with diverse regional characteristics. Methods Women completed measures of anxiety in early, mid-, late-pregnancy and postpartum. Participants were included from three regions of the UK: Region 1 = North East England & North Cumbria n = 512; Region 2 = London North Thames n = 665; Region 3 = West Midlands n = 705. Results Prevalence of perinatal anxiety was lower in Region 1 (OR 0.63 95% CI 0.45 to 0.89) and Region 2 (OR 0.72 95% CI 0.52 to 0.98) relative to Region 3. Analysis showed the effect of neighbourhood socioeconomic deprivation on perinatal anxiety differed by region. In more affluent regions, living in a deprived neighbourhood had a greater impact on perinatal anxiety than living in a deprived neighbourhood in a deprived region. Other factors associated with risk of anxiety in the perinatal period included physical health problems and identifying as being from ‘mixed or multiple’ ethnic groups. Conclusions Neighbourhood deprivation relative to regional deprivation is a better predictor of perinatal anxiety than either regional deprivation or neighbourhood deprivation alone. Women of mixed ethnic backgrounds and women with physical health problems may warrant more attention in terms of screening and support for perinatal anxiety. Self-reported desire for treatment was found to be low.

Abstract Background Inequity in asthma and COVID-19 outcomes and research among Hispanic or Latino individuals is well established. Patient centered outcomes research (PCOR) may help address these inequalities. This report describes the development, implementation, and evaluation of a virtual conference series program titled “Unidos Hablemos de/United, Let’s Talk About” intended to address the health literacy of the Hispanic/Latino community regarding asthma and COVID-19 and to encourage involvement in PCOR. Methods A Project Advisory Group consisting of Hispanic/Latino patient advisors who had been diagnosed with asthma and/or COVID-19, healthcare providers, researchers, a Hispanic faith-based leader, and a program evaluator designed and implemented a six-month series of monthly one-hour virtual sessions. Speakers and topics were selected that fit the Hispanic/Latino community and culture regarding asthma, COVID-19, and PCOR. Recruitment was through a multichannel digital promotion strategy, including social media. The virtual sessions were free on the ZOOM webinar platform and included interactive polling questions, live chat box, and Q&A. All audio and written materials from the sessions were translated into Spanish and English. Evaluations were used to rate the overall satisfaction with the program. Results An average of 382 participants attended each of the six sessions, and participation generally increased with each session. The proportion of participants who considered themselves a Hispanic/Latino patient with asthma, caregiver, or clergy who served Hispanic/Latino communities increased by 100% from session one to session two. Preference for materials in Spanish ranged from 12 to 20% of participants over the six sessions. Among the sessions, 74–84% of polling question respondents indicated they would be willing to participate in research or a study, and 88% said they would be willing to serve as a patient partner/advocate. Program evaluations consistently indicated high satisfaction with the session content, session format, and feeling of inclusion. Conclusions Unidos Hablemos provided a voice to the Hispanic/Latino community that will inform future strategies to improve equity in asthma management, COVID-19, and PCOR. Patient speakers generated trust from the participants and “bridged the gap” between physicians, researchers, and the Hispanic/Latino community. Providing evidence-based, current information will empower patients and caregivers to make informed healthcare decisions.

Abstract Background A dementia diagnosis can lead to a decline in cognitive, social, and physical health, but people with dementia can live meaningful lives and participate actively in society with psychosocial support. This single-arm, non-randomised feasibility study explored the feasibility and acceptability of a Comprehensive REsilience-building psychoSocial intervenTion (CREST) for people with dementia, their caregivers, General Practitioners (GPs), and the public. Methods Nine people with dementia and their primary caregivers living in the community (n = 9 dyads) completed the CREST intervention which had three components (cognitive stimulation therapy [CST], physical exercise, and dementia education). Quantitative secondary outcomes were assessed at baseline and following the 15-week intervention; qualitative interviews were conducted during and post-intervention. All study components were assessed against pre-defined criteria, to determine the feasibility of conducting a future definitive trial. Results Recruitment of people with dementia and their caregiver was a significant challenge and led to considerable delays to the onset and conduct of the intervention. Only 13% of eligible GP practices agreed to assist in recruitment and achieved a 6% enrolment rate; a community-based recruitment strategy proved more effective, yielding a 29% enrolment rate. However, once recruited, participants maintained high attendance and adherence to the content of each component with average adherence rates of 98% for CST, exercise sessions and caregiver education. Adherence to secondary exercise measures was lower, with home exercise diary completion at 37% and Fitbit wear adherence at 80% during the day and 67% at night. The people with dementia felt their concentration and fitness had improved over the 15-week intervention and particularly enjoyed the social aspects (e.g. group classes, exercising with partners from the community). Caregivers felt they had better knowledge and understanding following their education component and reported that the social aspects (interacting and sharing experiences with each other) were important. Overall, participants reported that the three components of the intervention were feasible and acceptable. In addition, the quantitative measures and health economic tools employed were feasible. However, the secondary elements of the exercise component (recording home exercise diaries and Fitbit use) were not considered feasible. Overall, pre-defined criteria for progression to a definitive intervention were fulfilled in terms of acceptability, retention and fidelity but not recruitment. Conclusion While overall, the CREST intervention was feasible and acceptable to participants, significant difficulties with recruitment of people with dementia and their caregiver through GP practices impacted the viability of delivering the intervention. Recruitment through community-based groups proved a more feasible option and further work is needed to overcome barriers to recruiting this cohort before a larger-scale trial can be conducted. Trial registration ISRCTN25294519.

Abstract Background Integration of symptom and palliative care for people with advanced cancer is established in many tumour types, but its role in people with hepatocellular carcinoma (HCC) has not been clearly defined. This study aims to evaluate the clinical and cost effectiveness of an intervention involving a suite of strategies designed to assess and treat palliative care symptoms and needs in adult outpatients with HCC attending four New South Wales (NSW) metropolitan tertiary hospitals. Methods This trial will use a pragmatic cluster-based randomised-controlled design, with ambulatory HCC services as the clusters. HCC patients will be recruited if they have Barcelona Clinical Liver Cancer (BCLC) stage A disease with active tumour or a current or prior diagnosis of BCLC stage B or C disease regardless of tumour activity. Patients with BCLC stage D disease will be excluded as palliative care is the standard of care (SOC) in this group. Cluster sites will be randomised to the study intervention or control where patients are managed according to SOC. All participants will complete the liver-specific Edmonton Symptom Assessment Scale (ESAS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire at regular ambulatory clinic appointments. At intervention sites, patients scoring ≥ 5 on any liver-specific ESAS symptom will be referred to palliative care physicians for consultation. The primary clinical outcome will be improvement in all symptoms scored ≥ 5 on the liver-specific ESAS by 50% within 3 months and the primary implementation outcome will recording the liver-specific ESAS in ≥ 80% of all participants attending clinic appointments. Caregivers of patients enrolled in the trial will be invited to perform Carer Support Needs Assessment Tool at each appointment. Discussion This trial will inform if earlier palliative care involvement significantly reduces the symptom burden associated with HCC. If found to be effective, earlier implementation of palliative care consultation should be included in HCC treatment guidelines. Trial registration ACTRN12623000010695. Registered on September 1, 2023.

