Effects of microgravity on circadian rhythms in insects.
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Animals↗
Biomedical subjects
G Wassmer
Publications and source records attributed to G Wassmer.
A comparison of two methods for adaptive interim analyses in clinical trials.
Recently, two methods for planning and conducting two-stage procedures were proposed (Bauer and Köhne, 1994, Biometrics 50, 1029-1041; Proschan and Hunsberger, 1995, Biometrics 51, 1315-1324). Both procedures allow the termination of the trial with the early acceptance of H0 in the absence of a treatment effect after performing the first stage of the study. Furthermore, the observed treatment effect at stage I can be used for planning and redesigning the second stage of the study in a way that protects the Type I error rate. The exact Type I error rate of the Proschan and Hunsberger approach is derived. It is shown that the two methods lead to similar decision rules with negligibly small differences in power and expected sample size. In terms of providing design tools and practical applicability, however, they differ. The practical performance of the procedures is discussed and recommendations for their use are given.
Biometry↗
The association between baseline lung function and bronchial responsiveness to methacholine.
It has been reported that females show an increased frequency of bronchial hyperresponsiveness (BHR) compared to males and that this difference is abolished after taking into account differences in baseline FEV1. The aim of our study was to analyse how the distribution of BHR in males and females depends on the definition of BHR. Special emphasis was paid to the question whether the prevalence rates of BHR according to different definitions were related to baseline characteristics of the subjects and baseline lung function in the same manner. We analysed the data obtained within the European Community Respiratory Health Survey (ECRHS) in the Eastern German population sample of Erfurt aged 20-65 years (n = 931). In logistic regression analyses of different definitions of BHR, we used as parameters age, height, gender, smoking habits, baseline forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1 as a percent of FVC (FEV1% FVC). Symptoms and reported diagnosis of asthma did not significantly depend on gender or age. When BHR was defined as the provocative dose causing a 20% fall in FEV1, BHR was more prevalent in females than in males (27.6% vs. 13.2%). Similar gender differences were found when defining BHR via a 10% fall in FEV1 or by using corresponding cut-off values of the linear dose-response slopes of the percent decline in FEV1 (DRS). Multiple linear regression analyses of various transformations of the DRS also indicated a higher degree of BHR in females. Independently of the definition chosen, however, the gender difference in the prevalence of BHR disappeared when height and FEV1 or FEV1% FVC or appropriate combinations were included in the model. The reciprocally transformed DRS showed the best resolution of the spectrum of bronchial responsiveness. These data are compatible with the hypotheses that (1) estimates of the distribution of BHR are distorted by differences in the methacholine dosage per lung size and that (2) airway geometry affects the measurement of BHR. It appears that these factors and not intrinsic differences in BHR between males and females contribute to the gender differences in the prevalence of BHR. Furthermore, our data support the superiority of the dose response slope for the analysis of bronchial responsiveness in epidemiologic surveys.
Adult↗
Prevalence of respiratory symptoms, bronchial hyperresponsiveness and atopy among adults: west and east Germany.
The prevalence of respiratory symptoms, atopic sensitization and bronchial hyperresponsiveness was compared in a random sample of adults, 20-44 yrs of age, in two cities in West and East Germany, Hamburg and Erfurt, respectively. There were much higher levels of outdoor air pollution due to sulphur dioxide and suspended particulates in Erfurt, and major differences in living conditions during the last 40 yrs. Within the European Respiratory Health Survey, a short questionnaire was answered by 3,156 (80% response rate) subjects in Hamburg and 3,272 (74%) in Erfurt. A subset of responders to the short questionnaire completed a long questionnaire, spirometry, methacholine or bronchodilator test, skin test, and total and specific immunoglobulin E (IgE) measurements, with a total number of 1,159 participants in Hamburg and 731 in Erfurt. Six out of 8 questions on respiratory symptoms and diagnoses were answered in the affirmative more frequently in Hamburg than in Erfurt. In Hamburg, mean forced expiratory volume in one second (FEV1)% of predicted was 105 vs 107% in Erfurt (p < 0.0001), and bronchial hyperresponsiveness was more frequently observed in Hamburg than in Erfurt (25 vs 19%; p < 0.05). Atopic sensitization was more prevalent in Hamburg than in Erfurt regarding the results of skin tests against grass pollen (24 vs 19%; p < 0.05), birch pollen (19 vs 8%; p < 0.0005), cat (10 vs 2%; p < 0.0005), and Dermatophagoides pteronyssinus (14 vs 10%; p < 0.05). This was reflected by the prevalences of positive specific IgE values, which were higher in Hamburg than in Erfurt for grass (26 vs 20%; p < 0.05), birch (20 vs 10%; p < 0.0005) and cat (12 vs 8%; p < 0.05). In Hamburg, compared to Erfurt, there was: a lower mean number of siblings (p < 0.005); a higher degree of childhood and current exposure to environmental tobacco smoke (p < 0.005); and a higher frequency of fitted carpets and reported mould or mildew inside the house (p < 0.005). Therefore, these data may support the hypothesis that childhood factors and exposure to indoor allergens and irritants may have been more relevant for the development of asthma and atopy than the potential long-term exposure to high concentrations of sulphur dioxide and particulate matter.
