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Abstract Background Infants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial). Design The PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4–8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved. Trial registration ClinicalTrials.gov NCT04373902 (registered April 2020).

Abstract Background Healthcare professionals (HCPs) are increasingly recommended to play an important role in supporting people with chronic disease in work participation. An intervention for HCPs to provide work-related support to their patients in clinical care was developed with intervention mapping (Maastricht Work-Related Support; Maastricht WRS). Action research proposes ‘combining research and practice’, which allows us to incorporate experiences of HCPs while implementing and to realize intervention’s full potential. Therefore, the aim of this study is to explore, by integrating action research into an intervention mapping approach, how experiences of HCPs with early implementation can be used to optimize the Maastricht WRS in clinical care. Methods Semi-structured interviews were held with nine HCPs (response rate 82%), involved in care for people with inflammatory arthritis, knee problems or inflammatory bowel disease. Some of them were not yet trained in the Maastricht WRS while others had received the training and were providing the Maastricht WRS. Results All participants regarded WRS an important part of clinical care. Untrained HCPs indicated a lack of knowledge and skills in providing the Maastricht WRS, and a need for tools. Trained HCPs were satisfied with the training and tools, but stressed that practical limitations hindered providing the Maastricht WRS. Action research showed that the intervention meets the needs of HCPs, but need some optimizations: (1) organizing ‘intervision’ for HCPs, (2) inform and activate patients to discuss work with their HCP, (3) update initial tools and (4) including patients’ work status in the electronic patient system. Conclusions Action research integrated into intervention mapping proved to improve the Maastricht WRS intervention. By involving HCPs, the intervention could be optimized to provide to support people with chronic diseases in clinical care in healthy and sustainable work participation.

Abstract The iconic European stag beetle (Lucanus cervus) (Coleoptera: Lucanidae) is one of the largest terrestrial beetles in Europe. Due to decreasing population numbers, thought to be a consequence of habitat loss, this beetle has become a near-threatened species across much of Europe, and a reliable monitoring system is required to measure its future population trends. As part of a programme aimed at conserving UK populations, we have investigated the chemical ecology of the beetle, with a view to developing an efficient semiochemical-based monitoring system. Such a scheme will be beneficial not only in the UK but across the European range of the species, where the beetle is of conservation concern. Here, we report on a surprising discovery of a male-produced pheromone, which provokes initial sexual receptivity in females, and which has not been previously identified in the animal kingdom. Furthermore, we assign sex pheromone function to a previously described female-specific compound.

Abstract Background Tumor regression following immune checkpoint blockade (ICB) is often associated with immune-related adverse events (irAEs), marked by inflammation in non-cancerous tissues. This study was undertaken to investigate the functional relationship between anti-tumor and anti-self immunity, to facilitate irAE management while promoting anti-tumor immunity. Methods Multiple biopsies from tumor and inflamed tissues were collected from a patient with melanoma experiencing both tumor regression and irAEs on ICB, who underwent rapid autopsy. Immune cells infiltrating melanoma lesions and inflamed normal tissues were subjected to gene expression profiling with multiplex qRT-PCR for 122 candidate genes. Subsequently, immunohistochemistry was conducted to assess the expression of 14 candidate markers of immune cell subsets and checkpoints. TCR-beta sequencing was used to explore T cell clonal repertoires across specimens. Results While genes involved in MHC I/II antigen presentation, IFN signaling, innate immunity and immunosuppression were abundantly expressed across specimens, irAE tissues over-expressed certain genes associated with immunosuppression (CSF1R, IL10RA, IL27/EBI3, FOXP3, KLRG1, SOCS1, TGFB1), including those in the COX-2/PGE2 pathway (IL1B, PTGER1/EP1 and PTGER4/EP4). Immunohistochemistry revealed similar proportions of immunosuppressive cell subsets and checkpoint molecules across samples. TCRseq did not indicate common TCR repertoires across tumor and inflammation sites, arguing against shared antigen recognition between anti-tumor and anti-self immunity in this patient. Conclusions This comprehensive study of a single patient with melanoma experiencing both tumor regression and irAEs on ICB explores the immune landscape across these tissues, revealing similarities between anti-tumor and anti-self immunity. Further, it highlights expression of the COX-2/PGE2 pathway, which is known to be immunosuppressive and potentially mediates ICB resistance. Ongoing clinical trials of COX-2/PGE2 pathway inhibitors targeting the major COX-2 inducer IL-1B, COX-2 itself, or the PGE2 receptors EP2 and EP4 present new opportunities to promote anti-tumor activity, but may also have the potential to enhance the severity of ICB-induced irAEs.

