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Objective: To estimate the relative risk of injury among horses deemed to be at increased risk of injury on the basis of prerace physical inspection findings and to examine the association of injury during races with race-related characteristics., Design: Cohort study., Animals: 2,187 Thoroughbred horses that started 3,227 races in Kentucky., Procedure: All race starts for which a horse was deemed to be at increased risk of injury on the basis of prerace physical inspection findings and a random sample of race starts for which horses were not deemed at increased risk of injury were included in the study. Findings of prerace physical inspection, race-related characteristics, and outcome of the race (race results and whether the horse incurred an injury) were recorded for each race start. Race starts in which a horse incurred an injury during a race were compared with race starts in which injuries were not incurred to identify factors associated with injury during races., Results: Abnormality of the suspensory ligament of the forelimbs detected during prerace physical inspection, racetrack, class of race (claiming race < or = $25,000 vs other classes), and distance of race (< 7 furlongs vs other distances) were significantly associated with increased risk of injury., Conclusions and Clinical Relevance: Prerace physical inspection findings, particularly abnormalities of the suspensory ligament, may be used to identify horses at increased risk of injury during races. Rate of injury differed among racetracks, and horses in certain types of races (lower-priced claiming races and races of shorter distance) may be at increased risk of injury during races.

While more than 80% of childhood asthmatics are allergic to one or more inhaled allergens, the role of inhaled allergens in the induction of wheeze in the first year of life is unknown. In a prospective birth-cohort study of 499 children of asthmatic/allergic parents from metropolitan Boston, we examined home allergen concentrations measured within the first 3 mo of life as predictors of repeated wheeze episodes in the first year of life. In multivariate analyses adjusting for maternal asthma and dog in the home, predictors of two or more wheeze episodes in the first year of life included maternal smoking during pregnancy (relative risk [RR] = 1.83; 95% confidence limit [CL]: 1.12, 3.00), lower respiratory illness in the first year of life (croup, bronchitis, bronchiolitis, or pneumonia) (RR = 2.25; 95% CL:1.58, 3.19), low birthweight (RR = 1.28, 95% confidence interval [CI]: 1.04, 1.58 for an interquartile difference), and Bla g 1 or 2 (cockroach) allergen level in the family room > 0.05 U/g dust (RR = 1.76; 95% CL: 1.20, 2.57). Cockroach allergen in the family room and repeated wheeze remained significant after adjustment for socioeconomic factors including race and income (RR = 1.63; 95% CL: 1.05, 2.55). It is unknown whether the association between cockroach and repeated wheeze in infancy represents a cockroach-related increased risk of bronchial inflammation through nonallergenic or allergenic mechanisms.

Context: Obesity is a well-established risk factor for coronary heart disease (CHD), but whether regional fat distribution contributes independently to risk remains unclear., Objective: To compare waist-hip ratio (WHR) and waist circumference in determining risk of CHD in women., Design and Setting: Prospective cohort study among US female registered nurses participating in the Nurses' Health Study conducted between 1986, when the nurses completed a questionnaire, and follow-up in June 1994., Participants: A total of 44702 women aged 40 to 65 years who provided waist and hip circumferences and were free of prior CHD, stroke, or cancer in 1986., Main Outcome Measures: Incidence of CHD (nonfatal myocardial infarction or CHD death)., Results: During 8 years of follow-up 320 CHD events (251 myocardial infarctions and 69 CHD deaths) were documented. Higher WHR and greater waist circumference were independently associated with a significantly increased age-adjusted risk of CHD. After adjusting for body mass index (BMI) (defined as weight in kilograms divided by the square of height in meters) and other cardiac risk factors, women with a WHR of 0.88 or higher had a relative risk (RR) of 3.25 (95% confidence interval [CI], 1.78-5.95) for CHD compared with women with a WHR of less than 0.72. A waist circumference of 96.5 cm (38 in) or more was associated with an RR of 3.06 (95% CI, 1.54-6.10). The WHR and waist circumference were independently strongly associated with increased risk of CHD also among women with a BMI of 25 kg/m2 or less. After adjustment for reported hypertension, diabetes, and high cholesterol level, a WHR of 0.76 or higher or waist circumference of 76.2 cm (30 in) or more was associated with more than a 2-fold higher risk of CHD., Conclusions: The WHR and waist circumference are independently associated with risk of CHD in women.

