Long-term exposure to ambient ozone and mortality: a quantitative systematic review and meta-analysis of evidence from cohort studies.

OBJECTIVES: While there is good evidence for associations between short-term exposure to ozone and a range of adverse health outcomes, the evidence from narrative reviews for long-term exposure is suggestive of associations with respiratory mortality only. We conducted a systematic, quantitative evaluation of the evidence from cohort studies, reporting associations between long-term exposure to ozone and mortality. METHODS: Cohort studies published in peer-reviewed journals indexed in EMBASE and MEDLINE to September 2015 and PubMed to October 2015 and cited in reviews/key publications were identified via search strings using terms relating to study design, pollutant and health outcome. Study details and estimate information were extracted and used to calculate standardised effect estimates expressed as HRs per 10 ppb increment in long-term ozone concentrations. RESULTS: 14 publications from 8 cohorts presented results for ozone and all-cause and cause-specific mortality. We found no evidence of associations between long-term annual O3 concentrations and the risk of death from all causes, cardiovascular or respiratory diseases, or lung cancer. 4 cohorts assessed ozone concentrations measured during the warm season. Summary HRs for cardiovascular and respiratory causes of death derived from 3 cohorts were 1.01 (95% CI 1.00 to 1.02) and 1.03 (95% CI 1.01 to 1.05) per 10 ppb, respectively. CONCLUSIONS: Our quantitative review revealed a paucity of independent studies regarding the associations between long-term exposure to ozone and mortality. The potential impact of climate change and increasing anthropogenic emissions of ozone precursors on ozone levels worldwide suggests further studies of the long-term effects of exposure to high ozone levels are warranted.

Associations between short/medium-term variations in black smoke air pollution and mortality in the Glasgow conurbation, UK.

OBJECTIVES: To examine associations between short/medium-term variations in black smoke air pollution and mortality in the population of Glasgow and the adjacent towns of Renfrew and Paisley over a 25-year period at different time lags (0-30 days). METHODS: Generalised linear (Poisson) models were used to investigate the relationship between lagged black smoke concentrations and daily mortality, with allowance for confounding by cold temperature, between 1974 and 1998. RESULTS: When a range of lag periods were investigated significant associations were noted between temperature-adjusted black smoke exposure and all-cause mortality at lag periods of 13-18 and 19-24 days, and respiratory mortality at lag periods of 1-6, 7-12, and 13-18 days. Significant associations between cardiovascular mortality and temperature-adjusted black smoke were not observed. After adjusting for the effects of temperature a 10 µgm(-3) increase in black smoke concentration on a given day was associated with a 0.9% [95% Confidence Interval (CI): 0.3-1.5%] increase in all cause mortality and a 3.1% [95% CI: 1.4-4.9%] increase in respiratory mortality over the ensuing 30-day period. In contrast for a 10 µgm(-3) increase in black smoke concentration over 0-3 day lag period, the temperature adjusted exposure mortality associations were substantially lower (0.2% [95% CI: -0.0-0.4%] and 0.3% [95% CI: -0.2-0.8%] increases for all-cause and respiratory mortality respectively). CONCLUSIONS: This study has provided evidence of association between black smoke exposure and mortality at longer lag periods than have been investigated in the majority of time series analyses.

The production and degradation of trichloroacetic acid in soil: results from in situ soil column experiments.

