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The education sector is becoming increasingly interested in augmented reality (AR) technology. Research has revealed that AR offers a multitude of benefits in supporting learning. Nevertheless, the implementation of AR in the classroom remains limited. As teachers play a pivotal role in the integration of AR in the classroom, it is essential to understand their perspectives to comprehend the factors hindering the widespread adoption of AR at schools. However, few studies have explored teacher attitudes towards integrating AR into educational practice. The present questionnaire study thus seeks to elucidate the perspectives of 158 mentor teachers in German-speaking Switzerland on the implementation of AR in the classroom. The findings suggest that although mentor teachers have a moderately positive attitude towards AR, they have only limited experience with the technology and appear to lack the requisite technical and pedagogical skills and resources. Furthermore, certain teacher characteristics impact the perception of AR as a useful tool and its integration into teaching practice. Teachers seem to require enhanced information, training, and support if augmented reality (AR) is to become a prevalent feature in schools in the future. To this end, further studies need to consider teacher characteristics in more detail.

Background More efficient therapeutic options for non-small cell lung cancer (NSCLC) are needed as the survival at 5 years of metastatic disease is near zero. In this regard, we used a preclinical model of metastatic lung adenocarcinoma (SV2-OVA) to assess the safety and efficacy of novel radio-immunotherapy combining hypofractionated radiotherapy (HRT) with muPD1-IL2v immunocytokine and muFAP-CD40 bispecific antibody.Methods We evaluated the changes in the lung immune microenvironment at multiple timepoints following combination therapies and investigated their underlying antitumor mechanisms. Additionally, we analyzed the tumor clonal heterogeneity upon the combination treatments to explore potential mechanisms associated with the lack of complete response.Results The combination of HRT with muPD1-IL2v had a potent antitumor effect and increased survival in the SV2-OVA lung cancer model. Importantly, this combination therapy was devoid of measurable toxicity. It induced remodeling of the immune contexture through the increase of CD8+ T and natural killer (NK) cells. The addition of muFAP-CD40 to the combination treatment further increased infiltrating CD8+ T cells, expressing high levels of effector molecules, both in the periphery and core tumor regions. An accumulation of CD8+ PD-1+ TOX+ (exhausted) T cells, already at the ‘early’ timepoint, is consistent with the limited clinical benefits provided by the various combination treatments in this model. The study of the clonal dynamics of tumor cells during disease progression and therapy highlighted a clonal selection upon HRT+muPD1-IL2v therapy.Conclusions We demonstrated that HRT+muPD1-IL2v combination is a potent therapeutic strategy to delay tumor growth and increase survival in a metastatic lung cancer model, but additional studies are required to completely understand the resistance mechanisms associated with the lack of complete response in this model.

IntroductionLearning to write is a complex task involving peripheral (e.g., handwriting speed and legibility) and central (e.g., spelling) processes. Coordinating these processes is particularly demanding for novice writers who have not yet automated their handwriting skills. To better support children in developing handwriting, it is crucial to understand the development and interactions of these peripheral and central processes over time.MethodsThis longitudinal study (n = 363; 49.8% girls) investigated the development and interrelations of handwriting speed (time spent on writing tasks), legibility, and spelling in German-speaking first-grade children (Mage = 7 years) across 12 months. The children were assessed at three time points, spaced 6 months apart, from the beginning of the first grade to the start of the second grade.Results and discussionWhile performance in all domains of handwriting (time, legibility, and spelling) improved over the school year, these skills were particularly strongly interrelated at the beginning of writing acquisition but became increasingly independent towards the second grade. Surprisingly, the results from the structural equation model showed that the relations between handwriting legibility and time reversed over time: Initially, faster handwriting was associated with more legible handwriting, while with increasing practice a trade-off appeared. Furthermore, when considering cross-lagged paths, the structural equation model revealed that handwriting legibility at the beginning of the first grade significantly predicted subsequent handwriting time and spelling abilities at the end of the school year. In summary, handwriting proficiency stabilizes quickly, while patterns of associations between peripheral and central handwriting processes change across the first year of handwriting instruction.

ABSTRACT Background Regulators and oncology healthcare providers are increasingly interested in using observational studies of real‐world data (RWD) to complement clinical evidence from randomized controlled trials for informed decision‐making. To generate valid evidence, RWD studies must be carefully designed to avoid systematic biases. The clone‐censor‐weight (CCW) method has been proposed to address immortal time and other time‐related biases. Methods The objective of this manuscript is to de‐mystify the CCW method for cancer researchers by describing and presenting its core components in an accessible and digestible format, using visualizations and examples from cancer‐relevant studies. The CCW method has been applied in diverse settings, including investigations of the effects of surgery within a certain time after cancer diagnosis, the continuation of annual screening mammography, and chemotherapy duration on survival. Results The method handles complex data wherein the treatment group to which an individual belongs is unknown at the start of follow‐up. The three steps of the CCW method involve cloning or duplicating the patient population and assigning one clone to each treatment strategy, artificially censoring the clones when their observed data are inconsistent with the assigned strategy and weighting the cloned and censored population to address selection bias created by the artificial censoring. Conclusions The CCW method is a powerful tool for designing RWD studies in cancer that are free from time‐related biases and successfully, to the extent possible, emulate features of a randomized clinical trial.

