The synthesis of novel chromogenic enzyme substrates for detection of bacterial glycosidases and their applications in diagnostic microbiology

The preparation and evaluation of chromogenic substrates for detecting bacterial glycosidase enzymes is reported. These substrates are monoglycoside derivatives of the metal chelators catechol, 2,3-dihydroxynaphthalene (DHN) and 6,7-dibromo-2,3-dihydroxynaphthalene (6,7-dibromo-DHN). When hydrolysed by appropriate bacterial enzymes these substrates produced coloured chelates in the presence of ammonium iron(III) citrate, thus enabling bacterial detection. A β-D-riboside of DHN and a β-D-glucuronide derivative of 6,7-dibromo-DHN were particularly effective for the detection of S. aureus and E. coli respectively

Ubiquitous giant Ly α\alpha nebulae around the brightest quasars at z∼3.5z\sim3.5 revealed with MUSE

Direct Ly $\alpha$ imaging of intergalactic gas at $z\sim2$ has recently revealed giant cosmological structures around quasars, e.g. the Slug Nebula (Cantalupo et al. 2014). Despite their high luminosity, the detection rate of such systems in narrow-band and spectroscopic surveys is less than 10%, possibly encoding crucial information on the distribution of gas around quasars and the quasar emission properties. In this study, we use the MUSE integral-field instrument to perform a blind survey for giant Ly $\alpha$ nebulae around 17 bright radio-quiet quasars at $3<z<4$ that does not suffer from most of the limitations of previous surveys. After data reduction and analysis performed with specifically developed tools, we found that each quasar is surrounded by giant Ly $\alpha$ nebulae with projected sizes larger than 100 physical kpc and, in some cases, extending up to 320 kpc. The circularly averaged surface brightness profiles of the nebulae appear very similar to each other despite their different morphologies and are consistent with power laws with slopes $\approx-1.8$. The similarity between the properties of all these nebulae and the Slug Nebula suggests a similar origin for all systems and that a large fraction of gas around bright quasars could be in a relatively "cold" (T$\sim$10$^4$K) and dense phase. In addition, our results imply that such gas is ubiquitous within at least 50 kpc from bright quasars at $3<z<4$ independently of the quasar emission opening angle, or extending up to 200 kpc for quasar isotropic emission.Comment: 19 pages, 9 figures, 3 Tables, accepted to Ap

Traumatic brain injuries and problem gambling in youth: Evidence from a population-based study of secondary students in Ontario, Canada

Traumatic brain injury (TBI) is characterized by a change in brain function after an external force or sudden movement to the head. TBI is associated with risk-taking, impulsivity, psychological distress, substance abuse, and violent crime. Previous studies have also linked problem gambling to TBI, but these studies have not controlled for possible confounding variables such as mental health problems and hazardous drinking which are also linked to TBI. This study examines the relationship between problem gambling and TBI among adolescents. Data were obtained from the 2011, 2013 and 2015 cycles of the OSDUHS, a biennial cross-sectional school-based study of children in grades 7 to 12 (N = 9,198). Logistic regression was used to estimate adjusted odds ratios (AOR) in controlled and uncontrolled analyses. Adjusting for sex and grade only, problem gambling was associated with a history of TBI (AOR = 2.8). This association remained significant after adjusting for hazardous drinking and suicidality (AOR = 2.0). In addition, problem gambling had a statistically significant relationship with being male (AOR = 4.7), hazardous drinking (AOR = 4.5), and suicidality (AOR = 3.1). This study provides further data to suggest a link between TBI and problem gambling. However, research is needed on the causal relationship between these variables and the potential implications for treatment and prevention

Development of a transparent interactive decision interrogator to facilitate the decision-making process in health care.