Previous work has indicated that the soil is important to understanding biogeochemical fluxes of trichloroacetic acid (TCA) in the rural environment, in forests in particular. Here, the hydrological and TCA fluxes through 22 in situ soil columns in a forest and moorland-covered catchment and an agricultural grassland field in Scotland were monitored every 2 weeks for several months either as controls or in TCA manipulation (artificial dosing) experiments. This was supplemented by laboratory experiments with radioactively-labelled TCA and with irradiated (sterilised) soil columns. Control in situ forest soil columns showed evidence of net export (i.e. in situ production) of TCA, consistent with a net soil TCA production inferred from forest-scale mass balance estimations. At the same time, there was also clear evidence of substantial in situ degradation within the soil ( approximately 70% on average) of applied TCA. The laboratory experiments showed that both the formation and degradation processes operate on time scales of up to a few days and appeared related more with biological rather than abiotic processes. Soil TCA activity was greater in more organic-rich soils, particularly within forests, and there was strong correlation between TCA and soil biomass carbon content. Overall it appears that TCA soil processes exemplify the substantial natural biogeochemical cycling of chlorine within soils, independent of any anthropogenic chlorine flux.

A time-series study of the health effects of water-soluble and total-extractable metal content of airborne particulate matter.

OBJECTIVES: To assess whether adverse acute cardiopulmonary health outcomes are associated with concentration of trace metals in airborne particulate matter. METHODS: Daily PM(10) and PM(2.5) were collected for 1 year in Edinburgh, UK, and the water-soluble and total-extractable content of 11 trace metals determined in each sample. Time series were analysed using generalised additive Poisson regression models, including adjustment for minimum temperature and less smoothing of trends. Methods were explored of extending the time series of metal concentration in daily PM(10) for the previous 7 years using multiple regression of the variation in metal content for the 1 year of measurements and the associated variation in air mass source region and other concurrently-measured potential predictor variables. RESULTS: The 1 year of direct measurements showed no evidence of significant associations of particle-bound metal concentration with health outcomes beyond that expected by chance. Analysis of the extended time series showed significant positive associations with cardiovascular admissions both for total PM(10) and for a number of the metals (eg, Cu, Fe, Ni, V, Zn) but the metal effects were no longer significant after adjusting for PM(10). CONCLUSIONS: Within the limitations of the study power, the epidemiological results have not provided evidence for associations between particle-bound metal concentrations and adverse health outcomes that are substantially greater than for total PM. The generally strong correlations between metal and total PM suggest that quantifying independent effects of PM metal exposure on health will be difficult, even using more powerful time series of direct measurements.

Soluble transition metals in welding fumes cause inflammation via activation of NF-kappaB and AP-1.

We previously reported that the molecular pro-inflammatory effects of welding fumes in vitro were caused by soluble transition metals via an oxidative stress-mediated mechanism. Herein, we tested the hypothesis that transition metals in welding fume drive the in vivo inflammatory response caused by welding fume. Rats were instilled with either whole, soluble extract or washed welding fume particulates or soluble extracts pre-treated with a transition metal chelator. Markers of pulmonary inflammation were measured in the bronchoalveolar lavage fluid (BALF) and nuclear translocation of transcription factor was assessed in BAL cells by electrophoretic mobility shift assay. Instillation of either whole or soluble fractions of welding fume caused a significant influx of inflammatory cells and other markers of inflammation in the BALF 24 h later. MIP-2 protein in BALF and nuclear translocation of NF-kappaB and AP-1 were significantly greater following instillation of whole and soluble fractions than in saline-instilled lungs. Chelation of the soluble fraction, to remove transition metals, abolished the ability to cause inflammation, MIP-2 increase or transcription factor translocation to the nucleus. Instillation of washed particulates alone caused no significant change in any end-point compared to saline. This study demonstrates that soluble transition metals present in welding fumes cause inflammation via activation of the redox-sensitive transcription factors NF-kappaB and AP-1 and confirms the validity of utilising in vitro models to assess inflammatory responses to such particles.

Fluxes of trichloroacetic acid through a conifer forest canopy.