Abstract Background Older adults often experience adverse health outcomes including malnutrition following discharge from emergency departments (ED). Discharge to community care is a transitionary time where nutritional vulnerability could be mitigated with the instigation of targeted nutrition care pathways in ED settings. Aims and objectives This scoping review aimed to establish and describe the level of nutrition care provided to older adults admitted and subsequently discharged from EDs. Research design Systematic searches of nine academic and grey literature databases (Medline (Ovid), Pubmed, CINAHL Complete (EBSCOhost), EMBASE, Cochrane Library and Scopus), grey literature sources (DART-Europe E-theses portal, Open Grey, and Trip Medical database) and four websites (Google, Google Scholar, NICE and LENUS) for relevant professional and organisational publications of research, policy, practice, and guidelines between January 2011 to 2023 were completed. Eligible studies included a population of older adults (≥ 65 years) with an ED attendance and subsequent community discharge, and where nutrition screening had identified malnutrition. Data were extracted on the level of nutrition and dietetic care initiated for older adults in the ED according to the Nutrition Care Process Model and summarised descriptively. Results Overall, 22 studies were included in the review. Nutrition status was screened on admission to the ED using validated tools: Mini Nutritional Assessment-Short Form (n = 13), Malnutrition Universal Screening Tool (n = 2), Short Nutritional Assessment Questionnaire (n = 2), NRS-2002 (n = 1) and the Mini Nutritional Assessment – Full Form (n = 1). A full nutrition assessment was reported by 5 studies. Only one study referred to documentation of malnutrition in healthcare records. Subsequent nutrition intervention after discharge from the ED for older adults was not described in any study. Conclusion While there is evidence to support malnutrition screening is taking place in EDs, there is a lack of information about subsequent nutrition care including assessment and therapy interventions. This points to the need for comprehensive exploration of nutrition care pathways, practice, policy, and research to inform models of integrated care for older persons.

The bacterium Vibrio parahaemolyticus is ubiquitous in tropical and temperate waters throughout the world and causes infections in humans resulting from water exposure and from ingestion of contaminated raw or undercooked seafood, such as oysters. We describe a nationwide outbreak of enteric infections caused by Vibrio parahaemolyticus in Australia during September 2021–January 2022. A total of 268 persons were linked with the outbreak, 97% of whom reported consuming Australia-grown oysters. Cases were reported from all states and territories of Australia. The outbreak comprised 2 distinct strains of V. parahaemolyticus, sequence types 417 and 50. We traced oysters with V. parahaemolyticus proliferation back to a common growing region within the state of South Australia. The outbreak prompted a national recall of oysters and subsequent improvements in postharvest processing of the shellfish.

In Kenya, influenza virus circulates year-round, raising questions about optimum strategies for vaccination. Given national interest in introducing influenza vaccination for young children 6–23 months of age, we modeled total influenza-associated illnesses (inclusive of hospitalizations, outpatient illnesses, and non‒medically attended illnesses) averted by multiple potential vaccination strategies: year-round versus seasonal-campaign vaccination, and vaccination starting in April (Southern Hemisphere influenza vaccine availability) versus October (Northern Hemisphere availability). We modeled average vaccine effectiveness of 50% and annual vaccination coverage of 60%. In the introduction year, year-round vaccination averted 6,410 total illnesses when introduced in October and 7,202 illnesses when introduced in April, whereas seasonal-campaign vaccination averted 10,236 (October) to 11,612 (April) illnesses. In the year after introduction, both strategies averted comparable numbers of illnesses (10,831–10,868 for year-round, 10,175–11,282 for campaign). Campaign-style vaccination would likely have a greater effect during initial pediatric influenza vaccine introduction in Kenya; however, either strategy could achieve similar longer-term effects.

Abstract Incarcerated adults in the United States are a vulnerable group with substantially low skills and educational attainment. However, the extent to which various, malleable prison factors are related to the skills of adults from diverse backgrounds remains scarcely explored. Therefore, the purpose of the present study was to explore such factors in order to examine which prison programs and activities are associated with higher skills for incarcerated adults in the United States. The sample included 1247 inmates who participated in the Program for the International Assessment of Adult Competencies survey. Regression analysis results revealed that completing more than high school education in prison was linked to higher performance in literacy and numeracy. Also, higher performance was associated with more time in prison, suggesting that program benefits for inmates with shorter time in prison might go unnoticed. Lastly, the most notable differences in performance were related to participation in prison job training. Even though many incarcerated adults partake in various prison programs and activities, participation in these programs was not consistently associated with higher literacy or numeracy skills. Potentially, prison programs might not be providing sufficient applied opportunities for enhancing skills. Findings from this study suggest a need for a closer evaluation of the malleable prison factors and programs relating to the literacy and numeracy skills of incarcerated adults in the United States.

Abstract The generation of antibody-drug conjugates with optimal functionality depends on many parameters. These include binder epitope, antibody format, linker composition, conjugation site(s), drug-to-antibody ratio, and conjugation method. The production of matrices that cover all possible parameters is a major challenge in identifying optimal antibody-drug conjugates. To address this bottleneck, we adapted our Format Chain Exchange technology (FORCE), originally established for bispecific antibodies, toward the generation of binder-format-payload matrices (pair-FORCE). Antibody derivatives with exchange-enabled Fc-heterodimers are combined with payload-conjugated Fc donors, and subsequent chain-exchange transfers payloads to antibody derivatives in different formats. The resulting binder-format-conjugate matrices can be generated with cytotoxic payloads, dyes, haptens, and large molecules, resulting in versatile tools for ADC screening campaigns. We show the relevance of pair-FORCE for identifying optimal HER2-targeting antibody-drug conjugates. Analysis of this matrix reveals that the notion of format-defines-function applies not only to bispecific antibodies, but also to antibody-drug conjugates.

Abstract Background In emergency care settings, screening for disease or risk factors for poor health outcomes among older adults can identify those in need of specialist and early intervention. The aim of this study was to identify barriers and facilitators to implementing older person-centred screening in emergency care settings in the Mid-West of Ireland. Methods This study employed a qualitative descriptive design underpinned by the theoretical domains framework (TDF). This design informs implementation strategy by establishing a theoretical foundation for focused objectives. One on one semi-structured interviews were conducted with a purposive sample of healthcare workers (HCWs) to explore their screening experiences with older adults in emergency care settings. Information power guided sample size calculation. In data analysis, verbatim interview transcripts were deductively mapped to TDF constructs forming meta-themes that revealed specific barriers and facilitators to person-centred screening for older individuals. These findings will directly inform implementation strategies. Results Three themes were identified; Preconditions to Implementing Older Person-Centred Screening; Knowledge and Skills Required to Implement Older Person-centred Screening and Motivation to Deliver Older Person-Centred Screening. Overall, screening in emergency care settings is a complicated process which is ideally undertaken by knowledgeable and skilled practitioners with a keen awareness of team dynamics and environmental challenges in acute care settings. These practitioners serve as champions and sources of specialist knowledge and practice. Less experienced clinicians seek supervision and support to undertake screening competently and confidently. Education on frailty and aged related syndromes facilitates screening uptake. Recognition of the value of screening is a clear motivator and leadership is vital to sustain screening practices. Conclusions Screening serves as an entry point for specialist intervention, necessitating a specialist multidisciplinary team (MDT) approach for effective implementation in emergency care settings. Strengthening screening practices for older adults who attend emergency care settings involves employing audit, supervision and tailored supports. Skilled and experienced practitioners play a key role in mentoring and supporting the broader MDT in screening engagement. Long-term and sustainable implementation relies on utilising existing managerial, practice development and educational resources to underpin screening practices. Communication between Emergency Department (ED) staff, the specialist team and wider geriatric team is vital to ensure a cohesive approach to delivering older person-centred care in the ED.

