Inflammation dynamically regulates steroid hormone metabolism and action within macrophages in rheumatoid arthritis.

RATIONALE: In inflammatory diseases such as rheumatoid arthritis (RA), steroid metabolism is a central component mediating the actions of immuno-modulatory glucocorticoids and sex steroids. However, the regulation and function of cellular steroid metabolism within key leukocyte populations such as macrophages remain poorly defined. In this study, the inflammatory regulation of global steroid metabolism was assessed in RA macrophages. METHODS: Bulk RNA-seq data from RA synovial macrophages was used to assess transcripts encoding key enzymes in steroid metabolism and signalling. Changes in metabolism were assessed in synovial fluids, correlated to measures of disease activity and functionally validated in primary macrophage cultures. RESULTS: RNA-seq revealed a unique pattern of differentially expressed genes, including changes in genes encoding the enzymes 11ß-HSD1, SRD5A1, AKR1C2 and AKR1C3. These correlated with disease activity, favouring increased glucocorticoid and androgen levels. Synovial fluid 11ß-HSD1 activity correlated with local inflammatory mediators (TNFα, IL-6, IL-17), whilst 11ß-HSD1, SRD5A1 and AKR1C3 activity correlated with systemic measures of disease and patient pain (ESR, DAS28 ESR, global disease activity). Changes in enzyme activity were evident in inflammatory activated macrophages in vitro and revealed a novel androgen activating role for 11ß-HSD1. Together, increased glucocorticoids and androgens were able to suppress inflammation in macrophages and fibroblast-like-synoviocytes. CONCLUSIONS: This study underscores the significant increase in androgen and glucocorticoid activation within inflammatory polarized macrophages of the synovium, contributing to local suppression of inflammation. The diminished profile of inactive steroid precursors in postmenopausal women may contribute to disturbances in this process, leading to increased disease incidence and severity.

COVID-19 vaccine safety in Scotland - background rates of adverse events of special interest.

OBJECTIVES: Mass COVID-19 vaccination commenced in December 2020 in Scotland. Monitoring vaccine safety relies on accurate background incidence rates (IRs) for health outcomes potentially associated with vaccination. This study aimed to quantify IRs in Scotland of adverse events of special interest (AESI) potentially associated with COVID-19 vaccination. STUDY DESIGN AND METHODS: IRs and 95% confidence intervals (CIs) for 36 AESI were calculated retrospectively for the pre-COVID-19 pandemic period (01 January 2015-31 December 2019) and the COVID-19 pandemic period (01 April 2020-30 November 2020), with age-sex stratification, and separately by calendar month and year. Incident cases were determined using International Classification of Diseases-10th Revision (ICD-10)-coded hospitalisations. RESULTS: Prepandemic population-wide IRs ranged from 0.4 (0.3-0.5 CIs) cases per 100,000 person-years (PYRS) for neuromyelitis optica to 478.4 (475.8-481.0 CIs) cases per 100,000 PYRS for acute renal failure. Pandemic population-wide IRs ranged from 0.3 (0.2-0.5 CIs) cases per 100,000 PYRS for Kawasaki disease to 483.4 (473.2-493.7 CIs) cases per 100,000 PYRS for acute coronary syndrome. All AESI IRs varied by age and sex. Ten AESI (acute coronary syndrome, acute myocardial infarction, angina pectoris, heart failure, multiple sclerosis, polyneuropathies and peripheral neuropathies, respiratory failure, rheumatoid arthritis and polyarthritis, seizures and vasculitis) had lower pandemic than prepandemic period IRs overall. Only deep vein thrombosis and pulmonary embolism had a higher pandemic IR. CONCLUSION: Lower pandemic IRs likely resulted from reduced health-seeking behaviours and healthcare provision. Higher IRs may be associated with SARS-CoV-2 infections. AESI IRs will facilitate future vaccine safety studies in Scotland.

Exploiting Real-Time Genomic Surveillance Data To Assess 4CMenB Meningococcal Vaccine Performance in Scotland, 2015 to 2022.

