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Nationally, more than 75% of individuals who are credentialed to teach are prepared in traditional college- or university-based teacher education programs (TEPs). But the college and employment pathways that prospective teachers take to TEP enrollment and completion have not been comprehensively examined. A better understanding of how credentialed individuals find their way into TEPs helps us understand the sources of new teacher supply early in the prospective teacher pipeline. With that in mind, we analyze pathways into and through TEPs using historical postsecondary and unemployment insurance data from Washington State. We find that the pathways are quite varied, with around 40% of bachelor's-level TEP completers spending at least some time in community colleges and fewer than 40% enrolling and finishing at the same university directly after high school. Pathways to master's TEP completion are even more varied, with almost half of the completers having prior employment experience. For researchers, this varied landscape raises important questions about the relationship between pathways, candidate persistence, and eventual job performance. For policymakers, the results suggest that efforts to recruit the next generation of teachers need to look beyond the pool of students already enrolled at a 4-year university to include students at 2-year colleges or in the labor force who might be interested in entering a TEP.

Postgraduate engagement in delivering outreach activities is more commonplace than it once was. However, the impact on postgraduate students (typically studying for a Ph.D. degree) of participating in the delivery of these outreach activities has rarely, if ever, been recorded. The Bristol ChemLabS Outreach program has been running for ca. 17 years, and in that time, many postgraduate students have been involved (approximately 500), with around 250 typically for up to 3 years. We sought to investigate the impact of outreach engagement on postgraduate alumni who were involved in the program for over 3 years (32) and how the experiences and training of the outreach program had impacted on their careers postgraduation. Thirty of the 32 postgraduates engaged and ~70% reported that their outreach experience had influenced their decision making on future careers. Many respondents reported that the skills and experiences gained through outreach participation had contributed to success in applying for and interviewing at their future employers. All respondents reported that outreach had helped them to develop key skills that were valued in the workplace, specifically, communication, teamwork, organizational skills, time planning, event planning, and event management. Rather than a pleasant distraction or an opportunity to supplement income, all participants noted that they felt there were many additional benefits and that this was time well spent. Outreach should not be viewed as a distraction to science research but rather an important enhancement to it provided that the program is well constructed and seeks to develop those delivering the outreach activities.

Despite numerous female contraceptive options, nearly half of all pregnancies are unintended. Family planning choices for men are currently limited to unreliable condoms and invasive vasectomies with questionable reversibility. Here, we report the development of an oral contraceptive approach based on transcriptional disruption of cyclical gene expression patterns during spermatogenesis. Spermatogenesis involves a continuous series of self-renewal and differentiation programs of spermatogonial stem cells (SSCs) that is regulated by retinoic acid (RA)-dependent activation of receptors (RARs), which control target gene expression through association with corepressor proteins. We have found that the interaction between RAR and the corepressor silencing mediator of retinoid and thyroid hormone receptors (SMRT) is essential for spermatogenesis. In a genetically engineered mouse model that negates SMRT-RAR binding (SMRTmRID mice), the synchronized, cyclic expression of RAR-dependent genes along the seminiferous tubules is disrupted. Notably, the presence of an RA-resistant SSC population that survives RAR de-repression suggests that the infertility attributed to the loss of SMRT-mediated repression is reversible. Supporting this notion, we show that inhibiting the action of the SMRT complex with chronic, low-dose oral administration of a histone deacetylase inhibitor reversibly blocks spermatogenesis and fertility without affecting libido. This demonstration validates pharmacologic targeting of the SMRT repressor complex for non-hormonal male contraception.

Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction.

Bile acids (BAs) affect the intestinal environment by ensuring barrier integrity, maintaining microbiota balance, regulating epithelium turnover, and modulating the immune system. As a master regulator of BA homeostasis, farnesoid X receptor (FXR) is severely compromised in patients with inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). At the front line, gut macrophages react to the microbiota and metabolites that breach the epithelium. We aim to study the role of the BA/FXR axis in macrophages. This study demonstrates that inflammation-induced epithelial abnormalities compromised FXR signaling and altered BAs' profile in a mouse CAC model. Further, gut macrophage-intrinsic FXR sensed aberrant BAs, leading to pro-inflammatory cytokines' secretion, which promoted intestinal stem cell proliferation. Mechanistically, activation of FXR ameliorated intestinal inflammation and inhibited colitis-associated tumor growth, by regulating gut macrophages' recruitment, polarization, and crosstalk with Th17 cells. However, deletion of FXR in bone marrow or gut macrophages escalated the intestinal inflammation. In summary, our study reveals a distinctive regulatory role of FXR in gut macrophages, suggesting its potential as a therapeutic target for addressing IBD and CAC.

Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age. Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age. Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable. Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.

Objective: Short-term RCTs have demonstrated that MPH-treatment significantly reduces ADHD-symptoms, but is also associated with adverse events, including sleep problems. However, data on long-term effects of MPH on sleep remain limited. Methods: We performed a 2-year naturalistic prospective pharmacovigilance multicentre study. Participants were recruited into three groups: ADHD patients intending to start MPH-treatment (MPH-group), those not intending to use ADHD-medication (no-MPH-group), and a non-ADHD control-group. Sleep problems were assessed with the Children's-Sleep-Habits-Questionnaire (CSHQ). Results: 1,410 participants were enrolled. Baseline mean CSHQ-total-sleep-scores could be considered clinically significant for the MPH-group and the no-MPH-group, but not for controls. The only group to show a significant increase in any aspect of sleep from baseline to 24-months was the control-group. Comparing the MPH- to the no-MPH-group no differences in total-sleep-score changes were found. Conclusion: Our findings support that sleep-problems are common in ADHD, but don't suggest significant negative long-term effects of MPH on sleep.

Prior work on teacher candidates in Washington State has shown that about two thirds of individuals who trained to become teachers between 2005 and 2015 and received a teaching credential did not enter the state's public teaching workforce immediately after graduation, while about one third never entered a public teaching job in the state at all. In this analysis, we link data on these teacher candidates to unemployment insurance data in the state to provide a descriptive portrait of the future earnings and wages of these individuals inside and outside of public schools. Candidates who initially became public school teachers earned considerably more, on average, than candidates who were initially employed either in other education positions or in other sectors of the state's workforce. These differences persisted ten years into the average career and across transitions into and out of teaching. There is therefore little evidence that teacher candidates who did not become teachers were lured into other professions by higher compensation. Instead, the patterns are consistent with demand-side constraints on teacher hiring during this time period that resulted in individuals who wanted to become teachers taking positions that offered lower wages but could lead to future teaching positions.

Oncogenic lesions in pancreatic ductal adenocarcinoma (PDAC) hijack the epigenetic machinery in stromal components to establish a desmoplastic and therapeutic resistant tumor microenvironment (TME). Here we identify Class I histone deacetylases (HDACs) as key epigenetic factors facilitating the induction of pro-desmoplastic and pro-tumorigenic transcriptional programs in pancreatic stromal fibroblasts. Mechanistically, HDAC-mediated changes in chromatin architecture enable the activation of pro-desmoplastic programs directed by serum response factor (SRF) and forkhead box M1 (FOXM1). HDACs also coordinate fibroblast pro-inflammatory programs inducing leukemia inhibitory factor (LIF) expression, supporting paracrine pro-tumorigenic crosstalk. HDAC depletion in cancer-associated fibroblasts (CAFs) and treatment with the HDAC inhibitor entinostat (Ent) in PDAC mouse models reduce stromal activation and curb tumor progression. Notably, HDAC inhibition (HDACi) enriches a lipogenic fibroblast subpopulation, a potential precursor for myofibroblasts in the PDAC stroma. Overall, our study reveals the stromal targeting potential of HDACi, highlighting the utility of this epigenetic modulating approach in PDAC therapeutics.

Abstract Background Disordered amino acid metabolism is observed in cerebral malaria (CM). This study sought to determine whether abnormal amino acid concentrations were associated with level of consciousness in children recovering from coma. Twenty-one amino acids and coma scores were quantified longitudinally and the data were analysed for associations. Methods In a prospective observational study, 42 children with CM were enrolled. Amino acid levels were measured at entry and at frequent intervals thereafter and consciousness was assessed by Blantyre Coma Scores (BCS). Thirty-six healthy children served as controls for in-country normal amino acid ranges. Logistic regression was employed using a generalized linear mixed-effects model to assess associations between out-of-range amino acid levels and BCS. Results At entry 16/21 amino acid levels were out-of-range. Longitudinal analysis revealed 10/21 out-of-range amino acids were significantly associated with BCS. Elevated phenylalanine levels showed the highest association with low BCS. This finding held when out-of-normal-range data were analysed at each sampling time. Conclusion Longitudinal data is provided for associations between abnormal amino acid levels and recovery from CM. Of 10 amino acids significantly associated with BCS, elevated phenylalanine may be a surrogate for impaired clearance of ether lipid mediators of inflammation and may contribute to CM pathogenesis.

