Search

Karolina Nemes,1 Pascal D Johann,1,2 Stefanie Tüchert,3 Patrick Melchior,4 Christian Vokuhl,5 Reiner Siebert,6 Rhoikos Furtwängler,7 Michael C Frühwald1 1Paediatrics and Adolescent Medicine, Swabian Children’s Cancer Center, University Medical Center Augsburg, Augsburg, Germany; 2Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; 3Department of Diagnostic and Interventional Radiology, University Hospital Augsburg, Augsburg, Germany; 4Department of Radiation Oncology, University of Saarland, Homburg, Germany; 5Section of Pediatric Pathology, Department of Pathology, University Hospital Bonn, Bonn, Germany; 6Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany; 7Department of Pediatric Hematology and Oncology, University of Saarland, Homburg, GermanyCorrespondence: Michael C FrühwaldEU-RHAB Registry, Swabian Children’s Cancer Center, Paediatrics and Adolescent Medicine, University Medical Center Augsburg, Stenglinstr. 2, Augsburg, 86156, Germany, Tel +49 821 400 9342, Fax +49 821 400 179201, Email Michael.fruehwald@uk-augsburg.deAbstract: Extracranial malignant rhabdoid tumors (extracranial MRT) are rare, highly aggressive malignancies affecting mainly infants and children younger than 3 years. Common anatomic sites comprise the kidneys (RTK – rhabdoid tumor of kidney) and other soft tissues (eMRT – extracranial, extrarenal malignant rhabdoid tumor). The genetic origin of these diseases is linked to biallelic pathogenic variants in the genes SMARCB1, or rarely SMARCA4, encoding subunits of the SWI/SNF chromatin-remodeling complex. Even if extracranial MRT seem to be quite homogeneous, recent epigenome analyses reveal a certain degree of epigenetic heterogeneity. Use of intensified therapies has modestly improved survival for extracranial MRT. Patients at standard risk profit from conventional therapies; most high-risk patients still experience a dismal course and often therapy resistance. Discoveries of clinical and molecular hallmarks and the exploration of experimental therapeutic approaches open exciting perspectives for clinical and molecularly stratified experimental treatment approaches. To ultimately improve the outcome of patients with extracranial MRTs, they need to be characterized and stratified clinically and molecularly. High-risk patients need novel therapeutic approaches including selective experimental agents in phase I/II clinical trials.Keywords: extracranial malignant rhabdoid tumors, eMRT, RTK, experimental therapy, immunotherapy

Improving equity and inclusion for underrepresented groups in the field of Computer Science (CS) has garnered much attention. In particular, there is a long-standing need for diversity efforts that center on the experiences of Black women, and specific actions to increase their representation--especially given the biases that they often encounter in the field. There is limited research concerning Black women in CS, specifically their conceptions of the field and their overarching CS identity development. More research in this area is especially important given the marginalization that Black women often experience at the intersections of their race and gender. Guided by a combination of critical theoretical lenses, this qualitative study examines Black women's conceptions of what it means to be a computer scientist and the degree to which those conceptions map onto how they see themselves in the field. Moreover, we explore experiences that help to bolster Black women's CS identity. The findings highlight key aspects of what it means to be a computer scientist for the Black women in this study--notably the ability to use computing to make societal contributions. Also, the results accentuate key nuances in the participants' personal CS identification, particularly as it relates to the resilience required to overcome unique barriers that many Black women encounter when engaging within the field. Moreover, the findings highlight the importance of social support systems to facilitate Black women's CS identity development. Implications for policy and practice within education and industry are discussed.

The mouse pathogen Citrobacter rodentium is utilized as a model organism for studying infections caused by the human pathogens enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) and to elucidate mechanisms of mucosal immunity. In response to C. rodentium infection, innate lymphoid cells and T cells secrete interleukin (IL)-22, a cytokine that promotes mucosal barrier function. IL-22 plays a pivotal role in enabling mice to survive and recover from C. rodentium infection, although the exact mechanisms involved remain incompletely understood. Here, we investigated whether particular components of the host response downstream of IL-22 contribute to the cytokine's protective effects during C. rodentium infection. In line with previous research, mice lacking the IL-22 gene (Il22-/- mice) were highly susceptible to C. rodentium infection. To elucidate the role of specific antimicrobial proteins modulated by IL-22, we infected the following knockout mice: S100A9-/- (calprotectin), Lcn2-/- (lipocalin-2), Reg3b-/- (Reg3β), Reg3g-/- (Reg3γ), and C3-/- (C3). All knockout mice tested displayed a considerable level of resistance to C. rodentium infection, and none phenocopied the lethality observed in Il22-/- mice. By investigating another arm of the IL-22 response, we observed that C. rodentium-infected Il22-/- mice exhibited an overall decrease in gene expression related to intestinal barrier integrity as well as significantly elevated colonic inflammation, gut permeability, and pathogen levels in the spleen. Taken together, these results indicate that host resistance to lethal C. rodentium infection may depend on multiple antimicrobial responses acting in concert, or that other IL-22-regulated processes, such as tissue repair and maintenance of epithelial integrity, play crucial roles in host defense to attaching and effacing pathogens.