The United Kingdom implemented the first national infant immunization schedule for the meningococcal vaccine 4CMenB (Bexsero) in September 2015, targeting serogroup B invasive meningococcal disease (IMD). Bexsero contains four variable subcapsular proteins, and postimplementation IMD surveillance was necessary, as nonhomologous protein variants can evade Bexsero-elicited protection. We investigated postimplementation IMD cases reported in Scotland from 1 September 2015 to 30 June 2022. Patient demographics and vaccination status were combined with genotypic data from the causative meningococci, which were used to assess vaccine coverage with the meningococcal deduced vaccine antigen reactivity (MenDeVAR) index. Eighty-two serogroup B IMD cases occurred in children >5 years of age, 48 (58.5%) of which were in unvaccinated children and 34 (41%) of which were in children who had received ≥1 Bexsero dose. Fifteen of the 34 vaccinated children had received one dose, 17 had received two doses, and two had received three doses. For 39 cases, meningococcal sequence data were available, enabling MenDeVAR index deductions of vaccine-preventable (M-VP) and non-vaccine-preventable (M-NVP) meningococci. Notably, none of the 19 of the children immunized ≥2 times had IMD caused by M-VP meningococci, with 2 cases of NVP meningococci, and no deduction possible for 17. Among the 15 children partially vaccinated according to schedule (1 dose), 7 were infected by M-VP meningococci and 2 with M-NVP meningococci, with 6 for which deductions were not possible. Of the unvaccinated children with IMD, 40/48 were ineligible for vaccination and 20/48 had IMD caused by M-VP meningococci, with deductions not being possible for 14 meningococci. IMPORTANCE This study demonstrates the value of postimplementation genomic surveillance of vaccine-preventable pathogens in providing information on real-world vaccine performance. The data are consistent with 2 and 3 doses of Bexsero, delivered according to schedule, providing good protection against invasive disease caused by meningococci deduced from genomic data to be vaccine preventable. Single doses provide poorer protection to infants. In practical terms, these data can provide public health reassurance when vaccinated individuals develop IMD with non-vaccine-preventable variants. They further indicate that additional testing is needed on variants for which no immunological data exist to improve estimates of protection, although these data suggest that the uncharacterized variants are unlikely to be covered by Bexsero. Finally, the confirmation that incomplete or absent doses in infancy lead to reduced protection supports public health and general practitioners in promoting vaccination according to schedule.

Effectiveness of strategies to increase participation in school-based epidemiological surveys: a rapid review.

OBJECTIVE: Rapid review of the literature on strategies to increase participation rates in school-based epidemiological surveys. BASIC RESEARCH DESIGN: Rapid review. MEDLINE and Embase databases were searched for articles written in English from 2000 onwards. Synthesised evidence and primary research were included as data sources from peer reviewed journals and reports. INTERVENTIONS: Any strategy aiming to increase participation in school-based health surveys. The comparator was usual procedure or an alternative strategy to increase participation. MAIN OUTCOME MEASURES: Primary outcomes included participation and consent rates. Secondary outcomes were feasibility, acceptability and adverse effects. RESULTS: The search identified 591 unique records, of which 587 were excluded. Four studies were suitable for inclusion, including one systematic review, one randomised controlled trial, one cross-sectional study and one retrospective analysis. Based on very low certainty evidence, recommendations for maximising participation rates in one systematic review of US studies included: promoting the survey to school staff, parents and students; disseminating study information using direct rather than mediated methods; offering incentives to schools, staff and participants; following up non-responders; and employing a research team member to co-ordinate and monitor recruitment. However, UK studies found that different strategies did not increase participation more than that achieved by a standard approach (delivery of covering letter/consent forms via the child with no follow-up of non-responders). CONCLUSION: Given the lack of evidence of effectiveness of alternative strategies in the UK, additional measures beyond existing standard approaches for active consent cannot be recommended.

Exploring how fire spread mode shapes the composition of pyrogenic carbon from burning forest litter fuels in a combustion wind tunnel.

In this study, solid state 13C nuclear magnetic resonance (NMR) spectroscopy was used to explore the carbon-containing functional groups present in pyrogenic carbon (PyC) produced during different fire spread modes to forest litter fuels from a dry sclerophyll eucalypt forest burnt in a combustion wind tunnel. A replicated experimental study was performed using three different fire spread modes: heading fires (i.e. fires which spread with the wind), flanking fires (i.e. fires which spread perpendicular to the wind) and backing fires (i.e. fires which spread against the wind). In addition to 13C NMR measurements of PyC, detailed fire behaviour measurements were recorded during experiments. Experiments showed that heading fires produced significantly more aryl carbon in ash samples than flanking fires. All other experimental comparisons for burnt fuel samples involving different fire spread modes were statistically insignificant. Principal component analysis (PCA) was used to explore the relationship between 13C NMR functional groups and fire behaviour observations. Results from PCA indicate that maximising the residence time of high temperature combustion and the combustion factor (i.e. the fraction of pre-fire biomass consumed by fire) could be a method for increasing the amount of aryl carbon in PyC. Maximising the amount of aryl carbon could be beneficial for the overall PyC balance from fire, since more recalcitrant carbon (e.g. carbon with a higher aryl carbon content) that is not emitted to the atmosphere has been shown to have longer residence times in environmental media such as soils or sediments.

