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BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

Team coordination is essential for effective performance during critical, stressful events. To better understand processes and states involved at multiple levels of team coordination, we assessed the correspondence between low- and high-level coordination in teams participating in simulation-based medical team training. We computed a measure of low-level team coordination with Multidimensional Recurrence Quantification Analysis, applied to arm movement, heart rate, and skin conductance data. High-level team coordination was captured by annotating video recordings for explicit and implicit, information and action coordination. Three linear mixed-effects model were run, each predicting a type of low-level coordination, based on high-level coordination annotations, accounting for multiple observations per team. Our findings showed that, compared to periods without annotated coordination, explicit- and implicit- information coordination corresponded to significantly different low-level team coordination across each of the studied modalities. Further research is required to assess additional factors related to the temporal variability observed in low-level coordination.

Satellite remote sensing of ocean colour properties allows observation of the ocean with high temporal and spatial coverage, facilitating the better assessment of changes in marine primary production. Ocean productivity is often assessed using satellite-derived chlorophyll a concentrations, a commonly used proxy for phytoplankton concentration. We used the Copernicus GlobColour remote sensing chlorophyll a surface concentration to investigate seasonal and non-seasonal variability, temporal trends, and changes in spring bloom chlorophyll a magnitude. Complementary, we analysed the chlorophyll a relationship with sea surface temperature and mixed-layer depth in the German Bight from 1998 to 2020. Empirical orthogonal functions were employed in order to investigate dominant spatial and temporal patterns (modes) related to the main processes of chlorophyll a variability. Multi covariance analysis was used to extract the dominant structures that maximize the covariance between chlorophyll a and sea surface temperature mixed-layer depth fields. High levels of chlorophyll a were found near the coast, showing a decreasing gradient towards offshore waters. A significant chlorophyll a positive trend was observed close to the Elbe estuary and adjacent area, while 55 % of the German Bight was characterized by a significant chlorophyll a negative trend. The chlorophyll a non-seasonal variability showed that the first four modes explained around 45 %, with the first and second modes related to inter- and intra-annual variability, respectively, observed in the temporal principal components spectral analyses. Monthly chlorophyll a concentration anomalies co-varied by 45 % with sea surface temperature anomalies and 23 % with mixed-layer depth anomalies. The monthly averages of chlorophyll a anomaly fields were suitable to investigate long-term trends and variability. The rising water temperature, combined with its indirect effects on other variables, can partially explain the observed trends in chlorophyll a.

Abstract Background National Medicines Regulatory Authorities like the Pharmacy Board of Sierra Leone are responsible for protecting and promoting public health, implementing regulatory standards, and maintaining a supply chain with an assured supply of medical products that are safe, effective, and of good quality. This retrospective study assesses the identification of substandard and falsified medicines, the changes in the functions and key indicators of assessment, and the quality improvement changes of the Pharmacy Board of Sierra Leone. Methods Data was obtained from 2013 to 2021 records using a data collection tool to collate and review all relevant information to address the different objectives. All data were sourced from the Department of Quality Assurance and the Department of Enforcement and Narcotics at the Pharmacy Board of Sierra Leone. The review also included, identified substandard and falsified medicines, the World Health Organisation Global benchmarking self-assessment tool, and internal and external audit records of the quality management system of all twelve departments of the Pharmacy Board of Sierra Leone. Results The study showed marked changes in identifying substandard and falsified medicines by the Pharmacy Board of Sierra Leone during ISO 9001:2015 implementation (2017- 2020) compared to Pre-ISO 9001:2015 implementation (2013- 2016). Critical functions of the Pharmacy Board of Sierra Leone from the assessment of the WHO GBT ML in 2016 and 2021 showed that several indicators had been addressed during ISO 9001:2015 certification with improvement in the level of maturity for the quality management systems and Pharmacovigilance functions. There was also an improvement in identifying non-conformances and a commitment to continuous improvement of processes during ISO 9001:2015 implementation. Conclusions This study revealed that regular checks through standard assessment, internal audits, and standard management review processes that generate follow-up actions, timelines, and a commitment to identifying correction, and corrective actions for non-conformances are essential quality improvement tools for the efficient functioning of an institution (Pharmacy Board of Sierra Leone). Our study revealed that commitment to continuous implementation of proper quality management system could significantly improve institutional efficiency, thereby improving service delivery and customer satisfaction.

