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Superellipse sector particles (SeSPs) are segments of superelliptical curves that form a tunable set of hard-particle shapes for granular and colloidal systems. SeSPs allow for continuous parametrization of corner sharpness, aspect ratio, and particle curvature; rods, circles, rectangles, and staples are examples of shapes SeSPs can model. We compare three computational processes: pair-wise Monte Carlo simulations that explore particle-particle geometric constraints, Monte Carlo simulations that reveal how these geometric constraints play out over dispersions of many particles, and Molecular Dynamics simulations that form random loose and close packings. We investigate the dependence of critical random loose and close packing fractions on particle parameters, finding that both values increase with opening aperture and decrease with increasing corner sharpness. The identified packing fractions are compared with the mean-field prediction of the random contact model; we find deviations from the model's prediction due to correlations between particle orientations. The complex interaction of spatial proximity and orientational alignment is also explored with a generalized spatioorientational distribution area (SODA) plot, which shows how higher density packings are achieved through particles assuming a small number of preferred configurations that depend sensitively on particle shape and system preparation.

Study Design: Observational study of ribcage motion in scoliosis., Objective: To see whether noninvasive ventilation corrected paradoxical inward motion of the ribs during inspiration., Summary of Background Data: Paradoxical inward motion of the ribs is observed after rib fractures, low cervical cord injury, and in chronic obstructive pulmonary disease. It is not well recognized in scoliosis and the mechanism in this group has not been studied., Methods: Linearized magnetometers were used to measure the diameter of the ribcage. Changes in diameter during tidal breathing were recorded during spontaneous ventilation and noninvasive ventilation in 10 subjects with idiopathic or congenital thoracic scoliosis., Results: During spontaneous breathing, the median change in ribcage diameter during inspiration was -1.5 (range -2.3 to -0.8) cm. The median change in ribcage diameter during noninvasive ventilation was +0.5 (range -1.1 to +1.2) cm. Noninvasive ventilation improved paradoxical motion in all subjects, completely correcting it in six., Conclusion: Paradoxical inward motion of the ribcage is seen in some subjects with severe scoliosis. This abnormal motion is improved or abolished by noninvasive ventilation. Since noninvasive ventilation takes over the work of breathing from the respiratory muscles, we suggest that inspiratory muscle contraction causes distortion of part of the ribcage in scoliosis, probably because of the abnormal orientation of diaphragmatic muscle fibers., Level of Evidence: 2.

The management of excessive secretions in patients with motor neurone disease can be challenging. In this paper, we highlight the main issues from the perspectives of a patient, specialist nurse and neurologist and the importance of a multidisciplinary approach., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

During non-invasive ventilation (NIV), tidal volume ( V t ) will depend upon the difference between inspiratory and expiratory positive airway pressure (IPAP and EPAP, respectively), provided the respiratory muscles are relaxed and the lungs and chest wall therefore move along their passive pressure-volume curves. To test this hypothesis, we studied the effect of increasing EPAP during pressure-controlled modes of NIV in 30 long-term ventilator users (10 each with scoliosis, obesity hypoventilation or neuromuscular disorders). While maintaining the same IPAP, addition of 5 cmH 2 O of EPAP reduced mean V t by 167 ml; 10 cmH 2 O reduced V t by 367 ml. This pattern was seen in all three patient groups. EPAP has several potential advantages, for example maintaining upper airway patency, preventing basal atelectasis and facilitating triggering. EPAP does, however, appear to reduce V t . Decreasing EPAP is an alternative to increasing IPAP if measurements of gas exchange during NIV indicate that ventilation is inadequate.

Long-term non-invasive ventilation (NIV) was introduced in the 1980s, initially mainly for patients with poliomyelitis, muscular dystrophy (MD) or scoliosis. The obesity-hypoventilation syndrome has since become the commonest reason for referral to most centres providing home-NIV. Patients with MD are numerically a much smaller part of the workload, but as their disease progresses the need for ventilatory support changes and they require regular comprehensive assessment of their condition. We have examined the trend in MD use of home-NIV in our unit over the last 25 years. The number of new referrals appears to be stabilizing at around 20-25 over a 5-year period, equivalent to approximately 0.5 per 100,000 of population per year. The mean age at commencement of home-NIV is now 37.5 years, with 5-year survival rates of 70-75%. Ten-year survival rates are just over 40%. The distance of usual place of residence from our unit is fairly stable, currently at a mean of 27 km. Excellent survival rates mean that patients with MD, while numerically small, are likely to remain an important part of the workload of centres providing home-NIV. Our data should prove useful in the planning of future services for this group of patients.

Background: Renal cell carcinoma (RCC) has a higher incidence in blacks than in whites. Physical activity may influence the risk of renal cell cancer, but the evidence is inconsistent. No previous study has investigated this relationship in the black population., Methods: We examined the association between self-reported physical activity at different ages and risk of RCC in a population based case-control study of 1217 cases (361 black, 856 white) and 1235 controls (523 black, 712 white) frequency-matched on age, race, and gender. Multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression., Results: Among whites, increased risks of RCC were observed among participants reporting low levels of transportation-related activity in their 20's (OR <1 hr/wk vs >7 hr/wk (95% CI): 1.42 (1.10, 1.83)) and leisure time activity in their 50's (OR <1 hr/wk vs >7 hr/wk (95% CI): 1.49 (1.00, 2.20)). We found no association between physical activity and RCC risk among blacks., Conclusion: Our results suggest that physical activity may be inversely associated with RCC risk in whites, but there was no evidence of such an association in blacks. As this is the first study evaluating the effect of physical activity on RCC risk among blacks, further investigations are needed to clarify the relationship in this population.