The need for integrated public health surveillance to address sexually transmitted and blood-borne syndemics.

A national approach to addressing sexually transmitted and blood-borne infections (STBBIs) was recently articulated in the Public Health Agency of Canada's new A Pan-Canadian Framework for Action: Reducing the health impact of sexually transmitted and blood-borne infections in Canada by 2030. This Framework promotes an integrated approach, with a focus on the key populations that are affected by overlapping epidemics (i.e., syndemics). We advance the idea that integrating surveillance would be helpful in characterizing and understanding the populations, locations, risk behaviours and other drivers that contribute to STBBI syndemics. The creation of matched or linked data systems that would allow routine reporting of integrated data is challenged by the technical barriers of integrating data silos as well as by the privacy and ethical considerations of merging sensitive individual-level data. Lessons can be learned from jurisdictions where an improved understanding of syndemics, through integrated STBBI surveillance, has led to more efficient and effective operational, program and policy decisions. Emerging enablers include the development of data standards and guidelines, investment in resources to overcome technical challenges and community engagement to support the ethical and non-stigmatizing use of integrated data. The Framework's call to action offers an opportunity for national discussion on priorities and resources needed to advance STBBI syndemic surveillance for local, regional and national reporting in Canada.

Economic evaluation of a publicly funded hepatitis A travel vaccination program in Ontario, Canada.

BACKGROUND: Hepatitis A virus (HAV) causes acute liver infection and is spread through the fecal-oral route. Travel to countries in HAV-endemic regions (e.g., Asia and Latin America) is a well-described risk factor for infection. Currently, Ontario publicly funds hepatitis A vaccination for some populations at high risk of HAV infection but not for all travellers to endemic countries. The objective of this study was to determine the cost-effectiveness of expanding publicly funded HAV vaccination to people planning travel to HAV-endemic regions, from the Ontario healthcare payer perspective. METHODS: We conducted a cost-utility analysis comparing an expanded high-risk publicly-funded hepatitis A vaccination program including funded vaccine for travellers to endemic regions to the current high risk program in Ontario. A Markov state transition model was developed, including six possible health states. Model parameters were informed through targeted literature searches and included hepatitis A disease probabilities, utilities associated with health states, health system expenditures, and vaccine costs. Future costs and health outcomes were discounted at 1.5%. Primary outcomes included cost, incremental cost-effectiveness ratio (ICER) and quality adjusted life years (QALYs) over a lifetime time horizon. We conducted one-way, two-way, and probabilistic sensitivity analysis. RESULTS: The expanded high risk HAV vaccine program provided few incremental health gains in the travel population (mean 0.000037 QALYs/person), at an incremental cost of $124.31. The ICER of the expanded program compared to status quo is $3,391,504/QALY gained. The conclusion of the model was robust to changes in key parameters across reasonable ranges. CONCLUSIONS: The expanded vaccination program substantially exceeds commonly accepted cost-effectiveness thresholds. Further research concerning possible cost-effective implementation of high-risk travel hepatitis A vaccination should focus on a more integrated understanding of the risk of acquiring hepatitis A during travel to endemic regions (e.g., purpose, length of stay).

The effect of fire affected Pinus radiata litter and char addition on soil nitrogen cycling.

In pine forest litters, decomposition rate is directly affected by the pathway the needle followed to the ground, whether that was via programmed apoptosis and abscission or via stress induced loss through branch damage or tree death. Stress induced losses may occur due to fire damage, which leads to a post-fire litter layer composed of non-senescent debris that fell during or after the event. This study investigates decomposition and nitrogen cycling in soils amended with two litters from Pinus radiata plantations that had different recent fire histories. Litters were incubated in the presence or absence of field collected char for up to 94 days. These soil treatments were analysed for microbial activity (soil respiration) and N pools (microbial, mineral, and potentially mineralisable). Soil and litter treatments were additionally incubated in the presence of ammonium nitrate solution to determine N absorption potential of the litters. Respiration was greatest in soils that received fire affected (FA) litter regardless of the presence or absence of char. Nitrogen pools were largely similar between the control (no litter) treatment and not fire affected (NFA) litter treatments. Measured N pools were exceedingly low (92% of samples <2 µg-N g soil-1 where detected) or not detectable (37% of samples below detection limits) in all FA litter treatments at most times. Char appeared inert throughout and had no effects on microbial activity or nitrogen cycling. This study indicates that fire affected pine litter collected four months post fire has strong N absorption properties with or without the presence of char. The presence of fire affected litter is likely to affect N availability for regeneration of forest growth.

Results from the third Scottish National Prevalence Survey: is a population health approach now needed to prevent healthcare-associated infections?