BACKGROUND: Decisions about the use of new technologies in health care are often based on complex economic models. Decision makers frequently make informal judgments about evidence, uncertainty, and the assumptions that underpin these models. OBJECTIVES: Transparent interactive decision interrogator (TIDI) facilitates more formal critique of decision models by decision makers such as members of appraisal committees of the National Institute for Health and Clinical Excellence in the UK. By allowing them to run advanced statistical models under different scenarios in real time, TIDI can make the decision process more efficient and transparent, while avoiding limitations on pre-prepared analysis. METHODS: TIDI, programmed in Visual Basic for applications within Excel, provides an interface for controlling all components of a decision model developed in the appropriate software (e.g., meta-analysis in WinBUGS and the decision model in R) by linking software packages using RExcel and R2WinBUGS. TIDI's graphical controls allow the user to modify assumptions and to run the decision model, and results are returned to an Excel spreadsheet. A tool displaying tornado plots helps to evaluate the influence of individual parameters on the model outcomes, and an interactive meta-analysis module allows the user to select any combination of available studies, explore the impact of bias adjustment, and view results using forest plots. We demonstrate TIDI using an example of a decision model in antenatal care. CONCLUSION: Use of TIDI during the NICE appraisal of tumor necrosis factor-alpha inhibitors (in psoriatic arthritis) successfully demonstrated its ability to facilitate critiques of the decision models by decision makers

Moderate to severe gambling problems and traumatic brain injury: A population-based study

Traumatic brain injury (TBI) is a common injury characterized by a change in brain function after an external blow to the head and is associated with substance abuse, psychological distress, risk-taking, and impulsivity. Convenience and clinical samples have also linked TBI to problem gambling, but have not ruled out confounding variables such as hazardous drinking and psychological distress. This study examines the relationship between TBI and moderate to severe problem gambling in a general population probability sample controlling for hazardous drinking and psychological distress. The data were obtained from a 2015–2016 cross-sectional general population telephone survey of adults ages 18+from Ontario, Canada (N = 3809). Logistic regression was used to estimate the association as adjusted odds ratios (AOR). Moderate to severe problem gambling was independently associated with a history of TBI after adjusting for potential confounders (AOR: 2.80), and had a statistically significant relationship with psychological distress (AOR = 2.74), hazardous drinking (AOR = 2.69), and lower educational levels (AOR = 0.37). This study provides further data to suggest a link between TBI and moderate to severe problem gambling; however, more research is needed to determine if there is a causal relationship or the potential implications for prevention and treatment

Moderate to severe gambling problems and traumatic brain injury: A population-based study

Traumatic brain injury (TBI) is a common injury characterized by a change in brain function after an external blow to the head and is associated with substance abuse, psychological distress, risk-taking, and impulsivity. Convenience and clinical samples have also linked TBI to problem gambling, but have not ruled out confounding variables such as hazardous drinking and psychological distress. This study examines the relationship between TBI and moderate to severe problem gambling in a general population probability sample controlling for hazardous drinking and psychological distress. The data were obtained from a 2015–2016 cross-sectional general population telephone survey of adults ages 18+from Ontario, Canada (N = 3809). Logistic regression was used to estimate the association as adjusted odds ratios (AOR). Moderate to severe problem gambling was independently associated with a history of TBI after adjusting for potential confounders (AOR: 2.80), and had a statistically significant relationship with psychological distress (AOR = 2.74), hazardous drinking (AOR = 2.69), and lower educational levels (AOR = 0.37). This study provides further data to suggest a link between TBI and moderate to severe problem gambling; however, more research is needed to determine if there is a causal relationship or the potential implications for prevention and treatment

Effectiveness and cost-effectiveness of a patient-initiated botulinum toxin treatment model for blepharospasm and hemifacial spasm: a study protocol for a randomised controlled trial

