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Selected AbstractsCandidate-gene association studies with pedigree data: Controlling for environmental covariatesGENETIC EPIDEMIOLOGY, Issue 4 2003S.L. Slager Abstract Case-control studies provide an important epidemiological tool to evaluate candidate genes. There are many different study designs available. We focus on a more recently proposed design, which we call a multiplex case-control (MCC) design. This design compares allele frequencies between related cases, each of whom are sampled from multiplex families, and unrelated controls. Since within-family genotype correlations will exist, statistical methods will need to take this into account. Moreover, there is a need to develop methods to simultaneously control for potential confounders in the analysis. Generalized estimating equations (GEE) are one approach to analyze this type of data; however, this approach can have singularity problems when estimating the correlation matrix. To allow for modeling of other covariates, we extend our previously developed method to a more general model-based approach. Our proposed methods use the score statistic, derived from a composite likelihood. We propose three different approaches to estimate the variance of this statistic. Under random ascertainment of pedigrees, score tests have correct type I error rates; however, pedigrees are not randomly ascertained. Thus, through simulations, we test the validity and power of the score tests under different ascertainment schemes, and an illustration of our methods, applied to data from a prostate cancer study, is presented. We find that our robust score statistic has estimated type I error rates within the expected range for all situations we considered whereas the other two statistics have inflated type I error rates under nonrandom ascertainment schemes. We also find GEE to fail at least 5% of the time for each simulation configuration; at times, the failure rate reaches above 80%. In summary, our robust method may be the only current regression analysis method available for MCC data. Genet Epidemiol 24:273,283, 2003. © 2003 Wiley-Liss, Inc. [source] Algebraic preconditioning versus direct solvers for dense linear systems as arising in crack propagation problemsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING, Issue 2 2005Erik Bängtsson Abstract Preconditioned iterative solution methods are compared with the direct Gaussian elimination method to solve dense linear systems Ax=b which originate from problems, discretized by boundary element method (BEM) techniques. Numerical experiments are presented and compared with the direct solution method available in a commercial BEM package, which show that the preconditioned iterative schemes are highly competitive with respect to both arithmetic operations required and memory demands. Copyright © 2004 John Wiley & Sons, Ltd. [source] In vitro testing to assess the UVA protection performance of sun care productsINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 1 2001Applied Cosmetics) Task Force, Members of the DGK (German Society for Scientific, Sun Protection'. Synopsis The UVA protection delivered by sunscreens is an issue of increasing importance due to the increasing knowledge about UVA-induced skin damage. In Europe there is no officially accepted method available to determine the degree of UVA protection. Therefore, the objective of the present study was to design a protocol combining the merits of an in vitro model, which are simple and reproducible, with aspects known to be relevant from in vivo studies. The principle is: an UV-transparent support to which the test product is applied, a (pre)irradiation and a transmission measurement. Transpore® tape (standard support for SPF determinations) was found to be incompatible with many preparations on prolonged contact times. Roughened quartz was adopted as a suitable alternative. Transmission measurements on this support are not reliable with a layer of 2 mg cm,2 (standard for SPF) due to detection limitations of spectrophotometers, hence a reduced layer of 0.75 mg cm,2 was adopted. Overall, it is very difficult to apply products in a reproducible thin layer on appropriate substrates. As a consequence, absolute parameters derived from the transmission profile show relatively large dispersion, whereas relative parameters, such as critical wavelength ,c[1] or UVA/UVB ratio are much less sensitive to unavoidable variations in layer thickness. An increase in deviations was observed when the samples were irradiated before measurement. It is crucial to control the output carefully (spectral distribution and even more importantly, irradiance and dose delivered) of the light source. By doing so and also taking into account the previous learning steps, a protocol was drafted and tested in a ringtest (four samples in six laboratories). The results are encouraging and show that if relative parameters (e.g. ,c, UVA/UVB ratio) are considered, the intra- as well as interlaboratory reproducibility is clearly better than can be obtained in vivo. In general, we describe a suitable method, which can be considered in any future official discussions about the methodology to determine UVA protection. Résumé La protection contre les UVA apportée par les écrans solaires est un sujet d'importance croissante en raison de la progression des connaissances concernant les dommages à la peau causés par les UVA. En Europe il n'existe pas de méthode disponible