Controlled-dosing experiments with conifer seedlings have demonstrated an above-ground route of uptake for trichloroacetic acid (TCA) from aqueous solution into the canopy, in addition to uptake from the soil. The aim of this work was to investigate the loss of TCA to the canopy in a mature conifer forest exposed only to environmental concentrations of TCA by analysing above- and below-canopy fluxes of TCA and within-canopy instantaneous reservoir of TCA. Concentrations and fluxes of TCA were quantified for one year in dry deposition, rainwater, cloudwater, throughfall, stemflow and litterfall in a 37-year-old Sitka spruce and larch plantation in SW Scotland. Above-canopy TCA deposition was dominated by rainfall (86%), compared with cloudwater (13%) and dry deposition (1%). On average only 66% of the TCA deposition passed through the canopy in throughfall and stemflow (95% and 5%, respectively), compared with 47% of the wet precipitation depth. Consequently, throughfall concentration of TCA was, on average, approximately 1.4 x rainwater concentration. There was no significant difference in below-canopy fluxes between Sitka spruce and larch, or at a forest-edge site. Annual TCA deposited from the canopy in litterfall was only approximately 1-2% of above-canopy deposition. On average, approximately 800 microg m(-2) of deposited TCA was lost to the canopy per year, compared with estimates of above-ground TCA storage of approximately 400 and approximately 300 microg m(-2) for Sitka spruce and larch, respectively. Taking into account likely uncertainties in these values ( approximately +/- 50%), these data yield an estimate for the half-life of within-canopy elimination of TCA in the range 50-200 days, assuming steady-state conditions and that all TCA lost to the canopy is transferred into the canopy material, rather than degraded externally. The observations provide strong indication that an above-ground route is important for uptake of TCA specifically of atmospheric origin into mature forest canopies, as has been shown for seedlings (in addition to uptake from soil via transpiration), and that annualized within-canopy elimination is similar to that in controlled-dosing experiments.

Trichloroacetic acid cycling in Sitka spruce saplings and effects on sapling health following long term exposure.

Trichloroacetic acid (TCA, CCl(3)COOH) has been associated with forest damage but the source of TCA to trees is poorly characterised. To investigate the routes and effects of TCA uptake in conifers, 120 Sitka spruce (Picea sitchensis (Bong.) Carr) saplings were exposed to control, 10 or 100 microg l(-1) solutions of TCA applied twice weekly to foliage only or soil only over two consecutive 5-month growing seasons. At the end of each growing season similar elevated TCA concentrations (approximate range 200-300 ng g(-1) dwt) were detected in both foliage and soil-dosed saplings exposed to 100 microg l(-1) TCA solutions showing that TCA uptake can occur from both exposure routes. Higher TCA concentrations in branchwood of foliage-dosed saplings suggest that atmospheric TCA in solution is taken up indirectly into conifer needles via branch and stemwood. TCA concentrations in needles declined slowly by only 25-30% over 6 months of winter without dosing. No effect of TCA exposure on sapling growth was measured during the experiment. However at the end of the first growing season needles of saplings exposed to 10 or 100 microg l(-1) foliage-applied TCA showed significantly more visible damage, higher activities of some detoxifying enzymes, lower protein contents and poorer water control than needles of saplings dosed with the same TCA concentrations to the soil. At the end of each growing season the combined TCA storage in needles, stemwood, branchwood and soil of each sapling was <6% of TCA applied. Even with an estimated half-life of tens of days for within-sapling elimination of TCA during the growing season, this indicates that TCA is eliminated rapidly before uptake or accumulates in another compartment. Although TCA stored in sapling needles accounted for only a small proportion of TCA stored in the sapling/soil system it appears to significantly affect some measures of sapling health.

Fluxes and reservoirs of trichloroacetic acid at a forest and moorland catchment.

