La modélisation des effets centre dans le cadre des données de survie repose souvent sur l'utilisation de modèles de Cox à effets mixtes. Tester un effet centre revient alors à tester à zéro la variance de l'effet aléatoire correspondant. La distribution sous l'hypothèse nulle des statistiques des tests paramétriques usuels n'est alors pas toujours connue. Les procédures de permutation ont été proposées comme alternative, pour les modèles linéaires généralisés mixtes.L'objectif est de développer, pour l'analyse des effets centre dans un modèle de survie de Cox à effets mixtes, une procédure de test de permutation pour les effets aléatoires.La première partie du travail présente la procédure de permutation développée pour le test d'un unique effet centre sur le risque de base, avec une application à la recherche d'un effet centre dans un essai clinique chez des patients atteints de leucémie myéloïde aiguë. La seconde partie porte sur l'extension de la procédure au test d'effets aléatoires multiples afin d’étudier à la fois des effets centre sur le risque de base et sur l'effet de variables, avec des illustrations sur deux cohortes de patients atteints de leucémie aiguë. Dans une troisième partie, les méthodes proposées sont appliquées à une cohorte multicentrique de patients en réanimation atteints d'hémopathies malignes, pour étudier les facteurs déterminant les effets centre sur la mortalité hospitalière. Les procédures de permutation proposées constituent une approche robuste et d'implémentation relativement aisée pour le test, en routine, d'effets aléatoires, donc un outil adapté pour l'analyse d'effets centre en épidémiologie clinique, afin de comprendre leur origine. / Centre effects modelling within the framework of survival data often relies on the estimation of Cox mixed effects models. Testing for a centre effect consists in testing to zero the variance component of the corresponding random effect. In this framework, the identification of the null distribution of usual tests statistics is not always straightforward. Permutation procedures have been proposed as an alternative, for generalised linear mixed models.The objective was to develop a permutation test procedure for random effects in a Cox mixed effects model, for the test of centre effects.We first developed and evaluated permutation procedures for the test of a single centre effect on the baseline risk. The test was used to investigate a centre effect in a clinical trial of induction chemotherapy for patients with acute myeloid leukaemia.The second part consisted in extending the procedure for the test of multiple random effects, in survival models. The aim was to be able to examine both center effects on the baseline risk and centre effects on the effect of covariates. The procedure was illustrated on two cohorts of acute leukaemia patients. In a third part, the permutation approach was applied to a cohort of critically ill patients with hematologic malignancies, to investigate centre effects on the hospital mortality.The proposed permutation procedures appear to be robust approaches, easily implemented for the test of random centre effect in routine practice. They are an appropriate tool for the analysis of centre effects in clinical epidemiology, with the purpose of understanding their sources.

In the educational literature on peer effects, attention has been brought to the fact that the mechanisms creating peer effects are still to a large extent hidden in obscurity. The hypothesis in this study is that the Frame Factor Theory can be used to explain these mechanisms. At heart of the theory is the concept of “time needed” for students to learn a certain curricula unit. The relations between class-aggregated time needed and the actual time available, steers and hinders the actions possible for the teacher. Further, the theory predicts that the timing and pacing of the teachers’ instruction is governed by a “steering criterion group” (SCG), namely the pupils in the 10th-25th percentile of the aptitude distribution in class. The class composition hereby set the possibilities and limitations for instruction, creating peer effects on individual outcomes. To test if the theory can be applied to the issue of peer effects, the study employs multilevel structural equation modelling (M-SEM) on Swedish TIMSS 2015-data (Trends in International Mathematics and Science Study; students N=3761, teachers N=179). Using confirmatory factor analysis (CFA) in the SEM-framework, latent variables are specified according to the theory, such as “limitations of instruction” from TIMSS survey items. The results indicate a good model fit to data of the measurement model. The SEM-model verify a strong relation between the mean level of the SCG and the latent variable of limitations on instruction, a variable which in turn has a great impact on individual students’ test results. Thus, the analysis indicates a confirmation of the predictions derived from the frame factor theory and reveals that one of the important mechanisms creating peer effects in student outcomes is the effect the class composition has upon the teachers’ instruction in class.