Abstract Background Student-led clinics can provide low-cost speciality care and practical interprofessional education (IPE) opportunities. In Australia, there are currently limited speciality services available that provide neurodevelopmental assessments that consider fetal alcohol spectrum disorder (FASD) as one possible outcome. The aim of the current study was to understand student experiences in a novel interprofessional student-led clinic for children and adolescents with suspected or confirmed prenatal alcohol exposure. Method Seventeen allied health university students (11 occupational therapy; 6 psychology) participated in individual semi-structured interviews following completion of a 10-week clinic placement. Reflexive thematic analysis was undertaken using NVivo12. Results Four main themes were generated: (1) Interprofessional practice a key for students’ development as future healthcare professionals; (2) Meaningful relationships and students’ belief they made a difference; (3) Novel challenges tested students’ capabilities on placement; and (4) Supervisor attitude and approach to learning supported student development. Conclusions The current study demonstrated that the interprofessional student-led neurodevelopmental clinic provided a valuable IPE opportunity for students.

Abstract Introduction The COVID-19 pandemic period (2020 to 2022) challenged and overstretched the capacity of primary health care services to deliver health care globally. The sector faced a highly uncertain and dynamic period that encompassed anticipation of a new, unknown, lethal and highly transmissible infection, the introduction of various travel restrictions, health workforce shortages, new government funding announcements and various policies to restrict the spread of the COVID-19 virus, then vaccination and treatments. This qualitative study aims to document and explore how the pandemic affected primary health care utilisation and delivery in remote and regional Aboriginal and Torres Strait Islander communities. Methods Semi-structured interviews were conducted with staff working in 11 Aboriginal Community-Controlled Health Services (ACCHSs) in outer regional, remote and very remote Australia. Interviews were transcribed, inductively coded and thematically analysed. Results 248 staff working in outer regional, remote and very remote primary health care clinics were interviewed between February 2020 and June 2021. Participants reported a decline in numbers of primary health care presentations in most communities during the initial COVID-19 lock down period. The reasons for the decline were attributed to community members apprehension to go to the clinics, change in work priorities of primary health care staff (e.g. more emphasis on preventing the virus entering the communities and stopping the spread) and limited outreach programs. Staff forecasted a future spike in acute presentations of various chronic diseases leading to increased medical retrieval requirements from remote communities to hospital. Information dissemination during the pre-vaccine roll-out stage was perceived to be well received by community members, while vaccine roll-out stage information was challenged by misinformation circulated through social media. Conclusions The ability of ACCHSs to be able to adapt service delivery in response to the changing COVID-19 strategies and policies are highlighted in this study. The study signifies the need to adequately fund ACCHSs with staff, resources, space and appropriate information to enable them to connect with their communities and continue their work especially in an era where the additional challenges created by pandemics are likely to become more frequent. While the PHC seeking behaviour of community members during the COVID-19 period were aligned to the trends observed across the world, some of the reasons underlying the trends were unique to outer regional, remote and very remote populations. Policy makers will need to give due consideration to the potential effects of newly developed policies on ACCHSs operating in remote and regional contexts that already battle under resourcing issues and high numbers of chronically ill populations.

Colorectal cancer (CRC) is driven by genomic alterations in concert with dietary influences, with the gut microbiome implicated as an effector in disease development and progression. While meta-analyses have provided mechanistic insight into patients with CRC, study heterogeneity has limited causal associations. Using multi-omics studies on genetically controlled cohorts of mice, we identify diet as the major driver of microbial and metabolomic differences, with reductions in α diversity and widespread changes in cecal metabolites seen in high-fat diet (HFD)-fed mice. In addition, non-classic amino acid conjugation of the bile acid cholic acid (AA-CA) increased with HFD. We show that AA-CAs impact intestinal stem cell growth and demonstrate that Ileibacterium valens and Ruminococcus gnavus are able to synthesize these AA-CAs. This multi-omics dataset implicates diet-induced shifts in the microbiome and the metabolome in disease progression and has potential utility in future diagnostic and therapeutic developments.

This article reflects on findings from a qualitative evaluation of the Narnian Virtues Character Education English Curriculum (NV) in the context of critical engagement with the field of character education. We recognise many people argue for or against character education based on ideological positions. This article will reflect on how those positions relate to our data, recognising in practice dominant neoliberal and deficit narratives influence the operationalising of the curriculum. It is then argued that character education has the potential to promote the wellbeing of young people where there exists robust conceptualisions of character and young people, whilst also making an overt effort to resist and challenge dominant ideologies.

