Bayesian design and conduct of phase II single-arm clinical trials with binary outcomes: a tutorial

The aim of phase II single-arm clinical trials of a new drug is to determine whether it has sufficient promising activity to warrant its further development. For the last several years Bayesian statistical methods have been proposed and used. Bayesian approaches are ideal for earlier phase trials as they take into account information that accrues during a trial. Predictive probabilities are then updated and so become more accurate as the trial progresses. Suitable priors can act as pseudo samples, which make small sample clinical trials more informative. Thus patients have better chances to receive better treatments. The goal of this paper is to provide a tutorial for statisticians who use Bayesian methods for the first time or investigators who have some statistical background. In addition, real data from three clinical trials are presented as examples to illustrate how to conduct a Bayesian approach for phase II single-arm clinical trials with binary outcomes.

Robust background model for pixel based people counting using a single uncalibrated camera

Several pixel-based people counting methods have been developed over the years. Among these the product of scale-weighted pixel sums and a linear correlation coefficient is a popular people counting approach. However most approaches have paid little attention to resolving the true background and instead take all foreground pixels into account. With large crowds moving at varying speeds and with the presence of other moving objects such as vehicles this approach is prone to problems. In this paper we present a method which concentrates on determining the true-foreground, i.e. human-image pixels only. To do this we have proposed, implemented and comparatively evaluated a human detection layer to make people counting more robust in the presence of noise and lack of empty background sequences. We show the effect of combining human detection with a pixel-map based algorithm to i) count only human-classified pixels and ii) prevent foreground pixels belonging to humans from being absorbed into the background model. We evaluate the performance of this approach on the PETS 2009 dataset using various configurations of the proposed methods. Our evaluation demonstrates that the basic benchmark method we implemented can achieve an accuracy of up to 87% on sequence ¿S1.L1 13-57 View 001¿ and our proposed approach can achieve up to 82% on sequence ¿S1.L3 14-33 View 001¿ where the crowd stops and the benchmark accuracy falls to 64%.

On the validity of single-parcel energetics to assess the importance of internal energy and compressibility effects in stratified fluids

It is often assumed on the basis of single-parcel energetics that compressible effects and conversions with internal energy are negligible whenever typical displacements of fluid parcels are small relative to the scale height of the fluid (defined as the ratio of the squared speed of sound over gravitational acceleration). This paper shows that the above approach is flawed, however, and that a correct assessment of compressible effects and internal energy conversions requires considering the energetics of at least two parcels, or more generally, of mass conserving parcel re-arrangements. As a consequence, it is shown that it is the adiabatic lapse rate and its derivative with respect to pressure, rather than the scale height, which controls the relative importance of compressible effects and internal energy conversions when considering the global energy budget of a stratied fluid. Only when mass conservation is properly accounted for is it possible to explain why available internal energy can account for up to 40 percent of the total available potential energy in the oceans. This is considerably larger than the prediction of single-parcel energetics, according to which this number should be no more than about 2 percent.

CHEMICAL EVOLUTION OF THE GALACTIC BULGE: SINGLE AND DOUBLE INFALL MODELS

Recent work, has produced a wealth of data concerning the chemical evolution of the Galactic bulge, both for stars and nebulae. Present theoretical models generally adopt it limited range of such constraints, frequenfly using it single chemical element (usually iron), which is not enough to describe it unambiguously. In this work, we take into account contraints involving,9 Many chemical elements as possible, basically obtained from bulge nebulae and stars. Our main goal is to show that different scenarios can describe, at least partially the abundance distribution and several dishuice-independent correlations for these objects . Three classes of models were developed. The first is it one-zone, single-infall model, the. Second is it one-zone, double-infall model and the third is a multizone, double-infall model. We show that a one-zone model with it single infall episode is able to reproduce some of the observational data, but the best results tire achieved using it multizone, double-infall model.

Sample stacking in CZE using dynamic thermal junctions II: Analytes with high dpK(a)/dT crossing a single thermal junction in a BGE with low dpH/dT

In a previous work [M. Mandaji, et al., this issue] a sample stacking method was theoretically modeled and experimentally demonstrated for analytes with low dpK(a)/dT (analytes carrying carboxylic groups) and BGEs with high dpH/dT (high pH-temperature-coefficients). In that work, buffer pH was modulated with temperature, inducing electrophoretic mobility changes in the analytes. In the present work, the opposite conditions are studied and tested, i.e. analytes with high dpK(a)/dT and BGEs that exhibit low dpH/dT. It is well known that organic bases such as amines, imidazoles, and benzimidazoles exhibit high dpK(a)/dT. Temperature variations induce instantaneous changes on the basicity of these and other basic groups. Therefore, the electrophoretic velocity of some analytes changes abruptly when temperature variations are applied along the capillary. This is true only if BGE pH remains constant or if it changes in the opposite direction of pK(a) of the analyte. The presence of hot and cold sections along the capillary also affects local viscosity, conductivity, and electric field strength. The effect of these variables on electrophoretic velocity and band stacking efficacy was also taken into account in the theoretical model presented. Finally, this stacking method is demonstrated for lysine partially derivatized with naphthalene-2,3-dicarboxaldehyde. In this case, the amino group of the lateral chain was left underivatized and only the alpha amino group was derivatized. Therefore, the basicity of the lateral amino group, and consequently the electrophoretic mobility, was modulated with temperature while the pH of the buffer used remained unchanged.

