P-T-X conditions of fluids in the Sunrise Dam Gold Deposit, Western Australia: implications for the interplay between deformation and fluids in the orogenic gold systems

[Extract] The formation of orogenic gold deposits is generally described as a complex interplay between deformation, permeability, rock strength and hydrothermal fluid pressure. Despite it being widely known that orogenic gold deposits form from low salinity, carbon dioxide-bearing fluids, the importance of this fluid composition in the context of the physical processes of deformation and fluid behaviour is commonly overlooked. In this study we combined fluid inclusion research with structural and numerical modeling in order to link these processes in the world class (10Moz.) Late Archean Sunrise Dam gold deposit

Usage, Engagement and Impact: Evaluating the usage of and measuring impact and engagement with library resources at Leeds Beckett University Library

In 2017–18 Leeds Beckett University Library undertook a project to assess the feasibility of using OpenAthens and student record data to enable in-depth analysis of learning resources usage and costs, student engagement and library impact. This article describes the different approaches taken to evaluate usage of the Library’s e-resources to identify levels of engagement at school and course level. These include evaluating the impact of induction attendance on e-resource usage, reviewing school e-resource usage and return on investment, analysing usage trends at school and year level and examining the correlation between National Student Survey (NSS) results and e-resource usage for specific courses. The project confirmed the feasibility of using OpenAthens and student record data for in-depth analysis of learning resources usage, student engagement and library impact. Successful analysis was performed for schools, courses and levels of study and provided significant insight that informed resource provision and NSS action. Library managers, academic librarians and academics have consequently engaged with and benefited from the project and its outputs. This article builds on a breakout session presented at the 42nd UKSG Annual Conference in April 2019

The Blood Neutrophil Count After 1 Month of Treatment Predicts the Radiologic Severity of Lung Disease at Treatment End

BACKGROUND: Post-tuberculous lung disease confers significant morbidity. However, the determinants of persistent lung damage in tuberculosis are not well established. We investigated associations between tuberculosis-associated radiological changes and socio-demographic factors, surrogates of bacillary burden and blood inflammatory markers at initiation of therapy and after 1 month. RESEARCH QUESTION: What are the predictors of radiological severity at the end of tuberculosis treatment for tuberculosis? STUDY DESIGN AND METHODS: We collected data from patients treated for drug sensitive pulmonary tuberculosis at our centre over a 5.5-year period. We recorded age, sex, ethnicity, smoking status, symptom duration, sputum smear grade, time to culture positivity and blood results (C-reactive protein and neutrophil count) at baseline and after 1 month of treatment. Chest x-rays performed at baseline, 2 months and end of treatment were assessed independently by two radiologists and scored using a validated system. Relationships between predictor variables and radiological outcomes were assessed using linear or binary logistic regression. RESULTS: We assessed 154 individuals, mean age 37 years, 63% male. In multivariate analysis, baseline radiological severity correlated with sputum smear grade (p=0.003) and neutrophil count (p<0.001). At end of treatment, only the 1-month neutrophil count was significantly associated with overall radiological severity in multivariate analysis (r=0.34, p=0.003), and remained significant after controlling for baseline radiological scores. The 1-month neutrophil count was also the only independent correlate of volume loss and pleural thickening at end of treatment and was significantly higher in patients with persistent cavitation or effusion versus those without. INTERPRETATION: Persistent neutrophilic inflammation after 1 month of tuberculosis therapy is associated with poor radiological outcome, suggesting a target for interventions to minimise post-tuberculous lung disease

Current and future management of non-tuberculous mycobacterial pulmonary disease (NTM-PD) in the UK

A rising number of non-tuberculous mycobacterial (NTM) isolates are being identified in UK clinical practice. There are many uncertainties around the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD), including its epidemiology, diagnosis, treatment and prevention. Regional variations in how patients with NTM-PD are managed reflects the lack of standardised pathways in the UK. Service optimisation and multidisciplinary working can improve the quality of care for patients with NTM-PD, including (1) better identification of patients at risk of NTM-PD and modification of risk factors where applicable; (2) standardisation of reference laboratory testing to offer clinicians access to accurate and prompt information on NTM species and drug sensitivities; (3) development of recognised specialist NTM nursing care; (4) standardisation of NTM-PD imaging strategies for monitoring of treatment and disease progression; (5) establishment of a hub-and-spoke model of care, including clear referral and management pathways, dedicated NTM-PD multidisciplinary teams, and long-term patient follow-up; (6) formation of clinical networks to link experts who manage diseases associated with NTM; (7) enabling patients to access relevant support groups that can provide information and support for their condition; and (8) development of NTM research groups to allow patient participation in clinical trials and to facilitate professional education

C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins

An expanded GGGGCC repeat in C9orf72 is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. A fundamental question is whether toxicity is driven by the repeat RNA itself and/or by dipeptide repeat proteins generated by repeat-associated, non-ATG translation. To address this question we developed in vitro and in vivo models to dissect repeat RNA and dipeptide repeat protein toxicity. Expression of pure repeats in Drosophila caused adult-onset neurodegeneration attributable to poly-(glycine-arginine) proteins. Thus, expanded repeats promoted neurodegeneration through neurotoxic proteins. Expression of individual dipeptide repeat proteins with a non-GGGGCC RNA sequence showed both poly-(glycine-arginine) and poly-(proline-arginine) proteins caused neurodegeneration. These findings are consistent with a dual toxicity mechanism, whereby both arginine-rich proteins and repeat RNA contribute to C9orf72-mediated neurodegeneration

Selective Pressure for Biofilm Formation in Bacillus subtilis: Differential Effect of Mutations in the Master Regulator SinR on Bistability

Kampf J, Gerwig J, Kruse K, et al. Selective Pressure for Biofilm Formation in Bacillus subtilis: Differential Effect of Mutations in the Master Regulator SinR on Bistability. mBio. 2018;9(5): e01464-18

A novel knockout mouse for the small EDRK-rich factor 2 (Serf2) showing developmental and other deficits

The small EDRK-rich factor 2 (SERF2) is a highly conserved protein that modifies amyloid fibre assembly in vitro and promotes protein misfolding. However, the role of SERF2 in regulating age-related proteotoxicity remains largely unexplored due to a lack of in vivo models. Here, we report the generation of Serf2 knockout mice using an ES cell targeting approach, with Serf2 knockout alleles being bred onto different defined genetic backgrounds. We highlight phenotyping data from heterozygous Serf2^{+/-} mice, including unexpected male-specific phenotypes in startle response and pre-pulse inhibition. We report embryonic lethality in Serf2^{-/-} null animals when bred onto a C57BL/6 N background. However, homozygous null animals were viable on a mixed genetic background and, remarkably, developed without obvious abnormalities. The Serf2 knockout mice provide a powerful tool to further investigate the role of SERF2 protein in previously unexplored pathophysiological pathways in the context of a whole organism