Liver-on-chip model and application in predictive genotoxicity and mutagenicity of drugs.

Currently, there is no test system, whether in vitro or in vivo, capable of examining all endpoints required for genotoxicity evaluation used in pre-clinical drug safety assessment. The objective of this study was to develop a model which could assess all the required endpoints and possesses robust human metabolic activity, that could be used in a streamlined, animal-free manner. Liver-on-chip (LOC) models have intrinsic human metabolic activity that mimics the in vivo environment, making it a preferred test system. For our assay, the LOC was assembled using primary human hepatocytes or HepaRG cells, in a MPS-T12 plate, maintained under microfluidic flow conditions using the PhysioMimix® Microphysiological System (MPS), and co-cultured with human lymphoblastoid (TK6) cells in transwells. This system allows for interaction between two compartments and for the analysis of three different genotoxic endpoints, i.e. DNA strand breaks (comet assay) in hepatocytes, chromosome loss or damage (micronucleus assay) and mutation (Duplex Sequencing) in TK6 cells. Both compartments were treated at 0, 24 and 45 h with two direct genotoxicants: methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS), and two genotoxicants requiring metabolic activation: benzo[a]pyrene (B[a]P) and cyclophosphamide (CP). Assessment of cytochrome activity, RNA expression, albumin, urea and lactate dehydrogenase production, demonstrated functional metabolic capacities. Genotoxicity responses were observed for all endpoints with MMS and EMS. Increases in the micronucleus and mutations (MF) frequencies were also observed with CP, and %Tail DNA with B[a]P, indicating the metabolic competency of the test system. CP did not exhibit an increase in the %Tail DNA, which is in line with in vivo data. However, B[a]P did not exhibit an increase in the % micronucleus and MF, which might require an optimization of the test system. In conclusion, this proof-of-principle experiment suggests that LOC-MPS technology is a promising tool for in vitro hazard identification genotoxicants.

Meeting the long-term health needs of Ukrainian refugees.

OBJECTIVES: Since Russia's full-scale invasion of Ukraine on 24 February 2022, millions of people have fled the country. Most people have gone to the neighbouring countries of Poland, Slovakia, Hungary, Romania, and Moldova. This vulnerable population has significant healthcare needs. Among the most challenging to address will be chronic non-communicable diseases (NCDs), including mental disorders, as these require long-term, continuous care and access to medicines. Host country health systems are faced with the challenge of ensuring accessible and affordable care for NCDs and mental disorders to this population. Our objectives were to review host country health system experiences and identify priorities for research to inform sustainable health system responses to the health care needs of refugees from Ukraine. STUDY DESIGN: In-person conference workshop. METHODS: A workshop on this subject was held in November 2022 at the European Public Health Conference in Berlin. RESULTS: The workshop included participants from academia and non-governmental organisations, health practitioners, and World Health Organisation regional and country offices. This short communication reports the main conclusions from the workshop. CONCLUSION: Addressing the challenges and research priorities identified will require international solidarity and co-operation.

Design and testing of the safety of the SARUS-CPR hood for novice resuscitators.

BACKGROUND AND AIMS: Bystanders should be protected against aerosols, droplets, saliva, blood and vomitus during resuscitation after cardiac arrest The SARUS (safer - airway - resuscitation) CPR airway hood™ is a clear plastic cover and integrated mask that envelopes the head and torso. Our objectives were to test leakage using saline aerosol generation tests, then assess the performance of the hood during mock cardio-pulmonary resuscitation on a manikin. METHODS: A checklist was validated by comparing the performance of 10 novices against 10 experts during mock resuscitation. Thereafter, 15 novices were tested with and without the hood, in a randomised cross-over study, one week apart. RESULTS: Laboratory analysis showed a > 99% reduction of saline particles detected 5 cm, 75 cm and 165 cm above volunteers wearing the hood. On manikins, experts scored better compared to novices, 8.5 (0.7) vs 7.6 (1.2), difference (95%CI) 0.9 (0.4-1.3), P = 0.0004. Novice performance was equivalent using the hood and standard equipment, 7.3 (1.4) vs 7.3 (1.1) respectively, difference (90%CI) 0.0 (-0.3 - 0.3), P = 0.90. CONCLUSION: Aerosol transmission reduced in the breathing zone. Simulated resuscitation by novices was equivalent with and without the hood.

