National Safe Schools Framework: Policy and Practice to Reduce Bullying in Australian Schools

In 2003 Australia was one of the first countries to develop an integrated national policy, called the National Safe Schools Framework (NSSF), for the prevention and management of violence, bullying, and other aggressive behaviors. The effectiveness of this framework has not yet been formally evaluated. Cross-sectional data collected in 2007 from 7,418 students aged 9 to 14 years old and 453 teachers from 106 representative Australian schools were analyzed to determine teachers’ perceptions about the extent of implementation of the NSSF, teachers’ capacity to address student bullying, and students’ reports of bullying in their school, 4 years following the framework’s dissemination. While methodological issues limit the findings, schools appear not to have widely implemented the recommended safe school practices, teachers appear to need more training to address bullying, especially covert bullying, and bullying prevalence among students seems relatively unchanged compared to Australian data collected 4 years prior to the launch of the NSSF

Alterations of the gut mycobiome in patients with MS

BACKGROUND: The mycobiome is the fungal component of the gut microbiome and is implicated in several autoimmune diseases. However, its role in MS has not been studied. METHODS: In this case-control observational study, we performed ITS sequencing and characterised the gut mycobiome in people with MS (pwMS) and healthy controls at baseline and after six months. FINDINGS: The mycobiome had significantly higher alpha diversity and inter-subject variation in pwMS than controls. Saccharomyces and Aspergillus were over-represented in pwMS. Saccharomyces was positively correlated with circulating basophils and negatively correlated with regulatory B cells, while Aspergillus was positively correlated with activated CD16 INTERPRETATION: There is an alteration of the gut mycobiome in pwMS, compared to healthy controls. Further study is required to assess any causal association of the mycobiome with MS and its direct or indirect interactions with bacteria and autoimmunity. FUNDING: This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS102633-04 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-1805-31003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG- 1907-34474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health

Transdisciplinary Science: A Path to Understanding the Interactions Among Ocean Acidification, Ecosystems, and Society

The global nature of ocean acidification (OA) transcends habitats, ecosystems, regions, and science disciplines. The scientific community recognizes that the biggest challenge in improving understanding of how changing OA conditions affect ecosystems, and associated consequences for human society, requires integration of experimental, observational, and modeling approaches from many disciplines over a wide range of temporal and spatial scales. Such transdisciplinary science is the next step in providing relevant, meaningful results and optimal guidance to policymakers and coastal managers. We discuss the challenges associated with integrating ocean acidification science across funding agencies, institutions, disciplines, topical areas, and regions, and the value of unifying science objectives and activities to deliver insights into local, regional, and global scale impacts. We identify guiding principles and strategies for developing transdisciplinary research in the ocean acidification science community

UK research priority setting for childhood neurological conditions

Aim: To identify research priorities regarding the effectiveness of interventions for children and young people (CYP) with childhood neurological conditions (CNCs). These include common conditions such as epilepsies and cerebral palsy, as well as many rare conditions. Method: The National Institute for Health and Care Research (NIHR) and the James Lind Alliance (JLA) champion and facilitate priority setting partnerships (PSPs) between patients, caregivers, and clinicians (stakeholders) to identify the most important unanswered questions for research (uncertainties). A NIHR–JLA and British Paediatric Neurology Association collaboration used the JLA PSP methodology. This consisted of two surveys to stakeholders: survey 1 (to identify uncertainties) and survey 2 (a prioritization survey). The final top 10 priorities were agreed by consensus in a stakeholder workshop. Results: One hundred and thirty‐two charities and partner organizations were invited to participate. In survey 1, 701 participants (70% non‐clinicians, including CYP and parent and caregivers) submitted 1800 uncertainties from which 44 uncertainties were identified for prioritization in survey 2; from these, 1451 participants (83% non‐clinicians) selected their top 10 priorities. An unweighted amalgamated score across participant roles was used to select 26. In the final workshop, 14 health care professionals, 11 parent and caregivers, and two CYP ranked the 26 questions to finalize the top 10 priorities. Ten top priority questions were identified regarding interventions to treat CYP with CNCs and their associated comorbidities, for example, sleep, emotional well‐being, and distressing symptoms. Interpretation: The results of this study will inform research into the effectiveness of interventions for children with neurological conditions

