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Abstract Extensive genetic studies have elucidated cardiomyocyte differentiation and associated gene networks using single-cell RNA-seq, yet the intricate transcriptional mechanisms governing cardiac conduction system (CCS) development and working cardiomyocyte differentiation remain largely unexplored. Here we show that mice deleted for Dhx36 (encoding the Dhx36 helicase) in the embryonic or neonatal heart develop overt dilated cardiomyopathy, surface ECG alterations related to cardiac impulse propagation, and (in the embryonic heart) a lack of a ventricular conduction system (VCS). Heart snRNA-seq and snATAC-seq reveal the role of Dhx36 in CCS development and in the differentiation of working cardiomyocytes. Dhx36 deficiency directly influences cardiomyocyte gene networks by disrupting the resolution of promoter G-quadruplexes in key cardiac genes, impacting cardiomyocyte differentiation and CCS morphogenesis, and ultimately leading to dilated cardiomyopathy and atrioventricular block. These findings further identify crucial genes and pathways that regulate the development and function of the VCS/Purkinje fiber (PF) network.

Abstract Mantle plumes are responsible for the Earth’s largest volcanic provinces. In the prevailing paradigm, the deep mantle is less degassed than convecting shallow mantle, implying that plume-derived lavas have higher concentrations of primordial volatiles such as helium (He). Demonstrating this has led to explanations that question the established Earth model. Here, we show that the 3He/4He of basalts from the Red Sea display coherent relationships with trace elements, allowing the helium concentration of the Afar plume to be calculated. Contrary to the prevailing model it appears the helium concentration of the Afar plume is 10-25% of the upper mantle. This contradiction is resolved if the plume material itself is a mixture of helium-rich high-3He/4He deep mantle with helium-depleted low-3He/4He recently subducted oceanic crust. This implies that helium-depleted domains may exist in convecting mantle and that moderately high 3He/4He plumes likely do not contain a notable contribution of the deep mantle.

Abstract Gene-gene interactions are crucial to the control of sub-cellular processes but our understanding of their stochastic dynamics is hindered by the lack of simulation methods that can accurately and efficiently predict how the distributions of gene product numbers vary across parameter space. To overcome these difficulties, here we present Holimap (high-order linear-mapping approximation), an approach that approximates the protein or mRNA number distributions of a complex gene regulatory network by the distributions of a much simpler reaction system. We demonstrate Holimap’s computational advantages over conventional methods by applying it to predict the stochastic time-dependent dynamics of various gene networks, including transcriptional networks ranging from simple autoregulatory loops to complex randomly connected networks, post-transcriptional networks, and post-translational networks. Holimap is ideally suited to study how the intricate network of gene-gene interactions results in precise coordination and control of gene expression.

Abstract Background Road traffic accidents(RTA) are a major public health problem worldwide, accounting for almost 1.24 million deaths per year and it is the number one cause of death among those aged group 15–29 years. Even though there are great benefits from access to road transportation there also poses a great challenge in the individual’s daily activities ranging from minor injury to death. Objective This study aimed to assess the magnitude and outcome of road traffic accidents among patients admitted in Dessie Town Governmental Hospitals, Northeast Amhara, Ethiopia, 2022. Methods A five-year hospital-based retrospective descriptive cross-sectional study design was conducted among 377 road traffic accident patients admitted to Dessie Town Governmental hospitals. Data were collected by simple random methods based on patient chart reviews from June 7/, 2022 to May 23/ 2017 using a checklist adapted from the WHO standard hospital-based road traffic accident questionnaires after obtaining consent from the concerned authority. EPI-Data software version 7.2 for data entry and SPSS version 25 for statistical analysis were used. Descriptive and inferential statistics were used. Statistical significance was declared at a p-value of