The microstructure, crystallographic phases, and mechanical properties of a newly developed Al2O3 – TiO2 – ZrO2 ternary ceramic coating were characterized. The coatings were produced by atmospheric plasma spraying as a preblended powder on Ti-6Al-4 V substrates using the new generation of the Debye-Larmor cascaded plasma torch. The 400 μm thick as-sprayed ternary ceramic coating is compact and neither delamination nor inter-/trans-granular cracks were found. The coating consists of single phase α-Al2O3, monoclinic m-ZrO2, and a nanocrystalline dual phase structure of α-Al2O3 and m-ZrO2. Ti is either present as ZrTiO4 or as solute in the dual phase. Cracking from the tip of the indent is rare and delamination was not observed after the progressive scratch test. The coating has potential in high wear applications for example in medical devices.

This study aimed to create a model to identify land suitable for growing sunn hemp (Crotalaria juncea) and pigeon pea (Cajanus cajan) in the Okavango River basin of the Kavango East region of Namibia. Advanced tree-based ensemble learning models, including Random Forest, Extra Trees, Gradient Boosting, XGBoost and multivariate regression analysis , were employed to enhance analytical accuracy. The Random Forest and XGboost models exhibited outstanding performance, as evidenced by their respective accuracy values of 0.97 and 0.96. In addition, this study proposed an innovative approach through the integration of subjective and objective analytical methods, which are independent of one another. The subjective component of the analysis employed a Multi-Criteria Decision Making-Analytic Hierarchy Process (MCDM-AHP). On the other hand, the objective component used a data-driven multivariate approach supported by tree-based learning algorithms. Twenty-two variables were considered, encompassing climatic conditions, hydro-geomorphologic features, soil characteristics, vegetation patterns, and socio-economic factors. These variables played a crucial role to identify the most suitable areas for growing the selected leguminous crops. The MCDM-AHP method utilised expert evaluations to rank the importance of variables, identifying water sources, slope, and soil properties as key factors. A suitability mapping analysis revealed that 17.63% of the area was highly suitable and 62.77% moderately suitable, while 10% was less suitable and 9.59% unsuitable for growing these two legumes. According to the data driven methodology, soil fertility and nitrogen content emerged as key determinants for land suitability. This is particularly relevant for nitrogen-fixing leguminous crops such as sunn hemp and pigeon pea, which play a central role in improving soil quality and ensuring food security.

Effective and sustainable strategies are needed to address the burden of preventable deaths among children under-five in resource-constrained settings. The Tools for Integrated Management of Childhood Illness (TIMCI) project aims to support healthcare providers to identify and manage severe illness, whilst promoting resource stewardship, by introducing pulse oximetry and clinical decision support algorithms (CDSAs) to primary care facilities in India, Kenya, Senegal and Tanzania. Health impact is assessed through: a pragmatic parallel group, superiority cluster randomised controlled trial (RCT), with primary care facilities randomly allocated (1:1) in India to pulse oximetry or control, and (1:1:1) in Tanzania to pulse oximetry plus CDSA, pulse oximetry, or control; and through a quasi-experimental pre-post study in Kenya and Senegal. Devices are implemented with guidance and training, mentorship, and community engagement. Sociodemographic and clinical data are collected from caregivers and records of enrolled sick children aged 0–59 months at study facilities, with phone follow-up on Day 7 (and Day 28 in the RCT). The primary outcomes assessed for the RCT are severe complications (mortality and secondary hospitalisations) by Day 7 and primary hospitalisations (within 24 hours and with referral); and, for the pre-post study, referrals and antibiotic. Secondary outcomes on other aspects of health status, hypoxaemia, referral, follow-up and antimicrobial prescription are also evaluated. In all countries, embedded mixed-method studies further evaluate the effects of the intervention on care and care processes, implementation, cost and cost-effectiveness. Pilot and baseline studies started mid-2021, RCT and post-intervention mid-2022, with anticipated completion mid-2023 and first results late-2023. Study approval has been granted by all relevant institutional review boards, national and WHO ethical review committees. Findings will be shared with communities, healthcare providers, Ministries of Health and other local, national and international stakeholders to facilitate evidence-based decision-making on scale-up. Study registration: NCT04910750 and NCT05065320