officiellement reconnue pour déterminer le degré de protection contre les UVA. Par conséquent, l'objectif de la présente étude est de concevoir un protocole associant les avantages d'un modèle in vitro, qui est simple et reproductible, avec des aspects connus comme appartenant aux études in vivo. Le principe est le suivant: un support transparent aux UV auquel le produit testé est appliqué, une (pré)irradiation et une mesure de transmission. Le ruban Transpore® (support standard pour la détermination des SPF) se révèle incompatible avec de nombreuses préparations lors de temps de contact prolongés. Le quartz rugueux est adopté comme alternative appropriée. Les mesures de transmission sur ce support ne sont pas fiables avec une couche de 2 mg/cm2 (norme pour les SPF) en raison des limites de détection des spectrophotomètres, et on adopte donc une couche réduite de 0,75 mg/cm2. Il est surtout très difficile d'appliquer des produits en une couche fine reproductible sur des substrats appropriés. En conséquence, les paramètres absolus tirés du profil de transmission montrent une assez grande dispersion, tandis que les paramètres relatifs, tels que la longueur d'onde critique ,c[l] ou le rapport UVA/UVB sont beaucoup moins sensibles aux variations inévitables de l'épaisseur de la couche. On observe une augmentation des écarts lorsque les échantillons sont irradiés avant la mesure. Il est crucial de contrôler soigneusement la sortie (distribution spectrale et encore plus important, irradiation et dose délivrée) de la source lumineuse. Dans ces conditions, et en tenant aussi compte des enseignements des étapes précédentes, un protocole a étéébauché et testé lors d'un essai tournant (quatre échantillons dans six laboratoires). Les résultats sont encourageants et montrent que si on considère les paramètres relatifs (par exemple ,c, rapport UVA/UVB), la reproductibilité intra et interlaboratoires est clairement meilleures que ce qu'on peut obtenir in vivo. D'une façon générale, nous décrivons une méthode appropriée, qui peut être considérée dans tout échange officiel futur concernant la méthodologie pour déterminer la protection contre les UVA. [source] Where will pathogen inactivation have the greatest impact?ISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue 1 2007T. Hervig Blood safety has always been a major task in transfusion medicine. A strategy to obtain this aim should include donor education, donor selection, and testing of blood donations. Pathogen inactivation adds another level of safety. In the fractionation industry, pathogen inactivation methods are mandatory. Several countries also use pathogen-inactivated plasma , from pools or single donors. Concerning the cellular blood components, there is still no method available for red cell concentrates, whereas methods for platelet concentrates are available in some countries and others are in the pipeline for commercialization. The efficiency of the ,old' methods to increase blood safety and the costs of the methods seem to be major obstacles for the introduction of the systems. There are also concerns on product quality and loss of volume during the inactivation process. As the importance of pathogen inactivation is largest in countries with blood donors who carry infections it is impossible to protect against, either due to high incidence of the infection or due to shortage of tests, cost will be a major question when pathogen inactivation is considered. Pathogen inactivation of red cell concentrates will also be a necessity. When pathogen inactivation methods are available for all blood components, they will have great impact to protect the patients in countries where a high percentage of the population is infected by agents transmissible through blood transfusion, and in all situations to protect against new pathogens and ,old' pathogens that become more virulent. The total risk of contracting infectious diseases through blood transfusion will probably be important when implementation of new methods for pathogen inactivation is considered. [source] Peptide and protein quantification: A map of the minefieldPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2010Marc Vaudel Abstract The increasing popularity of gel-free proteomics technologies has created a strong demand for compatible quantitative analysis methods. As a result, a plethora of different techniques has been proposed to perform gel-free quantitative analysis of proteomics samples. Each of these methods comes with certain strengths and shortcomings, and they often are dedicated to a specific purpose. This review will present a brief overview of the main methods, organized by their underlying concepts, and will discuss the issues they raise with a focus on data processing. Finally, we will list the available software that can help with the data processing from quantitative experiments. We hope that this review will thus enable researchers to find the most appropriate method available for their research objectives, and can also serve as a basis for creating a reliable data processing strategy. [source] The Animal Research DebateTHE POLITICAL QUARTERLY, Issue 4 2005SIMON FESTING Animal rights extremism has encouraged the media to examine the benefits and justification of animal research. There is broad support from the scientific community and government for carefully conducted animal research; however, Parliament is hindered, as many MPs are ill-informed. The recent Nuffield Council on Bioethics