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Initial teacher education programs have been criticised for their failure to deliver classroom-ready graduates. Problems of concern for preservice teachers (PSTs) identified in the literature are insufficient time in the classroom, lack of confidence, inadequate pedagogical knowledge and a theory practice divide. This research examines a school-university partnership approach to science teacher education from the perspective of PSTs, school students, teachers and teacher educators where university tutorials were conducted in a school environment. This research is underpinned by practice architectures theory, it follows collaborative participatory action research methodology using mixed methods of data collection including surveys, interviews and focus groups. The research findings revealed how the program built on PSTs' pedagogical knowledge and confidence and connected theory with practice. Teachers observed high level student engagement and students building on their prior science knowledge in innovative science lessons. The research provides rich data that illuminate aspects in this school-university partnership approach from a range of perspectives.

A 38-year-old pregnant patient was managed by the cardio-obstetrics multidisciplinary team for severe degenerative bioprosthetic aortic valve failure. She was medically managed utilizing echocardiogram and brain natriuretic peptide until she demonstrated worsening heart failure. A valve and cardio-obstetrics team evaluation led to valve-in-valve transcatheter aortic valve replacement at 30 weeks’ gestation.

Abstract Background Individuals with Friedreich ataxia (FRDA) can find it difficult to access specialized clinical care. To facilitate best practice in delivering healthcare for FRDA, clinical management guidelines (CMGs) were developed in 2014. However, the lack of high-certainty evidence and the inadequacy of accepted metrics to measure health status continues to present challenges in FRDA and other rare diseases. To overcome these challenges, the Grading of Recommendations Assessment and Evaluation (GRADE) framework for rare diseases developed by the RARE-Bestpractices Working Group was adopted to update the clinical guidelines for FRDA. This approach incorporates additional strategies to the GRADE framework to support the strength of recommendations, such as review of literature in similar conditions, the systematic collection of expert opinion and patient perceptions, and use of natural history data. Methods A panel representing international clinical experts, stakeholders and consumer groups provided oversight to guideline development within the GRADE framework. Invited expert authors generated the Patient, Intervention, Comparison, Outcome (PICO) questions to guide the literature search (2014 to June 2020). Evidence profiles in tandem with feedback from individuals living with FRDA, natural history registry data and expert clinical observations contributed to the final recommendations. Authors also developed best practice statements for clinical care points that were considered self-evident or were not amenable to the GRADE process. Results Seventy clinical experts contributed to fifteen topic-specific chapters with clinical recommendations and/or best practice statements. New topics since 2014 include emergency medicine, digital and assistive technologies and a stand-alone section on mental health. Evidence was evaluated according to GRADE criteria and 130 new recommendations and 95 best practice statements were generated. Discussion and conclusion Evidence-based CMGs are required to ensure the best clinical care for people with FRDA. Adopting the GRADE rare-disease framework enabled the development of higher quality CMGs for FRDA and allows individual topics to be updated as new evidence emerges. While the primary goal of these guidelines is better outcomes for people living with FRDA, the process of developing the guidelines may also help inform the development of clinical guidelines in other rare diseases.

Abstract Objectives Friedreich ataxia (FRDA) is a rare disorder with progressive neurodegeneration and cardiomyopathy. Luvadaxistat (also known as TAK‐831; NBI‐1065844), an inhibitor of the enzyme d‐amino acid oxidase, has demonstrated beneficial effects in preclinical models relevant to FRDA. This phase 2, randomized, double‐blind, placebo‐controlled, parallel‐arm study evaluated the efficacy and safety of oral luvadaxistat in adults with FRDA. Methods Adult patients with FRDA were randomized 2:1:2 to placebo, luvadaxistat 75 mg twice daily (BID), or luvadaxistat 300 mg BID for 12 weeks. The primary endpoint changed from baseline at week 12 on the inverse of the time to complete the nine‐hole peg test (9‐HPT−1), a performance‐based measure of the function of the upper extremities and manual dexterity. Comparisons between luvadaxistat and placebo were made using a mixed model for repeated measures. Results Of 67 randomized patients, 63 (94%) completed the study. For the primary endpoint, there was no statistically significant difference in change from baseline on the 9‐HPT−1 (seconds−1) at week 12 between placebo (0.00029) and luvadaxistat 75 mg BID (−0.00031) or luvadaxistat 300 mg BID (−0.00059); least squares mean differences versus placebo (standard error) were −0.00054 (0.000746) for the 75 mg dose and −0.00069 (0.000616) for the 300 mg dose. Luvadaxistat was safe and well tolerated; the majority of reported adverse events were mild in intensity. Interpretation Luvadaxistat was safe and well tolerated in this cohort of adults with FRDA; however, it did not demonstrate efficacy as a treatment for this condition.

