Deletion diagnostics for the generalised linear mixed model with independent random effects.

The Generalised linear mixed model (GLMM) is widely used for modelling environmental data. However, such data are prone to influential observations, which can distort the estimated exposure-response curve particularly in regions of high exposure. Deletion diagnostics for iterative estimation schemes commonly derive the deleted estimates based on a single iteration of the full system holding certain pivotal quantities such as the information matrix to be constant. In this paper, we present an approximate formula for the deleted estimates and Cook's distance for the GLMM, which does not assume that the estimates of variance parameters are unaffected by deletion. The procedure allows the user to calculate standardised DFBETAs for mean as well as variance parameters. In certain cases such as when using the GLMM as a device for smoothing, such residuals for the variance parameters are interesting in their own right. In general, the procedure leads to deleted estimates of mean parameters, which are corrected for the effect of deletion on variance components as estimation of the two sets of parameters is interdependent. The probabilistic behaviour of these residuals is investigated and a simulation based procedure suggested for their standardisation. The method is used to identify influential individuals in an occupational cohort exposed to silica. The results show that failure to conduct post model fitting diagnostics for variance components can lead to erroneous conclusions about the fitted curve and unstable confidence intervals.

Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells.

BACKGROUND: Evidence suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) increases atopy; it is unclear how PAH exposure is linked to increased severity of atopic diseases. OBJECTIVE: We hypothesized that ambient PAH exposure is linked to impairment of immunity in atopic children (defined as children with asthma and/or allergic rhinitis) from Fresno, California, an area with elevated ambient PAHs. METHODS: We recruited 256 subjects from Fresno, CA. Ambient PAH concentrations (ng/m(3) ) were measured using a spatial-temporal regression model over multiple time periods. Asthma diagnosis was determined by current NHLBI criteria. Phenotyping and functional immune measurements were performed from isolated cells. For epigenetic measurements, DNA was isolated and pyrosequenced. RESULTS: We show that higher average PAH exposure was significantly associated with impaired Treg function and increased methylation in the forkhead box protein 3 (FOXP3) locus (P < 0.05), conditional on atopic status. These epigenetic modifications were significantly linked to differential protein expression of FOXP3 (P < 0.001). Methylation was associated with cellular functional changes, specifically Treg dysfunction, and an increase in total plasma IgE levels. Protein expression of IL-10 decreased and IFN-γ increased as the extent of PAH exposure increased. The strength of the associations generally increased as the time window for average PAH exposure increased from 24 hr to 1 year, suggesting more of a chronic response. Significant associations with chronic PAH exposure and immune outcomes were also observed in subjects with allergic rhinitis. CONCLUSIONS AND CLINICAL RELEVANCE: Collectively, these results demonstrate that increased ambient PAH exposure is associated with impaired systemic immunity and epigenetic modifications in a key locus involved in atopy: FOXP3, with a higher impact on atopic children. The results suggest that increased atopic clinical symptoms in children could be linked to increased PAH exposure in air pollution.

Possible pro-carcinogenic association of endotoxin on lung cancer among Shanghai women textile workers.

BACKGROUND: Endotoxin (lipopolysaccharide) is a widespread contaminant in many environmental settings. Since the 1970s, there has been generally consistent evidence indicating reduced risks for lung cancer associated with occupational endotoxin exposure. METHODS: We updated a case-cohort study nested within a cohort of 267,400 female textile workers in Shanghai, China. We compared exposure histories of 1456 incident lung cancers cases diagnosed during 1989-2006 with those of a reference subcohort of 3022 workers who were free of lung cancer at the end of follow-up. We applied Cox proportional hazards modelling to estimate exposure-response trends, adjusted for age and smoking, for cumulative exposures lagged by 0, 10, and 20 years, and separately for time windows of ⩽15 and >15 years since first exposure. RESULTS: We observed no associations between cumulative exposure and lung cancer, irrespective of lag interval. In contrast, analyses by exposure time windows revealed modestly elevated, but not statistically significant relative risks (∼1.27) at the highest three exposure quintiles for exposures that occurred >15 years since first exposure. CONCLUSIONS: The findings do not support a protective effect of endotoxin, but are suggestive of possible lung cancer promotion with increasing time since first exposure.

