Quality of and access to green space in relation to psychological distress: results from a population-based cross-sectional study as part of the EURO-URHIS 2 project.

Background: Psychological distress (PD) (mental ill-health) has a frequency between 5 and 25% in urban populations, and there is mounting evidence that access to green space might reduce its occurrence. Evidence suggests that the quality of green space is as important as accessibility in promoting mental well-being. A pilot study for EURO-URHIS 2 allowed investigation of access to green space in relation to PD in a deprived urban population in the UK. Methods: An adult urban health indicator questionnaire, including the GHQ-12 and validated questions on access to and quality of green space, was sent to a stratified random sample of 1680 adults drawn from one general practice list in Sandwell, UK. Multivariable logistic regression was used to determine associations between attributes of green space and PD adjusting for age, sex and levels of deprivation. Results: There were 578 (35%) completed responses. The reported prevalence of PD [n = 131 (22.7%)] was significantly greater than national England and Wales estimates. As well as accessibility (OR = 0.58; 95% CI = 0.35, 0.96) and sufficiency (OR = 0.12; 95% CI = 0.39, 0.89) of green spaces, having the ability to use them for relaxation and recreation were significantly associated with reduced PD [OR = 0.13 (0.42, 0.94) and OR = 0.11 (0.34, 0.80), respectively]. In addition, a dose-response relationship between number of positive green space attributes and PD was identified (P < 0.05). Conclusion: This population-based study in a deprived urban UK population demonstrates an association, and some dose-response relationship, between access to and quality of green spaces with reduced PD. The cross-sectional design and use of subjective measures limit interpretation of causality. More knowledge is needed on how UK planning affects green spaces and the potential mental health consequences.

Collecting standardized urban health indicator data at an individual level for school-aged children living in urban areas: methods from EURO-URHIS 2.

Background: Measuring health and its determinants in urban populations is essential to effectively develop public health policies maximizing health gain within this context. Adolescents are important in this regard given the origins of leading causes of morbidity and mortality develop pre-adulthood. Comprehensive, accurate and comparable information on adolescent urban health indicators from heterogeneous urban contexts is an important challenge. EURO-URHIS 2 aimed to develop standardized tools and methodologies collecting data from adolescents across heterogenous European urban contexts. Questionnaires were developed including (i) comprehensive assessment of urban health indicators from 7 pre-defined domains, (ii) use of previously validated questions from a literature review and other European surveys, (iii) translation/back-translation into European languages and (iv) piloting. Urban area-specific data collection methodologies were established through literature review, consultation and piloting. School-based surveys of 14-16-year olds (400-800 per urban area) were conducted in 13 European countries (33 urban areas). Participation rates were high (80-100%) for students from schools taking part in the surveys from all urban areas, and data quality was generally good (low rates of missing/spoiled data). Overall, 13 850 questionnaires were collected, coded and entered for EURO-URHIS 2. Dissemination included production of urban area health profiles (allowing benchmarking for a number of important public health indicators in young people) and use of visualization tools as part of the EURO-URHIS 2 project. EURO-URHIS 2 has developed standardized survey tools and methodologies for assessing key measures of health and its determinants in adolescents from heterogenous urban contexts and demonstrated the utility of this data to public health practitioners and policy makers.

Sixteen-week analysis of unaltered elastomeric chain relating in-vitro force degradation with in-vivo extraction space tooth movement.

INTRODUCTION: The purposes of this study were to evaluate whether unaltered elastomeric chain can continue to move teeth for 16 weeks and to relate it to the amount of force remaining for the same batch of elastomeric chains. METHODS: The in-vivo portion of the study had a sample of 30 paired extraction space sites from 22 subjects who were measured for closure of the space every 28 days. The altered side elastomeric chain served as the control and was replaced at 28-day intervals whereas the experimental side remained unaltered. In the in-vitro portion of the study, 100 each of 2-unit and 3-unit segments of the same batch of elastomeric chains were placed in a water bath, and the force was measured for 20 of each segment length at the 28-day measurement points. RESULTS: Statistically significant amounts of space closure occurred at both the altered and unaltered sites at all measurement time points. The mean space closure at the altered sites was minimally greater than that observed at the paired unaltered sites. The mean differences of space closure between the altered and unaltered sites ranged from a minimum of -0.05 mm at 4 weeks to a maximum of -0.14 mm at 8 weeks. The elastomeric chain force degraded rapidly by 4 weeks but continued a gradual diminution of force to 86 g at 16 weeks. CONCLUSIONS: Unaltered elastomeric chain continued to move teeth into extraction spaces for 16 weeks in this sample from both statistically and clinically significant standpoints. There were minimal and statistically insignificant differences in the mean space closure measurements between the paired altered and unaltered sites. The elastomeric chain force at 16 weeks was less than 100 g, yet at the same time point, teeth continued to move clinically.