Several polycyclic aromatic hydrocarbons (PAHs) are known or probable human carcinogens. We evaluated the relationship between PAH exposure and risk of childhood acute lymphoblastic leukemia (ALL) using concentrations in residential dust as an exposure indicator. We conducted a population-based case-control study (251 ALL cases, 306 birth-certificate controls) in Northern and Central California from 2001 to 2007. We collected residential dust using a high volume small surface sampler (HVS3) (n=185 cases, 212 controls) or by sampling from participants' household vacuum cleaners (n=66 cases, 94 controls). We evaluated log-transformed concentrations of 9 individual PAHs, the summed PAHs, and the summed PAHs weighted by their carcinogenic potency (the toxic equivalence). We calculated odds ratios (ORs) and 95% confidence intervals (CI) using logistic regression adjusting for demographic characteristics and duration between diagnosis/reference date and dust collection. Among participants with HVS3 dust, risk of ALL was not associated with increasing concentration of any PAHs based on OR perln(ng/g). Among participants with vacuum dust, we observed positive associations between ALL risk and increasing concentrations of benzo[a]pyrene (OR perln[ng/g]=1.42, 95% CI=0.95, 2.12), dibenzo[a,h]anthracene (OR=1.98, 95% CI=1.11, 3.55), benzo[k]fluoranthene (OR=1.71, 95% CI=0.91, 3.22), indeno[1,2,3-cd]pyrene (OR=1.81, 95% CI=1.04, 3.16), and the toxic equivalence (OR=2.35, 95% CI=1.18, 4.69). The increased ALL risk among participants with vacuum dust suggests that PAH exposure may increase the risk of childhood ALL; however, reasons for the different results based on HVS3 dust samples deserve further study., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Metalworking has been associated with bladder cancer risk in many studies. Metalworking fluids (MWFs) are suspected as the putative exposure, but epidemiologic data are limited. Based on state-of-the-art, quantitative exposure assessment, we examined MWF exposure and bladder cancer risk in the New England Bladder Cancer Study., Method: Male cases (n = 895) and population controls (n = 1031) provided occupational histories and information on use of each of three MWF types: (1) straight (mineral oil, additives), (2) soluble (mineral oil, water, additives), and (3) synthetic (water, organics, additives) or semi-synthetic (soluble/synthetic hybrid), in response to exposure-oriented modules administered during personal interviews. We estimated the probability, frequency, and intensity of exposure to each MWF type and, if probability exceeded 50%, cumulative exposure. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for smoking and other risk factors., Results: Risk was increased for men reporting use of straight MWFs (OR=1.7, 95% CI=1.1-2.8), with a significant trend with increasing cumulative exposure (p = 0.024). Use of soluble MWFs conferred a 50% elevated risk (95% CI=0.96-2.5). ORs were nonsignificantly elevated for synthetic MWFs, based on small numbers. Men who were never metalworkers, but held jobs with possible exposure to mineral oil, had a 40% increased risk (95% CI=1.1-1.8)., Conclusions: In the most comprehensive assessment of MWF exposure in a bladder cancer case-control study, exposure to straight MWFs significantly increased bladder cancer risk, as did employment in non-metalworking jobs with possible mineral oil exposure. Our results strengthen prior evidence for mineral oil as a bladder carcinogen., (© 2014, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: The incidence of renal cell carcinoma (RCC) has increased rapidly in the U.S., particularly among African Americans. Despite a well-established link between obesity and RCC, the mechanism through which obesity increases cancer risk has yet to be established. Adipokines, such as leptin and adiponectin, may link obesity and cancer, with different quantitative effects by race., Design and Methods: We evaluated the association between leptin and adiponectin concentrations and RCC risk among Caucasians (581 cases, 558 controls) and African Americans (187 cases, 359 controls) in a case-control study conducted in Detroit and Chicago. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated using unconditional logistic regression., Results: Among controls, Caucasians had higher median adiponectin than African Americans (males: 8.2 vs. 7.0 μg/ml, P = 0.001; females: 13.4 vs. 8.4 μg/ml, P < 0.0001), and lower median leptin than African Americans (males: 11.8 vs. 14.1 ng/ml, P = 0.04; females: 28.3 vs. 45.9 ng/ml, P < 0.0001). Among Caucasians, the ORs for RCC comparing the highest (Q4) to the lowest (Q1) sex-specific quartile of leptin were 3.2 (95% CI: 1.9-5.2) for males and 4.7 (95% CI: 2.6-8.6) for females. Serum leptin was not significantly associated with RCC among African American males (OR 1.5, 95% CI: 0.7-3.1) or females (OR 2.1, 95% CI: 0.8-5.5). Higher adiponectin was associated with RCC risk among African American males (Q4 vs. Q1: OR 2.3, 95% CI: 1.1-4.6) and females (OR 2.1, 95% CI: 1.2-6.7), but not significantly among Caucasian males (OR 1.6, 95% CI: 0.99-2.7) and females (OR 1.6, 95% CI: 0.9-3.1)., Conclusion: We observed an association between both leptin and adiponectin concentrations and risk of RCC, which may differ by race. Confirmation in further investigations is needed., (Copyright © 2012 The Obesity Society.)

Determinants of levels of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) in dust in U.S. homes are not well characterized. We conducted a pilot study to evaluate the relationship between concentrations of PCDD/F in house dust and residential proximity to known sources, including industrial facilities and traffic. Samples from vacuum bag dust from homes of 40 residents of Detroit, Los Angeles, Seattle, or Iowa who participated in a population-based case-control study of non-Hodgkin lymphoma conducted in 1998-2000 were analyzed using high resolution gas chromatography/high resolution mass spectrometry for 7 PCDD and 10 PCDF congeners considered toxic by the U.S. Environmental Protection Agency (EPA). Locations of 10 types of PCDD/F-emitting facilities were obtained from the EPA; however only 4 types were located near study homes (non-hazardous waste cement kilns, coal-fired power plants, sewage sludge incinerators, and medical waste incinerators). Relationships between concentrations of each PCDD/F and proximity to industrial facilities, freight routes, and major roads were evaluated using separate multivariate regression models for each congener. The median (inter-quartile range [IQR]) toxic equivalence (TEQ) concentration of these congeners in the house dust was 20.3 pg/g (IQR=14.3, 32.7). Homes within 3 or 5 km of a cement kiln had 2 to 9-fold higher concentrations of 5 PCDD and 5 PCDF (p<0.1 in each model). Proximity to freight routes and major roads was associated with elevated concentrations of 1 PCDD and 8 PCDF. Higher concentrations of certain PCDD/F in homes near cement kilns, freight routes, and major roads suggest that these outdoor sources are contributing to indoor environmental exposures. Further study of the contribution of these sources and other facility types to total PCDD/F exposure in a larger number of homes is warranted., (Published by Elsevier B.V.)

Background: Despite many studies on diet and bladder cancer, there are areas that remain unexplored including meat mutagens, specific vegetable groups, and vitamins from diet., Methods: We conducted a population-based case-control study of bladder cancer in Maine, New Hampshire, and Vermont. A total of 1171 cases were ascertained through hospital pathology records and cancer registries from 2001 to 2004. Overall, 1418 controls were identified from the Department of Motor Vehicles (<65 years) and Center for Medicaid and Medicare Services (65-79 years) and were frequency-matched to cases by state, sex, and age (within 5 years). Diet was assessed with a self-administered Diet History Questionnaire. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI)., Results: Processed meat intake was positively associated with bladder cancer (highest vs lowest quartile OR: 1.28; 95% CI: 1.00-1.65; P(trend)=0.035), with a stronger association for processed red meat (OR: 1.41; 95% CI: 1.08-1.84; P(trend)=0.024). There were no associations between intake of fruits or vegetables and bladder cancer. We did, however, observe an inverse association with vitamin B12 intake (OR: 0.77; 95% CI: 0.61-0.99; P=0.019)., Conclusion: Vitamin B12 from diet may be protective against bladder cancer, whereas consuming processed meat may increase risk., (© 2012 Cancer Research UK)

Background: There are few known risk factors for renal cell carcinoma (RCC). Two small hospital-based case-control studies suggested an association between short blood telomere length (TL) and increased RCC risk., Methods: We conducted a large population-based case-control study in two metropolitan regions of the United States comparing relative TL in DNA derived from peripheral blood samples from 891 RCC cases and 894 controls. Odds ratios and 95% confidence intervals were estimated using unconditional logistic regression in both unadjusted and adjusted models., Results: Median TL was 0.85 for both cases and controls (P=0.40), and no differences in RCC risk by quartiles of TL were observed. Results of analyses stratified by age, sex, race, tumour stage, and time from RCC diagnosis to blood collection were similarly null. In multivariate analyses among controls, increasing age and history of hypertension were associated with shorter TL (P<0.001 and P=0.07, respectively), and African Americans had longer TL than Caucasians (P<0.001)., Conclusion: These data do not support the hypothesis that blood TL is associated with RCC. This population-based case-control study is, to our knowledge, the largest investigation to date of TL and RCC.