Effects of gonadal steroids on reward circuitry function and anhedonia in women with a history of postpartum depression.

BACKGROUND: Reward system dysfunction is evident across neuropsychiatric conditions. Here we present data from a double-blinded pharmaco-fMRI study investigating the triggering of anhedonia and reward circuit activity in women. METHODS: The hormonal states of pregnancy and parturition were simulated in euthymic women with a history of postpartum depression (PPD+; n = 15) and those without such a history (PPD-; n = 15) by inducing hypogonadism, adding back estradiol and progesterone for 8 weeks ("addback"), and then withdrawing both steroids ("withdrawal"). Anhedonia was assessed using the Inventory of Depression and Anxiety Symptoms (IDAS) during each hormone phase. Those who reported a 30 % or greater increase in IDAS anhedonia, dysphoria, or ill temper during addback or withdrawal, compared with pre-treatment, were identified as hormone sensitive (HS+) and all others were identified as non-hormone sensitive (HS-). The monetary incentive delay (MID) task was administered during fMRI sessions at pre-treatment and during hormone withdrawal to assess brain activation during reward anticipation and feedback. RESULTS: On average, anhedonia increased during addback and withdrawal in PPD+ but not PPD-. During reward feedback, both HS+ (n = 10) and HS- (n = 18) showed decreased activation in clusters in the right putamen (p < .031, FWE-corrected) and left postcentral and supramarginal gyri (p < .014, FWE-corrected) at the withdrawal scans, relative to pre-treatment scans. LIMITATIONS: A modest sample size, stringent exclusion criteria, and relative lack of diversity in study participants limit the generalizability of results. CONCLUSION: Although results do not explain differential hormone sensitivity in depression, they demonstrate significant effects of reproductive hormones on reward-related brain function in women.

Determination of the Discriminating Concentration Towards Permethrin for Surveying Resistance in Amblyomma americanum.

Amblyomma americanum Linnaeus (Ixodida: Ixodidae) is ubiquitously present throughout the southeastern United States and is capable of vectoring several pathogens. White-tailed deer are the main host for adult A. americanum. However, this tick species is a generalist that will feed on most vertebrates, including humans, deer, livestock, and pets. Management of this species can be challenging due to a lack of cost-effective strategies. Acaricides are often utilized, however, this may lead to pesticide resistance. The Food and Agriculture Organization of the United Nations (FAO) larval packet test (LPT) was performed on susceptible A. americanum to determine the lethal concentration (LC) and discriminating concentration (DC) values for permethrin. The FAO LPT was used at these pre-established values to compare levels of resistance in ticks collected from a captive deer farm and wild areas representing high and low permethrin exposure settings, respectively. Resistance ratios (RR) calculated from the LC values for the ticks collected from farmed and wild deer ranged between 1 and 2. A. americanum collected from farmed and wild deer were not found to be resistant, however, some samples had slightly elevated RRs as compared to the susceptible laboratory strain, which may suggest tolerance development. Although the A. americanum sampled in this study were not resistant to permethrin, the DC calculated in this study will allow for rapid evaluation of resistance in a permethrin resistance monitoring program such that alternate management strategies can be adopted if resistance is detected.

Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett's Esophagus: A Phase 1 Pilot Study.

BACKGROUND: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. AIMS: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. METHODS: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. RESULTS: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1ß, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. CONCLUSIONS: When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.

Production performance and nutrient digestibility of lactating dairy cows fed low-forage diets with and without the addition of a live-yeast supplement.

