The burden of heat-related mortality attributable to recent human-induced climate change.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

Mental Component Score (MCS) from Health-Related Quality of Life Predicts Incidence of Dementia in U.S. Males.

BACKGROUND: The Medical Outcomes Study Questionnaire Short Form 36 health survey (SF-36) measures health-related quality of life (HRQoL) from the individual's point of view and is an indicator of overall health status. OBJECTIVE: To examine whether HRQoL shows differential changes over time prior to dementia onset and investigate whether HRQoL predicts incidence of dementia. DESIGN: Prevention of Alzheimer's Disease (AD) by Vitamin E and Selenium (PREADViSE) trial, which recruited 7,547 non-demented men between 2002 and 2009. A subset of 2,746 PREADViSE participants who completed up to five SF-36 assessments at annual visits was included in the current analysis. SETTING: Secondary data analysis of PREADViSE data. PARTICIPANTS: A subset of 2,746 PREADViSE participants who completed up to five SF-36 assessments at annual visits was included in the current analysis. MEASUREMENTS: Two summary T scores were generated for analysis: physical component score (PCS) and mental component score (MCS), each with a mean of 50 (standard deviation of 10); higher scores are better. Linear mixed models (LMM) were applied to determine if mean component scores varied over time or by eventual dementia status. Cox proportional hazards regression was used to determine if the baseline component scores were associated with dementia incidence, adjusting for baseline age, race, APOE-4 carrier status, sleep apnea, and self-reported memory complaint at baseline. RESULTS: The mean baseline MCS score for participants who later developed dementia (mean± SD: 53.9±9.5) was significantly lower than for those participants who did not develop dementia during the study (mean±SD: 56.4±6.5; p = 0.005). Mean PCS scores at baseline (dementia: 49.3±7.9 vs. non-dementia: 49.8±7.8) were not significantly different (p = 0.5) but LMM analysis showed a significant time effect. For MCS, the indicator for eventual dementia diagnosis was significantly associated with poorer scores after adjusting for baseline age, race, and memory complaint. Adjusted for other baseline risk factors, the Cox model showed that a 10-unit increase in MCS was associated with a 44% decrease in the hazard of a future dementia diagnosis (95% CI: 32%-55%). CONCLUSION: The SF-36 MCS summary score may serve as a predictor for future dementia and could be prognostic in longitudinal dementia research.

Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer: risk and mortality in The Pooling Project of Prospective Studies of Diet and Cancer.

BACKGROUND: Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk. PATIENTS AND METHODS: We carried out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models. RESULTS: No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95-1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12-2.07) comparing BMI ≥35.0 kg/m2 with 21-22.9 kg/m2. When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI <25.0 kg/m2 in early adulthood and BMI ≥30.0 kg/m2 at baseline compared with BMI <25.0 kg/m2 in early adulthood and BMI <30.0 kg/m2 at baseline. Baseline waist circumference, comparing ≥110 cm with <90 cm, and waist-to-hip ratio, comparing ≥1.00 with <0.90, were associated with significant 14%-16% increases in high-grade prostate cancer risk and suggestive or significant 20%-39% increases in prostate cancer mortality risk. Height was associated with suggestive or significant 33%-56% risks of advanced or advanced restricted prostate cancer and prostate cancer mortality, comparing ≥1.90 m with <1.65 m. CONCLUSION: Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer.

The treatment of uncertainties in reactive pollution dispersion models at urban scales.