Background and Objectives: Magnetoencephalography (MEG) could be a valuable tool in the presurgical evaluation of drug-resistant epilepsy (DRE), especially when the initial evaluation is inconclusive. In this retrospective study, we describe the profile of MEG in patients with DRE and normal magnetic resonance imaging (MRI). Methods: We included patients with focal epilepsy and normal MRI who underwent presurgical evaluation for DRE. MEG profiles of these patients, including the frequency of spikes, density of clusters, number of clusters, and concordance with video electroencephalography (VEEG), were analyzed. Results: Of the 73 patients included, magnetic source imaging (MSI) provided localizing information in 51 (69.9%) patients. Among patients with localizing MEG findings, localizing information on VEEG too was noted in 42 (57.5% of the whole cohort). Thirty-one (42.5%) patients had concordant findings with region-specific localization, six (8.2%) patients had partial concordance, and five (6.8%) subjects showed discordant findings. There was a moderate agreement for the presumed epileptogenic zone in comparing findings derived from MEG and VEEG (kappa value of 0.451, P < 0.001). The agreement was lower when MEG localized to the frontal lobe (kappa value of 0.379, P = 0.001) than the temporal lobe (kappa value 0.442, P = 0.002). Conclusions: MEG can provide localizing information in most patients with a normal MRI. A moderate degree of agreement between localization by MEG and VEEG was noted. These findings highlight the usefulness of MSI in the presurgical evaluation of MRI-negative DRE.

Abstract Background Crohn’s disease (CD) is characterized by chronic intestinal inflammation. Diet is a key modifiable factor influencing the gut microbiome (GM) and a risk factor for CD. However, the impact of diet modulation on GM function in CD patients is understudied. Herein, we evaluated the effect of a high-fiber, low-fat diet (the Mi-IBD diet) on GM function in CD patients. All participants were instructed to follow the Mi-IBD diet for 8 weeks. One group of CD patients received one-time diet counseling only (Gr1); catered food was supplied for the other three groups, including CD patients (Gr2) and dyads of CD patients and healthy household controls (HHCs) residing within the same household (Gr3-HHC dyads). Stool samples were collected at baseline, week 8, and week 36, and analyzed by liquid chromatography-tandem mass spectrometry. Results At baseline, the metaproteomic profiles of CD patients and HHCs differed. The Mi-IBD diet significantly increased carbohydrate and iron transport and metabolism. The predicted microbial composition underlying the metaproteomic changes differed between patients with ileal only disease (ICD) or colonic involvement: ICD was characterized by decreased Faecalibacterium abundance. Even on the Mi-IBD diet, the CD patient metaproteome displayed significant underrepresentation of carbohydrate and purine/pyrimidine synthesis pathways compared to that of HHCs. Human immune-related proteins were upregulated in CD patients compared to HHCs. Conclusions The Mi-IBD diet changed the microbial function of CD patients and enhanced carbohydrate metabolism. Our metaproteomic results highlight functional differences in the microbiome according to disease location. Notably, our dietary intervention yielded the most benefit for CD patients with colonic involvement compared to ileal-only disease. Video Abstract

Objectives: To verify the effect of strength, aerobic, and concurrent training on the memory of cognitively preserved older adults. Methods: A randomized controlled clinical trial will be conducted. Sedentary older adults (aged 60 to 75 years) of both genders will participate. Outcome measures will include blood biomarkers, cognitive tests, depressive symptoms, socioeconomic data, and physical assessments. Participants will be randomized into the following groups: strength training, aerobic training, concurrent training, or control. Interventions will be conducted for 12 weeks, with adherence to training sessions monitored. Pre-training values will be compared between groups using a one-way ANOVA test. Training effects will be evaluated through two-way ANOVA (time × group). The research protocol was registered in The Brazilian Registry of Clinical Trials (ReBEC) (RBR-655vxdd). Expected results: We believe that concurrent training may yield greater efficacy in improving memory outcomes, combining the benefit of both training modalities. Relevance: Considering the increase in population aging and that few studies have evaluated the chronic effect ofphysical exercise on the memory of cognitively preserved older adults, this is a relevant topic, since much of the literature has focused on investigating older adults with some cognitive decline. Furthermore, our aim is to provide an alternative training option by combining the benefits of aerobic and strength training, thereby optimizing time and enhancing both physical capacity and memory.

Abstract Background Non-inferiority trials are recommended by the World Health Organization (WHO) to demonstrate that health products show comparable efficacy to that of existing standard of care. As part of the WHO Global Malaria Programme (GMP) process of assessment of malaria vector control products, a second-in-class insecticide-treated net (ITN) must be shown to be non-inferior to a first-in-class product based on mosquito mortality. The public health impact of the first-in-class pyrethroid-piperonyl butoxide (PBO) ITN, Olyset® Plus, has been demonstrated in epidemiological trials in areas with insecticide-resistant mosquitoes, but there is a need to determine the efficacy of other pyrethroid-PBO nets to ensure timely market availability of nets in order to increase access to ITNs. The non-inferiority of a deltamethrin-PBO ITN Yorkool® G3 was evaluated entomologically against Olyset® Plus in experimental huts in Tanzania, following WHO guidelines for non-inferiority trials. Methods The trial of the two pyrethroid-PBO ITNs was conducted in experimental huts in Lupiro, Tanzania, using a randomized 7 × 7 Latin square block design. The study ran for 49 nights in 14 huts assessing the mosquito mortality and blood-feeding of wild, free-flying, pyrethroid-resistant Anopheles arabiensis. Using the non-inferiority approach, the comparative efficacy (primary endpoint was mosquito mortality at 24 h and secondary endpoint was blood-feeding) of unwashed and 20 times field-washed pyrethroid-PBO Yorkool® G3 ITNs, were compared with the first-in-class product Olyset® Plus and against a pyrethroid-only ITN, PermaNet® 2.0 ITNs, as a standard comparator. Results The experimental hut trial demonstrated non-inferiority and superiority of Yorkool® G3 to Olyset® Plus based on mosquito mortality [51% vs. 39%, OR 1.68 (95% CI 1.50–1.88)], given that lower 95% CI exceeded 0.74 (delta of 39%) and the margin of no difference (1). Blood-feeding inhibition was high for all treated ITNs (> 90%) and Yorkool® G3 was non-inferior to Olyset® Plus [4% vs. 2%, OR 1.81 (95% CI 1.46–2.39)], given that upper 95% CI was less than 4.85 (delta of 4%). The pyrethroid-PBO ITNs were superior to the pyrethroid-only net, PermaNet® 2.0, as determined by both the proportion of mortality and blood-feeding of mosquitoes (p-value

Abstract Background Comprehensive summaries on real-world outcomes in pulmonary arterial hypertension (PAH)—a rare, incurable condition, are lacking. Main body of the abstract We conducted a systematic literature review to describe current survival, morbidity, and quality of life (QoL) outcomes in adult and pediatric PAH patients. We searched Medline and Embase electronic databases, clinicaltrials.gov, and encepp.eu entries, and grey literature to identify outcome estimates for right-heart catheterization-confirmed PAH patients from population-based observational studies (search date: 25 Nov 2021). Data were synthesized using a narrative approach and post-hoc subgroup meta-analyses were conducted to explore adult survival by region, disease severity, representativeness, and study period. The search yielded 7473 records. Following screening and full text review, 22 unique studies with 31 individual reports of outcomes were included. Studies were mostly national registries (n = 21), European (n = 13) and covering adults (n = 17); only six had systematic countrywide coverage of centers. Survival was the most frequently reported outcome (n = 22). Global adult 1-, 3-, and 5-year survival ranged from 85 to 99% (n = 15), 65 to 95% (n = 14), and 50 to 86% (n = 9), respectively. Subgroup meta-analysis showed that 1-, 3-, and 5-year survival in Europe was 90% (95% CI 86–94%; n = 8), 78% (95% CI 68–86%; n = 8), and 61% (95% CI 49–72%; n = 6), respectively; 1-year survival in North America was 88% (95% CI 83–93%; n = 3) and 3-year survival in Asia was 85% (95% CI 82–88%; n = 3). No difference in survival between regions was observed. Subgroup analysis suggested higher survival in patients with better baseline functional class; however, interpretation should be cautioned due to large subgroup heterogeneity and potential missingness of data. Short conclusion This review describes current disease outcomes based on well-defined and representative PAH populations. There is an overall lack of follow-up data for morbidity and QoL outcomes; survival estimates for pediatric patients are scarce and may not be generalizable to the current treatment era, although publications from large pediatric registries became available after our search date. This study demonstrated a remaining unmet need world-wide to improve long-term prognosis in PAH in the current era.