The chemokine CCL28 is highly expressed in mucosal tissues, but its role during infection is not well understood. Here, we show that CCL28 promotes neutrophil accumulation in the gut of mice infected with Salmonella and in the lung of mice infected with Acinetobacter. Neutrophils isolated from the infected mucosa expressed the CCL28 receptors CCR3 and, to a lesser extent, CCR10, on their surface. The functional consequences of CCL28 deficiency varied between the two infections: Ccl28-/- mice were highly susceptible to Salmonella gut infection but highly resistant to otherwise lethal Acinetobacter lung infection. In vitro, unstimulated neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. Moreover, CCL28 stimulation enhanced neutrophil antimicrobial activity, production of reactive oxygen species, and formation of extracellular traps, all processes largely dependent on CCR3. Consistent with the different outcomes in the two infection models, neutrophil stimulation with CCL28 boosted the killing of Salmonella but not Acinetobacter. CCL28 thus plays a critical role in the immune response to mucosal pathogens by increasing neutrophil accumulation and activation, which can enhance pathogen clearance but also exacerbate disease depending on the mucosal site and the infectious agent.

Abstract Background Metastatic urothelial carcinoma (mUC) has a poor prognosis, despite recent therapeutic advancements. Prostaglandin Reductase 1 (PTGR1) is essential for activating acylfulvens, a promising class of drugs for treating a subset of urothelial carcinoma (UC) patients. The efficacy of acylfulvens depends on PTGR1 activity and defects in the nucleotide excision repair (NER) pathway, notably ERCC2 mutations present in 10–15% of bladder tumors. This study identifies patients eligible to be included in acylfulven clinical trials based on the presence of PTGR-1 by immunohistochemistry (IHC) staining, RNA expression level and mutations in the NER pathway. Additionally, it evaluates PTGR-1 expression as a prognostic biomarker. Methods Three PTGR-1 antibodies were tested in a kidney cancer cell line A498 and in tissues with known PTGR1 expression (liver, tonsils, pancreas, small intestine, etc.). Patients with untreated mUC receiving 1st line platinum from Dec. 2019 to Dec. 2021 in the Capital Region, Denmark, were included retrospectively. FFPE tumor samples were collected, and tissue microarrays (TMAs) were constructed. TMAs were stained with the best-performing PTGR1 antibody, RNA expression was analyzed using Nanostring nCounter PanCancer panel and gene mutations were assessed using a targeted genomic panel (TSO-500). Kaplan-Meier and multivariate Cox regression assessed overall survival and covariate impacts. Results The AB181131 PTGR1 antibody was the most reliable in validation tissues. Tumors from 71 mUC patients were used to construct the TMA, and 40% of tumors scored positive for PTGR1 by IHC staining. A normalized PTGR1 RNA cutoff at 2,550 normalized counts achieved an AUC of 0.9, defining 35 samples as positive with a sensitivity of 96% and specificity of 85% in relation to IHC-positivity. Differential expression showed a significant upregulation of PTGR1 RNA in PTGR1 IHC-positive cases. NER-deficiency and PTGR1 positivity (mutations in ERCC1, ERCC2, ERCC3, ERCC4) was seen in 9 patients (13%). Median overall survival was 16 months in the cohort. Overall survival (OS) analysis indicates that overexpression of PTGR1 RNA was associated with a reduced median OS (12 months vs. 25 months, p = 0.039, log-rank). Conclusion PTGR1 IHC staining pattern using the Abcam AB181131 antibody is highly correlated with PTGR1 RNA expression. 13% in our cohort were identified as NER deficient and PTGR1 positive. Lower levels of PTGR1 indicates better outcome in this cohort.