The ability to predict NO2 concentrations ([NO2]) within urban street networks is important for the evaluation of strategies to reduce exposure to NO2. However, models aiming to make such predictions involve the coupling of several complex processes: traffic emissions under different levels of congestion; dispersion via turbulent mixing; chemical processes of relevance at the street-scale. Parameterisations of these processes are challenging to quantify with precision. Predictions are therefore subject to uncertainties which should be taken into account when using models within decision making. This paper presents an analysis of mean [NO2] predictions from such a complex modelling system applied to a street canyon within the city of York, UK including the treatment of model uncertainties and their causes. The model system consists of a micro-scale traffic simulation and emissions model, and a Reynolds averaged turbulent flow model coupled to a reactive Lagrangian particle dispersion model. The analysis focuses on the sensitivity of predicted in-street increments of [NO2] at different locations in the street to uncertainties in the model inputs. These include physical characteristics such as background wind direction, temperature and background ozone concentrations; traffic parameters such as overall demand and primary NO2 fraction; as well as model parameterisations such as roughness lengths, turbulent time- and length-scales and chemical reaction rate coefficients. Predicted [NO2] is shown to be relatively robust with respect to model parameterisations, although there are significant sensitivities to the activation energy for the reaction NO + O3 as well as the canyon wall roughness length. Under off-peak traffic conditions, demand is the key traffic parameter. Under peak conditions where the network saturates, road-side [NO2] is relatively insensitive to changes in demand and more sensitive to the primary NO2 fraction. The most important physical parameter was found to be the background wind direction. The study highlights the key parameters required for reliable [NO2] estimations suggesting that accurate reference measurements for wind direction should be a critical part of air quality assessments for in-street locations. It also highlights the importance of street scale chemical processes in forming road-side [NO2], particularly for regions of high NOx emissions such as close to traffic queues.

International scale implementation of the CNOSSOS-EU road traffic noise prediction model for epidemiological studies.

The EU-FP7-funded BioSHaRE project is using individual-level data pooled from several national cohort studies in Europe to investigate the relationship of road traffic noise and health. The detailed input data (land cover and traffic characteristics) required for noise exposure modelling are not always available over whole countries while data that are comparable in spatial resolution between different countries is needed for harmonised exposure assessment. Here, we assess the feasibility using the CNOSSOS-EU road traffic noise prediction model with coarser input data in terms of model performance. Starting with a model using the highest resolution datasets, we progressively introduced lower resolution data over five further model runs and compared noise level estimates to measurements. We conclude that a low resolution noise model should provide adequate performance for exposure ranking (Spearman's rank = 0.75; p < 0.001), but with relatively large errors in predicted noise levels (RMSE = 4.46 dB(A)).

Intraprostatic inflammation is positively associated with serum PSA in men with PSA <4 ng ml(-1), normal DRE and negative for prostate cancer.

BACKGROUND: Biopsies performed for elevated serum PSA often show inflammatory infiltrates. However, the influence of intraprostatic inflammation on serum PSA in men without biopsy indication and negative for prostate cancer has not been described in detail. METHODS: We studied 224 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT) who underwent end-of-study biopsy per trial protocol, had PSA <4 ng ml(-1), normal digital rectal examination and a biopsy negative for cancer. We analyzed data from hematoxylin and eosin-stained slides containing a mean of three biopsy cores. Inflammation measures included the extent (percentage of tissue area with inflammation) and intensity (product of scores for extent and grade) of total, acute and chronic inflammation in the entire tissue area examined, and by tissue compartment. We calculated median measures of inflammation by prebiopsy serum PSA tertile (>0 to ≤0.8, >0.8 to ≤1.5 and >1.5 to <4.0 ng ml(-1)). We estimated the association between percentage of tissue area with inflammation and natural logarithm of PSA using linear regression adjusting for age at biopsy. RESULTS: Median percentage of tissue area with inflammation increased from 2 to 5 to 9.5% across PSA tertiles (P-trend <0.0001). For every 5% increase in tissue area with inflammation, log PSA increased by 0.061 ng ml(-1) (P=0.0002). Median extent and intensity scores increased across PSA tertiles in luminal and intraepithelial compartments for acute inflammation and in stromal and intraepithelial compartments for chronic inflammation (all P-trend ≤0.05). CONCLUSIONS: In men without clinical suspicion of prostate cancer, greater overall inflammation, luminal and intraepithelial acute inflammation and stromal and intraepithelial chronic inflammation were associated with higher serum PSA.

