Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of α-synuclein protein implicated in Parkinson's disease

Abstractα-Synuclein (α-syn) protein has been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the α-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We report here that human wild-type α-syn, PD-linked mutant α-syn(Ala30Pro) and mutant α-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. The mutant α-syn forms more β-sheet and mature filaments than the wild-type protein. These findings suggest that accumulation of α-syn as insoluble deposits of amyloid may play a major role in the pathogenesis of these neurodegenerative diseases

Effectiveness of common household cleaning agents in reducing the viability of human influenza A/H1N1

In the event of an influenza pandemic, the majority of people infected will be nursed at home. It is therefore important to determine simple methods for limiting the spread of the virus within the home. The purpose of this work was to test a representative range of common household cleaning agents for their effectiveness at killing or reducing the viability of influenza A virus

Geology of Rum Cay, Bahamas: A Field Trip Guide

See other Smith authored Field Trip Guides of Gerace Research Centre

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Evaluating the use of a 22-pathogen TaqMan array card for rapid diagnosis of respiratory pathogens in Intensive Care

Introduction. Pneumonia is highly prevalent in intensive care units (ICUs), with high associated mortality. Empirical treatment prioritizes breadth of coverage while awaiting laboratory diagnosis, often at the expense of antimicrobial stewardship. Microarrays use multiple parallel polymerase chain reactions to enable a rapid syndromic approach to laboratory diagnosis. Aim. To evaluate the clinical and laboratory implications of introducing a bespoke 22-pathogen TaqMan Array Card (TAC) for rapid pathogen detection in deep respiratory samples from adult ICUs. Methodology. TAC results from all ICU patients prospectively tested over a 9-month period at Cambridge’s Clinical Microbiology and Public Health Laboratory were compared to those of corresponding conventional microbiological assays (culture-, PCR- or serology-based) in terms of result agreement and time-to-result availability. Clinical impact was assessed by retrospective review of medical records. Results. Seventy-one patients were included [45 (63 %) male, median age 59). Overall result agreement was 94 %, with TAC detecting more pathogens than conventional methods. TAC detected Streptococcus pneumoniae more readily than culture (7 vs 0 cases; P=0.02). TAC did not detect Aspergillus spp. in eight culture- or galactomannan-positive cases. The median turnaround time (1 day) was significantly shorter than that of bacterial/fungal culture, Pneumocystis jirovecii PCR and galactomannan testing (each 3 days; P<0.001), atypical bacteria serology (13 days; P<0.001) and Mycobacterium tuberculosis culture (46 days; P<0.001). Earlier result availability prompted discontinuation of unnecessary antimicrobials in 15/71 (21 %) cases, but had no bearing on patient isolation/deisolation. Conclusion. TAC provided greater overall yield of pathogen detection and faster turnaround times, permitting earlier discontinuation of unnecessary antimicrobials.A. C. M. is supported by a Wellcome Trust Clinical Research Career Development Fellowship (WT 2055214/Z/16/Z)

Detailed optical and near-infrared polarimetry, spectroscopy and broadband photometry of the afterglow of GRB 091018: Polarisation evolution

[Abridged] A number of phenomena have been observed in GRB afterglows that defy explanation by simple versions of the standard fireball model, leading to a variety of new models. Polarimetry can be a major independent diagnostic of afterglow physics, probing the magnetic field properties and internal structure of the GRB jets. In this paper we present the first high quality multi-night polarimetric light curve of a Swift GRB afterglow, aimed at providing a well calibrated dataset of a typical afterglow to serve as a benchmark system for modelling afterglow polarisation behaviour. In particular, our dataset of the afterglow of GRB 091018 (at redshift z=0.971) comprises optical linear polarimetry (R band, 0.13 - 2.3 days after burst); circular polarimetry (R band) and near-infrared linear polarimetry (Ks band). We add to that high quality optical and near-infrared broadband light curves and spectral energy distributions as well as afterglow spectroscopy. The linear polarisation varies between 0 and 3%, with both long and short time scale variability visible. We find an achromatic break in the afterglow light curve, which corresponds to features in the polarimetric curve. We find that the data can be reproduced by jet break models only if an additional polarised component of unknown nature is present in the polarimetric curve. We probe the ordered magnetic field component in the afterglow through our deep circular polarimetry, finding P_circ < 0.15% (2 sigma), the deepest limit yet for a GRB afterglow, suggesting ordered fields are weak, if at all present. Our simultaneous R and Ks band polarimetry shows that dust induced polarisation in the host galaxy is likely negligible.Comment: 20 pages, 14 figures, 3 tables. Accepted for publication in MNRAS. Some figures are reduced in quality to comply with arXiv size requirement

Slogging and Stumbling Toward Social Justice in a Private Elementary School: The Complicated Case of St. Malachy

This case study examines St. Malachy, an urban Catholic elementary school primarily serving children traditionally marginalized by race, class, linguistic heritage, and disability. As a private school, St. Malachy serves the public good by recruiting and retaining such traditionally marginalized students. As empirical studies involving Catholic schools frequently juxtapose them with public schools, the author presents this examination from a different tack. Neither vilifying nor glorifying Catholic schooling, this study critically examines the pursuit of social justice in this school context. Data gathered through a 1-year study show that formal and informal leaders in St. Malachy adapted their governance, aggressively sought community resources, and focused their professional development to build the capacity to serve their increasingly pluralistic student population. The analysis confirms the deepening realization that striving toward social justice is a messy, contradictory, and complicated pursuit, and that schools in both public and private sectors are allies in this pursuit

A qualitative investigation of paediatric intensive care staff attitudes towards the diagnosis of lower respiratory tract infection in the molecular diagnostics era

Background In the past decade, molecular diagnostic syndromic arrays incorporating a range of bacterial and viral pathogens have been described. It is unclear how paediatric intensive care unit (PICU) staff diagnose lower respiratory tract infection (LRTI) and integrate diagnostic array results into antimicrobial decision-making. Methods An online survey with eleven questions was distributed throughout paediatric intensive care societies in the UK, continental Europe and Australasia with a total of 755 members. Participants were asked to rate the clinical factors and investigations they used when prescribing for LRTI. Semi-structured interviews were undertaken with staff who participated in a single-centre observational study of a 52-pathogen diagnostic array. Results Seventy-two survey responses were received; most responses were from senior doctors. Whilst diagnostic arrays were used less frequently than routine investigations (i.e. microbiological culture), they were of comparable perceived utility when making antimicrobial decisions. Prescribers reported that for arrays to be clinically impactful, they would need to deliver results within 6 h for stable patients and within 1 h for unstable patients to inform their immediate decision to prescribe antimicrobials. From 16 staff interviews, we identified that arrays were helpful for the diagnosis and screening of bacterial LRTI. Staff reported it could be challenging to interpret results in some cases due to the high sensitivity of the test. Therefore, results were considered within the context of the patient and discussed within the multidisciplinary team. Conclusions Diagnostic arrays were considered of comparable value to microbiological investigations by PICU prescribers. Our findings support the need for further clinical and economic evaluation of diagnostic arrays in a randomised control trial. Trial registration Clinicaltrials.gov, NCT04233268. Registered on 18 January 2020

Economics methods in Cochrane systematic reviews of health promotion and public health related interventions.

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