Within the scope of the Helmholtz Metadata Collaboration (HMC), the ADVANCE project – Advanced metadata standards for biodiversity survey and monitoring data: supporting of research and conservation – aimed at supporting rich metadata generation with interoperable metadata standards and semantic artefacts that facilitate data access, integration and reuse across terrestrial, freshwater and marine realms. HMC's mission is to facilitate the discovery, access, machine-readability, and reuse of research data across and beyond the Helmholtz Association.We revised, adapted and expanded existing metadata schemas, vocabularies and thesauri to build a FAIR metadata schema and a metadata entry form built on it for users to provide their metadata instances focused on biodiversity monitoring data. The schema is FAIR because it is both machine-interpretable and follows domain-relevant community standards. This report provides a general overview of the project results and instructions on how to access, re-use and complete the metadata form.

Indigenous communities, linguists, teachers, and language activists have been developing methods to revitalise endangered languages over several decades. Not only are these methods diverse, they are usually implemented in various ways according to local needs and aspirations. Language revitalisation methods focus on proficiency, but there is also interest in strengthening identity, resilience, and wellbeing. Aside from a handful of successes, programs may not be achieving desired outcomes. One could try to evaluate specific programs. However, we believe that a necessary first step is to examine published literature of revitalisation efforts to develop initial understandings of how they work. In particular, we seek to understand how revitalisation efforts tap into the speech community, how local participation affects outcomes, and how this involvement is supported and sustained by external programs, with a focus on language revitalisation efforts in Australia. We conduct a realist synthesis, and through analysis of 125 pieces of literature, we identify 13 initial theories. In analysing these theories, we identify two major gaps in our understanding of language revitalisation: how revitalisation programs work to strengthen communities and promote commitment. We propose these as significant, under-theorised elements of successful revitalisation which can guide exploration at the level of individual programs.

In Spring 2020, the UK Government announced the cessation of in-person teaching for the vast majority of school-aged children in response to the COVID-19 pandemic. Prompting an accelerated shift towards digital learning across the curriculum, this announcement was accompanied by a rise in market-based solutions to address the problem of keeping young people active, 'healthy' and 'positive' whilst at home. The most prominent of these was offered by Joe Wicks, who broadcasted "PE with Joe" live globally via "YouTube" for five days per week for eighteen weeks. The aim of this paper is to critically explore some of the contextual factors that enabled Joe Wicks to create and legitimise a public health intervention under the title of physical education, and henceforth position himself (whether intentionally or not) as an authoritative agent for change within the discipline. After outlining who Joe Wicks is, we unpack the discursive framing of "PE with Joe" in order to locate Wicks' intervention amid the perennial politics of physical education. We then consider the meaning of "PE with Joe" and why Joe Wicks' involvement in physical education matters, reflecting upon the effects of Joe Wicks on the future of physical education practice and research. Among our conclusions is that the COVID-19 pandemic provided an opportunity for Joe Wicks -- here positioned and understood as a branded, celebrity lifestyle enterprise -- to manoeuvre himself (and his products) from the periphery to the centre of physical education's public imagery and discourse. Furthermore, we argue that exploring the ways in which Wicks' presence in the physical education space has been received, embraced, modified, challenged and resisted is vital in discerning "PE with Joe's" actual or perceived effects on the social construction of physical education, and the educational engagements of young people in physical activity in the post-COVID-19 landscape.

Social class inequalities in accessing sport persist across the western world as a result of financial, social and cultural factors. Research to date largely explores how inequalities impact both accessing and practicing sport and physical activity - identifying patterns and differences between social classes but failing to identify the long-term implications such as how students exchange these as official qualifications and knowledge in Physical Education (PE) degrees. In this paper, we use Bourdieu's concepts of capital, and to a lesser extent habitus and field to theorise about sport as sites of socialisation that shapes the composition and volume of capital students enter PE degrees with. To date, research suggests the role socialisation and informal learning plays in shaping PE students' development of valued dispositions, but often overlooks the intersecting impact of social class. We draw on data from seventeen undergraduate students, studying a non-teacher training PE degree, in the UK. The data presented is selected from interviews exploring how the fields of family, school, extra-curricular sport and the geo-demography of the area they grew up in shaped their access to and practice of Sport/PA. Furthermore, it indicates class differences exist in both the key sites and agents of socialisation. We suggest this has ramifications, in relation to the volume and composition of capital PE students enter Higher Education (HE) with, highlighting the importance for PE staff in HE to be aware of this. Consequently, we demonstrate prior socialisation contributes to students' differing experiences of PE degrees, potentially shaping inequalities resulting from their capacity to exchange capital when studying PE at university. This paper encourages PE staff in universities to question the assumption parity of entry qualification results in all students entering HE with same access to knowledge and experiences valued in PE degrees.