Abstract Background Social inequalities in child mental health are an important public health concern. Whilst previous studies have examined inequalities at a single time point, very few have used repeated measures outcome data to describe how these inequalities emerge. Our aims were to describe social inequalities in child internalising and externalising problems across multiple countries and to explore how these inequalities change as children age. Methods We used longitudinal data from eight birth cohorts containing participants from twelve countries (Australia, Belgium, Denmark, France, Germany, Greece, Italy, Netherlands, Poland, Norway, Spain and the United Kingdom). The number of included children in each cohort ranged from N = 584 (Greece) to N = 73,042 (Norway), with a total sample of N = 149,604. Child socio‐economic circumstances (SEC) were measured using self‐reported maternal education at birth. Child mental health outcomes were internalising and externalising problems measured using either the Strengths and Difficulties Questionnaire or the Child Behavior Checklist. The number of data collection waves in each cohort ranged from two to seven, with the mean child age ranging from two to eighteen years old. We modelled the slope index of inequality (SII) using sex‐stratified multi‐level models. Results For almost all cohorts, at the earliest age of measurement children born into more deprived SECs had higher internalising and externalising scores than children born to less deprived SECs. For example, in Norway at age 2 years, boys born to mothers of lower education had an estimated 0.3 (95% CI 0.3, 0.4) standard deviation higher levels of internalising problems (SII) compared to children born to mothers with high education. The exceptions were for boys in Australia (age 2) and both sexes in Greece (age 6), where we observed minimal social inequalities. In UK, Denmark and Netherlands inequalities decreased as children aged, however for other countries (France, Norway, Australia and Crete) inequalities were heterogeneous depending on child sex and outcome. For all countries except France inequalities remained at the oldest point of measurement. Conclusions Social inequalities in internalising and externalising problems were evident across a range of EU countries, with inequalities emerging early and generally persisting throughout childhood.

High-resolution, spatially distributed process-based (PB) simulators are widely employed in the study of complex catchment processes and their responses to a changing climate. However, calibrating these PB simulators using observed data remains a significant challenge due to several persistent issues, including the following: (1) intractability stemming from the computational demands and complex responses of simulators, which renders infeasible calculation of the conditional probability of parameters and data, and (2) uncertainty stemming from the choice of simplified representations of complex natural hydrologic processes. Here, we demonstrate how simulation-based inference (SBI) can help address both of these challenges with respect to parameter estimation. SBI uses a learned mapping between the parameter space and observed data to estimate parameters for the generation of calibrated simulations. To demonstrate the potential of SBI in hydrologic modeling, we conduct a set of synthetic experiments to infer two common physical parameters – Manning's coefficient and hydraulic conductivity – using a representation of a snowmelt-dominated catchment in Colorado, USA. We introduce novel deep-learning (DL) components to the SBI approach, including an “emulator” as a surrogate for the PB simulator to rapidly explore parameter responses. We also employ a density-based neural network to represent the joint probability of parameters and data without strong assumptions about its functional form. While addressing intractability, we also show that, if the simulator does not represent the system under study well enough, SBI can yield unreliable parameter estimates. Approaches to adopting the SBI framework for cases in which multiple simulator(s) may be adequate are introduced using a performance-weighting approach. The synthetic experiments presented here test the performance of SBI, using the relationship between the surrogate and PB simulators as a proxy for the real case.

Abstract Background Peripheral veno-arterial extracorporeal membrane oxygenation (pECMO) has become the first-line device in refractory cardiogenic shock (rCS). Some pECMO complications can preclude any bridging strategies and a peripheral-to-central ECMO (cECMO) switch can be considered as a bridge-to-decision. We conducted this study to appraise the in-hospital survival and the bridging strategies in patients undergoing peripheral-to-central ECMO switch. Methods This retrospective monocenter study included patients admitted to a ECMO-dedicated intensive care unit from February 2006 to January 2023. Patients with rCS requiring pECMO switched to cECMO were included. Patients were not included when the cECMO was the first mechanical circulatory support. Results Eighty patients, with a median [IQR25-75] age of 44 [29–53] years at admission and a female-to-male sex ratio of 0.6 were included in the study. Refractory pulmonary edema was the main switching reason. Thirty patients (38%) were successfully bridged to: heart transplantation (n = 16/80, 20%), recovery (n = 10/80, 12%) and ventricle assist device (VAD, n = 4/30, 5%) while the others died on cECMO (n = 50/80, 62%). The most frequent complications were the need for renal replacement therapy (76%), hemothorax or tamponade (48%), need for surgical revision (34%), mediastinitis (28%), and stroke (28%). The in-hospital and one-year survival rates were 31% and 27% respectively. Myocardial infarction as the cause of the rCS was the only variable independently associated with in-hospital mortality (HR 2.5 [1.3–4.9], p = 0.009). Conclusions The switch from a failing pECMO support to a cECMO as a bridge-to-decision is a possible strategy for a very selected population of young patients with a realistic chance of heart function recovery or heart transplantation. In this setting, cECMO allows patients triage preventing from wasting expensive and limited resources.

