Air pollution and public health vulnerabilities, susceptibilities and inequalities in Wales, UK.

BACKGROUND: Outdoor air pollution is the largest environmental risk to health. Air pollution, deprivation and poor health status are inextricably linked; highlighting issues of environmental injustice, social and health inequalities. METHODS: Air pollution (nitrogen dioxide, NO2 and fine particulate matter, PM2.5), population and deprivation data were identified at Lower Super Output Area level in Wales, UK, for 2012-18. Air pollution data were categorized according to different air pollution concentrations. Population and deprivation data were considered simultaneously to describe population vulnerabilities, susceptibilities and inequalities. Simple statistical analyses were performed using a difference in proportions method with 95% confidence intervals. RESULTS: Over time, the majority of Welsh people transitioned to living in areas of lower NO2 and PM2.5 pollution. Areas of worse air pollution comprised more young people than people aged 65+; both populations are known to be susceptible to air pollution exposure. By 2018, significant socioeconomic inequality gaps were found where 'most deprived' population groups for both pollutants experienced greater disadvantage. CONCLUSION: Air quality in Wales is improving. However, local-level variations in exposure risk still exist. System-wide action must ensure that air quality improvement-related benefits are equitable and acknowledge current evidence about the harms that even low levels of air pollution can have on health.

Fatal Unintentional Non-Fire Related Carbon Monoxide Poisoning: Data from Narrative Verdicts in England and Wales, 1998-2019.

Unintentional non-fire related (UNFR) carbon monoxide (CO) poisoning continues to cause fatalities. The narrative verdicts from coroners concerning fatal UNFR CO poisoning in England and Wales, 1998-2019, were collated by the Office for National Statistics. Search terms related to CO exposure were used to obtain information regarding the circumstances of death. Findings were grouped by the location of death, the source of CO, and the reason or behaviour underlying the exposure. There were 750 deaths (77% male). The annual number of deaths decreased over the period studied. Two thirds (68%) of the deaths occurred in the autumn or winter. From the records with information, 59% of deaths occurred within a dwelling (67% male). Males also predominated deaths within vehicles (91%) and garages or outbuildings (95%). From the deaths with information, domestic piped gas was the most common source of CO (36%) and the most frequent underlying factor was inadequate ventilation of exhaust gases (39%, 91% male). Despite the decrease in the annual number of deaths over the study period, there remains a clear need for measures that raise awareness of the dangers of CO poisoning, especially amongst men working alone in garages or outbuildings. Education campaigns and fitting and maintaining CO alarms in high-risk areas should be encouraged.

Epidemiology and mapping of child road casualties.

BACKGROUND: Paediatric trauma following road traffic collisions (RTCs) represents a significant public health burden. This study aims to influence road safety in Wales. METHODS: Police (STATS19) and healthcare databases covering all or part of Wales were analysed, compared and mapped from 2017 to 2019 for RTCs involving children aged 0-16 years. RESULTS: STATS19 under-reports RTCs, recording 1859 road traffic injuries (RTIs) for all Wales compared with 1170 RTIs at one tertiary hospital in South East Wales. Boys aged 11-16 years had the highest injury rates (92.2 per 100 000 population). Injuries peaked at school journey times. The rate ratio of injury was 2.0 (95% CI 1.7 to 2.4) for the most deprived compared with the least deprived areas. CONCLUSION: Improvements in data quality are essential to influence road policy. Improved road safety is needed in all communities but must be further enhanced in the most deprived areas, where the burden of injury is highest.

Identifying the Coping Strategies of Nonoffending Pedophilic and Hebephilic Individuals From Their Online Forum Posts.