Abstract We developed and evaluated an electronic health record (EHR)-based model for suicide risk specific to an American Indian patient population. Using EHR data for all patients over 18 with a visit between 1/1/2017 and 10/2/2021, we developed a model for the risk of a suicide attempt or death in the 90 days following a visit. Features included demographics, medications, diagnoses, and scores from relevant screening tools. We compared the predictive performance of logistic regression and random forest models against existing suicide screening, which was augmented to include the history of previous attempts or ideation. During the study, 16,835 patients had 331,588 visits, with 490 attempts and 37 deaths by suicide. The logistic regression and random forest models (area under the ROC (AUROC) 0.83 [0.80–0.86]; both models) performed better than enhanced screening (AUROC 0.64 [0.61–0.67]). These results suggest that an EHR-based suicide risk model can add value to existing practices at Indian Health Service clinics.

The schwa sound [ə] in the English language remains challenging and it appears to be overlooked by EFL learners. In practice, the word ‘submit’ is mispronounced by English learners: */sʌbˈmɪt/, instead of /səbˈmɪt/. Some studies have discussed schwa but their data sources were not the Holy Quran. Hence, this article investigated the schwa sound in English vocabulary items collected from the Holy Quran and represented by the letters 'o' and 'u' as in ‘polite’ and ‘submit’. Employing a descriptive qualitative method, the researchers collected 97 vocabulary items containing schwa sounds taken from surah Al-Baqarah verses 1-286. The results indicate that the schwa term that represents the unstressed syllable can be renewed with the terms proposed in this study such as 'astressed' and 'disaccented'. In addition, to maintain the schwa term, a change of its pronunciation is proposed becoming /ʃwə/ and not /ʃwɑː/. Most of the written vowels 'o' and 'u' are pronounced in a strong form, and unstressed vowels 'o' and 'u' are pronounced as a schwa. The appearance of unstressed schwa in the vowels 'o' and 'u' is not determined by its location whether it is in the first or second syllable. Schwa could appear anywhere as long as he was not stressed. Schwa was not found in stressed syllables. Lastly, all -ion [ən] and -ous [əs] suffixes must be pronounced with a schwa. The results imply that EFL learners ought to consult an excellent dictionary to ensure correct pronunciation. Future researchers are expected to examine further patterns of a schwa sound in English vocabulary items to assist EFL learners in improving their pronunciation.

Abstract Introduction Triphallia, a rare congenital anomaly describing the presence of three distinct penile shafts, has been reported only once in the literature. This case report, based on an extensive literature review, describes the serendipitous discovery during cadaveric dissection of the second reported human case of triphallia, distinctly morphologically different from the previous case. Case presentation Despite the normal appearance of external genitalia on examination, the dissection of a 78-year-old white male revealed a remarkable anatomical variation: two small supernumerary penises stacked in a sagittal orientation posteroinferiorly to the primary penis. Each penile shaft displayed its own corpora cavernosa and glans penis. The primary penis and largest and most superficial of the supernumerary penises shared a single urethra, which coursed through the secondary penis prior to its passage through the primary penis. A urethra-like structure was absent from the smallest supernumerary penis. Conclusion This case report provides a comprehensive description of the anatomical features of triphallia in a cadaver, shedding light on the morphology, embryology, and clinical implications of this anomaly. Without dissection, this anatomical variation would have remained undiscovered, suggesting the prevalence of polyphallia may be greater than expected. The single tortuous urethra present in this case, as well as the supernumerary and blind ending urethras present in many cases of penile duplication, may pose significant risk of infection, sexual dysfunction, subfertility, and traumatic catheterization. Significance These findings underscore the importance of meticulous anatomical dissections and may act as a resource for anatomists and those studying genitourinary anomalies. Although we can only speculate as to which functional implications this patient may have experienced, understanding such anatomical variations contributes to both knowledge of human anatomy and clinical management should the condition be encountered in living individuals.

Abstract Cocoa bean shell (CBS) remains a commonly produced by-product of cocoa bean processing. It is usually obtained from fermented and dried cocoa beans that are roasted. The study investigated the potential use of Near-infrared spectroscopy (NIRS) analysis for discriminating roasted and unroasted CBS among cocoa clones and quantifying some nutritional and bioactive components in Ghana. Five clones, comprising four important seed gardens clones used across West Africa and one criollo were evaluated. Cocoa beans from the different clones (T60/887, VENC 4, MO 20, PA 150 and T60/887 × POUND 7) were divided into two parts, with one part roasted at a temperature of 120 °C for 50 min while the other part was kept unroasted. The CBSs were milled and passed through a 425 μm pore-sized sieve to obtain the powder. A handheld portable NIRS was used to scan the CBS powder in Ziplock bags. The nutritional and bioactive characterisation was carried out using official methods. NIRS discriminated the various clones of roasted and unroasted CBS. Carbohydrate was the predominant macronutrient, and ash content ranged from 5.25 to 8.24%. The CBS was high in potassium (2382–3144 mg/100 g) and low in sodium (25.67–51.33 mg/100 g). Total flavonoids and phenolics ranged from 8.61 to 40.71 mgQE/g and 6.34–12.25 mgGAE/g, respectively, for the roasted and unroasted CBS. To ensure better differentiation of cocoa beans from different clones using NIRS, incorporating roasting as a processing parameter is recommended.

Abstract Background Pregnancy is a time of great change for women, both mentally and physically. For any pregnant woman, this time of change can be difficult as the woman needs to constantly adapt to the rapidly changing body. This change could be especially challenging for a woman who has previously struggled with symptoms of body dysmorphic disorder (BDD), which cause individuals to perceive part(s) of their body as particularly ugly or deformed, creating distress that affects several areas of functioning. These distorted perceptions have been associated with low self-reported functioning in physical and psychological areas. The present study assessed the effects of BDD symptoms on the physical and psychological functioning of pregnant women at different points throughout their pregnancy. Methods During July 2021 through April 2022, one hundred and fifty-eight women were recruited from various mothers’ Facebook groups, women’s centers across a city in Southern Texas, and through Prolific. The sample consisted of women in their first, second and third trimesters, as well as women three months postpartum. Information about the presence of BDD symptoms, quality of life, and body image was collected. Results We found that women in their second trimester possess the highest quality of life compared to women in their first trimester, third trimester or postpartum. Women with high BDD symptoms have lower quality of life and lower body image compared to women with low BDD, especially for those in their first or third trimesters. Conclusions These findings illustrate the necessity of targeted interventions and support for pregnant women, especially those with BDD symptoms, in order to promote their well-being throughout pregnancy and postpartum.