Background: High-temperature cooked meat contains two families of carcinogens, heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Given the kidneys' role in metabolism and urinary excretion of these compounds, we investigated meat-derived mutagens, as well as meat intake and cooking methods, in a population-based case-control study conducted in metropolitan Detroit and Chicago., Methods: Newly diagnosed, histologically confirmed adenocarcinoma of the renal parenchyma (renal cell carcinoma (RCC)) cases (n=1192) were frequency matched on age, sex, and race to controls (n=1175). The interviewer-administered Diet History Questionnaire (DHQ) included queries for meat-cooking methods and doneness with photographic aids. Levels of meat mutagens were estimated using the DHQ in conjunction with the CHARRED database., Results: The risk of RCC increased with intake of barbecued meat (P(trend)=0.04) and the PAH, benzo(a)pyrene (BaP) (multivariable-adjusted odds ratio and 95% confidence interval, highest vs lowest quartile: 1.50 (1.14, 1.95), P(trend)=0.001). With increasing BaP intake, the risk of RCC was more than twofold in African Americans and current smokers (P(interaction)<0.05). We found no association for HCAs or overall meat intake., Conclusion: BaP intake, a PAH in barbecued meat, was positively associated with RCC. These biologically plausible findings advocate further epidemiological investigation into dietary intake of BaP and risk of RCC.

Background: Ingestion of inorganic arsenic in drinking water is recognized as a cause of bladder cancer when levels are relatively high (≥ 150 µg/L). The epidemiologic evidence is less clear at the low-to-moderate concentrations typically observed in the United States. Accurate retrospective exposure assessment over a long time period is a major challenge in conducting epidemiologic studies of environmental factors and diseases with long latency, such as cancer., Objective: We estimated arsenic concentrations in the water supplies of 2,611 participants in a population-based case-control study in northern New England., Methods: Estimates covered the lifetimes of most study participants and were based on a combination of arsenic measurements at the homes of the participants and statistical modeling of arsenic concentrations in the water supply of both past and current homes. We assigned a residential water supply arsenic concentration for 165,138 (95%) of the total 173,361 lifetime exposure years (EYs) and a workplace water supply arsenic level for 85,195 EYs (86% of reported occupational years)., Results: Three methods accounted for 93% of the residential estimates of arsenic concentration: direct measurement of water samples (27%; median, 0.3 µg/L; range, 0.1-11.5), statistical models of water utility measurement data (49%; median, 0.4 µg/L; range, 0.3-3.3), and statistical models of arsenic concentrations in wells using aquifers in New England (17%; median, 1.6 µg/L; range, 0.6-22.4)., Conclusions: We used a different validation procedure for each of the three methods, and found our estimated levels to be comparable with available measured concentrations. This methodology allowed us to calculate potential drinking water exposure over long periods.

Background: Residential proximity to agricultural pesticide applications has been used as a surrogate for exposure in epidemiologic studies, although little is known about the relationship with levels of pesticides in homes., Objective: We identified determinants of concentrations of agricultural pesticides in dust., Methods: We collected samples of carpet dust and mapped crops within 1,250 m of 89 residences in California. We measured concentrations of seven pesticides used extensively in agriculture (carbaryl, chlorpyrifos, chlorthal-dimethyl, diazinon, iprodione, phosmet, and simazine). We estimated use of agricultural pesticides near residences from a statewide database alone and by linking the database with crop maps. We calculated the density of pesticide use within 500 and 1,250 m of residences for 180, 365, and 730 days before collection of dust and evaluated relationships between agricultural pesticide use estimates and pesticide concentrations in carpet dust., Results: For five of the seven pesticides evaluated, residences with use of agricultural pesticides within 1,250 m during the previous 365 days had significantly higher concentrations of pesticides than did residences with no nearby use. The highest correlation with concentrations of pesticides was generally for use reported within 1,250 m of the residence and 730 days before sample collection. Regression models that also accounted for occupational and home use of pesticides explained only a modest amount of the variability in pesticide concentrations (4-28%)., Conclusions: Agricultural pesticide use near residences was a significant determinant of concentrations of pesticides in carpet dust for five of seven pesticides evaluated.

Associations between bladder cancer risk and NAT2 and GSTM1 polymorphisms have emerged as some of the most consistent findings in the genetic epidemiology of common metabolic polymorphisms and cancer, but their interaction with tobacco use, intensity and duration remain unclear. In a New England population-based case-control study of urothelial carcinoma, we collected mouthwash samples from 1088 of 1171 cases (92.9%) and 1282 of 1418 controls (91.2%) for genotype analysis of GSTM1, GSTT1 and NAT2 polymorphisms. Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the 'null' genotype) were 1.26 (0.85-1.88) and 1.54 (1.05-2.25), respectively (P-trend = 0.008), compared with those with two active copies. GSTT1 inactive alleles were not associated with risk. NAT2 slow acetylation status was not associated with risk among never (1.04; 0.71-1.51), former (0.95; 0.75-1.20) or current smokers (1.33; 0.91-1.95); however, a relationship emerged when smoking intensity was evaluated. Among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (1.82; 1.14-2.91, P-interaction = 0.07) and current heavy smokers (3.16; 1.22-8.19, P-interaction = 0.03) compared with rapid acetylators in each category; but was not observed at lower intensities. In contrast, the effect of GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. Findings from this large USA population-based study provided evidence that the NAT2 slow acetylation genotype interacts with tobacco smoking as a function of exposure intensity.

Background: The association between renal cell carcinoma (RCC) risk and family history of cancer has not been examined with an adequate number of African Americans (AAs)., Methods: In a population-based case-control study, unconditional logistic regression was used to calculate the association between RCC risk and a family history of cancer among 1217 RCC cases and 1235 controls., Results: Increased RCC risk was shown for subjects with at least one first-degree relative with kidney cancer (odds ratio=2.29; 95% confidence interval=1.31-4.00). No differences in risk were observed when analyses were stratified by race. For Caucasians, excess risk was observed among those reporting a sibling with kidney cancer, whereas for AAs, increased risk occurred among subjects reporting either a sibling or parent affected with the disease. A family history of non-renal cancers, and those related to smoking or to the von Hippel-Lindau syndrome, revealed no association with RCC risk., Conclusion: The RCC risk associated with a family history of kidney cancer is similar among Caucasians and AAs.

