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Robust school-university partnerships can create continuous systems of educator learning that focus on systemic change and the simultaneous renewal of both educators and the organizations within which they work to improve outcomes, opportunities, and access for P-12 students and their teachers. This article is a case of the Project PREP school-university partnership, a complex integrated systems approach towards rethinking recruitment, preparation, support, and development of diverse teachers and leaders. We show how Project PREP has begun to design aligned and enhanced systems for teacher education that embody clinical practice, coaching, and high-quality professional learning for both practicing and future teachers and leaders.

This survey-based study examined how the intensity of the beliefs of novice in-service teachers about reform-based mathematics instruction changed as they crossed the threshold into their first year of teaching. It also investigated the relationship between the influence of new mentors, or "transitional faculty," including mentor teachers, instructional coaches, and administrators, along with curriculum materials, and the changes belief intensity. Results obtained indicated belief changes were highly influenced by transitional faculty and curriculum materials. This study highlights the importance of creating systems to improve mentor selection and training so the work of university personnel is not undone during the novice's first year of teaching.

Adults with Down syndrome are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease and is linked to a diagnosis of dementia in adults with Down syndrome via structural imaging markers of cerebrovascular disease and atrophy. The study included participants with Down syndrome from the Alzheimers Disease - Down Syndrome study (n = 195, age = 50.6 ± 7.2 years, 44% women, 18% diagnosed with dementia). Higher pulse pressure was associated with greater global, parietal and occipital white matter hyperintensity volume but not with enlarged perivascular spaces, microbleeds or infarcts. Using a structural equation model, we found that pulse pressure was associated with greater white matter hyperintensity volume, which in turn was related to increased neurodegeneration, and subsequent dementia diagnosis. Pulse pressure is an important determinant of brain health and clinical outcomes in individuals with Down syndrome despite the low likelihood of frank hypertension.

INTRODUCTION: Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimers disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS. METHODS: T1-weighted structural magnetic resonance imaging (MRI) data were collected from 101 participants with DS. Hippocampus and EC volume, as well as EC subregional cortical thickness, were derived. In a subset of participants, plasma NfL concentrations and modified Cued Recall Test scores were obtained. Partial correlation and mediation were used to test relationships between medial temporal lobe (MTL) atrophy, plasma NfL, and episodic memory. RESULTS: Hippocampus volume, left anterolateral EC (alEC) thickness, and plasma NfL were correlated with each other and were associated with memory. Plasma NfL mediated the relationship between left alEC thickness and memory as well as hippocampus volume and memory. DISCUSSION: The relationship between MTL gray matter and memory is mediated by plasma NfL levels, suggesting a link between neurodegenerative processes underlying axonal injury and frank gray matter loss in key structures supporting episodic memory in people with DS.

Zika virus (ZIKV) infections are spreading silently with limited global surveillance in at least 89 countries and territories. There is a pressing need to develop an effective vaccine suitable for equitable distribution globally. Consequently, we previously developed a proprietary DNA vaccine encoding secreted non-structural protein 1 of ZIKV (pVAX-tpaNS1) to elicit rapid protection in a T cell-dependent manner in mice. In the current study, we evaluated the stability, efficacy, and immunogenicity of delivering this DNA vaccine into the skin using a clinically effective and proprietary high-density microarray patch (HD-MAP). Dry-coating of pVAX-tpaNS1 on the HD-MAP device resulted in no loss of vaccine stability at 40°C storage over the course of 28 days. Vaccination of mice (BALB/c) with the HD-MAP-coated pVAX-tpaNS1 elicited a robust anti-NS1 IgG response in both the cervicovaginal mucosa and systemically and afforded protection against live ZIKV challenge. Furthermore, the vaccination elicited a significantly higher magnitude and broader NS1-specific T helper and cytotoxic T cell response in vivo compared with traditional needle and syringe intradermal vaccination. Overall, the study highlights distinctive immunological advantages coupled with an excellent thermostability profile of using the HD-MAP device to deliver a novel ZIKV DNA vaccine.