The concentrations and input/output fluxes of trichloroacetic acid (TCA) were measured in all relevant media for one year at a 0.86 km2 upland conifer plantation and moorland catchment in SW Scotland (n > 380 separate samples analyzed). Annual wet precipitation to the catchment was 2.5 and 0.4 m for rain and cloud, respectively. TCA input to the catchment for the year was 2100 g, predominantly in rainwater (86%), with additional input via cloudwater (13%) and gas plus particle dry deposition (1%). There were no seasonal trends in TCA deposition, and cloudwater concentration was not enhanced over rainwater. TCA in precipitation exceeded concentrations estimated using currently accepted routes of gas-phase oxidation from anthropogenic chlorinated hydrocarbon precursors, in agreement with previous studies. Export of TCA from the catchment in streamwater totalled 1970 g for the year of study. The TCA concentration in streamwater at outflow (median 1.2 microg L(-1)) was significantly greater than that before the stream had passed through the conifer plantation. To well-within measurement uncertainties, the catchment is currently at steady-state with respect to TCA input/output. The catchment reservoir of TCA was dominated by soils (approximately 90%), with the remainder distributed in forest litter (approximately 9%), forest branchwood and stemwood (approximately 0.7%), forest foliage (approximately 0.5%), and moorland foliage (approximately 0.1%). Although TCA is clearly taken up into foliage, which consequently may be important for the vegetation, this was a relatively minor process for TCA at the catchment scale. If it is assumed, on the basis of laboratory extraction experiments, that only approximately 20% of "whole soil" TCA measured in this work was water extractable, then total mass of TCA in the catchment is reduced from approximately 13 to approximately 3.5 kg. Comparing the latter value with the annual flux yields an average steady-state residence time for TCA in the catchment of approximately 1-2 y, if all TCA is involved in catchment turnover. Considering that other evidence indicates the lifetime of TCA in soil and biota is considerably shorter than this (weeks rather than years), the magnitude of the TCA reservoir is suggested to be strong evidence for net natural TCA production in soils and/or that the majority of TCA in the reservoir is not involved with external fluxes.

Atmospheric concentrations and deposition of trichloroacetic acid in Scotland: results from a 2-year sampling campaign.

The first long-term concurrent measurements of trichloroacetic acid (TCA) in rainwater, in cloudwater, and in air (both gas and particle phase) are reported. Measurements were made weekly between June 1998 and April 2000 at a rural forested upland site in SE Scotland. Rainwater TCA concentration did not differ significantly between two elevations (602 and 275 m asl), with precipitation-weighted mean values of 0.77 and 0.70 microg L(-1), respectively (n > 75). The precipitation-weighted mean concentration of TCA in cloudwater at the highest elevation was 0.92 microg L(-1), yielding an average cloudwater enrichment factor of 1.2, considerably lower than for other inorganic ions measured. Rainwater and cloudwater TCA concentrations did not vary systematically with season. Since wet precipitation depth also did not vary systematically with season, the wet deposition fluxes of TCA were likewise invariant (annual fluxes at the highest elevation of 880 and 130 microg m(-2), respectively, for rain and cloud interception to spruce forest). Weekly integrated concentrations of TCA in air (gas and particle) were very low (median 25 pg m(-3), range < LOD-110 pg m(-3)). The estimated upper limit for annual dry deposition of TCA at this site was approximately 20 microg m(-2), assuming a deposition velocity of 2 cm s(-1). Concentrations of TCA in air correlated reasonably strongly with concentrations in rainwater, with a partition ratio approximately equal to the Henry's law coefficient. On average, only about 23% of TCA measured in Edinburgh air was associated with the particle phase. These measurements are consistent with the observed high scavenging ratio of TCA (ratio of concentration in air to concentration in rainwater). Overall, these data confirm that the atmosphere is an important source of TCA to the environment and that precipitation is the dominant transfer mechanism. In line with previous work, the atmospheric deposition flux is greater than expected from the current understanding of atmospheric production of TCA from anthropogenic precursors. It is suggested that aqueous-phase processes could lead to greater atmospheric conversion of chlorinated solvent precursors to TCA than is currently accepted.

The Henry's law coefficient of 2-nitrophenol over the temperature range 278-303 K.