We aimed to evaluate the use of a live-yeast product as a means to attenuate plausible nutritional disturbances when feeding relatively low-forage diets containing rapidly fermentable carbohydrates (i.e., wheat) to high-producing cows in early to mid lactation. Eight primiparous [mean ± SD; 569 ± 35 kg of body weight (BW) and 80 ± 29 d in milk (DIM) at the beginning of the experiment] and 16 multiparous (665 ± 67 kg of BW and 64 ± 10 DIM at the beginning of the experiment) Holstein cows were blocked by parity and DIM, and randomly assigned to 1 of 2 diets (control vs. yeast) for a 12-wk-long period according to randomized complete block design. The formulated diets contained 36.7% corn silage, 8.3% alfalfa hay, and 55% concentrate. The yeast diet was formulated to provide approximately 5.4 × 1011 cfu/d of Saccharomyces cerevisiae (BeneSacc; Global Nutritech Biotechnology LLC, Richmond, VA). Total-tract nutrient digestibility was estimated using 240-h undigested neutral detergent fiber (NDF) as an internal marker. Dry matter intake, milk yield, and milk component concentrations and yields were analyzed using repeated measures. The statistical model for these variables included the effects of block, treatment, the block by treatment interaction, week, the treatment by week interaction, and the random residual error. The statistical model for analyzing BW gain, body condition score gain, and dry matter and nutrient digestibilities included the effects of block, treatment, and the random residual error. Supplementing live yeast to lactating dairy cows did not affect dry matter intake (26.0 kg/d), milk yield (48.1 kg/d), milk fat concentration (3.61%), milk fat yield (1.72 kg/d), milk protein concentration (2.96%), milk protein yield (1.43 kg/d), milk lactose concentration (4.84%), milk lactose yield (2.35 kg/d), milk urea nitrogen (7.99 mg/dL), body weight gain (0.62 kg/d), and body condition score gain (0.02 units; all averages of the 2 treatments). The digestibilities of dry matter (70.2%), crude protein (71.4%), NDF (36.4%), and starch (99.8%) were not affected by treatments. In conclusion, the supplementation of the live yeast did not affect production performance and nutrient digestibility of high-producing dairy cows. A potential interaction between live-yeast supplementation and NDF passage rate, which may have hindered the beneficial effects of live-yeast supplementation on production performance and nutrient utilization, deserves further research.

Mental health care utilisation among internally displaced persons in Ukraine: results from a nation-wide survey.

AimsThere are an estimated 1.5 million internally displaced persons (IDPs) in Ukraine because of the armed conflict in the east of the country. The aim of this paper is to examine utilisation patterns of mental health and psychosocial support (MHPSS) care among IDPs in Ukraine. METHODS: A cross-sectional survey design was used. Data were collected from 2203 adult IDPs throughout Ukraine between March and May 2016. Data on mental health care utilisation were collected, along with outcomes including post-traumatic stress disorder (PTSD), depression and anxiety. Descriptive and multivariate regression analyses were used. RESULTS: PTSD prevalence was 32%, depression prevalence was 22%, and anxiety prevalence was 17%. Among those that likely required care (screened positive with one of the three disorders, and also self-reporting a problem) there was a large treatment gap, with 74% of respondents who likely required MHPSS care over the past 12 months not receiving it. For the 26% (N = 180) that had sought care, the most common sources of services/support were pharmacies, family or district doctor/paramedic (feldsher), neurologist at a polyclinic, internist/neurologist at a general hospital, psychologists visiting communities, and non-governmental organisations/volunteer mental health/psychosocial centres. Of the 180 respondents who did seek care, 163 could recall whether they had to pay for their care. Of these 163 respondents, 72 (44%) recalled paying for the care they received despite government care officially being free in Ukraine. The average costs they paid for care was US$107 over the previous 12 months. All 180 respondents reported having to pay for medicines and the average costs for medicines was US$109 over the previous 12 months. Among the 74% had not sought care despite likely needing it; the principal reasons for not seeking care were: thought that they would get better by using their own medications, could not afford to pay for health services or medications, no awareness of where to receive help, poor understanding by health care providers, poor quality of services, and stigma/embarrassment. The findings from multivariate regression analysis show the significant influence of a poor household economic situation on not accessing care. CONCLUSIONS: The study highlights a high burden of mental disorders and large MHPSS treatment gap among IDPs in Ukraine. The findings support the need for a scaled-up, comprehensive and trauma-informed response to provision of MHPSS care of IDPs in Ukraine alongside broader health system strengthening.

Increased risk of reproductive dysfunction in women prescribed long-term opioids for musculoskeletal pain: A matched cohort study in the Clinical Practice Research Datalink.