Comparison of colour duplex ultrasound with computed tomography to measure the maximum abdominal aortic aneurysmal diameter.

Introduction. Maximum diameter of an abdominal aortic aneurysm (AAA) is the main indication for surgery. This study compared colour duplex ultrasound (CDU) and computed tomography (CT) in assessing AAA diameter. Patients and Methods. Patients were included if they had both scans performed within 90 days. Pearson's correlation coefficient, paired t-test, and limits of agreement (LOA) were calculated for the whole group. Subgroup analysis of small (<5.0 cm), medium (5.0-6.5 cm), and large (>6.5 cm) aneurysms was performed. A P value of <0.05 was considered statistically significant. Results. 389 patients were included, giving 130 pairs of tests for comparison. Excellent correlation was in the whole group (r = 0.95) and in the subgroups (r = 0.94; 0.69; 0.96, resp.). Small LOA between the two imaging modalities was found in all subgroups. Conclusion. Small aneurysms can be accurately measured using CDU. CDU is preferable for small AAAs, but cannot supplant CT for planning aortic intervention.

Chest radiography for predicting the cause of febrile illness among inpatients in Moshi, Tanzania.

AIM: To describe chest radiographic abnormalities and assess their usefulness for predicting causes of fever in a resource-limited setting. MATERIALS AND METHODS: Febrile patients were enrolled in Moshi, Tanzania, and chest radiographs were evaluated by radiologists in Tanzania and the United States. Radiologists were blinded to the results of extensive laboratory evaluations to determine the cause of fever. RESULTS: Of 870 febrile patients, 515 (59.2%) had a chest radiograph available; including 268 (66.5%) of the adolescents and adults, the remainder were infants and children. One hundred and nineteen (44.4%) adults and 51 (20.6%) children were human immunodeficiency virus (HIV)-infected. Among adults, radiographic abnormalities were present in 139 (51.9%), including 77 (28.7%) with homogeneous and heterogeneous lung opacities, 26 (9.7%) with lung nodules, 25 (9.3%) with pleural effusion, 23 (8.6%) with cardiomegaly, and 13 (4.9%) with lymphadenopathy. Among children, radiographic abnormalities were present in 87 (35.2%), including 76 (30.8%) with homogeneous and heterogeneous lung opacities and six (2.4%) with lymphadenopathy. Among adolescents and adults, the presence of opacities was predictive of Streptococcus pneumoniae and Coxiella burnetii, whereas the presence of pulmonary nodules was predictive of Histoplasma capsulatum and Cryptococcus neoformans. CONCLUSIONS: Chest radiograph abnormalities among febrile inpatients are common in northern Tanzania. Chest radiography is a useful adjunct for establishing an aetiologic diagnosis of febrile illness and may provide useful information for patient management, in particular for pneumococcal disease, Q fever, and fungal infections.

A randomized controlled Alzheimer's disease prevention trial's evolution into an exposure trial: the PREADViSE Trial.

