Low-energy quasiparticle excitations in dirty d-wave superconductors and the Bogoliubov-de Gennes kicked rotator

We investigate the quasiparticle density of states in disordered d-wave superconductors. By constructing a quantum map describing the quasiparticle dynamics in such a medium, we explore deviations of the density of states from its universal form ($\propto E$), and show that additional low-energy quasiparticle states exist provided (i) the range of the impurity potential is much larger than the Fermi wavelength [allowing to use recently developed semiclassical methods]; (ii) classical trajectories exist along which the pair-potential changes sign; and (iii) the diffractive scattering length is longer than the superconducting coherence length. In the classically chaotic regime, universal random matrix theory behavior is restored by quantum dynamical diffraction which shifts the low energy states away from zero energy, and the quasiparticle density of states exhibits a linear pseudogap below an energy threshold $E^* \ll \Delta_0$.Comment: 4 pages, 3 figures, RevTe

Quantum information processing with superconducting qubits in a microwave field

We investigate the quantum dynamics of a Cooper-pair box with a superconducting loop in the presence of a nonclassical microwave field. We demonstrate the existence of Rabi oscillations for both single- and multi-photon processes and, moreover, we propose a new quantum computing scheme (including one-bit and conditional two-bit gates) based on Josephson qubits coupled through microwaves.Comment: 7 pages, 1 figur

Psychological Support for Personality (PSP) versus treatment as usual: study protocol for a feasibility randomized controlled trial of a low intensity intervention for people with personality disorder

Background: Previous research has demonstrated the clinical effectiveness of long-term psychological treatment for people with some types of personality disorder. However, the high intensity and cost of these interventions limit their availability. Lower-intensity interventions are increasingly being offered to people with personality disorder, but their clinical and cost effectiveness have not been properly tested in experimental studies. We therefore set out to develop a low intensity intervention for people with personality disorder and to test the feasibility of conducting a randomized controlled trial to compare the clinical effectiveness of this intervention with that of treatment as usual (TAU). Methods: A two-arm, parallel-group, single-blind, randomized controlled trial of Psychological Support for Personality (PSP) versus TAU for people aged over 18 years, who are using secondary care mental health services and have personality disorder. We will exclude people with co-existing organic or psychotic mental disorders (dementia, bipolar affective disorder, delusional disorder, schizophrenia, schizoaffective disorder, or schizotypal disorder), those with cognitive or language difficulties that would preclude them from providing informed consent or compromise participation in study procedures, and those who are already receiving psychological treatment for personality disorder. Participants will be randomized via a remote system in a ratio of PSP to TAU of 1:1. Randomization will be stratified according to the referring team and gender of the participant. A single follow-up assessment will be conducted by masked researchers 24 weeks after randomization to assess mental health (using the Warwick and Edinburgh Well-Being Schedule), social functioning (using the Work and Social Adjustment Scale), health-related quality of life (EQ-5D-5 L), incidence of suicidal behavior, satisfaction with care (Client Satisfaction Questionnaire), and resource use and costs using a modified version of the Adult Service Use Schedule. In addition to this, each participant will be asked to complete the patient version of the Clinical Global Impression Scale. Feasibility and acceptability will primarily be judged by study recruitment rate and engagement and retention in treatment. The analysis will focus principally on descriptive data on the rate of recruitment, characteristics of participants, attrition, adherence to therapy, and follow-up. We will explore the distribution of study outcomes to investigate assumptions of normality in order to plan the analysis and sample size of a future definitive trial. Discussion: Most people with personality disorder do not currently receive evidence-based interventions. While a number of high intensity psychological treatments have been shown to be effective, there is an urgent need to develop effective low intensity approaches to help people unable to use existing treatments. PSP is a low intensity intervention for individuals, which was developed following extensive consultation with users and providers of services for people with personality disorder. This study aims to examine the feasibility of a randomized trial of PSP compared to TAU for people with personality disorder

Disentangling the heterogeneity of autism spectrum disorder through genetic findings

Autism spectrum disorder (ASD) represents a heterogeneous group of disorders, which presents a substantial challenge to diagnosis and treatment. Over the past decade, considerable progress has been made in the identification of genetic risk factors for ASD that define specific mechanisms and pathways underlying the associated behavioural deficits. In this Review, we discuss how some of the latest advances in the genetics of ASD have facilitated parsing of the phenotypic heterogeneity of this disorder. We argue that only through such advances will we begin to define endophenotypes that can benefit from targeted, hypothesis-driven treatments. We review the latest technologies used to identify and characterize the genetics underlying ASD and then consider three themes—single-gene disorders, the gender bias in ASD, and the genetics of neurological comorbidities—that highlight ways in which we can use genetics to define the many phenotypes within the autism spectrum. We also present current clinical guidelines for genetic testing in ASD and their implications for prognosis and treatment