Injury representation against ballistic threats using three novel numerical models.

Injury modelling of ballistic threats is a valuable tool for informing policy on personal protective equipment and other injury mitigation methods. Currently, the Ministry of Defence (MoD) and Centre for Protection of National Infrastructure (CPNI) are focusing on the development of three interlinking numerical models, each of a different fidelity, to answer specific questions on current threats. High-fidelity models simulate the physical events most realistically, and will be used in the future to test the medical effectiveness of personal armour systems. They are however generally computationally intensive, slow running and much of the experimental data to base their algorithms on do not yet exist. Medium fidelity models, such as the personnel vulnerability simulation (PVS), generally use algorithms based on physical or engineering estimations of interaction. This enables a reasonable representation of reality and greatly speeds up runtime allowing full assessments of the entire body area to be undertaken. Low-fidelity models such as the human injury predictor (HIP) tool generally use simplistic algorithms to make injury predictions. Individual scenarios can be run very quickly and hence enable statistical casualty assessments of large groups, where significant uncertainty concerning the threat and affected population exist. HIP is used to simulate the blast and penetrative fragmentation effects of a terrorist detonation of an improvised explosive device within crowds of people in metropolitan environments. This paper describes the collaboration between MoD and CPNI using an example of all three fidelities of injury model and to highlight future areas of research that are required.

Clinical audit of a lymphoedema bandaging system: a foam roll and cohesive short stretch bandages.

OBJECTIVE: Late-stage lymphoedema is characterised by chronic swelling, shape distortion, inflammatory processes and tissue fibrosis. Our aim was to perform a clinical audit of a lymphoedema compression bandaging system (Rosidal Soft foam roll layer and figure-of-eight application of Actico cohesive inelastic bandages) specifically designed for patients with late stage lower limb lymphoedema. METHOD: The audit explored suitability of the bandaging system, benchmarking limb volume changes with research evidence, and reporting patient and practitioner evaluations. RESULTS: A mean reduction (33%) in excess limb volume was reported for the 11 patients with unilateral lymphoedema who completed a course of bandaging over 12 days. Mean percentage reduction of absolute limb volume after treatment was 8%. Patient and practitioner evaluations indicated the suitability of this bandage system for patients with late stage lymphoedema in terms of comfort and effectiveness. CONCLUSION: The bandaging system is suitable for patients with late stage chronic swelling. Two parameters for calculating change in limb volume are not interchangeable. Future evaluation of the bandaging system, using validated outcome measures within a comprehensive research study is required. DECLARATION OF INTEREST: Activa Healthcare provided financial support to the project and supplied the materials.

The challenges in developing a finite element injury model of the neck to predict the penetration of explosively propelled projectiles.

INTRODUCTION: Neck injuries sustained by UK service personnel serving on current operations from explosively propelled fragments result in significant mortality and long-term morbidity. Many of these injuries could potentially have been prevented had the soldiers been wearing their issued neck collars at the time of injury. The aim of this research is to develop an accurate method of predicting the resultant damage to cervical neurovascular structures from explosively propelled fragments. CURRENT STATUS: A finite element numerical model has been developed based on an anatomically accurate, anthropometrically representative 3D mathematical mesh of cervical neurovascular structures. Currently, the model simulates the passage of a fragment simulating projectile through all anatomical components of the neck using material models based upon 20% ballistic gelatin on the simplification that all tissue types act like homogenous muscle. FUTURE RESEARCH: The material models used to define the properties of each element within the model will be sequentially replaced by ones specific to each individual tissue within an anatomical structure. However, the cumulative effect of so many additional variables will necessitate experimental validation against both animal models and post-mortem human subjects to improve the credibility of any predictions made by the model. We believe this approach will in the future have the potential to enable objective comparisons between the mitigative effects of different body armour systems to be made with resultant time and financial savings.

Modelling the blast environment and relating this to clinical injury: experience from the 7/7 inquest.

