833 research outputs found

    A Multicenter Examination and Strategic Revisions of the Yale Global Tic Severity Scale

    Get PDF
    Objective To examine the internal consistency and distribution of the Yale Global Tic Severity Scale (YGTSS) scores to inform modification of the measure. Methods This cross-sectional study included 617 participants with a tic disorder (516 children and 101 adults), who completed an age-appropriate diagnostic interview and the YGTSS to evaluate tic symptom severity. The distributions of scores on YGTSS dimensions were evaluated for normality and skewness. For dimensions that were skewed across motor and phonic tics, a modified Delphi consensus process was used to revise selected anchor points. Results Children and adults had similar clinical characteristics, including tic symptom severity. All participants were examined together. Strong internal consistency was identified for the YGTSS Motor Tic score (α = 0.80), YGTSS Phonic Tic score (α = 0.87), and YGTSS Total Tic score (α = 0.82). The YGTSS Total Tic and Impairment scores exhibited relatively normal distributions. Several subscales and individual item scales departed from a normal distribution. Higher scores were more often used on the Motor Tic Number, Frequency, and Intensity dimensions and the Phonic Tic Frequency dimension. By contrast, lower scores were more often used on Motor Tic Complexity and Interference, and Phonic Tic Number, Intensity, Complexity, and Interference. Conclusions The YGTSS exhibits good internal consistency across children and adults. The parallel findings across Motor and Phonic Frequency, Complexity, and Interference dimensions prompted minor revisions to the anchor point description to promote use of the full range of scores in each dimension. Specific minor revisions to the YGTSS Phonic Tic Symptom Checklist were also proposed

    [Pemetrexed + Sorafenib] lethality is increased by inhibition of ERBB1/2/3-PI3K-NFκB compensatory survival signaling

    Get PDF
    In the completed phase I trial NCT01450384 combining the anti-folate pemetrexed and the multi-kinase inhibitor sorafenib it was observed that 20 of 33 patients had prolonged stable disease or tumor regression, with one complete response and multiple partial responses. The pre-clinical studies in this manuscript were designed to determine whether [pemetrexed + sorafenib] –induced cell killing could be rationally enhanced by additional signaling modulators. Multiplex assays performed on tumor material that survived and re-grew after [pemetrexed + sorafenib] exposure showed increased phosphorylation of ERBB1 and of NFκB and IκB; with reduced IκB and elevated G-CSF and KC protein levels. Inhibition of JAK1/2 downstream of the G-CSF/KC receptors did not enhance [pemetrexed + sorafenib] lethality whereas inhibition of ERBB1/2/4 using kinase inhibitory agents or siRNA knock down of ERBB1/2/3 strongly promoted killing. Inhibition of ERBB1/2/4 blocked [pemetrexed + sorafenib] stimulated NFκB activation and SOD2 expression; and expression of IκB S32A S36A significantly enhanced [pemetrexed + sorafenib] lethality. Sorafenib inhibited HSP90 and HSP70 chaperone ATPase activities and reduced the interactions of chaperones with clients including c-MYC, CDC37 and MCL-1. In vivo, a 5 day transient exposure of established mammary tumors to lapatinib or vandetanib significantly enhanced the anti-tumor effect of [pemetrexed + sorafenib], without any apparent normal tissue toxicities. Identical data to that in breast cancer were obtained in NSCLC tumors using the ERBB1/2/4 inhibitor afatinib. Our data argue that the combination of pemetrexed, sorafenib and an ERBB1/2/4 inhibitor should be explored in a new phase I trial in solid tumor patients

    Volumetric, relaxometric and diffusometric correlates of psychotic experiences in a non-clinical sample of young adults

    Get PDF
    BackgroundGrey matter (GM) abnormalities are robust features of schizophrenia and of people at ultra high-risk for psychosis. However the extent to which neuroanatomical alterations are evident in non-clinical subjects with isolated psychotic experiences is less clear.MethodsIndividuals (mean age 20 years) with (n = 123) or without (n = 125) psychotic experiences (PEs) were identified from a population-based cohort. All underwent T1-weighted structural, diffusion and quantitative T1 relaxometry MRI, to characterise GM macrostructure, microstructure and myelination respectively. Differences in quantitative GM structure were assessed using voxel-based morphometry (VBM). Binary and ordinal models of PEs were tested. Correlations between socioeconomic and other risk factors for psychosis with cortical GM measures were also computed.ResultsGM volume in the left supra-marginal gyrus was reduced in individuals with PEs relative to those with no PEs. The greater the severity of PEs, the greater the reduction in T1 relaxation rate (R1) across left temporoparietal and right pre-frontal cortices. In these regions, R1 was positively correlated with maternal education and inversely correlated with general psychopathology.ConclusionsPEs in non-clinical subjects were associated with regional reductions in grey-matter volume reduction and T1 relaxation rate. The alterations in T1 relaxation rate were also linked to the level of general psychopathology. Follow up of these subjects should clarify whether these alterations predict the later development of an ultra high-risk state or a psychotic disorder