Objective: To describe the natural history of somatic growth in HIV infection by constructing age-specific growth velocity norms and to assess specific prognostic information available using these norms., Design: Observations on 1338 HIV-infected children aged 3 months to 15 years who participated in one of four US clinical trials of pediatric anti-HIV therapies were pooled; baseline growth velocity data were obtained using the first 6 months of observation for each child., Methods: Distributions of physical growth velocities in HIV-infected children in the Pediatric AIDS Clinical Trials Group were computed. Statistical smoothing of growth histories was employed to derive velocity estimates, and quantile regression analysis of growth velocities was performed to allow comparisons of growth rates in age- and gender-heterogeneous cohorts in the context of HIV infection. The quantile regressions provide corrected z-scores for growth velocity that appropriately compare HIV-infected children with one another for the purpose of distinguishing more from less favorable prognoses., Results: Consistent deficits in growth velocity amongst HIV-infected children were revealed when compared with the Fels Institute velocity standards. Approximately 33% of height (and 20% of weight) age- and sex-corrected velocity measurements obtained in the first 6 months of clinical trial participation lay beneath the corresponding third percentiles of the Fels reference distributions, which are commonly regarded as critical indicators of growth failure. Proportional hazards regression tests indicated that both weight and height velocity contributed significant information on the risk of death among children with AIDS after adjusting for antiretroviral therapy received, CD4 cell counts, and age at trial enrollment. Comparing subjects who differ in initial weight velocity by one age- and sex-corrected SD, the relative hazard of death was 0.63 (95% confidence interval, 0.55-0.72; P < or = 0.0001) in favor of the child with greater weight velocity, controlling for antiretroviral therapy received, age and CD4 cell count at baseline. The analogous hazard ratio for height velocity was 0.68 (95% confidence interval, 0.57-0.79; P < or = 0.0001)., Conclusions: Suitably normalized growth velocities are informative and inexpensive criteria for pediatric AIDS prognosis; the growth velocity distributions presented will be useful for comparing growth effects of new therapeutic strategies to those of single and combination antiretrovirals employed for maintenance of pediatric HIV infection in the mid-1990s.

Although heredity plays a major role in asthma and in other allergic diseases, mechanisms underlying the inheritance of these disorders are poorly understood, as is the relative contribution of maternal and paternal conditions to risk of disease. We investigated doctor-diagnosed maternal and paternal asthma, eczema, and hay fever as cross-sectional predictors of childhood asthma and allergic disease in 306 children with a median age of 3.5 yr from families in which at least one parent had a history of either asthma or other allergic conditions. For both childhood asthma and eczema, the strongest parental predictors were the same conditions in the parents. For asthma in particular, maternal asthma was most strongly associated with asthma in the child over all ages in both univariate (OR = 3.2, 95% CI = 1.5 to 6.7) and multivariable (OR = 4.1, 95% CI = 1.7 to 10.1) models. Paternal asthma was weakly associated with childhood asthma in the univariate model (OR = 1.4, 95% CI = 0.6 to 3.2), but this association increased in magnitude in the multivariable model (OR = 2.7, 95% CI = 1.0 to 7.2). Among the children < 5 yr of age, the risk for childhood asthma associated with maternal asthma (OR = 5.0, 95% CI = 1.7 to 14.9) was greater than the risk associated with paternal asthma (OR = 1.6, 95% CI = 0. 5 to 5.9), whereas both maternal asthma and paternal asthma were associated with similar risks among children >= 5 yr of age (OR = 4. 6, 95% CI = 1.1 to 19.0 and OR = 4.1, 95% CI = 1.0 to 16.0, respectively). The odds of having a child with asthma were three times greater in families with one asthmatic parent and six times greater in families with two asthmatic parents than in families where only one parent had inhalant allergy without asthma; furthermore, inhalant allergy in one parent also conferred additional risk in the presence of asthma in the other parent. Further investigation is needed into the relative importance of genetic factors and in utero and postnatal exposures in determining the differential effects of maternal and paternal asthma on the development of childhood asthma.