Early childhood caries (ECC) is a common chronic infectious disease of childhood with a complex etiology and many contributing risk factors. Its prevalence is greater in certain racial and ethnic minority groups and populations with low socioeconomic status. Among the species of bacteria that contribute to the progression of dental caries, Streptococcus mutans (SM) has long been considered a primary etiological agent of the disease. We report here on the genotypic diversity, commonality, and fidelity of mother-child transmission of S. mutans in mother-child dyads in two high-risk populations.MethodsThirty-eight mother-child dyads from a Southeast Iowa population and 40 dyads from a Northern Plains American Indian Tribe were selected for a comparison of S. mutans genotype profiles within and between populations. S. mutans was isolated from whole mouth plaque samples collected from each subject. DNA was extracted and AP-PCR using OPA2 primer was performed. Amplified DNA was electrophoresed and images of the resulting patterns were compared via GelCompar®IIv6.5 software.ResultsThirty unique S. mutans genotypes were identified from the 1,638 S. mutans isolates analyzed. Fifteen genotypes (50%) were seen in both cohorts, while 11 were unique to the American Indian (AI) cohort and 4 were unique to the Southeast Iowa (SEI) population. Within the AI cohort, 61.5% (16/26) of the S. mutans genotypes identified were seen in ≥2 individuals and 14 of the 26 (53.8%) were seen in ≥2 dyads. In the SEI cohort, 78.9% (15/19) of the S. mutans genotypes identified were seen in ≥2 individuals and 13 of the 19 (68.4%) were present in ≥2 dyads. Fifty-seven percent of AI children and 23% of SEI children displayed fidelity of mother-child transmission of ≥1 S. mutans genotype.ConclusionIn comparing the populations, we observed large variation in genotypic diversity and fidelity of mother-child transmission, while the amount of commonality seen in both cohorts was similarly high in both groups. This study furthers our understanding of the genotypic diversity of S. mutans in both of these populations and provides a basis for further comparison to other populations at greater risk for developing ECC.

Education systems across the globe have enacted national testing regimes to monitor and report student achievement progress as an outcome of teaching performance. This paper reports on an investigation of strategies that Principals of high achieving schools use to achieve school results, based on NAPLAN reports (the National Assessment Program in Australia) and interpreted via the Alignment, Capability and Engagement (ACE) model of organisational readiness. Our findings identified specific Principal behaviours, actions and attitudes as necessary for effective school-wide improvement programs, as well as the existence of commonly shared strategies and approaches that help to explain why these particular Principals have been successful in their pursuit of school improvement. These include a shared vision for improvement, use of data-driven decision making, and building positive, “transparent” relationships to encourage teacher buy-in. Importantly, these findings identified “organisational readiness”, a foundational principle of the ACE model, as a fundamental requisite to effective school improvement.