Alzheimer's disease (AD) is the most common type of dementia, characterized by early memory impairments and gradual worsening of daily functions. AD-related pathology, such as amyloid-beta (Aβ) plaques, begins to accumulate many years before the onset of clinical symptoms. Predicting risk for AD via related pathology is critical as the preclinical stage could serve as a therapeutic time window, allowing for early management of the disease and reducing health and economic costs. Current methods for detecting AD pathology, however, are often expensive and invasive, limiting wide and easy access to a clinical setting. A non-invasive, cost-efficient platform, such as computerized cognitive tests, could be potentially useful to identify at-risk individuals as early as possible. In this study, we examined the diagnostic value of an episodic memory task, the mnemonic discrimination task (MDT), for predicting risk of cognitive impairment or Aβ burden. We constructed a random forest classification algorithm, utilizing MDT performance metrics and various neuropsychological test scores as input features, and assessed model performance using area under the curve (AUC). Models based on MDT performance metrics achieved classification results with an AUC of 0.83 for cognitive status and an AUC of 0.64 for Aβ status. Our findings suggest that mnemonic discrimination function may be a useful predictor of progression to prodromal AD or increased risk of Aβ load, which could be a cost-efficient, noninvasive cognitive testing solution for potentially wide-scale assessment of AD pathological and cognitive risk.

Abstract Aurora B kinase (AURKB) inhibitors have been trialled in a range of different tumour types but are not approved for any indication. Expression of the human papilloma virus (HPV) oncogenes and loss of retinoblastoma (RB) protein function has been reported to increase sensitivity to AURKB inhibitors but the mechanism of their contribution to sensitivity is poorly understood. Two commonly reported outcomes of AURKB inhibition are polyploidy and senescence, although their relationship is unclear. Here we have investigated the major cellular targets of the HPV E6 and E7, p53 and RB, to determine their contribution to AURKB inhibitor induced polyploidy and senescence. We demonstrate that polyploidy is a universal feature of AURKB inhibitor treatment in all cell types including normal primary cells, but the subsequent outcomes are controlled by RB and p53. We demonstrate that p53 by regulating p21 expression is required for an initial cell cycle arrest by inhibiting both CDK2 and CDK4 activity, but this arrest is only triggered after cells have undergone two failed mitosis and cytokinesis. However, cells can enter senescence in the absence of p53. RB is essential for AURKB inhibitor-induced senescence. AURKB inhibitor induces rapid hypophosphorylation of RB independent of inhibition of CDK2 or CDK4 kinases and p53. This work demonstrates that p53 activation determines the timing of senescence onset, but RB is indispensable for senescence.

ABSTRACT Floating offshore wind (FOW) is a renewable energy source that is set to play an essential role in addressing climate change and the need for sustainable development. However, due to the increasing threat of climate emergency, more wind turbines are required to be deployed in deep water locations, further offshore. This presents heightened challenges for accessing the turbines and performing maintenance, leading to increased costs. Naturally, methods to reduce operational expenditure (OpEx) are highly desirable. One method that shows potential for reducing OpEx of FOW is LIDAR‐assisted pitch control. This approach uses wind velocity measurements from a nacelle‐mounted LIDAR to enable feedforward control of floating offshore wind turbines (FOWTs) and can result in reductions to the variations of structural loads. Results obtained from a previous study of combined feedforward collective and individual pitch control (FFCPC + FFIPC) are translated to OpEx reductions via reduced component failure rates for future FOW developments, namely, in locations awarded in the recent ScotWind leasing round. The results indicate that LIDAR‐assisted pitch control may allow for an up to 5% reduction in OpEx, increasing to up to 11% with workability constraints included. The results varied across the three ScotWind sites considered, with sites furthest from shore reaping the greatest benefit from LIDAR‐assisted control. This work highlights the potential savings and reduction in the overall levelised cost of energy for future offshore wind turbine projects deliverable through the implementation of LIDAR‐assisted pitch control.

Abstract High‐dose melphalan followed by stem cell rescue is the standard consolidative therapy for transplant‐eligible patients with multiple myeloma (MM) in the United Kingdom. A melphalan dose of 200 mg/m2 (Mel200) is considered the “gold standard” for autologous stem cell transplant (ASCT) conditioning for fit patients ≤70 years old; however, with a peak diagnosis incidence at 80–89 years old in the UK dose adjustments will be inevitable to limit toxicities. In this single‐centre UK‐based retrospective analysis, data was collected from patients with plasma cell dyscrasias who underwent a first reduced‐intensity, Mel140, ASCT from 2006 to 2019, a total of 81 patients. We found that the procedure was overall safe with seven (9%) of patients requiring ITU admission and a single transplant‐related death within the initial autograft admission. The progression‐free survival (PFS) and overall survival were comparable with those previously reported in the literature with median PFS for our cohort of 31 months. Univariate analysis of our data showed an inferior PFS for patients aged ≥70 years. In conclusion, although this is a retrospective analysis, it demonstrates that dose‐reduced melphalan conditioning is safe and effective in patients deemed unfit for standard‐intensity conditioning.