BACKGROUND: Healthcare-associated infections (HCAIs) are a major public health concern and a significant cause of morbidity and mortality. A robust and current evidence base that is specific to local, national and Europe-wide settings is necessary to inform the development of strategies to reduce HCAI and contain antimicrobial resistance. AIM: To measure the prevalence of HCAI and antimicrobial prescribing and identify key priority areas for interventions to reduce the burden of infection. METHODS: A national rolling point-prevalence survey (PPS) in National Health Service (NHS) acute, NHS non-acute, NHS paediatric, and independent hospitals was carried out between September and November 2016 using the European Centre for Disease Prevention and Control protocol designed for the European PPS. FINDINGS: The prevalence of HCAI was 4.6%, 2.7%, and 3.2% in acute adults, paediatric and non-acute patient groups, respectively. The most frequent HCAI types reported in adult patients were urinary tract infection and pneumonia. The prevalence of antimicrobial prescribing was 35.7%, 29.3%, and 13.8% in acute adults, paediatric, and non-acute patient groups, respectively. Respiratory, skin and soft tissue, gastrointestinal, and urinary tract infections were the most common infections being treated at the time of survey. CONCLUSION: HCAI continues to be a public health concern in Scotland. Urinary tract infection and pneumonia continue to place a significant burden on patients and on healthcare delivery, including those that develop in the community and require hospital admission. A broader population health approach which focuses on reducing the risk of infection upstream would reduce these infections in both community and hospital settings.

Characterization of highly multiplexed monolithic PET / gamma camera detector modules.

PET detectors use signal multiplexing to reduce the total number of electronics channels needed to cover a given area. Using measured thin-beam calibration data, we tested a principal component based multiplexing scheme for scintillation detectors. The highly-multiplexed detector signal is no longer amenable to standard calibration methodologies. In this study we report results of a prototype multiplexing circuit, and present a new method for calibrating the detector module with multiplexed data. A [Formula: see text] mm3 LYSO scintillation crystal was affixed to a position-sensitive photomultiplier tube with [Formula: see text] position-outputs and one channel that is the sum of the other 64. The 65-channel signal was multiplexed in a resistive circuit, with 65:5 or 65:7 multiplexing. A 0.9 mm beam of 511 keV photons was scanned across the face of the crystal in a 1.52 mm grid pattern in order to characterize the detector response. New methods are developed to reject scattered events and perform depth-estimation to characterize the detector response of the calibration data. Photon interaction position estimation of the testing data was performed using a Gaussian Maximum Likelihood estimator and the resolution and scatter-rejection capabilities of the detector were analyzed. We found that using a 7-channel multiplexing scheme (65:7 compression ratio) with 1.67 mm depth bins had the best performance with a beam-contour of 1.2 mm FWHM (from the 0.9 mm beam) near the center of the crystal and 1.9 mm FWHM near the edge of the crystal. The positioned events followed the expected Beer-Lambert depth distribution. The proposed calibration and positioning method exhibited a scattered photon rejection rate that was a 55% improvement over the summed signal energy-windowing method.

Universal videolaryngoscopy: a structured approach to conversion to videolaryngoscopy for all intubations in an anaesthetic and intensive care department.

BACKGROUND: Videolaryngoscopy (VL) is increasingly used, but not yet routine practice, for tracheal intubation. Few departments formally trial equipment before adopting it into practice. We describe the decision-making and implementation processes that our department used when introducing universal VL, with the C-MAC© (Karl Storz, Germany), throughout our anaesthesia and intensive care departments. METHODS: We used a structured process to assess the feasibility of a change to universal VL. After departmental training, we undertook a 2 month trial period of mandating VL for all adult in-theatre intubations. Thereafter, VL remained widely available, but not mandated. We regularly surveyed anaesthetists and anaesthetic assistants to evaluate departmental opinion regarding the introduction of universal VL. RESULTS: Before the trial period, one-third of anaesthetists judged that universal VL would be of overall benefit to patient safety, team dynamics, and quality of care. Reservations from both junior and senior anaesthetists focused on training concerns. Support for a changeover to VL, amongst both anaesthetists and anaesthetic assistants, increased throughout the trial period. Six months after the 2 month trial, support had grown further and was almost unanimous. Anaesthetists reported significant benefits in clinical performance, teaching, and human factors, especially teamwork and situation awareness. CONCLUSIONS: Performing a formal and prolonged trial of mandatory VL in theatre led to changes in perceptions and departmental consensus. As a result of the trial, the department agreed to the use of C-MAC© videolaryngoscopy as the default intubation technique throughout theatres and intensive care, with removal of standard Macintosh laryngoscopes from routine use.

