Taking the Pulse: perceptions of crime trends and community safety and support for crime control methods in the Canadian Prairies

The present study analyzed crime survey data extracted from the 2012 Saskatchewan Taking the Pulse survey on a sample of 1,700 adult Saskatchewan residents. The focus was on examining perceptions of crime trends, perceived effectiveness of various methods for controlling crime, and their sociodemographic correlates. The majority of survey respondents perceived crime in general to be on the rise (37%) or to have not changed at all (48%) over the last three years. Individuals who perceived crime to have decreased were significantly more likely to support alternatives to punishment as effective methods for reducing crime, while individuals who perceived crime to be on the rise were twice as likely to support the use of punitive methods. Perceptions of community safety were unrelated to preference for one crime reduction method over another. Education level was inversely related to crime trend perceptions (r = -.14) and preference for punitive methods to reduce crime (r = -.20). Finally, the results of logistic regression indicated higher levels of education, higher income, and perceptions of crime decreasing were all uniquely associated with a preference for alternatives to punishment in reducing crime. In these analyses, younger age was predictive of a preference for alternatives in reducing youth crime, while urban residential setting was associated with a preference for alternatives to punishment in reducing crime in general

2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia.

The metabolic response to endotoxemia closely mimics those seen in sepsis. Here, we show that the urinary excretion of the metabolite 2-hydroxyglutarate (2HG) is dramatically suppressed following lipopolysaccharide (LPS) administration in vivo, and in human septic patients. We further show that enhanced activation of the enzymes responsible for 2-HG degradation, D- and L-2-HGDH, underlie this effect. To determine the role of supplementation with 2HG, we carried out co-administration of LPS and 2HG. This co-administration in mice modulates a number of aspects of physiological responses to LPS, and in particular, protects against LPS-induced hypothermia. Our results identify a novel role for 2HG in endotoxemia pathophysiology, and suggest that this metabolite may be a critical diagnostic and therapeutic target for sepsis

A synthetic cell permeable antioxidant protects neurons against acute oxidative stress

Funding: Royal Society University Fellowship and grant (RF 120645) (JEL).Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson’s disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and moderate mitochondrial enrichment of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against cell loss in a zebrafish model of dopaminergic neurodegeneration.Publisher PDFPeer reviewe

Pseudomonas fluorescens SBW25 produces furanomycin, a non-proteinogenic amino acid with selective antimicrobial properties

Background: Pseudomonas fluorescens SBW25 has been extensively studied because of its plant growth promoting properties and potential as a biocontrol agent. The genome of SBW25 has been sequenced, and among sequenced strains of pseudomonads, SBW25 appears to be most closely related to P. fluorescens WH6. In the authors' laboratories, WH6 was previously shown to produce and secrete 4-formylaminooxyvinylglycine (FVG), a non-proteinogenic amino acid with selective herbicidal and antimicrobial activity. Although SBW25 does not have the genetic capacity to produce FVG, we were interested in determining whether this pseudomonad might produce some other type of non-proteinogenic amino acid. Results: P. fluorescens SBW25 was found to produce and secrete a ninhydrin-reactive compound with selective antimicrobial properties. This compound was purified from SBW25 culture filtrate and identified as the non-proteinogenic amino acid L-furanomycin [2S,2'R,5'S)-2-amino-2-(5'methyl-2',5'-dihydrofuran-2'-yl)acetic acid]. Conclusions: The identification of furanomycin as a secondary metabolite of SBW25 is the first report of the production of furanomycin by a pseudomonad. This compound was known previously only as a natural product produced by a strain of Streptomyces. This report adds furanomycin to the small list of non-proteinogenic amino acids that have been identified as secondary products of pseudomonads. This study also extends the list of bacteria that are inhibited by furanomycin to include several plant pathogenic bacteria.Keywords: Non-proteinogenic amino acids, 4-formylaminooxyvinylglycine, Pseudomonas fluorescens SBW25, Pseudomonas fluorescens WH6, Furanomycin, Secondary metabolites, Antimicrobial activit

Prevalence of Bleeding and Thrombosis in Critically Ill Patients with Chronic Liver Disease

INTRODUCTION:  Hemorrhage and venous thromboembolism (VTE) are recognized complications of chronic liver disease (CLD), but their prevalence and risk factors in critically ill patients are uncertain. PATIENTS AND METHODS:  We studied a retrospective cohort of patients with CLD nonelectively admitted to a specialist intensive care unit (ICU) determining the prevalence and timing of major bleeding and VTE (early, present on admission/diagnosed within 48 hours; later, diagnosed >48 hours post-ICU admission). Associations with baseline clinical and laboratory characteristics, multiorgan failure (MOF), blood product administration, and mortality were explored. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. RESULTS:  Of 623 patients with median age 52, bleeding (>48 hours after admission) occurred in 87 (14%) patients. Bleeding was associated with greater illness severity and increased mortality. Gastrointestinal bleeding accounted for 72% of events, secondary to portal hypertension in >90%. Procedure-related bleeding was uncommon. VTE occurred in 125 (20%) patients: early VTE in 80 (13%) and involving the portal vein in 85%. Later VTE affected 45 (7.2%) patients. Hepatocellular carcinoma (HCC) and nonalcoholic liver disease were independently associated with early VTE (OR: 2.79, 95% CI: 1.5-5.2 and OR: 2.32, 95% CI: 1.4-3.9, respectively), and HCC, sepsis, and cryoprecipitate use with late VTE (OR: 2.45, 95% CI: 1.11-5.43; OR: 2.26, 95% CI: 1.2-4.3; and OR: 2.60, 95% CI: 1.3-5.1). CONCLUSION:  VTE was prevalent on admission to critical care and less commonly developed later. Bleeding was associated with MOF and increased mortality. Severe MOF was not associated with an increased rate of VTE which was linked with HCC, and specific etiologies of CLD