Background Blepharospasm and hemifacial spasm are debilitating conditions that significantly impact on patient quality of life. Cyclical treatment with botulinum toxin injections offers temporary relief, but the duration of treatment efficacy is variable. The standard model of patient care defines routine fixed-time based scheduled treatment cycles which may lead to unnecessarily frequent treatment for some patients and experience of distressing symptoms in others, if symptoms return before the scheduled follow-up period. Methods/Design A randomised controlled trial will compare a patient-initiated model of care, where patients determine botulinum toxin treatment timing, to the standard model of care in which care is scheduled by the clinical team. A sample of 266 patients with blepharospasm or hemifacial spasm will be recruited from Moorfields Eye Hospital (MEH), London. The trial will be accompanied by a mixed methods evaluation of acceptability of the new service. Patients who meet eligibility criteria will be assessed at baseline and those in the intervention group will be provided instructions on how to book their own treatment appointments. Patients in both groups will be followed up 3 and 9 months into the trial and all patients will be returned to usual care after 9 months to meet safety protocols. Primary outcome measures include disease severity (questionnaire), functional disability (questionnaire) and patient satisfaction with care (questionnaire). Secondary outcomes include disease-specific quality of life (questionnaire), mood (questionnaire), illness and treatment perceptions (questionnaire and semi-structured interviews), economic impact (questionnaire) and acceptability (questionnaire and semi-structured interviews). Discussion This trial will assess the effectiveness and cost-effectiveness of a patient-led care model for botulinum toxin therapy. If the new model is shown to be effective in reducing distress and disability in these populations and is found to be acceptable to patients, whilst being cost-effective, this will have significant implications for service organisation across the NHS. Trial registration UK Clinical Research Network (UKCRN) Portfolio 18660. Clinicaltrials.gov ID NCT102577224 (registered 29th October 2015

Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen.

PURPOSE: The relationship between body mass index (BMI) and prostate cancer remains unclear. However, there is an inverse association between BMI and prostate-specific antigen (PSA), used for prostate cancer screening. We conducted this review to estimate the associations between BMI and (1) prostate cancer, (2) advanced prostate cancer, and (3) PSA. METHODS: We searched PubMed and Embase for studies until 02 October 2017 and obtained individual participant data from four studies. In total, 78 studies were identified for the association between BMI and prostate cancer, 21 for BMI and advanced prostate cancer, and 35 for BMI and PSA. We performed random-effects meta-analysis of linear associations of log-PSA and prostate cancer with BMI and, to examine potential non-linearity, of associations between categories of BMI and each outcome. RESULTS: In the meta-analyses with continuous BMI, a 5 kg/m2 increase in BMI was associated with a percentage change in PSA of - 5.88% (95% CI - 6.87 to - 4.87). Using BMI categories, compared to normal weight men the PSA levels of overweight men were 3.43% lower (95% CI - 5.57 to - 1.23), and obese men were 12.9% lower (95% CI - 15.2 to - 10.7). Prostate cancer and advanced prostate cancer analyses showed little or no evidence associations. CONCLUSION: There is little or no evidence of an association between BMI and risk of prostate cancer or advanced prostate cancer, and strong evidence of an inverse and non-linear association between BMI and PSA. The association between BMI and prostate cancer is likely biased if missed diagnoses are not considered

Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen.

PURPOSE: The relationship between body mass index (BMI) and prostate cancer remains unclear. However, there is an inverse association between BMI and prostate-specific antigen (PSA), used for prostate cancer screening. We conducted this review to estimate the associations between BMI and (1) prostate cancer, (2) advanced prostate cancer, and (3) PSA. METHODS: We searched PubMed and Embase for studies until 02 October 2017 and obtained individual participant data from four studies. In total, 78 studies were identified for the association between BMI and prostate cancer, 21 for BMI and advanced prostate cancer, and 35 for BMI and PSA. We performed random-effects meta-analysis of linear associations of log-PSA and prostate cancer with BMI and, to examine potential non-linearity, of associations between categories of BMI and each outcome. RESULTS: In the meta-analyses with continuous BMI, a 5 kg/m2 increase in BMI was associated with a percentage change in PSA of - 5.88% (95% CI - 6.87 to - 4.87). Using BMI categories, compared to normal weight men the PSA levels of overweight men were 3.43% lower (95% CI - 5.57 to - 1.23), and obese men were 12.9% lower (95% CI - 15.2 to - 10.7). Prostate cancer and advanced prostate cancer analyses showed little or no evidence associations. CONCLUSION: There is little or no evidence of an association between BMI and risk of prostate cancer or advanced prostate cancer, and strong evidence of an inverse and non-linear association between BMI and PSA. The association between BMI and prostate cancer is likely biased if missed diagnoses are not considered