OBJECTIVES: To summarize the ongoing prevention of Alzheimer's disease (AD) by vitamin E and selenium (PREADViSE) trial as an ancillary study to SELECT (a large prostate cancer prevention trial) and to present the blinded results of the first year as an exposure study. DESIGN: PREADViSE was designed as a double blind randomized controlled trial (RCT). SETTING: SELECT terminated after median of 5.5 years of exposure to supplements due to a futility analysis. Both trials then converted into an exposure study. PARTICIPANTS: In the randomized component PREADViSE enrolled 7,547 men age 62 or older (60 if African American). Once the trial terminated 4,246 of these men volunteered for the exposure study. Demographics were similar for both groups with exposure volunteers having baseline mean age 67.3 ± 5.2 years, 15.3 ± 2.4 years of education, 9.8% African Americans, and 22.0% reporting a family history of dementia. INTERVENTION: In the RCT men were randomly assigned to either daily doses of 400 IU of vitamin E or placebo and 200 µg of selenium or placebo using a 2x2 factorial structure. MEASUREMENTS: In the RCT, participants completed the memory impairment screen (MIS), and if they failed, underwent a longer screening (based on an expanded Consortium to Establish a Registry in AD [CERAD] battery). CERAD failure resulted in visits to their clinician for medical examination with records of these examinations forwarded to the PREADViSE center for further review. In the exposure study, men are contacted by telephone and complete the telephone version of the memory impairment screen (MIS-T) screen. If they fail the MIS-T, a modified telephone interview of cognitive status (TICS-M) exam is given. A failed TICS-M exam also leads to a visit to their clinician for an in-depth examination and forwarding of records for a centralized consensus diagnosis by expert clinicians. A subgroup of the men who pass the MIS-T also take the TICS-M exam for validation purposes. RESULTS: While this ancillary trial was open to all 427 SELECT clinical sites, only 130 (30.0%) of the sites chose to participate in PREADViSE. Staff turnover at the sites presented challenges when training persons unfamiliar with cognitive testing procedures to conduct the memory screens. In the RCT few participants (1.6%) failed the MIS screen and among those who passed this screen a significant practice effect was encountered. In the exposure study 3,581 men were reached by phone in year 1, 15.7% could not be reached after 5 calls, and of those contacted 6.0% refused the screen even after consenting to the procedures at their clinical site. Most notable is that the failure rate for the MIS-T increased fourfold to 7.2%. Of the 257 men who took the TICS-M, 84.0% failed and were asked to contact their physicians for a more detailed memory assessment, and approximately half of these had some form of dementia or cognitive impairment. Several of these dementia cases are not AD. CONCLUSION: Partnering with SELECT led to an AD prevention trial conducted at a very reasonable cost by taking advantage of the experience and efficient clinical trial management found in a cancer cooperative group (Southwest Oncology Group or SWOG). Once unblinded, the RCT and exposure study data have the potential to yield new information on long term exposure to antioxidant supplements under controlled conditions.

Use of colour duplex ultrasound as a first line surveillance tool following EVAR is associated with a reduction in cost without compromising accuracy.

INTRODUCTION: CT scanning remains the postoperative surveillance imaging modality of choice following EVAR. Concerns regarding cost, exposure to ionising radiation and intravenous contrast have led to a search for a less expensive, equally efficacious and safer method of monitoring EVAR patients after endograft deployment. This study evaluated the cost saving obtained if CDUS was employed as a first line surveillance tool following EVAR, as well as comparing the two entities in terms of efficacy. PATIENTS & METHODS: Postoperative surveillance CTs and CDUS scans in the 145 patients who have undergone EVAR from 1st June 2003 to 1st July 2010 were compared for the detection of endoleak and determination of residual sac size. RESULTS: Adopting a protocol where CDUS was employed as the first line surveillance tool following EVAR would result in a reduction in the number of postoperative CTs required in 2010 from 235 to 36. Based on 2010 costings, this would equate to an estimated reduction in expenditure from €117,500 to €34,915 a saving of €82,585. CDUS had a sensitivity of 100% and a specificity of 85% in the detection of endoleaks compared to CT. The positive predictive value was 28% and negative predictive value 100%. The Pearson Coefficient correlation of 0.96 indicates a large degree of correlation between CDUS and CT when measuring residual aneurysm size following EVAR. CONCLUSION: CDUS can replace CT as the first line surveillance tool following EVAR. This is associated with a significant reduction in the cost of surveillance without any loss of imaging accuracy.

Should any workplace be exempt from smoke-free law: the Irish experience.