Industrial pollution has been suspected as a cause of non-Hodgkin lymphoma (NHL), based on associations with chemical exposures in occupational studies. We conducted a case-control study of NHL in four SEER regions of the United States, in which residential locations of 864 cases and 684 controls during the 10 years before recruitment were used to characterize proximity to industrial facilities reporting chemical releases to the Environmental Protection Agency's Toxics Release Inventory (TRI). For each of 15 types of industry (by 2-digit SIC code), we evaluated the risk of NHL associated with having lived within 2 miles of a facility, the distance to the nearest facility (miles categories of < or =0.5, >0.5-1.0, >1.0-2.0, >2 [referent]), and the duration of residence within 2miles (years categories of 10, 1-9, 0 [referent]), using logistic regression. Increased risk of NHL was observed in relation to lumber and wood products facilities (SIC 24) for the shortest distance of residential proximity (< or =0.5 mile: odds ratio [OR]=2.2, 95% confidence interval [CI]: 0.4-11.8) or the longest duration (10 years: OR=1.9, 95% CI: 0.8-4.8); the association with lumber facilities was more apparent for diffuse large B-cell lymphoma (lived within 2 miles: OR=1.7, 95% CI: 1.0-3.0) than for follicular lymphoma (OR=1.1, 95% CI: 0.5-2.2). We also observed elevated ORs for the chemical (SIC 28, 10 years: OR=1.5, 95% CI: 1.1-2.0), petroleum (SIC 29, 10 years: OR=1.9, 95% CI: 1.0-3.6), rubber/miscellaneous plastics products (SIC 30, < or =0.5mile: OR=2.7, 95% CI: 1.0-7.4), and primary metal (SIC 33, lived within 2miles: OR=1.3, 95% CI: 1.0-1.6) industries; however, patterns of risk were inconsistent between distance and duration metrics. This study does not provide strong evidence that living near manufacturing industries increases NHL risk. However, future studies designed to include greater numbers of persons living near specific types of industries, along with fate-transport modeling of chemical releases, would be informative.

Lipid peroxidation is considered a unifying mechanistic pathway through which known risk factors induce renal cell carcinoma (RCC). We hypothesized that genes selected a priori for their role in lipid peroxidation would modify cancer risk. We genotyped 635 single nucleotide polymorphisms (SNP) in 38candidate genes in 777 Caucasian RCC cases and 1,035 controls enrolled in a large European case-control study. Top candidate SNPs were confirmed among 718 Caucasian cases and 615 controls in a second study in the United States. Two of the three SNPs (rs8106822 and rs405509) that replicated in the U.S. study were within a regulatory region of the APOE promoter. The OR for rs8106822 A>G variant was 1.22(AG) and 1.41(GG) (P(trend) = 0.01) in the European study, 1.05(AG) and 1.51(GG) (P(trend) = 0.03) in the U.S. study, and 1.15(AG) and 1.44(GG) (P(trend) = 0.001) among 1,485 cases and 1,639 controls combined. The rs405509 G>T variant was associated with risk in the European (OR, 0.87(TG); OR, 0.71(TT); P(trend) = 0.02), the U.S. (OR, 0.68(TG); OR, 0.71(TT); P(trend) = 0.02), and both studies combined (OR(TG), 0.79; OR(TT), 0.71; P(trend) = 0.001), as was the G-G haplotype (r(2) = 0.64; P= 4.7 x 10(-4)). This association is biologically plausible as SNP rs405509 was shown to modify protein binding and transcriptional activity of the APOE protein in vitro and is in linkage disequilibrium with key known variants defining the e2, e3, and e4 alleles that modify risk of atherosclerosis, Alzheimer's disease risk, and progression to AIDS. In two large case-control studies, our findings further define a functional region of interest at the APOE locus that increases RCC susceptibility.

Objective: To investigate the relationship between selected solvent-related workplace tasks (degreasing, painting, gluing, stripping paint, staining) and risk of non-Hodgkin lymphoma (NHL)., Methods: We analysed occupational data from a large population-based case-control study of NHL conducted in the USA. For participants reporting occupations with possible exposure to organic solvents, job-specific interview modules were administered to elicit in-depth information on solvent-related workplace tasks and other exposure-related factors (225 cases, 189 controls). Unconditional logistic regression models were fit to calculate odds ratios (ORs) and 95% CI for average frequency, maximal frequency and cumulative number of hours having performed each task. Individuals with jobs rated as unexposed to organic solvents in the workplace (180 cases, 213 controls) were used as a reference group., Results: We observed an increased risk of NHL among subjects in the highest category of maximal degreasing frequency (>520 h/year: OR 2.1, 95% CI 0.9 to 4.9, trend test p = 0.02). We found similar associations for the highest levels of average frequency and, among men, cumulative number of hours. Other solvent-related tasks were not associated with NHL., Conclusion: Findings from this case-control analysis of solvent-related tasks suggest that frequent degreasing work may be associated with an elevated risk of NHL.

Aims: To identify occupations and industries associated with non-Hodgkin's lymphoma (NHL) in a large population-based, case-control study in the USA., Methods: Cases (n = 1189) of histologically confirmed malignant NHL ages 20-74 were prospectively identified in four geographic areas covered by the National Cancer Institute SEER Program. Controls (n = 982) were selected from the general population by random digit dialling (<65 years of age) and from residents listed in Medicare files (65-74 years of age). Odds ratios and 95% confidence intervals for occupations and industries were calculated by unconditional logistic regression analyses, adjusting for age, gender, ethnicity and study centre. Further analyses stratified for gender and histological subtype were also performed., Results: Risk of NHL was increased for a few occupations and industries. Several white collar occupations, with no obvious hazardous exposures, had elevated risks, including purchasing agents and buyers, religious workers, physical therapists and information clerks. Occupations with excesses that may have exposures of interest include launderers and ironers, service occupations, food/beverage preparation supervisors, hand packers and packagers, roofing and siding, leather and leather products, transportation by air, nursing and personal care facilities, and specialty outpatient clinics. Significantly decreased risks of NHL were found for a number of occupations and industries including post-secondary teachers and chemical and allied products., Conclusions: The results of this study suggest that several occupations and industries may alter the risk of NHL. Our results support previously reported increased risks among farmers, printers, medical professionals, electronic workers and leather workers. These findings should be evaluated further in larger studies that have the power to focus on specific exposures and histological subtypes of NHL.