This article presents a series of recommendations for the publication of archaeological data, to improve their usability. These 12 recommendations were formulated by archaeological data experts who mined thousands of publications for different data types (including funerary practices, accelerator mass spectrometry dating, stable isotopes, zooarchaeology, archaeobotany and pathologies) during the initial construction of the Big Interdisciplinary Archaeological Database (BIAD). We also include data harmonisation vocabularies utilised for the integration of data from different recording systems. The case studies we cite to illustrate the recommendations are grounded in examples from the published literature and are presented in a problem/solution format. Though practically oriented towards the facilitation of efficient databasing, these recommendations – which we refer to as the BIAD Standards – are broadly applicable by those who want to extract scientific data from archaeological information, those who work with a specific region or theoretical focus and journal editors and manuscript authors. We anticipate that the use of the BIAD Standards will increase the usability, visibility, interoperability and longevity of published data and also increase the citations of those publications from which data were mined. The Standards will also help frame a unified foundation to support the continued integration of the natural sciences with archaeological research in the future.

Abstract In the United Kingdom, the management of bovine tuberculosis (bTB) challenges the coexistence of people and wildlife. Control of this cattle disease is hindered by transmission of its causative agent, Mycobacterium bovis, between cattle and badgers Meles meles. Badger culling has formed an element of bTB control policy for decades, but current government policy envisions expanding badger vaccination. Farming leaders are sceptical, citing concerns that badger vaccination would be impractical and potentially ineffective. We report on a 4‐year badger vaccination initiative in an 11 km2 area which, atypically, was initiated by local farmers, delivered by scientists and conservationists, and co‐funded by all three. Participating landholders cited controversies around culling and a desire to support neighbours as their primary reasons for adopting vaccination. The number of badgers vaccinated per km2 (5.6 km−2 in 2019) exceeded the number culled on nearby land (2.9 km−2 in 2019), and the estimated proportion vaccinated (74%, 95% confidence interval [CI] 40%–137%) exceeded the 30% threshold predicted by models to be necessary to control M. bovis. Farmers were content with how vaccination was delivered, and felt that it built trust with wildlife professionals. The percentage of badgers testing positive for M. bovis declined from 16.0% (95% CI 4.5%–36.1%) at the start of vaccination to 0% (95% CI 0%–9.7%) in the final year. With neither replication nor unvaccinated controls, this small‐scale case study does not demonstrate a causal link between badger vaccination and bTB epidemiology, but it does suggest that larger‐scale evaluation of badger vaccination would be warranted. Farmers reported that their enthusiasm for badger vaccination had increased after participating for 4 years. They considered vaccination to have been effective, and good value for money, and wished to continue with it. Synthesis and applications: Although small‐scale, this case study suggests that badger vaccination can be a technically effective and socially acceptable component of bTB control. A wider rollout of badger vaccination is more likely if it is led by the farming community, rather than by conservationists or government, and is combined with scientific monitoring. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background Nurses contribute to the largest demographic of the healthcare workforce. However, given current global shortages of workforce capacity, this often leads to limited capacity to engage in extracurricular educational developments beyond their immediate role. Consequently, this significantly limits the range of workforce training and development opportunities that are available to them, which could enhance the variety of skills that are brought to the National Health Service (NHS). Objective We aimed to understand prior, current, and future participation in global health activities such as global health conferences, networks, and placements, among National Health Service (NHS) staff. Furthermore, we investigated the barriers and facilitators to participation in global health activities for nurses in our sample. Method Qualitative and quantitative data was gathered from an online survey conducted in England from July to November 2021. Thematic analysis was used to examine the qualitative data collected from one open-ended question, whereas statistical analysis was used to examine the remaining quantitative data. Results Most (84%) nurses in our sample had not participated in a global health activity. Our results highlighted three barriers to participation, including insufficient communication, a lack of awareness, and capacity issues. Conclusion This study showed that, despite low levels of prior participation, there is a strong desire among surveyed nurses to be involved in global health activities and education. Our findings also suggest that enhanced communication of opportunities available is needed, in addition to organisational support which incorporates strategies to overcome capacity constraints.

Abstract Background The COVID-19 pandemic disrupted routine health care and antenatal and birth services globally. The Shoklo Malaria Research Unit (SMRU) based at the Thailand-Myanmar border provides cross border antenatal care (ANC) and birth services to marginalised pregnant women. The border between the countries entered lockdown in March 2020 preventing cross-border access for women from Myanmar to Thailand. SMRU adapted by opening a new clinic during the COVID-19 pandemic in Myanmar. This study explored the impact of the COVID-19 pandemic and response on access to ANC and pregnancy outcomes for marginalised pregnant women in the border regions between Thailand and Myanmar. Methods A retrospective review of medical records of all pregnancies delivered or followed at antenatal clinics of the SMRU from 2017 to the end of 2022. Logistic regression was done to compare the odds of maternal and neonatal outcomes between women who delivered pre-COVID (2017–2019) and women who delivered in the COVID-19 pandemic (2020–2022), grouped by reported country of residence: Thailand or Myanmar. Results Between 2017 and the end of 2022, there were 13,865 (5,576 resident in Thailand and 8,276 in Myanmar) marginalised pregnant women who followed ANC or gave birth at SMRU clinics. Outcomes of pregnancy were known for 9,748 women with an EGA ≥ 28 weeks. Unknown outcome of pregnancy among women living in Thailand did not increase during the pandemic. However, there was a high (60%) but transient increase in unknown outcome of pregnancy for women with Myanmar residence in March 2020 following border closure and decreasing back to the baseline of 20–30% after establishment of a new clinic. Non-literate women were more likely to have an unknown outcome during the pandemic. There was no statistically significant increase in known stillbirths or maternal deaths during the COVID pandemic in this population but homebirth was over represented in maternal and perinatal mortality. Conclusion Decreasing barriers to healthcare for marginalised pregnant women on the Thailand-Myanmar border by establishment of a new clinic was possible in response to sudden border closure during the COVID-19 pandemic and most likely preventing an increase in maternal and perinatal mortality.

The purpose of this study was to explore the readiness of the Internal School Quality Assurance Teams (ISQATs) to supervise instruction in Tanzanian public secondary schools. The study employed a qualitative approach, and data were collected through semi-structured interviews and documentary reviews. A purposeful sampling technique was used to select 18 participants from the Kilimanjaro Region of Tanzania. The findings indicate that many Internal School Quality Assurance Officers (ISQAOs) had limited professional profiles despite having adequate teaching qualifications. Their supervisory practices included regular checking of academic records, reminding teachers of their responsibilities, and recommendations on academic matters. It was also found that ISQATs faced challenges such as heavy workloads, poor cooperation from teachers, a lack of supervision guidelines, and different perspectives regarding lesson planning. This study concludes that ISQATs were not fully ready to supervise instructions as professionals, implying that the existing ISQAOs need to receive professional training and that a supervision policy that requires possession of instructional supervision skills as a pre-requisite for teachers’ promotion to an instructional supervision role be implemented.

Abstract The Architect's registration crisis in Nigeria for eight straight years (2015–2023) has significantly impacted the architectural profession, creating a pressing need for effective solutions to restore stability and ensure a sustainable future. This research investigated the challenges and consequences the crisis has caused the architectural profession in Nigeria and potential strategies for resolving the situation. The study relied on thirty-four (34) structured interviews with Provisionally Stage II registered architects and fully registered architects from different parts of Nigeria and a literature review involving a thorough analysis to identify key issues and challenges related to the Architect's registration crisis in Nigeria. Findings reveal the major factors contributing to the registration crisis include institutional issues, legislative and policy issues, power-mongering, and personality battles within professional associations and the regulatory body. Some of the proposed solutions involve strengthening accreditation standards and monitoring, addressing issues about the HND degree holders, advocating for fair registration practices, fostering collaboration and professionalism, overcoming internal issues and power struggles within professional associations and regulatory bodies, and the study proposed a framework for the registration of architects in different cadres. Ultimately, this research provided valuable insights for policymakers, professional bodies, and stakeholders. By identifying viable pathways to resolution, this study paves the way for a sustainable future for the architectural profession in Nigeria, ensuring its continued growth in the built environment.