This paper addresses the computational modelling of a series of specific blast-related incidents and the relationships of clinical and engineering interpretations. The Royal Centre for Defence Medicine and the Defence Science and Technology Laboratory were tasked in 2010 by the UK Ministry of Defence to assist the Coroner's inquests into the 7 July 2005 London bombings. A three phase approach was taken. The first phase included an engineering expert in blast effects on structures reviewing photographs of the damaged carriages and bus to give a view on the likely physical effects on people close to the explosions. The second phase was a clinical review of the evidence by military clinicians to assess blast injury in the casualties. The third phase was to model the blast environment by structural dynamics experts to assess likely blast loading on victims to evaluate the potential blast loading on individuals. This loading information was then assessed by physiology experts. Once all teams (engineering, clinical and modelling/physiological) had separately arrived at their conclusions, the information streams were integrated to arrive at a consensus. The aim of this paper is to describe the methodology used as a potential model for others to consider if faced with a similar investigation, and to show the benefit of the transition of military knowledge to a civilian environment.

Chimaeric analysis reveals role of Pdgf receptors in all muscle lineages.

Blood vessels originate as simple endothelial cell tubes. It has been proposed that platelet-derived growth factor B polypeptide (Pdgfb) secreted by these endothelial cells drives the formation of the surrounding muscular wall by recruiting nearby mesenchymal cells. However, targetted inactivation of the Pdgfb gene or the Pdgf receptor beta (Pdgfrb) gene, by homologous recombination, does not prevent the development of apparently normal large arteries and connective tissue. We have used an in vivo competition assay in which we prepared chimaeric blastocysts, composed of a mixture of wild-type (Pdgfrb[+/+]) and Pdgfrb(+/-) or wild-type and Pdgfrb(-/-) cells, and quantified the relative success of cells of the two component genotypes in competing for representation in different cell lineages as the chimaeric embryos developed. This study revealed that the participation of Pdgfrb(-/-) cells in all muscle lineages (smooth, cardiac, skeletal and pericyte) was reduced by eightfold compared with Pdgfrb(+/+) cells, and that participation of Pdgfrb(+/-) cells was reduced by twofold (eightfold for pericytes). Pdgfrb inactivation did not affect cell contribution to non-muscle mesodermal lineages, including fibroblasts and endothelial cells. Chimaera competition is therefore a sensitive, quantitative method for determining developmental roles of specific genes, even when those roles are not apparent from analysis of purebred mutants; most likely because they are masked by homeostatic mechanisms.

Injury modelling for strategic planning in protecting the national infrastructure from terrorist explosive events.

Terrorist events in the form of explosive devices have occurred and remain a threat currently to the population and the infrastructure of many nations worldwide. Injuries occur from a combination of a blast wave, energised fragments, blunt trauma and burns. The relative preponderance of each injury mechanism is dependent on the type of device, distance to targets, population density and the surrounding environment, such as an enclosed space, to name but a few. One method of primary prevention of such injuries is by modification of the environment in which the explosion occurs, such as modifying population density and the design of enclosed spaces. The Human Injury Predictor (HIP) tool is a computational model which was developed to predict the pattern of injuries following an explosion with the goal to inform national injury prevention strategies from terrorist attacks. HIP currently uses algorithms to predict the effects from primary and secondary blast and allows the geometry of buildings to be incorporated. It has been validated using clinical data from the '7/7' terrorist attacks in London and the 2017 Manchester Arena terrorist event. Although the tool can be used readily, it will benefit from further development to refine injury representation, validate injury scoring and enable the prediction of triage states. The tool can assist both in the design of future buildings and methods of transport, as well as the situation of critical emergency services required in the response following a terrorist explosive event. The aim of this paper is to describe the HIP tool in its current version and provide a roadmap for optimising its utility in the future for the protection of national infrastructure and the population.

Health planning for the future: comparative risk assessment of five major lifestyle risk factors: evidence from the Wirral, UK.

BACKGROUND: The aim of this study was to quantify and compare the burden of disease attributable to five major lifestyle-related risk factors in a UK Primary Care Trust (Wirral) using World Health Organizations' (WHO) comparative risk assessment (CRA) methodology to demonstrate its practical utility for informing local policy initiatives. METHODS: WHO CRA methodology was adopted using exposure data from a local lifestyle survey, disease risk factor relationships published by the WHO and local mortality data to calculate risk factor attributable deaths and years of life lost (YLL). RESULTS: Smoking remains by far the leading cause of deaths followed by overweight and obesity and low fruit and vegetable intake. Alcohol ranked last by number of deaths, but second by YLL indicating its high contribution to deaths at younger ages. CONCLUSIONS: We have demonstrated the utility of WHO CRA methodology to influence health-related policy-making at a local level. Primary prevention should remain high on the agenda of government initiatives to reduce the future burden of ill health. Future research in this area could look at more in-depth national data to cover a wider range of risk factors addressing some of the methodological and data shortcomings identified in this study.

