Statistical analysis of the primary outcome in acute stroke trials

Common outcome scales in acute stroke trials are ordered categorical or pseudocontinuous in structure but most have been analyzed as binary measures. The use of fixed dichotomous analysis of ordered categorical outcomes after stroke (such as the modified Rankin Scale) is rarely the most statistically efficient approach and usually requires a larger sample size to demonstrate efficacy than other approaches. Preferred statistical approaches include sliding dichotomous, ordinal, or continuous analyses. Because there is no best approach that will work for all acute stroke trials, it is vital that studies are designed with a full understanding of the type of patients to be enrolled (in particular their case mix, which will be critically dependent on their age and severity), the potential mechanism by which the intervention works (ie, will it tend to move all patients somewhat, or some patients a lot, and is a common hazard present), a realistic assessment of the likely effect size, and therefore the necessary sample size, and an understanding of what the intervention will cost if implemented in clinical practice. If these approaches are followed, then the risk of missing useful treatment effects for acute stroke will diminish

Backpropagation training in adaptive quantum networks

We introduce a robust, error-tolerant adaptive training algorithm for generalized learning paradigms in high-dimensional superposed quantum networks, or \emph{adaptive quantum networks}. The formalized procedure applies standard backpropagation training across a coherent ensemble of discrete topological configurations of individual neural networks, each of which is formally merged into appropriate linear superposition within a predefined, decoherence-free subspace. Quantum parallelism facilitates simultaneous training and revision of the system within this coherent state space, resulting in accelerated convergence to a stable network attractor under consequent iteration of the implemented backpropagation algorithm. Parallel evolution of linear superposed networks incorporating backpropagation training provides quantitative, numerical indications for optimization of both single-neuron activation functions and optimal reconfiguration of whole-network quantum structure.Comment: Talk presented at "Quantum Structures - 2008", Gdansk, Polan

Exchange bias and interface electronic structure in Ni/Co3O4(011)

A detailed study of the exchange bias effect and the interfacial electronic structure in Ni/Co3O4(011) is reported. Large exchange anisotropies are observed at low temperatures, and the exchange bias effect persists to temperatures well above the Neel temperature of bulk Co3O4, of about 40 K: to ~80 K for Ni films deposited on well ordered oxide surfaces, and ~150 K for Ni films deposited on rougher Co3O4 surfaces. Photoelectron spectroscopy measurements as a function of Ni thickness show that Co reduction and Ni oxidation occur over an extended interfacial region. We conclude that the exchange bias observed in Ni/Co3O4, and in similar ferromagnetic metallic/Co3O4 systems, is not intrinsic to Co3O4 but rather due to the formation of CoO at the interface.Comment: 8 pages, 6 figures. Accepted for publication in Physical Review B

Dynamical properties of ultracold bosons in an optical lattice

We study the excitation spectrum of strongly correlated lattice bosons for the Mott-insulating phase and for the superfluid phase close to localization. Within a Schwinger-boson mean-field approach we find two gapped modes in the Mott insulator and the combination of a sound mode (Goldstone) and a gapped (Higgs) mode in the superfluid. To make our findings comparable with experimental results, we calculate the dynamic structure factor as well as the linear response to the optical lattice modulation introduced by Stoeferle et al. [Phys. Rev. Lett. 92, 130403 (2004)]. We find that the puzzling finite frequency absorption observed in the superfluid phase could be explained via the excitation of the gapped (Higgs) mode. We check the consistency of our results with an adapted f-sum-rule and propose an extension of the experimental technique by Stoeferle et al. to further verify our findings.Comment: 13 pages, 5 figure

Dynamics of allosteric transitions in GroEL

The chaperonin GroEL-GroES, a machine which helps some proteins to fold, cycles through a number of allosteric states, the $T$ state, with high affinity for substrate proteins (SPs), the ATP-bound $R$ state, and the $R^{\prime\prime}$ ($GroEL-ADP-GroES$) complex. Structures are known for each of these states. Here, we use a self-organized polymer (SOP) model for the GroEL allosteric states and a general structure-based technique to simulate the dynamics of allosteric transitions in two subunits of GroEL and the heptamer. The $T \to R$ transition, in which the apical domains undergo counter-clockwise motion, is mediated by a multiple salt-bridge switch mechanism, in which a series of salt-bridges break and form. The initial event in the $R \to R^{\prime\prime}$ transition, during which GroEL rotates clockwise, involves a spectacular outside-in movement of helices K and L that results in K80-D359 salt-bridge formation. In both the transitions there is considerable heterogeneity in the transition pathways. The transition state ensembles (TSEs) connecting the $T$, $R$, and $R^{\prime\prime}$ states are broad with the the TSE for the $T \to R$ transition being more plastic than the $R\to R^{\prime\prime}$ TSE. The results suggest that GroEL functions as a force-transmitting device in which forces of about (5-30) pN may act on the SP during the reaction cycle.Comment: 32 pages, 10 figures (Longer version than the one published

Use of methods for specifying the target difference in randomised controlled trial sample size calculations : Two surveys of trialists' practice

© The Author(s), 2014.Peer reviewedPublisher PD

A robust and reliable method for detecting signals of interest in multiexponential decays