Abstract Background Elevated mammographic density (MD) for a woman’s age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). Methods ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35–85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. Results Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (β: − 0.05, 95% confidence interval (CI): − 0.07, − 0.03) and √DA (β: − 0.08, 95% CI: − 0.12, − 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (β:0.06, 95% CI:0.03, 0.10) and √DA (β:0.06, 95% CI:0.02, 0.10), and lower √NDA (β: − 0.06, 95% CI: − 0.11, − 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. Conclusions Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

The black ant (Dolichoderus thoracicus) is known as a natural enemy of Hypothenemus hampei Ferr., the Coffee Berry Borer (CBB). The conservation efforts for this natural enemy can be carried out by using ant nest technology with artificial feed. This research explored artificial nesting and feeding methods for black ant colonies in coffee plantations in Jember District, Indonesia, to combat the CBB. Utilizing a Randomized Block Design, the study examines different nest materials and shapes, various artificial feeds, and the influence of environmental factors on ant colony growth. Cocoa leaves are the most effective nesting material, significantly increasing ant populations (11,532 individuals on average) compared to coconut leaves (4,645.83 individuals); no significant impact of nest shape on ant attraction; granulated sugar is the preferred artificial feed. A notable increase in ant populations was observed with a longer nest placement duration of four weeks. Environmental factors, especially humidity and temperature, significantly influence nests' and feed interactions. The study highlights the importance of specific nesting materials and environmental considerations in effective pest management strategies in tropical agriculture, offering a sustainable approach to enhancing coffee plantation productivity.

Abstract Background Suicide is a leading cause of death in the United States with rates increasing over the past two decades. The rate of suicide is higher in rural areas, but a greater number of people in urban areas die by suicide; understanding risk factors for suicide in this context is critically important to public health. Additionally, while many studies have focused on individual-level risk factors, few studies have identified social or structural features associated with suicide or firearm suicide, especially among young people. Methods Study outcomes included total firearm suicide, total youth (age 10–29) firearm suicide, total suicide, and total youth suicide in Detroit, Michigan from 2012 through 2019. The predictors in this study included 58 census-tract level variables characterizing the physical features, residential stability, socioeconomic status, and demographics of neighborhoods in Detroit over the study period. We used random forest, extreme gradient boosting (XGBoost), and generalized linear mixed models to predict the four outcomes. Results We found that the tract-level variables used in all three modeling approaches performed poorly at predicting the suicide outcomes, with area under the curve values at times exceeding 0.60 but with extremely low sensitivity (ranging from 0.05 to 0.45). However, the percentage of parcels sold in arms-length transfers in the previous 5 years, the count of vacant lots per square mile, and the percentage of children aged three and older who were enrolled in preschool each demonstrated associations with at least two of the outcomes studied. Conclusions Our findings suggest place-based factors at the tract level do not provide meaningful insight into the risk of suicide or firearm suicide among youth or the general population in Detroit, Michigan. Future practice and study should consider focusing on both larger and smaller areas, including city and individual-level factors. For example, studies might benefit from the use of both neighborhood and individual-level measures and their interactions to improve our understanding of place-based risk factors and suicide risk.

Abstract Cerebral vasospasm (CVS) is an important contributor to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), leading to high morbidity and long-term disability. While several microRNAs (miRNAs) have been implicated in vasospasm, the underlying mechanisms for CVS remain poorly understood. Our study aims to identify miRNAs that may contribute to the development of CVS. Whole-blood samples were obtained during or outside of vasospasm from aSAH patients whose maximal vasospasm was moderate or severe. MiRNAs were isolated from serial whole-blood samples, and miRNA sequencing was performed. Differentially expressed miRNAs were identified and the expression levels in patients’ samples were verified using real-time qPCR. The biological functions of identified miRNA were evaluated in human brain endothelial cells (HBECs). MiRNA profiling revealed significant upregulation of miR-148b-3p in patients during CVS. We demonstrated that miR-148b-3p directly targeted and decreased the expression of ROCK1, affecting cell proliferation, migration, and invasion of HBECs through the ROCK-LIMK-Cofilin pathway. We propose that the upregulation of miRNA-148b-3p plays a role in the development of CVS by regulating actin cytoskeletal dynamics in HBECs, which is crucial for vascular function. Our study highlights miR-148b-3p as a potential diagnostic marker as well as therapeutic target for CVS following aSAH.

Abstract Background A novel Complex REsilience-building psychoSocial intervenTion (CREST) targeted at people with dementia, their informal carers, general practitioners and the wider community with the aim of increasing resilience and strengthening the personal attributes or external assets of people with dementia living at home, in the community, was developed. It included three components: cognitive stimulation therapy (CST), physical exercise and dementia education. A non-randomised feasibility study was conducted of the CREST intervention, the aim of which was to inform the design of a future randomised controlled trial. This article presents the findings from the qualitative component of the CREST intervention feasibility study, describing the experience of the people with dementia and their caregivers who participated and the volunteer older adults who supported the intervention. Methods A descriptive qualitative research approach using semi-structured interviews was undertaken. Key stakeholders (people with dementia (n = 9), their caregivers (n = 9) and the volunteer older adults from the physical exercise component (n = 9)) were interviewed about the intervention and the perceived impact of their participation. Results The social aspect of the CREST intervention proved to be important for all three groups. Attendance remained high throughout the intervention. The people with dementia spoke positively about their participation in the CST and exercise components of the CREST intervention. The caregivers liked receiving coping strategies focused on how to communicate better with the person they cared for and how to better manage their own self-care and they liked the group element of the programme. The volunteer older adults supported the people with dementia in taking part in the exercise component, motivating them to do the exercises and helping with social interaction within the group. The volunteers gained exposure to the illness and as a result understood more about dementia and felt better equipped to communicate and deal with people with dementia. Conclusion Participation in the CREST intervention produced a positive impact on all three groups. The social element of the intervention was noted by everybody and was regarded as being beneficial. Qualitative insights emphasised the value of embedding qualitative research within feasibility studies to inform future intervention design. Further research should focus on conducting a full-scale randomised controlled trial to evaluate CREST’s effectiveness and explore its application to individuals with more advanced dementia. Trial registration ISRCTN25294519.

Abstract We introduce a proof-of-concept extended reality (XR) environment for discussing cancer, presenting genomic information from multiple tumour sites in the context of 3D tumour models generated from CT scans. This tool enhances multidisciplinary discussions. Clinicians and cancer researchers explored its use in oncology, sharing perspectives on XR’s potential for use in molecular tumour boards, clinician-patient communication, and education. XR serves as a universal language, fostering collaborative decision-making in oncology.