Abstract Objective To assess the prevalence of anxiety and depression and their associated risk factors throughout the pregnancy and postpartum process using a new screening for the early detection of mental health problems. Design A prospective cross-sectional descriptive multicentred study. Participants were consecutively enrolled at ≥ 12 weeks’ gestation and followed at three different time points: at 12–14 weeks of pregnancy, at 29–30 weeks of pregnancy, and 4–6 weeks postpartum. All women completed a mental screening at week 12–14 of pregnancy consisting of two questions from the Generalised Anxiety Disorder Scale (GAD-2) and the two Whooley questions. If this screening was positive, the woman completed the Edinburgh Postnatal Depression Scale (EPDS). Setting Seven primary care centres coordinated by a Gynaecology and Obstetrics Department in the city of Terrassa (Barcelona) in northern Spain. Participants Pregnant women (N = 335, age 18–45 years), in their first trimester of pregnancy, and receiving prenatal care in the public health system between July 2018 and July 2020. Findings The most relevant factors associated with positive screening for antenatal depression or anxiety during pregnancy, that appear after the first trimester of pregnancy, are systematically repeated throughout the pregnancy, and are maintained in the postpartum period were: a history of previous depression, previous anxiety, abuse, and marital problems. In weeks 12–14 early risk factors for positive depression and anxiety screening and positive EPDS were: age, smoking, educational level, employment status, previous psychological/psychiatric history and treatment, suicide in the family environment, voluntary termination of pregnancy and current planned pregnancy, living with a partner and partner’s income. In weeks 29–30 risk factors were: being a skilled worker, a history of previous depression or anxiety, and marital problems. In weeks 4–6 postpartum, risk factors were: age, a history of previous depression or anxiety or psychological/psychiatric treatment, type of treatment, having been mistreated, and marital problems. Conclusions Early screening for anxiety and depression in pregnancy may enable the creation of more effective healthcare pathways, by acting long before mental health problems in pregnant women worsen or by preventing their onset. Assessment of anxiety and depression symptoms before and after childbirth and emotional support needs to be incorporated into routine practice.

Objectives The purpose of the article is to explore public awareness of knowledge autism and the phenomenon of discrimination in the school environment, their social and legal aspects. The scope of the study included the identification of problems related to the knowledge of the child's functioning, affected by autism , diagnosis and psychological-educational and medical assistance, the role of institutions and the family, the attitude towards children at school and outside school, and respect for the rights of children with autism. Material and methods A survey was conducted using a survey questionnaire. The survey was addressed to parents of students from three elementary schools witch were chosen for their variation in academic performance. The ranking was divided into a national part and a summary for eighteen provincial cities, in which 10,306 elementary schools qualified. In addition, a face-to-face interview was conducted with school principals. Results The results of the study are disturbing and indicate limited public awareness and unsatisfacto-ry understanding by the public of the occurring problem regarding people affected by autism. Studies show that society is is quite negative about the parents of children with dysfunctions. Conclusions The results of the survey indicate moderate public awareness among respondents regarding those affected by autism. The results obtained can contribute to a deeper reflection and awareness of the disorders and functioning of the child, and the implementation of measures to better understand the issues related to the functioning of a student with this condition. The results of the study may help in the decision of the Polish school to promote the discussed issues.

Landscapes have been shaped and reshaped by humans to meet the changing needs of shifting subsistence strategies and demographic patterns. In the Mediterranean region, a widespread subsistence strategy that has left a major imprint is pastoralism, often tied with transhumance. Pastoralism and the associated tensions between pastoralists and settled agriculturalists have political and legal dimensions which are sometimes overlooked in mainstream accounts of national “patrimony”. The rapid transformations of subsistence strategies witnessed in the twentieth century have changed pastoral landscapes in diverse ways. This paper focusses on the central Mediterranean archipelago of Malta to explore how the values and management of such landscapes require holistic assessment, taking into account the intangible practices and embedded legal rights and obligations that maintained these systems. While in Malta pastoralism has practically disappeared, its physical imprint persists in the form of a network of droveways, which was once a carefully regulated form of commons. Burgeoning demographic growth is erasing large tracts of the historic environment. Against this backdrop of contestation, this paper draws on interdisciplinary approaches to interrogate the shifting legal and historical narratives through which pastoral landscapes have been managed, in the process revealing how dominant epistemological and legal frameworks are also implicated in the erasure of these landscapes.

Abstract Cells are the fundamental units of life, and like all life forms, they change over time. Changes in cell state are driven by molecular processes; of these many are initiated when molecule numbers reach and exceed specific thresholds, a characteristic that can be described as “digital cellular logic”. Here we show how molecular and cellular noise profoundly influence the time to cross a critical threshold—the first-passage time—and map out scenarios in which stochastic dynamics result in shorter or longer average first-passage times compared to noise-less dynamics. We illustrate the dependence of the mean first-passage time on noise for a set of exemplar models of gene expression, auto-regulatory feedback control, and enzyme-mediated catalysis. Our theory provides intuitive insight into the origin of these effects and underscores two important insights: (i) deterministic predictions for cellular event timing can be highly inaccurate when molecule numbers are within the range known for many cells; (ii) molecular noise can significantly shift mean first-passage times, particularly within auto-regulatory genetic feedback circuits.

The rapid expansion in recent fintech innovations has garnered researchers’ attention to evaluate its influence on the banking industry.