Change in airway responsiveness is used frequently as a clinical as well as an epidemiological tool. Changes in airway responsiveness can be superior to other measures of lung function in that they are more sensitive indicators of an environmental effect. However, normal variation in test results must be defined before change can be interpreted. To characterize annual variability in airways responsiveness, we administered a high-dose methacholine challenge at 1 yr intervals for up to 4 yrs to 105 healthy, nonasthmatic working subjects. Using this high-dose protocol, the majority of tests (83%) produced at least a 20 % fall in forced expiratory volume in one second (FEV1), allowing standard calculation of the provocative dose of methacholine causing a 20% fall in FEV1 (PD20). An annual change in methacholine responsiveness by one or more doubling doses was seen in at least 30% of subjects each year. The components of variance of airways responsiveness measures were estimated to allow direct comparison of within-subject and between-subject variability. The within-subject variability in PD20, was markedly greater than the comparable within-subject variability in FEV1. Level of FEV1 and age were both significant determinants of methacholine responsiveness. Comparison of two methods of expressing methacholine responsiveness (PD20 using the full challenge up to 250 mg x mL(-1) methacholine, and the dose-response slope using data up to 32 mg x mL(-1) methacholine as the maximum dose) had similar annual variability in censored data and mixed-effects models. We then developed an approach to statistical analysis of "right-censored" methacholine challenge data using a maximum likelihood estimation under a censored Gaussian model. These studies of methacholine responsiveness provide normative data on annual test variability in healthy, nonasthmatic working adults, and show that a shorter low-dose challenge has comparable annual variability to a lengthier high-dose challenge.

Context: Gestational diabetes mellitus (GDM) affects 3% to 5% of pregnancies. Knowledge of risk factors for GDM is needed to identify possible preventive strategies., Objective: To assess whether recognized determinants of noninsulin-dependent diabetes mellitus also may be markers for increased risk of GDM., Design: Prospective cohort study., Setting: The Nurses' Health Study II, which involves female US nurses aged 25 to 42 years at entry., Participants: The analyses included 14613 women without previous GDM or other known diabetes who reported a singleton pregnancy between 1990 and 1994. Of these women, 722 (4.9%) reported a new diagnosis of GDM., Main Outcome Measure: Self-report of GDM, validated by medical record review in a subset., Results: In multivariate analyses including age, pregravid body mass index (BMI), and other GDM risk factors, the risk for GDM increased significantly with increasing maternal age (P for trend, <.01) and family history of diabetes mellitus (relative risk, 1.68; 95% confidence interval [CI], 1.39-2.04). Relative risks for GDM were 2.13 (95% CI, 1.65-2.74) for pregravid BMI of 25 to 29.9 kg/m2 and 2.90 (95% CI, 2.15-3.91) for BMI of 30 kg/m2 or more (vs BMI of <20 kg/m2). Risk for GDM increased with greater weight gain in early adulthood, and it also increased among nonwhite women. Pregravid current smokers had a relative risk for GDM of 1.43 (95% CI, 1.14-1.80), and pregravid vigorous exercise was associated with a nonsignificant reduction in GDM risk., Conclusions: Advanced maternal age, family history of diabetes mellitus, nonwhite ethnicity, higher BMI, weight gain in early adulthood, and cigarette smoking predict increased GDM risk. These observations may facilitate the identification of women at particular risk for GDM and suggest potential strategies for reducing this risk even before a woman becomes pregnant, such as avoiding substantial weight gain and smoking.

This investigation characterizes the normal growth, variability, and effects of gender and smoking on passive respiratory mechanics in healthy infants. Passive respiratory mechanics were assessed at 193 test sessions on 127 infants (55 boys, 72 girls) between 2 wk and 18 mo of age using the single-occlusion passive flow-volume technique. Respiratory compliance (Crs) increased significantly with increasing infant length, whereas respiratory resistance (Rrs) declined. No significant gender differences were apparent for Crs, although there was a tendency for this measure to be both lower at birth and increase at a slower rate in girls than in boys. Rrs was significantly higher at birth in infant boys than in infant girls, but the rate of the normal decline in Rrs during the first 18 mo also occurred at a significantly greater rate in boys. The passive respiratory time constant (Trs) overall showed little change over this age range, but it was both lower near birth and increased at a significantly greater rate versus infant length in girls than in boys. Maternal smoking during pregnancy was associated with lower levels of Rrs at birth, as well as with significantly slower growth of Crs and natural decline of Rrs in the first 18 mo of life. These data suggest that infant girls may have more mature respiratory mechanics at birth, but that postnatal growth/maturation may be faster in boys.