Cotton dust, endotoxin and cancer mortality among the Shanghai textile workers cohort: a 30-year analysis.

BACKGROUND: Although occupational exposure to cotton dust and endotoxin is associated with adverse respiratory health, associations with cancer are unclear. We investigated cancer mortality in relation to cotton dust and endotoxin exposure in the Shanghai textile workers cohort. METHODS: We followed 444 cotton textile and a reference group of 467 unexposed silk workers for 30 years (26 777 person-years). HRs for all cancers combined (with and without lung cancer) and gastrointestinal cancer were estimated in Cox regression models as functions of cotton textile work and categories of cumulative exposure (low, medium, high), after adjustment for covariates including pack-years smoked. Different lag years accounted for disease latency. RESULTS: Risks of mortality from gastrointestinal cancers and all cancers combined, with the exclusion of lung cancer, were increased in cotton workers relative to silk workers. When stratified by category of cumulative cotton exposure, in general, risks were greatest for 20-year lagged medium exposure (all cancers HR=2.7 (95% CI 1.4 to 5.2); cancer excluding lung cancer HR=3.4 (1.7-7.0); gastrointestinal cancer HR=4.1 (1.8-9.7)). With the exclusion of lung cancer, risks of cancer were more pronounced. When stratified by category of cumulative endotoxin exposure, consistent associations were not observed for all cancers combined. However, excluding lung cancer, medium endotoxin exposure was associated with all cancers and gastrointestinal cancer in almost all lag models. CONCLUSIONS: Cotton dust may be associated with cancer mortality, especially gastrointestinal cancer, and endotoxin may play a causative role. Findings also indirectly support a protective effect of endotoxin on lung cancer.

Circulating adhesion molecules after short-term exposure to particulate matter among welders.

BACKGROUND: Studies from several countries indicate that welders experience increased risk of mortality and morbidity from ischaemic heart disease. Although the underlying mechanisms are unclear, vascular responses to particulate matter contained in welding fumes may play a role. To investigate this, we studied the acute effects of welding fume exposure on the endothelial component of vascular function, as measured by circulating adhesion molecules involved in leukocyte adhesion (sICAM-1 and sVCAM-1) and coagulation (vWF). METHODS: A panel of 26 male welders was studied repeatedly across a 6 h work-shift on a high exposure welding day and/or a low exposure non-welding day. Personal PM(2.5) exposure was measured throughout the work-shift. Blood samples were collected in the morning (baseline) prior to the exposure period, immediately after the exposure period, and the following morning. To account for the repeated measurements, we used linear mixed models to evaluate the effects of welding (binary) and PM(2.5) (continuous) exposure on each blood marker, adjusting for baseline blood marker concentration, smoking, age and time of day. RESULTS: Welding and PM(2.5) exposure were significantly associated with a decrease in sVCAM-1 in the afternoon and the following morning and an increase in vWF in the afternoon. CONCLUSIONS: The data suggest that welding and short-term occupational exposure to PM(2.5) may acutely affect the endothelial component of vascular function.

Chronic obstructive pulmonary disease mortality in railroad workers.

BACKGROUND: There is little information describing the risk of non-malignant respiratory disease and occupational exposure to diesel exhaust. METHODS: US railroad workers have been exposed to diesel exhaust since diesel locomotives were introduced after World War II. In a retrospective cohort study we examined the association of chronic obstructive pulmonary disease (COPD) mortality with years of work in diesel-exposed jobs. To examine the possible confounding effects of smoking, multiple imputation was used to model smoking history. A Cox proportional hazards model was used to estimate an incidence rate ratio, adjusted for age, calendar year, and length of follow-up after leaving work (to reduce bias due to a healthy worker survivor effect). RESULTS: Workers in jobs with diesel exhaust exposure had an increased risk of COPD mortality relative to those in unexposed jobs. Workers hired after the introduction of diesel locomotives had a 2.5% increase in COPD mortality risk for each additional year of work in a diesel-exposed job. This risk was only slightly attenuated after adjustment for imputed smoking history. CONCLUSIONS: These results support an association between occupational exposure to diesel exhaust and COPD mortality.