Individuals who identify as pedophilic or hebephilic, and who do not offend, are increasingly visible in online discourse and as a focus of research. Developing knowledge about this population will offer insights into their psychological needs and, potentially, into the mechanisms and strategies individuals use to live offense-free lives. This study examined coping strategies among members of an online forum supporting pedohebephilic individuals who do not wish to offend. Forum users' posts were analyzed using thematic analysis. Eleven themes emerged, which were classifiable into three superordinate themes around (a) the acceptance of pedophilia, (b) strategies to stay safe, and (c) dealing with sexual arousal. These themes offer insight into the varying strategies used by these individuals to cope with stress and/or to remain offense-free. Understanding whether these strategies are adaptive or maladaptive may help develop better support services for those who have not offended and may inform prevention efforts.

Stabilizing Hydrogen Adsorption through Theory-Guided Chalcogen Substitution in Chevrel-Phase Mo6X8 (X=S, Se, Te) Electrocatalysts.

In this work, we implement a facile microwave-assisted synthesis method to yield three binary Chevrel-Phase chalcogenides (Mo6X8; X = S, Se, Te) and investigate the effect of increasing chalcogen electronegativity on hydrogen evolution catalytic activity. Density functional theory predictions indicate that increasing chalcogen electronegativity in these materials will yield a favorable electronic structure for proton reduction. This is confirmed experimentally via X-ray absorption spectroscopy as well as traditional electrochemical analysis. We have identified that increasing the electronegativity of X in Mo6X8 increases the hydrogen adsorption strength owing to a favorable shift in the p-band position as well as an increase in the Lewis basicity of the chalcogen, thereby improving hydrogen evolution reaction energetics. We find that Mo6S8 exhibits the highest hydrogen evolution activity of the Mo6X8 series of catalysts, requiring an overpotential of 321 mV to achieve a current density of 10 mA cm-2ECSA, a Tafel slope of 74 mV per decade, and an exchange current density of 6.01 × 10-4 mA cm-2ECSA. Agreement between theory and experiment in this work indicates that the compositionally tunable Chevrel-Phase chalcogenide family is a promising framework for which electronic structure can be predictably modified to improve catalytic small-molecule reduction reactivity.

If electric cars are the answer, what was the question?

INTRODUCTION: Roads facilitate trade, development and communication, as well as spread illness and disease, but since mass car use began, the disbenefits, including injuries, pollution and physical inactivity have been significantly magnified. Electric cars are now being seen by many as the solution to the problems associated with internal combustion engine cars. SOURCES OF DATA: This article reviews existing literature to determine the extent to which a switch to electrification can solve many of the problems that cars have wrought. AREAS OF AGREEMENT: It concludes that there may be some benefits in rural areas, where public transport is poor. AREAS OF CONTROVERSY: However, it also argues that even in rural areas it may be better to invest in public transport for many, rather than electric car infrastructure for some. It is clear that even for air quality, where electric cars are suggested to offer benefits these are unlikely to be as great as has been suggested. Overall, the negative health consequences of electric cars seem likely to be at least those of internal combustion engine cars.

Girls crash too: trends in single vehicle crash rates in young and adult, male and female drivers.

Young adult drivers (YADs) are over-represented in crashes mainly because of their age and inexperience. Studying single vehicle crashes by age and sex may identify new approaches to intervention. In 2014, male YAD (17-19 years) crash casualty rates were 11.4 times higher than older drivers (30-59 years), compared with 17.6 times higher in 2005, and 1.9 times female YAD, compared with 2.5 times higher in 2005. Crash casualty rates involving male and female YADs are declining. Action is needed to address YAD crash casualties involving both males and females. Graduated driver licensing is a universal approach that has the potential to do this.

Twenty miles per hour speed limits: a sustainable solution to public health problems in Wales.