BACKGROUND: In 2004, the Irish Government introduced national legislation banning smoking in workplaces; with exemptions for "a place of residence". This paper summarises three Irish studies of exempted premises; prisons, psychiatric hospitals and nursing homes. METHODS: PM(2.5) and nicotine were measured in nursing homes and psychiatric hospitals, in addition to ultrafine particles in the hospitals. In the prisons, officers (n = 30) completed exhaled breath Carbon Monoxide (CO) measurements. Questionnaires determined officers' opinion on introducing smoking prohibitions in prisons. Nursing home smoking policies were examined and questionnaires completed by staff regarding workplace secondhand smoke (SHS) exposure. FINDINGS: Ultrafine particle concentrations in psychiatric hospitals averaged 130,000 cm(3), approximately 45% higher than Dublin pub (35.5 µg/m(3)) pre ban. PM(2.5) levels in psychiatric hospitals (39.5 µg/m(3)) were similar to Dublin pubs (35.5 µg/m(3)) pre ban. In nursing homes permitting smoking, similar PM(2.5) levels (33 µg/m(3)) were measured, with nicotine levels (0.57 µg/m(3)) four times higher than "non-smoking" nursing homes (0.13 µg/m(3)). In prisons, 44% of non-smoking officers exhibited exhaled breath CO criteria for light to heavy smokers. CONCLUSIONS: With SHS exposure levels in some exempted workplaces similar to Dublin pubs levels pre ban, policies ensuring full protection must be developed and implemented as a right for workers, inmates and patients.

Active smoking and second-hand-smoke exposure at home among Irish children, 1995-2007.

OBJECTIVE: This study hypothesised a continual decline in current smoking prevalence over four calendar years (1995, 1998, 2002/03 and 2007) and no significant increase in second-hand-smoke (SHS) exposure levels at home after the workplace smoking ban of March 2004 (2007 versus 2002/03 survey) among Irish school children. METHODS: A modified ISAAC (International Study of Asthma and Allergies in Childhood) protocol was used. Children aged 13-14 years from randomly selected representative post-primary schools were studied: 2670 in 1995, 2273 in 1998, 2892 in 2002-2003, and 2805 in 2007. ISAAC is a cross-sectional self-administered questionnaire survey. Smoking history was self-reported. beta Coefficients (slopes) of smoking rates across the four surveys were computed. Odds ratios for smoking rates were also computed using the baseline year (1995) as the reference period. All analyses were performed using SAS software (v 9.1). RESULTS: There were significant reductions in active smoking rates between 1995 and 2007 (from 19.9% to 10.6%, respectively) resulting in 3.3% survey-to-survey reductions, with a significantly greater survey-to-survey decline among girls compared to boys (3.8% vs 2.7%, respectively). 45% of children were exposed to SHS at home in 2007. There was a statistically non-significant 2% overall decline in SHS exposure levels at home in 2007 relative to 2002/03, which was more pronounced in girls. CONCLUSIONS: The continual reduction in active smoking prevalence in children is welcome. That there was no significant increase in SHS exposure at home after the nationwide workplace smoking ban suggests that the ban did not increase smoking inside homes.

Second-hand smoke exposure in cars and respiratory health effects in children.

We examined potential associations of ever asthma, and symptoms of wheeze (past 12 months), hay fever, eczema and bronchitis (cough with phlegm) among school children exposed to second-hand smoke (SHS) in cars, using a modified Irish International Study of Asthma and Allergies in Childhood (ISAAC) protocol. 2,809 children of 13-14 yrs old and who selected randomly from post-primary schools throughout Ireland completed the 2007 ISAAC self-administered questionnaire. Adjusted OR (adjusted for sex, active smoking status of children interviewed and their SHS exposure at home) were estimated for the associations studied, using multivariable logistic regression techniques. Overall, 14.8% (13.9% in young males, 15.4% in young females) of Irish children aged 13-14 yrs old were exposed to SHS in cars. Although there was a tendency towards increased likelihood of both respiratory and allergic symptoms with SHS exposure in cars, wheeze and hay fever symptoms were significantly higher (adjusted OR 1.35 (95% CI 1.08-1.70) and 1.30 (1.01-1.67), respectively), while bronchitis symptoms and asthma were not significant (1.33 (0.92-1.95) and 1.07 (0.81-1.42), respectively). Approximately one in seven Irish schoolchildren are exposed to SHS in cars and could have adverse respiratory health effects. Further studies are imperative to explore such associations across different population settings.