The early childhood education teacher workforce is consistently relied upon to bolster children's academic and socioemotional development in preparation for kindergarten and long-term outcomes. This is especially true of children who, historically overlooked and marginalized, are labeled "at risk." While research has focused on pervasive stressors as obstacles to these classroom professionals (e.g., teacher/teaching stress, curricular mandates, quality assessments, COVID-19), there is less research on stress in relation to the formation of teacher identity; specifically, how stress contributes to and detracts from the formation of a teacher's micro-identity, and how negative impacts of stress to the micro-identity may contribute to teachers' decisions to leave the field. Although once considered to be one of the fastest growing industries, The Great Resignation, as it has come to be known, estimates up to 25-30% of the workforce leave annually. To better understand the choices teachers make to leave the profession, the current study examined the influence of stress on teachers' microidentity by centering the voices of six Head Start teachers. Implementing a qualitative design, this investigation asked (a) Who are the Head Start teachers in the workforce today? (b) What are the particular stressors with which they contend? (c) How does the micro-identity of these teachers change as a result of stress, and what are the potential choices that follow? Results and findings indicated that Head Start teachers experience (1) stress as reality, (2) stress-shaped identities, and (3) identity-mediated choice. Implications and insights are discussed.

Introduction Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for TB preventive therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs. Our study aims to describe the pharmacokinetic and pharmacogenomics of 3HP used for TPT, the ADRs and their association with completion rates, and TPT outcomes, providing vital insights for TB control strategies in resource-limited settings.Methods This is an observational cohort study with a nested case–control study. We enrolled consecutive patients who had been initiated on TPT using the 3HP regimen. These are followed up biweekly and then monthly during the active phase of treatment and 3 monthly for 2 years following completion of TPT. ADR evaluation includes clinical assessment and liver function tests. Cases are selected from those who experience ADRs and controls from those who do not. Serum isoniazid and rifapentine concentrations are measured and pharmacogenomic analysis for NAT2, AADAC and CYP2E1 polymorphisms are done. Participants are followed up for 2 years to determine TPT outcomes.Analysis The safety profile of 3HP will be assessed using descriptive statistics, including proportions of patients experiencing ADRs and grade 3 or above events related to treatment. χ2 tests and regression models will determine predictors of ADRs and their impact on treatment completion. Pharmacokinetic-pharmacodynamic modelling will establish population parameters and factors influencing rifapentine and isoniazid concentrations.Ethics and dissemination Ethical approval of this study inclusive of all the appropriate documents was obtained from the Infectious Diseases Institute Research and Ethics Committee and the Uganda National Council of Science and Technology. The study adheres to legal, ethical and Good Clinical Practice (GCP) guidelines. Deidentified genotype data from 300 patients will be shared after publication. The protocol and phenotype data will be publicly accessible. Abstracts will be submitted to conferences, and a manuscript will be published poststudy.

IntroductionSkill-based curricula supplementing Head Start programming have shown great promise as early interventions improving school readiness of children from socioeconomically under-resourced families. The Getting Ready for School (GRS) intervention builds on such research by providing a supplemental skill-based curriculum targeting three core school readiness domains—language/literacy, math, and self-regulation—using learning activities aligned across the classroom and home contexts. The goal of this study was to examine the effects of the GRS intervention on school readiness skills in children in Head Start programs.MethodsParticipants were 3- to 4-year-olds (N = 463, 46% male, 81% Hispanic/Latine). Classrooms were non-randomly assigned to the GRS intervention (n = 20) or Head-Start-as-usual comparison group (n = 17). At pretest and posttest, children completed assessments of early language/literacy, math, and self-regulation. Multilevel modeling was used to examine the group-by-time interaction in prediction of children's school readiness skills.ResultsSignificant group-by-time interactions were found for early language/literacy (vocabulary, print knowledge) and math skills. Children in the intervention group demonstrated significantly greater gains over time in these skills compared to children in the comparison group. At posttest, children in the intervention group had significantly higher vocabulary than children in the comparison group (effect size = 0.34). Intervention effects were not found for self-regulation.DiscussionThe GRS intervention may support early language/literacy and math skills in preschool children from socioeconomically under-resourced families. Future studies focused on a modified version of the intervention could demonstrate larger effect sizes and improvements in self-regulation.