Objective: Infants born to mothers infected with human immunodeficiency virus (HIV) experience heightened morbidity and mortality, likely due to systemic immune dysregulation potentially linked to gut microbial dysbiosis. However, the degree of variation in biomarkers and systemic inflammation between HIV-exposed uninfected (HEU) infants and their HIV-unexposed uninfected (HUU) peers remains uncertain. Materials and Methods: A total of 78 infants, including one set of twins, were enrolled in this study at approximately 6 weeks of age. We collected sociodemographic and clinical data, along with stool samples, to characterize the infant gut microbiota using 16S rRNA gene sequencing. Additionally, whole blood samples were obtained from the infants, and plasma was isolated for MesoScale Discovery (MSD) V-Plex assays to quantify plasma inflammatory and endothelial dysfunction biomarkers. Results: Among the 78 infants investigated, 35.9% were exposed to HIV in utero and during breastfeeding. At 6 weeks of age, 84.6% of the infants were exclusively breastfed, while 15.4% were mixed-fed with fluids and semi-solids. The gut microbiota comprised predominantly of Bifidobacterium (56.6%), Streptococcus (21.8%), Bacteroides (5.4%), Collinsella (2.8%) and Parabacteroides (2.7%). We did not observe significant differences in infant stool Shannon (p=0.760) and Simpson (p=0.510) indices by infant exposure to maternal HIV. The gut microbiota composition (Bray-Curtis dissimilarity) did not differ between HEU and HUU infants. Furthermore, plasma inflammatory and endothelial dysfunction biomarker levels did not significantly differ between HEU and HUU infants (p>0.05 after multiple test corrections). Notably, several significant positive correlations were observed between inflammatory and endothelial dysfunction biomarker levels (p

CONTEXT AND GOAL: This research addresses the issue of suicide and attempted suicide, which have a significant impact on global premature mortality and disability. Particularly noteworthy is the prevalence among adolescents, in whom suicide ranks among the top four causes of death according to the World Health Organization (WHO). In Switzerland, suicide has remained the leading cause of death in individuals under 50 since 1990. At the same time, the burden of attempted suicides remains poorly understood. Although the legality of assisted suicide in Switzerland influences the overall suicide data, this analysis focuses solely on non-assisted suicides, as they are relevant for accurately assessing the burden of disease of suicide and attempted suicide. Amid challenges posed by limited reporting infrastructure, this analysis aims to contribute to the existing literature by investigating the cumulative impact of non-assisted suicide and attempted suicide on the population living in Switzerland. METHODOLOGY: Pre-existing data from 2009 to 2021 were collected and analysed, drawing from a variety of sources including official health records from the federal offices of statistics and public health, surveys and retrospective studies. From this data, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life-years (DALYs) were calculated in order to estimate the burden of disease. Sensitivity analyses were conducted to determine the robustness of the data and the effect of variables (suicide attempt incidence, sex distribution, disability weight, average duration) on the DALYs. RESULTS: The analysis of the data spanning from 2009 to 2021 revealed a decrease in suicide. The present study determined that, in 2021, 32,771 DALYs were attributable to non-assisted suicide and attempted suicide and 6.4% of all years of life lost (n = 30,516) were attributable to suicide, not including assisted suicide. Using a reference incidence of 33,000 attempted suicides per year in Switzerland, the morbidity associated with attempted suicides was 2255 YLDs (range: 552–6557 YLDs). Further analysis of the data highlighted a stark sex gap in the prevalence of non-assisted suicide: male suicides account for around 2% of all male deaths, whereas female suicides account for approximately 0.8% of all female deaths. Sensitivity analyses found that incidence and sex distribution of attempted suicide were the most impactful factors, while disability weights and average duration of disability had little impact on the variation in YLD estimates. CONCLUSION: In conclusion, this study provides a detailed analysis of the burden of non-assisted suicide and attempted suicide in Switzerland. With non-assisted suicide accounting for 6.4% of all years of life lost and 30% of deaths in people aged 20–24 in Switzerland in 2021, it emerges that suicide contributes significantly to the country’s overall disease burden, particularly in terms of years of life lost. The stark sex disparity in suicide rates further underscores the need for sex-sensitive approaches. These insights can help guide policy-making and the allocation of resources towards reducing the incidence and impact of suicide and attempted suicide, both in Switzerland and in broader international contexts where similar patterns prevail.

