Comparative total mortality in 25 years in Italian and Greek middle aged rural men.
STUDY OBJECTIVE: Mortality over 25 years has been low in the Italian and very low in the Greek cohorts of the Seven Countries Study; factors responsible for this particularity were studied in detail. PARTICIPANTS AND SETTINGS: 1712 Italian and 1215 Greek men, aged 40-59 years, cohorts of the Seven Countries Study, representing over 95% of the populations in designated rural areas. DESIGN: Entry (1960-61) data included age, systolic blood pressure (SBP), smoking habits, total serum cholesterol, body mass index (BMI), arm circumference, vital capacity (VC), and forced expiratory volume in 3/4 seconds (FEV); the same data were obtained 10 years later. Multivariate Cox analysis was performed with all causes death in 25 years as end point. MAIN RESULTS: Italian men had higher entry levels of SBP, arm circumference, BMI, and VC; Greek men had higher cholesterol levels, smoking habits, and FEV. Mortality of Italian men was higher throughout; at 25 years cumulative mortality was 48.3% and 35.3% respectively. Coronary heart disease and stroke mortality increased fivefold in Italy and 10-fold in Greece between years 10 and 25. The only risk factor with a significantly higher contribution to mortality in Italian men was cholesterol. However, differences in entry SBP (higher in Italy) and FEV (higher in Greece) accounted for, according to the Lee method, 75% of the differential mortality between the two populations. At 10 years increases in SBP, cholesterol, BMI, and decreases in smoking habits, VC, FEV, and arm circumference had occurred (deltas). SBP increased more and FEV and VC decreased more in Italy than in Greece. Deltas, fed stepwise in the original model for the prediction of 10 to 25 years mortality, were significant for SBP, smoking, arm circumference, and VC in Greece, and for SBP and VC in Italy. CONCLUSION: Higher mortality in Italian men is related to stronger positive effects of entry SBP and weaker negative (protective) effects of FEV; in addition 10 year increases in SBP are higher and 10 year decreases in FEV are larger in Italy. Unaccounted factors, however, related to, for example, differences in the diet, may also have contributed to the differential mortality of these two Mediterranean populations. (+info)
Activity-dependent metaplasticity of inhibitory and excitatory synaptic transmission in the lamprey spinal cord locomotor network.
Paired intracellular recordings have been used to examine the activity-dependent plasticity and neuromodulator-induced metaplasticity of synaptic inputs from identified inhibitory and excitatory interneurons in the lamprey spinal cord. Trains of spikes at 5-20 Hz were used to mimic the frequency of spiking that occurs in network interneurons during NMDA or brainstem-evoked locomotor activity. Inputs from inhibitory and excitatory interneurons exhibited similar activity-dependent changes, with synaptic depression developing during the spike train. The level of depression reached was greater with lower stimulation frequencies. Significant activity-dependent depression of inputs from excitatory interneurons and inhibitory crossed caudal interneurons, which are central elements in the patterning of network activity, usually developed between the fifth and tenth spikes in the train. Because these interneurons typically fire bursts of up to five spikes during locomotor activity, this activity-dependent plasticity will presumably not contribute to the patterning of network activity. However, in the presence of the neuromodulators substance P and 5-HT, significant activity-dependent metaplasticity of these inputs developed over the first five spikes in the train. Substance P induced significant activity-dependent depression of inhibitory but potentiation of excitatory interneuron inputs, whereas 5-HT induced significant activity-dependent potentiation of both inhibitory and excitatory interneuron inputs. Because these metaplastic effects are consistent with the substance P and 5-HT-induced modulation of the network output, activity-dependent metaplasticity could be a potential mechanism underlying the coordination and modulation of rhythmic network activity. (+info)
The significance of non-significance.
We discuss the implications of empirical results that are statistically non-significant. Figures illustrate the interrelations among effect size, sample sizes and their dispersion, and the power of the experiment. All calculations (detailed in Appendix) are based on actual noncentral t-distributions, with no simplifying mathematical or statistical assumptions, and the contribution of each tail is determined separately. We emphasize the importance of reporting, wherever possible, the a priori power of a study so that the reader can see what the chances were of rejecting a null hypothesis that was false. As a practical alternative, we propose that non-significant inference be qualified by an estimate of the sample size that would be required in a subsequent experiment in order to attain an acceptable level of power under the assumption that the observed effect size in the sample is the same as the true effect size in the population; appropriate plots are provided for a power of 0.8. We also point out that successive outcomes of independent experiments each of which may not be statistically significant on its own, can be easily combined to give an overall p value that often turns out to be significant. And finally, in the event that the p value is high and the power sufficient, a non-significant result may stand and be published as such. (+info)
Capture-recapture models including covariate effects.