Deformation and annealing of (011)[011] oriented A1 single crystals

High purity Al single crystals of the (011)[011] orientation have been deformed in plane strain compression in a channel die. Deformation was carried out at a strain rate of 0.01 s−1 to true strains of 0.5 and 1.0, and at temperatures of 25, 200 and 300 °C. The as-deformed microstructure has been characterized using electron backscattered diffraction (EBSD) and X-ray diffraction (XRD). No recrystallization was detected after deformation, and the deformation texture analysis showed that the stability of the orientation decreased with increasing temperature, contrary to reports for other orientations.

Annealing was carried out for various times at 300 °C. Nucleation of recrystallization exhibited periodicity, with distinct bands of recrystallized grains forming parallel to the transverse direction. This recrystallized microstructure has been examined using EBSD. A model is proposed to account for the origin of the periodicity of nucleation and the retention of rods or cylinders of unrecrystallized material after significant annealing times.

A study on the accuracy of frequency measures and its impact on knowledge discovery in single sequences

In knowledge discovery in single sequences, different results could be discovered from the same sequence when different frequency measures are adopted. It is natural to raise such questions as (1) do these frequency measures reflect actual frequencies accurately? (2) what impacts do frequency measures have on discovered knowledge? (3) are discovered results accurate and reliable? and (4) which measures are appropriate for reflecting frequencies accurately? In this paper, taking three major factors (anti-monotonicity, maximum-frequency and window-width restriction) into account, we identify inaccuracies inherent in seven existing frequency measures, and investigate their impacts on the soundness and completeness of two kinds of knowledge, frequent episodes and episode rules, discovered from single sequences. In order to obtain more accurate frequencies and knowledge, we provide three recommendations for defining appropriate frequency measures. Following the recommendations, we introduce a more appropriate frequency measure. Empirical evaluation reveals the inaccuracies and verifies our findings. 

Drag models comparison by single injection in vacuum fluidised beds

Single bubble injection simulations inside a minimally fluidized bed have been studied widely and are often used to validate the accuracy of different numerical models. Bubble shape, size and voidage distribution are the important parameters that are validated from the experiments. In the present work, the most widely used drag model (Gidaspow’s drag model) is compared to a new proposed slip flow drag model which takes into account the presence of the slip flow regime, often encountered in vacuum fluidized beds and characterised by Knudsen no. (Kn). Shape and size prediction of the bubble evolution inside the bed is carried out numerically by using the two fluid model, comparing the results predicted by the drag models. It is seen that the predictions are different for the two drag models only under high vacuum conditions corresponding to Kn in slip/transition flow regime. The predictions are also found sensitive to pressure gradient in the bed and fluid velocity.

Bats from Fazenda Intervales, Southeastern Brazil: species account and comparison between different sampling methods

Assessing the composition of an area's bat fauna is typically accomplished by using captures or by monitoring echolocation calls with bat detectors. The two methods may not provide the same data regarding species composition. Mist nets and harp traps may be biased towards sampling low flying species, and bat detectors biased towards detecting high intensity echolocators. A comparison of the bat fauna of Fazenda Intervales, southeastern Brazil, as revealed by mist nets and harp trap captures, checking roosts and by monitoring echolocation calls of flying bats illustrates this point. A total of 17 species of bats was sampled. Fourteen bat species were captured and the echolocation calls of 12 species were recorded, three of them not revealed by mist nets or harp traps. The different sampling methods provided different pictures of the bat fauna. Phyllostomid bats dominated the catches in mist nets, but in the field their echolocation calls were never detected. No single sampling approach provided a complete assessment of the bat fauna in the study area. In general, bats producing low intensity echolocation calls, such as phyllostomids, are more easily assessed by netting, and bats producing high intensity echolocation calls are better surveyed by bat detectors. The results demonstrate that a combined and varied approach to sampling is required for a complete assessment of the bat fauna of an area.

A procedure to estimate parameters of a line segment taking into account its representation through pi circuits: Theoretical development

The objective of this paper is to show an alternative methodology to estimate per unit length parameters of a line segment of a transmission line. With this methodology the line segment parameters can be obtained starting from the phase currents and -voltages in receiving and sending end of the line segment. If the line segment is represented as being one or more pi circuits whose frequency dependent parameters are considered lumped, its impedance and admittance can be easily expressed as functions of the currents and voltages at the sending and receiving end. Because we are supposing that voltages and currents at the sending and receiving end of the tine segment (in frequency domain) are known, it is possible to obtains its impedance and admittance and consequently its per unit length longitudinal and transversal parameters. The procedure will be applied to estimate the longitudinal and transversal parameters of a small segment of a single-phase line that is already built.