Variation in the Care of Acute Liver Failure: A Survey of Intensive Care Professionals

Introduction: Acute liver failure (ALF) is a rare disease with potentially high mortality. We sought to assess the individual approach to ALF by intensive care unit (ICU) professionals. Methods: Cross-sectional survey of ICU professionals. Web-based survey capturing data on respondents’ demographics, characteristics of patients with ALF admitted to ICU, and their management. Results: Among 204 participants from 50 countries, 140 (68.6%) worked in Europe, 146 (71.6%) were intensivists, 142 (69.6%) admitted <25 patients with ALF per year, and 166 (81.8%) reported <25% of patients had paracetamol-related ALF. On patients’ outcomes, 126 (75.0%) reported an emergency liver transplantation (ELT) rate <25% and 140 (73.3%) a hospital mortality rate <50%. The approach to ALF in the ICU varied with age, region, level of training, type of hospital, and etiology (prescribing N-acetylcysteine for paracetamol toxicity, triggers for endotracheal intubation, measurement of and strategies for lowering serum ammonia, extracorporeal device deployment, and prophylactic antibiotics). Conclusions: The management of patients with ALF by ICU professionals differed substantially concerning the relevant clinical measures taken. Further education and high-quality research are warranted

Bioactivity in silica/poly(γ-glutamic acid) sol–gel hybrids through calcium chelation

Bioactive glasses and inorganic/organic hybrids have great potential as biomedical implant materials. Sol–gel hybrids with interpenetrating networks of silica and biodegradable polymers can combine the bioactive properties of a glass with the toughness of a polymer. However, traditional calcium sources such as calcium nitrate and calcium chloride are unsuitable for hybrids. In this study calcium was incorporated by chelation to the polymer component. The calcium salt form of poly(γ-glutamic acid) (γCaPGA) was synthesized for use as both a calcium source and as the biodegradable toughening component of the hybrids. Hybrids of 40 wt.% γCaPGA were successfully formed and had fine scale integration of Ca and Si ions, according to secondary ion mass spectrometry imaging, indicating a homogeneous distribution of organic and inorganic components. 29Si magic angle spinning nuclear magnetic resonance data demonstrated that the network connectivity was unaltered with changing polymer molecular weight, as there was no perturbation to the overall Si speciation and silica network formation. Upon immersion in simulated body fluid a hydroxycarbonate apatite surface layer formed on the hybrids within 1 week. The polymer molecular weight (Mw 30–120 kDa) affected the mechanical properties of the resulting hybrids, but all hybrids had large strains to failure, >26%, and compressive strengths, in excess of 300 MPa. The large strain to failure values showed that γCaPGA hybrids exhibited non-brittle behaviour whilst also incorporating calcium. Thus calcium incorporation by chelation to the polymer component is justified as a novel approach in hybrids for biomedical materials

General Practitioner perspectives on factors that influence implementation of secondary care-initiated treatment in primary care: exploring implementation beyond the context of a clinical trial

Background The Beta-blockers Or Placebo for Primary Prophylaxis of oesophageal varices (BOPPP) trial is a 3-year phase IV, multi-centre clinical trial of investigational medicinal product (CTIMP) that aims to determine the effectiveness of carvedilol in the prevention of variceal bleeding for small oesophageal varices in patients with cirrhosis. Early engagement of General Practitioners (GPs) in conversations about delivery of a potentially effective secondary care-initiated treatment in primary care provides insights for future implementation. The aim of this study was to understand the implementation of trial findings by exploring i) GP perspectives on factors that influence implementation beyond the context of the trial and ii) how dose titration and ongoing treatment with carvedilol is best delivered in primary care. Methods This qualitative study was embedded within the BOPPP trial and was conducted alongside site opening. GP participants were purposively sampled and recruited from ten Clinical Commissioning Groups in England and three Health Boards across Wales. Semi-structured telephone individual interviews were conducted with GPs (n = 23) working in England and Wales. Data were analysed using reflexive thematic analysis. Findings Five overarching themes were identified: i) primary care is best placed for oversight, ii) a shared approach led by secondary care, iii) empower the patient to take responsibility, iv) the need to go above and beyond and v) develop practice guidance. The focus on prevention, attention to holistic care, and existing and often long-standing relationships with patients provides an impetus for GP oversight. GPs spoke about the value of partnership working with secondary care and of prioritising patient-centred care and involving patients in taking responsibility for their own health. An agreed pathway of care, clear communication, and specific, accessible guidance on how to implement the proposed treatment strategy safely and effectively are important determinants in the success of implementation. Conclusions Our findings for implementing secondary care-initiated treatment in primary care are important to the specifics of the BOPPP trial but can also go some way in informing wider learning for other trials where work is shared across the primary-secondary care interface, and where findings will impact the primary care workload. We propose a systems research perspective for addressing implementation of CTIMP findings at the outset of research. The value of early stakeholder involvement is highlighted, and the need to consider complexity in terms of the interaction between the intervention and the context in which it is implemented is acknowledged

Who watches the watchmen? Evaluating evaluations of El Sistema

Within the growing field of publications on El Sistema and Sistema-inspired programmes around the world, a marked divide can be observed between the findings of critical academic studies and commissioned evaluations. Using evaluations of El Sistema in Venezuela and Aotearoa New Zealand as our principal case studies, we argue that this gulf can be explained at least partly by methodological problems in the way that some evaluations are carried out. We conclude that many Sistema evaluations display an alignment with advocacy rather than explorative research, and that the foundation for El Sistema's claims of social transformation is thus weak