Power Calculations for Preclinical Studies Using a K-Sample Rank Test and the Lehmann Alternative Hypothesis

Power calculations in a small sample comparative study, with a continuous outcome measure, are typically undertaken using the asymptotic distribution of the test statistic. When the sample size is small, this asymptotic result can be a poor approximation. An alternative approach, using a rank based test statistic, is an exact power calculation. When the number of groups is greater than two, the number of calculations required to perform an exact power calculation is prohibitive. To reduce the computational burden, a Monte Carlo resampling procedure is used to approximate the exact power function of a k-sample rank test statistic under the family of Lehmann alternative hypotheses. The motivating example for this approach is the design of animal studies, where the number of animals per group is typically small.

Immunohistochemical localization of RANK, RANKL and OPG in healthy and arthritic canine elbow joints

OBJECTIVE: To determine if the receptor activator of nuclear factor-kappaB-receptor activator of nuclear factor-kappaB ligand-osteoprotegerin (RANK-RANKL-OPG) system is active in bone remodeling in dogs and, if so, whether differences in expression of these mediators occur in healthy and arthritic joints. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Fragmented processus coronoidei (n=20) were surgically removed from dogs with elbow arthritis and 5 corresponding healthy samples from dogs euthanatized for reasons other than elbow joint disease. METHODS: Bright-field immunohistochemistry and high-resolution fluorescence microscopy were used to investigate the distribution of RANK, RANKL, and OPG in healthy and arthritic joints. RESULTS: All 3 molecules were identified by immunostaining of canine bone tissue. In elbow dysplasia, the number of RANK-positive osteoclasts was increased. In their vicinity, cells expressing RANKL, a mediator of osteoclast activation, were abundant whereas the number of osteoblasts having the potential to limit osteoclastogenesis and bone resorption via OPG was few. CONCLUSIONS: The RANK-RANKL-OPG system is active in bone remodeling in dogs. In elbow dysplasia, a surplus of molecules promoting osteoclastogenesis was evident and is indicative of an imbalance between the mediators regulating bone resorption and bone formation. Both OPG and neutralizing antibodies against RANKL have the potential to counterbalance bone resorption. CLINICAL RELEVANCE: Therapeutic use of neutralizing antibodies against RANKL to inhibit osteoclast activation warrants further investigation.

Increasingly Rank: The Use and Misuse of Rankings in Economic Development

Debates over the merits of competing schemes for ranking metropolitan areas as hightech centers shed little light on the important policy questions that should be the core of economic development policy. There are no strong theoretical reasons for preferring one ranking system to others. Rankings often conflate different industries and ignore history, obscuring the varied and often idiosyncratic processes that drive growth in different regions. Although an occupational perspective is a useful one for examining economic activity, it is a supplement to, not a replacement for, a careful understanding of metropolitan industrial specialization. Practitioners should not put too much weight on any ranking system but instead should work to develop detailed knowledge of their region’s special economic niche and to develop relationships and strategies that build on established strengths.

A SIMULATION STUDY OF THE SIZE AND POWER OF SOME TWO-SAMPLE TESTS FOR UNEQUALLY CENSORED SURVIVAL DATA (RANK TESTS, LOGRANK, PROPORTIONAL HAZARDS, WILCOXON TESTS, EXPONENTIAL DISTRIBUTION)

Sizes and power of selected two-sample tests of the equality of survival distributions are compared by simulation for small samples from unequally, randomly-censored exponential distributions. The tests investigated include parametric tests (F, Score, Likelihood, Asymptotic), logrank tests (Mantel, Peto-Peto), and Wilcoxon-Type tests (Gehan, Prentice). Equal sized samples, n = 18, 16, 32 with 1000 (size) and 500 (power) simulation trials, are compared for 16 combinations of the censoring proportions 0%, 20%, 40%, and 60%. For n = 8 and 16, the Asymptotic, Peto-Peto, and Wilcoxon tests perform at nominal 5% size expectations, but the F, Score and Mantel tests exceeded 5% size confidence limits for 1/3 of the censoring combinations. For n = 32, all tests showed proper size, with the Peto-Peto test most conservative in the presence of unequal censoring. Powers of all tests are compared for exponential hazard ratios of 1.4 and 2.0. There is little difference in power characteristics of the tests within the classes of tests considered. The Mantel test showed 90% to 95% power efficiency relative to parametric tests. Wilcoxon-type tests have the lowest relative power but are robust to differential censoring patterns. A modified Peto-Peto test shows power comparable to the Mantel test. For n = 32, a specific Weibull-exponential comparison of crossing survival curves suggests that the relative powers of logrank and Wilcoxon-type tests are dependent on the scale parameter of the Weibull distribution. Wilcoxon-type tests appear more powerful than logrank tests in the case of late-crossing and less powerful for early-crossing survival curves. Guidelines for the appropriate selection of two-sample tests are given. ^