Ab initio electronic structure applications are among the most widely used in High-Performance Computing (HPC), and the eigenvalue problem is often their main computational bottleneck. This article presents our initial efforts in porting these codes to a RISC-V prototype platform leveraging a wide Vector Processing Unit (VPU). Our software tester is based on a mini-app extracted from the ELPA eigensolver library. The user-space emulator Vehave and a RISC-V vector architecture implemented on an FPGA were tested. Metrics from both systems and different vectorisation strategies were extracted, ranging from the simplest and most portable one (using autovectorisation and assisting this by fusing loops in the code) to the more complex one (using intrinsics). We observed a progressive reduction in the number of vectorised instructions, executed instructions and computing cycles with the different methodologies, which will lead to a substantial speed-up in the calculations. The obtained outcomes are crucial in advancing the porting of computational materials and molecular science codes to (post)-exascale architectures using RISC-V-based technologies fully developed within the EU. Our evaluation also provides valuable feedback for hardware designers, engineers and compiler developers, making this use case pivotal for co-design efforts.

Ab initio electronic structure applications are among the most widely used in High-Performance Computing (HPC), and the eigenvalue problem is often their main computational bottleneck. This article presents our initial efforts in porting these codes to a RISC-V prototype platform leveraging a wide Vector Processing Unit (VPU). Our software tester is based on a mini-app extracted from the ELPA eigensolver library. The user-space emulator Vehave and a RISC-V vector architecture implemented on an FPGA were tested. Metrics from both systems and different vectorisation strategies were extracted, ranging from the simplest and most portable one (using autovectorisation and assisting this by fusing loops in the code) to the more complex one (using intrinsics). We observed a progressive reduction in the number of vectorised instructions, executed instructions and computing cycles with the different methodologies, which will lead to a substantial speed-up in the calculations. The obtained outcomes are crucial in advancing the porting of computational materials and molecular science codes to (post)-exascale architectures using RISC-V-based technologies fully developed within the EU. Our evaluation also provides valuable feedback for hardware designers, engineers and compiler developers, making this use case pivotal for co-design efforts.

Abstract Differential use of resources among bird species has been examined extensively in diet and nesting sites, but few studies have assessed this regarding avian nest materials. We assessed the structure and composition of nests in a group of co‐existing passerine shrubland birds at a site in Massachusetts, USA. We found, measured, collected, and dissected nests, and then weighed nest materials in morphological groups (e.g., bark, twigs, feathers) to determine if our seven focal species were using different nest materials. Among species, we compared proportional material masses in complete nests, and also separately in the exterior, structural part of the nest and the interior, cup lining. We found that the proportional masses of all 17 material types that we examined in nests differed among species. The compositions of nests among all seven bird species were distinct in multivariate ordination space and only a few pairs of species had substantial niche overlap. Proportional masses of materials within discrete sections (exterior and interior) also varied among species. Although some differences in nest composition could be partially explained by bird species size, nest materials differed even within the three larger bodied species and within four smaller bodied species. Our study builds upon previous studies that have shown species‐specificity in avian nest composition and supports the notion that birds using the same environment have distinct niches in relation to the materials placed in their nests. Niche partitioning due to interspecific competition could partially explain our findings, as certain materials are limited as resources, and searching for suitable nest materials is energetically costly. Additionally, other factors, such as partitioned nest sites, may have led to differential nest material use. We recommend further research to help elucidate underlying mechanisms of nest composition partitioning in birds and potentially other nest‐building taxa.