BACKGROUND: Prevention, rather than treatment, is the key to longer healthier lives. Identifying interventions that will impact positively on road traffic injuries, air quality and encourage active travel is a significant public health challenge. This paper aimed to explore whether 20 mph limits could be useful in achieving this. METHODS: Research evidence was reviewed to identify the effect of 20 mph zones and limits on health and well-being. The evidence was then used to estimate the effect of a change to a 20 mph limit on road traffic casualties and air pollution. It was then mapped against the seven goals of the Well-being of Future Generations Act (2015). RESULTS: If all current 30 mph limit roads in Wales became 20 mph limits, it is estimated that 6-10 lives would be saved and 1200-2000 casualties avoided each year, at a value of prevention of £58M-£94M. In terms of air pollution, deaths attributed to nitrogen dioxide (NO2) may increase by 63, and years of life lost by 753. However, deaths attributed to particulates (PM2.5) may decrease by 117 and years of life lost by 1400. Evidence review suggests benefits in terms of road traffic casualties, air quality, active travel, noise pollution, greater social inclusion, greater community cohesion and local business viability. CONCLUSIONS: Road traffic injuries, air pollution and obesity are an inter-related, interdependent triad. The challenge facing public health today is identifying robust interventions that will have positive effects on all three as a minimum; default 20 mph limits is the solution to increasing public health problems in Wales.

Deaths of teenagers in car crashes: a child death review.

MVCs are a leading cause of death and disability for teenagers. In Wales, a child death review process has been established to carry out thematic reviews of deaths; this approach is believed to highlight opportunities for prevention that individual case review could not. Cases were 13-year-old to 17-year-old Welsh residents who died as car drivers or passengers between 1 January 2006 and 31 December 2010. An expert panel was convened to review these cases. 28 MVCs occurred and 34 13-17 year olds died; 24 males, 10 females. 51 vehicles were involved; 23 driven by 17-year-old to 19-year-old males. 19 of the 28 MVCs occurred between 21:00 and 05:00. The risk factors identified were consistent with global research on MVC deaths and injuries to teenagers. However, there is a lack of effective interventions to tackle these in the UK. It is recommended that the implementation of Graduated Driver Licensing is considered.

All Wales Injury Surveillance System revised: development of a population-based system to evaluate single-level and multilevel interventions.

BACKGROUND: Injury surveillance has been established since the 1990s, but is still largely based upon single-source data from sentinel sites. The growth of electronic health records and developments in privacy protecting linkage technologies provide an opportunity for more sophisticated surveillance systems. OBJECTIVE: To describe the evolution of an injury surveillance system to support the evaluation of interventions, both simple and complex in terms of organisation. METHODS: The paper describes the evolution of the system from one that relied upon data only from emergency departments to one that include multisource data and are now embedded in a total population privacy protecting data linkage system. Injury incidence estimates are compared by source and data linkage used to aid understanding of data quality issues. Examples of applications, challenges and solutions are described. RESULTS: The age profile and estimated incidence of injuries recorded in general practice, emergency departments and hospital admissions differ considerably. Data linkage has enabled the evaluation of complex interventions and measurement of longer-term impact of a wide range of exposures. CONCLUSIONS: Embedding injury surveillance within privacy protecting data linkage environment can transform the utility of a traditional single-source surveillance system to a multisource system. It also facilitates greater involvement in the evaluation of simple and complex healthcare and non-healthcare interventions and contributes to the growing evidence basis underlying the science of injury prevention and control.

Activation of Akt at T308 and S473 in alcohol, tobacco and HPV-induced HNSCC: is there evidence to support a prognostic or diagnostic role?

BACKGROUND: Tobacco, alcohol and HPV infection are associated with increased risk of HNSCC. However, little is known about the underlying signaling events influencing risk. We aimed to investigate the relationship between these risk factors and Akt phosphorylation, to determine prognostic value. METHOD: VEGF-positive HNSCC biopsies, with known HPV status, were analyzed by immunohistochemistry (IHC) for Akt, phosphorylated at residues S473 and T308. Comparisons between the tissues were carried out using a Mann-Whitney U test. Associations between the variables and continuous immunohistochemical parameters were evaluated with general linear models. Patient characteristics and pAkt IHC score were analyzed for possible association with overall survival by Cox proportional hazard models. RESULTS: Immunohistochemistry revealed that cancer patients had significantly higher levels of pAkt T308 than S473 (P < 0.001). Smoking and alcohol were found to be independent risk factors for Akt phosphorylation at T308 (P = 0.022 and 0.027, respectively). Patients with tumors positive for HPV or pAkt S473 had a poorer prognosis (P = 0.005, and 0.004, respectively). Patients who were heavy drinkers were 49 times more likely to die than non-drinkers (P = 0.003). Patients with low pAkt T308 were more likely to be HPV positive (P = 0.028). Non-drinkers were also found to have lower levels of pAkt T308 and were more likely to have tumors positive for HPV than heavy drinkers (P = 0.044 and 0.007, respectively). CONCLUSION: This study suggests different mechanisms of carcinogenesis are initiated by smoking, alcohol and HPV. Our data propose higher phosphorylation of Akt at T308 as a reliable biomarker for smoking and alcohol induced HNSCC progression and higher phosphorylation of Akt at S473 as a prognostic factor for HNSCC.