Outbreak of Salmonella Reading in persons of Eastern Mediterranean origin in Canada, 2014-2015.

BACKGROUND: Salmonella Reading (S. Reading) is a rare serotype of Salmonella subspecies (spp.) in Canada with less than nine cases reported each year (2011-2013). An increase in S. Reading was identified in several Canadian provinces in early 2015, prompting the initiation of a national outbreak investigation. OBJECTIVES: To describe a multi-provincial S. Reading outbreak in Canada that affected over 30 people. METHODS: Cases were defined as laboratory-confirmed S. Reading with related pulsed-field gel electrophoresis (PFGE) patterns. Onset dates were between November 2014 and September 2015.​: Early in the investigation, investigators noted cases were predominantly of Eastern Mediterranean origin, mainly Afghan and Lebanese and many of those affected had consumed food items not typically captured on standard enteric outbreak hypothesis-generating questionnaires. An open-ended three day food consumption survey was conducted with a convenience sample of community informants to better understand food preferences of the affected ethnocultural populations. Results of the survey were used to design a focused questionnaire for case re-interviews and subsequent outbreak cases. Public health investigators obtained food samples from case homes and relevant food premises. Food safety authorities conducted traceback of suspected food items and collected food samples for laboratory testing. RESULTS: There were 31 confirmed cases (Ontario=23, Alberta=7, New Brunswick=1) and three probable (Ontario=2, Alberta=1) cases of S. Reading identified as part of the outbreak. The median age was 31 years (range less than one to 85 years) and 53% (18/34) of cases were female. Seven cases were hospitalized. No deaths were reported. Most cases were of Eastern Mediterranean origin (n=23) or had reported consuming Eastern Mediterranean foods (n=3). The predominant ethnic origins reported by cases were Afghan in Ontario (n=12) and Lebanese in Alberta (n=3). Genetic similarity of clinical isolates was further confirmed using whole genome sequencing.​: Three ethnic bakeries were identified as possible common exposures for the cases; however, traceback of foods of interest from these bakeries did not identify a common supplier and the source of the illness was not identified. In total, 227 food samples from retail premises (n=142), restaurants (n=13) and case homes (n=72) were tested; two food samples, kalonji seeds and tahini, were positive for S. Ruiru and S. Meleagridis. These products were recalled from the marketplace. CONCLUSION: Despite extensive epidemiological, microbiological and food traceback investigations, a common source was not identified for this S. Reading outbreak. Challenges included lack of familiarity with the food items consumed in affected ethnocultural groups, as well as a lack of background data on expected food exposures in the outbreak population. Engaging local partners helped build understanding of food preferences in affected communities. Given Canada's ethnic and cultural diversity, culturally competent approaches to enteric outbreak investigations and food consumption surveys may be useful.

Public health surveillance for the Toronto 2015 Pan/Parapan American Games.

BACKGROUND: Public health surveillance for previous Olympic and Paralympic Games have been described in the literature, but surveillance for regional, multisport events on a smaller scale have rarely been explored. OBJECTIVE: To describe the public health surveillance planning, implementation, results, and lessons learned from the 2015 Pan/Parapan American Games in Toronto, Ontario, Canada. INTERVENTION: Public health surveillance planning for the Games began two years in advance and involved local, provincial and federal partners, primarily focusing on infectious disease. From June to August, 2015, enhanced public health surveillance was conducted to support situational awareness and to facilitate the detection of infectious diseases and outbreaks, environmental health hazards and impacts and other major health events. OUTCOMES: No major public health incidents occurred that were associated with or a result of hosting the Games. There were two cases of reportable infectious diseases associated with the Games, and 18 public health investigations involving Games-accredited individuals (six related to vaccine-preventable diseases and 12 related to gastrointestinal illnesses or food/water safety violations). Enhanced communication mechanisms, rather than routine and syndromic surveillance systems, were the primary sources of initial notification to surveillance partners on investigations. CONCLUSION: Working with its partners, Ontario created a robust public health surveillance system for the 2015 Pan/Parapan American Games. Lessons learned, as well as the relationships and capacity developed through this experience, will be applied towards public health surveillance planning for future events.

Theory analysis of the Dental Hygiene Human Needs Conceptual Model.