Genetically improved forest reproductive materials are now widely accessible in many European countries due to decades of continuous breeding efforts. Tree breeding does not only contribute to higher-value end products but allows an increase in the rate of carbon capture and sequestration, helping to mitigate the effects of climate change. The usefulness of breeding programmes depends on (i) the relevance of the set of selected traits and their relative weights (growth, drought tolerance, phenology, etc.); (ii) the explicit management of targeted and “neutral” diversity; (iii) the genetic gain achieved; and (iv) the efficiency of transferring diversity and gain to the plantation. Several biological factors limit both operational breeding and mass reproduction. To fully realise the potential of tree breeding, the introduction of new technologies and concepts is pivotal for overcoming these constraints. We reviewed several European breeding programmes, examining their current status and factors that are likely to influence tree breeding in the coming decades. The synthesis was based on case studies developed for the European Union-funded B4EST project, which focused on eight economically important tree species with breeding histories and intensities ranging from low-input breeding (stone pine, Douglas-fir and ash) to more complex programmes (eucalyptus, maritime pine, Norway spruce, poplar, and Scots pine). Tree breeding for these species is managed in a variety of ways due to differences in species’ biology, breeding objectives, and economic value. Most programmes are managed by governmental institutes with full or partial public support because of the relatively late return on investment. Eucalyptus is the only tree species whose breeding is entirely sponsored and managed by a private company. Several new technologies have emerged for both phenotyping and genotyping. They have the potential to speed up breeding processes and make genetic evaluations more accurate, thereby reducing costs and increasing genetic gains per unit of time. In addition, genotyping has allowed the explicit control of genetic diversity in selected populations with great precision. The continuing advances in tree genomics are expected to revolutionise tree breeding by moving it towards genomic-based selection, a perspective that requires new types of skills that are not always available in the institutions hosting the programmes. We therefore recognise the importance of promoting coordination and collaboration between the many groups involved in breeding. Climate change is expected to bring in new pests and diseases and increase the frequency of extreme weather events such as late frosts and prolonged droughts. Such stresses will cause slow growth and mortality, reducing forest productivity and resilience. Most of these threats are difficult to predict, and the time-consuming nature of conventional breeding does not allow for an adequate and timely reaction. We anticipate that most breeding programmes will need to revise their selection criteria and objectives to place greater emphasis on adaptive performance, tolerance to multiple environmental stresses, stability in different environments, and conservation of genetic diversity. Testing breeding materials in a variety of environments, including potentially contrasting climates, will become increasingly important. Climate change may also force the incorporation of new genetic resources that provide new useful adaptations, which may involve the use of new, previously unexplored gene pools or hybridisation, with the enormous challenge of incorporating useful alleles without adding along an unfavourable genetic background. Decision-support tools to help landowners and foresters select the best-performing forest reproductive material in each specific environment could also help reduce the impact of climate change.

SCDS (Sovereign Credit Default Swaps) are becoming more widely used as a country risk indicator after 2008 and stand out for providing real-time information rather than periodic reporting. The COVID-19 pandemic has led to economic disruptions and a decline in international trade. Understanding how the Pandemic affects SCDS return volatility in emerging economies like BRICS forms the motivation for our research. With this study, we aim to determine the impact of the COVID-19 Pandemic on SCDS return volatility in Brazil, Russia, India, China and South Africa, known as the BRICS countries. We used the Exponential Generalized Autoregressive Conditional Heteroskedasticity (EGARCH) model to analyze the data, which consisted of the daily closing price data for SCDS. The date of the first COVID-19 case in each country has been taken as the beginning of the COVID-19 Pandemic in each country. The results of the estimated GARCH models show that the volatility processes of the SCDS return series differ between periods. EGARCH model results indicate that shocks created by news in these countries during the Pandemic have a small and persistent effect on Brazil and Russia's SCDS return volatility, while they have a large and enduring effect on China and South Africa's SCDS return volatility. The findings will guide policymakers and portfolio managers in determining risk management models.

Ab initio electronic structure applications are among the most widely used in High-Performance Computing (HPC), and the eigenvalue problem is often their main computational bottleneck. This article presents our initial efforts in porting these codes to a RISC-V prototype platform leveraging a wide Vector Processing Unit (VPU). Our software tester is based on a mini-app extracted from the ELPA eigensolver library. The user-space Vehave and a RISC-V vector architecture implemented on an FPGA were tested. Metrics from both systems and different vectorisation strategies were extracted, ranging from the most simple and portable one (using autovectorisation and assisting this by fusing loops in the code) to the more complex one (using intrinsics). We observed a progressive reduction in the number of vectorial instructions, executed instructions and computing cycles with the different methodologies, which will lead to a substantial speed-up in the calculations. The obtained outcomes are crucial in advancing the porting of computational materials and molecular science codes to (post)-exascale architectures using RISC-V-based technologies fully developed within the EU. Our evaluation also provides valuable feedback for hardware designers, engineers and compiler developers, making this use case pivotal for co-design efforts.

Abstract There is ample evidence for ice layers and lenses within glacial firn. The standard model for ice layer formation localizes the refreezing by perching of meltwater on pre‐existing discontinuities. Here we argue that even extreme melting events provide insufficient flux for this mechanism. Using a thermomechanical model we demonstrate a different mechanism of ice layer formation. After a melting event when the drying front catches up with the wetting front and arrests melt percolation, conductive heat loss freezes the remaining melt in place to form an ice layer. This model reproduces the depth of a new ice layer at the Dye‐2 site in Greenland. It provides a deeper insight into the interpretation of firn stratigraphy and past climate variability. It also improves the simulation of firn densification processes, a key source of uncertainty in assessing and attributing ice sheet mass balance based on satellite altimetry and gravimetry data.