The concept of rejecting the null hypothesis for definitively detecting a signal was extended to relaxation spectrum space for multiexponential reconstruction. The novel test was applied to the problem of detecting the myelin signal, which is believed to have a time constant below 40ms, in T2 decays from MRI's of the human brain. It was demonstrated that the test allowed the detection of a signal in a relaxation spectrum using only the information in the data, thus avoiding any potentially unreliable prior information. The test was implemented both explicitly and implicitly for simulated T2 measurements. For the explicit implementation, the null hypothesis was that a relaxation spectrum existed that had no signal below 40ms and that was consistent with the T2 decay. The confidence level by which the null hypothesis could be rejected gave the confidence level that there was signal below the 40ms time constant. The explicit implementation assessed the test's performance with and without prior information where the prior information was the nonnegative relaxation spectrum assumption. The test was also implemented implicitly with a data conserving multiexponential reconstruction algorithm that used left invertible matrices and that has been published previously. The implicit and explicit implementations demonstrated similar characteristics in detecting the myelin signal in both the simulated and experimental T2 decays, providing additional evidence to support the close link between the two tests. [Full abstract in paper]Comment: 23 pages with 8 figure

International standards for early fetal size and pregnancy dating based on ultrasound measurement of crown-rump length in the first trimester of pregnancy.

OBJECTIVES: There are no international standards for relating fetal crown-rump length (CRL) to gestational age (GA), and most existing charts have considerable methodological limitations. The INTERGROWTH-21(st) Project aimed to produce the first international standards for early fetal size and ultrasound dating of pregnancy based on CRL measurement. METHODS: Urban areas in eight geographically diverse countries that met strict eligibility criteria were selected for the prospective, population-based recruitment, between 9 + 0 and 13 + 6 weeks' gestation, of healthy well-nourished women with singleton pregnancies at low risk of fetal growth impairment. GA was calculated on the basis of a certain last menstrual period, regular menstrual cycle and lack of hormonal medication or breastfeeding in the preceding 2 months. CRL was measured using strict protocols and quality-control measures. All women were followed up throughout pregnancy until delivery and hospital discharge. Cases of neonatal and fetal death, severe pregnancy complications and congenital abnormalities were excluded from the study. RESULTS: A total of 4607 women were enrolled in the Fetal Growth Longitudinal Study, one of the three main components of the INTERGROWTH-21(st) Project, of whom 4321 had a live singleton birth in the absence of severe maternal conditions or congenital abnormalities detected by ultrasound or at birth. The CRL was measured in 56 women at < 9 + 0 weeks' gestation; these were excluded, resulting in 4265 women who contributed data to the final analysis. The mean CRL and SD increased with GA almost linearly, and their relationship to GA is given by the following two equations (in which GA is in days and CRL in mm): mean CRL = -50.6562 + (0.815118 × GA) + (0.00535302 × GA(2) ); and SD of CRL = -2.21626 + (0.0984894 × GA). GA estimation is carried out according to the two equations: GA = 40.9041 + (3.21585 × CRL(0.5) ) + (0.348956 × CRL); and SD of GA = 2.39102 + (0.0193474 × CRL). CONCLUSIONS: We have produced international prescriptive standards for early fetal linear size and ultrasound dating of pregnancy in the first trimester that can be used throughout the world

Survival Analysis Part I: Basic concepts and first analyses

Survival analysis is a collection of statistical procedures for data analysis where the outcome variable of interest is time until an event occurs. Because of censoring - the nonobservation of the event of interest after a period of follow-up - a proportion of the survival times of interest will often be unknown. It is assumed that those patients who are censored have the same survival prospects as those who continue to be followed, that is, the censoring is uninformative. Survival data are generally described and modelled in terms of two related functions, the survivor function and the hazard function. The survivor function represents the probability that an individual survives from the time of origin to some time beyond time t. It directly describes the survival experience of a study cohort, and is usually estimated by the KM method. The logrank test may be used to test for differences between survival curves for groups, such as treatment arms. The hazard function gives the instantaneous potential of having an event at a time, given survival up to that time. It is used primarily as a diagnostic tool or for specifying a mathematical model for survival analysis. In comparing treatments or prognostic groups in terms of survival, it is often necessary to adjust for patient-related factors that could potentially affect the survival time of a patient. Failure to adjust for confounders may result in spurious effects. Multivariate survival analysis, a form of multiple regression, provides a way of doing this adjustment, and is the subject the next paper in this series

Mean Field Theory of Josephson Junction Arrays with Charge Frustration

Using the path integral approach, we provide an explicit derivation of the equation for the phase boundary for quantum Josephson junction arrays with offset charges and non-diagonal capacitance matrix. For the model with nearest neighbor capacitance matrix and uniform offset charge $q/2e=1/2$, we determine, in the low critical temperature expansion, the most relevant contributions to the equation for the phase boundary. We explicitly construct the charge distributions on the lattice corresponding to the lowest energies. We find a reentrant behavior even with a short ranged interaction. A merit of the path integral approach is that it allows to provide an elegant derivation of the Ginzburg-Landau free energy for a general model with charge frustration and non-diagonal capacitance matrix. The partition function factorizes as a product of a topological term, depending only on a set of integers, and a non-topological one, which is explicitly evaluated.Comment: LaTex, 24 pages, 8 figure