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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.

Black Americans (AA) face a confluence of challenges when seeking care including unaffordable costs, negative experiences with providers, racism, and distrust in the healthcare system. This study utilized linear regressions and mediation analysis to explore the interconnectedness of these challenges within a community-based sample of 313 AA women aged 45 and older. Approximately 23% of participants reported affordability problems, while 44% had a negative experience with a provider. In the initial linear regression model excluding perceived racism, higher levels of distrust were observed among women reporting affordability problems (β = 2.66; p = 0.003) or negative experiences with a healthcare provider (β = 3.02; p =

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.

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.

Within this brief report, the authors, who are mostly neurodivergent and a majority autistic, outline some of the challenges and historical failings of participatory research with the autistic community. There is an urgent need to explore creative ways to ensure that research engages with autistic people in an active, meaningful, and valuable way (Den Houting et al., 2021; Fletcher-Watson et al., 2019; Garfield & Yudell, 2019). The authors detail the process of using reflective dialogue to explore the participatory research group’s personal experiences of mental health at a university. The participatory group later presented their experiences at a webinar attended by more than 200 strategic and supporting staff from UK universities. The group found reflective dialogue to be useful in addressing many of the failings of participatory research with the autistic community, such as redressing power imbalances and finding it to be personally beneficial and validating. The authors detail how this might be implemented and argue that this approach has valuable applications within autism research and beyond and should be explored further.

The role of myeloid cells (granulocytes and monocytes) in neurodegeneration and neurodegenerative disorders (NDD) is indisputable. Here we discuss the roles of myeloid cells in neurodegenerative diseases, and the recent advances in biofluid and imaging myeloid biomarker research with a focus on methods that can be used in the clinic. For this review, evidence from three neurodegenerative diseases will be included, Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). We discuss the potential for these biomarkers to be used in humans with suspected NDD as prognostic, diagnostic, or monitoring tools, identify knowledge gaps in literature, and propose potential approaches to further elucidate the role of myeloid cells in neurodegeneration and better utilize myeloid biomarkers in the understanding and treatment of NDD.

Previous cross-sectional studies have shown that sympathetic nervous system (SNS) arousal is positively associated with posttraumatic stress disorder (PTSD) symptoms in children with trauma exposure. One of the ways that SNS activity is measured is through skin conductance response (SCR), which has been shown to predict future PTSD severity in adults. In this study, we explored the utility of a novel, low-cost mobile SCR device, eSense, to predict future PTSD symptom severity in trauma exposed children. We recruited children (N = 43, age 9 years at initial visit) for a longitudinal study in which SCR was recorded at baseline visit, and PTSD symptoms were assessed two years later. Results indicated an interaction between SCR and trauma exposure, such that children with lower trauma exposure who demonstrated greater SCR reported higher PTSD severity two years later. This association remained significant even after controlling for baseline PTSD symptoms. Children with higher levels of trauma exposure did not show this association, potentially due to ceiling effects of PTSD symptoms. Together these findings suggest the utility of SCR as a biomarker for predicting trauma related disorders in children, and that it may be a valuable tool in clinical interventions targeting sympathetic arousal.

The International Secure Data Facility Professionals Network (ISDFPN) was set up in 2022 as part of the Social Sciences and Humanities Open Cloud project (SSHOC) with the aim of bringing together international colleagues working in or towards Trusted Research Environments (TREs), to share expertise and experiences, and to spark collaboration as well as develop new ideas. While various international networks and collaborations exist currently, these aim to improve the international data infrastructure landscape, and mainly focus on establishing connections between TREs. However, there is also a Forum needed for those working in these TREs, which provides a platform for regular knowledge exchange as well as opportunities of driving innovation. ISDFPN is not a network for developing infrastructure, rather it is a place to share experience, expertise, and ideas, which is not yet formally available internationally. As the fast-changing secure data landscape evolves, this Network will be a vital resource for collaborative work towards finding solutions for shared and newly emerging problems experienced by TRE staff. Where TREs are at different stages in their development, such a forum is vital as services seek to learn from each another. The ISDFPN held its first virtual meeting on 30 March 2022, and, although the SSHOC project finished in April 2022, has continued to meet twice yearly, co-Chaired by the UK Data Service, and GESIS Leibniz Institute for the Social Sciences. This paper traces the ISDFPN from its origins and highlights both its aims and objectives as well as its activities so far.