ABSTRACT The malaria parasite Plasmodium falciparum employs antigenic variation of the virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1) to escape adaptive immune responses during blood infection. Antigenic variation of PfEMP1 occurs through epigenetic switches in the mutually exclusive expression of individual members of the multi-copy var gene family. var genes are located in perinuclear clusters of transcriptionally inactive heterochromatin. Singular var gene activation is linked to locus repositioning into a dedicated zone at the nuclear periphery and deposition of histone 3 lysine 4 di-/trimethylation (H3K4me2/3) and H3K9 acetylation marks in the promoter region. While previous work identified the putative H3K4-specific methyltransferase PfSET10 as an essential enzyme and positive regulator of var gene expression, a recent study reported conflicting data. Here, we used iterative genome editing to engineer a conditional PfSET10 knockout line tailored to study the function of PfSET10 in var gene regulation. We demonstrate that PfSET10 is not required for mutually exclusive var gene expression and switching. We also show that PfSET10 is dispensable not only for asexual parasite proliferation but also for sexual conversion and gametocyte differentiation. Furthermore, comparative RNA-seq experiments revealed that PfSET10 plays no obvious role in regulating gene expression during asexual parasite development and gametocytogenesis. Interestingly, however, PfSET10 shows different subnuclear localization patterns in asexual and sexual stage parasites and female-specific expression in mature gametocytes. In summary, our work confirms in detail that PfSET10 is not involved in regulating var gene expression and is not required for blood-stage parasite viability, indicating PfSET10 may be important for life cycle progression in the mosquito vector or during liver stage development.IMPORTANCEThe malaria parasite Plasmodium falciparum infects hundreds of millions of people every year. To survive and proliferate in the human bloodstream, the parasites need to escape recognition by the host’s immune system. To achieve this, P. falciparum can change the expression of surface antigens via a process called antigenic variation. This fascinating survival strategy is based on infrequent switches in the expression of single members of the var multigene family. Previous research reported conflicting results on the role of the epigenetic regulator PfSET10 in controlling mutually exclusive var gene expression and switching. Here, we unequivocally demonstrate that PfSET10 is neither required for antigenic variation nor the expression of any other proteins during blood-stage infection. This information is critical in directing our attention toward exploring alternative molecular mechanisms underlying the control of antigenic variation and investigating the function of PfSET10 in other life cycle stages.

Microorganisms are used in a variety of sectors, including food and feed production, agricultural or environmental applications, and can be optimized for efficacy, safety and sustainability using modern biotechnology techniques. In the EU, genetically modified microorganisms (GMMs) are typically used as production organisms for food and feed products, including enzymes, amino acids, vitamins, flavourings, and oligosaccharides under the Contained Use Directive. Applications involving live GMMs would fall under the Deliberate Release Directive. However, its relevant regulations and guidelines are so far not supporting the access to market of GMMs. In this literature review, we examine what is already known or can be inferred about the safety of microorganisms deliberately released into the environment across sectors. We conclude that there is sufficient evidence supporting the establishment of a European framework for the risk assessment of GMMs deliberately released into the environment, which would enable timely market access for live GMM products.

Objectives: To investigate the associations of n-3 fatty acid intake with handgrip strength and muscle mass indices in older adults. A secondary aim was to investigate whether these associations differed by physical activity status. Research methods & procedures: A cross-sectional study included 53,170 participants aged 60 years and over from the UK biobank (25,324 men and 27,846 women). The primary outcomes were grip strength index and muscle mass index, the predictor variable was n-3 fatty acid intake and the covariates were age, ethnicity, Townsend deprivation index, physical activity, multimorbidity count, total energy intake, body fat percentage and the month of assessment. Multivariable linear regression analyses were performed across 5 models. Model 1 was unadjusted; model 2 adjusted for age, ethnicity, deprivation index and month of assessment; model 3 adjusted as in model 2 plus total energy intake; model 4 as in model 2 plus multimorbidity count; and model 5 as in model 4 plus body fat percentage. Results: In model 5, higher n-3 fatty acid intake was positively associated with the grip strength index in women. For each additional gram of n-3 fatty acid consumed per day, there was an increase of 0.03 kg/m2 (95% CI: 0.00 to 0.06 kg/m2) in active women and 0.04 kg/m2 (95% CI: 0.00 to 0.07 kg/m2) in inactive women. However, no significant associations were observed in men, whether active (p = 0.405) or inactive (p = 0.323). Additionally, no significant associations were found between n-3 fatty acid intake and muscle mass index in either active (p = 0.858) or inactive (p = 0.250) men, or in active (p = 0.909) or inactive (p = 0.187) women. Conclusion: Although n-3 fatty acid intake was associated with grip strength index in older women, regardless of their activity status, the magnitude of this association was very small and unlikely to be clinically relevant. Additionally, n-3 fatty acid was not associated with muscle mass index.

The shift from the traditional self-contained classroom to the departmentalized classroom structure in upper-elementary classrooms is increasing as the pressure to maximize student outcomes is higher than ever for public schools. Teachers prefer departmentalization but findings as to its benefits for students are mixed. This study considers the relationship between classroom structure and student achievement and whether the relationship varies by student socio-economic status. Using fourth grade data from one school district in Florida, we use Ordinary Least Squares (OLS) regression and logistic regression to examine the relationship between departmentalization and three measures of student achievement based on the Florida Standards Assessment. The findings indicate a negative relationship between all three measures of student achievement and classroom structure with some variation by student socio-economic status.