Although 2-nitrophenol has been identified as an important environmental chemical there is scarcity in the literature regarding the temperature dependence of its Henry's law coefficient, H. Here a bubble purge method was used to measure H for 2-nitrophenol over the temperature range 278-303 K. A novel approach in the data treatment allowed correction of the data for non-equilibrium partitioning in the apparatus to obtain the true equilibrium H value. The experimentally derived temperature-dependent expression for H of 2-nitrophenol is lnH (M atm(-1)) = (6290/T (K)) - 16.6. The standard enthalpy and entropy of gas-to-liquid transfer for 2-nitrophenol in aqueous solution are -52.3 +/- 8.1 kJ mol(-1) and -138 +/- 28 J mol(-1) K(-1), respectively. (Errors are 95% confidence intervals.)

A new method for the determination of trichloroacetic acid in spruce foliage and other environmental media.

Trichloroacetic acid (TCAA) is a phytotoxic chemical, present throughout the environment. The majority of methods for analysis of TCAA require chemical derivatisation and multiple extraction steps prior to analysis by gas-chromatography. Here, a new analytical method for TCAA determination in environmental matrices is reported. The method is based on a modified Nielsen-Kryger steam distillation that combines into one 1 h reflux the thermal decarboxylation of TCAA to CHCl3 and the partitioning and concentration of the CHCl3 into 5 ml of hexane, which is analysed by GC. Sample preparation is minimal and no matrix standard additions are required. The background CHCl3 in the sample is removed prior to extraction by degassing the solution for 1 h with nitrogen. Optimisation of the method gave recoveries from three separate solutions of 0.31 ppb aqueous TCAA standards of 93 +/- 15% (n = 9), 110 +/- 9% (n = 9) and 105 +/- 11% (n = 6). The extraction method has been compared with a decarboxylation and headspace GC method for determination of TCAA in Sitka spruce needles. No significant difference in TCAA concentration or replicate precision between the two methods was observed.

Intercomparison of five PM10 monitoring devices and the implications for exposure measurement in epidemiological research.

Five different instruments for the determination of the mass concentration of PM10 in air were compared side-by-side for up to 33 days in an undisturbed indoor environment: a tripod mounted BGI Inc. PQ100 gravimetric sampler with a US EPA certified Graseby Andersen PM10 inlet; an Airmetrics Minivol static gravimetric sampler; a Casella cyclone gravimetric personal sampler; an Institute of Occupational Medicine gravimetric PM10 personal sampler; and two TSI Inc. Dustrak real-time optical scattering personal samplers. For 24 h sampling of ambient PM10 concentrations around 10 microg m(-3), the estimated measurement uncertainty for the two gravimetric personal samplers was larger (approximately +/- 20%) compared with estimated measurement uncertainty for the PQ100/Graseby Andersen sampler (< +/- 5%). Measurement uncertainty for the Dustraks was lower (approximately +/- 15% on average) but calibration of the optical response against a reference PM10 method is essential since the Dustraks systematically over-read PM10 determined gravimetrically by a factor approximately 2.2. However, once calibrated, the Dustrak devices demonstrated excellent functionality in terms of ease of portability and real-time data acquisition. Estimated measurement uncertainty for PM10 concentrations determined with the Minivol were +/- 5%. The Minivol data correlated well with PQ100/Graseby Andersen data (r= 0.97, n = 18) but were, on average, 23% greater. The reason for the systematic discrepancy could not be traced. Intercomparison experiments such as these are essential for assessing measurement error and revealing systematic bias. Application of two Dustraks demonstrated the spatial and temporal variability of exposure to PM10 in different walking and transport microenvironments in the city of Edinburgh, UK. For example, very large exposures to PM10 were identified for the lower deck of a double-decker tour bus compared with the open upper deck of the same vehicle. The variability observed emphasises the need to determine truly personal exposure profiles of PM10 for quantifying exposure response relationships for epidemiological studies.

Circumcision: how do urologists do it?

