Radio Jet-Ambient Medium Interactions on Parsec Scales in the Blazar 1055+018

As part of our study of the magnetic fields of AGN we have recently observed a large sample of blazars with the Very Long Baseline Array. Here we report the discovery of a striking two-component jet in the source 1055+018, consisting of an inner spine with a transverse magnetic field, and a fragmentary but distinct boundary layer with a longitudinal magnetic field. The polarization distribution in the spine strongly supports shocked-jet models while that in the boundary layer suggests interaction with the surrounding medium. This behavior suggests a new way to understand the differing polarization properties of strong- and weak-lined blazars.Comment: LaTex; 10 pages; 6 figures; reference fix; to appear in ApJL, 518, 1999 June 2

A Natural Plasmid Uniquely Encodes Two Biosynthetic Pathways Creating a Potent Anti-MRSA Antibiotic

Background Understanding how complex antibiotics are synthesised by their producer bacteria is essential for creation of new families of bioactive compounds. Thiomarinols, produced by marine bacteria belonging to the genus Pseudoalteromonas, are hybrids of two independently active species: the pseudomonic acid mixture, mupirocin, which is used clinically against MRSA, and the pyrrothine core of holomycin. Methodology/Principal Findings High throughput DNA sequencing of the complete genome of the producer bacterium revealed a novel 97 kb plasmid, pTML1, consisting almost entirely of two distinct gene clusters. Targeted gene knockouts confirmed the role of these clusters in biosynthesis of the two separate components, pseudomonic acid and the pyrrothine, and identified a putative amide synthetase that joins them together. Feeding mupirocin to a mutant unable to make the endogenous pseudomonic acid created a novel hybrid with the pyrrothine via “mutasynthesis” that allows inhibition of mupirocin-resistant isoleucyl-tRNA synthetase, the mupirocin target. A mutant defective in pyrrothine biosynthesis was also able to incorporate alternative amine substrates. Conclusions/Significance Plasmid pTML1 provides a paradigm for combining independent antibiotic biosynthetic pathways or using mutasynthesis to develop a new family of hybrid derivatives that may extend the effective use of mupirocin against MRSA

COVID-19 and ENT SLT services, workforce and research in the UK: A discussion paper

Background. The COVID‐19 pandemic and the UK government's subsequent coronavirus action plan have fundamentally impacted on every aspect of healthcare. One area that is severely affected is ear, nose and throat (ENT)/laryngology where speech and language therapists (SLTs) engage in a diverse range of practice with patients with a range of conditions, including voice disorders, airway problems, and head and neck cancers (HNCs). A large majority of these patients are in high‐risk categories, and many specialized clinical practices are vulnerable. In addition, workforce and research issues are challenged in both the immediate context and the future. Aims. To discuss the threats and opportunities from the COVID‐19 pandemic for SLTs in ENT/laryngology with specific reference to clinical practice, workforce and research leadership. Methods & Procedures. The relevant sections of the World Health Organisation's (WHO) health systems building blocks framework (2007) were used to structure the study. Expert agreement was determined by an iterative process of multiple‐group discussions, the use of all recent relevant policy documentation, and other literature and shared documentation/writing. The final paper was verified and agreed by all authors. Main Contribution. The main threats to ENT/laryngology SLT clinical services include increased patient complexity related to COVID‐19 voice and airway problems, delayed HNC diagnosis, reduced access to instrumental procedures and inequitable care provision. The main clinical opportunities include the potential for new modes of service delivery and collaborations, and harnessing SLT expertise in non‐instrumental assessment. There are several workforce issues, including redeployment (and impact on current services), training implications and psychological impact on staff. Workforce opportunities exist for service innovation and potential extended ENT/SLT practice roles. Research is threatened by a reduction in immediate funding calls and high competition. Current research is affected by very limited access to participants and the ability to conduct face‐to‐face and instrumental assessments. However, research opportunities may result in greater collaboration, and changes in service delivery necessitate robust investigation and evaluation. A new national set of research priorities is likely to emerge. Conclusions & Implications. The immediate impact of the pandemic has resulted in major disruption to all aspects of clinical delivery, workforce and research for ENT/laryngology SLT. It is unclear when any of these areas will resume operations and whether permanent changes to clinical practice, professional remits and research priorities will follow. However, significant opportunity exists in the post‐COVID era to re‐evaluate current practice, embrace opportunities and evaluate new ways of working

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

Point prevalence of hip symptoms, radiographic, and symptomatic OA at five time points: The Johnston County Osteoarthritis Project, 1991-2018