We live in a neurodiverse world, and therefore need to ensure that equally diverse educational opportunities are accessible to all learners. The term "neurodiversity," coined by Judith Singer (1999) describes the broad, and complex, spectrum of human brain functionality. Terms like "neurodivergent" or "neurodistinct" (Goldstein 2020) include a wide range of neurotypes (such as autism, ADHD, ADD, dyslexia, dysgraphia and others). These neurotypes may present with challenging characteristics such as sensory issues, difficulty with executive function, or intense focus on specific interests. However, some of these characteristics can also be strengths when learners are understood, supported, and valued. Informal learning settings can be especially supportive environments for neurodivergent learners because there are often fewer time constraints for accomplishing tasks, activities are frequently hands-on and visual, learners are able to move about the space as they wish, and they can pursue activities in which they are most interested. Many kinds of learners can benefit from settings with these qualities, but they are particularly beneficial for those with sensory, attention, and social difficulties, which neurodivergent people often have. This is why understanding how to make connections between informal and formal education environments is so important for educators seeking to create educational opportunities that are accessible to a broad and neurodiverse learner population.

Clusters of galaxies trace the most non-linear peaks in the cosmic density field. The weak gravitational lensing of background galaxies by clusters can allow us to infer their masses. However, galaxies associated with the local environment of the cluster can also be intrinsically aligned due to the local tidal gradient, contaminating any cosmology derived from the lensing signal. We measure this intrinsic alignment in Dark Energy Survey (DES) Year 1 REDMAPPER clusters. We find evidence of a non-zero mean radial alignment of galaxies within clusters between redshifts 0.1–0.7. We find a significant systematic in the measured ellipticities of cluster satellite galaxies that we attribute to the central galaxy flux and other intracluster light. We attempt to correct this signal, and fit a simple model for intrinsic alignment amplitude (AIA) to the measurement, finding AIA = 0.15 ± 0.04, when excluding data near the edge of the cluster. We find a significantly stronger alignment of the central galaxy with the cluster dark matter halo at low redshift and with higher richness and central galaxy absolute magnitude (proxies for cluster mass). This is an important demonstration of the ability of large photometric data sets like DES to provide direct constraints on the intrinsic alignment of galaxies within clusters. These measurements can inform improvements to small-scale modelling and simulation of the intrinsic alignment of galaxies to help improve the separation of the intrinsic alignment signal in weak lensing studies.

Abstract In contrast to transplant recipients, there is a paucity of data regarding frequency and clinical significance of viraemia in children receiving conventional chemotherapy. In a prospective observational study, we assessed the frequency of and clinical impact of viraemia with cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, human herpesvirus-6 (HHV6) and herpes-simplex virus 1/2 (HSV1/2) in paediatric cancer patients at diagnosis, at a routine examination during intensive chemotherapy, and during febrile neutropenia (FN). Seventy-nine patients (median age 6 years; 66 children with haematological malignancies) were included in the study. Overall, 362 blood samples were analysed, 72 from the time at diagnosis (11.1% with positive PCR result), 118 during a regular control after chemotherapy (11.0% positive), and 159 during FN (8.8% positive). The overall positivity rate was 9.6% (CMV 3.3%, HHV6 2.7%, HSV 2.2%, EBV 0.8% and adenovirus 0.3%). There were no significant differences between FN episodes with and without viraemia in terms of duration of fever or neutropenia/lymphopenia, severity of mucositis (> II0), incidence of diarrhea and ICU admission. Our results indicate that viraemia in paediatric cancer patients generally does not have a major clinical impact, and may help in the decision regarding the indication of routine evaluation for viraemia in febrile neutropenic, but otherwise asymptomatic children.