Capture-recapture methods are used to estimate the incidence of a disease, using a multiple-source registry. Usually, log-linear methods are used to estimate population size, assuming that not all sources of notification are dependent. Where there are categorical covariates, a stratified analysis can be performed. The multinomial logit model has occasionally been used. In this paper, the authors compare log-linear and logit models with and without covariates, and use simulated data to compare estimates from different models. The crude estimate of population size is biased when the sources are not independent. Analyses adjusting for covariates produce less biased estimates. In the absence of covariates, or where all covariates are categorical, the log-linear model and the logit model are equivalent. The log-linear model cannot include continuous variables. To minimize potential bias in estimating incidence, covariates should be included in the design and analysis of multiple-source disease registries. (+info)
Effect of coronary occlusion on left ventricular function with and without collateral supply during beating heart coronary artery surgery.
OBJECTIVE: To study the effects of coronary occlusion and collateral supply on left ventricular (LV) function during beating heart coronary artery surgery. DESIGN: Prospective intraoperative study, performed at baseline, during wall stabilisation, coronary artery occlusion, and 2 and 10 minutes after reperfusion. Transoesophageal M mode echocardiograms, simultaneous high fidelity LV pressure, and thermodilution cardiac output were measured. LV anterior wall thickening, thinning velocities, thickening fraction, regional work, and power production were derived. Asynchrony during the isovolumic periods was quantified as cycle efficiency. SETTING: Tertiary referral cardiac centre. PATIENTS: 14 patients with stable angina, mean (SD) age 62 (7) years, undergoing left anterior descending artery grafting using the "Octopus" device. RESULTS: Collaterals were absent in nine patients and present in five. Epicardial stabilisation did not affect LV function. Results are expressed as mean (SD). Coronary occlusion (15.6 (2) minutes) depressed anterior wall thickening (1.4 (0.6) v 2.6 (0.6) cm/s) and thinning velocities (1.4 (0.5) v 3.0 (0.6) cm/s), regional work (2.2 (0.8) v 4.6 (0.6) mJ/cm2), and power (21 (4) v 33 (5) mW/cm2) in patients without collaterals (p < 0.05 for all), but only wall thinning (3.5 (0.5) v 4.8 (0.5) cm/s, p < 0.05) in patients with collaterals. All returned to baseline within 10 minutes of reperfusion. Cycle efficiency and regional work were impaired at baseline and fell during occlusion, regardless of collaterals. Within 10 minutes of reperfusion both had increased above baseline. CONCLUSIONS: Coronary occlusion for up to 15 minutes during beating heart coronary artery surgery depressed standard measurements of systolic and diastolic anterior wall function in patients without collaterals, but only those of diastolic function in patients with collaterals. Regional synchrony decreased in both groups. All disturbances regressed within 10 minutes of reperfusion. (+info)
Acquisition of nicotine discrimination and discriminative stimulus effects of nicotine in rats chronically exposed to caffeine.
Caffeine and nicotine are the main psychoactive ingredients of coffee and tobacco, with a high frequency of concurrent use in humans. This study examined the effects of chronic caffeine exposure on 1) rates of acquisition of a nicotine discrimination (0.1 or 0.4 mg/kg, s.c., training doses) and 2) the pharmacological characteristics of the established nicotine discrimination in male Sprague-Dawley rats. Once rats learned to lever-press reliably under a fixed ratio of 10 schedule for food pellets, they were randomly divided into two groups; 12 animals were maintained continuously on caffeine added to the drinking water (3 mg/ml) and another 12 control rats continued to drink tap water. In each group of water- and caffeine-drinking rats, there were six rats trained to discriminate 0.1 mg/kg of nicotine from saline and six rats trained to discriminate 0.4 mg/kg of nicotine from saline. Regardless of the training dose of nicotine, both water- and caffeine-drinking groups required a comparable number of training sessions to attain reliable stimulus control, although there was a trend for a slower acquisition in the caffeine-drinking group trained with 0.1 mg/kg of nicotine. Tests for generalization to different doses of nicotine revealed no significant differences in potency of nicotine between water- and caffeine-drinking groups. The nicotinic-receptor antagonist mecamylamine blocked the discriminative effects of 0.1 and 0.4 mg/kg nicotine with comparable potency and efficacy in water- and caffeine-drinking groups. There was a dose-related generalization to both the 0.1 and 0.4 mg/kg nicotine cue (maximum average of 51-83%) in water-drinking rats after i.p. treatment with d-amphetamine, cocaine, the selective dopamine uptake inhibitor GBR-12909, apomorphine, and the selective dopamine D1 receptor agonist SKF-82958, but not in caffeine-drinking rats (0-22%). There was no generalization to the nicotine cues after