PURPOSE: Theories provide a structural knowing about concept relationships, practice intricacies, and intuitions and thus shape the distinct body of the profession. Capturing ways of knowing and being is essential to any professions' practice, education and research. This process defines the phenomenon of the profession - its existence or experience. Theory evaluation is a systematic criterion-based assessment of a specific theory. This study presents a theory analysis of the Dental Hygiene Human Needs Conceptual Model (DH HNCM). METHODS: Using the Walker and Avant Theory Analysis, a seven-step process, the DH HNCM, was analysed and evaluated for its meaningfulness and contribution to dental hygiene. The steps include the following: (i) investigate the origins; (ii) examine relationships of the theory's concepts; (iii) assess the logic of the theory's structure; (iv) consider the usefulness to practice; (v) judge the generalizability; (vi) evaluate the parsimony; and (vii) appraise the testability of the theory. FINDINGS: Human needs theory in nursing and Maslow's Hierarchy of Need Theory prompted this theory's development. The DH HNCM depicts four concepts based on the paradigm concepts of the profession: client, health/oral health, environment and dental hygiene actions, and includes validated eleven human needs that evolved overtime to eight. It is logical, simplistic, allows scientific predictions and testing, and provides a unique lens for the dental hygiene practitioner. With this model, dental hygienists have entered practice, knowing they enable clients to meet their human needs. CONCLUSION: For the DH HNCM, theory analysis affirmed that the model is reasonable and insightful and adds to the dental hygiene professions' epistemology and ontology.

Evaluation of event position reconstruction in monolithic crystals that are optically coupled.

A PET detector featuring a pseudo-monolithic crystal is being developed as a more cost-effective alternative to a full monolithic crystal PET detector. This work evaluates different methods to localize the scintillation events in quartered monolithic crystals that are optically coupled. A semi-monolithic crystal assembly was formed using four 26 × 26 × 10 mm3 LYSO crystals optically coupled together using optical adhesive, to mimic a 52 × 52 × 10 mm3 monolithic crystal detector. The crystal assembly was coupled to a 64-channel multi-anode photomultiplier tube using silicon grease. The detector was calibrated using a 34 × 34 scan grid. Events were first filtered and depth separated using a multi-Lorentzian fit to the collected light distribution. Next, three different techniques were explored to generate the look up tables for the event positioning. The first technique was 'standard interpolation' across the interface. The second technique was 'central extrapolation', where a bin was placed at the midpoint of the interface and events positioned within the interface region were discarded. The third technique used a 'central overlap' method where an extended region was extrapolated at each interface. Events were then positioned using least-squares minimization and maximum likelihood methods. The least-squares minimization applied to the look up table generated with the standard interpolation technique had the best full width at half maximum (FWHM) intrinsic spatial resolution and the lowest bias. However, there were discontinuities in the event positioning that would most likely lead to artifacts in the reconstructed image. The central extrapolation technique also had discontinuities and a 30% sensitivity loss near the crystal-crystal interfaces. The central overlap technique had slightly degraded performance metrics, but it still provided ~2.1 mm intrinsic spatial resolution at the crystal-crystal interface and had a symmetric and continuously varying response function. Results using maximum likelihood positioning were similar to least-squares minimization for the central overlap data.

Are housing tenure and car access still associated with health? A repeat cross-sectional study of UK adults over a 13-year period.

BACKGROUND: It is usually assumed that housing tenure and car access are associated with health simply because they are acting as markers for social class or income and wealth. However, previous studies conducted in the late 1990s found that these household assets were associated with health independently of social class and income. Here, we set out to examine if this is still the case. METHODS: We use data from our 2010 postal survey of a random sample of adults (n=2092) in 8 local authority areas in the West of Scotland. Self-reported health measures included limiting longstanding illness (LLSI), general health over the last year and the Hospital Anxiety and Depression Scale. RESULTS: We found a statistically significant relationship between housing tenure and all 4 health measures, regardless of the inclusion of social class or income as controls. Compared with owner occupiers, social renters were more likely to report ill-health (controlling for social class-LLSI OR: 3.24, general health OR: 2.82, anxiety η2: 0.031, depression η2: 0.048, controlling for income-LLSI OR: 3.28, general health OR: 2.82, anxiety η2: 0.033, depression η2: 0.057) (p<0.001 for all models). Car ownership was independently associated with depression and anxiety, with non-owners at higher risk of both (controlling for income-anxiety η2: 0.010, depression η2: 0.023, controlling for social class-anxiety η2: 0.013, depression η2: 0.033) (p<0.001 for all models). CONCLUSIONS: Our results show that housing tenure and car ownership are still associated with health, after taking known correlates (age, sex, social class, income) into account. Further research is required to unpack some of the features of these household assets such as the quality of the dwelling and access to and use of different forms of transport to determine what health benefits or disbenefits they may be associated with in different contexts.

Interventions for treating oral leukoplakia to prevent oral cancer.