Abstract Background Familial partial lipodystrophy (FPLD) is an inherited disorder of white adipose tissue that causes premature cardiometabolic disease. There is no clear diagnostic criteria for FPLD, and this may explain the under-detection of this condition. Aim This pilot study aimed to describe the clinical features of women with FPLD and to explore the value of adipose tissue measurements that could be useful in diagnosis. Methods In 8 women with FPLD and 4 controls, skinfold measurements, DXA and whole-body MRI were undertaken. Results Whole genome sequencing was negative for monogenic metabolic causes, but polygenic scores for partial lipodystrophy were elevated in keeping with FPLD type 1. The mean age of diagnosis of DM was 31 years in the FPLD group. Compared with controls, the FPLD group had increased HOMA-IR (10.3 vs 2.9, p = 0.028) and lower mean thigh skinfold thickness (19.5 mm vs 48.2 mm, p = 0.008). The FPLD group had lower percentage of leg fat and an increased ratio of trunk to leg fat percentage on DXA. By MRI, the FPLD group had decreased subcutaneous adipose tissue (SAT) volume in the femoral and calf regions (p

Objective/Background: Sleep problems challenge overall wellbeing. Magnesium has been implicated to benefit sleep, although the clinical evidences varied based on the magnesium source used. Magnesium L-threonate (MgT) is a promising intervention due to its brain bioavailability and effects on cognition, memory and mood. We investigated MgT supplementation on sleep quality and daily function. Patients/methods: Eighty 35–55-year-olds with self-assessed sleep problems participated in a randomized, double-blind, placebo-controlled, parallel-arm study, taking 1 g/day of MgT or placebo for 21 days. Sleep and daily behaviors were measured subjectively using standardized questionnaires including the Insomnia Severity Index, Leeds Sleep Evaluation Questionnaire, and Restorative Sleep Questionnaire, and objectively using an Oura ring. The Profile of Mood States questionnaire and a daily diary were used to evaluate mood, energy and productivity, and record any safety concerns. Results: The MgT group maintained good sleep quality and daytime functioning, while placebo declined. From objective Oura ring measurements, MgT significantly (p

This paper introduces the ‘Australian Park Life Project’ and describes a protocol to standardise the capture and collation of public open greenspace spatial data across Australian cities. This method will progress greenspace research allowing for unique coherent national analyses and comparative research across Australia. We also outline the development of the Park Life public participatory geographic information system (PPGIS) to spatially explore what, and how, public open greenspaces are being used by Australian communities. The combination of community crowdsourced spatial data providing location-specific information on the green public open spaces used, in combination with the national spatial layer of greenspace allows for unique analyses exploring the role of greenspace provision and design on use and represents a transformative strategy in shaping public open space policy and strategy. • A spatial layer of public open greenspace was created for the eight Australian State and Territory capital cities using a standardised data capture and collection method from local government planning schemes and land use data, and listings of managed and demarcated parks and reserves. • The Park Life public participatory geographic information system (PPGIS) was built to capture spatially referenced information on the use of greenspaces - specifically what spaces are used, and how they are used.

Objective: To develop, assess, and refine an online educational tool, Plan for Clarity, to support financial and legal planning in dementia. Methods: A Delphi mixed-method study with three rounds of anonymous review by lay and professional stakeholders was designed to reach consensus about the content of the online tool and explore the socio-cultural and behavioral factors that could affect access and use. Results: Consensus showed that the online tool covered key information, knowledge, and communication skills for financial and legal planning. Study themes: 1) the online tool had to be easy to navigate with relevant, easily understood information; 2) people with early signs of memory difficulties would be able to use the tool; 3) a referral from a trusted source is a primary way to facilitate access and use of the tool; and 4) discussions about financial and legal issues should be held early, ahead of barriers that can block discussion. Conclusion: These data suggest this online tool is relevant and feasible for dementia care and support as well as aging more generally. Innovation: Plan for Clarity is innovative as an evidence and theory-driven online education tool to address financial and legal planning for dementia care, particularly among underserved older adults.