BACKGROUND: Assessment of nystagmus fixation suppression can be used as an additional diagnostic tool for patients with an acute vestibular syndrome to distinguish between a central or peripheral cause. We investigated the ability of physicians to detect fixation suppression using a nystagmus simulation model. METHODS: We used a nystagmus simulator to measure the accuracy of the nystagmus fixation suppression test. Fixation suppression was assessed randomly in 6170 trials by 20 otorhinolaryngologists and neurologists, segregated into 2 groups based on their neurootological experience, a beginner and an experienced group. The simulator presented random nystagmus slow velocity (SPV) reductions and presented 3 conditions with either changed nystagmus frequency, amplitude, or both. RESULTS: The cutoff for the discernment of fixation suppression ranged from 1.2 to 14°/s nystagmus velocity difference. The more intense the baseline nystagmus was, the more difficult was the detection of fixation suppression. There was not significant difference (P > .05) in the cutoff values in the experts group compared to the novices for all 3 different conditions. Both, novices and experts, detected frequency changes easier than differences of the nystagmus amplitude. Test sensitivity was very low (19%-65%) for discernment of small nystagmus velocity differences of ≤2°/s by experts. CONCLUSION: In our study, there was no difference between experts and novices in detection of nystagmus suppression by visual fixation. The examiners could only detect large suppression effects at low-intensity baseline nystagmus. Overall, the sensitivity and accuracy of a clinical fixation suppression test is low and the assistance with a video-oculography device is highly recommended.

A year of COVID-19 quarantine required educators to switch from in-person to virtual learning platforms, causing a dramatic reimagining of their daily praxis. Their experiences are likely to influence new norms for K-12 education. While virtual learning can be effective, student engagement, student retention, and student attention can be challenging. This paper discusses how we adapted a materials-heavy, hands-on, annual summer teacher professional development (PD) program from an in-person to a virtual platform in the initial months of the pandemic. We successfully maintained effective and hands-on components, giving authentic learning experiences to the participants. The 2020 virtual version of the program effectively engaged in-service teachers with high daily participation and retention rates. Nearly all participants rated the workshops as very good or excellent, and an assessment of participants' learning outcomes was comparable to that of the highly-rated in-person 2018 version of the program. Following the PD session, teachers reported feeling more prepared to facilitate their students' learning, increased inquiry-based science teaching knowledge and skills, and their enthusiasm for utilizing workshop strategies. While there are challenges to implementing virtual learning, virtual teacher PD can be widely adaptable and replicable for many institutions, especially in situations in which distance or finances deter in-person participation.

AIMS: The aim of the present study was to evaluate the performance of various artificial intelligence (AI)-powered chatbots (commercially available in Switzerland up to June 2023) in solving a theoretical cardiology board exam and to compare their accuracy with that of human cardiology fellows. METHODS: For the study, a set of 88 multiple-choice cardiology exam questions was used. The participating cardiology fellows and selected chatbots were presented with these questions. The evaluation metrics included Top-1 and Top-2 accuracy, assessing the ability of chatbots and fellows to select the correct answer. RESULTS: Among the cardiology fellows, all 36 participants successfully passed the exam with a median accuracy of 98% (IQR 91–99%, range from 78% to 100%). However, the performance of the chatbots varied. Only one chatbot, Jasper quality, achieved the minimum pass rate of 73% correct answers. Most chatbots demonstrated a median Top-1 accuracy of 47% (IQR 44–53%, range from 42% to 73%), while Top-2 accuracy provided a modest improvement, resulting in a median accuracy of 67% (IQR 65–72%, range from 61% to 82%). Even with this advantage, only two chatbots, Jasper quality and ChatGPT plus 4.0, would have passed the exam. Similar results were observed when picture-based questions were excluded from the dataset. CONCLUSIONS: Overall, the study suggests that most current language-based chatbots have limitations in accurately solving theoretical medical board exams. In general, currently widely available chatbots fell short of achieving a passing score in a theoretical cardiology board exam. Nevertheless, a few showed promising results. Further improvements in artificial intelligence language models may lead to better performance in medical knowledge applications in the future.