Work area measurements as predictors of personal exposure to endotoxin and cotton dust in the cotton textile industry.

OBJECTIVES: To determine if work area measurements of endotoxin and/or cotton dust obtained from the vertical elutriator (VE) can be used to predict levels of personal endotoxin exposure as measured by the Institute of Occupational Medicine (IOM) inhalable dust sampler in the cotton textile industry. METHODS: Fifty-six work area cotton dust samples were collected from 14 areas and 82 personal cotton dust samples were collected from 41 workers in three textile mills (Mills A, B and C) in Shanghai, China. Cotton dust concentrations were determined gravimetrically from sample filters, of which endotoxin concentrations were determined using a kinetic chromogenic modification of the limulus amoebocyte lysate assay. Linear regression models were used to determine the association between log IOM personal endotoxin concentration and log VE area endotoxin concentration. RESULTS: Median cotton dust and endotoxin concentrations measured from VE area samples in the three mills were 0.36 mg m(-3) and 1280.76 endotoxin units per cubic meter (EU m(-3)), respectively, compared to 1.74 mg m(-3) and 2226.83 EU m(-3) from IOM personal samples. Excluding samples from weaving processes, we observed linear associations between VE area measures of endotoxin and IOM personal endotoxin concentrations; VE area concentration of endotoxin explained 83 and 89% of the total variation in IOM personal endotoxin concentration for Mills A and B, respectively (Mill A: R2 = 0.83, P < 0.0001; Mill B: R2 = 0.89, P < 0.0001). Although area measures of cotton dust was also a significant predictor of person endotoxin, the model explained less of the variance in personal endotoxin measurements. CONCLUSIONS: Specific to the conditions of the textile mills investigated in this study, work area measurements of endotoxin, but not cotton dust, may be reasonable proxies for personal levels, at least for rank-ordering exposures.

A case control study of lung cancer and exposure to chrysotile and amphibole at a slovenian asbestos-cement plant.

A lung cancer case-control study was conducted in a Slovenian asbestos-cement factory for which unusually good records of asbestos exposures were available. The cohort consisted of all 6714 workers employed at the Salonit Anhovo factory after 31 December 1946 who worked there for at least one day between 1964 and 1994. Fifty-eight histologically confirmed cases of primary lung cancer and 290 controls were selected from the cohort. Working life exposure histories to amphibole and chrysotile forms of asbestos were estimated separately. Airborne asbestos concentrations were low. For example, the arithmetic mean exposure to all forms of asbestos in the highest exposure period (1947-1971) was 1.2 f/cm(3). Chrysotile asbestos made up about 90% of this exposure (mean 1.1 f/cm(3)), whereas amphibole accounted for 10% (0.1 f/cm(3)). Comparing those above and below the 90 percentile of cumulative exposure, the odds ratios for all asbestos, chrysotile and amphibole were 1.5, 1.6 and 2.0, respectively, but confidence intervals were wide. There are only a few asbestos-lung cancer studies with high-quality exposure data and exposures in this low range. Though imprecise, the findings are important to the ongoing debate about asbestos risks.

DNA adducts among asphalt paving workers.