The prevalence and predictors of wheeze syndromes, including asthma, were examined among 475 non-Hispanic (NH) white and 371 Hispanic pregnant women enrolled in a population-based study in East Boston, Massachusetts. Respiratory symptoms and risk factors were ascertained by questionnaire early in pregnancy. Hispanic and NH white women were of similar age (mean +/- SD, 26 +/- 5 yr), but Hispanics reported less schooling (30 versus 50% completed high school), a lower frequency of household pets (4 versus 47%), and a lower frequency of parental asthma (6 versus 12%). Hispanics smoked significantly less than NH whites did, both in prevalence (8 versus 50%) and number of cigarettes per day among current smokers (12 +/- 9 versus 22 +/- 10; p < 0.0001). Hispanics reported a lower frequency than NH whites did of doctor-diagnosed asthma (6 versus 12%), persistent wheeze (5 versus 19%), and either persistent wheeze or asthma (11 versus 30%). In multivariate analysis, active cigarette smoking and parental history of asthma were associated most strongly with wheeze syndromes. When these two factors as well as educational level, presence of household pets, and height2-adjusted FEV1 were controlled, Hispanics remained at lower risk of asthma (odds ratio [OR] 0.71; 95% confidence interval [CI], 0.37-1.37) and persistent wheeze (OR 0.48; 95% CI, 0.25-0.95) than NH whites. These results suggest that chronic wheeze syndromes are common among young urban women and are associated with both active smoking and a parental history of asthma. Hispanic women from Central and South America living in urban environments in the United States may be at less risk for these conditions than NH white women, in contrast to those from Puerto Rico.

To describe the role of airways responsiveness in predicting incidence of wheeze in early adolescence and to examine the association between airways responsiveness and active asthma symptoms, children who had been tested for airways hyperresponsiveness were assessed prospectively. Of 770 children in the East Boston Childhood Respiratory Disease Cohort who were between 5 and 9 yr of age at time of entry into the study, 281 children received airways challenges during voluntary follow-up conducted between 1980 and 1986. Each subject presented a sequence of wheeze or asthma diagnosis reports along with a sequence of time-varying covariates, including airways challenge results and symptom and exposure information. A robust "pooled repeated observations" analog of the proportional hazard regression model was used to assess associations among risk factors and the probability of incident wheeze or active asthma. In the analysis of wheeze incidence, airways responsiveness (elicited via eucapnic hyperventilation with cold air or methacholine challenge) among those free of a history of wheeze at a given visit was found to be associated with a greater tendency to develop wheezing in the next visit (odds ratio [OR] = 3.91, 95% confidence interval [CI] = 1.21, 12.66), after controlling for a constellation of known risk factors. In the analysis of recurrent asthma episodes, airways responsiveness at a given visit was associated with a greater tendency to have an asthma diagnosis reported at the subsequent visit (OR = 4.2, 95% CI = 1.92, 9.23). For subjects presenting multiple airways responsiveness challenge studies, two successive positive airways responsiveness results were independently associated with a higher likelihood of recurrent asthma episodes. These results confirm the predictive importance of airways responsiveness in the natural history of the development and persistence of asthmatic symptoms.

Following a decade of accumulating clinical reports on child drowning in domestic swimming pools, paediatricians began advocating legislation that would require all pools to be 'isolation' fenced. In 1990, the New South Wales Government introduced and then repeated such legislation following intense lobbying and media advocacy from a group of pool owners. This paper reviews the ways in which isolation fence advocates and opponents framed their public arguments. Five main areas of competing public discourse are identified: why pool drownings occur; the effects of fencing; expert views and community support; the role of the state in prevention; and personalised references to the value systems of those involved in the debate. Two factors seem likely to have contributed most to the overthrow of the legislation: fence opponents inhabiting the same noninterventionist ideological frame of reference as the government; and fence advocates' refusal to compromise on retrospective fencing seems likely to have inspired a commitment in opposition which would have been absent if an incrementalist, prospective fencing policy had been adopted.