This article seeks to bring evidence on public value co-creation between public auditors and auditees, with a focus on the environment, as a matter of pressing interest for the citizens. We analyse data from performance audit reports issued by the European Court of Auditors: the tonality of audit conclusions and the corresponding auditees’ replies and the degree of acceptance and implementation of audit recommendations by the auditees. The analysis is performed using the theoretical perspectives of institutional logics and public value co-creation. We use qualitative and quantitative methods, including sentiment analysis and bivariate analysis. We find evidence that the EU public auditors increased their focus on environmental issues, following an increasingly trending institutional logic of focusing on non-financial topics of public interest. However, the tonality of environment-related audit conclusions and the auditees’ replies does not differ from the non-environment-related ones. We also demonstrate that public auditors co-created public value together with the auditees through a significantly higher acceptance of their recommendations in environmental than in non-environmental audits. The article contributes to the existing literature by using data from a supranational supreme audit institution and by applying an innovative research methodology in the audit field (sentiment analysis). It also offers practitioners valuable insights on performance audit’s evolution and impact. Although the data is limited to one supreme audit institution, this research can open future research avenues to perform comparative analysis with other supreme audit institutions or extend the research scope to content analysis of the substance of audit findings.

Abstract Bright basal reflections from the Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) have been proposed to be consistent with permittivities characteristic of a wet material beneath the south polar layered deposits (SPLD). The characterization of a recently formed impact crater highlight the existence of a several meters thick ice‐poor layer associated to a unit blanketing a large portion of the SPLD. We revise the radar propagation model used to invert the basal permittivity by including a surficial thin layer. We find that the inverted basal permittivity is highly sensitive to the properties of such a layer, with solutions ranging from common dry rocks to an unambiguously wet base. We advocate toward a better characterization of the surficial cover to assess the wet or dry nature for the base, and possibly reconcile most of the literature on the topic.

Acute gastroenteritis (AGE) is a gastrointestinal tract disease often caused by consuming food or water contaminated by bacteria, viruses, or parasites, that can lead to severe symptoms requiring hospitalization. A retrospective study on patients admitted for AGE between 2021 and 2023 at the Pediatrics and Infectious Diseases Departments of Lecce Hospital was conducted. Demographic characteristics, year and month of admission, length of hospital stay, etiological agents, co-infections, and blood chemistry data of patients were collected. The study included 103 patients ranging in age from 0 to 15 years, with 58.25% being male. A total of 78 bacterial, 35 viral, and 7 parasitic infections were identified. The most commonly detected pathogens were Escherichia coli (38.83%), Norovirus (28.16%), Campylobacter jejuni (22.33%), and Salmonella typhi/paratyphi (10.68%). Only a few cases of Cryptosporidium (5.83%) were identified. Additionally, 17 co-infections (16.50%) were detected. Viral infections are the primary cause of hospitalization for AGE in children

Risk management has reduced vulnerability to floods and droughts globally1,2, yet their impacts are still increasing3. An improved understanding of the causes of changing impacts is therefore needed, but has been hampered by a lack of empirical data4,5. On the basis of a global dataset of 45 pairs of events that occurred within the same area, we show that risk management generally reduces the impacts of floods and droughts but faces difficulties in reducing the impacts of unprecedented events of a magnitude not previously experienced. If the second event was much more hazardous than the first, its impact was almost always higher. This is because management was not designed to deal with such extreme events: for example, they exceeded the design levels of levees and reservoirs. In two success stories, the impact of the second, more hazardous, event was lower, as a result of improved risk management governance and high investment in integrated management. The observed difficulty of managing unprecedented events is alarming, given that more extreme hydrological events are projected owing to climate change3.

This article introduces a suite of mini-applications (mini-apps) designed to optimise computational kernels in ab initio electronic structure codes. The suite is developed from flagship applications participating in the NOMAD Center of Excellence, such as the ELPA eigensolver library and the GW implementations of the exciting, Abinit, and FHI-aims codes. The mini-apps were identified by targeting functions that significantly contribute to the total execution time in the parent applications. This strategic selection allows for concentrated optimisation efforts. The suite is designed for easy deployment on various High-Performance Computing (HPC) systems, supported by an integrated CMake build system for straightforward compilation and execution. The aim is to harness the capabilities of emerging (post)exascale systems, which necessitate concurrent hardware and software development — a concept known as co-design. The mini-app suite serves as a tool for profiling and benchmarking, providing insights that can guide both software optimisation and hardware design. Ultimately, these developments will enable more accurate and efficient simulations of novel materials, leveraging the full potential of exascale computing in material science research.