Prostate cancer has heterogeneous growth patterns, and its prognosis is the poorest when it progresses to a neuroendocrine phenotype. Using bioinformatic analysis, we evaluated RNA expression of neuroendocrine genes in a panel of five different cancer types: prostate adenocarcinoma, breast cancer, kidney chromophobe, kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. Our results show that specific neuroendocrine genes are significantly dysregulated in these tumors, suggesting that they play an active role in cancer progression. Among others, synaptophysin (SYP), a conventional neuroendocrine marker, is upregulated in prostate adenocarcinoma (PRAD) and breast cancer (BRCA). Our analysis shows that SYP is enriched in small extracellular vesicles (sEVs) derived from plasma of PRAD patients, but it is absent in sEVs derived from plasma of healthy donors. Similarly, classical sEV markers are enriched in sEVs derived from plasma of prostate cancer patients, but weakly detectable in sEVs derived from plasma of healthy donors. Overall, our results pave the way to explore new strategies to diagnose these diseases based on the neuroendocrine gene expression in patient tumors or plasma sEVs.

Cooperation in food acquisition is a hallmark of the human species. Given that costs and benefits of cooperation vary among production regimes and work activities, the transition from hunting-and-gathering to agriculture is likely to have reshaped the structure of cooperative subsistence networks. Hunter-gatherers often forage in groups and are generally more interdependent and experience higher short-term food acquisition risk than horticulturalists, suggesting that cooperative labour should be more widespread and frequent for hunter-gatherers. Here we compare female cooperative labour networks of Batek hunter-gatherers of Peninsular Malaysia and Tsimane forager-horticulturalists of Bolivia. We find that Batek foraging results in high daily variation in labour partnerships, facilitating frequent cooperation in diffuse networks comprised of kin and non-kin. By contrast, Tsimane horticulture involves more restricted giving and receiving of labour, confined mostly to spouses and primary or distant kin. Tsimane women also interact with few individuals in the context of hunting/fishing activities and forage mainly with spouses and primary kin. These differences give rise to camp- or village-level networks that are more modular (have more substructure when partitioned) among Tsimane horticulturalists. Our findings suggest that subsistence activities shape the formation and extent of female social networks, particularly with respect to connections with other women and non-kin. We discuss the implications of restricted female labour networks in the context of gender relations, power dynamics and the adoption of farming in humans. This article is part of the theme issue Cooperation among women: evolutionary and cross-cultural perspectives.

While it is commonly thought that patrilocality is associated with worse outcomes for women and their children due to lower social support, few studies have examined whether the structure of female social networks covaries with post-marital residence. Here, we analyse scan sample data collected among Tsimane forager-farmers. We compare the social groups and activity partners of 181 women residing in the same community as their parents, their husbands parents, both or neither. Relative to women living closer to their in-laws, women living closer to their parents are less likely to be alone or solely in the company of their nuclear family (odds ratio (OR): 0.6, 95% CI: 0.3-0.9), and more likely to be observed with others when engaging in food processing and manufacturing of market or household goods, but not other activities. Women are slightly more likely to receive childcare support from outside the nuclear family when they live closer to their parents (OR = 1.8, 95% CI 0.8-3.9). Their social group size and their childrens probability of receiving allocare decrease significantly with distance from their parents, but not their in-laws. Our findings highlight the importance of womens proximity to kin, but also indicate that patrilocality per se is not costly to Tsimane women. This article is part of the theme issue Cooperation among women: evolutionary and cross-cultural perspectives.

A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype-phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands. We focused most intensively on the Tsimane, because long-term anthropological work with this group has shown that they have a high burden of both macro and microparasites, as well as minimal cardiometabolic disease or dementia. We therefore generated genome-wide genotype data for Tsimane individuals to study natural selection, and paired this with blood mRNA-seq as well as cardiometabolic and immune biomarker data generated from a larger sample that included both populations. In the Tsimane, we identified 21 regions that are candidates for selective sweeps, as well as 5 immune traits that show evidence for polygenic selection (e.g., C-reactive protein levels and the response to coronaviruses). Genes overlapping candidate regions were strongly enriched for known involvement in immune-related traits, such as abundance of lymphocytes and eosinophils. Importantly, we were also able to draw on extensive phenotype information for the Tsimane and Moseten and link five regions (containing PSD4, MUC21 and MUC22, TOX2, ANXA6, and ABCA1) with biomarkers of immune and metabolic function. Together, our work highlights the utility of pairing evolutionary analyses with anthropological and biomedical data to gain insight into the genetic basis of health-related traits.