Hypomorphic PCNA mutation underlies a novel human DNA repair disorder

A number of human disorders, including Cockayne syndrome, UV-sensitive syndrome, xeroderma pigmentosum and trichothiodystrophy, result from the mutation of genes encoding molecules important for nucleotide excision repair. Here, we describe a novel syndrome in which the cardinal clinical features include postnatal growth retardation, hearing loss, premature aging, telangiectasia, neurological signs and photosensitivity, resulting from a homozygous missense (p.Ser228Ile) sequence alteration of the proliferating cell nuclear antigen (PCNA). PCNA is a highly conserved sliding clamp protein essential for DNA replication and repair. Due to this fundamental role, mutations in PCNA that profoundly impair protein function would be incompatible with life. Interestingly, while the p.Ser228Ile alteration appears to have no effect on protein levels or DNA replication, patient cells exhibit significant abnormalities in response to UV irradiation displaying substantial reductions in both UV survival and RNA synthesis recovery. The p.Ser228Ile change also profoundly alters PCNA’s interaction with Flap endonuclease 1 and DNA Ligase 1, DNA metabolism enzymes. Taken together our findings detail the first mutation of PCNA in humans, associated with a unique neurodegenerative disease displaying clinical and molecular features common to other DNA repair disorders, which we show to be attributable to a hypomorphic amino acid alteration

Measuring intracellular pH in the heart using hyperpolarized carbon dioxide and bicarbonate: a 13C and 31P magnetic resonance spectroscopy study

AIMS: Technological limitations have restricted in vivo assessment of intracellular pH (pH(i)) in the myocardium. The aim of this study was to evaluate the potential of hyperpolarized [1-(13)C]pyruvate, coupled with (13)C magnetic resonance spectroscopy (MRS), to measure pH(i) in the healthy and diseased heart. METHODS AND RESULTS: Hyperpolarized [1-(13)C]pyruvate was infused into isolated rat hearts before and immediately after ischaemia, and the formation of (13)CO(2) and H(13)CO(3)(-) was monitored using (13)C MRS. The HCO(3)(-)/CO(2) ratio was used in the Henderson-Hasselbalch equation to estimate pH(i). We tested the validity of this approach by comparing (13)C-based pH(i) measurements with (31)P MRS measurements of pH(i). There was good agreement between the pH(i) measured using (13)C and (31)P MRS in control hearts, being 7.12 +/- 0.10 and 7.07 +/- 0.02, respectively. In reperfused hearts, (13)C and (31)P measurements of pH(i) also agreed, although (13)C equilibration limited observation of myocardial recovery from acidosis. In hearts pre-treated with the carbonic anhydrase (CA) inhibitor, 6-ethoxyzolamide, the (13)C measurement underestimated the (31)P-measured pH(i) by 0.80 pH units. Mathematical modelling predicted that the validity of measuring pH(i) from the H(13)CO(3)(-)/(13)CO(2) ratio depended on CA activity, and may give an incorrect measure of pH(i) under conditions in which CA was inhibited, such as in acidosis. Hyperpolarized [1-(13)C]pyruvate was also infused into healthy living rats, where in vivo pH(i) from the H(13)CO(3)(-)/(13)CO(2) ratio was measured to be 7.20 +/- 0.03. CONCLUSION: Metabolically generated (13)CO(2) and H(13)CO(3)(-) can be used as a marker of cardiac pH(i) in vivo, provided that CA activity is at normal levels

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

iTRAQ Identification of Candidate Serum Biomarkers Associated with Metastatic Progression of Human Prostate Cancer

A major challenge in the management of patients with prostate cancer is identifying those individuals at risk of developing metastatic disease, as in most cases the disease will remain indolent. We analyzed pooled serum samples from 4 groups of patients (n = 5 samples/group), collected prospectively and actively monitored for a minimum of 5 yrs. Patients groups were (i) histological diagnosis of benign prostatic hyperplasia with no evidence of cancer ‘BPH’, (ii) localised cancer with no evidence of progression, ‘non-progressing’ (iii) localised cancer with evidence of biochemical progression, ‘progressing’, and (iv) bone metastasis at presentation ‘metastatic’. Pooled samples were immuno-depleted of the 14 most highly abundant proteins and analysed using a 4-plex iTRAQ approach. Overall 122 proteins were identified and relatively quantified. Comparisons of progressing versus non-progressing groups identified the significant differential expression of 25 proteins (p<0.001). Comparisons of metastatic versus progressing groups identified the significant differential expression of 23 proteins. Mapping the differentially expressed proteins onto the prostate cancer progression pathway revealed the dysregulated expression of individual proteins, pairs of proteins and ‘panels’ of proteins to be associated with particular stages of disease development and progression. The median immunostaining intensity of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1), one of the candidates identified, was significantly higher in osteoblasts in close proximity to metastatic tumour cells compared with osteoblasts in control bone (p = 0.0353, Mann Whitney U). Our proteomic approach has identified leads for potentially useful serum biomarkers associated with the metastatic progression of prostate cancer. The panels identified, including eEF1A1 warrant further investigation and validation