i.p. treatment with caffeine or the selective D2 (NPA) and D3 (PD 128,907) dopamine-receptor agonists in water- and caffeine-drinking rats. The dopamine-release inhibitor CGS 10746B reduced the discriminative effects of 0.4 mg/kg nicotine in water-drinking rats, but not in caffeine-drinking rats. There was no evidence of development of tolerance or sensitization to nicotine's effects throughout the study. In conclusion, chronic caffeine exposure (average, 135 mg/kg/day) did not affect the rate of acquisition of the nicotine discrimination, but it did reduce the dopaminergic component of the nicotine-discriminative cue. The reduction of the dopaminergic component of the nicotine cue was permanent, as this effect was still evident after the caffeine solution was replaced with water in caffeine-drinking rats. That nicotine could reliably serve as a discriminative stimulus in the absence of the dopaminergic component of its discriminative cue may differentiate nicotine from "classical dopaminergic" drugs of abuse such as cocaine and amphetamine. (+info)
Hierarchical cluster analysis applied to workers' exposures in fiberglass insulation manufacturing.
The objectives of this study were to explore the application of cluster analysis to the characterization of multiple exposures in industrial hygiene practice and to compare exposure groupings based on the result from cluster analysis with that based on non-measurement-based approaches commonly used in epidemiology. Cluster analysis was performed for 37 workers simultaneously exposed to three agents (endotoxin, phenolic compounds and formaldehyde) in fiberglass insulation manufacturing. Different clustering algorithms, including complete-linkage (or farthest-neighbor), single-linkage (or nearest-neighbor), group-average and model-based clustering approaches, were used to construct the tree structures from which clusters can be formed. Differences were observed between the exposure clusters constructed by these different clustering algorithms. When contrasting the exposure classification based on tree structures with that based on non-measurement-based information, the results indicate that the exposure clusters identified from the tree structures had little in common with the classification results from either the traditional exposure zone or the work group classification approach. In terms of the defining homogeneous exposure groups or from the standpoint of health risk, some toxicological normalization in the components of the exposure vector appears to be required in order to form meaningful exposure groupings from cluster analysis. Finally, it remains important to see if the lack of correspondence between exposure groups based on epidemiological classification and measurement data is a peculiarity of the data or a more general problem in multivariate exposure analysis. (+info)
Racial differences in the outcome of left ventricular dysfunction.
BACKGROUND: Population-based studies have found that black patients with congestive heart failure have a higher mortality rate than whites with the same condition. This finding has been attributed to differences in the severity, causes, and management of heart failure, the prevalence of coexisting conditions, and socioeconomic factors. Although these factors probably account for some of the higher mortality due to congestive heart failure among blacks, we hypothesized that racial differences in the natural history of left ventricular dysfunction might also have a role. METHODS: Using data from the Studies of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials, in which all patients received standardized therapy and follow-up, we conducted a retrospective analysis of the outcomes of asymptomatic and symptomatic left ventricular systolic dysfunction among black and white participants. The mean (+/-SD) follow-up was 34.2+/-14.0 months in the prevention trial and 32.3+/-14.8 months in the treatment trial among the black and white participants. RESULTS: The overall mortality rates in the prevention trial were 8.1 per 100 person-years for blacks and 5.1 per 100 person years for whites. In the treatment trial, the rates were 16.7 per 100 person-years and 13.4 per 100 person-years, respectively. After adjustment for age, coexisting conditions, severity and causes of heart failure, and use of medications, blacks had a higher risk of death from all causes in both the SOLVD prevention trial (relative risk, 1.36; 95 percent confidence interval, 1.06 to 1.74; P=0.02) and the treatment trial (relative risk, 1.25; 95 percent confidence interval, 1.04 to 1.50; P=0.02). In both trials blacks were also at higher risk for death due to pump failure and for the combined end point of death from any cause or hospitalization for heart failure, our two predefined indicators of the progression of left ventricular systolic dysfunction. CONCLUSIONS: Blacks with mild-to-moderate left ventricular systolic dysfunction appear to be at higher risk for progression of heart failure and death from any cause than similarly treated whites. These results suggest that there may be racial differences in the outcome of asymptomatic and symptomatic left ventricular systolic dysfunction. (+info)