BACKGROUND: In industrialized populations, low male testosterone is associated with higher rates of cardiovascular mortality. However, coronary risk factors like obesity impact both testosterone and cardiovascular outcomes. Here, we assess the role of endogenous testosterone on coronary artery calcium in an active subsistence population with relatively low testosterone levels, low cardiovascular risk and low coronary artery calcium scores. METHODOLOGY: In this cross-sectional community-based study, 719 Tsimane forager-horticulturalists in the Bolivian Amazon aged 40+ years underwent computed tomography (49.8% male, mean age 57.6 years). RESULTS: Coronary artery calcium levels were low; 84.5% had no coronary artery calcium. Zero-inflated negative binomial models found testosterone was positively associated with coronary artery calcium for the full sample (Incidence Rate Ratio [IRR] = 1.477, 95% Confidence Interval [CI] 1.001-2.170, P = 0.031), and in a male-only subset (IRR = 1.532, 95% CI 0.993-2.360, P = 0.053). Testosterone was also positively associated with clinically relevant coronary atherosclerosis (calcium >100 Agatston units) in the full sample (Odds Ratio [OR] = 1.984, 95% CI 1.202-3.275, P = 0.007) and when limited to male-only sample (OR = 2.032, 95% CI 1.118-4.816, P = 0.024). Individuals with coronary artery calcium >100 had 20% higher levels of testosterone than those with calcium

IntroductionWe evaluated the prevalence of dementia and mild cognitive impairment (MCI) in indigenous Tsimane and Moseten, who lead a subsistence lifestyle.MethodsParticipants from population-based samples ≥ 60 years of age (n = 623) were assessed using adapted versions of the Modified Mini-Mental State Examination, informant interview, longitudinal cognitive testing and brain computed tomography (CT) scans.ResultsTsimane exhibited five cases of dementia (among n = 435; crude prevalence = 1.2%, 95% confidence interval [CI]: 0.4, 2.7); Moseten exhibited one case (among n = 169; crude prevalence = 0.6%, 95% CI: 0.0, 3.2), all age ≥ 80 years. Age-standardized MCI prevalence was 7.7% (95% CI: 5.2, 10.3) in Tsimane and 9.8% (95% CI: 4.9, 14.6) in Moseten. Cognitive impairment was associated with visuospatial impairments, parkinsonian symptoms, and vascular calcification in the basal ganglia.DiscussionThe prevalence of dementia in this cohort is among the lowest in the world. Widespread intracranial medial arterial calcifications suggest a previously unrecognized, non-Alzheimer's disease (AD) dementia phenotype.

BackgroundHealth systems are increasingly interested in collaborative dementia care. Implementation challenges include the limited dementia specialist workforce, time pressures of high-volume care, increasing use of telemedicine, and inadequate reimbursement. The Care Ecosystem is a telephone-based collaborative dementia care model designed to augment existing healthcare services and be amenable to scale. Here we present the latest evidence for the Care Ecosystem, including the effects among subpopulations at risk for health disparities (rural and Hispanic/Latino), and facilitators from the early phase of Care Ecosystem implementation at 6 diverse health systems.MethodEffectiveness was evaluated in a single-blind, randomized clinical trial (N = 804). Persons with dementia (PWD)-caregiver dyads were randomized to receive 12 months of the intervention (N = 527) or usual care (N = 277). Outcomes were measured via telephone surveys at 6 and 12 months after randomization and medical record review. Subgroup analyses were performed for the 124 dyads who identified as Hispanic/Latino, and the 66 who lived in rural Nebraska or Iowa. The intervention was primarily delivered by an unlicensed, trained care team navigator, who provided education, support and care coordination with supervision and help from a dementia specialist team (advanced practice nurse, social worker, and pharmacist). Implementation facilitators were evaluated through observation and qualitative interviews with clinical teams at 6 health systems implementing the model.ResultsThe PWD-caregiver dyads lived in California (n = 476), Nebraska (n = 286), or Iowa (n = 42). Compared with usual care, the Care Ecosystem improved PWD quality of life, reduced emergency department visits, reduced the use of potentially inappropriate medications, and decreased caregiver depression and caregiver burden. Effect sizes were similar or greater in Hispanic/Latino and rural subgroups on most outcomes. Facilitators of Care Ecosystem implementation included open-access implementation tools (online training, care protocols), the adaptability of the care model, the care team navigator role, and remote care delivery.ConclusionEffective dementia care can be delivered by care team navigators via telephone to mitigate the burdens of dementia, including for underserved PWD living in rural areas or who identify as Hispanic/Latino. Implementation is a challenge although features of the care model appear to facilitate adoption.