To quantify nonresponse bias and estimate its potential impact, the authors compared census-based socioeconomic and demographic factors and geographic locations among respondents and nonrespondents in a multicenter case-control study of non-Hodgkin lymphoma (1998-2000). Using a geographic information system, the authors mapped current addresses and linked them to the 2000 US Census database to determine group-level demographic and socioeconomic information. They used logistic regression analysis to compute the risk of being a nonrespondent, separately for cases and controls. They used spatial scan methods to evaluate spatial clustering at each study center. Among cases at one or more centers, nonresponse was significantly associated with non-White race, lower household income, a greater proportion of multiple-unit housing, fewer years of education, and living in a more urbanized area. For most factors, the authors observed similar patterns among controls, although findings were mostly nonsignificant. They found two nonrandom elliptical clusters in Los Angeles, California, and Detroit, Michigan, that disappeared after adjustment for the demographic factors. The authors determined the bias in non-Hodgkin lymphoma risk associated with census-tract educational level by comparing risks among respondents and all subjects. The bias was 8%, indicating that the socioeconomic and demographic differences between respondents and nonrespondents did not result in a large bias in the risk estimate for education.

Objective: Since adult immune responsiveness is influenced by early childhood exposures, we examined the role of family size, history of atopic disease, and other childhood immune-related exposures in a multi-center case-control study of NHL., Methods: Interviews were completed with 1,321 cases ascertained from population-based cancer registries in Seattle, Detroit, Los Angeles and Iowa, and with 1,057 frequency-matched controls, selected by random-digit dialing and from the Medicare files database. Multivariable logistic regression was used to estimate risk., Results: A history of any allergy (excluding drug allergies), decreased risk of all NHL (Odds Ratio [OR] = 0.7, 95% Confidence Interval [CI] = 0.6-1.0), diffuse large B-cell lymphoma [DLBCL] (OR = 0.6, 95% CI = 0.4-0.9), and follicular NHL (OR = 0.7, 95 CI = 0.5, 1.0). A similar effect was observed for hay fever. A history of eczema was associated with an increased risk of follicular lymphoma (OR = 1.9, 95% CI = 1.1-3.4), but not DLBCL (OR = 1.1, 95% CI = 0.6-2.0). Asthma did not affect risk. Youngest compared to oldest siblings had a 90% increased risk of DLBCL (95% CI = 1.2-3.1; p for trend with increasing birth order = 0.006), but not follicular lymphoma (OR = 1.1, 95% CI = 0.6-1.8)., Conclusions: We infer that some childhood and immune-related factors may alter NHL risk.

Dramatic increase in hand-held cellular telephone use since the 1980s and excess risk of lymphoproliferative malignancies associated with radio-frequency radiation (RFR) exposures in epidemiological and experimental studies motivated assessment of cellular telephones within a comprehensive US case-control investigation of non-Hodgkin lymphoma (NHL). A questionnaire ascertained cellular telephone use in 551 NHL cases and 462 frequency-matched population controls. Compared to persons who had never used cellular telephones, risks were not increased among individuals whose lifetime use was fewer than 10 (odds ratio (OR) = 0.9, 95% confidence intervals (CI): 0.6, 1.3), 10-100 (OR = 1.0, 95 % CI: 0.7, 1.5) or more than 100 times (e.g., regular users, OR = 0.9, 95% CI: 0.6, 1.4). Among regular users compared to those who had never used hand-held cellular telephones, risks of NHL were not significantly associated with minutes per week, duration, cumulative lifetime or year of first use, although NHL was non-significantly higher in men who used cellular telephones for more than 8 years. Little evidence linked use of cellular telephones with total, diffuse large B-cell lymphoma or follicular NHL. These findings must be interpreted in the context of less than 5% of the population reporting duration of use of 6 or more years or lifetime cumulative use of 200 or more hours.

Background: Factors related to DNA damage and altered immunologic responses, such as reactive oxygen species production, are associated with the risk of non-Hodgkin lymphoma (NHL)., Objective: The aim was to evaluate NHL risk with intakes of vegetables, fruit, and nutrients involved in antioxidant activities., Design: Incident case subjects aged 20-74 y were identified between 1998 and 2000 from a National Cancer Institute-sponsored study by using four Surveillance, Epidemiology, and End Results registries. Control subjects, who were selected by random dialing (< 65 y) and from Medicare files (> or = 65 y), were matched to cases by age, center, race, and sex. Of 1321 case and 1057 control subjects who enrolled, dietary data were collected on a subset (466 cases and 391 controls). Carotenoid intakes were estimated by using updated values from the US Department of Agriculture nutrient databases. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs., Results: NHL risk was inversely associated with higher number of weekly servings of all vegetables (multivariable OR for highest compared with lowest quartile: 0.58; 95% CI: 0.35, 0.95; P for trend = 0.04), green leafy vegetables (OR: 0.59; 95% CI: 0.36, 0.96; P for trend = 0.01), and cruciferous vegetables (OR: 0.62; 95% CI: 0.39, 1.00; P for trend = 0.05) and with higher daily intakes of lutein and zeaxanthin (OR: 0.54; 95% CI: 0.32, 0.91; P for trend = 0.06) and zinc (OR: 0.58; 95% CI: 0.36, 0.91; P for trend = 0.02). An effect modification by exercise and NHL subtype was observed with some food groups and nutrients., Conclusion: Higher intakes of vegetables, lutein and zeaxanthin, and zinc are associated with a lower NHL risk.

Study Objective: To investigate the possible relation between bladder cancer mortality among white men and women and private water use in New England, USA, where rates have been persistently raised and use of private water supplies (wells) common., Design: Ecological study relating age adjusted cancer mortality rates for white men and women during 1985-1999 and proportion of persons using private water supplies in 1970. After regressing mortality rates on population density, Pearson correlation coefficients were computed between residual rates and the proportion of the population using private water supplies, using the state economic area as the unit of calculation. Calculations were conducted within each of 10 US regions., Setting: The 504 state economic areas of the contiguous United States., Participants: Mortality analysis of 11 cancer sites, with the focus on bladder cancer., Main Results: After adjusting for the effect of population density, there was a statistically significant positive correlation between residual bladder cancer mortality rates and private water supply use among both men and women in New England (men, r = 0.42; women, r = 0.48) and New York/New Jersey (men, r = 0.49; women, r = 0.62)., Conclusions: Use of well water from private sources, or a close correlate, may be an explanatory variable for the excess bladder cancer mortality in New England. Analytical studies are underway to clarify the relation between suspected water contaminants, particularly arsenic, and raised bladder cancer rates in northern New England.