Sedan 2010 kan en friskola överklaga kommunens beslut om skolpeng ifall den anser att lika villkor inte har uppnåtts. Reformen har lett till att tusentals konflikter mellan friskolor och kommuner har tagits till domstol. I denna studie kartläggs och beskrivs de konflikter som rör kompensation till friskolor för kommunala underskott. Därtill prövas hypoteser om samband mellan politisk ideologi, kommunstorlek, nivå på skolpeng respektive andel friskolor och konflikt genom regressioner av paneldata.Resultaten visar substantiella samband mellan vänsterstyre, en hög andel friskolor respektive kommunstorlek och ökad sannolikhet för konflikt. Därtill visar kartläggningen att Sveriges största friskolekoncern är överrepresenterad i konflikterna. Det indikerar att reformen – vars syfte var att stärka friskolornas roll i bidragsprocessen – i första hand stärkt stora aktörer.

Most prior investigations of visual working memory (VWM) presented the to-be-remembered items simultaneously in a static configuration (e.g., Luck & Vogel, 1997). However, in everyday situations, such as driving on a busy multilane highway, items (e.g., cars) are presented sequentially and must be retained to support later actions (e.g., knowing if it’s safe to change lanes). In a simultaneous presentation, the relative positions of items are apparent but for sequential presentation, relative positions must be inferred in relation to the background structure (e.g., highway lane markings). To examine sequential encoding in VWM, we developed a novel task in which dots were presented slowly, one at a time, with each dot appearing in one of six boxes (Experiment 1), or in invisible boxes within a visible encompassing outer frame (Experiment 2). Experiment 1 found strong recency effects for judgments of color at the end of the sequence but not for the location of dots. In contrast, without dividing lines, Experiment 2 found strong recency effects for both color and location judgments. These results held true for accuracy, reaction time, and an integrated measure of speed and accuracy. We hypothesize that background structure allows the updating of VWM, slotting each new item into that structure to provide a new configuration that retains both old and new items, whereas in the absence of structure, VWM suffers from severe retroactive interference.

Objective: To investigate the association of previously reported single nucleotide polymorphisms (SNPs) in relation to orofacial clefts and assess their interaction with environmental factors. Methods: Genome-wide SNP genotypes were obtained for case-parent triads from the EUROCRAN and ITALCLEFT studies. Candidate SNPs were selected from a previous genome-wide association study (Shi et al., 2012) along with surrounding SNPS for a total of 2142 genotyped and imputed SNPs. A total of 411 case-parent triads and 25 case-parent dyads were analyzed using log-linear models to test for maternal and parent-of-origin effects along with their interaction with maternal smoking and maternal folic acid consumption. Results: A significant association (q = 0.025) was detected for a region in the ATXN3 gene. This significance refers to the interaction between maternal periconceptional smoking and maternal genetic effects. Nominally significant associations in genes relating to the brain were also detected. Conclusion: SNPs in the ATXN3 region warrant further investigation.

No description available.

This thesis was focused on monitoring the viability of eukaryotic and prokaryotic cells after exposure of termites-isolated chemicals. Recently, evidence of antibacterial and antifungal properties of these defense substances has grown, and they can find a wide range of uses not only in the pharmaceutical industry. In this work, three defensive substances from termites were studied: nerolidol, nitropentadecene and methylanthranilate. Their antibacterial effects, minimal inhibitory concentrations and minimal bactericidal concentrations against Escherichia coli STBL3 strain were monitored. Further, their cytotoxic effects on eukaryotic non-tumor (HEK293FT) and tumor cells (MCF7) as well as their effect on plasmid DNA were studied. Antibiotic ampicillin and cytostatic cisplatin were used as control substances for antibacterial and cytotoxic effects, respectively. In the case of the action of nerolidol, nitropentadecene and methylanthranilate on the STBL3 strain, antibacterial activity was not demonstrated. Cytotoxic effects were observed nerolidol and nitropentadecene. None of the examined substances modified the plasmid DNA.