Trauma-exposed veterans receiving mental health care may have an elevated risk of experiencing COVID-19-related difficulties. Using data from several ongoing clinical trials (N = 458), this study examined exposure to COVID-19-related stressors and their associations with key sociodemographic factors and mental health outcomes. The results showed that exposure to COVID-19-related stressors was common, higher among veterans who were racial/ethnic minorities d = 0.32, and associated with elevated posttraumatic stress disorder (PTSD), r = .288, and depressive symptom severity, r = .246. Women veterans experienced more difficulty accessing social support, d = 0.31, and higher levels of COVID-19-related distress, d = 0.31, than men. Qualitative data were consistent with survey findings and highlighted the broader societal context in veterans' experience of COVID-19-related distress. These findings may inform future research on the impact of the pandemic on veterans, particularly those who are women and members of minoritized racial/ethnic groups, as well as mental health treatment planning for this population.

BackgroundCarbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole-genome sequence comparison is useful for identifying CRE clonal transmission and outbreaks, but high-frequency horizontal gene transfer (HGT) of carbapenem resistance genes and subsequent genome rearrangement complicate tracing the local persistence and mobilization of these genes across organisms.MethodsTo overcome this limitation, we developed a new approach to identify recent HGT of large, near-identical plasmid segments across species boundaries, which also allowed us to overcome technical challenges with genome assembly. We applied this to complete and near-complete genome assemblies to examine the local spread of CRE in a systematic, prospective collection of all CRE, as well as time- and species-matched carbapenem-susceptible Enterobacterales, isolated from patients from four US hospitals over nearly 5 years.ResultsOur CRE collection comprised a diverse range of species, lineages, and carbapenem resistance mechanisms, many of which were encoded on a variety of promiscuous plasmid types. We found and quantified rearrangement, persistence, and repeated transfer of plasmid segments, including those harboring carbapenemases, between organisms over multiple years. Some plasmid segments were found to be strongly associated with specific locales, thus representing geographic signatures that make it possible to trace recent and localized HGT events. Functional analysis of these signatures revealed genes commonly found in plasmids of nosocomial pathogens, such as functions required for plasmid retention and spread, as well survival against a variety of antibiotic and antiseptics common to the hospital environment.ConclusionsCollectively, the framework we developed provides a clearer, high-resolution picture of the epidemiology of antibiotic resistance importation, spread, and persistence in patients and healthcare networks.

IntroductionDespite successful efforts to improve clinical access and skilled birth attendance in Malawi, it still faces high rates of maternal and neonatal mortality. In 2017, the UCSF-GAIN partnership began a nurse-midwifery clinical education and longitudinal mentorship program. While it has received positive reviews, it is unclear whether routinely collected indicators can assess such a program's impact.MethodA longitudinal review of the Malawian DHIS2 database explored variables associated with maternal and newborn care and outcomes before and after the intervention. Data were analyzed using generalized estimating equations (GEE) to account for facility-level correlations over time.ResultsQuality issues with DHIS2 data were identified. Significant changes potentially associated with the GAIN intervention were noted.DiscussionThe GAIN approach appears to be associated with positive trends in maternal and neonatal care. National summary databases are problematic, however, for evaluating targeted interventions and the provision of care to specific outcomes.

Summary: Tumor self-seeding is a process whereby circulating tumor cells (CTCs) recolonize the primary tumor, which promotes tumor growth, angiogenesis, and invasion. However, the detailed nature and functions of tumor self-seeded cells (TSCs) have not been well defined due to challenges in tracking and isolating TSCs. Here, we report an accurate animal model using photoconvertible tagging to recapitulate the spontaneous process of tumor self-seeding and identify TSCs as a subpopulation of primary tumor cells with enhanced invasiveness and survival. We demonstrate transmembrane-4-L-six-family-1 (TM4SF1) as a marker of TSCs, which promotes migration, invasion, and anchorage-independent survival in cancer cells. By analyzing single-cell RNA sequencing datasets, we identify a potential TSC population with a metastatic profile in patients with cancer, which is detectable in early-stage disease and expands during cancer progression. In summary, we establish a framework to study TSCs and identify emerging cell targets with diagnostic, prognostic, or therapeutic potential in cancers.

