33 research outputs found

    Non-equilibrium noise in the (non-)Abelian fractional quantum Hall effect

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    We analyse the noise of the edge current of a generic fractional quantum Hall state in a tunnelling point contact system. We show that the non-symmetrized noise in the edge current for the system out-of-equilibrium is completely determined by the noise in the tunnelling current and the Nyquist-Johnson (equilibrium) noise of the edge current. Simply put, the noise in the tunnelling current does not simply add up the equilibrium noise of the edge current. A correction term arises associated with the correlation between the tunnelling current and the edge current. We show, using a non-equilibrium Ward identity, that this correction term is determined by the anti-symmetric part of the noise in the tunnelling current. This leads to a non-equilibrium fluctuation-dissipation theorem and related expressions for the excess and shot noise of the noise in the edge current. Our approach makes use of simple properties of the edge, such as charge conservation and chirality, and applies to generic constructions of the edge theory which includes edges of non-Abelian states and edges with multiple charged channels. Two important tools we make use of are the non-equilibrium Kubo formula and the non-equilibrium Ward identity. We discuss these identities in the appendix.Comment: 20 pages, 5 figure

    Tunnelling current through fractional quantum Hall interferometers

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    We calculate the tunnelling current through a Fabry-P\'{e}rot interferometer in the fractional quantum Hall regime. Within linear response theory (weak tunnelling but arbitrary source-drain voltage) we find a general expression for the current due to tunnelling of quasiparticles in terms of Carlson's RR function. Our result is valid for fractional quantum Hall states with an edge theory consisting of a charged channel and any number of neutral channels, with possibly different edge velocities and different chiralities. We analyse the case with a single neutral channel in detail, which applies for instance to the edge of the Moore-Read state. In addition we consider an asymmetric interferometer with different edge lengths between the point contacts on opposite edges, and we study the behaviour of the current as a function of varying edge length. Recent experiments attempted to measure the Aharanov-Bohm effect by changing the area inside the interferometer using a plunger gate. Theoretical analyses of these experiments have so far not taken into account the accompanying change in the edge lengths. We show that the tunnelling current exhibits multiple osculations as a function of this edge length, with frequencies proportional to the injected edge current and inversely proportional to the edge velocities. In particular the edge velocities can be measured by looking at the Fourier spectrum of the edge current. We provide a numerical scheme to calculate and plot the RR function, and include sample plots for a variety of edge states with parameter values which are experimentally relevant.Comment: 30 pages, 14 figure

    SMPD4 regulates mitotic nuclear envelope dynamics and its loss causes microcephaly and diabetes

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    Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder with progressive congenital microcephaly and early death. SMPD4 encodes a sphingomyelinase that hydrolyses sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope and interacts with nuclear pore complexes (NPC). We refine the clinical phenotype of loss-of-function SMPD4 variants by describing five individuals from three unrelated families with longitudinal data due to prolonged survival. All individuals surviving beyond infancy developed insulin-dependent diabetes, besides presenting with a severe neurodevelopmental disorder and microcephaly, making diabetes one of the most frequent age-dependent non-cerebral abnormalities. We studied the function of SMPD4 at the cellular and organ levels. Knock-down of SMPD4 in human neural stem cells causes reduced proliferation rates and prolonged mitosis. Moreover, SMPD4 depletion results in abnormal nuclear envelope breakdown and reassembly during mitosis and decreased post-mitotic NPC insertion. Fibroblasts from affected individuals show deficient SMPD4-specific neutral sphingomyelinase activity, without changing (sub)cellular lipidome fractions, which suggests a local function of SMPD4 on the nuclear envelope. In embryonic mouse brain, knockdown of Smpd4 impairs cortical progenitor proliferation and induces premature differentiation by altering the balance between neurogenic and proliferative progenitor cell divisions. We hypothesize that, in individuals with SMPD4-related disease, nuclear envelope bending, which is needed to insert NPCs in the nuclear envelope, is impaired in the absence of SMPD4 and interferes with cerebral corticogenesis and survival of pancreatic beta cells.</p

    Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: The CADDementia challenge

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    Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n = 30) and optionally on data from other sources (e.g., the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0% and an area under the receiver-operating-characteristic curve (AUC) of 78.8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http://caddementia.grand-challenge.org

    LEARN 2 MOVE 2-3: a randomized controlled trial on the efficacy of child-focused intervention and context-focused intervention in preschool children with cerebral palsy