Effect of patient accrual patterns on power and size of log-rank test for time-to-event outcome in clinical trials

The determination of size as well as power of a test is a vital part of a Clinical Trial Design. This research focuses on the simulation of clinical trial data with time-to-event as the primary outcome. It investigates the impact of different recruitment patterns, and time dependent hazard structures on size and power of the log-rank test. A non-homogeneous Poisson process is used to simulate entry times according to the different accrual patterns. A Weibull distribution is employed to simulate survival times according to the different hazard structures. The current study utilizes simulation methods to evaluate the effect of different recruitment patterns on size and power estimates of the log-rank test. The size of the log-rank test is estimated by simulating survival times with identical hazard rates between the treatment and the control arm of the study resulting in a hazard ratio of one. Powers of the log-rank test at specific values of hazard ratio (≠1) are estimated by simulating survival times with different, but proportional hazard rates for the two arms of the study. Different shapes (constant, decreasing, or increasing) of the hazard function of the Weibull distribution are also considered to assess the effect of hazard structure on the size and power of the log-rank test. ^

Mean dynamic topography and oceanographic parameters estimated from an inverse model and satellite geodesy, with link to model result in one single NetCDF file (392 MB), including the inverse data error covariance

Geostrophic surface velocities can be derived from the gradients of the mean dynamic topography-the difference between the mean sea surface and the geoid. Therefore, independently observed mean dynamic topography data are valuable input parameters and constraints for ocean circulation models. For a successful fit to observational dynamic topography data, not only the mean dynamic topography on the particular ocean model grid is required, but also information about its inverse covariance matrix. The calculation of the mean dynamic topography from satellite-based gravity field models and altimetric sea surface height measurements, however, is not straightforward. For this purpose, we previously developed an integrated approach to combining these two different observation groups in a consistent way without using the common filter approaches (Becker et al. in J Geodyn 59(60):99-110, 2012, doi:10.1016/j.jog.2011.07.0069; Becker in Konsistente Kombination von Schwerefeld, Altimetrie und hydrographischen Daten zur Modellierung der dynamischen Ozeantopographie, 2012, http://nbn-resolving.de/nbn:de:hbz:5n-29199). Within this combination method, the full spectral range of the observations is considered. Further, it allows the direct determination of the normal equations (i.e., the inverse of the error covariance matrix) of the mean dynamic topography on arbitrary grids, which is one of the requirements for ocean data assimilation. In this paper, we report progress through selection and improved processing of altimetric data sets. We focus on the preprocessing steps of along-track altimetry data from Jason-1 and Envisat to obtain a mean sea surface profile. During this procedure, a rigorous variance propagation is accomplished, so that, for the first time, the full covariance matrix of the mean sea surface is available. The combination of the mean profile and a combined GRACE/GOCE gravity field model yields a mean dynamic topography model for the North Atlantic Ocean that is characterized by a defined set of assumptions. We show that including the geodetically derived mean dynamic topography with the full error structure in a 3D stationary inverse ocean model improves modeled oceanographic features over previous estimates.

Relaciones de similitud y valor discriminativo de los indicadores bibliométricos: el caso de los indicadores de Scimago Journal and Country Rank aplicados a las revistas generalistas de paleontología

Los objetivos de este trabajo son: (1) analizar las relaciones de similitud de los indicadores bibliométricos; y (2) estudiar el valor de estos para discriminar/agrupar revistas científicas. Como unidades de estudio se utilizaron los 15 indicadores brindados por SCImago Journal Rank (SCImagoJR), aplicados a las 11 revistas paleontológicas generalistas listadas en dicha fuente durante el lapso 1999-2013. Las relaciones de similitud entre los indicadores se estimaron mediante un fenograma, mientras que el valor de los indicadores para agrupar/discriminar revistas se estimó mediante un análisis de componentes principales. Los resultados permiten concluir que, al menos para las revistas consideradas en este estudio, los 15 indicadores utilizados por SCImagoJR muestran redundancia por grupos, debido a las correlaciones existentes entre indicadores de producción, por una parte, y de citación, por otra. Sin embargo, esto es válido solo a los efectos de agrupar las revistas, ya que al considerar cada indicador por separado se aprecian variaciones entre los mismos, que permiten establecer una caracterización más específica de cada revista e, incluso, colaboran a explicar los resultados del análisis multivariado. Por otra parte, los resultados coinciden con los obtenidos por otros autores al reunir en un mismo grupo al SJR y al número de citas/documento en un período de dos años y en otro al índice h y al indicador número total de citas en un lapso de tres años.