IntroductionDrug development for neurodegenerative diseases such as Friedreich's ataxia (FRDA) is limited by a lack of validated, sensitive biomarkers of pharmacodynamic response in affected tissue and disease progression. Studies employing neuroimaging measures to track FRDA have thus far been limited by their small sample sizes and limited follow up. TRACK-FA, a longitudinal, multi-site, and multi-modal neuroimaging natural history study, aims to address these shortcomings by enabling better understanding of underlying pathology and identifying sensitive, clinical trial ready, neuroimaging biomarkers for FRDA.Methods200 individuals with FRDA and 104 control participants will be recruited across seven international study sites. Inclusion criteria for participants with genetically confirmed FRDA involves, age of disease onset ≤ 25 years, Friedreich's Ataxia Rating Scale (FARS) functional staging score of ≤ 5, and a total modified FARS (mFARS) score of ≤ 65 upon enrolment. The control cohort is matched to the FRDA cohort for age, sex, handedness, and years of education. Participants will be evaluated at three study visits over two years. Each visit comprises of a harmonized multimodal Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) scan of the brain and spinal cord; clinical, cognitive, mood and speech assessments and collection of a blood sample. Primary outcome measures, informed by previous neuroimaging studies, include measures of: spinal cord and brain morphometry, spinal cord and brain microstructure (measured using diffusion MRI), brain iron accumulation (using Quantitative Susceptibility Mapping) and spinal cord biochemistry (using MRS). Secondary and exploratory outcome measures include clinical, cognitive assessments and blood biomarkers.DiscussionPrioritising immediate areas of need, TRACK-FA aims to deliver a set of sensitive, clinical trial-ready neuroimaging biomarkers to accelerate drug discovery efforts and better understand disease trajectory. Once validated, these potential pharmacodynamic biomarkers can be used to measure the efficacy of new therapeutics in forestalling disease progression.Clinical trial registrationClinicalTrails.gov Identifier: NCT04349514.

Aim: The purpose of this study was to investigate the presence of Streptococcus mutans, Streptococcus sobrinus, and Lactobacillus species in an American Indian population displaying a high incidence of severe early childhood caries (S-ECC) and to explore the genotypic diversity and fidelity of transmission of S. sobrinus in this population.Methods: We report here on the microbial profiles of 71 children compiled from birth to 36 months of age and initial exploration of genotypic diversity in a subset of 40 mother/child dyads. Whole mouth plaque samples were collected from mother/child dyads in a Northern Plains American Indian cohort. Mutans streptococci (MS) and Lactobacillus counts were recorded and presence/absence of S. mutans, S. sobrinus, and Lactobacillus was noted for each child. S. sobrinus was isolated and genotyped via arbitrarily primed-polymerase chain reaction (AP-PCR).Results: The children in this study were divided into caries active (CA) and caries free (CF) groups. S. mutans, S. sobrinus, and Lactobacillus species were detected more frequently in CA groups. Distribution of MS and Lactobacillus counts was significantly different between the two groups, as was the distribution of three species colonization profiles. Twelve S. sobrinus genotypes were detected in the subset of mother/child dyads. Individual participants displayed a range of 0–3 distinct genotypes while mother/child pairs displayed a range of 1–5 genotypes. Eighty-three percent of children shared at least one genotype with his/her mother.Conclusion: Caries active children in this population display different microbial profiles than the caries free children in this cohort. A small number of S. sobrinus genotypes appear to be very common in this population. A high rate of vertical transmission of S. sobrinus from mother to child is seen in these mother/child dyads.

Background Gene mutation analysis from plasma circulating tumor DNA (ctDNA) can provide timely information regarding the mechanism of resistance that could translate to personalised treatment. We compared concordance rate of next generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) in the detection of the EGFR activating and T790M mutation from plasma ctDNA with diagnostic tissue biopsy‐based assays. The second objective was to test whether putative osimertinib resistance associated mutations were detectable from plasma using NGS. Methods From January 2016 to December 2017, we prospectively collected plasma samples from patients prior to commencement of second‐ or third‐line osimertinib therapy and upon disease progression, in a single tertiary hospital in South Western Sydney, Australia. Amplicon‐based NGS and ddPCR assays were used to detect activating epidermal growth factor receptor (EGFR) and T790M mutations in 18 plasma samples from nine patients; all patients were required to have tissue biopsies with known EGFR status. Results High concordance of allelic fractions were seen in matched plasma NGS and ddPCR for activating EGFR mutations and T790M mutations (R2 = 0.92, P