OBJECTIVE: Asphalt is used extensively in the highway construction industry and contains a complex mixture of polycyclic aromatic hydrocarbons, some of which are known or suspected to be human carcinogens. Though numerous epidemiologic studies have described an excess cancer risk among asphalt workers, a causal relationship has not been established. Accordingly, the primary objective of this study was to use DNA adducts as a biomarker of biologically effective dose and determine whether DNA damage resulted from occupational exposure to asphalt among paving workers. METHODS: Over a 12 month period, four peripheral blood samples (spring, summer, fall and winter) were obtained from 49 asphalt paving workers (169 samples) and 36 non-paving construction workers (103 samples). The spring, summer and fall samples were collected during the work-season, whereas the winter samples were collected during the off-season (due to the seasonality of paving work). Mononuclear white blood cells were isolated and analyzed for DNA adducts via the (32)P-postlabeling assay and generalized linear models were used to evaluate the DNA adduct data. RESULTS: Among paving workers during the work-season, DNA adducts increased during each day of the workweek such that mean adduct levels were lowest on Mondays (3 adducts per 10(10) nucleotides) and highest on Fridays (46 adducts per 10(10) nucleotides). Additionally, a 3-fold difference in adduct burden was observed by paving task such that mean adduct levels were lowest among roller operators (7 adducts per 10(10) nucleotides) and highest among screedmen (23 adducts per 10(10) nucleotides). Using adducts as a measure of biologically effective dose, these findings (weekday trend and task-based differences) were consistent with a previous evaluation of absorbed dose in the same population. Adduct levels were not, however, higher among paving workers than among non-pavers. Adducts were also highest during the winter months, suggestive of a seasonal effect that has been observed in previous studies. CONCLUSION: These findings indicate that adduct burden increased throughout the workweek among paving workers, suggesting that DNA damage may be associated with occupational exposure to hot-mix asphalt. However, the lack of contrast with non-paving workers, as well as the seasonal variation warrants additional investigation.

Characterization of a line of pigs previously selected for increased litter size for RBP4 and follistatin.

The objective of this study was to determine if selection response for increased litter size in pigs could be partially attributed to three type 1 marker loci coding for genes known to affect litter size: oestrogen receptor (ESR), retinol-binding protein 4 (RBP4) and follistatin (FS). In the high litter size line (LS), pigs from the largest litters, based on number of pigs born alive (NBA), were retained to parent the next generation. A randomly selected control line (LC) was maintained. Gilts were reared in litters of 10 pigs or less to minimize maternal effects. Pigs were measured at generations 10-12. Additional traits scored were number of fully formed pigs (NFF) and number of mummified fetuses (MUM). Breeding values for NFF and NBA were greater (p < 0.05) in LS than LC in generations 11 and 12, but no significant line differences were found for MUM. The A allele of the ESR locus was fixed in both lines. After adjustment for effects of genetic drift, frequency of the two alleles segregating for the FS and RBP4 loci did not differ significantly between lines. No significant additive or dominance effects of the FS markers were detected for NFF, NBA and MUM in either LS or LC. Response to selection for increased litter size could not be attributed to effects at the ESR, RBP4 or FS loci.

A 20-year follow-up study on chronic respiratory effects of exposure to cotton dust.

In order to evaluate chronic effects of long-term exposure to cotton dust on respiratory health, and the role of dust and endotoxin, longitudinal changes in lung function and respiratory symptoms were observed prospectively from 1981 to 2001 in 447 cotton textile workers, along with 472 silk textile controls. The results from five surveys conducted over the 20-yr period are reported, including standardised questionnaires, pre- and post-shift spirometric measurements, work-area inhalable dust sample collections and airborne Gram-bacterial endotoxin analysis. Cotton workers had more persistent respiratory symptoms and greater annual declines in forced expiratory volume in one second (FEV1) and forced vital capacity as compared with silk workers. After exposure cessation, in the final 5-yr period, the rate of FEV1 decline tended to slow in nonsmoking males, but not in nonsmoking females. Workers who reported byssinotic symptoms more persistently suffered greater declines in FEV1. Chronic loss in lung function was more strongly associated with exposure to endotoxin than to dust. In conclusion, the current study suggests that long-term exposure to cotton dust, in which airborne endotoxin appears to play an important role, results in substantial adverse chronic respiratory effects.

Conjugated linoleic acid evokes de-lipidation through the regulation of genes controlling lipid metabolism in adipose and liver tissue.