A procedure to estimate parameters of a line segment taking into account its representation through π circuits: Theoretical development

The objective of this paper is to show an alternative methodology to estimate per unit length parameters of a line segment of a transmission line. With this methodology the line segment parameters can be obtained starting from the phase currents and voltages in receiving and sending end of the line segment. If the line segment is represented as being one or more π circuits whose frequency dependent parameters are considered lumped, its impedance and admittance can be easily expressed as functions of the currents and voltages at the sending and receiving end. Because we are supposing that voltages and currents at the sending and receiving end of the line segment (in frequency domain) are known, it is possible to obtains its impedance and admittance and consequently its per unit length longitudinal and transversal parameters. The procedure will be applied to estimate the longitudinal and transversal parameters of a small segment of a single-phase line that is already built. © 2006 IEEE.

Postural control under visual and proprioceptive perturbations during double and single limb stances: Insights for balance training

Single Limb Stance under visual and proprioceptive disturbances is largely used in clinical settings in order to improve balance in a wide range of functional disabilities. However, the proper role of vision and proprioception in SLS is not completely understood. The objectives of this study were to test the hypotheses that when ankle proprioception is perturbed, the role of vision in postural control increases according to the difficulty of the standing task. And to test the effect of vision during postural adaptation after withdrawal of the somesthetic perturbation during double and single limb stance. Eleven males were submitted to double (DLS) and single limb (SLS) stances under conditions of normal or reduced vision, both with normal and perturbed proprioception. Center of pressure parameters were analyzed across conditions. Vision had a main effect in SLS, whereas proprioception perturbation showed effects only during DLS. Baseline stability was promptly achieved independently of visual input after proprioception reintegration. In conclusion, the role of vision increases in SLS. After proprioception reintegration, vision does not affect postural recovery. Balance training programs must take that into account. © 2011 Elsevier Ltd.

The swing-by effect in the Vesta-Magnya case. Single and multiple encounters.

It was verified that the asteroid Magnya has some physical and chemical characteristics similar to the bodies from Vesta family. However, astronomical observations revealed that Magnya is distant from these bodies. In the present work, we assumed that Magnya originated from Vesta and we try to justify its current distant orbital location taking into account the effects of close encounters between Magnya and Vesta. The methodology adopted involved an analytical approach considering the technique of the gravity assisted maneuver, also known as swing-by. We found that the energy variation achieved through a single swing-by between Vesta and Magnya are very small when compared to the variation that would be required to change the orbit of Magnya. The effects of multiple close encounters were also considered and discussed. We concluded that the possibility of multiple encounters is limited, and therefore, that Magnya should suffer other perturbations (such as resonances, collisions or close encounters with other bodies, for instance) that would provide the supposed change in its orbit.

Taking account of dependent species in management of the Southern Ocean krill fishery: estimating crabeater seal abundance off east Antarctica

1. The crabeater seal Lobodon carcinophaga is considered to be a key species in the krill-based food web of the Southern Ocean. Reliable estimates of the abundance of this species are necessary to allow the development of multispecies, predator–prey models as a basis for management of the krill fishery in the Southern Ocean. 2. A survey of crabeater seal abundance was undertaken in 1500 000 km2 of pack-ice off east Antarctica between longitudes 64–150° E during the austral summer of 1999/2000. Sighting surveys, using double observer line transect methods, were conducted from an icebreaker and two helicopters to estimate the density of seals hauled out on the ice in survey strips. Satellite-linked dive recorders were deployed on a sample of seals to estimate the probability of seals being hauled out on the ice at the times of day when sighting surveys were conducted. Model-based inference, involving fitting a density surface, was used to infer densities in the entire survey region from estimates in the surveyed areas. 3. Crabeater seal abundance was estimated to be between 0.7 and 1.4 million animals (with 95% confidence), with the most likely estimate slightly less than 1 million. 4. Synthesis and applications. The estimation of crabeater seal abundance in Convention for the Conservation of Antarctic Marine Living Resources (CCAMLR) management areas off east Antarctic where krill biomass has also been estimated recently provides the data necessary to begin extending from single-species to multispecies management of the krill fishery. Incorporation of all major sources of uncertainty allows a precautionary interpretation of crabeater abundance and demand for krill in keeping with CCAMLR’s precautionary approach to management. While this study focuses on the crabeater seal and management of living resources in the Southern Ocean, it has also led to technical and theoretical developments in survey methodology that have widespread potential application in ecological and resource management studies, and will contribute to a more fundamental understanding of the structure and function of the Southern Ocean ecosystem.

Unifying Representations and Responses: Perseverative Biases Arise From a Single Behavioral System

A dominant account of perseverative errors in early development contends that such errors reflect a failure to inhibit a prepotent response. This study investigated whether perseveration might also arise from a failure to inhibit a prepotent representation. Children watched as a toy was hidden at an A location, waited during a delay, and then watched the experimenter find the toy. After six observation-only A trials, the toy was hidden at a B location, and children were allowed to search for the toy. Two- and 4-year-olds’ responses on the B trials were significantly biased toward A even though they had never overtly responded to this location. Thus, perseverative biases in early development can arise as a result of prepotent representations, demonstrating that the prepotent-response account is incomplete. We discuss three alternative interpretations of these results, including the possibility that representational and response-based biases reflect the operation of a single, integrated behavioral system.