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1.
A simulation approach for power calculation in large cohort studies based on multistate models
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Bastian Jenny Jan Beyersmann Martin Schumacher 《Biometrical journal. Biometrische Zeitschrift》2018,60(4):671-686
Realistic power calculations for large cohort studies and nested case control studies are essential for successfully answering important and complex research questions in epidemiology and clinical medicine. For this, we provide a methodical framework for general realistic power calculations via simulations that we put into practice by means of an R‐based template. We consider staggered recruitment and individual hazard rates, competing risks, interaction effects, and the misclassification of covariates. The study cohort is assembled with respect to given age‐, gender‐, and community distributions. Nested case‐control analyses with a varying number of controls enable comparisons of power with a full cohort analysis. Time‐to‐event generation under competing risks, including delayed study‐entry times, is realized on the basis of a six‐state Markov model. Incidence rates, prevalence of risk factors and prefixed hazard ratios allow for the assignment of age‐dependent transition rates given in the form of Cox models. These provide the basis for a central simulation‐algorithm, which is used for the generation of sample paths of the underlying time‐inhomogeneous Markov processes. With the inclusion of frailty terms into the Cox models the Markov property is specifically biased. An “individual Markov process given frailty” creates some unobserved heterogeneity between individuals. Different left‐truncation‐ and right‐censoring patterns call for the use of Cox models for data analysis. p‐values are recorded over repeated simulation runs to allow for the desired power calculations. For illustration, we consider scenarios with a “testing” character as well as realistic scenarios. This enables the validation of a correct implementation of theoretical concepts and concrete sample size recommendations against an actual epidemiological background, here given with possible substudy designs within the German National Cohort. 相似文献
2.
N Brinkmann M Malissard M Ramuz U R?mer T Schumacher E G Berger L Elling C Wandrey A Liese 《Bioorganic & medicinal chemistry letters》2001,11(18):2503-2506
The alpha-Gal trisaccharide Gal(alpha)(1-->3)Galbeta(1-->4)GlcNAc 11 was synthesized on a homogeneously soluble polymeric support (polyethylene glycol, PEG) by use of a multi-enzyme system consisting of beta-1,4-galactosyltransferase (EC 2.4.1.38), alpha-1,3-galactosyltransferase (EC 2.4.1.151), sucrose synthase (EC 2.4.1.13) and UDP-glucose-4-epimerase (EC 5.1.3.2). In addition workup was simplified by use of dia-ultrafiltration. Thus the advantages of classic chemistry/enzymology and solid-phase synthesis could be united in one. Subsequent hydrogenolytic cleavage afforded the free alpha-Gal trisaccharide. 相似文献
3.
Duodenal goblet cells and Brunner's-gland cells obtained from two species of New World monkeys (Saimiri sciureus and Saguinus fuscicollis) were studied using conventional histochemical methods and by applying a panel of 17 labelled lectins. The secretions of both goblet and Brunner's-gland cells were found to contain neutral mucosubstances, while those of goblet cells also exhibit acid and sulphated carbohydrate components. Lectin binding studies allowed a more detailed analysis of the mucus glycoproteins. Marked differences between the two examined species were not detected. N-Acetyl-galactosamine, galactose, fucose and N-Acetyl-glucosamine were found to be the predominant sugar residues in Brunner's-glands glycoproteins, with mannose and glucose being only minor components. 相似文献
4.
Berthold Lausen Torsten Hothorn Frank Bretz Martin Schumacher 《Biometrical journal. Biometrische Zeitschrift》2004,46(3):364-374
The identification and assessment of prognostic factors is one of the major tasks in clinical research. The assessment of one single prognostic factor can be done by recently established methods for using optimal cutpoints. Here, we suggest a method to consider an optimal selected prognostic factor from a set of prognostic factors of interest. This can be viewed as a variable selection method and is the underlying decision problem at each node of various tree building algorithms. We propose to use maximally selected statistics where the selection is defined over the set of prognostic factors and over all cutpoints in each prognostic factor. We demonstrate that it is feasible to compute the approximate null distribution. We illustrate the new variable selection test with data of the German Breast Cancer Study Group and of a small study on patients with diffuse large B‐cell lymphoma. Using the null distribution for a p‐value adjusted regression trees algorithm, we adjust for the number of variables analysed at each node as well. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
5.
M Schumacher C Alexandre J Balthazart 《Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie》1987,305(14):569-574
Castrated male quail were injected with the synthetic oestrogen, diethylstylbestrol (DES) or the synthetic androgen, methyltrienolone (R 1881) or both compounds simultaneously. Both R 1881 and DES activated male sexual behaviour, inhibited LH and FSH secretion and increased hypothalamic aromatase activity. Additive effects between R 1881 and DES were observed for the induction of brain aromatase and for the inhibition of FSH secretion. As a consequence, mechanisms mediated by androgen and estrogen receptors must be involved in the control of these reproductive characteristics. 相似文献
6.