Abstract Background Large conductance calcium-activated potassium (BKCa) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BKCa channel opener) could induce migraine-like headache in persons with PPTH. Methods This is a randomized double-blind, placebo-controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic saline) that was infused intravenously over 20 minutes. The two experiment sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. The secondary endpoint was the area under the curve (AUC) values for headache intensity scores between MaxiPost and placebo over the same 12-hour observation period. Results Twenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P = .02). Furthermore, the median headache intensity scores, represented by AUC values, were higher following MaxiPost than after placebo (P < .001). Conclusions Our results indicate that BKCa channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BKCa channels might present a novel avenue for drug discovery. Additional investigations are nonetheless needed to confirm these insights and explore the therapeutic prospects of BKCa channel blockers in managing PPTH. ClinicalTrials.gov Identifier NCT05378074.

Abstract The demand for open data and open science is on the rise, fueled by expectations from the scientific community, calls to increase transparency and reproducibility in research findings, and developments such as the Final Data Management and Sharing Policy from the U.S. National Institutes of Health and a memorandum on increasing public access to federally funded research, issued by the U.S. Office of Science and Technology Policy. This paper explores the pivotal role of data repositories in biomedical research and open science, emphasizing their importance in managing, preserving, and sharing research data. Our objective is to familiarize readers with the functions of data repositories, set expectations for their services, and provide an overview of methods to evaluate their capabilities. The paper serves to introduce fundamental concepts and community-based guiding principles and aims to equip researchers, repository operators, funders, and policymakers with the knowledge to select appropriate repositories for their data management and sharing needs and foster a foundation for the open sharing and preservation of research data.

ABSTRACT: We present the first systematic follow-up of Planck Sunyaev–Zeldovich effect (SZE) selected candidates down to signal-to-noise (S/N) of 3 over the 5000 deg2 covered by the Dark Energy Survey. Using the MCMF cluster confirmation algorithm, we identify optical counterparts, determine photometric redshifts, and richnesses and assign a parameter, fcont, that reflects the probability that each SZE-optical pairing represents a random superposition of physically unassociated systems rather than a real cluster. The new PSZ-MCMF cluster catalogue consists of 853 MCMF confirmed clusters and has a purity of 90 per cent. We present the properties of subsamples of the PSZ-MCMF catalogue that have purities ranging from 90 per cent to 97.5 per cent, depending on the adopted fcont threshold. Halo mass estimates M500, redshifts, richnesses, and optical centres are presented for all PSZ-MCMF clusters. The PSZ-MCMF catalogue adds 589 previously unknown Planck identified clusters over the DES footprint and provides redshifts for an additional 50 previously published Planck-selected clusters with S/N>4.5. Using the subsample with spectroscopic redshifts, we demonstrate excellent cluster photo-z performance with an RMS scatter in Δz/(1 + z) of 0.47 per cent. Our MCMF based analysis allows us to infer the contamination fraction of the initial S/N>3 Planck-selected candidate list, which is ∼50 per cent. We present a method of estimating the completeness of the PSZ-MCMF cluster sample. In comparison to the previously published Planck cluster catalogues, this new S/N>3 MCMF confirmed cluster catalogue populates the lower mass regime at all redshifts and includes clusters up to z∼1.3.

Purpose The Management of Post-transplant Infections in Collaborating Hospitals (MATCH) programme, initiated in 2011 and still ongoing, was created to 1) optimise the implementation of existing preventive strategies against viral infections in solid organ transplant (SOT) recipients and allogenic haematopoietic stem-cell transplant (HSCT) recipients and 2) advance research in the field of transplantation by collecting data from a multitude of sources.Participants All SOT and HSCT recipients at Copenhagen University Hospital, Rigshospitalet, are followed in MATCH. By February 2021, a total of 1192 HSCT recipients and 2039 SOT recipients have been included. Participants are followed life long. An automated electronic data capture system retrieves prospective data from nationwide registries. Data from the years prior to transplantation are also collected.Findings to date Data entries before and after transplantation include the following: biochemistry: 13 995 222 and 26 127 817; microbiology, cultures: 242 023 and 410 558; other microbiological analyses: 265 007 and 566 402; and pathology: 170 884 and 200 394. There are genomic data on 2431 transplant recipients, whole blood biobank samples from 1003 transplant recipients and faeces biobank samples from 207 HSCT recipients. Clinical data collected in MATCH have contributed to 50 scientific papers published in peer-reviewed journals and have demonstrated success in reducing cytomegalovirus disease in SOT recipients. The programme has established international collaborations with the Swiss Transplant Cohort Study and the lung transplant cohort at Toronto General Hospital.Future plans Enrolment into MATCH is ongoing with no planned end date for enrolment or follow-up. MATCH will continue to provide high-quality data on transplant recipients and expand and strengthen international collaborations.

