RocA truncation underpins hyper-encapsulation, carriage longevity and transmissibility of serotype M18 group A streptococci

Group A streptococcal isolates of serotype M18 are historically associated with epidemic waves of pharyngitis and the non-suppurative immune sequela rheumatic fever. The serotype is defined by a unique, highly encapsulated phenotype, yet the molecular basis for this unusual colony morphology is unknown. Here we identify a truncation in the regulatory protein RocA, unique to and conserved within our serotype M18 GAS collection, and demonstrate that it underlies the characteristic M18 capsule phenotype. Reciprocal allelic exchange mutagenesis of rocA between M18 GAS and M89 GAS demonstrated that truncation of RocA was both necessary and sufficient for hyper-encapsulation via up-regulation of both precursors required for hyaluronic acid synthesis. Although RocA was shown to positively enhance covR transcription, quantitative proteomics revealed RocA to be a metabolic regulator with activity beyond the CovR/S regulon. M18 GAS demonstrated a uniquely protuberant chain formation following culture on agar that was dependent on excess capsule and the RocA mutation. Correction of the M18 rocA mutation reduced GAS survival in human blood, and in vivo naso-pharyngeal carriage longevity in a murine model, with an associated drop in bacterial airborne transmission during infection. In summary, a naturally occurring truncation in a regulator explains the encapsulation phenotype, carriage longevity and transmissibility of M18 GAS, highlighting the close interrelation of metabolism, capsule and virulence

Early onset cannabis use and progression to other drug use in a sample of Dutch twins

One possible explanation of the commonly reported associations between early onset cannabis use and elevated risks of other illicit drug use is that early onset cannabis use increases access and availability to other drugs. It was this argument that in part motivated policy changes in the Netherlands that led to the de facto legalization of cannabis there. This study examines, using a co-twin control design, whether previously observed associ- ations between early onset cannabis use and elevated lifetime rates of other illicit drug use would also be observed in a sample of 219 same sex Dutch twin pairs discordant for cannabis use before age 18. After adjustment for covariates, rates of lifetime party drug use (OR = 7.4, 95% CI = 2.3-23.4), hard drug use (OR = 16.5, 95% CI = 2.4-111.3), but not regular cannabis use (OR= 1.3, 95% CI = 0.3-5.1) were significantly elevated in individuals who reported early onset cannabis use, relative to their co-twin who had not used cannabis by age 18. The elevated odds of subsequent illicit drug use in early cannabis users relative to their non early using cotwins suggests that this association could not be explained by common familial risk factors, either genetic or environmental, for which our co-twin methodology provided rigorous control. © 2006 Springer Science+Business Media, Inc

The enduring culture and limits of political song

The connection between song and politics is well documented, but in recent years is said to be severed. This is not the case. The relationship between politics and song endures, reflecting and revivifying a culture of political struggle. In this essay, I survey political song, outlining how it is approached, before arguing for a tighter definition after working through the claim that all song is political. In doing so, I build a platform for discussion of songs by English singer-songwriter Leon Rosselson. For over 50 years, Rosselson’s songwriting has illuminated historical and topical events from a left-wing perspective, but he is also clear a song converts noone and changes nothing. To think otherwise misunderstands that songs are neither mobilisers or opiates, but an idiom for people to express their everyday lives and struggles. The essay concludes by assessing Rosselson’s insights on the power and limits of song

Substance use and psychological disorders among art and non-art university students: an empirical self-report survey

Media stories often suggest that those working in the creative arts appear to use and abuse psychoactive substances. The aim of the present study was to analyze the relationship between the use of psychoactive substances and the presence of psychological disorders among art and non-art students. Questionnaires related to these two areas were completed by 182 art students in higher education and a control group of 704 non-art university students. To assess psychoactive substance use, a structured questionnaire including the Cannabis Abuse Screening Test (CAST) and the Alcohol Use Disorders Identification Test (AUDIT) was administered to participants. Psychological disorders were assessed using the Hungarian version of the Brief Symptom Inventory (BSI) and the Global Severity Index (GSI). After analyzing the data, significant differences were found between the two groups regarding their first use of psychoactive substances. Art students' current substance use was found to be significantly more frequent compared to the control group. In relation to psychological disorders, art students scored significantly higher on three scales of the BSI (i.e., psychoticism, hostility, and phobic anxiety). Overall, a significantly higher proportion of artists were labeled as "problematic" using the GSI. The results suggest that artists have a higher risk of both substance use and experiencing psychological disorders

The value of real world evidence: the case of medical cannabis

Randomised controlled trials (RCTs) have long been considered the gold standard of medical evidence. In relation to cannabis based medicinal products (CBMPs), this focus on RCTs has led to very restrictive guidelines in the UK, which are limiting patient access. There is general agreement that RCT evidence in relation to CBPMs is insufficient at present. As well as commercial reasons, a major problem is that RCTs do not lend themselves well to the study of whole plant medicines. One solution to this challenge is the use of real world evidence (RWE) with patient reported outcomes (PROs) to widen the evidence base. Such data increasingly highlights the positive impact medical cannabis can have on patients’ lives. This paper outlines the value of this approach which involves the study of interventions and patients longitudinally under medical care. In relation to CBMPs, RWE has a broad range of advantages. These include the study of larger groups of patients, the use of a broader range and ratio of components of CBMPs, and the inclusion of more and rarer medical conditions. Importantly, and in contrast to RCTs, patients with significant comorbidities–and from a wider demographic profile–can also be studied, so providing higher ecological validity and increasing patient numbers, whilst offering significant cost savings. We conclude by outlining 12 key recommendations of the value of RWE in relation to medical cannabis. We hope that this paper will help policymakers and prescribers understand the importance of RWE in relation to medical cannabis and help them develop approaches to overcome the current situation which is detrimental to patients

Designing an Agent-Based Model for Childhood Obesity Interventions: A Case Study of ChildObesity180

Complex systems modeling can provide useful insights when designing and anticipating the impact of public health interventions. We developed an agent-based, or individual-based, computation model (ABM) to aid in evaluating and refining implementation of behavior change interventions designed to increase physical activity and healthy eating and reduce unnecessary weight gain among school-aged children. The potential benefits of applying an ABM approach include estimating outcomes despite data gaps, anticipating impact among different populations or scenarios, and exploring how to expand or modify an intervention. The practical challenges inherent in implementing such an approach include data resources, data availability, and the skills and knowledge of ABM among the public health obesity intervention community. The aim of this article was to provide a step-by-step guide on how to develop an ABM to evaluate multifaceted interventions on childhood obesity prevention in multiple settings. We used data from 2 obesity prevention initiatives and public-use resources. The details and goals of the interventions, overview of the model design process, and generalizability of this approach for future interventions is discussed