No description available.

Odds ratios and risk ratios are useful measures of effect size in 2-group studies in which the response variable is dichotomous. Confidence interval methods are proposed for combining and comparing odds ratios and risk ratios in multistudy designs. Unlike the traditional fixed-effect meta-analysis methods, the proposed varying coefficient methods do not require effect-size homogeneity, and unlike the randomeffects meta-analysis methods, the proposed varying coefficient methods do not assume that the effect sizes from the selected studies represent a random sample from a normally distributed superpopulation of effect sizes. The results of extensive simulation studies suggest that the proposed varying coefficient methods have excellent performance characteristics under realistic conditions and should provide useful alternatives to the currently used meta-analysis methods.

In the investigation of radiation accidents, it is of great importance to estimate the dose absorbed by exposed persons in order to plan their therapy. Although occasionally in these situations physical dose measurements are possible, most often biological methods are required for dose estimation. The aim of this investigation was to assess the suitability of the cytokinesis blocked (CB) micronucleus assay as a biodosimetric method using lymphocytes irradiated in vivo. The approach adopted to achieve this was to estimate whole body doses by relating micronuclei yields in patients undergoing radiotherapy treatment with an in vitro radiation dose-response curve. These biologically derived estimates were then compared with the corresponding doses obtained by physical measurement and calculation. As a first approach a study was performed of the in vitro dose-response of gamma-ray induced micronuclei following cytokinesis-block in the lymphocytes of peripheral blood samples obtained from 4 healthy donors. The results indicated that the distribution of the induced micronuclei were overdispersed. Furthermore, a linear dose-response relationship was established when a curve was fitted to the data by an iteratively reweighted least squares method. By means of an analysis of covariance it was demonstrated that this result is in agreement with the dose-response relationships found by various other workers (Fenech et al., 1985; Fenech et al., 1986; Fenech et al., 1989; Balasem et al., 1992, and Slabbert, 1993). To assess the suitability and accuracy of dose assessment using the CB micronucleus assay for in vivo exposure of lymphocytes, blood samples obtained from 8 patients undergoing radiotherapy before, during and after treatment were examined. The physical doses of these patients were determined according to conventional radiation treatment plans and cumulative dose-volume histograms. The dose-volume histograms permitted calculation of integral doses and subsequently the estimate of equivalent whole-body doses. The results of the CB micronucleus assay applied to peripheral blood lymphocytes of 6 patients undergoing fractionated partial-body irradiation showed a dose-related increase in micronucleus frequency in each of the patients studied. This demonstrated that micronuclei analysis may serve as a quantitative biological measure of such exposures. The pooled data of these patients compared to the pooled data of the healthy donors show that there was no statistically significant difference between in vitro and in vivo results, however a slightly lower induced micronuclei frequency was observed after in vivo exposure. When the biological dose estimates for equivalent whole-body doses obtained from the in vitro dose response curve were compared with calculated physical doses, it was found that: biologically estimated dose = 0.936 physical dose. However, there was inadequate statistical evidence to discard the hypothesis that the gradient of the equation was equal to one. Therefore, the analysis of micronuclei induced in lymphocytes in vivo yields highly quantitative information on the equivalent whole-body dose. The negative binomial method was used for analysing the micronucleus data from two patients who received single, relatively larger tumour doses of 10 Gy each, with the objective to obtain estimates of the exposed body fraction and the dose to this fraction. The dose estimates to the irradiated volume were found to be within 30% of the physical tumour dose. The irradiated volume estimates seemed to be higher than the physically calculated volumes but by discarding the correction for the loss of cells due to interphase death the agreement was good between the physically and biologically determined integral doses. This study has revealed that the CB micronucleus assay appears to offer a reliable, consistent and relatively rapid biological method of whole body dose estimation. It is recognised that further corroborative work using the techniques described in this thesis is required for estimating localized exposure.