Introduction Brace treatment is common to address radiological dysplasia in infants with developmental dysplasia of the hip (DDH); however, it is unclear whether bracing provides significant benefit above careful observation by ultrasound. If observation alone is non-inferior to bracing for radiological dysplasia, unnecessary treatment may be avoided. Therefore, the purpose of this study is to determine whether observation is non-inferior to bracing for infants with radiological dysplasia.Methods and analysis This will be a multicentre, global, randomised, non-inferiority trial performed under the auspices of a global prospective registry for infants and children diagnosed with DDH. Patients will be included if they present with radiological dysplasia (centred hip, alpha angle 43–60°, percent femoral head coverage greater than 35% measured on ultrasound) of a clinically stable hip under 3 months old. Patients will be excluded if they present with clinical hip instability, have received prior treatment or have known/suspected neuromuscular, collagen, chromosomal or lower-extremity congenital abnormalities or syndromic-associated hip abnormalities. Patients will be enrolled and randomised to undergo observation alone or brace treatment with a Pavlik harness for a minimum of 6 weeks. Follow-up visits will occur at 6 weeks, 1 year and 2 years post-enrolment. The primary outcome will be the norm-referenced acetabular index measured on the 2-year radiograph with a 3° non-inferiority margin. A total of 514 patients will be included.The study is anticipated to start in April 2024 and end in September 2028.The primary outcome will be compared between arms with a mixed-effects model with a random intercept for study centre, and a single covariate for the treatment group. If the lower bound of the 95% CI lies within 3° of the mean, we will treat this as evidence for non-inferiority.Ethics and dissemination Ethics approval has been obtained from the lead site’s ethics board (University of British Columbia, Children’s and Women’s Research Ethics Board). Ethics approval will be obtained from the local ethics committees or institutional review boards at each institution prior to patient enrolment. It is intended that the results of this study shall be published in peer-reviewed journals and presented at suitable conferences.Trial registration number NCT05869851.

Abstract With the evolution of interferometric synthetic aperture radar into a tool for active hazard monitoring, new methods are sought to quickly and automatically interpret the large number of interferograms that are created. We present a convolutional neural network (CNN) that is able to both classify the type of deformation, and to locate the deformation within an interferogram in a single step. We achieve this through building a “two headed model,” which returns both outputs after one forward pass of an interferogram through the network. We train our model by first creating a data set of synthetic interferograms, but find that our model's performance is improved through the inclusion of real Sentinel‐1 data. We also investigate how model performance can be improved by best organizing interferograms such that they can exploit the three channel nature of computer vision models trained on very large databases of labeled color images, but find that using different data in each of the three input channels degrades performance when compared to the simple case of repeating wrapped or unwrapped phase across each channel. We also release our labeled Sentinel‐1 interferograms as a database named VolcNet, which consists of ∼500,000 labeled interferograms. VolcNet comprises of time series of unwrapped phase and labels of the magnitude, location, and duration of deformation, which allows for the automatic creation of interferograms between any two acquisitions, and greatly increases the amount of data available compared to other labeling strategies.

BackgroundTrachoma causes blindness due to repeated conjunctival infection by Chlamydia trachomatis (Ct). Transmission intensity is estimated, for programmatic decision-making, by prevalence of the clinical sign trachomatous inflammation-follicular (TF) in children aged 1-9 years. Research into complementary indicators to field-graded TF includes work on conjunctival photography, tests for ocular Ct infection, and serology. The perceived acceptability and feasibility of these indicators among a variety of stakeholders is unknown.MethodologyFocus group discussions (FGDs) with community members and in-depth interviews (IDIs) with public health practitioners in Tanzania were conducted. FGDs explored themes including participants' experience with, and thoughts about, different diagnostic approaches. The framework method for content analysis was used. IDIs yielded lists of perceived strengths of, and barriers to, implementation for programmatic use of each indicator. These were used to form an online quantitative survey on complementary indicators distributed to global stakeholders via meetings, mailing lists, and social media posts.ResultsSixteen FGDs and 11 IDIs were conducted in October-November 2022. In general, all proposed sample methods were deemed acceptable by community members. Common themes included not wanting undue discomfort and a preference for tests perceived as accurate. Health workers noted the importance of community education for some sample types. The online survey was conducted in April-May 2023 with 98 starting the questionnaire and 81 completing it. Regarding barriers to implementing diagnostics, the highest agreement items related to feasibility, rather than acceptability. No evidence of significant differences was found in responses pertaining to community acceptability based on participant characteristics.ConclusionsAll of the indicators included were generally deemed acceptable by all stakeholders in Tanzania, although community education around the benefits and risks of different sample types, as well as addressing issues around feasibility, will be key to successful, sustainable integration of these indicators into trachoma programs.