    Superconducting fluctuation corrections to ultrasound attenuation in layered superconductors

    Full text link
    We consider the temperature dependence of the sound attenuation and sound velocity in layered impure metals due to superconducting fluctuations of the order parameter above the critical temperature. We obtain the dependence on material properties of these fluctuation corrections in the hydrodynamic limit, where the electron mean free path is much smaller than the wavelength of sound and where the electron collision rate is much larger than the sound frequency. For longitudinal sound propagating perpendicular to the layers, the open Fermi surface condition leads to a suppression of the divergent contributions to leading order, in contrast with the case of paraconductivity. The leading temperature dependent corrections, given by the Aslamazov-Larkin, Maki-Thompson and density of states terms, remain finite as T->Tc. Nevertheless, the sensitivity of new ultrasonic experiments on layered organic conductors should make these fluctuations effects measurable.Comment: 13 pages, 6 figures. Accepted for PRB. Added discussion on incoherent interlayer tunneling and other small modifications suggested by referee

    Optical Splitting Trees for High-Precision Monocular Imaging

    Full text link

    Complications following surgical intervention for stress urinary incontinence: A national perspective

    Full text link
    Aims Stress urinary incontinence (SUI) impacts many women. Treatment is primarily surgical. Post-operative morbidity considerably affects individuals and the health care system. Our objective is to describe complications following surgery for SUI and how they affect resource utilization. Methods Utilizing the Nationwide Inpatient Sample (a nationally representative dataset), 147,473 patients who underwent surgery for SUI from 1988 to 2000 were identified by ICD-9 codes. Comorbid conditions/complications were extracted using ICD-9 codes, including complication rates, length of stay (LOS), hospital charges, and discharge status. Results Overall complication rate was 13.0% (not equal to sum of complication sub-types, as each woman may have had = 1 complication), with 2.8% bleeding, 1.4% surgical injury, 4.3% urinary/renal, 4.4% infectious, 0.1% wound, 1.1% pulmonary insufficiency, 0.5% myocardial infarction, 0.2% thromboembolic. The “gold standard” surgical technique for SUI, the pubovaginal sling, had the lowest morbidity at 12.5%. Mean LOS increased with morbidity: from 2.9 to 4.1 to 6.1 days for those with 0, 1, and =2 complications respectively ( P  < 0.001). Similarly, inflation-adjusted hospital charges increased with morbidity: from 7,918to7,918 to 9,828 to $15,181 for those with 0, 1, and =2 complications respectively ( P  < 0.001). The percentage of patients requiring post-discharge subacute or home care increased with morbidity: from 4.4% to 8.4% to 14.3% for those with 0, 1, and =2 complications ( P  < 0.001). Conclusions A substantial percentage of women experience complications following surgery for SUI. Post-operative morbidity leads to dramatically increased resource utilization. Prospective studies are needed to identify pre-operative risk factors and intraoperative process measures to optimize the quality of care. Neurourol. Urodynam. © 2005 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34912/1/20186_ftp.pd

    Long-term ecological research in a human-dominated world

    Get PDF
    Author Posting. © American Institute of Biological Sciences, 2012. This article is posted here by permission of American Institute of Biological Sciences for personal use, not for redistribution. The definitive version was published in BioScience 62 (2012): 342-253, doi:10.1525/bio.2012.62.4.6.The US Long Term Ecological Research (LTER) Network enters its fourth decade with a distinguished record of achievement in ecological science. The value of long-term observations and experiments has never been more important for testing ecological theory and for addressing today's most difficult environmental challenges. The network's potential for tackling emergent continent-scale questions such as cryosphere loss and landscape change is becoming increasingly apparent on the basis of a capacity to combine long-term observations and experimental results with new observatory-based measurements, to study socioecological systems, to advance the use of environmental cyberinfrastructure, to promote environmental science literacy, and to engage with decisionmakers in framing major directions for research. The long-term context of network science, from understanding the past to forecasting the future, provides a valuable perspective for helping to solve many of the crucial environmental problems facing society today.2012-10-0

    Causal hierarchy within the thalamo-cortical network in spike and wave discharges

    Get PDF
    Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al
    corecore