BACKGROUND: Oral leukoplakia is a relatively common oral lesion that, in a small proportion of people, precedes the development of oral cancer. Most leukoplakias are asymptomatic; therefore, the primary objective of treatment should be to prevent onset of cancer. This review updates our previous review, published in 2006. OBJECTIVES: To assess the effectiveness, safety and acceptability of treatments for leukoplakia in preventing oral cancer. SEARCH METHODS: We searched the following electronic databases: Cochrane Oral Health's Trials Register (to 16 May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 4), MEDLINE Ovid (1946 to 16 May 2016), Embase Ovid (1980 to 16 May 2016) and CancerLit via PubMed (1950 to 16 May 2016). We searched the metaRegister of Controlled Trials (to 10 February 2015), ClinicalTrials.gov (to 16 May 2016) and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (to 16 May 2016). We placed no restrictions on the language or date of publication when searching electronic databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled people with a diagnosis of oral leukoplakia and compared any treatment versus placebo or no treatment. DATA COLLECTION AND ANALYSIS: We collected data using a data extraction form. Oral cancer development, demonstrated by histopathological examination, was our primary outcome. Secondary outcomes were clinical resolution of the lesion, improvement of histological features and adverse events. We contacted trial authors for further details when information was unclear. When valid and relevant data were available, we conducted a meta-analysis of the data using a fixed-effect model when we identified fewer than four studies with no heterogeneity. For dichotomous outcomes, we calculated risk ratios (RRs) and 95% confidence intervals (CIs). We assessed risk of bias in studies by using the Cochrane tool. We assessed the overall quality of the evidence by using standardised criteria (Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE)). MAIN RESULTS: We included 14 studies (909 participants) in this review. Surgical interventions, including laser therapy and cryotherapy, have never been studied by means of an RCT that included a no treatment or placebo arm. The included trials tested a range of medical and complementary treatments, in particular, vitamin A and retinoids (four studies); beta carotene or carotenoids (three studies); non-steroidal anti-inflammatory drugs (NSAIDs), specifically ketorolac and celecoxib (two studies); herbal extracts (four studies), including tea components, a Chinese herbal mixture and freeze-dried black raspberry gel; bleomycin (one study); and Bowman-Birk inhibitor (one study).We judged one study to be at low risk of bias, seven at unclear risk and six at high risk. In general, we judged the overall quality of the evidence to be low or very low, so findings are uncertain and further research is needed.Five studies recorded cancer incidence, only three of which provided useable data. None of the studies provided evidence that active treatment reduced the risk of oral cancer more than placebo: systemic vitamin A (RR 0.11, 95% CI 0.01 to 2.05; 85 participants, one study); systemic beta carotene (RR 0.71, 95% CI 0.24 to 2.09; 132 participants, two studies); and topical bleomycin (RR 3.00, 95% CI 0.32 to 27.83; 20 participants, one study). Follow-up ranged between two and seven years.Some individual studies suggested effectiveness of some proposed treatments, namely, systemic vitamin A, beta carotene and lycopene, for achieving clinical resolution of lesions more often than placebo. Similarly, single studies found that systemic retinoic acid and lycopene may provide some benefit in terms of improvement in histological features. Some studies also reported a high rate of relapse.Side effects of varying severity were often described; however, it seems likely that interventions were well accepted by participants because drop-out rates were similar between treatment and control groups. AUTHORS' CONCLUSIONS: Surgical treatment for oral leukoplakia has not been assessed in an RCT that included a no treatment or placebo comparison. Nor has cessation of risk factors such as smoking been assessed. The available evidence on medical and complementary interventions for treating people with leukoplakia is very limited. We do not currently have evidence of a treatment that is effective for preventing the development of oral cancer. Treatments such as vitamin A and beta carotene may be effective in healing oral lesions, but relapses and adverse effects are common. Larger trials of longer duration are required to properly evaluate the effects of leukoplakia treatments on the risk of developing oral cancer. High-quality research is particularly needed to assess surgical treatment and to assess the effects of risk factor cessation in people with leukoplakia.

Young people's exposure to point-of-sale tobacco products and promotions.