Conjugated linoleic acid (CLA) is a unique lipid that elicits dramatic reductions in adiposity in several animal models when included at < or = 1% of the diet. Despite a flurry of investigations, the precise mechanisms by which conjugated linoleic acid elicits its dramatic effects in adipose tissue and liver are still largely unknown. In vivo and in vitro analyses of physiological modifications imparted by conjugated linoleic acid on protein and gene expression suggest that conjugated linoleic acid exerts its de-lipidating effects by modulating energy expenditure, apoptosis, fatty acid oxidation, lipolysis, stromal vascular cell differentiation and lipogenesis. The purpose of this review shall be to examine the recent advances and insights into conjugated linoleic acid's effects on obesity and lipid metabolism, specifically focused on changes in gene expression and physiology of liver and adipose tissue.

Inhalation and dermal exposure among asphalt paving workers.

The primary objective of this study was to identify determinants of inhalation and dermal exposure to polycyclic aromatic compounds (PACs) among asphalt paving workers. The study population included three groups of highway construction workers: 20 asphalt paving workers, as well as 12 millers and 6 roadside construction workers who did not work with hot-mix asphalt. During multiple consecutive work shifts, personal air samples were collected from each worker's breathing zone using a Teflon filter and cassette holder connected in series with an XAD-2 sorbent tube, while dermal patch samples were collected from the underside of each worker's wrist. All exposure samples were analyzed for PACs, pyrene and benzo[a]pyrene. Inhalation and dermal PAC exposures were highest among asphalt paving workers. Among paving workers, inhalation and dermal PAC exposures varied significantly by task, crew, recycled asphalt product (RAP) and work rate (inhalation only). Asphalt mix containing high RAP was associated with a 5-fold increase in inhalation PAC exposures and a 2-fold increase in dermal PAC exposure, compared with low RAP mix. The inhalation PAC exposures were consistent with the workers' proximity to the primary source of asphalt fume (paver operators > screedmen > rakers > roller operators), such that the adjusted mean exposures among paver operators (5.0 microg/m3, low RAP; 24 microg/m3, high RAP) were 12 times higher than among roller operators (0.4 microg/m3, low RAP; 2.0 microg/m3, high RAP). The dermal PAC exposures were consistent with the degree to which the workers have actual contact with asphalt-contaminated surfaces (rakers > screedmen > paver operators > roller operators), such that the adjusted mean exposures among rakers (175 ng/cm2, low RAP; 417 ng/cm2, high RAP) were approximately 6 times higher than among roller operators (27 ng/cm2, low RAP; 65 ng/cm2, high RAP). Paving task, RAP content and crew were also found to be significant determinants of inhalation and dermal exposure to pyrene. The effect of RAP content, as well as the fact that exposures were higher among paving workers than among millers and roadside construction workers, suggests that the PAC and pyrene exposures experienced by these paving workers were asphalt-related.

Smoothing in occupational cohort studies: an illustration based on penalised splines.

AIMS: To illustrate the contribution of smoothing methods to modelling exposure-response data, Cox models with penalised splines were used to reanalyse lung cancer risk in a cohort of workers exposed to silica in California's diatomaceous earth industry. To encourage application of this approach, computer code is provided. METHODS: Relying on graphic plots of hazard ratios as smooth functions of exposure, the sensitivity of the curve to amount of smoothing, length of the exposure lag, and the influence of the highest exposures was evaluated. Trimming and data transformations were used to down-weight influential observations. RESULTS: The estimated hazard ratio increased steeply with cumulative silica exposure before flattening and then declining over the sparser regions of exposure. The curve was sensitive to changes in degrees of freedom, but insensitive to the number or location of knots. As the length of lag increased, so did the maximum hazard ratio, but the shape was similar. Deleting the two highest exposed subjects eliminated the top half of the range and allowed the hazard ratio to continue to rise. The shape of the splines suggested a parametric model with log hazard as a linear function of log transformed exposure would fit well. CONCLUSIONS: This flexible statistical approach reduces the dependence on a priori assumptions, while pointing to a suitable parametric model if one exists. In the absence of an appropriate parametric form, however, splines can provide exposure-response information useful for aetiological research and public health intervention.

Urinary 1-hydroxypyrene and polycyclic aromatic hydrocarbon exposure among asphalt paving workers.