The molecular pathology of bladder cancer has been the subject of considerable interest, and current efforts are targeted toward elucidating the interrelationships between individual somatic gene loss and both etiologic and prognostic factors. Mutation of the TP53 gene has been associated with more invasive bladder cancer, and evidence suggests that TP53 mutation, independent of stage, may be predictive of outcome in this disease. However, there is no consensus in the literature that bladder carcinogen exposure is associated with inactivation of the TP53 gene. Work to date has been primarily hospital based and, as such, subject to possible bias associated with selection of more advanced cases for study. We examined exposure relationships with both TP53 gene mutation and TP53 protein alterations in a population-based study of 330 bladder cancer cases in New Hampshire. Tobacco smoking was not associated with TP53 alterations. We found a higher prevalence of TP53 inactivation (i.e., mutation and nuclear accumulation) among hair dye users (odd ratio [OR] = 4.1; 95% confidence interval [CI] 1.2-14.7), and the majority of these mutations were transversions. Men who had "at risk" occupations were more likely to have mutated TP53 tumors (OR = 2.9; 95% CI 1.1-7.6). There also was a relative absence of TP53 mutation (OR = 0.4; 95% CI 0.0-2.9) and TP53 protein alterations (OR = 0.6; 95% CI 0.3-1.4) in bladder cancers from individuals with higher arsenic exposure. Our data suggest that there is exposure-specific heterogeneity in inactivation of the TP53 pathway in bladder cancers and that integration of the spectrum of pathway alterations in population-based approaches (capturing the full range of exposures to bladder carcinogens) may provide important insights into bladder tumorigenesis., ((c) 2005 Wiley-Liss, Inc.)

Background: To evaluate the risk of the adult glioma associated with farming and agricultural pesticide use, the authors conducted a population based case control study in eastern Nebraska., Methods: Telephone interviews were conducted with men and women diagnosed with gliomas (n = 251) between 1988 and 1993 and controls (n = 498) randomly selected from the same geographical area. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) for farming and for use of individual and chemical classes of insecticides and herbicides, including pesticides classified as nitrosatable (able to form N-nitroso compounds upon reaction with nitrite). Non-farmers were used as the reference category for all analyses., Results: Among men, ever living or working on a farm and duration of farming were associated with significantly increased risks of glioma (> or =55 years on a farm OR = 3.9, 95% CI 1.8 to 8.6); however, positive findings were limited to proxy respondents. Among women, there were no positive associations with farming activities among self or proxy respondents. Specific pesticide families and individual pesticides were associated with significantly increased risks among male farmers; however, most of the positive associations were limited to proxy respondents. For two herbicides and three insecticides, use was positively associated with risk among both self and proxy respondents. Based on a small number of exposed cases, ORs were significantly increased for the herbicides metribuzin (OR = 3.4, 95% CI 1.2 to 9.7) and paraquat (OR = 11.1, 95% CI 1.2 to 101), and for the insecticides bufencarb (OR = 18.9, 95% CI 1.9 to 187), chlorpyrifos (OR = 22.6, 95% CI 2.7 to 191), and coumaphos (OR = 5.9, 95% CI 1.1 to 32)., Conclusion: The authors found significant associations between some specific agricultural pesticide exposures and the risk of glioma among male farmers but not among female farmers in Nebraska; however, most of the positive associations were limited to proxy respondents. These findings warrant further evaluation in prospective cohort studies where issues of recall bias are not a concern.

Background: An elevated risk of developing non-Hodgkin's lymphoma (NHL) has been associated with a family history of NHL and several other malignancies, but the magnitude of risks and mechanisms are uncertain., Methods: We used self-reported family history data from a recent multicenter U.S.-based case-control studies of NHL to evaluate familial aggregation of NHL with various hematolymphoproliferative and other cancers. Estimates of familial aggregation were obtained as hazard ratios (HR) that compare incidence of different cancers in first-degree relatives of NHL cases with that in the first-degree relatives of NHL controls. Limitations of the study included low participation rates (76% for cases and 52% for controls) and potential differential accuracy of recall., Results: Risk of NHL was elevated in relatives of NHL cases [HR, 2.9; 95% confidence interval (95% CI), 0.95-8.53]; the aggregation seems to be stronger for siblings (HR, 7.6; 95% CI, 0.98-58.8) and for male relatives (HR, 6.2; 95% CI, 0.77-50.0). Risk of Hodgkin's lymphoma seems to be also elevated among relatives of early-onset (<50 years) NHL cases (HR, 3.2; 95% CI, 0.88-11.6). Evaluation of family history of other cancers provided modest evidence for an increased risk of melanoma of the skin (HR, 2.9; 95% CI, 1.08-7.75), pancreatic cancer (HR, 2.1; 95% CI, 0.96-4.43), stomach cancer (HR, 1.8; 95% CI, 0.91-3.63), and prostate cancer (HR, 1.3; 95% CI, 0.87-1.99)., Conclusions: These results are consistent with previous findings of familial aggregation of NHL, Hodgkin's lymphoma, and a few other cancers. The pattern of male-specific and sibling-specific familial aggregation of NHL we observed, if confirmed, may shed new light on the possible mechanisms that underlie familial aggregation of the disease.

Background: Migrant and seasonal farmworkers have a high potential for pesticide exposures, yet are rarely included in epidemiologic studies. This study examined the feasibility of assessing prenatal exposures to pesticides and other compounds in pregnant Hispanic farmworkers., Methods: Nine women completed a survey about work experiences during pregnancy. Maternal urine, cord blood, and placenta samples were obtained at delivery for analysis of 51 analytes, including 6 phenoxy acid or triazine herbicides, 21 organochlorine insecticides, 10 PCBs, and 14 volatile organic compounds., Results: Seven of 51 analytes were found in the biological samples. DDE, DDT, dichlorbenzene, toluene, trimethylbenzene, and endosulfan sulfate were detected in cord blood samples, and 2,4-D in urine from one or more women., Conclusions: We documented the feasibility of following farmworkers to assess in utero exposure to pesticides and other contaminants, and demonstrated exposure to these compounds. Difficulties in measuring pesticides with short half lives were noted., (Copyright 2001 Wiley-Liss, Inc.)

Background: Migrant farmworkers have rarely been included in epidemiologic studies. To assess the feasibility of following farmworkers over extended periods, a critical feature of many study designs, we attempted to trace a sample of Mexican-American farmworkers identified in a clinic in Wisconsin., Methods: We randomly chose 100 farmworkers from a migrant health center registration list for 1984-85. In 1995, we searched recent clinic records, made telephone calls, and visited migrant camps to find these farmworkers in Wisconsin during the growing season. We also attempted to find 46 farmworkers at their homes in southwest Texas over a two-week period in 1996 using the address listed in the clinic records, local phone books, and conversations with next-door neighbors., Results: Although 25 farmworkers had reregistered at the clinic in recent years, we found only 6 of them in Wisconsin in 1995. In southwest Texas, we either located or ascertained information about the vital status of 25 of the 46 farmworkers (54%)., Conclusions: Tracing efforts must include extensive contacts in farmworkers' home states and must incorporate a variety of information sources. Tracing farmworkers in epidemiologic studies appears to be feasible but requires more intensive methods over longer periods of time than those used in this study., (Copyright 2001 Wiley-Liss, Inc.)