OBJECTIVE: To determine the range of surgical techniques, analgesic practice, post-operative care and follow-up procedures used in the circumcision of children by urologists in the United Kingdom, and to suggest changes which would improve patient care and medical training in the relatively simple procedure of circumcision. MATERIALS AND METHODS: In 1994, all consultant urologists in the United Kingdom were sent detailed questionnaires asking about their practices in the circumcision of children. RESULTS: Of 308 urologists, 61% replied; of these, 55% use the sleeve-resection technique and 39% the free-hand method, and 57% use diathermy, half of which is bipolar. There is wide variation in the type of post-operative analgesia; 95% use an initial dressing but few recommend any subsequent dressing, 70% perform all circumcisions as day cases and 48% review patients in the clinic. There is significant concern that circumcision is not taught adequately to junior surgeons. CONCLUSION: The sleeve technique of resection should be more widely used. Analgesic practice could be improved with greater use of regional anaesthetics. Most urologists promote no specific care after discharge. There is probably a place for increasing the use of alternative procedures to circumcision.

Postoperative spindle cell nodule of the bladder: a diagnostic problem.

A case of postoperative spindle cell nodule of the bladder is reported. Initial pathological analysis was interpreted as leiomyosarcoma for which the patient underwent radical cystectomy, but subsequent reviews were consistent with a postoperative spindle cell nodule. Recognition of this benign, yet rare lesion is of significant importance to urologists, pathologists, and to the patient who may undergo extensive surgical procedure unnecessarily.

Marker tumour response to Evans and Pasteur bacille Calmette-Guérin in multiple recurrent pTa/pT1 bladder tumours: report from the Medical Research Council Subgroup on Superficial Bladder Cancer (Urological Cancer Working Party).

OBJECTIVE: To compare the efficacy of Evans bacille Calmette-Guérin (BCG) and Pasteur BCG in eradicating marker bladder tumours and to compare the toxicity of the two strains. PATIENTS AND METHODS: Ninety-nine patients with multiple recurrent pTa or pT1 bladder tumours were allocated at random to six instillations at weekly intervals of either Evans BCG or Pasteur BCG. All tumours were resected except one marker tumour. At cystoscopy 3 months after randomization all tumours including the marker tumour, if still present, were resected. RESULTS: The incidence of adverse events was similar in the two groups but numbers were small and only large differences would have been detected. No statistically significant difference in efficacy regarding the response of the marker tumour or the appearance of other tumours at 3 months was noted in the two groups. There was no evidence of stage progression of the marker tumours. CONCLUSIONS: In multiple recurrent pTa or pT1 bladder tumours clearing the bladder of all except one marker tumour provides a safe and convenient way of measuring the response to intravesical therapy. No significant difference in efficacy or toxicity was detected between Evans BCG and Pasteur BCG.

Study of the seminal vesicles in acute epididymitis.

Although it has been suggested that seminal vesiculitis is present in patients with epididymitis, it has not been proven. We performed rectal ultrasound assessment of the seminal vesicles in 18 consecutive patients with epididymitis. The seminal vesicles on the same side as the epididymitis was significantly enlarged in 75% of cases; 92% of these enlarged vesicles returned to normal size in 12 weeks. A persistently enlarged seminal vesicle was associated with unresolved epididymitis, and further bacteriological studies in these cases demonstrated continued Chlamydia infection in some patients over 35 years of age.

An evaluation of techniques used for the production of temporary renal ischaemia.

Five techniques of producing temporary renal ischaemia have been evaluated in the rat. Damage was assessed by measuring inulin clearance, change in renal cortical intracellular water and 125I-fibrin deposition. Continuous renal artery occlusion produces significantly less renal damage than the other techniques commonly used.

Four years' experience with indwelling Silastic cannulae for long-term peritoneal dialysis.

Indwelling silicone rubber cannulae have been used for peritoneal dialysis in 41 uraemic patients for periods of up to 46 months. The simplicity of this treatment is particularly suited to patients awaiting transplantation.