Fas/FADD-mediated activation of a specific program of inflammatory gene expression in vascular smooth muscle cells.

Apoptosis of smooth muscle cells is a common feature of vascular lesions but its pathophysiological significance is not known. We demonstrate that signals initiated by regulated Fas-associated death domain protein overexpression in rat vascular smooth muscle cells in the carotid artery induce expression of monocyte-chemoattractant protein-1 and interleukin-8, and cause massive immigration of macrophages in vivo. These chemokines, and a specific set of other pro-inflammatory genes, are also upregulated in human vascular smooth muscle cells during Fas-induced apoptosis, in part through a process that requires interleukin-1alpha activation. Induction of a pro-inflammatory program by apoptotic vascular smooth muscle cells may thus contribute to the pathogenesis of vascular disease.

Isolation, characterization, and propagation in vitro of human glomerular endothelial cells.

Human glomerular endothelial cells have been isolated, cloned, and characterized. They appeared as the first outgrowth from human glomeruli in the presence of platelet-derived growth factor, which was also a requirement for continuous growth. By phase microscopy they appeared as monolayers of polygonal cells. Von Willebrand's factor (VWF) was detected in the cytoplasm of all clones. Their intermediate filaments differed antigenically from that present in human umbilical vein endothelial cells. Like other endothelial cells, they demonstrated high levels of membrane-associated angiotensin-converting enzyme (ACE).

Adaptive optical phase estimation using time-symmetric quantum smoothing.

Quantum parameter estimation has many applications, from gravitational wave detection to quantum key distribution. The most commonly used technique for this type of estimation is quantum filtering, using only past observations. We present the first experimental demonstration of quantum smoothing, a time-symmetric technique that uses past and future observations, for quantum parameter estimation. We consider both adaptive and nonadaptive quantum smoothing, and show that both are better than their filtered counterparts. For the problem of estimating a stochastically varying phase shift on a coherent beam, our theory predicts that adaptive quantum smoothing (the best scheme) gives an estimate with a mean-square error up to 2sqrt[2] times smaller than nonadaptive filtering (the standard quantum limit). The experimentally measured improvement is 2.24+/-0.14.

Regulation of proliferation and differentiation of myoblasts derived from adult mouse skeletal muscle by specific isoforms of PDGF.

The expression of receptors and the mitogenic response to PDGF by C2 myoblasts, derived from adult mouse skeletal muscle, was investigated. Employing 125I-PDGF binding assays, we showed that the cells exhibit high level binding of PDGF-BB (approximately 165 x 10(3) molecules/cell at saturation) and much lower binding of the PDGF-AA and PDGF-AB (6-12 x 10(3) molecules/cell at saturation). This indicates that the C2 myoblasts express high levels of PDGF receptor beta-subunits and low levels of alpha-subunits. PDGF-BB enhances the proliferation of C2 cells maintained in 2% FCS by about fivefold. PDGF-AB had a moderate effect on cell proliferation (less than twofold) and PDGF-AA had no effect. Inverse effects of PDGF isoforms on the frequency of differentiated myoblasts were observed; the frequency of myosin-positive cells was reduced in the presence of PDGF-BB while PDGF-AA and PDGF-AB had no effect. PDGF may thus act to increase the number of myoblasts that participate in muscle regeneration following muscle trauma by stimulating the proliferation and by inhibiting the differentiation of myogenic cells.

Interactions between the receptors for platelet-derived growth factor and epidermal growth factor.

Preincubation of Swiss 3T3 cells or human fibroblasts with purified platelet-derived growth factor (PDGF) at 4 degrees C or 37 degrees C rapidly inhibits subsequent binding of 125I-epidermal growth factor (125I-EGF). The effect does not result from competition by PDGF for binding to the EGF receptor since (a) very low concentrations of PDGF are effective, (b) cells with EGF receptors but no PDGF receptors are not affected, and (c) the inhibition persists even if the bound PDGF is eluted before incubating the cells with 125I-EGF. PDGF does not affect 125I-insulin binding nor does EGF affect 125I-PDGF binding under these conditions. Endothelial cell-derived growth factor also competes for binding to PDGF receptors and inhibits 125I-EGF binding. The inhibition demonstrated by PDGF seems to result from an increase in the Kd for 125I-EGF binding with no change in the number of EGF receptors.