The World Health Organization has developed target product profiles containing minimum and optimum targets for key characteristics for tests for tuberculosis treatment monitoring and optimization. Tuberculosis treatment optimization refers to initiating or switching to an effective tuberculosis treatment regimen that results in a high likelihood of a good treatment outcome. The target product profiles also cover tests of cure conducted at the end of treatment. The development of the target product profiles was informed by a stakeholder survey, a cost-effectiveness analysis and a patient-care pathway analysis. Additional feedback from stakeholders was obtained by means of a Delphi-like process, a technical consultation and a call for public comment on a draft document. A scientific development group agreed on the final targets in a consensus meeting. For characteristics rated of highest importance, the document lists: (i) high diagnostic accuracy (sensitivity and specificity); (ii) time to result of optimally [less than or equal to] 2 hours and no more than 1 day; (iii) required sample type to be minimally invasive, easily obtainable, such as urine, breath, or capillary blood, or a respiratory sample that goes beyond sputum; (iv) ideally the test could be placed at a peripheral-level health facility without a laboratory; and (v) the test should be affordable to low- and middle-income countries, and allow wide and equitable access and scale-up. Use of these target product profiles should facilitate the development of new tuberculosis treatment monitoring and optimization tests that are accurate and accessible for all people being treated for tuberculosis. L'Organisation mondiale de la sante a elabore des profils de produits cibles contenant des cibles minimales et optimales pour les caracteristiques principales des essais destines au suivi et a l'optimisation du traitement de la tuberculose. L'optimisation du traitement de la tuberculose fait reference a l'instauration d'un regime de traitement efficace de la tuberculose ou a l'adoption d'un tel regime, avec une probabilite elevee d'obtenir de bons resultats therapeutiques. Les profils de produits cibles couvrent egalement les essais de guerison effectues a l'issue du traitement. Les profils de produits cibles ont ete elabores sur la base d'un sondage aupres des parties prenantes, d'une analyse cout-efficacite et d'une analyse du parcours de soins du patient. Des retours supplementaires des parties prenantes ont ete obtenus au moyen d'un processus cree selon la methode Delphi, d'une consultation technique et d'un appel a commentaires publics sur un projet de document. Un groupe d'elaboration scientifique s'est mis d'accord sur les objectifs finaux lors d'une reunion de concertation. En ce qui concerne les caracteristiques jugees les plus importantes, le document enumere ce qui suit: (i) une grande precision diagnostique (sensibilite et specificite); (ii) un delai ideal d'obtention des resultats [less than or equal to] 2 heures et au maximum de 1 jour; (iii) le type d'echantillon requis doit etre peu invasif et facile a obtenir, comme l'urine, l'haleine ou le sang capillaire, ou bien un echantillon respiratoire au-dela des expectorations; (iv) idealement, l'essai pourrait avoir lieu dans un etablissement de sante peripherique sans laboratoire ; et (v) l'essai devrait etre abordable pour les pays a revenu faible et intermediaire et permettre un acces large et equitable ainsi qu'une mise a l'echelle. L'utilisation de ces profils de produits cibles devrait faciliter la mise au point de nouveaux essais de surveillance et d'optimisation du traitement de la tuberculose qui soient precis et accessibles a toutes les personnes suivant un traitement pour la tuberculose. La Organizacion Mundial de la Salud ha elaborado perfiles de productos objetivo que contienen objetivos minimos y optimos para las caracteristicas principales de las pruebas de seguimiento y optimizacion del tratamiento de la tuberculosis. La optimizacion del tratamiento de la tuberculosis consiste en iniciar o cambiar a un regimen eficaz de tratamiento de la tuberculosis que ofrezca una alta probabilidad de un buen resultado terapeutico. Los perfiles de productos objetivo tambien abarcan las pruebas de curacion realizadas al final del tratamiento. La elaboracion de los perfiles de los productos objetivo se baso en una encuesta a las partes interesadas, un analisis de rentabilidad y un analisis de la via de atencion al paciente. Se obtuvo informacion adicional de las partes interesadas mediante un proceso tipo Delphi, una consulta tecnica y una convocatoria de comentarios publicos sobre un borrador del documento. Un grupo de desarrollo cientifico acordo los objetivos finales en una reunion de consenso. Para las caracteristicas clasificadas de mayor importancia, el documento enumera: (i) alta precision diagnostica (sensibilidad y especificidad); (ii) tiempo hasta el resultado de optimamente [less than or equal to] 2 horas y no mas de 1 dia; (iii) el tipo de muestra requerida debe ser minimamente invasiva, facil de obtener, como orina, aliento o sangre capilar, o una muestra respiratoria que vaya mas alla del esputo; (iv) idealmente la prueba podria realizarse en un centro sanitario periferico sin laboratorio; y (v) la prueba debe ser asequible para los paises de ingresos bajos y medios y permitir un acceso amplio y equitativo y su expansion. El uso de estos perfiles de producto objetivo deberia facilitar el desarrollo de pruebas nuevas de seguimiento y optimizacion del tratamiento de la tuberculosis que sean precisas y accesibles para todas las personas que reciben tratamiento antituberculoso. [phrase omitted], Introduction Tuberculosis continues to be a major cause of morbidity and mortality globally, despite being curable and preventable. In 2021, an estimated 10.6 million people had tuberculosis disease and 1.6 [...]