Abstract Background Incident HIV during the perinatal period significantly impedes elimination of Mother-to-Child HIV Transmission (eMTCT) efforts. Pre-Exposure Prophylaxis (PrEP) effectively reduces HIV acquisition, and new agents like injectable Cabotegravir (CAB-LA) offer potential advantages for pregnant and breastfeeding women. The Pregnancy, Infant, and Maternal health Outcomes (PrIMO) study will compare rates of composite adverse pregnancy outcomes, and infant adverse events, growth and neurodevelopment between mother-infant dyads receiving CAB-LA and those receiving oral PrEP in Malawi. Methods PrIMO is an observational cohort study involving: (1) the development of a PrEP Pregnancy Registry for longitudinal surveillance of pregnant women on PrEP in Malawi; and (2) the enrolment of a prospective safety cohort of 621 pregnant women initiating oral PrEP or CAB-LA and their subsequent infants. The registry will include all women continuing or initiating PrEP during pregnancy across targeted sites in Lilongwe and Blantyre districts. The safety cohort will enrol a subset of those women and their infants from Bwaila District Hospital in Lilongwe, Malawi. We hypothesize that CAB-LA’s safety will be comparable to daily oral PrEP regarding adverse pregnancy outcomes, maternal/infant adverse events, and infant development. Participants in the cohort will choose either oral PrEP or CAB-LA and will be followed until 52 weeks post-delivery. Safety data will be collected from all mother-infant pairs and qualitative interviews will be conducted with a subset of purposively selected women (n = 50) to assess the acceptability of each PrEP modality. Discussion The PrIMO study will provide critical data on the safety of CAB-LA in pregnant and breastfeeding women and their infants. Results will guide clinical recommendations as the Malawi Ministry of Health prepares for the rollout of CAB-LA to this population. Evaluation of Registry implementation will inform its expansion to a nationwide safety monitoring system for PrEP use during pregnancy, with implications for similar systems in the region. Trial Registration number NCT06158126. The study was prospectively registered (5 December 2023) in ClinicalTrials.gov.

Abstract Background Antepartum hemorrhage (APH) is an obstetric emergency that complicates pregnancy worldwide and continues to lead to hemorrhagic conditions in parts of Tanzania. Midwifery education received by midwives consists theoretical knowledge on the subject but with no or minimal practical skills in the laboratory, which may reduce their practical capacity as graduated midwives. This study therefore aimed to explore midwives’ clinical actions and experiences regarding the care of women with APH in Mwanza region. Method Qualitative, inductive approach with critical incident technique was used. Data were analysed using the critical incident technique, and a question guide consisting of eleven open-ended questions was used to collect data from 44 out of 60 midwives who graduated not less than one year. A total of 522 critical incidents, with 199 actions and 323 experiences, were identified and categorized into five main areas. Ethical approval was obtained. Results Midwives’ clinical actions and experiences in caring for women with APH are affected by the knowledge and skills obtained during training at school. They have insufficient theoretical knowledge and practical skills, leading to inadequate identification of the problem and the implementation of care. A need for additional preventive care is described and structural issues, such as co-operation, referral to other instances, access to equipment and relevant treatments need to be improved. Conclusion The actions taken to provide care for women with APH were related to their ability to identify problems, implement care and carry out structural initiatives. However, the midwives’ experience was influenced by an attempt to understand the seriousness of the situation and the existence of an organizational challenge. The results can provide knowledge and tools to improve midwives’ education and clinical practice and in the long run, prevent complications, improves health and minimize suffering in women with APH.

Over the past decade, focused ultrasound (FUS) has emerged as a promising therapeutic modality for various medical conditions. However, the exponential growth in the published literature on FUS therapies has made the literature review process increasingly time-consuming, inefficient, and error-prone. Machine learning approaches offer a promising solution to address these challenges. Therefore, the purpose of our study is to (1) explore and compare machine learning techniques for the text classification of scientific abstracts, and (2) integrate these machine learning techniques into the conventional literature review process. A classified dataset of 3588 scientific abstracts related and unrelated to FUS therapies sourced from the PubMed database was used to train various traditional machine learning and deep learning models. The fine-tuned Bio-ClinicalBERT (Bidirectional Encoder Representations from Transformers) model, which we named FusBERT, had comparatively optimal performance metrics with an accuracy of 0.91, a precision of 0.85, a recall of 0.99, and an F1 of 0.91. FusBERT was then successfully integrated into the literature review process. Ultimately, the integration of this model into the literature review pipeline will reduce the number of irrelevant manuscripts that the clinical team must screen, facilitating efficient access to emerging findings in the field.

Abstract Background Bronchoalveolar lavage (BAL) is a common procedure for evaluation of the equine lower airways. Time to resolution of post‐BAL inflammation has not been clearly defined. Hypothesis Residual inflammation, evident by changes in immune cell populations and inflammatory cytokines, will resolve by 72 hours after BAL. Animals Six adult, healthy, institution‐owned horses. Methods Randomized, complete cross‐over design. Each horse underwent 3 paired BALs, including a baseline and then 48, 72, and 96 hours later, with a 7‐day washout between paired BALs. Each sample underwent cytological evaluation and cytokine concentrations were determined by a commercially available multiplex bead immunoassay. Statistical analysis was performed by multilevel mixed‐effects Poisson regression analysis. Data are reported as marginal means and 95% confidence interval (CI). Results Neutrophil, eosinophil and mast cell percentages were not significantly different at any time points. Macrophage percentages were higher at 72 hours (45.0 [95% CI, 41.6‐48.4]%) and 96 hours (45.3 [95% CI, 42.9‐47.7]%) vs baseline (37.4 [95% CI, 33.5‐41.4]%; P

Generating synthetic contrast-enhanced liver MRI scans from native MRI images can serve to mitigate the issue of sparse contrast-enhanced image datasets while concurrently circumventing the time-consuming and costly process of administering contrast agents during image acquisition. In this study, we conducted three experiments using paired image-to-image translation techniques. Native T1 sequences showing the abdominal liver region served as the input, while contrast-enhanced T1 sequences were the target. The data preprocessing methods and image boundaries were varied for the individual experiments in addition to the implementation of a 5-fold cross-validation for the top-performing approach. Focusing on liver regions achieved the best results with a mean absolute error (MAE) of 0.0837 ± 0.0068, a mean squared error (MSE) of 0.0128 ± 0.0023 and a peak signal-to-noise ratio (PSNR) of 18.99 ± 0.81 dB. Our findings serve as a proof-of-concept, demonstrating the feasibility of generating contrast-enhanced MRI images. However, the current state necessitates further enhancements for effectively addressing the challenge posed by limited dataset sizes with difficult anatomical circumstances as well as MR imaging-related heterogenous tissue contrasts.

The increased clinical relevance of image-guided procedures, particularly of interventional magnetic resonance imaging (iMRI), highlights the need for advanced devices and robotics to optimize those procedures. To enable a realistic integration of robotics into the clinical workflow, robotic-patient interfaces (RPI) are required to ensure both functionality and usability. However, current concepts have issues with patient accessibility and safety, user handling, or performing interventions on versatile body regions. This work presents a novel silicone-based RPI to flexibly mount the ’Micropositioning Robotics for Image-Guided Surgery’ (μRIGS) system on differently shaped body regions through vacuum, regulated with an electronic miniature pump. Maximum holding forces of 60N at −0.1 bar and 66N at −0.2 bar relative vacuum pressure were reached depending on the applied human body area and tensile force angles. MRI with the integrated metasurface indicated up to 200% signal enhancement, enabling improved tissue contrast within the first 20mm in depth. The multifunctional design supported the incorporation of the sterile iMRI workflow concept. This RPI enables a realistic integration of future technologies such as miniature robots, tracking markers, and instrument holders into complex interventional workflows. Further long-term studies are needed to evaluate the effects of vacuum application lasting for 1-2 hours on different skin types.

Abstract Microbial carbon use efficiency (CUE) affects the fate and storage of carbon in terrestrial ecosystems, but its global importance remains uncertain. Accurately modeling and predicting CUE on a global scale is challenging due to inconsistencies in measurement techniques and the complex interactions of climatic, edaphic, and biological factors across scales. The link between microbial CUE and soil organic carbon relies on the stabilization of microbial necromass within soil aggregates or its association with minerals, necessitating an integration of microbial and stabilization processes in modeling approaches. In this perspective, we propose a comprehensive framework that integrates diverse data sources, ranging from genomic information to traditional soil carbon assessments, to refine carbon cycle models by incorporating variations in CUE, thereby enhancing our understanding of the microbial contribution to carbon cycling.