AIMS OF THE STUDY: The 2021 European Society of Cardiology Guidelines on valvular heart disease recommend transcatheter aortic valve implantation (TAVI) for patients with symptomatic severe aortic stenosis at low surgical risk and age ≥75 years who are suitable for a transfemoral approach (recommendation class IA) based on two large randomised controlled trials (PARTNER 3 and Evolut Low Risk) comparing transcatheter aortic valve implantation with surgical aortic valve replacement (SAVR). Whether such an approach is cost-effective in Switzerland remains unclear. The aim of this cost-utility analysis was to compare transcatheter aortic valve implantation with SAPIEN 3 versus surgical aortic valve replacement in symptomatic severe aortic stenosis patients at low risk of surgical mortality from the perspective of Swiss compulsory health insurance using data from the PARTNER 3 trial (reflecting specifically the safety and efficacy of the SAPIEN 3 TAVI device). METHODS: A previously published two-stage Markov-based model that captured clinical outcomes from the PARTNER 3 trial was adapted from the perspective of the Swiss compulsory health insurance system, using local or geographically close general population mortality and utility data, unit costs and medical resource use from publicly available sources and based on expert opinion. The model had a lifetime horizon with a 3% yearly discounting factor. The cost–utility analysis estimated changes in both direct healthcare costs and health-related quality-adjusted life years for transcatheter aortic valve implantation compared with surgical aortic valve replacement in patients with symptomatic severe aortic stenosis at low risk of surgical mortality. RESULTS: Overall, transcatheter aortic valve implantation with SAPIEN 3 resulted in lifetime costs per patient of CHF 79,534 and quality-adjusted life years per patient of 9.64, compared with surgical aortic valve replacement lifetime costs and quality-adjusted life years per patient of CHF 76,891 and 8.96, respectively. Compared with surgical aortic valve replacement, transcatheter aortic valve implantation was estimated to offer an incremental improvement of +0.68 quality-adjusted life years per patient at an increased cost of +CHF 2643 per patient over a lifetime horizon. The incremental cost-effectiveness ratio was CHF 3866 per quality-adjusted life year gained and remained below CHF 50,000 per quality-adjusted life year gained across several sensitivity analyses. CONCLUSIONS: This analysis suggests that transcatheter aortic valve implantation using the SAPIEN 3 device is likely to be a highly cost-effective alternative for symptomatic severe aortic stenosis patients at a low risk of surgical mortality, treated in the contemporary Swiss setting. These findings may help to inform a holistic approach when making policy decisions for the management of this patient group.

IntroductionEnsuring young people receive adequate information and guidance about puberty is essential for healthy adolescent transitions. Although many countries are moving toward including comprehensive sexuality education in national curricula, content on puberty during early adolescence, including peer pressure and stigma related to physical and emotional changes, are rarely included. Limited evidence exists about the inclusion of puberty education in schools, and the role of teachers in delivering such content in low-and middle-income countries, including Sierra Leone.MethodsWe conducted a qualitative assessment using multiple methodologies (in-depth interviews with teachers; focus group discussions with girls and boys; key informant interviews with teacher training lecturers and government) to explore the feasibility and acceptability of a puberty education package (a teacher training guide and boys’ and girls’ puberty books) for primary school teachers to introduce puberty content in Sierra Leone.ResultsThree key themes were identified, including the importance of teacher comfort in discussing puberty, the value of the teacher’s guide for delivering puberty content, and system and resource constraints that impact the implementation of puberty education. Additional insights included how integrating puberty education into existing curriculum courses may be more effective than stand-alone puberty classes; education systems can enable in-service and pre-service teacher training, along with culturally appropriate puberty resources, to increase effective puberty education delivery in schools; and governments serve a key role in providing puberty education teacher training, ensuring sustainable funding to retain trained teachers, and offering guidance on national curriculum requirements on puberty education.DiscussionThere is a strong need to integrate puberty education into formal educational systems, with well trained teachers serving a valuable role in its delivery. Research is needed on how best to scale sustainable teacher training interventions to support the delivery of puberty education to adolescents in low- and middle-income contexts.

BackgroundSupporting individuals in managing their suicidality can prevent suicidal behavior. This study evaluated the suicide prevention project SERO, which was launched in Central Switzerland in 2021. SERO comprises four components: the suicide risk assessment technique PRISM-S, a personal safety plan, mental health first aid courses for relatives, and a self-management app. We assessed the mental health of individuals at increased suicide risk after hospital discharge and evaluated the usage and usefulness of SERO components.MethodsA cross-sectional study targeted former patients of Lucerne Psychiatry with an increased suicide risk. Between March 2023 and March 2024, we collected data from 24 individuals through a questionnaire administered six months post-discharge. Descriptive statistics characterized sociodemographics, assessed self-efficacy, self-management, and health literacy, and analyzed the usage and usefulness of SERO components. Associations between the usage of SERO components and mental health outcomes were investigated using Wilcoxon rank sum tests.ResultsMental health assessments indicated, on average, low to moderate levels of self-efficacy, self-management, and health literacy, with substantial variations across individuals. Participants’ exposure to SERO components varied: 83% used PRISM-S for suicide risk assessment, 67% developed a personal safety plan, 38% used the SERO app, and 8% reported that their relatives participated in a mental health first aid course. 50% of safety plan users and 44% of SERO app users found the tools helpful before or during a suicidal crisis. 78% of SERO app users would recommend the app to others.ConclusionLow to moderate levels of self-efficacy, self-management, and health literacy underscore the need for targeted interventions to support individuals at suicide risk. Positive feedback on the personal safety plan and the SERO app suggests their potential effectiveness in helping individuals manage their suicidality. Therefore, integrating structured measures for promoting self-management into standard care protocols in psychiatric hospitals and into patients’ lives may contribute to preventing suicides. The main limitation of our study is its small sample size. Future larger-scale studies should investigate user experiences in detail, assess the causal effects of SERO components on specific mental health and suicide outcomes, and evaluate the cost-effectiveness of each component separately and in combination.