Abstract Background Strategies to promote workplace mental health can target system, organization, team, and individual levels exclusively or in concert with each other. Creating toolkits that include these different levels is an emerging innovative strategy to support employees working in various sectors. Our paper describes the development, implementation, and refinement of two different online toolkits: the Healthy Professional Worker Toolkit for Education Workers and the Health Worker Burnout Toolkit. Methods The Knowledge to Action Framework guided the team during the development and early interventions phases of toolkit development. Stakeholder engagement regarding the intended use of the toolkit of promising practices for workplace interventions was integrated throughout with different forms of feedback in a research capacity between 2022 and 2024. Results Reflecting on the different phases of the KTA Framework, we describe first the engagement involved in building the toolkits and then on their utilization. Our toolkits were built to include different resources aimed at empowering workers, teams, and employers offering innovative ideas to address the mental health-leaves of absence and return to work cycle in one case and the different forms and consequences of burnout in the other. Criteria for inclusion were informed by ongoing research with a range of stakeholders and other intended toolkit users including managers, supervisors, executives, human resource specialists, staff, and others in healthcare and educational organizations and settings. In the implementation phase, the volume of resources available in each toolkit considered a strength by some was overwhelming for some partners and individual workers to navigate. Capacity, engagement, time, and readiness for change, are themes that heavily influenced if and when organizations interacted with each toolkit, and how much time they spent exploring the resources provided. Conclusion It is critical to ground toolkits in the experiential evidence of workplace mental health as is linking these to evidence-informed interventions that correspond to workplace concerns. Organizational readiness to adopt and adapt resources and implement changes is a key consideration. Ultimately, user engagement is what brought these toolkits to life.

Abstract Background National legislative guidelines for sleep and rest are lacking in the Canadian licensed childcare sector. No review of Canadian legislation for licensed childcare facilities has focused on sleep. This paper provides a review of the Canadian provincial and territorial legislative landscape, regarding sleep, rest, and naps in licensed childcare centers. Methods Childcare statutes and regulations for each province and territory were identified and downloaded on a particular date. Statutes and regulations were reviewed focusing on sections articulating licensed childcare facility mandates governing sleep, rest, naps, and sleep equipment. An excel file was used to facilitate systematic data retrieval and comparisons across provinces and territories. Two authors developed and discussed themes that summarized data from the documents. Results No statutes indicated recommendations for sleep, rest, or naps. Only one regulation defined rest (Alberta). Our analysis of regulations identified four themes representing sleep, rest, and naps: programming (general programming, daily programming); space (dedicated space, amount of space, age-specific space); equipment (developmental appropriateness, acceptable sleep equipment, age-specific equipment); and safety (staffing during sleep/rest, sleep position, sleep monitoring, sleep equipment safety, prohibited practices). In Canada, minimal regulatory consistency is evident in required sleep programming, space, acceptability of sleep equipment, and sleep safety considerations. Most jurisdictions’ regulations indicated necessity for developmentally appropriate rest or sleep areas and equipment, in particular for infants, but there was minimal consistency in defining infant age groups. Conclusions Although we identified themes related to sleep across regulations, childcare regulations differ in their definitions of infants and specifications for children’s sleep and rest in licensed Canadian childcare facilities. Without adequate definitions in legislative components of appropriate sleep duration linked to children’s developmental stages, childcare facilities lack guidance to support healthy sleep for children in their care. Future research can examine translation of healthy sleep guidelines into government legislation and mandates for sleep, rest, and naps among young children in licensed childcare.