Is there a pAkt between VEGF and oral cancer cell migration?

The PI3K-Akt signalling pathway is a well-established driver of cancer progression. One key process promoted by Akt phosphorylation is tumour cell motility; however the mechanism of VEGF-induced Akt phosphorylation leading to motility remains poorly understood. Previously, we have shown that Akt phosphorylation induced by different factors causes both stimulation and inhibition of motility in different cell types. However, differential phosphorylation of Akt at T308 and S473 residues by VEGF and its role in head and neck cancer cell motility and progression is unknown. The cell lines investigated in this study exhibited a change in phosphorylation of Akt in response to VEGF. However, in terms of motility, VEGF stimulated oral cancer and its associated cell lines, but not normal keratinocytes or oral mucosal fibroblasts. The addition of a PI3 kinase and mTOR inhibitor, inhibited the phosphorylation of Akt and also effectively blocked VEGF-induced oral cancer cell motility, whereas only the PI3 kinase inhibitor blocked oral cancer associated fibroblast cell motility. This study therefore discloses that two different mechanisms of Akt phosphorylation control the motility potential of different cell lines. Akt phosphorylated at both residues controls oral cancer cell motility. Furthermore, immunohistochemical analysis of VEGF positive human head and neck tumour tissues showed a significant increase in Akt phosphorylation at the T308 residue, suggesting that pAkt T308 may be associated with tumour progression in vivo.

'Do as we say, not as we do:' a cross-sectional survey of injuries in injury prevention professionals.

BACKGROUND: As the leading cause of death and among the top causes of hospitalisation in Canadians aged 1-44 years, injury is a major public health concern. Little is known about whether knowledge, training and understanding of the underlying causes and mechanisms of injury would help with one's own prevention efforts. Based on the Theory of Planned Behaviour, we hypothesised that injury prevention professionals would experience fewer injuries than the general population. METHODS: An online cross-sectional survey was distributed to Canadian injury prevention practitioners, researchers and policy makers to collect information on medically attended injuries. Relative risk of injury in the past 12 months was calculated by comparing the survey data with injury incidence reported by a comparable subgroup of adults from the (Canadian Community Health Survey (CCHS)) from 2009 to 2010. RESULTS: We had 408 injury prevention professionals complete the survey: 344 (84.5%) women and 63 (15.5%) men. In the previous 12 months, 86 individuals reported experiencing at least one medically attended injury (21,235 people per 100,000 people); with sports being the most common mechanism (41, 33.6%). Fully 84.8% individuals from our sample believed that working in the field had made them more careful. After accounting for age distribution, education level and employment status, injury prevention professionals were 1.69 (95% CI 1.41 to 2.03) times more likely to be injured in the past year. INTERPRETATION: Despite their convictions of increasing their own safety behaviour and that of others, injury prevention professionals' knowledge and training did not help them prevent their own injuries.

The control and importance of hyaluronan synthase expression in palatogenesis.