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    <p>Abstract</p> <p>Background</p> <p>Little is known about the efficacy and the working mechanisms of physical and occupational therapy interventions for children with cerebral palsy (CP). In recent years a shift from a child-focused intervention approach to a more context-focused intervention approach can be recognized. Until now the evidence on the efficacy and the working mechanisms of these interventions for children with CP is inconclusive. This study aims to evaluate the efficacy and working mechanisms of two intervention approaches compared to regular care intervention in improving mobility and self-care skills of children (2-3 years) with CP and their families: a child-focused intervention approach and a context-focused intervention approach.</p> <p>Methods/Design</p> <p>A multi-centre, randomized controlled trial research design will be used. Ninety-four children with CP (Gross Motor Function Classification System (GMFCS) level I-IV; age 2 to 3 years), their parents, and service providers (physical and occupational therapists) will be included. During a period of six months children will receive child-focused, context-focused or regular care intervention. Therapists will be randomly assigned to deliver either a child-focused intervention approach, a context-focused intervention approach or regular care intervention. Children follow their therapist into the allocated intervention arm. After the six months study-intervention period, all participants return to regular care intervention. Outcomes will be evaluated at baseline, after six months and at a three months follow-up period. Primary outcome is the capability of functional skills in self-care and mobility, using the Functional Skills Scale of the Pediatric Evaluation of Disability Inventory (PEDI). Other outcomes will be quality of life and the domains of the International Classification of Functioning, Disability and Health - for Children and Youth (ICF-CY), including body function and structure, activities (gross motor capacity and performance of daily activities), social participation, environmental variables (family functioning, parental empowerment).</p> <p>Discussion</p> <p>This paper presents the background information, design, description of interventions and protocol for this study on the efficacy and working mechanisms of child-focused intervention approach and context-focused intervention approach compared to regular care intervention in mobility and self-care skills of children (2-3 years) with CP.</p> <p>Trial registration</p> <p>This study is registered in the Dutch Trial Register as NTR1900</p

    Interferometry and non-equilibrium noise in the fractional quantum Hall effect

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    THESIS 10343We study theoretical aspects of fractional quantum Hall devices based on tunnelling point contacts. The fractional quantum Hall effect is the prime example of a (2 + 1) dimensional system with non-trivial topological order. Fractional quantum Hall systems exhibit quasiparticle excitations (anyons) which carry fractional charge and obey a generalized form of statistics. These anyons can be observed and studied in transport experiments using point contacts. In this work we use both perturbative and non-perturbative techniques to study the current through a double point contact interferometer and the properties of non-equilibrium noise in a single point contact

    Determinants of developmental gain in daily activities in young children with cerebral palsy

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    The aim of this study was to examine which child and family characteristics at the child's age of 2 years are determinants of development of self-care and mobility activities over a period of 2 years in young children with cerebral palsy (CP). Longitudinal data of 92 children, representing all levels of the Gross Motor Function Classification System (GMFCS), were analyzed. Children's self-care and mobility activities were assessed with the Functional Skills Scale of the Pediatric Evaluation of Disability Inventory. Development of self-care and mobility activities was related to several child determinants but no family determinants. GMFCS, type of CP, intellectual capacity, and epilepsy were related to the development of self-care and mobility activities, while manual ability and spasticity were related to development of mobility activities. Multivariate analysis indicated that GMFCS and intellectual capacity were the strongest determinants of development of self-care activities, and GMFCS was the strongest determinant of development of mobility activities. The change in self-care and mobility activities was less favorable in severely affected children with severe disability. Knowledge of GMFCS level and intellectual capacity is important in anticipating change over time and goal setting in young children with CP

    Determinants of developmental gain in daily activities in young children with cerebral palsy

    No full text
    The aim of this study was to examine which child and family characteristics at the child's age of 2 years are determinants of development of self-care and mobility activities over a period of 2 years in young children with cerebral palsy (CP). Longitudinal data of 92 children, representing all levels of the Gross Motor Function Classification System (GMFCS), were analyzed. Children's self-care and mobility activities were assessed with the Functional Skills Scale of the Pediatric Evaluation of Disability Inventory. Development of self-care and mobility activities was related to several child determinants but no family determinants. GMFCS, type of CP, intellectual capacity, and epilepsy were related to the development of self-care and mobility activities, while manual ability and spasticity were related to development of mobility activities. Multivariate analysis indicated that GMFCS and intellectual capacity were the strongest determinants of development of self-care activities, and GMFCS was the strongest determinant of development of mobility activities. The change in self-care and mobility activities was less favorable in severely affected children with severe disability. Knowledge of GMFCS level and intellectual capacity is important in anticipating change over time and goal setting in young children with CP

    Determinants of Developmental Gain in Daily Activities in Young Children with Cerebral Palsy

    No full text
    The aim of this study was to examine which child and family characteristics at the child's age of 2 years are determinants of development of self-care and mobility activities over a period of 2 years in young children with cerebral palsy (CP). Longitudinal data of 92 children, representing all levels of the Gross Motor Function Classification System (GMFCS), were analyzed. Children's self-care and mobility activities were assessed with the Functional Skills Scale of the Pediatric Evaluation of Disability Inventory. Development of self-care and mobility activities was related to several child determinants but no family determinants. GMFCS, type of CP, intellectual capacity, and epilepsy were related to the development of self-care and mobility activities, while manual ability and spasticity were related to development of mobility activities. Multivariate analysis indicated that GMFCS and intellectual capacity were the strongest determinants of development of self-care activities, and GMFCS was the strongest determinant of development of mobility activities. The change in self-care and mobility activities was less favorable in severely affected children with severe disability. Knowledge of GMFCS level and intellectual capacity is important in anticipating change over time and goal setting in young children with CP. 201
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