Objective: To describe the point prevalence of hip symptoms, radiographic hip osteoarthritis (rHOA), severe rHOA, and symptomatic rHOA (sxHOA) at five time points in the longitudinal, population-based Johnston County Osteoarthritis Project (JoCoOA). Design: Data were from 3068 JoCoOA participants who attended up to five study visits (1991-2018). Standardized supine pelvis radiographs were read by a single, expert musculoskeletal radiologist with high reliability. The four outcomes were: 1) self-reported hip symptoms: "On most days, do you have pain, aching, or stiffness in your right/left hip?"; 2) rHOA: Kellgren-Lawrence grade (KLG) of 2-4; 3) severe rHOA: KLG of 3-4; and 4) sxHOA: both symptoms and rHOA in the same joint. Weighted point prevalence and 95% confidence intervals (CI) were generated overall and by age group (45-54, 55-64, 65-74, 75+ years), sex, race (Black/White), and body mass index (BMI; 18.5-24.9; 25-29.9; 30+ kg/m2). Results: At the most recent follow-up (2017-2018), the point prevalence (%) of hip symptoms, rHOA, severe rHOA, and sxHOA were 30% (95% CI 25%, 35%), 53% (95% CI 48%, 58%), 9% (95% CI 6%, 12%), and 15% (95% CI 11%, 19%), respectively. RHOA and severe rHOA were most prevalent in those 75+ years. Women were more likely than men to have hip symptoms and sxHOA. No consistent trends were noted by race or BMI. Conclusion: These updated point prevalence estimates demonstrate a large and increasing burden of HOA in the general population, particularly with aging. Black and White individuals were affected similarly in this cohort

Learning to prescribe - pharmacists' experiences of supplementary prescribing training in England

Background: The introduction of non-medical prescribing for professions such as pharmacy and nursing in recent years offers additional responsibilities and opportunities but attendant training issues. In the UK and in contrast to some international models, becoming a non-medical prescriber involves the completion of an accredited training course offered by many higher education institutions, where the skills and knowledge necessary for prescribing are learnt. Aims: to explore pharmacists' perceptions and experiences of learning to prescribe on supplementary prescribing (SP) courses, particularly in relation to inter-professional learning, course content and subsequent use of prescribing in practice. Methods: A postal questionnaire survey was sent to all 808 SP registered pharmacists in England in April 2007, exploring demographic, training, prescribing, safety culture and general perceptions of SP. Results: After one follow-up, 411 (51%) of pharmacists responded. 82% agreed SP training was useful, 58% agreed courses provided appropriate knowledge and 62% agreed that the necessary prescribing skills were gained. Clinical examination, consultation skills training and practical experience with doctors were valued highly; pharmacology training and some aspects of course delivery were criticised. Mixed views on inter-professional learning were reported – insights into other professions being valued but knowledge and skills differences considered problematic. 67% believed SP and recent independent prescribing (IP) should be taught together, with more diagnostic training wanted; few pharmacists trained in IP, but many were training or intending to train. There was no association between pharmacists' attitudes towards prescribing training and when they undertook training between 2004 and 2007 but earlier cohorts were more likely to be using supplementary prescribing in practice. Conclusion: Pharmacists appeared to value their SP training and suggested improvements that could inform future courses. The benefits of inter-professional learning, however, may conflict with providing professionspecific training. SP training may be perceived to be an instrumental 'stepping stone' in pharmacists' professional project of gaining full IP status

Walk with Me: a protocol for a pilot RCT of a peer-led walking programme to increase physical activity in inactive older adults

Background: Levels of physical activity decline with age. Some of the most disadvantaged individuals in society, such as those from lower socio-economic position, are also the most inactive. Increasing physical activity levels, particularly among those most inactive, is a public health priority. Peer-led physical activity interventions may offer a model to increase physical activity in the older adult population. This study aims to test the feasibility of a peer-led, multicomponent physical activity intervention in socio-economically disadvantaged community dwelling older adults. Methods: The Medical Research Council framework for developing and evaluating complex interventions will be used to design and test the feasibility of a randomised controlled trial (RCT) of a multicomponent peer-led physical activity intervention. Data will be collected at baseline, immediately after the intervention (12 weeks) and 6 months after baseline measures. The pilot RCT will provide information on recruitment of peer mentors and participants and attrition rates, intervention fidelity, and data on the variability of the primary outcome (minutes of moderate to vigorous physical activity measured with an accelerometer). The pilot trail will also assess the acceptability of the intervention and identify potential resources needed to undertake a definitive study. Data analyses will be descriptive and include an evaluation of eligibility, recruitment, and retention rates. The findings will be used to estimate the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders to identify areas of success and necessary improvements. Discussion: This paper describes the protocol for the ‘Walk with Me’ pilot RCT which will provide the information necessary to inform the design and delivery of a fully powered trial should the Walk with Me intervention prove feasible