BACKGROUND: One-fifth of primary care attendees suffer chronic noncancer pain, with musculoskeletal conditions the leading cause. Twelve percent of patients with chronic noncancer pain are prescribed strong opioids. Evidence suggests long-term opioid use is related to hypogonadism in men, but the relationship in women is unclear. Our aim was to investigate reproductive dysfunction in women prescribed long-term opioids for musculoskeletal pain. METHODS: We undertook a matched (matched 1:1; for year of birth, year of start of follow-up and practice) cohort study of women aged 18-55 years old, with musculoskeletal pain and an opioid prescription in the Clinical Practice Research Datalink (a primary care database) between 2002 and 2013. Long-term opioid users (≥90 days) were compared with short-term opioid users (<90 days) for four reproductive conditions (abnormal menstruation, low libido, infertility and menopause) using Cox proportional hazards models. RESULTS: A total of 44,260 women were included; the median cohort age at baseline was 43 years (Interquartile Range 36-49). Long-term opioid use was associated with an increased risk of altered menstruation (hazard ratio 1.13 95% CI 1.05-1.21) and with an increased risk of menopause (hazard ratio 1.16 95% CI 1.10-1.23). No significant association was found for libido (hazard ratio 1.19 95% CI 0.96-1.48) or infertility (hazard ratio 0.82 95% CI 0.64-1.06). CONCLUSIONS: The risk of menopause and abnormal menstruation was increased in long-term opioid users. This has implications for clinicians as reproductive dysfunction will need to be considered when prescribing long-term opioids to women with musculoskeletal conditions. SIGNIFICANCE: This is a large-scale cohort examining the relationship between long-term opioid use and reproductive dysfunction using a UK national primary care database. There is an increased risk of reproductive dysfunction associated with long-term opioid use.

Resolution Requirements in Stochastic Field Simulation of Turbulent Premixed Flames.

The spatial resolution requirements of the Stochastic Fields probability density function approach are investigated in the context of turbulent premixed combustion simulation. The Stochastic Fields approach is an attractive way to implement a transported Probability Density Function modelling framework into Large Eddy Simulations of turbulent combustion. In premixed combustion LES, the numerical grid should resolve flame-like structures that arise from solution of the Stochastic Fields equation. Through analysis of Stochastic Fields simulations of a freely-propagating planar turbulent premixed flame, it is shown that the flame-like structures in the Stochastic Fields simulations can be orders of magnitude narrower than the LES filter length scale. The under-resolution is worst for low Karlovitz number combustion, where the thickness of the Stochastic Fields flame structures is on the order of the laminar flame thickness. The effect of resolution on LES predictions is then assessed by performing LES of a laboratory Bunsen flame and comparing the effect of refining the grid spacing and filter length scale independently. The usual practice of setting the LES filter length scale equal to grid spacing leads to severe under-resolution and numerical thickening of the flame, and to substantial error in the turbulent flame speed. The numerical resolution required for accurate solution of the Stochastic Fields equations is prohibitive for many practical applications involving high-pressure premixed combustion. This motivates development of a Thickened Stochastic Fields approach (Picciani et al. Flow Turbul. Combust. X, YYY (2018) in order to ensure the numerical accuracy of Stochastic Fields simulations.

A Thickened Stochastic Fields Approach for Turbulent Combustion Simulation.

The Stochastic Fields approach is an effective way to implement transported Probability Density Function modelling into Large Eddy Simulation of turbulent combustion. In premixed turbulent combustion however, thin flame-like structures arise in the solution of the Stochastic Fields equations that require grid spacing much finer than the filter scale used for the Large Eddy Simulation. The conventional approach of using grid spacing equal to the filter scale yields substantial numerical error, whereas using grid spacing much finer than the filter length scale is computationally-unaffordable for most industrially-relevant combustion systems. A Thickened Stochastic Fields approach is developed in this study in order to provide physically-accurate and numerically-converged solutions of the Stochastic Fields equations with reduced compute time. The Thickened Stochastic Fields formulation bridges between the conventional Stochastic Fields and conventional Thickened-Flame approaches depending on the numerical grid spacing utilised. One-dimensional Stochastic Fields simulations of freely-propagating turbulent premixed flames are used in order to obtain criteria for the thickening factor required, as a function of relevant physical and numerical parameters, and to obtain a model for an efficiency function that accounts for the loss of resolved flame surface area caused by applying the thickening transformation to the Stochastic Fields equations. The Thickened Stochastic Fields formulation is tested by performing LES of a laboratory premixed Bunsen flame. The results demonstrate that the Thickened Stochastic Fields method produces accurate predictions even when using a grid spacing equal to the filter scale. The present development therefore facilitates the accurate application of the Stochastic Fields approach to industrially-relevant combustion systems.