Adult↗
The relative efficiency of the Hardy-Weinberg equilibrium-likelihood and the conditional on parental genotype-likelihood methods for candidate-gene association studies.
Selecting a control group that is perfectly matched for ethnic ancestry with a group of affected individuals is a major problem in studying the association of a candidate gene with a disease. This problem can be avoided by a design that uses parental data in place of nonrelated controls. Schaid and Sommer presented two new methods for the statistical analysis using this approach: (1) a likelihood method (Hardy-Weinberg equilibrium [HWE] method), which rests on the assumption that HWE holds, and (2) a conditional likelihood method (conditional on parental genotype [CPG] method) appropriate when HWE is absent. Schaid and Sommer claimed that the CPG method can be more efficient than the HWE method, even when equilibrium holds. It can be shown, however that in the equilibrium situation the HWE method is always more efficient than the CPG method. For a dominant disease, the differences are slim. But for a recessive disease, the CPG method requires a much larger sample size to achieve a prescribed power than the HWE method. Additionally, we show how the relative risks for the various candidate-gene genotypes can be estimated without relying on iterative methods. For the CPG method, we represent an asymptotic power approximation that is sufficiently precise for planning the sample size of an association study.
Genetic Diseases, Inborn↗
Indoor factors and IgE levels in children.
The objective of the study was to determine indoor characteristics of households in relation to total serum IgE. In a population-based cross-sectional study, 1096 6-12-year-old children were examined in three East German towns (Eisleben, Hettstedt, and Zerbst). Of the questionnaires, 772 (70.4%) were returned by the parents. Serum IgE of 703 children and urinary cotinine in a random subsample of 224 children were analyzed. Linear regression on log(IgE) adjusted for the main covariates was used to assess indoor risk factors such as room size, and the presence of curtains, carpet, and plants in the child's room. Open-heating facilities indoors, passive smoking, and furniture made of chipboard had the most important effect. A higher urinary cotinine/creatinine ratio was associated with higher total IgE level. Total IGE increased also with the number of persons living in the household, independently of indoor smoking. We conclude that indoor air pollution from smoking and open-heating facilities may increase the IgE levels of children. The role of other factors such as chipboard, which could reflect the emission of formaldehyde, or the number of persons per household, which could reflect viral or helminthic infection, remains to be analyzed.
Air Pollution, Indoor↗
Comment on: on the design and analysis of randomized clinical trials with multiple endpoints.
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Biometry↗
Procedures for two-sample comparisons with multiple endpoints controlling the experimentwise error rate.
Clinical trials are often concerned with the comparison of two treatment groups with multiple endpoints. As alternatives to the commonly used methods, the T2 test and the Bonferroni method, O'Brien (1984, Biometrics 40, 1079-1087) proposes tests based on statistics that are simple or weighted sums of the single endpoints. This approach turns out to be powerful if all treatment differences are in the same direction [compare Pocock, Geller, and Tsiatis (1987, Biometrics 43, 487-498)]. The disadvantage of these multivariate methods is that they are suitable only for demonstrating a global difference, whereas the clinician is further interested in which specific endpoints or sets of endpoints actually caused this difference. It is shown here that all tests are suitable for the construction of a closed multiple test procedure where, after the rejection of the global hypothesis, all lower-dimensional marginal hypotheses and finally the single hypotheses are tested step by step. This procedure controls the experimentwise error rate. It is just as powerful as the multivariate test and, in addition, it is possible to detect significant differences between the endpoints or sets of endpoints.
Biometry↗
Neurospora circadian rhythms in space: a reexamination of the endogenous-exogenous question.
To test the functioning of circadian rhythms removed from periodicities of the earth's 24-hour rotation, the conidiation rhythm of the fungus Neurospora crassa was monitored in constant darkness during spaceflight. The free-running period of the rhythm was the same in space as on the earth, but there was a marked reduction in the clarity of the rhythm, and apparent arrhythmicity in some tubes. At the current stage of analysis of our results there is insufficient evidence to determine whether the effect seen in space was related to removal from 24-hour periodicities and whether the circadian timekeeping mechanism, or merely its expression, was affected.
Biological Clocks↗