Monte-Carlo Simulations of the Dynamical Behavior of the Coulomb Glass

We study the dynamical behavior of disordered many-particle systems with long-range Coulomb interactions by means of damage-spreading simulations. In this type of Monte-Carlo simulations one investigates the time evolution of the damage, i.e. the difference of the occupation numbers of two systems, subjected to the same thermal noise. We analyze the dependence of the damage on temperature and disorder strength. For zero disorder the spreading transition coincides with the equilibrium phase transition, whereas for finite disorder, we find evidence for a dynamical phase transition well below the transition temperature of the pure system.Comment: 10 pages RevTeX, 8 Postscript figure

Learning from the past and expecting the future in Parkinsonism: Dopaminergic influence on predictions about the timing of future events.

The prolonged reaction times seen in Parkinson's disease (PD) have been linked to a dopaminergic-dependent deficit in using prior information to prepare responses, but also have been explained by an altered temporal processing. However, an underlying cognitive mechanism linking dopamine, temporal processing and response preparation remains elusive. To address this, we studied PD patients, with or without medication, and age-matched healthy individuals using a variable foreperiod task requiring speeded responses to a visual stimulus occurring at variable onset-times, with block-wise changes in the temporal predictability of visual stimuli. Compared with controls, unmedicated patients showed impaired use of prior information to prepare their responses, as reflected by slower reaction times, regardless of the level of temporal predictability. Crucially, after dopamine administration normal performance was restored, with faster responses for high temporal predictability. Using Bayesian hierarchical drift-diffusion modelling, we estimated the parameters that determine temporal preparation. In this theoretical framework, impaired temporal preparation under dopaminergic depletion was driven by inflexibly high decision boundaries (i.e. participants were always extremely cautious). This indexes high levels of uncertainty about temporal predictions irrespectively of stimulus onset predictability. Our results suggest that dopaminergic depletion in PD affects the uncertainty of predictions about the timing of future events (temporal predictions), which are crucial for the anticipatory preparation of responses. Dopamine, which is affected in PD, controls the ability to predict the timing of future events

Intervening to alleviate word-finding difficulties in children: case series data and a computational modelling foundation

We evaluated a simple computational model of productive vocabulary acquisition, applied to simulating two case studies of 7-year-old children with developmental word-finding difficulties across four core behavioural tasks. Developmental models were created, which captured the deficits of each child. In order to predict the effects of intervention, we exposed the computational models to simulated behavioural interventions of two types, targeting the improvement of either phonological or semantic knowledge. The model was then evaluated by testing the predictions from the simulations against the actual results from an intervention study carried out with the two children. For one child it was predicted that the phonological intervention would be effective, and the semantic intervention would not. This was borne out in the behavioural study. For the second child, the predictions were less clear and depended on the nature of simulated damage to the model. The behavioural study found an effect of semantic but not phonological intervention. Through an explicit computational simulation, we therefore employed intervention data to evaluate our theoretical understanding of the processes underlying acquisition of lexical items for production and how they may vary in children with developmental language difficulties

Mechanism of action of HTX-011: a novel, extended-release, dual-acting local anesthetic formulation for postoperative pain

Background and objectives Obtaining consistent efficacy beyond 12–24 hours with local anesthetics, including extended-release formulations, has been a challenging goal. Inflammation resulting from surgery lowers the pH of affected tissues, reducing neuronal penetration of local anesthetics. HTX-011, an investigational, nonopioid, extended-release dual-acting local anesthetic combining bupivacaine and low-dose meloxicam, was developed to reduce postsurgical pain through 72 hours using novel extended-release polymer technology. Preclinical studies and a phase II clinical trial were conducted to confirm the mechanism of action of HTX-011. Methods In a validated postoperative pain pig model and a phase II bunionectomy trial, the analgesic effects of HTX-011, oral meloxicam (preclinical only), liposomal bupivacaine (preclinical only) and saline placebo were evaluated. The optimal meloxicam:bupivacaine ratio for HTX-011 and the effect of HTX-011 on incisional tissue pH were also evaluated preclinically. Results Preclinical data demonstrate the ability of HTX-011 to address local tissue inflammation as demonstrated by a less acidic tissue pH, which was associated with potentiated and prolonged analgesic activity. In the phase II bunionectomy study, HTX-011 achieved superior and sustained pain relief through 72 hours after surgery compared with each component in the polymer. Conclusions Preclinical animal and clinical results confirm that the low-dose meloxicam in HTX-011 normalizes the local pH in the incision, resulting in superior and synergistic analgesic activity compared with extended-release bupivacaine. HTX-011 represents an extended-release local anesthetic with a dual-acting mechanism of action that may provide an important advancement in the treatment of postoperative pain

Catalog of selected heavy duty transport energy management models

A catalog of energy management models for heavy duty transport systems powered by diesel engines is presented. The catalog results from a literature survey, supplemented by telephone interviews and mailed questionnaires to discover the major computer models currently used in the transportation industry in the following categories: heavy duty transport systems, which consist of highway (vehicle simulation), marine (ship simulation), rail (locomotive simulation), and pipeline (pumping station simulation); and heavy duty diesel engines, which involve models that match the intake/exhaust system to the engine, fuel efficiency, emissions, combustion chamber shape, fuel injection system, heat transfer, intake/exhaust system, operating performance, and waste heat utilization devices, i.e., turbocharger, bottoming cycle

Antibodies in the Diagnosis, Prognosis, and Prediction of Psychotic Disorders.

