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Selected AbstractsThe MRI-measured arterial input function resulting from a bolus injection of Gd-DTPA in a rat model of stroke slightly underestimates that of Gd-[14C]DTPA and marginally overestimates the blood-to-brain influx rate constant determined by Patlak plotsMAGNETIC RESONANCE IN MEDICINE, Issue 6 2010Tavarekere N. Nagaraja Abstract The hypothesis that the arterial input function (AIF) of gadolinium-diethylenetriaminepentaacetic acid injected by intravenous bolus and measured by the change in the T1 -relaxation rate (,R1; R1 = 1/T1) of superior sagittal sinus blood (AIF-I) approximates the AIF of 14C-labeled gadolinium-diethylenetriaminepentaacetic acid measured in arterial blood (reference AIF) was tested in a rat stroke model (n = 13). Contrary to the hypothesis, the initial part of the ,R1 -time curve was underestimated, and the area under the normalized curve for AIF-I was about 15% lower than that for the reference AIF. Hypothetical AIFs for gadolinium-diethylenetriaminepentaacetic acid were derived from the reference AIF values and averaged to obtain a cohort-averaged AIF. Influx rate constants (Ki) and proton distribution volumes at zero time (Vp + Vo) were estimated with Patlak plots of AIF-I, hypothetical AIFs, and cohort-averaged AIFs and tissue ,R1 data. For the regions of interest, the Kis estimated with AIF-I were slightly but not significantly higher than those obtained with hypothetical AIFs and cohort-averaged AIF. In contrast, Vp + Vo was significantly higher when calculated with AIF-I. Similar estimates of Ki and Vp + Vo were obtained with hypothetical AIFs and cohort-averaged AIF. In summary, AIF-I underestimated the reference AIF; this shortcoming had little effect on the Ki calculated by Patlak plot but produced a significant overestimation of Vp + Vo. Magn Reson Med 63:1502,1509, 2010. © 2010 Wiley-Liss, Inc. [source] Functional calculus under Kreiss type conditionsMATHEMATISCHE NACHRICHTEN, Issue 15 2005Pascale Vitse Abstract It is shown that for an algebraic Banach space operator T , the Kreiss condition, ,(zI , T ),1, , , |z | > 1, implies the following functional calculus estimate where deg(T ) is the degree of the minimal polynomial annihilating T . This result extends the known estimates of the powers of T for Kreiss operators on finite dimensional spaces. In the case of a general Kreiss operator, an estimate of the rational calculus is proved: Similar estimates hold for the polynomial calculus under generalized Kreiss conditions. A link is also established between the sharp constant in the first estimate and the norm of the best solution for a Nevanlinna,Pick type interpolation problem in analytic Besov classes. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] The effect of warfarin use on clinical stage and histological grade of prostate cancerPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2010V. Tagalakis MD Abstract Purpose Prolonged warfarin use may decrease the risk of prostate cancer. We aimed to assess the effect of warfarin on histological grade and clinical stage of prostate cancer at diagnosis. Methods We carried out a retrospective population-based cohort study of men older than 50 years of age diagnosed with prostate cancer between 1985 and 2002 and registered with the Saskatchewan Cancer Registry. We compared a composite score of histological grade and clinical stage of prostate cancer at diagnosis according to warfarin use in the 5 years preceding the diagnosis of prostate cancer. Results Compared with non-users, men with at least 2 years of cumulative warfarin use in the 5 year period preceding the diagnosis of prostate cancer were at a lower risk of a poor prognosis composite score at the time of their prostate cancer diagnosis (OR 0.40, 95%CI (0.19,0.83)), and when intermediate and poor prognosis scores were combined, a similar estimate of association was observed (OR 0.55, 95%CI (0.33,0.91)), adjusted for age at diagnosis and year of diagnosis. However, an increased risk of poor prognosis disease was observed with 4 years of cumulative warfarin use compared to never use (OR 2.2, 95%CI (1.03,4.81)). Conclusions There is a suggestion that at least 2 years of warfarin use is associated with a more favourable prognosis but that extended duration of use beyond 2 years may be associated with poor prognosis disease. Further investigation with a more complete assessment of confounders and that addresses potential detection biases is warranted. Copyright © 2010 John Wiley & Sons, Ltd. [source] A modelling strategy for the analysis of clinical trials with partly missing longitudinal dataINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2003Ian R. White Abstract Standard statistical analyses of randomized controlled trials with partially missing outcome data often exclude valuable information from individuals with incomplete follow-up. This may lead to biased estimates of the intervention effect and loss of precision. We consider a randomized trial with a repeatedly measured outcome, in which the value of the outcome on the final occasion is of primary interest. We propose a modelling strategy in which the model is successively extended to include baseline values of the outcome, then intermediate values of the outcome, and finally values of other outcome variables. Likelihood-based estimation of random effects models is used, allowing the incorporation of data from individuals with some missing outcomes. Each