Objectives This study presents the process evaluation of an effective stepped-care programme of eHealth interventions (Doing What Matters in Times of Stress [DWM] and Problem Management Plus [PM+]) for healthcare workers (HCWs) with psychological distress (RESPOND-HCWs trial) conducted in Spain. The aim is to analyse the context in which the programme was delivered, assess key implementation outcomes and explore mechanisms of action. Methods We used mixed methods. Quantitative data came from routine randomised control trial monitoring and structured observation, and qualitative data were collected using semi-structured, in-depth interviews with trial participants ( n = 12) and decision-makers ( n = 7) and a focus group discussion with intervention providers ( n = 7). We conducted a descriptive analysis of quantitative data using R software and a thematic analysis of qualitative data using NVivo. Results Context analysis revealed implementation barriers, including unrealistic expectations of participants about the programme and mental health-related stigma. The flexibility of interventions and the opportunity for mental health actions were enabling factors. Implementation outcomes showed that the trial was feasible, appropriate and timely, and that the intervention was delivered with minimal protocol deviations and good acceptance among participants. Mechanisms of action included confidence in the positive effect of the intervention, a good therapeutic relationship and specific intervention components. Conclusions These results supplement the outcome evaluation and can help inform large-scale implementation in similar settings. Specific recommendations include increasing mental health awareness and reducing stigma in the implementation setting, including a short orientation session and ensuring flexibility in schedules and peer support. Trial registration number NCT04980326.

Summary: Background: Early childcare attendance may be related to children's internalizing and externalizing symptoms throughout childhood and young adolescence, however evidence from Europe is limited. We aimed to assess this association across multiple population-based birth cohorts of children recruited in different European countries. Methods: Data come from six parent-offspring prospective birth cohort studies across five European countries within the EU Child Cohort Network. A total of 87,208 parent-child dyads were included in the study. To test associations between childcare attendance (centre-based or informal) anytime between ages 0 and 4 years and children's internalizing and externalizing symptoms in middle childhood and young adolescence (measured at: 5–6 years, 7–9 years, and 10–13 years) a two-stage individual participant data meta-analysis was implemented. Linear regression models were performed in each cohort separately; combined random-effects meta-analysis was then used to obtain overall association estimates. In secondary analyses, we tested interactions between childcare attendance and mother's post-partum depression, low education status, and the child's sex. Findings: Compared to children who were exclusively cared for by their parents prior to school entry, those who attended centre-based childcare had lower levels of internalizing symptoms in all age groups [5–6 years: β: −1.78 (95% CI: −3.39, −0.16); 7–9 years: β: −0.55 (95% CI: −0.88, −0.73); 10–13 years: β: −0.76 (95% CI: −1.15, −0.37)]. Children who attended informal childcare appeared to have elevated levels of internalizing symptoms between 7–9 and 10–13 years, respectively [β: 1.65 (95% CI: 1.25, 2.06); β: 1.25 (95% CI: 0.96, 1.54)]. Informal childcare attendance was also associated with increased levels of children's externalizing symptoms between 7–9 and 10–13 years, respectively [β: 2.84 (95% CI: 1.41, 4.26); β: 2.19 (95% CI: 0.54, 3.84)]. Interpretation: Early centre-based childcare is associated with decreased levels of children's internalizing symptoms compared to exclusive parental care. For informal childcare, opposite associations were observed. Overall, our results suggest that centre-based childcare attendance may be associated with slight positive impacts on children's emotional development and should be encouraged by public policies. In addition, children from socioeconomically disadvantaged families require special attention, as they may not sufficiently benefit from universal early childhood education and care (ECEC). Funding: This research was funded by the ERC Consolidator grant RESEDA (Horizon Europe, 101001420).