Abstract Natural climate solutions are critical actions of ecosystem stewardship to mitigate climate change. However, prioritizing locations and possible actions is challenging. We demonstrate a generalizable approach for identifying potential opportunities for natural climate solutions by creating a spatial hierarchy of land management restrictions. Global forest carbon stocks and flux models were then used to explore forest-based natural climate solutions in the high-carbon density coastal temperate rainforests of western North America. Our results show 13 million hectares are available for action, an area that holds 4,900 ± 640 megatonnes of carbon dioxide equivalent and represents 45% of regional and 0.5% of global aboveground forest carbon stocks. Based on historical trends, a 10% reduction in average annual forest carbon loss through improved forest management and conservation could reduce forest carbon emissions by 9.1 megatonnes of carbon dioxide equivalent per year, corresponding to 5.2% of the 2030 land-based climate commitments made by the United States and Canada. Large-scale implementation of natural climate solutions will require collaborative planning with forest-dependent communities, industry, governments, and Indigenous peoples.

Abstract Background Firearm purchasing records offer a potentially important administrative data source to identify individuals at elevated risk of perpetrating firearm violence. In this study, we describe individual, firearm, and transaction characteristics of purchasers in California who were arrested for a firearm-related violent crime (FRV) as compared to the general population of registered purchasers in the state. Methods Relying on a dataset of all individuals with transaction records in California (1996–2021), linked to criminal records (1980–2021), we enrolled a cohort of individuals for whom we could capture the legal firearm purchase history. We identified those arrested for FRV post purchase, and using incidence density sampling, gender-matched cases to ten purchasers (controls) who remained “at risk” at the time the case was arrested. We focused on the purchase closest in time prior to the arrest (“index” purchase). We implemented conditional logistic regression and included models with controls for individual- and community-level demographics, as well as interactions between firearm and purchasing characteristics and criminal history. Results The cohort included 1,212,144 individuals, of whom 6153 were arrested for FRV (0.5%). Cases were matched to 61,530 controls to form the study sample. The largest risk factor was a prior criminal history: purchasers had 5.84 times the risk of FRV if they had a prior arrest within three years of the index purchase (CI 5.44–6.27). Several transaction and firearm characteristics were also associated with FRV. For example, risk increased if the firearm was redeemed at a pawn shop (aIRR: 1.37, CI 1.05–1.77) and decreased if the transaction was a registered private party transfer (vs. retail purchase) (aIRR: 0.83, CI 0.76–0.90) or the firearm was a bolt action firearm (vs. semi-automatic) (aIRR: 0.64, CI 0.51–0.79). In the interaction models, most of the purchase and firearm features only remained significant among those with no criminal history. Conclusions Given limited data on firearm transactions, there has been little research on whether the type of firearm an individual purchases or the nature of the purchase might serve as indicators of risk for FRV. We found several transaction and firearm features were associated with risk of FRV. Notably, these features provided little evidence of additional risk for those with a prior criminal record.

Abstract Background Diagnostic radiology residents in low- and middle-income countries (LMICs) may have to provide significant contributions to the clinical workload before the completion of their residency training. Because of time constraints inherent to the delivery of acute care, some of the most clinically impactful diagnostic radiology errors arise from the use of Computed Tomography (CT) in the management of acutely ill patients. As a result, it is paramount to ensure that radiology trainees reach adequate skill levels prior to assuming independent on-call responsibilities. We partnered with the radiology residency program at the Aga Khan University Hospital in Nairobi (Kenya) to evaluate a novel cloud-based testing method that provides an authentic radiology viewing and interpretation environment. It is based on Lifetrack, a unique Google Chrome-based Picture Archiving and Communication System, that enables a complete viewing environment for any scan, and provides a novel report generation tool based on Active Templates which are a patented structured reporting method. We applied it to evaluate the skills of AKUHN trainees on entire CT scans representing the spectrum of acute non-trauma abdominal pathology encountered in a typical on-call setting. We aimed to demonstrate the feasibility of remotely testing the authentic practice of radiology and to show that important observations can be made from such a Lifetrack-based testing approach regarding the radiology skills of an individual practitioner or of a cohort of trainees. Methods A total of 13 anonymized trainees with experience from 12 months to over 4 years took part in the study. Individually accessing the Lifetrack tool they were tested on 37 abdominal CT scans (including one normal scan) over six 2-hour sessions on consecutive days. All cases carried the same clinical history of acute abdominal pain. During each session the trainees accessed the corresponding Lifetrack test set using clinical workstations, reviewed the CT scans, and formulated an opinion for the acute diagnosis, any secondary pathology, and incidental findings on the scan. Their scan interpretations were composed using the Lifetrack report generation system based on active templates in which segments of text can be selected to assemble a detailed report. All reports generated by the trainees were scored on four different interpretive components: (a) acute diagnosis, (b) unrelated secondary diagnosis, (c) number of missed incidental findings, and (d) number of overcalls. A 3-score aggregate was defined from the first three interpretive elements. A cumulative score modified the 3-score aggregate for the negative effect of interpretive overcalls. Results A total of 436 scan interpretations and scores were available from 13 trainees tested on 37 cases. The acute diagnosis score ranged from 0 to 1 with a mean of 0.68 ± 0.36 and median of 0.78 (IQR: 0.5-1), and there were 436 scores. An unrelated secondary diagnosis was present in 11 cases, resulting in 130 secondary diagnosis scores. The unrelated secondary diagnosis score ranged from 0 to 1, with mean score of 0.48 ± 0.46 and median of 0.5 (IQR: 0–1). There were 32 cases with incidental findings, yielding 390 scores for incidental findings. The number of missed incidental findings ranged from 0 to 5 with a median at 1 (IQR: 1–2). The incidental findings score ranged from 0 to 1 with a mean of 0.4 ± 0.38 and median of 0.33 (IQR: 0- 0.66). The number of overcalls ranged from 0 to 3 with a median at 0 (IQR: 0–1) and a mean of 0.36 ± 0.63. The 3-score aggregate ranged from 0 to 100 with a mean of 65.5 ± 32.5 and median of 77.3 (IQR: 45.0, 92.5). The cumulative score ranged from − 30 to 100 with a mean of 61.9 ± 35.5 and median of 71.4 (IQR: 37.4, 92.0). The mean acute diagnosis scores and SD by training period were 0.62 ± 0.03, 0.80 ± 0.05, 0.71 ± 0.05, 0.58 ± 0.07, and 0.66 ± 0.05 for trainees with ≤ 12 months, 12–24 months, 24–36 months, 36–48 months and > 48 months respectively. The mean acute diagnosis score of 12–24 months training was the only statistically significant greater score when compared to ≤ 12 months by the ANOVA with Tukey testing (p = 0.0002). We found a similar trend with distribution of 3-score aggregates and cumulative scores. There were no significant associations when the training period was categorized as less than and more than 2 years. We looked at the distribution of the 3-score aggregate versus the number of overcalls by trainee, and we found that the 3-score aggregate was inversely related to the number of overcalls. Heatmaps and raincloud plots provided an illustrative means to visualize the relative performance of trainees across cases. Conclusion We demonstrated the feasibility of remotely testing the authentic practice of radiology and showed that important observations can be made from our Lifetrack-based testing approach regarding radiology skills of an individual or a cohort. From observed weaknesses areas for targeted teaching can be implemented, and retesting could reveal their impact. This methodology can be customized to different LMIC environments and expanded to board certification examinations.