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a top-down approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging bottom-up or omics approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the antibody repertoire. Here we review the evidence for antibodies (to self-antigens as well as infectious organism and dietary antigens) as biomarkers of diagnosis, prognosis, and treatment response in psychotic disorders. Neuronal autoantibodies have current, and increasing, clinical utility in the diagnosis of organic or atypical psychosis syndromes. Antibodies to selected infectious agents show some promise in predicting cognitive impairment and possibly other symptom domains (eg, suicidality) within psychotic disorders. Finally, infectious antibodies and neuronal and other autoantibodies have recently emerged as potential biomarkers of response to anti-infective therapies, immunotherapies, or other novel therapeutic strategies in psychotic disorders, and have a clear role in stratifying patients for future clinical trials. As in nonpsychiatric disorders, combining biomarkers and large-scale use of bottom-up approaches to biomarker identification are likely to maximize the eventual clinical utility of antibody biomarkers in psychotic disorders

Intervention for children with word-finding difficulties: a parallel group randomised control trial

Purpose: The study investigated the outcome of a word-web intervention for children diagnosed with word-finding difficulties (WFDs). Method: Twenty children age 6–8 years with WFDs confirmed by a discrepancy between comprehension and production on the Test of Word Finding-2, were randomly assigned to intervention (n = 11) and waiting control (n = 9) groups. The intervention group had six sessions of intervention which used word-webs and targeted children’s meta-cognitive awareness and word-retrieval. Result: On the treated experimental set (n = 25 items) the intervention group gained on average four times as many items as the waiting control group (d = 2.30). There were also gains on personally chosen items for the intervention group. There was little change on untreated items for either group. Conclusion: The study is the first randomised control trial to demonstrate an effect of word-finding therapy with children with language difficulties in mainstream school. The improvement in word-finding for treated items was obtained following a clinically realistic intervention in terms of approach, intensity and duration

Correlation of plasma cell assessment by phenotypic methods and molecular profiles by NGS in patients with plasma cell dyscrasias.

BACKGROUND Next-generation sequencing (NGS) detects somatic mutations in a high proportion of plasma cell dyscrasias (PCD), but is currently not integrated into diagnostic routine. We correlated NGS data with degree of bone marrow (BM) involvement by cytomorphology (BMC), histopathology (BMH), and multiparameter flow cytometry (MFC) in 90 PCD patients. METHODS Of the 90 patients the diagnoses comprised multiple myeloma (n = 77), MGUS (n = 7), AL-amyloidosis (n = 4) or solitary plasmocytoma (n = 2). The NGS panel included eight genes CCND1, DIS3, EGR1, FAM46C (TENT5C), FGFR3, PRDM1, TP53, TRAF3, and seven hotspots in BRAF, IDH1, IDH2, IRF4, KRAS, NRAS. RESULTS Mutations were detected in 64/90 (71%) of cases. KRAS (29%), NRAS (16%) and DIS3 (16%) were most frequently mutated. At least one mutation/sample corresponded to a higher degree of BM involvement with a mean of 11% pathologic PC by MFC (range, 0.002-62%), and ~ 50% (3-100%) as defined by both BMC and BMH. CONCLUSIONS The probability of detecting a mutation by NGS in the BM was highest in samples with > 10% clonal PC by MFC, or > 20% PC by BMC/ BMH. We propose further evaluation of these thresholds as a practical cut-off for processing of samples by NGS at initial PCD diagnosis

Interacting electrons in a one-dimensional random array of scatterers - A Quantum Dynamics and Monte-Carlo study

The quantum dynamics of an ensemble of interacting electrons in an array of random scatterers is treated using a new numerical approach for the calculation of average values of quantum operators and time correlation functions in the Wigner representation. The Fourier transform of the product of matrix elements of the dynamic propagators obeys an integral Wigner-Liouville-type equation. Initial conditions for this equation are given by the Fourier transform of the Wiener path integral representation of the matrix elements of the propagators at the chosen initial times. This approach combines both molecular dynamics and Monte Carlo methods and computes numerical traces and spectra of the relevant dynamical quantities such as momentum-momentum correlation functions and spatial dispersions. Considering as an application a system with fixed scatterers, the results clearly demonstrate that the many-particle interaction between the electrons leads to an enhancement of the conductivity and spatial dispersion compared to the noninteracting case.Comment: 10 pages and 8 figures, to appear in PRB April 1