A comparison of intact and degraded desmin in cooked and uncooked pork longissimus thoracis and their relationship to pork quality.

The objective was to compare desmin abundance (intact, degraded, and the ratio of intact desmin to degraded desmin) in samples from cooked and uncooked pork and establish its relationship to pork quality traits. Pork chops (2.54-cm thick) from twenty-four pork loins were randomly assigned to treatment (cooked or uncooked). Intact and degraded desmin in cooked and uncooked chops aged 1d were weakly correlated (r<|0.35|) with Warner-Bratzler shear force at 1 and 14d postmortem aging. Intact and degraded desmin in cooked and uncooked chops aged 14d were moderately correlated (|0.35|

The International Spinal Cord Injury Pain Extended Data Set (Version 1.0).

OBJECTIVES: The objective of this study was to develop the International Spinal Cord Injury Pain Extended Data Set (ISCIPEDS) with the purpose of guiding the assessment and treatment of pain after spinal cord injury (SCI). SETTING: International. METHODS: The ISCIPEDS was reviewed by members of the International SCI Data Sets Committee, the International Spinal Cord Society Executive and Scientific Committees, American Spinal Injury Association and American Pain Society Boards, and the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain, individual reviewers and societies. RESULTS: The working group recommended four assessment domains for the ISCIPEDS: (i) Pain symptoms including variables related to pain type, temporal course, severity, unpleasantness, tolerability of pain and questionnaires assessing pain type and symptom severity; (ii) Sensory signs to detect and quantify sensory abnormalities commonly associated with neuropathic pain, including dynamic mechanical and thermal allodynia, and hyperalgesia; (iii) Treatments (ongoing and past 12 months); and (iv) Psychosocial factors and comorbid conditions. CONCLUSION: The ISCIPEDS was designed to be used together with the International SCI Pain Basic Data Set and provide a brief yet thorough assessment of domains related to chronic pain in individuals with SCI. The data set includes pain-relevant self-reported assessments, questionnaires and sensory examinations. The recommendations were based on (i) their relevance to individuals with SCI and chronic pain, (ii) the existence of published findings supporting the utility of the selected measures for use in individuals with SCI, and to the greatest extent possible (iii) their availability in the public domain free of charge.

The density of tobacco retailers in home and school environments and relationship with adolescent smoking behaviours in Scotland.

BACKGROUND: Neighbourhood retailing of tobacco products has been implicated in affecting smoking prevalence rates. Long-term smoking usually begins in adolescence and tobacco control strategies have often focused on regulating 'child spaces', such as areas in proximity to schools. This cross-sectional study examines the association between adolescent smoking behaviour and tobacco retail outlet density around home and school environments in Scotland. METHODS: Data detailing the geographic location of every outlet registered to sell tobacco products in Scotland were acquired from the Scottish Tobacco Retailers Register and used to create a retail outlet density measure for every postcode. This measure was joined to individual responses of the Scottish Schools Adolescent Lifestyle and Substance Use Survey (n=20 446). Using logistic regression models, we explored the association between the density of retailers, around both home and school address, and smoking behaviours. RESULTS: Those living in the areas of highest density of retailers around the home environment had 53% higher odds of reporting having ever smoked (95% CI 1.27 to 1.85, p<0.001) and 47% higher odds of reporting current smoking (95% CI 1.13 to 1.91 p<0.01). Conversely, those attending schools in areas of highest retail density had lower odds of having ever smoked (OR 0.66, 95% CI 0.50 to 0.86 p<0.01) and lower odds of current smoking (OR 0.75, 95% CI 0.59 to 0.95, p<0.05). CONCLUSIONS: The density of tobacco retail outlets in residential neighbourhoods is associated with increased odds of both ever smoked and current smoking among adolescents in Scotland. Policymakers may be advised to focus on reducing the overall density of tobacco outlets, rather than concentrating on 'child spaces'.

Optimizing the position resolution of a Z-stack microchannel plate resistive anode detector for low intensity signals.