Background Human resources are a key determinant for the quality of healthcare and health outcomes. Several human resource management approaches or practices have been proposed and implemented to better understand and address health workers’ challenges with mixed results particularly in low- and middle-income countries (LMICs). The aim of this framework synthesis was to review the human resources frameworks commonly available to address human resources for health issues in LMIC.Methods We searched studies in Medline, Embase, CAB Global Health, CINAHL (EBSCO) and WHO global Index Medicus up to 2021. We included studies that provided frameworks to tackle human resources for health issues, especially for LMICs. We synthesised the findings using a framework and thematic synthesis methods.Results The search identified 8574 studies, out of which 17 were included in our analysis. The common elements of different frameworks are (in descending order of frequency): (1) functional roles of health workers; (2) health workforce performance outcomes; (3) human resource management practises and levers; (4) health system outcomes; (5) contextual/cross-cutting issues; (6) population health outcomes and (7) the humanness of health workers. All frameworks directly or indirectly considered themes around the functional roles of health workers and on the outcomes of health workforce activities, while themes concerning the humanness of health workers were least represented. We propose a synthesised Human-Centred Health Workforce Framework.Conclusions Several frameworks exist providing different recurring thematic areas for addressing human resources for health issues in LMIC. Frameworks have predominantly functional or instrumental dimensions and much less consideration of the humanness of health workers. The paradigms used in policy making, development and funding may compromise the effectiveness of strategies to address human resources challenges in LMIC. We propose a comprehensive human resources for health framework to address these pitfalls.

ABSTRACT Aurora kinases are crucial regulators of mitotic cell cycle progression in eukaryotes. The protozoan malaria parasite Plasmodium falciparum replicates via schizogony, a specialized mode of cell division characterized by consecutive asynchronous rounds of nuclear division by closed mitosis followed by a single cytokinesis event producing dozens of daughter cells. P. falciparum encodes three Aurora-related kinases (PfARKs) that have been reported essential for parasite proliferation, but their roles in regulating schizogony have not yet been explored in great detail. Here, we engineered transgenic parasite lines expressing GFP-tagged PfARK1–3 to provide a systematic analysis of their expression timing and subcellular localization throughout schizogony as well as in the non-dividing gametocyte stages, which are essential for malaria transmission. We demonstrate that all three PfARKs display distinct and highly specific and exclusive spatiotemporal associations with the mitotic machinery. In gametocytes, PfARK3 is undetectable, and PfARK1 and PfARK2 show male-specific expression in late-stage gametocytes, consistent with their requirement for endomitosis during male gametogenesis in the mosquito vector. Our combined data suggest that PfARK1 and PfARK2 have non-overlapping roles in centriolar plaque maturation, assembly of the mitotic spindle, kinetochore–spindle attachment and chromosome segregation, while PfARK3 seems to be exquisitely involved in daughter cell cytoskeleton assembly and cytokinesis. These important new insights provide a reliable foundation for future research aiming at the functional investigation of these divergent and possibly drug-targetable Aurora-related kinases in mitotic cell division of P. falciparum and related apicomplexan parasites.IMPORTANCEMalaria parasites replicate via non-conventional modes of mitotic cell division, such as schizogony, employed by the disease-causing stages in the human blood or endomitosis during male gametogenesis in the mosquito vector. Understanding the molecular mechanisms regulating cell division in these divergent unicellular eukaryotes is not only of scientific interest but also relevant to identify potential new antimalarial drug targets. Here, we carefully examined the subcellular localization of all three Plasmodium falciparum Aurora-related kinases (ARKs), distantly related homologs of Aurora kinases that coordinate mitosis in model eukaryotes. Detailed fluorescence microscopy-based analyses revealed distinct, specific, and exclusive spatial associations for each parasite ARK with different components of the mitotic machinery and at different phases of the cell cycle during schizogony and gametocytogenesis. This comprehensive set of results closes important gaps in our fragmentary knowledge on this important group of kinases and offers a valuable source of information for future functional studies.