Elevated Urinary 3-Methoxytyramine at Diagnosis is Correlated with High Risk Disease and is Associated with Poor Clinical Outcome in Neuroblastoma Patients

Development and application of statistical models for medical scientific researc

Rapid screening for lipid storage disorders using biochemical markers Expert center data and review of the literature

Background: In patients suspected of a lipid storage disorder (sphingolipidoses, lipidoses), confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and genetic studies. New UPLC-MS/MS methods have been developed to measure lysosphingolipids and oxysterols, which, combined with chitotriosidase activity may represent a rapid first tier screening for lipid storage disorders. Material and methods: A lysosphingolipid panel consisting of lysoglobotriaosylceramide (LysoGb3), lysohexosylceramide (LysoHexCer: both lysoglucosylceramide and lysogalactosylceramide), lysosphingomyelin (LysoSM) and its carboxylated analogue lysosphingomyelin-509 (LysoSM-509) was measured in control subjects and plasma samples of predominantly untreated patients affected with lipid storage disorders (n = 74). In addition, the oxysterols cholestane-3 beta,5 alpha,6 beta-triol and 7-ketocholesterol were measured in a subset of these patients (n = 36) as well as chitotriosidase activity (n = 43). A systematic review of the literature was performed to assess the usefulness of these biochemical markers. Results: Specific elevations of metabolites, i.e. without overlap between controls and other lipid storage disorders, were found for several lysosomal storage diseases: increased LysoSM levels in acid sphingomyelinase deficiency (Niemann-Pick disease type A/B), LysoGb3 levels in males with classical phenotype Fabry disease and LysoHexCer (i.e. lysoglucosylceramide/lysogalactosylceramide) in Gaucher and Krabbe diseases. While elevated levels of LysoSM-509 and cholestane-3 beta,5 alpha,6 beta-triol did not discriminate between Niemann Pick disease type C and acid sphingomyelinase deficiency, LysoSM-509/LysoSM ratio was specifically elevated in Niemann-Pick disease type C. In Gaucher disease type I, mild increases in several lysosphingolipids were found including LysoGb3 with levels in the range of non-classical Fabry males and females. Chitotriosidase showed specific elevations in symptomatic Gaucher disease, and was mildly elevated in all other lipid storage disorders. Review of the literature identified 44 publications. Most findings were in line with our cohort. Several moderate elevations of biochemical markers were found across a wide range of other, mainly inherited metabolic, diseases. Conclusion: Measurement in plasma of LysoSLs and oxysterols by UPLC-MS/MS in combination with activity of chitotriosidase provides a useful first tier screening of patients suspected of lipid storage disease. The LysoSM-509/LysoSM ratio is a promising parameter in Niemann-Pick disease type C. Further studies in larger groups of untreated patients and controls are needed to improve the specificity of the finding

3-Methoxytyramine: An independent prognostic biomarker that associates with high-risk disease and poor clinical outcome in neuroblastoma patients

Introduction: Prognosis of neuroblastoma patients is very diverse, indicating the need for more accurate prognostic parameters. The excretion of catecholamine metabolites by most neuroblastomas is used for diagnostic purposes, but their correlation with prognosis has hardly been investigated. Therefore, we performed an in-depth analysis of a panel of elevated urinary catecholamine metabolites at diagnosis and their correlation with prognosis. Patients and methods: Retrospective study of eight urinary catecholamine metabolites in a test (n = 96) and validation (n = 205) cohort of patients with neuroblastoma (all stages) at diagnosis. Results: Multivariate analyses, including risk factors such as stage and MYCN amplification, revealed that 3-methoxytyramine (3MT) was an independent risk factor for event-free survival (EFS) and overall survival (OS). Furthermore, only 3MT appeared to be an independent risk factor for both EFS and OS in high-risk patients, which was independent of modern high-risk therapy and immunotherapy. Among high-risk patients, those with elevated 3MT and older than 18 months had an extremely poor prognosis compared to patients with non-elevated 3MT and younger than 18 months (5-year EFS of 14.3% +/- 4% and 66.7% +/- 18%, respectively, p = 0.001; 5-year OS of 21.8% +/- 5% and 87.5% +/- 12%, respectively, p <0.001). Conclusions: Elevated 3MT at diagnosis was associated with high-risk disease and poor prognosis. For high-risk patients, elevated 3MT at diagnosis was the only significant risk factor for EFS and OS. 3MT was also able to identify subgroups of high-risk patients with favourable and extremely poor prognosis. (C) 2017 Elsevier Ltd. All rights reserve