A method for achieving good position resolution of low-intensity electron signals using a microchannel plate resistive anode detector is demonstrated. Electron events at a rate of 7 counts s(-1) are detected using a Z-stack microchannel plate. The dependence of position resolution on both the distance and the potential difference between the microchannel plate and resistive anode is investigated. Using standard commercial electronics, a measured position resolution of 170 µm (FWHM) is obtained, which corresponds to an intrinsic resolution of 157 µm (FWHM).

Mercury and cortisol in Western Hudson Bay polar bear hair.

Non-invasive methods of assessing animal health and life history are becoming increasingly popular in wildlife research; hair samples from polar bears (Ursus maritimus), are being used to study an ever broader range of anthropogenic and endocrine compounds. A number of contaminants are known to disrupt endocrine function in polar bears. However, the relationship between mercury and cortisol remains unknown, although mercury is an endocrine disruptor in other species. Here, we examine the relationship between concentrations of cortisol and total mercury (THg) analyzed in guard hair from 378 polar bears (184 females, 194 males) sampled in Western Hudson Bay, 2004-2012. The difference in mean cortisol concentration between female (0.8 ± 0.6 pg/mg) and male (0.7 ± 0.5 pg/mg) polar bears bordered on significance (p = 0.054). However, mean mercury concentration was significantly greater (p = 0.009) in females (4.7 ± 1.4 µg/g) than males (4.3 ± 1.2 µg/g). Hair cortisol in males was significantly influenced by mercury, age, and fatness, as well as interactions between mercury and year, mercury and fatness, and year and fatness (all: p < 0.03) (multiple regression analysis, whole model: r(2) = 0.14, F(7,185) = 4.43, p = 0.0001). Fatness was the only significant variable in the multiple regression analysis for females (r(2) = 0.06, F(1,182) = 13.0, p = 0.0004). In conclusion, a significant, but complex, relationship was found between mercury and cortisol concentrations in hair from male, but not female, polar bears.

Is local alcohol outlet density related to alcohol-related morbidity and mortality in Scottish cities?

Alcohol consumption may be influenced by the local alcohol retailing environment. This study is the first to examine neighbourhood alcohol outlet availability (on- and off-sales outlets) and alcohol-related health outcomes in Scotland. Alcohol-related hospitalisations and deaths were significantly higher in neighbourhoods with higher outlet densities, and off-sales outlets were more important than on-sales outlets. The relationships held for most age groups, including those under the legal minimum drinking age, although were not significant for the youngest legal drinkers (18-25 years). Alcohol-related deaths and hospitalisations were higher in more income-deprived neighbourhoods, and the gradient in deaths (but not hospitalisations) was marginally larger in neighbourhoods with higher off-sales outlet densities. Efforts to reduce alcohol-related harm should consider the potentially important role of the alcohol retail environment.

Role of physical activity in the relationship between urban green space and health.

OBJECTIVES: Local availability of green space has been associated with a wide range of health benefits. Possible causative mechanisms underpinning the green space and health relationship include the provision of physical activity opportunities, the stress-relieving effects of nature and the facilitation of social contacts. This study sought to investigate whether urban green space was related to individual-level health outcomes, and whether levels of physical activity were likely to be a mediating factor in any relationships found. STUDY DESIGN: Cross-sectional analysis of anonymized individual health survey responses. METHODS: Neighbourhood-level green space availability was linked to 8157 respondents to the New Zealand Health Survey 2006/07 on the basis of their place of residence. Adjusted multilevel models were constructed for four health outcomes which are plausibly related to green space via physical activity: cardiovascular disease; overweight; poor general health; and poor mental health (Short Form 36). RESULTS: The greenest neighbourhoods had the lowest risks of poor mental health [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66-1.00]. Cardiovascular disease risk was reduced in all neighbourhoods with >15% green space availability (e.g. OR 0.80, 95% CI 0.64-0.99 for those with 33-70% green space), However, a dose-response relationship was not found. Green space availability was not related to overweight or poor general health. Overall, levels of physical activity were higher in greener neighbourhoods, but adjustment for this only slightly attenuated the green space and health relationships. CONCLUSIONS: Neighbourhood green space was related to better cardiovascular and mental health in a New Zealand Health Survey, independent of individual risk factors. Although physical activity was higher in greener neighbourhoods, it did not fully explain the green space and health relationship.