Abstract Friedreich ataxia is an autosomal recessive, neurodegenerative disease characterized by the deficiency of the iron‐sulfur cluster assembly protein frataxin. Loss of this protein impairs mitochondrial function. Mitochondria alter their morphology in response to various stresses; however, such alterations to morphology may be homeostatic or maladaptive depending upon the tissue and disease state. Numerous neurodegenerative diseases exhibit excessive mitochondrial fragmentation, and reversing this phenotype improves bioenergetics for diseases in which mitochondrial dysfunction is a secondary feature of the disease. This paper demonstrates that frataxin deficiency causes excessive mitochondrial fragmentation that is dependent upon Drp1 activity in Friedreich ataxia cellular models. Drp1 inhibition by the small peptide TAT‐P110 reverses mitochondrial fragmentation but also decreases ATP levels in frataxin‐knockdown fibroblasts and FRDA patient fibroblasts, suggesting that fragmentation may provide a homeostatic pathway for maintaining cellular ATP levels. The cardiolipin‐stabilizing compound SS‐31 similarly reverses fragmentation through a Drp1‐dependent mechanism, but it does not affect ATP levels. The combination of TAT‐P110 and SS‐31 does not affect FRDA patient fibroblasts differently from SS‐31 alone, suggesting that the two drugs act through the same pathway but differ in their ability to alter mitochondrial homeostasis. In approaching potential therapeutic strategies for FRDA, an important criterion for compounds that improve bioenergetics should be to do so without impairing the homeostatic response of mitochondrial fragmentation.

ObjectivePre- and post-operative neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) and other prognostic clinicopathological variables were correlated with progression free survival (PFS) and overall survival (OS) of Glioblastoma Multiforme (GBM) patients.MethodsGBM patients (n = 87, single-centre, recruited 2013-2019) were retrospectively divided into low and high groups using literature-derived cut-offs (NLR = 5.07, PNI = 46.97). Kaplan-Meier survival curves and log rank tests assessed PFS and OS. Univariate and multivariate analyses identified PFS and OS prognosticators.ResultsHigh vs low post-operative PNI cohort was associated with longer PFS (279 vs 136 days, p = 0.009), but significance was lost on multivariate analysis. Post-operative ECOG (p = 0.043), daily dexamethasone (p = 0.023) and IDH mutation (p = 0.046) were significant on multivariate analysis for PFS. High pre- and post-operative PNI were associated with improved OS (384 vs 114 days, p = 0.034 and 516 vs 245 days, p = 0.001, respectively). Low postoperative NLR correlated with OS (408 vs 249 days, p = 0.029). On multivariate analysis using forward selection process, extent of resection (EOR) (GTR vs biopsy, p = 0.004 and STR vs biopsy, p = 0.011), and any previous surgery (p = 0.014) were independent prognostic biomarkers for OS. On multivariate analysis of these latter variables with literature-derived prognostic biomarkers, EOR remained significantly associated with OS (p = 0.037).ConclusionsEOR, followed by having any surgery prior to GBM, are the most significant independent predictors of GBM patient's OS. Post-operative ECOG, daily dexamethasone and IDH mutation are independent prognostic biomarkers for PFS. PNI may be superior to NLR. Post- vs pre-operative serum inflammatory marker levels may be associated with survival.

One hundred human-derived coagulase negative staphylococci (CoNS) were screened for antimicrobial activity using agar-based deferred antagonism assays with a range of indicator bacteria. Based on the findings of the screen and subsequent well assays with cell free supernatants and whole cell extracts, one strain, designated CIT060, was selected for further investigation. It was identified as Staphylococcus capitis and herein we describe the purification and characterisation of the novel bacteriocin that the strain produces. This bacteriocin which we have named capidermicin was extracted from the cell-free supernatant of S. capitis CIT060 and purified to homogeneity using reversed-phase high performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometric (MS) analysis revealed that the capidermicin peptide has a mass of 5,464 Da. Minimal inhibitory concentration (MIC) experiments showed that capidermicin was active in the micro-molar range against all the Gram-positive bacteria that were tested. Antimicrobial activity was retained over a range of pHs (2-11) and temperatures (10-121°C x 15 mins). The draft genome sequence of S. capitis CIT060 was determined and the genes predicted to be involved in the biosynthesis of capidermicin were identified. These genes included the predicted capidermicin precursor gene, and genes that are predicted to encode a membrane transporter, an immunity protein and a transcriptional regulator. Homology searches suggest that capidermicin is a novel member of the family of class II leaderless bacteriocins.