Food system sustainability, and ways of measuring it, are widely explored and discussed in academic literature. Measurement efforts are challenging because food systems are inherently complex and multifaceted, spanning diverse components, indus­tries, sectors, and scales. Several systems of indica­tors and metrics have been proposed to measure sustainability; however, most existing research focuses either on narrow scales (e.g., farm level or within a single supply chain), expansive scales that can gloss over complexity (e.g., national or global assessments), or limited scopes (e.g., only consider­ing environmental factors). A gap in the literature is a holistic local or regional approach to food sys­tem sustainability that integrates components across the system at a regional scale. In this reflec­tive essay, we describe our development of a framework to measure and track sustainability in such systems. We use a tiered framework that includes five sustainability dimensions and a system of indices, indicators, and metrics that allows for the measurement of important food system charac­teristics in a feasible and reproducible way. We employ a collaborative, transdisciplinary, facilitated team science process to first propose, and then refine, a sustainability assessment framework, using the U.S. state of Vermont as a case study. This paper details our process and progress, as well as reflections on challenges and recommendations for other team scientists. We further propose a plan to implement the framework, collect data, and engage with community members. The experiences and findings described here serve as a foundation for our own team’s continued work, as well as a springboard for other similar research efforts.

Abstract Phytoplankton blooms provoke bacterioplankton blooms, from which bacterial biomass (necromass) is released via increased zooplankton grazing and viral lysis. While bacterial consumption of algal biomass during blooms is well-studied, little is known about the concurrent recycling of these substantial amounts of bacterial necromass. We demonstrate that bacterial biomass, such as bacterial alpha-glucan storage polysaccharides, generated from the consumption of algal organic matter, is reused and thus itself a major bacterial carbon source in vitro and during a diatom-dominated bloom. We highlight conserved enzymes and binding proteins of dominant bloom-responder clades that are presumably involved in the recycling of bacterial alpha-glucan by members of the bacterial community. We furthermore demonstrate that the corresponding protein machineries can be specifically induced by extracted alpha-glucan-rich bacterial polysaccharide extracts. This recycling of bacterial necromass likely constitutes a large-scale intra-population energy conservation mechanism that keeps substantial amounts of carbon in a dedicated part of the microbial loop.

Abstract Background In 2016, Uganda added Hydroxyurea (HU) to the list of essential drugs to treat sickle cell disease SCD. However, Hydroxyurea utilization has been low for several countries in sub-Saharan Africa. This study examined patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, in Uganda. Methods To understand the patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease, we conducted a parallel convergent mixed methods study at outpatient departments of two national referral hospitals in Uganda from October 2022 to January 2023. The cross-sectional mixed-methods study employed both quantitative and qualitative methods. We collected survey data from a systematic sample of 259 participants and conducted individual interviews with a purposive sample of 40 participants (20 adolescents or their caregivers and 20 adult patients with SCD) and interviewed them individually on their knowledge, perceptions, barriers, and facilitators of HU utilization. Descriptive data were analyzed using Stata 16, whereas qualitative data were analyzed thematically using an inductive approach supported by NVivo 12 software. We triangulated data to determine the concordance of qualitative and quantitative data. Results The study enrolled 40 participants for qualitative interviews and 259 patients for quantitative, with an average age of 16, over half being female, 46% having secondary education, and 96% unmarried. The prevalence of HU use was 78%. The study identified three themes as follows: Patient barriers at the individual including Inadequate knowledge about HU, Persistent pain, Poor adherence to HU, Poor communication with health care workers, and Psychosocial and emotional challenges. At the facility level, long queues and poor quality of care, drug-related side effects that affect HU, and drug stock-outs were reported. Myths, rumors, and misconceptions about HU, and gender-related barriers were reported to affect HU utilization at a community level. Facilitators for the use of HU and recommendations for improvement. Facilitators included perceived benefits, long duration on HU, information sharing by healthcare workers, availability of complementary drugs, confirmation of diagnosis, and availability of medication at public health facilities or private pharmacies. Patients suggested continuous adherence support, encouragement from healthcare workers, sensitization about benefits and risks, a peer-to-peer approach, and financial support for adolescents and women to start businesses to resolve financial problems. Conclusion Implementing the use of HU has been challenging in Uganda and needs improvement. Facilitators to hydroxyurea use have been highlighted, though Patient-identified barriers at individual, facility, and community levels that need to be resolved. The experiences and insights shared by our participants provide invaluable guidance for increasing the uptake of HU. Further studies are needed to establish validated instruments to assess patients’ pain communication and adherence to the HU regimen.