OBJECTIVES: Using urinary 1-hydroxypyrene (1-OHP) as a measure of total absorbed dose, the primary objective of this study was to evaluate the total effect of inhalation and dermal PAH exposures while considering other factors such as age, body mass index and smoking that may also have a significant effect on urinary 1-OHP. METHODS: The study population included two groups of highway construction workers: 20 paving workers and 6 milling workers. During multiple consecutive workshifts, personal air and dermal samples were collected from each worker and analyzed for pyrene. During the same work week, urine samples were collected pre-shift, post-shift and at bedtime each day and analyzed for 1-OHP. Distributed lag models were used to evaluate the independent effect of inhalation and dermal exposures that occurred at each of several preceding exposure periods and were used to identify the relevant period of influence for each pathway. RESULTS: The paving workers had inhalation (mean 0.3 micro g/m(3)) and dermal (5.7 ng/cm(2)) exposures to pyrene that were significantly higher than the milling workers. At pre-shift on Monday morning, following a weekend away from work, the pavers and millers had the same mean baseline urinary 1-OHP level of 0.4 micro g/g creatinine. The mean urinary 1-OHP levels among pavers increased significantly from pre-shift to post-shift during each work day, while the mean urinary 1-OHP levels among millers varied little and remained near the baseline level throughout the study period. Among pavers there was a clear increase in the pre-shift data during the work week, such that the average pre-shift level on day 4 (1.4 micro g/g creatinine) was 3.5 times higher than the average pre-shift results on day 1 (0.4 micro g/g creatinine). The results of the distributed lag model indicated that the impact of dermal exposure was approximately eight times the impact of inhalation exposure. Furthermore, dermal exposure that occurred during the preceding 32 h had a statistically significant effect on urinary 1-OHP, while the effect of inhalation exposure was not significant. CONCLUSIONS: We found that distributed lag models are a valuable tool for analyzing longitudinal biomarker data and our results indicate that dermal contact is the primary route of exposure to PAHs among asphalt paving workers. An exposure assessment of PAHs that does not consider dermal exposure may considerably underestimate cumulative exposure and control strategies aimed at reducing occupational exposure to asphalt-related PAHs should include an effort to reduce dermal exposure.

Determinants of isocyanate exposures in auto body repair and refinishing shops.

As part of the Survey of Painters and Repairers of Auto bodies by Yale (SPRAY), the determinants of isocyanate exposure in auto body repair shops were evaluated. Measurements (n = 380) of hexamethylene diisocyanate-based monomer and polyisocyanate and isophorone diisocyanate-based polyisocyanate were collected from 33 auto body shops. The median total reactive isocyanate concentrations expressed as mass concentration of the NCO functional group were: 206 microg NCO/m3 for spray operations; 0.93 microg NCO/m3 for samples collected in the vicinity of spray operations done on the shop floor (near spray); 0.05 microg NCO/m3 for office or other shop areas adjacent to spray areas (workplace background); 0.17 microg NCO/m3 for paint mixing and gun cleaning operations (mixing); 0.27 microg NCO/m3 for sanding operations. Exposure determinants for the sample NCO mass load were identified using linear regression, tobit regression and logistic regression models. For spray samples in a spray booth the significant determinants were the number of milliliters of NCO applied, the gallons of clear coat used by the shop each month and the type of spray booth used (custom built crossdraft, prefabricated crossdraft or downdraft/semi-downdraft). For near spray (bystander) samples, outdoor temperature >65 degrees F (18 degrees C) and shop size >5000 feet2 (465 m2) were significant determinants of exposure levels. For workplace background samples the shop annual income was the most important determinant. For sanding samples, the shop annual income and outdoor temperature >65 degrees F (18 degrees C) were the most significant determinants. Identification of these key exposure determinants will be useful in targeting exposure evaluation and control efforts to reduce isocyanate exposures.

Risk of upper aerodigestive tract cancers in a case-cohort study of autoworkers exposed to metalworking fluids.