BackgroundIntrauterine inflammation and the requirement for mechanical ventilation independently increase the risk of perinatal brain injury and adverse neurodevelopmental outcomes. We aimed to investigate the effects of mechanical ventilation for 24 h, with and without prior exposure to intrauterine inflammation, on markers of brain inflammation and injury in the preterm sheep brain.MethodsChronically instrumented fetal sheep at ~115 days of gestation were randomly allocated to receive a single intratracheal dose of 1 mg lipopolysaccharide (LPS) or isovolumetric saline, then further randomly allocated 1 h after to receive mechanical ventilation with room air or no mechanical ventilation (unventilated control + saline [UVC, n = 7]; in utero mechanical ventilation + saline [VENT, n = 8], unventilated control + intratracheal LPS [UVC + LPS, n = 7]; in utero ventilation + intratracheal LPS [VENT + LPS, n = 7]). Serial fetal blood and plasma samples were collected throughout the experimental protocol for assessment of blood biochemistry and plasma interleukin (IL)-6 levels. After 24 h of mechanical ventilation, fetal brains were collected for RT-qPCR and immunohistochemical analyses.ResultsLPS exposure increased numbers of microglia and upregulated pro-inflammatory related genes within the cortical gray matter (GM) and subcortical white matter (SCWM) (pLPS

In this contribution to the proceedings of the 182nd Nobel Symposium, I reflect on the concept of “discovery” as it is used by physicists and astronomers. In particular, I comment on how the scientific community distinguishes discoveries from propositions that are supported only by lesser forms of evidence, emphasizing the social nature of this process and remarking on the subjective factors that go into making such judgments. I advocate for an approach that is intentionally Bayesian in nature, in which individuals are encouraged to evaluate and publicly state their priors and to update them systematically. I close by applying these practices to the case example of the Galactic Center Gamma-Ray Excess.

What happened when a global pandemic shut down schools in March of 2020, causing an after-school graphic novel book club to be all but forgotten? Magic happened, when led by a determined instructional literacy coach and a local university professor. Undaunted, they decided to adapt the graphic novel book club into a synchronous virtual experience for third and fourth grade students. The lessons learned along the way about listening, connecting, technology, chance-taking, and superheroes proved to be helpful to their practices as they blazed new trails in delivering education virtually. The authors offer their story and reflections in the hopes to support other educators as they re-frame perspectives and revise curriculum.

The purpose of this article is to provide an example of how an EdD in Community College Leadership program is offered in an online format. First, the benefits of online programs, including increased access and flexibility for working professionals and higher levels of diversity among the student body are discussed. Then, several strategies to promote connection among students and to facilitate a supportive, engaging learning environment virtually are shared. For example, the value of using a cohort model, a carefully designed curriculum with assignments that have practical value, and a balance of synchronous and asynchronous learning activities are described. Finally, the important role of and strategies for incorporating models and mentors into an online doctoral program are discussed.

BackgroundTo facilitate mass distribution of azithromycin, trachoma control programmes use height instead of weight to determine dose for children 6 months to 15 years old. WHO has recommended azithromycin distribution to children 1-11 months old to reduce mortality in high mortality settings under carefully monitored conditions. Weight was used to determine dose in children 1-5 months old in studies of azithromycin distribution for child survival, but a simplified approach using age or height for all aged 1-11 months old could increase programme efficiency in real-world settings.MethodsThis secondary analysis used data from two cluster randomised trials of azithromycin distribution for child mortality in Niger and Burkina Faso. An exhaustive search algorithm was developed to determine the optimal dose for different age groups, using tolerance limits of 10-20 mg/kg for children 1-2 months old and 15-30 mg/kg for children 3-11 months old. Height-based dosing was evaluated against the existing trachoma dosing pole and with a similar exhaustive search.ResultsThe optimal two-tiered age-based approach suggested a dose of 80 mg (2 mL) for children 1-2 months old and 160 mg (4 mL) for children 3-11 months old. Under this schedule, 89%-93% of children would have received doses within tolerance limits in both study populations. Accuracy was 93%-94% with a three-tiered approach, which resulted in doses of 80 mg (2 mL), 120 mg (3 mL) and 160 mg (4 mL) for children 1-2, 3-4 and 5-11 months old, respectively. For children 1-5 months old, the existing height pole would result in 70% of doses within tolerance limits. The optimisation identified height-based dosing options with 95% accuracy, although this would require changes to the existing dosing pole as well as additional training to measure infants lying flat.ConclusionsOverall, an age-based approach with two age tiers resulted in high accuracy while considering both concerns about overdosing in this young population and simplicity of field operations.