Background: Epidemiologic studies, particularly case-control studies, often rely on proxy respondents to provide information about subjects' occupational histories. The quality of proxy-reported information in occupational histories has never been evaluated for migrant farmworkers., Methods: We compared occupational histories self-reported by 31 farmworkers with those reported by their wives. The work histories were obtained using an icon/calendar-based questionnaire that was designed to facilitate recall for migrant farmworkers, who typically have complex work histories., Results: The work histories provided by proxy respondents contained 32% fewer jobs and accounted for 24% fewer years than the self-reported histories. Correlations for lifetime duration of employment in different types of jobs were moderate to good for general agricultural jobs in Washington (0.70) and apple-related jobs (0.65), which were held by virtually all of the farmworkers; correlations were moderate to poor for less common jobs and for specific types of tasks. Agreement was better after marriage than before, and for jobs held in the current year compared to other time frames. Overall, the ability of the spouses to provide occupational histories for farmworkers was within the range observed in studies involving other occupations and industries., Conclusions: In studies involving farmworkers, when study subjects cannot be interviewed, spouses can provide useful information on occupational histories. However, the information should be used only for more generalized exposure assessments; it is most appropriate for estimating cumulative duration of agricultural work, or recent work, by place or for common crops., (Published 2001 Wiley-Liss, Inc.)

Background: US migrant and seasonal farmworkers may be exposed to potentially carcinogenic pesticides and other agents. Little epidemiologic research has been conducted on this population., Methods: We examined the proportionate mortality of 26,148 subjects (14,631 white men (WM), 7,299 nonwhite men (NM), 1,081 white women (WW), and 3,137 nonwhite women (NW)) who were identified as farmworkers on death certificates from 24 US states during 1984-1993., Results: Farmworkers had significantly elevated proportionate mortality from injuries, tuberculosis, mental disorders, cerebrovascular disease, respiratory diseases, ulcers, hypertension (NW), and cirrhosis (NW). There was significantly reduced mortality from infectious diseases (other than tuberculosis), endocrine disorders, nervous system diseases, pneumoconioses, arteriosclerotic heart disease (WM), and all cancers combined. Proportionate cancer mortality analyses found excess cancers of the buccal cavity, larynx, esophagus, stomach, skin (NW), and cervix, and deficits for cancers of the colon, breast, kidney, pancreas (NW), and lymphohematopoietic system., Conclusions: The excess deaths from injuries, respiratory disease, and stomach cancer, and the deficits of colon cancer and arteriosclerotic heart disease among farmworkers, are consistent with typical mortality patterns previously observed among farm owner/operators. The excess buccal, laryngeal, esophageal, and cervical cancers, and the deficits of breast cancer and lymphohematopoietic cancers have not generally been observed in studies of farm owner/operators., (Published 2001 Wiley-Liss, Inc.)

Background: Specialized methods are necessary to collect data from migrant farmworkers for epidemiologic research., Methods: We developed a questionnaire that collected lifetime occupational histories and other lifestyle risk factors via a life events/icon calendar, and administered the questionnaire to a convenience sample of 162 migrant farmworkers in nine areas of the U.S., Results: The average duration of the interviews was about 1 h 30 min, with an average of 45 min for the work history section. The occupational histories covered a median of 27.6 years per person for men and 20.8 years per person for women. The median number of years spent in farm jobs was 11.3 for men and 5.8 for women. The median number of farm jobs (crop/task combination) per person was 59 among men and 27 among women. Many farmworkers performed the same crop/task combinations at multiple times throughout their lives, yielding a median of 13 unique farm jobs and 8 unique crops among men and 7 jobs and 5 crops among women., Conclusions: The project demonstrated that it is feasible to collect detailed work histories and other risk factor data from farmworkers, documented the complexity of work histories encountered among farmworkers, and yielded recommendations for refining a questionnaire that will facilitate future epidemiologic research on farmworkers., (Copyright 2001 Wiley-Liss, Inc.)

Background: The health of farmworkers as related to pesticide exposure is of concern but assessing exposures for epidemiologic studies requires different techniques than approaches used for studies of industrial workers., Methods: A review of the literature identified possible factors that affect exposure intensity. A model was developed to estimate an exposure score. Exposures in the literature were estimated using the model and compared to the measurements in the literature., Results: Three studies were found with information appropriate for evaluation of the model. There was a statistical difference between the means of the scores corresponding to above and below the median of the measurements. The correlation coefficient between the scores and the measurements from the literature was 0.77., Conclusions: Although the evaluation was limited, the model appeared to work well, but more testing is needed. More research is also needed to increase understanding of what affects the exposures of these workers., (Published 2001 Wiley-Liss, Inc.)

Epidemiologic studies of the association between residential pesticide use and cancer risk require an assessment of past pesticide exposures. Pesticide levels in carpet dust are believed to reflect long-term pesticide use. Recent epidemiologic studies have found collection of dust samples using the high-volume surface sampler (HVS3) to be expensive and cumbersome. We compared the levels of pesticides and other compounds in dust obtained from subjects' personal used vacuum cleaner bags to that collected by the HVS3 to see if this simpler method could replace the HVS3 in epidemiologic research. We visited the homes of 15 subjects, took the used bags from their vacuums, and collected carpet dust samples with the HVS3. The samples were analyzed for 42 target compounds: 26 pesticides, 10 polycyclic aromatic hydrocarbons (PAHs), and six polychlorinated biphenyl (PCB) congeners using GC/MS in selected ion monitoring mode. The two methods agreed in detecting the presence of the target compounds between 80% and 100% of the time. Neither sampling method was consistently more sensitive. The median target compound concentrations were similar, and a paired t-test showed no significant differences. For many compounds, the concentrations of compounds in the HVS3 samples were higher than those in the used bag samples at the upper end of the concentration ranges. However, the Spearman rank correlation coefficients were 0.85 or higher for most compounds, indicating that homes would be ranked similarly using both methods. Overall, there appears to be no clear difference in the quality of the pesticide, PAH, or PCB concentration data for the two dust collection methods.

Occupational exposures of parents might be related to cancer in their offspring. Forty-eight published studies on this topic have reported relative risks for over 1000 specific occupation/cancer combinations. Virtually all of the studies employed the case-control design. Occupations and exposures of fathers were investigated much more frequently than those of the mother. Information about parental occupations was derived through interviews or from birth certificates and other administrative records. Specific exposures were typically estimated by industrial hygienists or were self-reported. The studies have several limitations related to the quality of the exposure assessment, small numbers of exposed cases, multiple comparisons, and possible bias toward the reporting of positive results. Despite these limitations, they provide evidence that certain parental exposures may be harmful to children and deserve further study. The strongest evidence is for childhood leukemia and paternal exposure to solvents, paints, and employment in motor vehicle-related occupations; and childhood nervous system cancers and paternal exposure to paints. To more clearly evaluate the importance of these and other exposures in future investigations, we need improvements in four areas: a) more careful attention must be paid to maternal exposures; b) studies should employ more sophisticated exposure assessment techniques; c) careful attention must be paid to the postulated mechanism, timing, and route of exposure; and d) if postnatal exposures are evaluated, studies should provide evidence that the exposure is actually transferred from the workplace to the child's environment.