Development of the lip and palate involves a complex series of events that requires the close co-ordination of cell migration, growth, differentiation, and apoptosis. Palatal shelf elevation is considered to be driven by regional accumulation and hydration of glycosoaminoglycans, principally hyaluronan (HA), which provides an intrinsic shelf force, directed by components of the extracellular matrix (ECM). During embryogenesis, the extracellular and pericellular matrix surrounding migrating and proliferating cells is rich in HA. This would suggest that HA may be important in both shelf growth and fusion. TGFß3 plays an important role in palatogenesis and the corresponding homozygous null (TGFß3(-/-)) mouse, exhibits a defect in the fusion of the palatal shelves resulting in clefting of the secondary palate. TGFß3 is expressed at the future medial edge epithelium (MEE) and at the actual edge epithelium during E14.5, suggesting a role for TGFß3 in fusion. This is substantiated by experiments showing that addition of exogenous TGFß3 can "rescue" the cleft palate phenotype in the null mouse. In addition, TGFß1 and TGFß2 can rescue the null mouse palate (in vitro) to near normal fusion. In vivo a TGFß1 knock-in mouse, where the coding region of the TGFß3 gene was replaced with the full-length TGFß1 cDNA, displayed complete fusion at the mid portion of the secondary palate, whereas the anterior and posterior regions failed to fuse appropriately. We present experimental data indicating that the three HA synthase (Has) enzymes are differentially expressed during palatogenesis. Using immunohistochemistry (IHC) and embryo sections from the TGFß3 null mouse at days E13.5 and E14.5, it was established that there was a decrease in expression of Has2 in the mesenchyme and an increase in expression of Has3 in comparison to the wild-type mouse. In vitro data indicate that HA synthesis is affected by addition of exogenous TGFß3. Preliminary data suggests that this increase in HA synthesis, in response to TGFß3, is under the control of the PI3kinase/Akt pathway.

Reducing young driver crash casualties in Great Britain - use of routine police crash data to estimate the potential benefits of graduated driver licensing.

Crashes involving young drivers (YD) cause significant morbidity and mortality in Great Britain (GB). Graduated Driver Licensing (GDL) is used in some countries to address this. This study assessed potential casualty and cost savings of possible GDL programmes in GB. Police road crash data were analysed to identify YD crashes at night or while carrying passengers. These data were then used to estimate the potential effects of GDL. 314,561 casualties and 3469 fatalities occurred in YD crashes. 25.1% of YD crashes occurred between 9 pm and 6 am and 24.4% occurred with a 15- to 24-year old passenger in the car. A 'strict' form of GDL in GB (night time restriction 9 pm-6 am, no 15-24 year old passengers) with 50% compliance would prevent 114 deaths and 872 serious casualties each year. The estimated value of prevention is £424M pa. A 'less strict' form of GDL (night time restriction 10 pm-5 am, maximum of one 15-19 year old passenger) with 50% compliance would prevent 81 deaths and 538 serious injuries. The estimated value of prevention is £273M pa. Implementing GDL in GB could save significant numbers of lives. Public health organisations have a duty to advocate for such legislation.

Bistable switch in migration stimulating factor expression: regulation by the concerted signalling of transforming growth factor-ß1 and the extracellular matrix.

Migration stimulating factor (MSF) is an oncofetal motogenic/angiogenic cytokine constitutively expressed by epithelial and stromal cells in fetal and neoplastic tissues. Fibroblasts derived from healthy adult skin do not express MSF but can be induced to do so by treatment with transforming growth factor-ß1 (TGF-ß1). As the bioactivities of both MSF and TGF-ß1 are modulated by the extracellular matrix, we investigated whether the induction of MSF expression by TGF-ß1 is also matrix dependent. We now report that adult fibroblasts are induced to express MSF by a transient treatment with TGF-ß1 (as short as 2 hr) but only when the cells are adherent to a "wound" matrix, such as denatured type I collagen, fibrin or plastic tissue culture dishes. Unexpectedly, this induction of MSF expression persists unabated for the entire subsequent lifespan of the treated cells in the absence of further TGF-ß1 and irrespective of the substratum. Such "activated" MSF expression may, however, be persistently switched off again by a second transient exposure to TGF-ß1 but this time only when the cells are adherent to a "healthy" matrix of native type I collagen. Significantly, the constitutive expression of MSF by fetal and cancer patient fibroblasts could also be persistently switched off by this means. We conclude that TGF-ß1 may both switch on and switch off MSF expression in a manner critically determined by the nature of the matrix substratum and suggest that this may be a possible mechanism underlying the observed dual functionality of TGF-ß1 as both a tumour suppressor and tumour promoter.

