Delay-distribution-dependent state estimation for discrete-time stochastic neural networks with random delay

This paper is concerned with the state estimation problem for a class of discrete-time stochastic neural networks (DSNNs) with random delays. The effect of both variation range and distribution probability of the time delay are taken into account in the proposed approach. The stochastic disturbances are described in terms of a Brownian motion and the time-varying delay is characterized by introducing a Bernoulli stochastic variable. By employing a Lyapunov-Krasovskii functional, sufficient delay-distribution-dependent conditions are established in terms of linear matrix inequalities (LMIs) that guarantee the existence of the state estimator which can be checked readily by the Matlab toolbox. The main feature of the results obtained in this paper is that they are dependent on not only the bound but also the distribution probability of the time delay, and we obtain a larger allowance variation range of the delay, hence our results are less conservative than the traditional delay-independent ones. One example is given to illustrate the effectiveness of the proposed result.     

MDR1 gene polymorphisms and response to acute risperidone treatment

Polymorphic multidrug resistant protein 1 (MDR1) transports drugs against a concentration gradient across the blood–brain barrier and reduces their accumulation in the brain. MDR1 may therefore influence antipsychotic brain availability contributing to inter-individual differences in treatment response and adverse effects, regardless of plasma concentrations. In the present study we investigated the influence of two common MDR1 polymorphisms on the improvement of psychopathological symptoms and occurrence of extrapyramidal side effects (EPS) in Slovenian schizophrenia patients acutely treated with risperidone. A total of 59 clinically well defined patients with first episode schizophrenia spectrum disorders or after tapering their maintenance treatment were genotyped for MDR1 C3435T and G2677T/A. Steady-state plasma concentrations of risperidone active moiety (sum of risperidone and the 9-hydroxyrisperidone) were determined. G2677T/A and C3435T genotypes were not associated to psychopathological symptoms, efficacy of treatment and risk for parkinsonism. Marginal associations with akathisia (p = 0.039 and p = 0.042, respectively) and dystonia (p = 0.013 and p = 0.034, respectively) were observed for both G2677T/A and C3435T genotypes. However, higher AIMS and BARS scores were observed only in heterozygous carriers of G2677T/A and C3435T polymorphisms and there was no tendency of gene–dose effect. The present study does not suggest a major influence of MDR1 G2677T/A and C3435T polymorphisms on treatment response during short-term risperidone therapy in patients with schizophrenia or schizoaffective disorder.     

Dissecting T-cell activation with high-resolution live-cell microscopy

Results from live-cell microscopy suggest that the behaviour of isolated components of the T-cell activation machinery in vitro does not represent the reality inside cells. Understanding the cellular-scale dynamics of microcluster migration can only be accomplished by in situ observation. Developments in 'super-resolution' microscopy have permitted investigators to move beyond tracking the movements of individual molecules, allowing the recognition of protein islands and nanodomains present in quiescent and active T cells. Many high-resolution techniques have their own susceptibilities to artefacts, so it is important to take a multifaceted approach to confirm results. A major challenge for the future will be to integrate all the new information into a coherent model of antigen recognition and T-cell activation.     

Expectation enhances event-related responses to affective stimuli

Extensive practice is associated with a higher level of learning than practice until performance stabilization. This is partially attributable to the changes in the variability of the structure that control the motor skill that occur during practice. However, because both conditions result in performance stabilization, the error in the task performance does not decrease further, and it is necessary to introduce higher demands (e.g., unpredictable perturbations) into the task for differences between the two conditions to arise. This study aimed to investigate whether extensive practice contributes to adaptation to unpredictable perturbations in a sequential motor skill task as compared to practice until performance stabilization. Thirty-four self-reported right handed young adults performed a sequential coincident timing task and were assigned to two groups during the first phase of experiment: the stabilization group (SG) or the extensive practice group (EG), which differs with respect to the quantity of practice. In the second phase, both groups performed under equal conditions and the subjects practiced the same task performed in the first phase, but unpredictable changes in the velocity of the visual stimulus were occasionally introduced. The results suggest that extensive practice improves adaptation to unpredictable perturbations better than practice until performance stabilization and indicates that the motor learning process continues after performance stabilization.     

