Evaluation of hypothesis testing for comparing two populations using NONMEM analysis

In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i)the ratio of mean clearance and (ii)the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations.Partial support from the Upjohn Company, NIH-BRSG SO RR 07066, and the Burroughs Wellcome Foundation.     

Image size magnification and power and dilation factors for optical instruments in general

Traditional treatments of spectacle magnification for distant objects consider only stigmatic spectacle lenses and they compare the retinal image size in a refractively fully compensated eye with the image size in the uncompensated eye. Spectacle magnification is expressed as a product of two factors, the power and shape factors of the lens. The power factor depends on the position of the entrance pupil of the eye. For an eye with an astigmatic cornea, however, the position of the entrance pupil is not well defined. Thus, the traditional approach to spectacle magnification does not generalize properly to allow for astigmatism. Within the constraints of linear optics and subject to the restriction that the eye's iris remains the aperture stop, this paper provides a complete, unified and exact treatment for optical instruments in general. It compares retinal image size in a generalized sense (including image shape and orientation) for any instrument in front of an eye with that of the eye alone irrespective of whether the instrument compensates or not. The approach does not make use of the concept of the entrance pupil at all and it allows for astigmatism and for non-alignment of refracting elements in the instrument and in the eye. The concept of spectacle magnification generalizes to the concept of instrument size magnification. Instrument size magnification can be expressed as the product of two matrix factors one of which can be interpreted as a power factor (as back-vertex power) and the other factor for which the name dilation factor is more appropriate in general. The general treatment is then applied to a number of special cases including afocal instruments, spectacle lenses (including obliquely crossing thick bitoric lenses), contact lenses, stigmatic systems and stigmatic eyes. In the case of spectacle lenses, the dilation factor reduces to the usual shape factor.     

Proximity factor in image size magnification for optical instruments in general

A general expression is derived for the proximity factor in near image size magnification for an arbitrary instrument in front of an arbitrary eye. The proximity factor is a 2 x 2 matrix. The instrument and eye may be astigmatic and have decentred elements. The image on the retina may be blurred or not. The analysis is exact within the limitations of linear optics. The general results are specialized for the case of a stigmatic instrument and a stigmatic eye. The results are applied to the case of a thick, possibly bitoric, spectacle lens. The Appendix treats two numerical examples.     

Force-time parameters during explosive isometric grip correlate with muscle power

Although explosive isometric contraction provides little work toward the outside, force-time parameters of the rising phase of the force-time curve may be able to predict muscle power. The purpose of this study was to examine the relationship between muscle power with work (power grip) and force-time parameters during the rising phase in explosive isometric grip. Fifteen healthy young adult males participated in this study. Power grip was measured using loads of 20%–50% of maximal voluntary contraction (MVC) (peak isometric force). Subjects pulled explosively on a grip bar held with the second digital joints without the thumb. Peak power was calculated from peak velocity and load. Explosive isometric grip was measured using a hand dynamometer. Time-series data of both tests were sampled by an analog-to-digital interface. Both tests were performed with the subjects seated with a sagittal and horizontal position of the arm supported by an armrest. Peak power in the power grip test tended to be larger with an increase of the load, but there was no significant difference between 40% and 50% MVC. Only the peak power in 50% MVC significantly correlated with peak grip force (r=0.52, p<0.05). The force-time parameters related to the peak rate of the rising force phase in explosive isometric grip significantly correlated with the peak powers (30%–50% MVC, r=|0.58−0.78|). Peak rate of the rising force phase in explosive isometric grip may be useful for predicting muscle power with loads between 30%–50% MVC.     

关于河南中医学院设置健康保险专业的思考

目的：探讨河南中医学院设置健康保险专业的论证。方法：从我国健康保险业的发展实际出发，集中分析河南中医学院设置健康保险专业的必要性，论证了河南中医学院在师资、设施、生源与就业等方面的可行性，以培养目标、课程设置和实习基地建设为轴线，提出了设置健康保险专业的建议。结果与结论：河南中医学院设置健康保险专业有必要、有可行性、有优势。     

Health policy, epidemiology and power: the interest web

The relation between epidemiological research results and policy-making is reviewed. Apparently, traditional models of policy-making(incrementalism, mixed scanning synoptic planning) do not explainwhy research findings are hardly used in policy-making procedures. It is suggested that this phenomenon is related to three determinantsof policy-making: (i) a bias stemming from sets of causal, finaland normative assumptions and presuppositions; (ii) interestwebs of groups in certain domains; and (iii) the power of organizationsto monitor and communicate. The conclusion is that epidemiologistsshould engage in the policy-making process more consciouslyand conscientiously.     