Relaciones de similitud y valor discriminativo de los indicadores bibliométricos: el caso de los indicadores de Scimago Journal and Country Rank aplicados a las revistas generalistas de paleontología

Los objetivos de este trabajo son: (1) analizar las relaciones de similitud de los indicadores bibliométricos; y (2) estudiar el valor de estos para discriminar/agrupar revistas científicas. Como unidades de estudio se utilizaron los 15 indicadores brindados por SCImago Journal Rank (SCImagoJR), aplicados a las 11 revistas paleontológicas generalistas listadas en dicha fuente durante el lapso 1999-2013. Las relaciones de similitud entre los indicadores se estimaron mediante un fenograma, mientras que el valor de los indicadores para agrupar/discriminar revistas se estimó mediante un análisis de componentes principales. Los resultados permiten concluir que, al menos para las revistas consideradas en este estudio, los 15 indicadores utilizados por SCImagoJR muestran redundancia por grupos, debido a las correlaciones existentes entre indicadores de producción, por una parte, y de citación, por otra. Sin embargo, esto es válido solo a los efectos de agrupar las revistas, ya que al considerar cada indicador por separado se aprecian variaciones entre los mismos, que permiten establecer una caracterización más específica de cada revista e, incluso, colaboran a explicar los resultados del análisis multivariado. Por otra parte, los resultados coinciden con los obtenidos por otros autores al reunir en un mismo grupo al SJR y al número de citas/documento en un período de dos años y en otro al índice h y al indicador número total de citas en un lapso de tres años.

Relaciones de similitud y valor discriminativo de los indicadores bibliométricos: el caso de los indicadores de Scimago Journal and Country Rank aplicados a las revistas generalistas de paleontología

Los objetivos de este trabajo son: (1) analizar las relaciones de similitud de los indicadores bibliométricos; y (2) estudiar el valor de estos para discriminar/agrupar revistas científicas. Como unidades de estudio se utilizaron los 15 indicadores brindados por SCImago Journal Rank (SCImagoJR), aplicados a las 11 revistas paleontológicas generalistas listadas en dicha fuente durante el lapso 1999-2013. Las relaciones de similitud entre los indicadores se estimaron mediante un fenograma, mientras que el valor de los indicadores para agrupar/discriminar revistas se estimó mediante un análisis de componentes principales. Los resultados permiten concluir que, al menos para las revistas consideradas en este estudio, los 15 indicadores utilizados por SCImagoJR muestran redundancia por grupos, debido a las correlaciones existentes entre indicadores de producción, por una parte, y de citación, por otra. Sin embargo, esto es válido solo a los efectos de agrupar las revistas, ya que al considerar cada indicador por separado se aprecian variaciones entre los mismos, que permiten establecer una caracterización más específica de cada revista e, incluso, colaboran a explicar los resultados del análisis multivariado. Por otra parte, los resultados coinciden con los obtenidos por otros autores al reunir en un mismo grupo al SJR y al número de citas/documento en un período de dos años y en otro al índice h y al indicador número total de citas en un lapso de tres años.

Mapping the Antarctic Polar Front: Weekly realizations from 2002 to 2014, links to NetCDF file and MPEG4 movie

We map the weekly position of the Antarctic Polar Front (PF) in the Southern Ocean over a 12-year period (2002-2014) using satellite sea surface temperature (SST) estimated from cloud-penetrating microwave radiometers. Our study advances previous efforts to map the PF using hydrographic and satellite data and provides a unique realization of the PF at weekly resolution across all longitudes. The mean path of the PF is asymmetric; its latitudinal position spans from 44 to 64° S along its circumpolar path. SST at the PF ranges from 0.6 to 6.9 °C, reflecting the large spread in latitudinal position. The average intensity of the front is 1.7 °C per 100 km, with intensity ranging from 1.4 to 2.3 °C per 100 km. Front intensity is significantly correlated with the depth of bottom topography, suggesting that the front intensifies over shallow bathymetry. Realizations of the PF are consistent with the corresponding surface expressions of the PF estimated using expendable bathythermograph data in the Drake Passage and Australian and African sectors. The climatological mean position of the PF is similar, though not identical, to previously published estimates. As the PF is a key indicator of physical circulation, surface nutrient concentration, and biogeography in the Southern Ocean, future studies of physical and biogeochemical oceanography in this region will benefit from the provided data set.