Abstract Solitons, the distinct balance between nonlinearity and dispersion, provide a route toward ultrafast electromagnetic pulse shaping, high-harmonic generation, real-time image processing, and RF photonic communications. Here we uniquely explore and observe the spatio-temporal breather dynamics of optical soliton crystals in frequency microcombs, examining spatial breathers, chaos transitions, and dynamical deterministic switching – in nonlinear measurements and theory. To understand the breather solitons, we describe their dynamical routes and two example transitional maps of the ensemble spatial breathers, with and without chaos initiation. We elucidate the physical mechanisms of the breather dynamics in the soliton crystal microcombs, in the interaction plane limit cycles and in the domain-wall understanding with parity symmetry breaking from third-order dispersion. We present maps of the accessible nonlinear regions, the breather frequency dependences on third-order dispersion and avoided-mode crossing strengths, and the transition between the collective breather spatio-temporal states. Our range of measurements matches well with our first-principles theory and nonlinear modeling. To image these soliton ensembles and their breathers, we further constructed panoramic temporal imaging for simultaneous fast- and slow-axis two-dimensional mapping of the breathers. In the phase-differential sampling, we present two-dimensional evolution maps of soliton crystal breathers, including with defects, in both stable breathers and breathers with drift. Our fundamental studies contribute to the understanding of nonlinear dynamics in soliton crystal complexes, their spatio-temporal dependences, and their stability-existence zones.

Reservoirs are ubiquitous water infrastructure, providing functional capability to manage, and often mitigate, hydrological variability across space and time. The presence and operation of a reservoir control the downstream flow regime, such that in many locations understanding reservoir operations is crucial to understanding the hydrological functioning of a catchment. Despite many advances in modelling reservoir operations, inclusion of reservoirs in large-scale hydrological modelling remains challenging, particularly when the number of reservoirs is large and data access is limited. Here we design a set of simple reservoir operating rules (with only two calibrated parameters) focused on simulating small water supply reservoirs across large scales with various types of open-access data (i.e. catchment attributes and flows at downstream gauges). We integrate our rules into a national-scale hydrological model of Great Britain and compare hydrological simulations with and without the new reservoir component. Our simple reservoir operating rules significantly increase model performance in reservoir-impacted catchments, particularly when the rules are calibrated individually at each downstream gauge. We also test the feasibility of using transfer functions (which transform reservoir and catchment attributes into operating rule parameters) to identify a nationally consistent calibration. This works well in ∼ 50 % of the catchments, while nuances in individual reservoir operations limit performance in others. We suggest that our approach should provide a lower benchmark for simulations in catchments containing water supply reservoirs and that more complex methods should only be considered where they outperform our simple approach.

In this paper, we present the view that an ontological shift to complexity thinking will be significant in the future of physical education (PE). Complexity thinking not only moves PE beyond long dominant modernist approaches but also offers the opportunity to integrate many of the postmodern perspectives that currently seek to frame PE. Four interconnected complexity commonalities, becoming, lived time, self-organisation and boundaries, are presented in an overarching frame to guide future PE developments in ways that are coherent, connected and emergent. PE is subsequently viewed as a complex phenomenon that is always in a non-linear, messy and never-ending process of becoming. Students, teachers and other stakeholders are also complex as their past, present and future experiences constantly merge in a lived time unity to create lifelong and life-wide PE journeys that are both personalised and holistic. Central to these personalised journeys is each stakeholder's ability to self-organise and influence the trajectory of their pathways. Self-organisation, however, is not a relativist 'anything goes' phenomenon but a process that takes place within a multiplicity of boundaries. While boundaries may traditionally be viewed as divisive features, complexity thinking recognises that many boundaries are flexible and enable the creation of 'boundary spaces' in which 'rich' discussions can take place to develop more coherent, connected and emergent forms of PE. Transdisciplinary Inquiry (TDI) and Ecologically Informed Practice (EIP) are presented as perspectives that can help teachers, and others, create the 'boundary spaces' in which ways to plan and introduce complexity-informed forms of PE can be explored. The paper concludes by proposing that the challenge for PE in the future will be for practitioners to develop the adaptability, openness, confidence and self-organising skills that will be needed to make the most effective use of the 'rich interactions' that these 'boundary spaces' offer.

Abstract Low skeletal muscle index/density (SMI/SMD) is prevalent in cancer, adversely prognostic and associated with tumour stage and the systemic inflammatory response (SIR). Age and SMI/SMD has not been widely studied. The present study analyses the association between age and SMI/SMD after adjustment for other clinicopathological factors. Patients undergoing resectional surgery for TNM Stage I-III disease within the West of Scotland between 2011 and 2014 were identified. A single CT slice was obtained from each patients staging CT scan. SMI and SMD were stratified normal/abnormal. The SIR was stratified using Systemic Inflammatory Grade (SIG). When stratified by age (