Building performance simulation has been adopted to support decision making in the building life cycle. An essential issue is to ensure a building energy simulation model can capture the reality and complexity of buildings and their systems in both the static characteristics and dynamic operations. Building energy model calibration is a technique that takes various types of measured performance data (e.g., energy use) and tunes key model parameters to match the simulated results with the actual measurements. This study performed an application and evaluation of an automated pattern-based calibration method on commercial building models that were generated based on characteristics of real buildings. A public building dataset that includes high-level building attributes (e.g., building type, vintage, total floor area, number of stories, zip code) of 111 buildings in San Francisco, California, USA, was used to generate building models in EnergyPlus. Monthly level energy use calibrations were then conducted by comparing building model results against the actual buildings’ monthly electricity and natural gas consumption. The results showed 57 out of 111 buildings were successfully calibrated against actual buildings, while the remaining buildings showed opportunities for future calibration improvements. Enhancements to the pattern-based model calibration method are identified to expand its use for: (1) central heating, ventilation and air conditioning (HVAC) systems with chillers, (2) space heating and hot water heating with electricity sources, (3) mixed-use building types, and (4) partially occupied buildings.

Abstract Background Breastfeeding provides many short- and long-term health benefits for mothers and their infants and is a particularly relevant strategy for women who experience Gestational Diabetes Mellitus (GDM) during pregnancy. However, breastfeeding rates are generally lower amongst this group of women than the general population. This review’s objective is to identify the factors that influence breastfeeding by exploring the experiences and outcomes of women in in high-income health care contexts when there is a history of GDM in the corresponding pregnancy. Methods A comprehensive search strategy explored the electronic databases Medline, CINAHL, Web of Science and Scopus for primary studies exploring breastfeeding practices for papers published between January 2011 and June 2023. All papers were screened independently by two researchers with included papers assessed using the Crowe Critical Appraisal tool. Findings were analysed using a narrative synthesis framework. Results From an initial search result of 1037 papers, 16 papers representing five high-income nations were included in this review for analysis – the United States of America (n = 10), Australia (n = 3), Finland (n = 1), Norway (n = 1), and Israel (n = 1). Fifteen papers used a quantitative design, and one used a qualitative design. The total number of participants represented in the papers is 963,718 of which 812,052 had GDM and 151,666 did not. Women with an immediate history of GDM were as likely to initiate breastfeeding as those without it. However, they were more likely to have the first feed delayed, be offered supplementation, experience delayed lactogenesis II and or a perception of low supply. Women were less likely to exclusively breastfeed and more likely to completely wean earlier than the general population. Maternity care practices, maternal factors, family influences, and determinants of health were contextual and acted as either a facilitator or barrier for this group. Conclusion Breastfeeding education and support need to be tailored to recognise the individual needs and challenges of women with a history of GDM. Interventions, including the introduction of commercial milk formula (CMF) may have an even greater impact and needs to be very carefully considered. Supportive strategies should encompass the immediate and extended family who are major sources of influence.

While satellite persistent scatterer synthetic aperture radar (SAR) interferometry is an effective technique to monitor the health of structures via selection of long-term coherent pixels, detailed interpretation of displacement measurements requires knowledge of which surfaces, the reflection is coming from. Ray tracing algorithms can be used to simulate SAR backscatter for structures, and link observed PS pixels to specific parts of structures. We investigate the reflectivity of three bridges in London for a high-resolution TerraSAR-X dataset, using a ray tracing technique. Artificial reflectors are mounted on one of the bridges. We compare the simulated backscatter with the location of points selected as PS pixels using a stack of 38 TerraSAR-X images. The results confirm that we can predict overall scattering behavior of a bridge using SAR simulation techniques when we have access to a 3-D model of the structure. However, the results of simulation depend on the level of details in the 3-D model and a high-detailed 3-D model including corner reflectors allows the ray tracing technique to perfectly simulate position of the strong scatterers. This approach can help designers increase the SAR reflectivity of a bridge in the design phase of structural bridge assets, or in a retrofit phase, by installing artificial reflectors. We also link the strong scatterers in the reflectivity map to the corresponding scattering surfaces in the structural model that contributed to the signal. This allows the end-users of the InSAR products to better understand which sections of a bridge are moving when a PS pixel indicates displacement.