Effects of cold weather on mortality: results from 15 European cities within the PHEWE project.

Weather-related health effects have attracted renewed interest because of the observed and predicted climate change. The authors studied the short-term effects of cold weather on mortality in 15 European cities. The effects of minimum apparent temperature on cause- and age-specific daily mortality were assessed for the cold season (October-March) by using data from 1990-2000. For city-specific analysis, the authors used Poisson regression and distributed lag models, controlling for potential confounders. Meta-regression models summarized the results and explored heterogeneity. A 1 degrees C decrease in temperature was associated with a 1.35% (95% confidence interval (CI): 1.16, 1.53) increase in the daily number of total natural deaths and a 1.72% (95% CI: 1.44, 2.01), 3.30% (95% CI: 2.61, 3.99), and 1.25% (95% CI: 0.77, 1.73) increase in cardiovascular, respiratory, and cerebrovascular deaths, respectively. The increase was greater for the older age groups. The cold effect was found to be greater in warmer (southern) cities and persisted up to 23 days, with no evidence of mortality displacement. Cold-related mortality is an important public health problem across Europe. It should not be underestimated by public health authorities because of the recent focus on heat-wave episodes.

The value of end-of-treatment chest radiograph in predicting pulmonary tuberculosis relapse.

SETTING: Patients with cavitary pulmonary tuberculosis (TB) on baseline chest radiograph (CXR) who remain culture-positive after 8 weeks of treatment are at high risk of relapse. The role of end-of-treatment (EOT) CXR in predicting relapse is unclear. OBJECTIVE: To determine whether EOT CXR independently predicts TB relapse. DESIGN: We conducted a secondary analysis of a randomized trial of intermittent treatment using rifapentine in the continuation phase of TB treatment among 1004 human immunodeficiency virus seronegative adults with culture-proven pulmonary TB. RESULTS: Relapse occurred in 17.3% of subjects with persistent cavity on EOT CXR, in 7.6% of subjects with a cavity that resolved by EOT, and 2.5% (P=0.002 for trend) of subjects who never had a cavity. In multivariable analysis, patients with persistent cavity on EOT CXR were significantly more likely to relapse than patients with no cavity on baseline or 2-month CXR (hazard ratio [HR] 4.22, 95%CI 2.00-8.91), and were more likely to relapse than subjects whose early cavity had resolved by EOT CXR (HR 1.92, 95%CI 1.09-3.39). CONCLUSION: A persistent cavity after 6 months of TB treatment was independently associated with disease relapse after controlling for other variables. EOT CXR may help predict those likely to relapse.

Rising prevalence of asthma but declining wheeze in teenagers (1995-2003): ISAAC protocol.

The results of the initial International Study of Asthma and Allergies in Childhood (ISAAC) undertaken in the mid 1990s demonstrated a substantial increase in asthma and wheeze symptoms prevalence in Irish teenagers aged 13-14 years from the 1980s. International research suggests that asthma has increased further in some countries and this study was undertaken to determine whether an upward trend in childhood asthma prevalence has continued in the Republic of Ireland in recent years. We therefore conducted two further national cross sectional studies in the same previously surveyed childhood population throughout the Republic of Ireland, one in 1998 (n=2580) and the other in 2002-3 (n=3089). We report here on rising prevalence trends of asthma (42.1% relative increase) but falling wheeze (10.4% relative reduction) prevalence in these teenage children in 2002-3.