Modeling subject-specific phase-dependent effects and variations in longitudinal responses via a geometric Brownian motion process

We address statistical issues regarding modeling a collection of longitudinal response trajectories characterized by the presence of subject-specific phase-dependent effects and variation. To accommodate these two time-varying individual characteristics, we employ a geometric stochastic differential equation for modeling based on a Brownian motion process and develop a two-step paradigm for statistical analysis. This paradigm reverses the order of statistical inference in random effects model. We first extract individual information about phase-dependent treatment effects and volatility parameters for all subjects. Then, we derive the association relationship between the parameters characterizing the individual longitudinal trajectories and the corresponding covariates by means of multiple regression analysis. The stochastic differential equation model and the two-step paradigm together provide significant advantages both in modeling flexibility and in computational efficiency. The modeling flexibility is due to the easy adaptation of temporal change points for subject-specific phase transition in treatment effects, whereas the computational efficiency benefits in part from the independent increment property of Brownian motion that avoids high-dimensional integration. We demonstrate our modeling approach and statistical analysis on a real data set of longitudinal measurements of disease activity scores from a rheumatoid arthritis study.     

Profit efficiency and ownership of German hospitals

This paper investigates the cost and profit efficiency of German hospitals and their variation with ownership type. It is motivated by the empirical finding that private (for-profit) hospitals - having been shown to be less cost efficient in the past - on average earn higher profits than public hospitals. We conduct a Stochastic Frontier Analysis on a multifaceted administrative German data set combined with the balance sheets of 541 hospitals of the years 2002-2006. The results show no significant differences in cost efficiency but higher profit efficiency of private than of publicly owned hospitals.     

Age-related changes in the control of perturbation-evoked and voluntary arm movements

Objective

This study examined how handrail location predictability affects perturbation-evoked arm responses in young and older adults and whether age-related changes in perturbation-evoked arm responses are specific to mechanisms associated with reactive postural control.

Methods

Young and older adults reached for a handrail in response to a support surface translation (perturbation-evoked) or to a visual cue (voluntary). For both movement tasks, the handrail location was made predictable or unpredictable to the participant. Electromyographic (EMG) activity and kinematics of the reaching arm were recorded to quantify the arm response.

Results

Posterior deltoid EMG activity during perturbation-evoked and voluntary movements were delayed by 15–74 ms (p < 0.001) and 16% smaller (p = 0.024) when the handrail was in an unpredictable compared to a predictable location. While ageing resulted in a 12–16 ms delayed initiation of EMG activity during perturbation-evoked reaching (p = 0.003), the effects of handrail predictability and movement task did not interact with age.

Conclusions

Age-related differences in perturbation-evoked arm responses are independent of both handrail location predictability and movement task.

Significance

Age-related differences in perturbation-evoked arm responses cannot be solely attributed to declines in reactive postural control. Rather, ageing leads to a deterioration of neural mechanisms common to both perturbation-evoked and voluntary arm movements.     

Role of stochastic processes in maintaining discrete strain structure in antigenically diverse pathogen populations

Many highly diverse pathogen populations appear to exist stably as discrete antigenic types despite evidence of genetic exchange. It has been shown that this may arise as a consequence of immune selection on pathogen populations, causing them to segregate permanently into discrete nonoverlapping subsets of antigenic variants to minimize competition for available hosts. However, discrete antigenic strain structure tends to break down under conditions where there are unequal numbers of allelic variants at each locus. Here, we show that the inclusion of stochastic processes can lead to the stable recovery of discrete strain structure through loss of certain alleles. This explains how pathogen populations may continue to behave as independently transmitted strains despite inevitable asymmetries in allelic diversity of major antigens. We present evidence for this type of structuring across global meningococcal isolates in three diverse antigens that are currently being developed as vaccine components.