A pragmatic harm reduction approach to manage a large outbreak of wound botulism in people who inject drugs, Scotland 2015

Abstract Background People who inject drugs (PWID) are at an increased risk of wound botulism, a potentially fatal acute paralytic illness. During the first 6 months of 2015, a large outbreak of wound botulism was confirmed among PWID in Scotland, which resulted in the largest outbreak in Europe to date. Methods A multidisciplinary Incident Management Team (IMT) was convened to conduct an outbreak investigation, which consisted of enhanced surveillance of cases in order to characterise risk factors and identify potential sources of infection. Results Between the 24th of December 2014 and the 30th of May 2015, a total of 40 cases were reported across six regions in Scotland. The majority of the cases were male, over 30 and residents in Glasgow. All epidemiological evidence suggested a contaminated batch of heroin or cutting agent as the source of the outbreak. There are significant challenges associated with managing an outbreak among PWID, given their vulnerability and complex addiction needs. Thus, a pragmatic harm reduction approach was adopted which focused on reducing the risk of infection for those who continued to inject and limited consequences for those who got infected. Conclusions The management of this outbreak highlighted the importance and need for pragmatic harm reduction interventions which support the addiction needs of PWID during an outbreak of spore-forming bacteria. Given the scale of this outbreak, the experimental learning gained during this and similar outbreaks involving spore-forming bacteria in the UK was collated into national guidance to improve the management and investigation of future outbreaks among PWID

Modifying patterns of movement in people with low back pain -does it help? A systematic review

Background: Physiotherapy for people with low back pain frequently includes assessment and modification of lumbo-pelvic movement. Interventions commonly aim to restore normal movement and thereby reduce pain and improve activity limitation. The objective of this systematic review was to investigate: (i) the effect of movement-based interventions on movement patterns (muscle activation, lumbo-pelvic kinematics or postural patterns) of people with low back pain (LBP), and (ii) the relationship between changes in movement patterns and subsequent changes in pain and activity limitation. Methods. MEDLINE, Cochrane Central, EMBASE, AMI, CINAHL, Scopus, AMED, ISI Web of Science were searched from inception until January 2012. Randomised controlled trials or controlled clinical trials of people with LBP were eligible for inclusion. The intervention must have been designed to influence (i) muscle activity patterns, (ii) lumbo-pelvic kinematic patterns or (iii) postural patterns, and included measurement of such deficits before and after treatment, to allow determination of the success of the intervention on the lumbo-pelvic movement. Twelve trials (25% of retrieved studies) met the inclusion criteria. Two reviewers independently identified, assessed and extracted data. The PEDro scale was used to assess method quality. Intervention effects were described using standardised differences between group means and 95% confidence intervals. Results: The included trials showed inconsistent, mostly small to moderate intervention effects on targeted movement patterns. There was considerable heterogeneity in trial design, intervention type and outcome measures. A relationship between changes to movement patterns and improvements in pain or activity limitation was observed in one of six studies on muscle activation patterns, one of four studies that examined the flexion relaxation response pattern and in two of three studies that assessed lumbo-pelvic kinematics or postural characteristics. Conclusions: Movement-based interventions were infrequently effec tive for changing observable movement patterns. A relationship between changes in movement patterns and improvement in pain or activity limitation was also infrequently observed. No independent studies confirm any observed relationships. Challenges for future research include defining best methods for measuring (i) movement aberrations, (ii) improvements in movements, and (iii) the relationship between changes in how people move and associated changes in other health indicators such as activity limitation

Design and construction of the DEAP-3600 dark matter detector

The Dark matter Experiment using Argon Pulse-shape discrimination (DEAP) has been designed for a direct detection search for particle dark matter using a single-phase liquid argon target. The projected cross section sensitivity for DEAP-3600 to the spin-independent scattering of Weakly Interacting Massive Particles (WIMPs) on nucleons is 10 cm for a 100 GeV/c WIMP mass with a fiducial exposure of 3 tonne-years. This paper describes the physical properties and construction of the DEAP-3600 detector. −46 2

dOCRL maintains immune cell quiescence in Drosophila by regulating endosomal traffic