estimated intervention effect is free of non-response bias under a different missing-at-random assumption. These assumptions become more plausible as the more complex models are fitted, so we propose using the trend in estimated intervention effects to assess the nature of any non-response bias. The methods are applied to data from a trial comparing intensive case management with standard case management for severely psychotic patients. All models give similar estimates of the intervention effect and we conclude that non-response bias is likely to be small. Copyright © 2003 Whurr Publishers Ltd. [source] Generalized marker regression and interval QTL mapping methods for binary traits in half-sib family designsJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 5 2001H. N. Kadarmideen A Generalized Marker Regression Mapping (GMR) approach was developed for mapping Quantitative Trait Loci (QTL) affecting binary polygenic traits in a single-family half-sib design. The GMR is based on threshold-liability model theory and regression of offspring phenotype on expected marker genotypes at flanking marker loci. Using simulation, statistical power and bias of QTL mapping for binary traits by GMR was compared with full QTL interval mapping based on a threshold model (GIM) and with a linear marker regression mapping method (LMR). Empirical significance threshold values, power and estimates of QTL location and effect were identical for GIM and GMR when QTL mapping was restricted to within the marker interval. These results show that the theory of the marker regression method for QTL mapping is also applicable to binary traits and possibly for traits with other non-normal distributions. The linear and threshold models based on marker regression (LMR and GMR) also resulted in similar estimates and power for large progeny group sizes, indicating that LMR can be used for binary data for balanced designs with large families, as this method is computationally simpler than GMR. GMR may have a greater potential than LMR for QTL mapping for binary traits in complex situations such as QTL mapping with complex pedigrees, random models and models with interactions. Generalisierte Marker Regression und Intervall QTL Kartierungsmethoden für binäre Merkmale in einem Halbgeschwisterdesign Es wurde ein Ansatz zur generalisierten Marker Regressions Kartierung (GMR) entwickelt, um quantitative Merkmalsloci (QTL) zu kartieren, die binäre polygenetische Merkmale in einem Einfamilien-Halbgeschwisterdesign beeinflussen. Das GMR basiert auf der Theorie eines Schwellenwertmodells und auf der Regression des Nachkommenphänotyps auf den erwarteten Markergenotyp der flankierenden Markerloci. Mittels Simulation wurde die statistische Power und Schiefe der QTL Kartierung für binäre Merkmale nach GMR verglichen mit vollständiger QTL Intervallkartierung, die auf einem Schwellenmodell (GIM) basiert, und mit einer Methode zur linearen Marker Regressions Kartierung (LMR). Empirische Signifikanzschwellenwerte, Power und Schätzer für die QTL Lokation und der Effekt waren für GIM und GMR identisch, so lange die QTL Kartierung innerhalb des Markerintervalls definiert war. Diese Ergebnisse zeigen, dass die Theorie der Marker Regressions-Methode zur QTL Kartierung auch für binäre Merkmale und möglicherweise auch für Merkmale, die keiner Normalverteilung folgen, geeignet ist. Die linearen und Schwellenmodelle, die auf Marker Regression (LMR und GMR) basieren, ergaben ebenfalls ähnliche Schätzer und Power bei großen Nachkommengruppen, was schlussfolgern lässt, dass LMR für binäre Daten in einem balancierten Design mit großen Familien genutzt werden kann. Schließlich ist diese Methode computertechnisch einfacher als GMR. GMR mag für die QTL Kartierung bei binären Merkmalen in komplexen Situationen ein größeres Potential haben als LMR. Ein Beispiel dafür ist die QTL Kartierung mit komplexen Pedigrees, zufälligen Modellen und Interaktionsmodellen. [source] Rapid estimation of chemical kinetics by implicit calibration.JOURNAL OF CHEMOMETRICS, Issue 2 2003Abstract This study continues the development of a method, implicit calibration, for estimating kinetic parameters from on-line measurements of batch reactions. The basic idea of implicit calibration is to combine non-linear parameter estimation with the calibration of measured spectra with concentrations calculated by an assumed kinetic model. A new example is studied, an esterification reaction with a rather complicated kinetic mechanism, where activities, instead of concentrations, and NIR spectra are used as measurements. The emphasis in the study is on estimating the uncertainty of the kinetic parameters. Two approaches, linearization and bootstrap, are applied. In the case studied, the two approaches give closely similar estimates of the uncertainty. As well, a new way is introduced to control the rigidity of the implicit calibration, based on minimizing the lack of fit of the model. It is also shown that ,mixed implicit calibration', i.e. implicit calibration combined with a few off-line calibrated concentrations, greatly enhances the identifiability of the kinetic model. Copyright © 2003 John Wiley & Sons, Ltd. [source] Effect of floating nest platforms on the breeding performance of Black TernsJOURNAL OF FIELD ORNITHOLOGY, Issue 2 2006David A. Shealer ABSTRACT In 2003 and 2004, we placed 41 floating nest platforms on Grassy Lake in southeastern Wisconsin (USA) to test the hypothesis that reproductive success of Black Terns (Chlidonias niger) is limited by the quality of suitable nesting habitat. Extreme differences in water levels between these 2 yr provided a natural experiment to evaluate the effectiveness of the nest platforms during a drought year (2003) when natural nesting substrate was abundant, and a flood year (2004) when natural substrate was limited during the peak nesting period. Terns nested on 27 of 41 (66%) of the platforms in 2003 and 26 of 41 (63%) in 2004. No difference in the occupancy rate of platforms and natural nests was evident in 2003, but the pattern of clutch initiations early in the season in 2004 indicated that platforms were preferred over natural substrates. In 2003, nest survival rates did not differ between nests placed on platforms and those placed on natural substrates, but platform nests had significantly higher hatching success and nest survival rates in 2004. Both the Kaplan-Meier and Apparent Nest Success methods of calculating nest survival provided similar estimates. In both years, eggs laid on platforms were significantly larger than those laid on natural substrates, suggesting that platforms were occupied by high-quality birds. Our study indicates that floating nest platforms can be an effective management tool to enhance nesting habitat for Black Terns and other aquatic birds that construct floating nests, primarily because platforms provide nest sites when natural sites are not available due to flooding. Nest platforms also may be useful for addressing questions concerning habitat selection and parental quality. SINOPSIS De 2003-2004 colocamos 41 plataformas flotantes para poner aprueba la hipótesis que el éxito reproductivo de la gaviota Chlidonias níger, esta limitado por la calidad y lo apropiado del hábitat de anidamiento. El estudio se llevó a cabo en el Grassy Lake, Wisconsin. Extremos (bajos y altos) en los niveles de agua, causados por sequía (2203) y fuertes lluvias (2004) proveyeron el escenario adecuado para evaluar la efectividad de las plataformas. Las gaviotas anidaron en 27 (66%) de las 41 plataformas en el 2003 y en 26 (63%) de las 41 en el 2004. No se encontraron diferencias en la tasa de uso de las plataformas y áreas naturales en el 2003, pero el inicio de las camadas temprano en la temporada durante el 2004, dieron a indicar que las plataformas fueron preferidas a los lugares naturales. Durante el 2003, no hubo diferencia en la tasa de supervivencia de nidos en plataformas y o en áreas naturales. Sin embargo, durante el 2004 el éxito de eclosionamiento, de los nidos y la supervivencia fue mas alto en las plataformas. Tanto el método Kaplan-Meier como el "Aparente Éxito de Anidamiento", utilizados para calcular la supervivencia de los nidos, ofrecieron resultados similares. En ambos años el tamaño de los huevos fue mayor en las plataformas que en áreas naturales, lo que implica que las primeras fueron utilizadas por aves sumamente vigorosas o de alta calidad. El estudio indica que las plataformas flotantes pueden ser una herramienta de manejo adecuada para mejorar el hábitat de anidamiento de la gaviota estudiada, al igual que otras aves que construyen nidos flotantes. Las plataformas proveen de lugares de anidamientos cuando no hay disponible lugares naturales debido a inundaciones. Las plataformas de anidamiento muy bien pudieran proveer de información útil con respecto a la selección de hábitat y la calidad del cuidado parental. [source] Genetic diversity, population structure, effective population size and demographic history of the Finnish wolf populationMOLECULAR ECOLOGY, Issue 6 2006J. ASPI Abstract The Finnish wolf population (Canis lupus) was sampled during three different periods (1996,1998, 1999,2001 and 2002,2004), and 118 individuals were genotyped with 10 microsatellite markers. Large genetic variation was found in the population despite a recent demographic bottleneck. No spatial population subdivision was found even though a significant negative relationship between genetic relatedness and geographic distance suggested isolation by distance. Very few individuals did not belong to the local wolf population as determined by assignment analyses, suggesting a low level of immigration in the population. We used the temporal approach and several statistical methods to estimate the variance effective size of the population. All methods gave similar estimates of effective population size, approximately 40 wolves. These estimates were slightly larger than the estimated census size of breeding individuals. A Bayesian model based on Markov chain Monte Carlo simulations indicated strong evidence for a long-term population decline. These results suggest that the contemporary wolf population size is roughly 8% of its historical size, and that the population decline dates back to late 19th century or early 20th century. Despite an increase of over 50% in the census size of the population during the whole study period, there was only weak evidence that the effective population size during the last period was higher than during the first. This may be caused by increased inbreeding, diminished dispersal within the population, and decreased immigration to the population during the last study period. [source] Determining the zone of reflection for posterior corneal surface comparison phakometryOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 1 2009Andrew Carkeet Abstract Although comparison phakometry has been used by a number of studies to measure posterior corneal shape, these studies