Background: Child sexual abuse (CSA) affects 1 in 5 girls and 1 in 12 boys before age 18. Universal school-based prevention programs are an effective and cost-efficient method of teaching students an array of personal safety skills. However, the programmatic reach of universal school-based programs is limited by the inherent reliance on the school infrastructure and a dearth of available alternative delivery modalities. Methods: The design for this study will use a rigorous cluster randomized design (N = 180 classrooms) to determine the equivalence of two delivery modalities of Safe Touches: as usual vs. modified. The as usual workshop will be delivered by two facilitators with live puppet skits (n = 90). Whereas, the modified workshop will be delivered by one facilitator using prerecorded skit videos (n = 90). We will determine the equivalence by measuring concept learning acquisition preworkshop to immediate postworkshop (Aim 1) and retention at 3-months postworkshop (Aim 2) among students in classrooms that receive the as usual or modified workshops. To conclude equivalence, it is imperative to also examine factors that may impact future dissemination and implementation, specifically program adoption among school personnel and implementation fidelity between the two modalities (Aim 3). Conclusion: Study findings will inform the ongoing development of effective CSA prevention programs and policy decisions regarding the sustainable integration of such programs within schools. Clinical trial registration: NCT06195852.

Analysis of impervious surface expansion in urban areas has been a great deal all over the world. The impact of this expansion has been challenging the environment, people in particular. This study has considered the expansion in urban imperviousness as one of the root causes of urban water accumulation and the subsequent disturbances that people incur in urban areas especially during rainstorms. Goal and Objectives: Analyzing the relationship between urban imperviousness and the resulting urban runoff Methodology: The determination of the impervious surface was through the Normalized Built-up Index (NDBI) from Landsat 5 (1995 and 2009) and Landsat 8 (2017) imagery whereas the determination of runoff of the area of interest was through the SCS-CN method Results: The two datasets were found to be positively correlating, i.e. an increase in the impervious surface resulted into an increase in urban runoff and vice versa. It was found that, although 2017 had the lowest runoff interval of 3.907-72.08 due to a least amount of rainfall, it had a maximum coverage (imperviousness) of 93.16 Sq.km for runoff compared to 1995 and 2009

# Background E-learning plays a key role in bridging competency gaps among the public health workforce to prevent, detect, and respond to public health emergencies. However, its implementation remains a challenge in resource-limited settings. In this study, we assessed the contextual fit and feasibility of a multi-communication online training (MOT) for its effective implementation. # Methods A mixed-methods study was conducted among public health workers in 16 West African countries between Aug 10, 2023, and Oct 10, 2023. Data were collected through an online survey and in-depth interviews. Through a One Health forum and subregionally coordinated efforts, participants were sampled for the survey and interviews using virtual snowball and voluntary response techniques respectively. Contextual fit was measured with MOT preference and acceptability, while feasibility was measured with MOT willingness to use and workplace ICT availability using a novel tool. Statistical weighting was applied, and interviews were thematically analysed. Quantitative data were analysed using SAS version 9.4 with inverse probability weights and post-stratification weights at the country level. Descriptive statistics were summarized as unweighted and weighted frequencies and weighted proportions. Rao-Scott Chi-square test and Fisher’s exact test were used to identify factors with prognostic potential that were subjected to bivariate and multivariate analyses with a binary logit regression model to assess associations. Qualitative data were managed using Microsoft Excel and MAXQDA 10. # Results A total of 231 survey responses were collected and seven interviews conducted. MOT was found to be of “somewhat” contextual fit with population estimates of (preference: 29.61%, CI= 23.96-35.27; acceptability: 95.99%, CI= 93.79-98.18), and “strong” feasibility (willingness to use: 95.56%, CI= 93.78-97.35; workplace ICT availability: 82.09%, CI= 77.50-86.68). Work area was found as a major predictor of MOT contextual fit and feasibility, where the probabilities of MOT preference, acceptability, willingness to use, and workplace ICT availability were 42% lower (CI= 0.58-0.59), 99% lower (CI= 0.01-0.14), 95% lower (CI= 0.01-0.40), and 2.57 (CI= 1.22-5.40) times higher respectively for public health workers in rural areas compared to those in urban areas. Triangulating the quantitative and qualitative data showed issues around training resources accessibility, training characteristics, and training environment as factors that contributed to the contextual fit and feasibility ratings. # Conclusions This study findings provided evidence for the contextual fit and feasibility of MOT with geographic disparities, including associated factors that could inform prioritization, adaptation, and scale up of e-learning interventions through the equity lens towards improving the public health workforce capacity for global health security.