OBJECTIVES: Point of sale (POS) displays are one of the most important forms of tobacco marketing still permitted in many countries. Reliable methods for measuring exposure to such displays are needed in order to assess their potential impact, particularly on smoking attitudes and uptake among young people. In this study we use a novel method for evaluating POS exposure based on young people's use of retail outlets and recall of tobacco displays and observational data on the characteristics of displays. STUDY DESIGN: Observational audit of retail outlets (n = 96) and school-based pupil survey (n = 1482) in four Scottish communities reflecting different levels of social deprivation and urbanisation, conducted in 2013 before legislation to remove POS displays was implemented in supermarkets. METHODS: Measures were taken of: visibility and placement of tobacco displays; internal and external advertising; display unit size, branding and design; visibility of pack warnings; proximity of tobacco products to products of potential interest to children and young people; pupils' self-reported frequency of visiting retail outlets; and pupils' recall of tobacco displays. Variation in POS exposure across social and demographic groups was assessed. RESULTS: Displays were highly visible within outlets and, in over half the stores, from the public footway outside. Tobacco products were displayed in close proximity to products of interest to children (e.g. confectionery, in 70% of stores). Eighty percent of pupils recalled seeing tobacco displays, with those from deprived areas more likely to recall displays in small shops. When confectioners, tobacconists and newsagents (CTNs) and grocery/convenience stores (two of the outlet types most often visited by young people) were examined separately, average tobacco display unit sizes were significantly larger in those outlets in more deprived areas. CONCLUSIONS: POS displays remain a key vector in most countries for advertising tobacco products, and it is important to develop robust measures of exposure. The data reported in this paper provide a baseline measure for evaluating the efficacy of legislation prohibiting such displays.

E-cigarette marketing in UK stores: an observational audit and retailers' views.

OBJECTIVES: To explore how e-cigarettes are being promoted at point of sale in the UK and how retailers perceive market trends. SETTING: Fixed retail outlets subject to a ban on the display of tobacco products. PARTICIPANTS: Observational audit of all stores selling tobacco products (n=96) in 4 Scottish communities, conducted over 2 waves 12 months apart (2013-2014), and qualitative interviews with small retailers (n=25) in 4 matched communities. PRIMARY AND SECONDARY OUTCOME MEASURES: The audit measured e-cigarette display characteristics, advertising materials and proximity to other products, and differences by area-level disadvantage. Interviews explored retailers' perceptions of e-cigarette market opportunities and risks, and customer responses. RESULTS: The number of e-cigarette point-of-sale display units and number of brands displayed increased between waves. E-cigarettes were displayed close to products of interest to children in 36% of stores. Stores in more affluent areas were less likely to have external e-cigarette advertising than those in deprived areas. Although e-cigarettes delivered high profit margins, retailers were confused by the diversity of brands and products, and uncertain of the sector's viability. Some customers were perceived to purchase e-cigarettes as cessation aids, and others, particularly low-income smokers, as a cheaper adjunct to conventional tobacco. CONCLUSIONS: E-cigarette point-of-sale displays and number of brands displayed increased over 12 months, a potential cause for concern given their lack of regulation. Further scrutiny is needed of the content and effects of such advertising, and the potentially normalising effects of placing e-cigarettes next to products of interest to children.

Accuracy of preoperative CT T staging of renal cell carcinoma: which features predict advanced stage?

AIMS: To characterise CT findings in renal cell carcinoma (RCC), and establish which features are associated with higher clinical T stage disease, and to evaluate patterns of discrepancy between radiological and pathological staging of RCC. MATERIALS AND METHODS: Preoperative CT studies of 92 patients with 94 pathologically proven RCCs were retrospectively reviewed. CT stage was compared with pathological stage using the American Joint Committee on Cancer (AJCC), 7(th) edition (2010). The presence or absence of tumour necrosis, perinephric fat standing, thickening of Gerota's fascia, collateral vessels were noted, and correlated with pT stage. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) for predicting pT stage ≥pT3a were derived separately for different predictors using cross-tabulations. RESULTS: Twenty-four lesions were pathological stage T1a, 21 were T1b, seven were T2a, 25 were T3a, 11 were T3b, four were T3c, and two were T4. There were no stage T2b. Sixty-three (67%) patients had necrosis, 27 (29%) thickening of Gerota's fascia (1 T1a), 25 had collateral vessels (0 T1a), 28 (30%) had fat stranding of <2 mm, 20 (21%) of 2-5mm and one (1%) of >5 mm. For pT stage ≥pT3a, the presence of perinephric fat stranding had a sensitivity, specificity, PPV and NPV of 74%, 65%, 63%, and 76%, respectively. Presence of tumour necrosis had a sensitivity, specificity, PPV, and NPV of 81%, 44%, 54%, and 72%, respectively. Thickening of Gerota's fascia had a sensitivity, specificity, PPV, and NPV of 52%, 90%, 81% and 70%, respectively; and enlarged collateral vessels had a sensitivity, specificity, PPV, and NPV value of 52%, 94%, 88%, and 71% respectively. CONCLUSION: The presence of perinephric stranding and tumour necrosis were not reliable signs for pT stage >T3a. Thickening of Gerota's fascia and the presence of collateral vessels in the peri- or paranephric fat had 90% and 94% specificity, with 82% and 88% PPV, respectively, for the presence of tumour stage for pT stage >T3a. These are considered reliable signs of locally advanced renal cancer.