Lowe Syndrome is a developmental disorder characterized by eye, kidney, and neurological pathologies, and is caused by mutations in the phosphatidylinositol-5-phosphatase OCRL. OCRL plays diverse roles in endocytic and endolysosomal trafficking, cytokinesis, and ciliogenesis, but it is unclear which of these cellular functions underlie specific patient symptoms. Here, we show that mutation of Drosophila OCRL causes cell-autonomous activation of hemocytes, which are macrophage-like cells of the innate immune system. Among many cell biological defects that we identified in docrl mutant hemocytes, we pinpointed the cause of innate immune cell activation to reduced Rab11-dependent recycling traffic and concomitantly increased Rab7-dependent late endosome traffic. Loss of docrl amplifies multiple immune-relevant signals, including Toll, Jun kinase, and STAT, and leads to Rab11-sensitive mis-sorting and excessive secretion of the Toll ligand Spåtzle. Thus, docrl regulation of endosomal traffic maintains hemocytes in a poised, but quiescent state, suggesting mechanisms by which endosomal misregulation of signaling may contribute to symptoms of Lowe syndrome

The clinical course of low back pain: a meta-analysis comparing outcomes in randomised clinical trials (RCTs) and observational studies.

BACKGROUND: Evidence suggests that the course of low back pain (LBP) symptoms in randomised clinical trials (RCTs) follows a pattern of large improvement regardless of the type of treatment. A similar pattern was independently observed in observational studies. However, there is an assumption that the clinical course of symptoms is particularly influenced in RCTs by mere participation in the trials. To test this assumption, the aim of our study was to compare the course of LBP in RCTs and observational studies. METHODS: Source of studies CENTRAL database for RCTs and MEDLINE, CINAHL, EMBASE and hand search of systematic reviews for cohort studies. Studies include individuals aged 18 or over, and concern non-specific LBP. Trials had to concern primary care treatments. Data were extracted on pain intensity. Meta-regression analysis was used to compare the pooled within-group change in pain in RCTs with that in cohort studies calculated as the standardised mean change (SMC). RESULTS: 70 RCTs and 19 cohort studies were included, out of 1134 and 653 identified respectively. LBP symptoms followed a similar course in RCTs and cohort studies: a rapid improvement in the first 6 weeks followed by a smaller further improvement until 52 weeks. There was no statistically significant difference in pooled SMC between RCTs and cohort studies at any time point:- 6 weeks: RCTs: SMC 1.0 (95% CI 0.9 to 1.0) and cohorts 1.2 (0.7to 1.7); 13 weeks: RCTs 1.2 (1.1 to 1.3) and cohorts 1.0 (0.8 to 1.3); 27 weeks: RCTs 1.1 (1.0 to 1.2) and cohorts 1.2 (0.8 to 1.7); 52 weeks: RCTs 0.9 (0.8 to 1.0) and cohorts 1.1 (0.8 to 1.6). CONCLUSIONS: The clinical course of LBP symptoms followed a pattern that was similar in RCTs and cohort observational studies. In addition to a shared 'natural history', enrolment of LBP patients in clinical studies is likely to provoke responses that reflect the nonspecific effects of seeking and receiving care, independent of the study design

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Acorn consumption improves the immune response of the dung beetle Thorectes lusitanicus

Thorectes lusitanicus, a typically coprophagous species is also actively attracted to oak acorns, consuming, burying them, and conferring ecophysiological and reproductive advantages to both the beetle and the tree. In this study, we explored the possible relation between diet shift and the health status of T. lusitanicus using a generalist entomopathogenic fungus (Metarhizium anisopliae) as a natural pathogen. To measure the health condition and immune response of beetles, we analysed the protein content in the haemolymph, prophenoloxidase (proPO) content, phenoloxidase (PO) activity and mortality of beetles with diets based on either acorns or cow dung. Protein content, proPO levels and PO levels in the haemolymph of T. lusitanicus were found to be dependent on the type of diet. Furthermore, the beetles fed with acorns developed a more effective proPO-PO system than the beetles fed with cow dung. Furthermore, a significant decrease in mortality was observed when infected individuals were submitted to an acorn-based diet. In addition to enhancing an understanding of the relevance of dietary change to the evolutionary biology of dung beetles, these results provide a more general understanding of the ecophysiological implications of differential dietary selection in the context of fitness.Financial support was provided by the Projects CGL2008/03878/BOS and CGL2011-25544 of the Secretaría de Estado de Investigación-Ministerio de Educación, Ciencia e Innovación (http://www.mecd.gob.es/portada-mecd/) and OAPN 762/2012, Ministerio de Agricultura, Alimentación y Medio Ambiente (http://www.magrama.gob.es/es/)