investigated the issue and determined that in carefully considered cases animal research is justified, scientifically valid, and has contributed to human health. The great majority of the public accept the need for animal research for medical progress when there is no alternative method available. Arguments used by anti-vivisectionists are discussed, many of which are unfounded and based on misconceptions. [source] Zinc ions in ,-cells of obese, insulin-resistant, and type 2 diabetic rats traced by autometallographyAPMIS, Issue 12 2003L. G. SØNDERGAARD Zinc ions in the secretory granules of ,-cells are known to glue insulin molecules, creating osmotically stable hexamers. When the secretory granules open to the surface, the zinc ion pressure decreases rapidly and pH levels change from acid to physiological, which results in free insulin monomers and zinc ions. The released zinc ions have been suggested to be involved in a paracrine regulation of ,- and ,-cells. Since zinc is intimately involved in insulin metabolism and because zinc homeostasis is known to be disturbed in type 2 diabetes, we decided to study the ultrastructural localisation of zinc ions in insulin-resistant and type 2 diabetic rats as compared to controls. By means of autometallography, the only method available for demonstrating zinc ions at ultrastructural levels, we found zinc ions in the secretory granules and adjacent to the plasma membrane. The membrane-related staining outside the plasma membrane reflects release of zinc ions during exocytosis. No apparent difference was found in the ultrastructural localisation of zinc ions when we compared the obese Zucker (fa/fa) rats, representing the insulin resistance syndrome, and the GK rats, representing type 2 diabetes, with controls. This suggests that the ultrastructural localisation of zinc ions is unaffected by the development of type 2 diabetes in rats in a steady state of glycaemia. [source] The incremental effect of positron emission tomography on diagnostic accuracy in the initial staging of esophageal carcinomaCANCER, Issue 1 2005Hiroyuki Kato M.D., Ph.D. Abstract BACKGROUND The purpose of the current study was to assess whether [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) provides incremental value (e.g., additional information on lymph node involvement or the presence of distant metastases) compared with computed tomography (CT) in patients with esophageal carcinoma. METHODS The authors examined 149 consecutive patients with thoracic esophageal carcinoma. Eighty-one patients underwent radical esophagectomy without pretreatment, 17 received chemoradiotherapy followed by surgery, 3 underwent endoscopic mucosal resection, and the remaining 48 patients received definitive radiotherapy and chemotherapy. The diagnostic accuracy of FDG-PET and CT was evaluated at the time of diagnosis. RESULTS The primary tumor was visualized using FDG-PET in 119 (80%) of 149 patients. Regarding lymph node metastases, FDG-PET had 32% sensitivity, 99% specificity, and 93% accuracy for individual lymph node group evaluation and 55% sensitivity, 90% specificity, and 72% accuracy for lymph node staging evaluation. PET exhibited incremental value over CT with regard to lymph node status in 14 of 98 patients who received surgery: 6 patients with negative CT findings were eventually shown to have lymph node metastases (i.e., they had positive PET findings and a positive reference standard [RS]); 6 patients with positive CT findings were shown not to have lymph node metastases (i.e., they had negative PET findings and a negative RS); and 2 patients were shown to have cervical lymph node metastases in addition to mediastinal or abdominal lymph node metastases. Among the remaining patients, PET showed incremental value over CT with regard to distant organ metastases in six patients. The overall incremental value of PET compared with CT with regard to staging accuracy was 14% (20 of 149 patients). CONCLUSIONS FDG-PET provided incremental value over CT in the initial staging of esophageal carcinoma. At present, combined PET-CT may be the most effective method available for the preoperative staging of esophageal tumors. Cancer 2005. © 2004 American Cancer Society. [source] Asymmetric Desymmetrization Based on an Intramolecular Haloetherification: A Highly Effective and Recyclable Chiral Nonracemic Auxiliary, 2- exo -Methyl-3- endo -phenyl-5-norbornene-2-carboxaldehyde, for meso -1,3- and meso -1,4-DiolsCHEMISTRY - A EUROPEAN JOURNAL, Issue 21 2004Hiromichi Fujioka Prof. Dr. Abstract A new chiral auxiliary, a 3- endo -phenyl norbornene aldehyde derivative, which is a crystalline, very stable, and easily handled, was developed for the desymmetrization of meso -1,3- and meso -1,4-diols. The key step of the method, an intramolecular bromoetherification, proceeded in a highly diastereoselective manner. A four-step sequence, 1) acetalization, 2) intramolecular bromoetherification followed by acid hydrolysis, 3) protection of the alcohol, and 4) retrobromoetherification, transformed the meso -diols into optically active derivatives. The 3- endo -phenyl norbornene aldehyde derivative was simultaneously reformed and could be used repeatedly. This is the first chemical example of a single auxiliary that is applicable for highly enantioselective desymmetrization of meso -1,3- and meso -1,4-diols; to the best of our knowledge, this is the best chemical method available for the desymmetrization of meso -1,4-diols. [source] | |||||||||||||