In epidemiological settings, we are often faced with numerous short time series, and a parsimonious parametrization of the correlation structure is desired in order to optimize the efficiency of the estimation procedure. We propose a damped exponential correlation structure for modeling multivariate Gaussian outcomes. The correlation between two observations separated by s units of time is modeled as gamma s theta, where gamma is the correlation between elements separated by one s-unit, and theta is a damping parameter. For (theta = 0), (theta = 1), and theta----infinity), the correlation structures of compound symmetry, first-order autoregressive, and first-order moving average processes are obtained. Although the AR(2) dependency structure, and the combination of random effects and AR(1) errors are not special cases of the proposed parametric family, these structures can be well approximated within the family for short time series. Maximum likelihood methods for parameter estimation and interpretations of intermediate models (0 less than theta less than 1) are discussed in the context of modeling pulmonary function in an adult population in The Netherlands and T-cell subsets in homosexual men infected with human immunodeficiency virus Type I.

In natural history studies of human immunodeficiency virus type 1 (HIV-1) infection a substantial proportion of participants are seropositive at time of enrollment in the study. These participants form a prevalent subcohort. Estimation of the unknown times since exposure to HIV-1 in the prevalent subcohort is of primary importance for estimation of the incubation time of AIDS. The subset of the cohort that tested negative for antibody to HIV-1 at study entry and was observed to seroconvert forms the incident subcohort that provides longitudinal data on markers of maturity (that is, duration) of infection. We use parametric life table regression models incorporating truncation to describe the conditional distribution (imputing model) of the times since seroconversion given a vector of the markers of maturity. Using the fitted model and the values of the markers of maturity of infection provided by the seroprevalent subcohort at entry into the study, we can impute the unknown times since seroconversion for the prevalent subcohort. We implement multiple imputation based on a model-robust estimate of the covariance matrix of parameters of the imputing model to provide confidence intervals for the geometric mean of the time since seroconversion in the prevalent subcohort, and to compare maturity of infection of cohorts recruited in different cities. The accuracy of imputation is further validated by comparisons of imputation-based estimates of AIDS incubation distribution in the seroprevalent subcohort with more direct estimates obtained from the seroincident subcohort.

In the statistical analysis of twinship and familial data, one often encounters the need for regression methods that control for the possibly different aggregation of the twins and the members of the families according to their type (e.g., monozygotic, dizygotic for twinship data). We present the maximum likelihood solution for the regression analysis of data in the presence of heterogeneous intraclass correlations. This work extends previous results for the case of a homogeneous intraclass correlation. An application of the methods for the analysis of twinship data is included.

The potential utility of Zymomonas mobilis as an organism for the commercial production of ethanol would be greatly enhanced by the addition of foreign genes which expand its range of fermentable substrates. We tested various plasmids and mobilizing factors for their ability to act as vectors and introduce foreign genes into Z. mobilis CP4. Plasmid pGC91.14, a derivative of RP1, was found to be transferred from Escherichia coli to Z. mobilis at a higher frequency than previously reported for any other plasmids. Both tetracycline resistance and the lactose operon from this plasmid were expressed in Z. mobilis CP4. Plasmid pGC91.14 was stably maintained in Z. mobilis at 30 degrees C but rapidly lost at 37 degrees C.

This study investigated whether seroconversion with respect to human immunodeficiency virus, type 1 (HIV-1) was associated with an increase in lymphocytes expressing the CD3+CD4-CD8- phenotype. Proportions and absolute numbers of CD3+, CD4+, and CD8+ lymphocytes were determined prospectively over a 2.5-year period on 4954 homosexual and/or bisexual men participating in the Multicenter AIDS Cohort Study. Of the 4808 men whose serostatus at entry could be verified, 1745 were seropositive (SP) for antibodies to HIV-1 at entry into study, 2795 were uniformly seronegative (SN) for HIV-1 for 30 months, and 268 were seroconverters (SC) with respect to HIV-1 during this period. For each of six semiannual evaluations, proportions and numbers of CD3+CD4-CD8- lymphocytes (calculated as CD3- (CD4 + CD8] were both significantly greater in the SP group than in the SN group (P less than 0.001). Mean CD3+CD4-CD8- levels in the SC group were indistinguishable from those in the SN group before seroconversion, but by 3-9 months after seroconversion the SC group demonstrated absolute numbers of CD3+CD4-CD8- lymphocytes which were significantly increased (P less than 0.001) compared to the SN group using linear regression methods with adjustment for correlation of measurements within an individual over time. An additional significant increase occurred by 21-27 months after seroconversion (P = 0.006). These results are consistent with an association of HIV-1 seroconversion with an increase in circulating T lymphocytes expressing the CD3+CD4-CD8- phenotype (double negative T cells), a decrease in CD3-CD4-CD8+ natural killer cells, or both. An increase in double negative T cells could reflect a host defense mechanism against HIV-1 or effects of HIV-1 on T cell development.