Effect of cycloheximide on development of methotrexate resistance of Chinese hamster ovary cells treated with inhibitors of DNA synthesis. 总被引:8,自引:0,他引:8
We examined the effects of 18 h of incubation of Chinese hamster ovary (CHO K1) cells with cycloheximide, hydroxyurea, and aphidicolin. Treatment of cells with cycloheximide alone at a concentration adequate to inhibit DNA synthesis to less than 10% of control was significantly less cytotoxic and clastogenic than treatment with hydroxyurea or aphidicolin, did not induce unbalanced cellular growth, and had no effect on the frequency of resistant cells in methotrexate selections compared with control cells. When combined with hydroxyurea or aphidicolin and compared with the effects of either drug alone, cycloheximide blocked the induction of unbalanced growth during drug treatment, reduced the frequency of chromosomal aberrations in recovering cell populations, and decreased cell killing. In addition, the increased frequency of methotrexate-resistant cells observed after treatment with hydroxyurea or aphidicolin was eliminated when cycloheximide was present during drug treatment. 相似文献
7.
The characterization of four monoclonal antibodies specific for mouse IL-5 and development of mouse and human IL-5 enzyme-linked immunosorbent 总被引:48,自引:0,他引:48
J H Schumacher A O'Garra B Shrader A van Kimmenade M W Bond T R Mosmann R L Coffman 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(5):1576-1581
Four rat mAb directed against mouse IL-5 have been characterized by their ability to remove and neutralize mouse IL-5 activity in various bioassays. All four mAb absorbed IL-5 activity from solution. Although all were able to neutralize mouse IL-5 bioactivity, two were significantly more effective. These two were also able to neutralize the activity of mouse IL-5 delivered to B cells during a cognate-linked interaction with a Th cell clone. A two-site sandwich ELISA specific for mouse IL-5 was developed by using pairs of mAb. The mouse IL-5 ELISA is capable of detecting natural or mouse rIL-5 in supernatants, crude bacterial lysates, and high concentrations of mouse serum, and has a detection limit of less than 20 pg. Two of these antibodies cross-reacted with and neutralized human rIL-5, and one of these was used for development of an ELISA for human IL-5. 相似文献
8.
Summary Duodenal goblet cells and Brunner's-gland cells obtained from two species of New World monkeys (Saimiri sciureus andSaguinus fuscicollis) were studied using conventional histochemical methods and by applying a panel of 17 labelled lectins. The secretions of both goblet and Brunner'-gland cells were found to contain neutral mucosubstances, while those of goblet cells also exhibit acid and sulphated carbohydrate components. Lectin binding studies allowed a more detailed analysis of the mucus glycoproteins. Marked differences between the two examined species were not detected.N-Acetyl-galactosamine, galactose, fucose andN-Acetyl-glucosamine were found to be the predominante sugar residues in Brunner's-glands glycoproteins, with mannose and glucose being only minor components.Dedicated to Professor Dr. T.H. Schiebler on the occasion of his 65th birthday 相似文献
9.
The correlation between strain fecundity and (i) development and (ii) rate of aneuploidy was studied in rabbit preimplantation embryos obtained from 2 strains of different fecundity. Embryos were investigated at Days 3-6 (preimplantation development) or Days 2, 4 and 6 post coitum (aneuploidy). Embryonic size and cell proliferation varied on the days of investigation, but with no consistent tendency in favour of one strain. The incidence of aneuploidy did not differ significantly between embryos from the 2 strains (P greater than 0.05). The multifactorially determined criterion of prolificacy was not selectively correlated with overall differences in embryonic preimplantation growth and rate of aneuploidy. 相似文献
10.
A. E. F. Neele H. J. Nab K. M. Louwes 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1991,82(3):264-272
Summary An incomplete diallel cross was used to study components of genetic variation in potatoes for a range of characters after early and late harvest. The progenies were also used to evaluate five predictors of progeny performance, namely the mean seedling performance, the mid-parent value and the means of the selfed progenies, of the diploid progenies and of the test-cross progenies. For almost all characters, the general combining ability effects were predominant, although the specific combining ability effects present were greater at late than at early harvests. The seedling performance for tuber yield, number of tubers and average tuber weight did not show any relevant relationship to the field performance. The midparent value provided, in general, satisfactory predictions of the mean progeny performance obtained in the diallel, except for ware tuber yield. The selfed and the diploid progenies did not improve the prediction of progeny means compared to the mid-parent value. The predictions based on the test-crosses surpassed those of the mid-parent value, particularly for tuber yield at ware potato harvest. Methods to identify superior parents are discussed. 相似文献