Certain characteristics of skin wound healing in the North American bullfrog, Rana catesbeiana, were studied grossly and histologically at various stages of development. The contraction kinetics of excisional skin wounds were monitored for 50 days in animals from four larval developmental stages (tadpoles) and from adults (frogs). The percentage of original wound area which remained after contraction had stopped in the four larval groups decreasing steadily from 59.2%+/- 6.8% for the least developed larvae to 9.9%+/- 2.3% for the most developed ones. Wounds in adults contracted at a much lower rate than for larvae and the percentage of original wound area remaining after 50 days was less than 10%. The morphologic features characterizing the intact dermis and epidermis outside the wound bed in the larvae were also observed in qualitatively similar detail inside the wound bed. In the adults, the subepidermal connective tissue inside the wound bed was distinctly different from the physiologic dermis outside and was classified as amphibian scar. We conclude that, during larval development, wound contraction increasingly displaced skin regeneration as a mechanism for wound closure. Adults closed skin wounds by a combination of contraction and synthesis of scar tissue. It is hypothesized that the mechanism for synthesis of scar in this amphibian is established during metamorphosis from larva to adult.

The effectiveness of inhibiting serosal tissue damage and preventing surgical adhesions by precoating tissues with dilute solutions of hyaluronic acid (HA) was evaluated in a rat cecal abrasion model. This study was performed at three independent laboratories using the same protocol. Three hundred and seventy-five adult rats were divided into five treatment groups (125 animals at each study site): 0.1% HA, 0.25% HA, 0.4% HA, phosphate-buffered saline solution (PBS), and no solution. The abdominal cavity of each animal was precoated with 4 ml of test solution or no solution, prior to a controlled abrasion of the cecum. One week later, the animals were sacrificed and adhesions were scored on a 0-4 scale. The data were pooled because no statistical difference was found in the trends at the three study sites. The PBS precoating and no tissue precoating treatment groups had the same high incidence of cecal adhesions, which was significantly higher than the incidence of adhesions in the HA treatment groups. As the HA concentration in the precoating solution increased from 0% (PBS group) to 0.4% HA, the mean incidence of cecal adhesions decreased in a concentration-dependent manner from 1.6 +/- 0.11 to 0.7 +/- 0.09 (P < 0.001). The percentage of animals with no cecal adhesions increased from 11% in the PBS group to 50% in the 0.4% HA treatment group (P < 0.001). In a separate histological study employing 150 rats, HA solutions significantly inhibited serosal tissue damage and ameliorated the inflammatory response due to abrasion and desiccation compared to that with no coating or precoating with buffered saline. Together, these studies demonstrate that tissue precoating with dilute HA solutions reduces damage to serosal tissues during surgery and thereby limits formation of postsurgical adhesions.

A useful laparoscopic product for adhesion prevention must be easy to apply with minimal handling and manipulation of tissue and product. With this objective in mind, we have developed an injectable gel (HALTM) based on hyaluronic acid that is intended to limit adhesion formation after laparoscopic and open surgical procedures. We tested the effectiveness of HALTM gels in a rat sidewall defect model. In 50 adult female rats a 1 cm x 1 cm peritoneal defect was made along the abdominal wall. The defect was enclosed with #3-0 silk suture to induce ischemia. The animals were randomized to gel treatment (0.5 ml placed on defect) or non-treatment control groups. Seven days after surgery the extent (0-4 scale) and severity (0-3 scale) of adhesions were scored. HALTM gel significantly reduced the extent and severity of sidewall adhesions. Moreover, the number of animals with no adhesions was significantly increased compared with non-treatment. These results indicate that HALTM gel, which is easily applied to tissue and organs, may be a useful adjuvant for adhesion prevention in open and laparoscopic surgical procedures. The effectiveness and safety of HALTM gels will be tested in human clinical studies.

The wide range of species reared, species requirements, water resources, and regional preferences create the need for a wide variety of aquaculture production systems. Factors such as the interaction between water temperature and water quality and the feeding, growth, and survival of aquatic species cause the design of aquatic production systems to be much more location-specific and site-specific than the designs of systems for terrestrial animal agriculture. Economic and regulatory pressures are continuing to change the characteristics of aquatic production systems.

We can never gauge where we are and where we are going without reviewing where we have been. A historical review is included to help give this perspective. This chapter documents the uses of intraoral orthotics in the past and how they have changed as philosophies and materials evolved.

A portable means of temperature control for thermodilution injectate syringes is described. This approach is relatively simple to produce and maintains constant satisfactory temperature in the injectate.

Vascular surgery involves multiple transfusions with their concomitant hazards. At the start of each vascular procedure, 20 per cent of each patient's blood (approximately 1,000 of 5,600 ml) is removed and replaced with colloid and crystalloid and the withdrawn blood returned at the end of surgery. Theoretically, if 40 per cent of the blood volume (2,000+ ml) could be withdrawn, essentially no banked blood would be required for a major vascular procedure. Therefore, 40 per cent (900+ ml) of the blood volume of twenty greyhounds was withdrawn under anesthesia and replaced with stroma-free hemoglobin solution (SFHS). Abdominal aortic resection and graft replacement was performed, and any blood lost during the procedure was replaced with SFHS. After surgery the withdrawn blood was returned to the dog and excess volume removed with postoperative hemodilution diuresis. The study included a battery of twenty tests for monitoring during the procedure and at intervals from this project that in greyhounds 40 per cent or more of the blood volume may be removed and replaced with SFHS and major vascular surgery done without undue risk and with unaltered kidney function.

We report the results of a random, prospective study of electrical clipping versus routine razor shaving in the removal of hair immediately before operation. Two hundred patients having elective inguinal herniorrhaphy according to strict protocol were included in this study. Unsatisfactory skin preparation, as evidenced by gross cuts made in the skin during hair removal, was noted in 7% of those shaved and 4% of those clipped. Two subcutaneous wound infections occurred in the shaved group (2%) and one in the clipped group (1%). This study indicates that preoperative clipping of hair with electric barber's clippers immediately before operation is a safe, well tolerated procedure that does not increase the risk of postoperative wound infection.

It appears that BGI Solution is a satisfactory graft irrigation media and does preserve the intima better than normal saline and as effective as whole blood. It also functions as a media for storage of vein grafts at 0-5 degrees C. Partially supported by grant from Arizona Heart Association.

Brachial, femoral (in the groin), popliteal, and tibial systolic blood pressures were determined with the Doppler technic. New indexes were developed: femoral/brachial (B/B), popliteal/femoral (P/F), ankle/femoral (A/F), and ankle/popliteal (A/P). Curves were plotted using these indexes and compared with established configurations. As a result the site or sites of obstruction were rapidly determined.