Developmental changes in intracellular pH buffering power in smooth muscle

 Intracellular pH (pH_i) is known to modulate contraction. Neonatal tissues can differ from adult tissue in contractile response to stimuli known to alter pH_i e.g. hypoxia. Changes of pH are attenuated by buffering, thus any difference in buffering power (β) between tissues could affect their functional response to pH_i perturbation. Similarly the extent to which any extracellular pH (pH_o) alteration is transmitted into a pH_i change will also influence function. We have therefore determined the intrinsic β and effect of pH_o change on pH_i in neonatal and adult ureteric, uterine and gastric smooth muscles using the pH-sensitive fluorophore carboxy-SNARF. β was found to be similar in the three adult tissues, but there were significant differences between neonatal tissues. In contrast, we found little difference in the amount of pH_i change produced by pH_o change between neonatal and adult tissues from the same smooth muscle, but a difference between smooth muscles. These data highlight significant differences between smooth muscles and their developmental state, which may contribute to different degrees of protection when pH is perturbed. Received: 17 October 1997 / Received after revision: 27 November 1997 / Accepted: 28 November 1997     

血流频谱分析在乳腺肿块鉴别诊断中的价值

目的：检验血流频谱分析在鉴别乳腺原发性肿块良恶性方面的价值并确立最佳的数值标准。方法：使用彩色多普勒血流显像和能量多普勒显像分别引导脉冲多普勒频谱分析，检查了１０４例乳腺原发性包块（良性５５例６３个病灶，恶性４９例６４个病灶），测量指标包括肿块周边与内部血流收缩期峰速、搏动指数及阻力指数，并分别绘制受试者工作曲线确定各自的最佳阈值。结果，以ＣＤＦＩ状态取频谱，乳癌病灶周边及内部血流的平均ＰＳＶ，Ｐ     

Wheezing at 8 and 13 years: changing importance of bronchiolitis and passive smoking

A group of 153 children (51 with a history of bronchiolitis and 102 matched controls) were evaluated in a historical cohort study at a mean age of 8 years and again at 13 years to test the primary hypothesis that mild bronchiolitis, far more common than severe (hospitalized) bronchiolitis, predicts wheezing. A secondary hypothesis was that passive smoking also predicts wheezing. Many potentially confounding variables such as family history of asthma were controlled in analyses. Analysis at 13 years produced results that were not anticipated from previous analysis of interviews at age 8. Although mild bronchiolitis was a powerful predictor of wheezing at age 8 years, it was no longer a strong predictor of wheezing at age 13 in either bivariate or multivariate analysis. Although epidemiologic studies, by their nature, cannot prove causality, findings are consistent with the hypothesis that sequelae often follow mild bronchiolitis but diminish during childhood. Maternal smoking was a powerful predictor of wheezing at age 13 in bivariate analysis (Kendall's Tau B = 0.19, P less than 0.01) and in multivariate analysis (odds ratio = 2.67, P less than 0.01). In children at highest risk for wheezing, males with a family history of asthma, multivariate analysis suggested that maternal smoking is associated with an increase in wheezing from 36% to 60%. We conclude that passive smoking, previously identified as a risk factor in this population for both bronchiolitis in infancy and wheezing at age 8, is a risk factor for wheezing-associated morbidity throughout the childhood years.     

Microstructure of the non-rapid eye movement sleep electroencephalogram in patients with newly diagnosed Parkinson's disease: effects of dopaminergic treatment.

We investigated non-rapid eye movement (non-REM) sleep in patients with newly diagnosed Parkinson's disease (PD) who had never previously received dopaminergic medication. There were no significant differences in the conventional sleep parameters between de novo patients with PD and a healthy control group, but the length of stage 1 sleep and the number of awakenings increased significantly upon administration of dopaminergic drugs. Analyzing the quantitative electroencephalogram (EEG), we observed a significant reduction in the low-delta frequency range and a nonsignificant increase in the sigma frequency range in de novo patients with PD. The dopaminergic medication also nonsignificantly reduced the low-delta and sigma frequencies, the latter to the level of the controls. Possible mechanisms that may account for the observed differences are discussed. It is suggested that Parkinson's disease as well as the application of dopaminergic drugs exerts a desynchronizing effect on the sleep EEG that is reflected in a disruption of sleep continuity.