AIMS: To re-examine aerodigestive cancer risk in a cohort of autoworkers exposed to metal working fluids (MWF), using improved case definition and more recently diagnosed cases. METHODS: The autoworker cohort included 31 100 hourly workers alive on 1 January 1985 who worked at three automobile plants in Michigan. A case-cohort design was carried out that included incident cases of cancers of the larynx, oesophagus, and stomach, and a 10% sample of the cohort. A Cox proportional hazards model was used to estimate MWF exposure effects. The smoothing method of penalised splines was used to explore the shape of the underlying exposure-response curves. RESULTS: The most important finding was the association between larynx cancer incidence and cumulative straight MWF exposure. The results for oesophageal cancer were less consistent. For stomach cancer there was no evidence of excess risk. CONCLUSION: This association between larynx cancer and straight MWF exposures was consistent with a previous finding in this cohort, providing further support for a causal relation.

A case-crossover study of transient risk factors for occupational acute hand injury.

BACKGROUND: Workers with acute hand injuries account for over 1 000 000 emergency department visits annually in the United States. AIMS: To determine potential transient risk factors for occupational acute hand injury. METHODS: Subjects were recruited from 23 occupational health clinics in five northeastern states in the USA. In a telephone interview, subjects were asked to report the occurrence of seven potential risk factors within a 90-minute time period before an acute hand injury. Each case also provided control information on exposures during the month before the injury. The self-matched feature of the study design controlled for stable between-person confounders. RESULTS: A total of 1166 subjects were interviewed (891 men, 275 women), with a mean age (SD) of 37.2 years (11.4). The median time interval between injury and interview was 1.3 days. Sixty three per cent of subjects had a laceration. The relative risk of a hand injury was increased when working with equipment, tools, or work pieces not performing as expected (11.0, 95% CI 9.4 to 12.8), or when using a different work method to do a task (10.5, 95% CI 8.7 to 12.7). Other transient factors in decreasing order of relative risk were doing an unusual task, being distracted, and being rushed. Wearing gloves reduced the relative risk by 60% (0.4, 95% CI 0.3 to 0.5). Occupational category, job experience, and safety training were found to alter several of these effects. CONCLUSION: The results suggest the importance of these transient, potentially modifiable factors in the aetiology of acute hand injury at work. Attempts to modify these exposures by various strategies may reduce the incidence of acute hand injury at work.

The effect of dietary phosphorus on heat shock protein mRNAs during acute heat stress in male broiler chickens (Gallus gallus).

A 2 x 2 factorially arranged completely randomized experimental design was used to study the relationship between inorganic phosphorus (Pi) and heat shock protein (HSP) mRNA expression in different organs of commercial broiler cockerels during acute heat stress (HS). Brain, heart, liver and spleen were assayed for hsp70, hsp90alpha and hsp90beta mRNA. At 1 day of age, chickens were assigned randomly to two dietary Pi treatment groups (Pi-: 0.16%; Pi+: 0.5%). At 3 weeks of age, half of the chickens in each Pi group were subjected to HS (Ta=41 degrees C, 60 min) while the other half was maintained in a thermoneutral environment (CN, Ta=25 degrees C). The results showed inter-organ variation in the expression of HSP mRNAs. Brain expressed the most HSP mRNAs while spleen expressed the least. When broilers were subjected to HS, the expression of HSP mRNAs was influenced positively by the consumption of the Pi+ diet. However, analysis of variance revealed that Ta influenced HSP transcription more than phosphorus availability. Thermal stress caused induction of hsp90alpha and hsp90beta in heart, liver and spleen, but hsp90alpha and hsp9beta mRNA levels were stable in brain. Transcription of hsp70 increased (P< or =0.05) in all organs from chickens in HS groups when compared to chickens in CN groups. Although Pi+ did not show any significant increases in the expression of hsp mRNAs, there were consistently larger HSP mRNA values in liver and spleen tissues. The high expression of hsp90alpha and hsp90beta in brain of chicks in both CN and HS conditions could be due to the involvement of hsp90 in steroid hormone receptors or the high metabolic activity of neurons in the central nervous system.