Abstract Proton‐beam therapy (PBT) is a cutting‐edge radiation therapy modality that is currently not available in Australia. Comparative photon‐proton (CPP) planning is required for the medical treatment overseas programme (MTOP) and will be required for access to PBT in Australia in the future. Comparative planning brings professional development benefits to all members of the radiation therapy team. This service was also created to support future proposals for a PBT facility in Victoria. We report our experience developing an in‐house CPP service at Peter MacCallum Cancer Centre. A set of resources to support CPP planning was established. Training of relevant staff was undertaken after which an in‐house training programme was developed. A standard protocol for PBT planning parameters was established. All CPP plans were reviewed. Future goals for the CPP planning programme were described. In total, 62 cases were comparatively planned over 54 months. Of these, 60% were paediatric cases, 14% were adolescents and young adults (15–25 years) and 26% were adults. The vast majority (over 75%) of patients comparatively planned required irradiation to the central nervous system including brain and cranio‐spinal irradiation. A variety of proton plans were reviewed by international PBT experts to confirm their deliverability. Our team at Peter MacCallum Cancer Centre has gained significant experience in CPP planning and will continue to develop this further. Local expertise will help support decentralisation of patient selection for proton treatments in the near future and the PBT business case in Victoria.

Abstract Proton beam therapy (PBT) is increasingly used to treat cancers, especially in the paediatric and adolescent and young adult (AYA) population. As PBT becomes more accessible, determining when PBT should be used instead of photon irradiation can be difficult. There is a need to balance patient, tumour and treatment factors when making this decision. Comparing the dosimetry between these two modalities plays an important role in this process. PBT can reduce low to intermediate doses to organs at risk (OAR), but photon irradiation has its dosimetric advantages. We present two cases with brain tumours, one paediatric and one AYA, in which treatment plan comparison between photons and protons showed dosimetric advantages of photon irradiation. The first case was an 18‐month‐old child diagnosed with posterior fossa ependymoma requiring adjuvant radiotherapy. Photon irradiation using volumetric modulated arc therapy (VMAT) had lower doses to the hippocampi but higher doses to the pituitary gland. The second case was a 21‐year‐old with an optic pathway glioma. There was better sparing of the critical optic structures and pituitary gland using fractionated stereotactic radiation therapy over PBT. The dosimetric advantages of photon irradiation over PBT have been demonstrated in these cases. This highlights the role of proton‐to‐photon comparative treatment planning to better understand which patients might benefit from photon irradiation versus PBT.

Land surface models are an important tool in the study of climate change and its impacts, but their use can be hampered by uncertainties in input parameter settings and by errors in the models. We apply uncertainty quantification (UQ) techniques to constrain the input parameter space and corresponding historical simulations of JULES-ES-1.0 (Joint UK Land Environment Simulator Earth System), the land surface component of the UK Earth System Model, UKESM1.0. We use an ensemble of historical simulations of the land surface model to rule out ensemble members and corresponding input parameter settings that do not match modern observations of the land surface and carbon cycle. As JULES-ES-1.0 is computationally expensive, we use a cheap statistical proxy termed an emulator, trained on the ensemble of model runs, to rule out parts of the parameter space where the simulator has not yet been run. We use history matching, an iterated approach to constraining JULES-ES-1.0, running an initial ensemble and training the emulator, before choosing a second wave of ensemble members consistent with historical land surface observations. We successfully rule out 88 % of the initial input parameter space as being statistically inconsistent with observed land surface behaviour. The result is a set of historical simulations and a constrained input space that are statistically consistent with observations. Furthermore, we use sensitivity analysis to identify the most (and least) important input parameters for controlling the global output of JULES-ES-1.0 and provide information on how parameters might be varied to improve the performance of the model and eliminate model biases.