As part of Ham Radio Science Citizen Investigation (HamSCI) Personal Space Weather Station (PSWS) project, a low-cost, commercial off-the-shelf magnetometer has been developed to provide quantitative and qualitative measurements of the geospace environment from the ground for both scientific and operational purposes at a cost that will allow for crowd-sourced data contributions. The PSWS magnetometers employ a magneto-inductive sensor technology to record three-axis magnetic field variations with a field resolution of ∼3 nT at a 1 Hz sample rate. The measurement range of the sensor is ±1.1×106 nT) and is valid over a temperature range of −40 °C to +85 °C. Data from the PSWS network will combine these magnetometer measurements with high frequency (HF, 3–30 MHz) radio observations to monitor large-scale current systems and ionospheric disturbances due to drivers from both space and the atmosphere. A densely-spaced magnetometer array, once established, will demonstrate their space weather monitoring capability to an unprecedented spatial extent. Magnetic field data obtained by the magnetometers installed at various locations in the US are presented and compared with the existing magnetometers nearby, demonstrating that the performance is very adequate for scientific investigations.

We study the effect of magnification in the Dark Energy Survey Year 3 analysis of galaxy clustering and galaxy-galaxy lensing, using two different lens samples: a sample of luminous red galaxies, redMaGiC, and a sample with a redshift-dependent magnitude limit, MagLim. We account for the effect of magnification on both the flux and size selection of galaxies, accounting for systematic effects using the Balrog image simulations. We estimate the impact of magnification on the galaxy clustering and galaxy-galaxy lensing cosmology analysis, finding it to be a significant systematic for the MagLim sample. We show cosmological constraints from the galaxy clustering autocorrelation and galaxy-galaxy lensing signal with different magnifications priors, finding broad consistency in cosmological parameters in ΛCDM and wCDM. However, when magnification bias amplitude is allowed to be free, we find the two-point correlation functions prefer a different amplitude to the fiducial input derived from the image simulations. We validate the magnification analysis by comparing the cross-clustering between lens bins with the prediction from the baseline analysis, which uses only the autocorrelation of the lens bins, indicating that systematics other than magnification may be the cause of the discrepancy. We show that adding the cross-clustering between lens redshift bins to the fit significantly improves the constraints on lens magnification parameters and allows uninformative priors to be used on magnification coefficients, without any loss of constraining power or prior volume concerns.

Adolescents with autism spectrum disorder (ASD) without an intellectual disability (ID) have daily living skills (DLS) that fall below their chronological age and affect their ability to achieve successful adult outcomes, but little is known about their specific DLS challenges. Utilizing the Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3) in a sample of 151 adolescents with ASD without an ID, we explored the VABS-3 DLS domain, subdomains, interview topics, and individual items. Results indicated that Community DLS was a relative strength, followed by Domestic DLS, and then Personal DLS. Adolescents with ASD demonstrated significant challenges in many age appropriate DLS subdomain interview topics and individual items, indicating a need for interventions to increase acquisition of DLS to improve adult outcomes.

Abstract Repetitive transcranial magnetic stimulation (rTMS) is an established non-invasive brain stimulation treatment for major depressive disorder, but there is marked inter-individual variability in response. Using latent class growth analysis with session-by-session patient global impression ratings from the recently completed BRIGhTMIND trial, we identified five distinct classes of improvement trajectory during a 20-session treatment course. This included a substantial class of patients noticing delayed onset of improvement. Contrary to prior expectations, members of a class characterised by early and continued improvement showed greatest inter-session variability in stimulated location. By relating target locations and inter-session variability to a well-studied atlas, we estimated an average of 3.0 brain networks were stimulated across the treatment course in this group, compared to 1.1 in a group that reported symptom worsening (p

Recent cosmological analyses rely on the ability to accurately sample from high-dimensional posterior distributions. A variety of algorithms have been applied in the field, but justification of the particular sampler choice and settings is often lacking. Here, we investigate three such samplers to motivate and validate the algorithm and settings used for the Dark Energy Survey (DES) analyses of the first 3 yr (Y3) of data from combined measurements of weak lensing and galaxy clustering. We employ the full DES Year 1 likelihood alongside a much faster approximate likelihood, which enables us to assess the outcomes from each sampler choice and demonstrate the robustness of our full results. We find that the ellipsoidal nested sampling algorithm MULTINEST reports inconsistent estimates of the Bayesian evidence and somewhat narrower parameter credible intervals than the sliced nested sampling implemented in POLYCHORD. We compare the findings from MULTINEST and POLYCHORD with parameter inference from the Metropolis–Hastings algorithm, finding good agreement. We determine that POLYCHORD provides a good balance of speed and robustness for posterior and evidence estimation, and recommend different settings for testing purposes and final chains for analyses with DES Y3 data. Our methodology can readily be reproduced to obtain suitable sampler settings for future surveys.