have not calculated the size of the posterior corneal zones of reflection they assessed. This paper develops paraxial equations for calculating posterior corneal zones of reflection, based on standard keratometry equations and equivalent mirror theory. For targets used in previous studies, posterior corneal reflection zone sizes were calculated using paraxial equations and using exact ray tracing, assuming spherical and aspheric corneal surfaces. Paraxial methods and exact ray tracing methods give similar estimates for reflection zone sizes less than 2 mm, but for larger zone sizes ray tracing methods should be used. [source] Peak quantification in surface-enhanced laser desorption/ionization by using mixture modelsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 19 2006Martijn Dijkstra Abstract Surface-enhanced laser desorption/ionization (SELDI) time of flight (TOF) is a mass spectrometry technology for measuring the composition of a sampled protein mixture. A mass spectrum contains peaks corresponding to proteins in the sample. The peak areas are proportional to the measured concentrations of the corresponding proteins. Quantifying peak areas is difficult for existing methods because peak shapes are not constant across a spectrum and because peaks often overlap. We present a new method for quantifying peak areas. Our method decomposes a spectrum into peaks and a baseline using so-called statistical finite mixture models. We illustrate our method in detail on 8 samples from culture media of adipose tissue and globally on 64 samples from serum to compare our method to the standard Ciphergen method. Both methods give similar estimates for singleton peaks, but not for overlapping peaks. The Ciphergen method overestimates the heights of such peaks while our method still gives appropriate estimates. Peak quantification is an important step in pre-processing SELDI-TOF data and improvements therein will pay off in the later biomarker discovery phase. [source] Some Methods of Propensity-Score Matching had Superior Performance to Others: Results of an Empirical Investigation and Monte Carlo simulationsBIOMETRICAL JOURNAL, Issue 1 2009Peter C. Austin Abstract Propensity-score matching is increasingly being used to reduce the impact of treatment-selection bias when estimating causal treatment effects using observational data. Several propensity-score matching methods are currently employed in the medical literature: matching on the logit of the propensity score using calipers of width either 0.2 or 0.6 of the standard deviation of the logit of the propensity score; matching on the propensity score using calipers of 0.005, 0.01, 0.02, 0.03, and 0.1; and 5 , 1 digit matching on the propensity score. We conducted empirical investigations and Monte Carlo simulations to investigate the relative performance of these competing methods. Using a large sample of patients hospitalized with a heart attack and with exposure being receipt of a statin prescription at hospital discharge, we found that the 8 different methods produced propensity-score matched samples in which qualitatively equivalent balance in measured baseline variables was achieved between treated and untreated subjects. Seven of the 8 propensity-score matched samples resulted in qualitatively similar estimates of the reduction in mortality due to statin exposure. 5 , 1 digit matching resulted in a qualitatively different estimate of relative risk reduction compared to the other 7 methods. Using Monte Carlo simulations, we found that matching using calipers of width of 0.2 of the standard deviation of the logit of the propensity score and the use of calipers of width 0.02 and 0.03 tended to have superior performance for estimating treatment effects (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Hypospadias: risk factor patterns and different phenotypesBJU INTERNATIONAL, Issue 2 2010Marijn M. Brouwers Study Type , Aetiologic (case-referent) Level of Evidence 2a OBJECTIVE To obtain more insight into the origin of hypospadias by exploring a wide range of potential risk factors in a case-referent study in which a distinction was made between different phenotypes. PATIENTS AND METHODS Cases and referents were 305 boys with hypospadias and 629 boys with middle ear effusion whose parents completed postal questionnaires. Hypospadias phenotype was classified as distal (195 boys), middle (67), and proximal (43). Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression. RESULTS Low birth weight, being a twin or triplet, mother being a diethylstilbestrol-daughter, fertility treatments, paternal subfertility, obesity, prescriptive drug use, and familial occurrence of hypospadias or testicular cancer were associated with hypospadias in general. For familial occurrence of hypospadias, there were high risk estimates for the distal and middle phenotypes with an OR (95%CI) of 10.4 (4.5,24.1) and 9.0 (3.1,26.0), but not for the proximal type at 1.8 (0.2,14.9). By contrast, the association with low birth weight (a proxy for placental dysfunction) seemed much stronger for proximal hypospadias with an OR (95%CI) of 9.1 (3.4,24.2) compared with distal and middle hypospadias at 2.6 (1.4,5.0) and 2.3 (0.8,6.5). There were similar estimates for pre-eclampsia. CONCLUSION These findings indicate aetiological heterogeneity of hypospadias and provide indications for the possible mechanisms through which specific risk factors may interfere with penile development. [source] | |||||||||||||||||||