A simplified method for titrations of biochemical systems is described as well as extensive error propagation through the data analysis. This work uses a Tronac Model 450 isoperibol titration calorimeter. Sample volumes of 2 ml are used and total heats of less than 5 mcal can be routinely measured. The binding of 3'-CMP to bovine pancreatic ribonuclease A is used to illustrate the methods. The binding enthalpy can be determined with a standard deviation of 1.5% and the free energy with a standard deviation of 2 to 3%.

Longitudinal data on four visits scheduled at 6 month intervals were available on a cohort of 1,827 homosexual men who were human immunodeficiency virus (HIV) seropositive at entry. To identify predictors of the rate of decline of CD4 T-lymphocytes, we used an autoregressive model that relates CD4 counts to predictor variables, while adjusting for previous CD4 counts. Significant predictors of steeper decline of CD4 counts were high CD8 count, low hemoglobin, low platelets, high serum IgA, high cytomegalovirus (CMV) antibody, and low HIV antibody. Using the fitted model, a subject with an initial deficit of 314 CD4 cells (median value of study sample) with respect to seronegative subjects and with average values in all other predictors is estimated to lose approximately 53 cells in a 6 month period (95% C.I. = 45-61 cells). Contrasting this estimate to the one obtained with similar methods in intravenous drug users, it is suggested that a faster rate of decline is present among i.v. drug users. This analysis provides evidence that several covariates in addition to previous number of CD4 counts have significant predictive power for estimating the decline in CD4 counts in HIV seropositive subjects.

We have examined the relationship between membrane fluidity and the alcohol-induced loss of righting reflex at different temperatures using the fish Gambusia affinis. The potency of ethanol and hexanol increased dramatically with temperature. Ethanol-induced narcosis could be antagonized by a reduction in incubation temperature. Both an increase in temperature and the addition of ethanol caused an increase in membrane fluidity. However, membrane fluidity itself did not correlate with narcosis and was primarily determined by incubation temperature. Narcotic concentrations of ethanol caused a change in fluidity equivalent to less than that caused by a 2 degree increase in temperature while an 8 degree increase in temperature did not induce narcosis. From these studies, we conclude that the ethanol-induced increase in bulk membrane fluidity as measured by diphenyl-hexatriene is not the causal event for narcosis although the magnitude of this change does correlate with the alcohol sensitivity. We have also examined the effects of temperature adaptation on the sensitivity of these animals to ethanol. Summer animals contained higher levels of saturated fatty acids, exhibited a higher temperature range than winter animals and were more resistant to ethanol, providing further evidence for membrane structure as a determinant of alcohol sensitivity.

The effect of personal cigarette smoking on the growth of lung function in children and adolescents has been assessed in a longitudinal study of a group of 669 subjects 5 to 19 yr of age at initial examination. Subjects were seen annually and assessed with standard questionnaires and measurements of forced expiratory volume in one second (FEV1) and forced expiratory flow during the middle half of the forced vital capacity (FEF25-75). Multiple regression analysis revealed that after correction for previous FEV1 or FEF25-75, age, sex, height, change in height, interactions of age and change in height, and sex and height, and mother's smoking, the personal smoking by the children led to a significant decrease in the rate of growth of FEV1 (p less than 0.001) and FEF25-75 (p = 0.033). On the basis of this analysis, it is estimated that, on average, children who begin to smoke at 15 yr of age and continue to smoke would achieve only 92% (95% confidence limit, 87 to 96%) of their expected FEV1 and 90% (95% confidence limit, 81 to 99%), of their expected FEF25-75 at 20 yr of age. These data suggest that relatively small amounts of cigarette use (median total consumption of 7,300 cigarettes in this study) by adolescents can lead to significant effects on the growth of lung function.