Smoking, occupancy and staffing levels in a selection of Dublin pubs pre and post a national smoking ban, lessons for all.

BACKGROUND: On the 29th March 2004 the Irish government introduced a comprehensive workplace smoking ban to protect the health of workers. This study evaluates the impact the ban had on staffing levels, customer numbers and smoking rates in a sample of 38 public houses in Dublin. METHODS: A total of 38 public houses were visited prior to the introduction of the ban, each visit lasted at least three hours, and the number of staff, customers and the number of people smoking was recorded each hour. Follow-up visits were conducted exactly one year later, on the same day of the week and at the same time of day, allowing controlling for seasonal and weekday effects. RESULTS: There was a decrease (8.82%) in average staff levels while customer numbers increased by 11% and there was a dramatic reduction in numbers smoking on a visit to a pub (77.8%). CONCLUSIONS: The hospitality industry predicted major job losses as a consequence of the introduction of the smoking ban; this work has shown that there was no significant decrease in the number of staff employed or in customer numbers. There was full compliance, with no customers smoking inside the public houses following the introduction of the ban. The ban has been good for the industry, staff, and customers.

Rational drug design of multifunctional phosphoramidate substituted nucleoside analogs.

This review focuses on our approach to the study of the effect of a series of phosphoramidate substituted nucleoside analogs on model systems for cancer, HIV and fertility. This approach allowed the development of compound WHI-07, an arylphosphoramidate derivative of zidavudine. This compound is a multifunctional agent showing potent activity in the above mentioned model systems. Our rational drug design provided such a powerful derivative with all the necessary characteristic of a drug candidate. Importantly, we have experimental evidence that each of the groups associated with the molecular frame of WHI-07 imparts the multifunctional ability for this agent. In addition, we have also suggested a possible biological pathway for WHI-07 including various products with their therapeutic targets that are formed during the course of its metabolism inside the cell. We also propose which individual moieties in the structure of WHI-07 are responsible for the biological activity from the formation of these metabolites. A detailed structure-activity relationship is presented in the review in connection with various structural modifications of the agent. Application of this active agent in animal models shows the potential usefulness of this agent as a drug candidate. We further plan to utilize gene-chip technology to identify new targets and modes of action using microarrays to measure expression changes in thousands of gene products. In conclusion, we have demonstrated the power of multifunctional drug design to discover drugs to combat various diseases. We believe this is the future direction of the drug discovery process.

Short-term effects of ambient particles on mortality in the elderly: results from 28 cities in the APHEA2 project.

Within the framework of the APHEA2 (Air Pollution on Health: a European Approach) project, the effects of ambient particles on mortality among persons > or = 65 yrs were investigated. Daily measurements for particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) and black smoke (BS), as well as the daily number of deaths among persons > or = 65 yrs of age, from 29 European cities, have been collected. Data on other pollutants and meteorological variables, to adjust for confounding effects and data on city characteristics, to investigate potential effect modification, were also recorded. For individual city analysis, generalised additive models extending Poisson regression, using a locally weighted regression (LOESS) smoother to control for seasonal effects, were applied. To combine individual city results and explore effect modification, second stage regression models were applied. The per cent increase (95% confidence intervals), associated with a 10 microg x m(-3) increase in PM10, in the elderly daily number of deaths was 0.8%, (0.7-0.9%) and the corresponding number for BS was 0.6%, (0.5-0.8%). The effect size was modified by the long-term average levels of nitrogen dioxide (higher levels were associated with larger effects), temperature (larger effects were observed in warmer countries), and by the proportion of the elderly in each city (a larger proportion was associated with higher effects). These results indicate that ambient particles have effects on mortality among the elderly, with relative risks comparable or slightly higher than those observed for total mortality and similar effect modification patterns. The effects among the older persons are of particular importance, since the attributable number of events will be much larger, compared to the number of deaths among the younger population.