Alpha-thrombin induces release of platelet-derived growth factor-like molecule(s) by cultured human endothelial cells.

Cultured endothelial cells secrete a platelet-derived growth factor-like molecule (PDGFc). We examined the effects of purified human alpha-thrombin on the production of PDGFc in cultures of human umbilical vein endothelial cells (HUVE) using a specific radioreceptor assay for PDGF. Addition of physiologically relevant concentrations of alpha-thrombin (0.1 to 10 U/ml) induced a time- and dose-dependent increase in the release of PDGFc into the culture medium. Significant stimulation of PDGFc release was observed as early as 1.5 h after addition of alpha-thrombin (10 U/ml) with a 4.9 +/- 1.1 fold increase at 24 h (mean +/- SEM of nine experiments, P less than 0.01). alpha-Thrombin treatment of HUVE did not affect cell viability as assessed by trypan blue dye exclusion. The receptor binding of PDGFc secreted by HUVE in response to alpha-thrombin was inhibited by monospecific antibody to purified human PDGF indicating that the molecule(s) is closely related to PDGF. alpha-Thrombin inactivated with diisopropylfluorophosphate was without stimulatory effect. Lysis of HUVE by repeated cycles of freeze/thaw released minimal PDGFc (less than 0.3 ng per 10(6) cells) compared to levels of PDGFc released into supernatant medium in response to alpha-thrombin (greater than 5.0 ng per 10(6) cells after a 24-h incubation with 10 U/ml alpha-thrombin). Moreover, incubation of freeze/thaw lysates of HUVE with alpha-thrombin failed to release PDGFc. Over a 3-h time course, however, alpha-thrombin-induced secretion of PDGFc was not prevented by cycloheximide. We conclude that alpha-thrombin induces secretion of PDGFc from HUVE by a nonlytic mechanism requiring the serine esterase activity of the enzyme. Although this effect does not initially require de novo protein synthesis, it does require cell-mediated conversion of PDGFc from an inactive to an active form.

PDGF ligand and receptor gene expression during repair of arterial injury.

Smooth muscle cells (SMC) in rat carotid artery leave the quiescent state and proliferate after balloon catheter injury, but the signals for mitogenesis are not known. In this study, the possibility that cells within damaged arteries produce a growth factor that could act locally to stimulate SMC replication and repair was examined. We found that the genes for PDGF-A and -B (ligand) and PDGF receptor (alpha and beta subunits) were expressed in normal and injured carotid arteries and were independently regulated during repair of carotid injury. Two phases of PDGF ligand and receptor gene expression were observed: (a) In the early stage, a large decrease in PDGF beta-receptor mRNA levels preceded 10- to 12-fold increases in PDGF-A transcript abundance in the first 6 h after wounding. No change in PDGF alpha-receptor or PDGF-B gene expression was found at these times. (b) In the chronic phase, 2 wk after injury, neointimal tissue had lower levels of PDGF alpha-receptor mRNA (threefold) and higher levels of PDGF beta-receptor mRNA (three- to fivefold) than did restored media. Moreover, in situ hybridization studies identified a subpopulation of neointimal SMC localized at or near the luminal surface with a different pattern of gene expression than the underlying carotid SMC. Luminal SMC were strongly positive for PDGF-A and PDGF beta-receptor transcripts, while showing little or no hybridization for PDGF-B or PDGF alpha-receptor. Immunohistochemical studies showed strongly positive staining for PDGF-A in SMC along the luminal surface. These data show that changes in PDGF ligand and receptor expression occur at specific times and locations in injured carotid artery and suggest that these changes may play a role in regulating arterial wound repair.

Detection of high molecular weight forms of platelet-derived growth factor by sequence-specific antisera.

Antisera to synthetic peptides representing sequences of both chains of platelet-derived growth factor (PDGF) were used to structurally analyze PDGF isolated from outdated human platelets and PDGF-like proteins in normal and transformed cells. Most PDGF isolated from platelets did not contain the carboxyl portion of PDGF-2 in contrast to p20sis, the major form of p28sis detected in simian sarcoma virus-transformed cells. In addition, higher molecular weight forms of molecules containing PDGF-1 and PDGF-2 sequences were detected in all cell lines tested. These lines were heterogeneous with respect to species, cell type, and transforming agent.