Migration-stimulating factor as a novel biomarker in salivary gland tumours.

BACKGROUND: The identification of novel stratification biomarkers would benefit the clinical management of patients with salivary gland tumours. Migration-stimulating factor (MSF) is a potent stimulator of cell invasion, matrix remodelling and angiogenesis. The aim of this study was to determine whether MSF was expressed in salivary gland tumours and its potential value as a diagnostic biomarker. METHODS: Paraffin-embedded archival specimens of small salivary gland tumours were stained with an MSF-specific antibody. The specimens included 27 malignant and seven benign tumours; histologically normal salivary gland adjacent to the tumour was present in 16 specimens. MSF expression was assessed by consensus of 2-4 independent observers according to various indices, including 'overall MSF grade', 'percentage of area stained' and 'intensity of the staining'. The motogenic effect of MSF on a salivary gland tumour cell line, HSG, was examined in the transmembrane assay. RESULTS: Overall MSF expression increased significantly in a step-wise fashion from normal salivary gland to benign and malignant tumours (P = 0.04-0.0001); with moderate/strong positive specimens representing 6%, 33% and 74% of the normal, benign and malignant specimens, respectively. MSF was heterogeneously expressed in both carcinoma and stromal cell compartments, its expression being higher in malignant than benign tumours regarding various MSF indices. In tissue culture studies, exogenous MSF stimulated the migration of HSG cells. CONCLUSIONS: These immunohistochemical and functional studies suggest that MSF expression is a potentially useful biomarker of salivary gland tumour progression.

Modification of the home environment for the reduction of injuries.

BACKGROUND: Injury in the home is common, accounting for approximately a third of all injuries. The majority of injuries to children under five and people aged 75 and older occur at home. Multifactorial injury prevention interventions have been shown to reduce injuries in the home. However, few studies have focused specifically on the impact of physical adaptations to the home environment and the effectiveness of such interventions needs to be ascertained. OBJECTIVES: To determine the effect of modifications to the home environment on the reduction of injuries due to environmental hazards. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE and other specialised databases. We also scanned conference proceedings and reference lists. We contacted the first author of all included randomised controlled trials. The searches were last updated to the end of December 2009, and were not restricted by language or publication status. SELECTION CRITERIA: Randomised controlled trials. DATA COLLECTION AND ANALYSIS: Two authors screened all abstracts for relevance, outcome and design. Two authors independently assessed methodological quality and extracted data from each eligible study. We performed meta-analysis to combine effect measures, using a random-effects model. We assessed heterogeneity using an I(2) statistic and a Chi(2) test. MAIN RESULTS: We found 28 published studies and one unpublished study. Only two studies were sufficiently similar to allow pooling of data for statistical analyses. Studies were divided into three groups; children, older people and the general population/mixed age group. None of the studies focusing on children or older people demonstrated a reduction in injuries that were a direct result of environmental modification in the home. One study in older people demonstrated a reduction in falls and one a reduction in falls and injurious falls that may have been due to hazard reduction. One meta-analysis was performed which examined the effects on falls of multifactorial interventions consisting of home hazard assessment and modification, medication review, health and bone assessment and exercise (RR 1.09, 95% CI 0.97 to 1.23). AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether interventions focused on modifying environmental home hazards reduce injuries. Further interventions to reduce hazards in the home should be evaluated by adequately designed randomised controlled trials measuring injury outcomes. Recruitment of large study samples to measure effect must be a major consideration for future trials. Researchers should also consider using factorial designs to allow the evaluation of individual components of multifactorial interventions.