Objective To describe a new co-design framework termed Evidence-informed, Experience-based Co-design (E2CD).Background Involving consumers and clinicians in planning, designing and implementing services results in the end-product being more likely to meet the needs of end-users and increases the likelihood of their uptake and sustainability. Different forms and definitions of co-design have been described in the literature and have had varying levels of success in health service redesign. However, many fall short of including people with lived experience in all aspects of the process, particularly in setting priorities for service (re)design. In addition, health services need to deliver evidence-based care as well as care that meets the needs of users, yet few ways of integrating research evidence into co-design processes are described. This paper describes a new framework to approach co-design which addresses these issues. We believe that it offers a roadmap to address some of healthcare’s most wicked problems and potentially improve outcomes for some of the most vulnerable people in our society. We use improving services for people with high healthcare service utilisation as a working example of the Framework’s application.Conclusion Evidence-informed experience-based co-design has the potential to be used as a framework for co-design that integrates research evidence with lived experience and provides people with lived experience a central role in decision-making about prioritising and designing services to meet their needs.

Summary: Animal behavior emerges from collective dynamics of neurons, making it vulnerable to damage. Paradoxically, many organisms exhibit a remarkable ability to maintain significant behavior even after large-scale neural injury. Molecular underpinnings of this extreme robustness remain largely unknown. Here, we develop a quantitative pipeline to measure long-lasting latent states in planarian flatworm behaviors during whole-brain regeneration. By combining >20,000 animal trials with neural network modeling, we show that long-range volumetric peptidergic signals allow the planarian to rapidly restore coarse behavior output after large perturbations to the nervous system, while slow restoration of small-molecule neuromodulator functions refines precision. This relies on the different time and length scales of neuropeptide and small-molecule transmission to generate incoherent patterns of neural activity that competitively regulate behavior. Controlling behavior through opposing communication mechanisms creates a more robust system than either alone and may serve as a generalizable approach for constructing robust neural networks.

In this work, we advocate agroforestry as a sustainable agricultural method that leverages biodiversity and ecosystem services, simultaneously tackling the problems of adaptation and mitigation to climate change, and of land restoration for sustainable agriculture across scales. While the rise of industrial agriculture has been instrumental in addressing the food demands of an expanding global population, enhancing food quality, yield, productivity, and efficiency, we must now reckon with the consequences. This advancement, which prioritizes simplification, specialization, and external inputs, has escalated detrimental externalities including deforestation, biodiversity loss, soil degradation, pollution, and an increase in greenhouse gases, contributing significantly to global warming and to exacerbated environmental crises. These demand urgent attention. In response, various agricultural methodologies such as organic, biodynamic, ecological, and biological farming have emerged, attempting to propose alternatives. However, these methods have yet to significantly alter the trajectory of mainstream agriculture. For over two decades, we have devoted our efforts to developing and refining a multispecies integrated agroforestry system for the sustainable cultivation of Ilex paraguariensis, “yerba mate,” in the subtropical north-east of Argentina. With “integrated” we mean that the trees are planted within the I. paraguariensis distribution, not between alleys as in “alley cropping” or “hedgrow intercropping.” The experimental work we present here was designed and implemented to enable data comparisons across consociations of multiple species of trees, at a relevant experimental scale. We achieve soil preservation and restoration, productivity comparable to or exceeding monocultures, and a significant increase in resiliency, particularly evidenced during the extreme climate events of spring and summer 2021 and 2022. These results underscore agroforestry’s potential for climate change mitigation and adaptation.

Der Beitrag stellt die Beschwerdemöglichkeit des Bundes im Opferhilferecht vor. Er behandelt die Frage, wann das Eidgenössische Justiz- und Polizeidepartement (EJPD) zur Behördenbeschwerde gegen kantonale Entscheide betreffend Opferhilfe berechtigt ist und welche Funktion dabei dem Bundesamt für Justiz (BJ) zukommt. Er nennt jüngere Anwendungsbeispiele und erläutert, weshalb das BJ im Namen des EJPD auch Behördenbeschwerden «pro Adressat» führen kann und was Anwältinnen und Anwälte angesichts der Behördenbeschwerde beachten sollten. -- L'article examine la possibilité pour la Confédération d'exercer un recours dans le cadre du droit de l'aide aux victimes. Il aborde la question de savoir à quel moment le Département fédéral de justice et police (DFJP) est en droit de contester les décisions cantonales relatives à l'aide aux victimes et décrit le rôle de l'Office fédéral de la justice (OFJ) dans ce contexte. L'article cite des exemples récents pour illustrer cette pratique et explique pourquoi l'OFJ peut également déposer des recours administratifs au nom du DFJP en tant que tiers agissant en faveur du destinataire de la décision contestée. Il souligne également les points auxquels les avocats doivent prêter attention lorsqu'ils traitent des recours administratifs.