Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study.

Background: In the EXIST-1 trial, initiated on Aug 10, 2009, more than 35% of patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex had at least 50% reduction in SEGA volume after 9·6 months of treatment with everolimus. In this Article, we report interim data (up to Jan 11, 2013) to support longer-term tolerability and efficacy of everolimus from the continuing 4-year extension phase of EXIST-1.

Methods: We assessed data from a prospective, open-label extension of a multicentre, phase 3, randomised, double-blind, placebo-controlled study in patients with tuberous sclerosis complex who had SEGA that was growing and needed treatment.

TOSCA - first international registry to address knowledge gaps in the natural history and management of tuberous sclerosis complex.

Background: Tuberous sclerosis complex (TSC) is a rare, multisystem, genetic disorder with an estimated prevalence between 1/6800 and 1/15000. Although recent years have seen huge progress in understanding the pathophysiology and in the management of TSC, several questions remain unanswered. A disease registry could be an effective tool to gain more insights into TSC and thus help in the development of improved management strategies.

Characterization of ANKRD11 mutations in humans and mice related to KBG syndrome.

Mutations in ANKRD11 have recently been reported to cause KBG syndrome, an autosomal dominant condition characterized by intellectual disability (ID), behavioral problems, and macrodontia. To understand the pathogenic mechanism that relates ANKRD11 mutations with the phenotype of KBG syndrome, we studied the cellular characteristics of wild-type ANKRD11 and the effects of mutations in humans and mice. We show that the abundance of wild-type ANKRD11 is tightly regulated during the cell cycle, and that the ANKRD11 C-terminus is required for the degradation of the protein.

Search for scalar diphoton resonances in the mass range 65-600 GeV with the ATLAS detector in pp collision data at √s=8 TeV.

A search for scalar particles decaying via narrow resonances into two photons in the mass range 65-600 GeV is performed using 20.3  fb(-1) of √s 8 TeV pp collision data collected with the ATLAS detector at the Large Hadron Collider. The recently discovered Higgs boson is treated as a background.

Evidence for electroweak production of W±W±jj in pp collisions at sqrt[s] = 8 TeV with the ATLAS detector.

This Letter presents the first study of W(±)W(±)jj, same-electric-charge diboson production in association with two jets, using 20.3 fb(-1) of proton-proton collision data at sqrt[s] = 8  TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with two reconstructed same-charge leptons (e(±)e(±), e(±)μ(±), and μ(±)μ(±)) and two or more jets are analyzed.

PTEN expression and function in adult cancer stem cells and prospects for therapeutic targeting.

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a non-redundant lipid phosphatase that restrains and fine tunes the phosphatidylinositol-3-kinase (PI3K) signaling pathway. PTEN is involved in inherited syndromes, which predispose to different types of cancers and is among the most frequently inactivated tumor suppressor genes in sporadic cancers. Indeed, loss of PTEN function occurs in a wide spectrum of human cancers through a variety of mechanisms, including mutations, deletions, transcriptional silencing, or protein instability.

Measurements of four-lepton production at the Z resonance in pp collisions at sqrt[s] = 7 and 8 TeV with ATLAS.

Measurements of four-lepton (4ℓ, ℓ=e,μ) production cross sections at the Z resonance in pp collisions at the LHC with the ATLAS detector are presented. For dilepton and four-lepton invariant mass regions m(ℓ+ℓ(-)) > 5 GeV and 80 View Article and Find Full Text PDF

Is the conditioned pain modulation paradigm reliable? A test-retest assessment using the nociceptive withdrawal reflex.

The aim of this study was to determine the reliability of the conditioned pain modulation (CPM) paradigm assessed by an objective electrophysiological method, the nociceptive withdrawal reflex (NWR), and psychophysical measures, using hypothetical sample sizes for future studies as analytical goals. Thirty-four healthy volunteers participated in two identical experimental sessions, separated by 1 to 3 weeks. In each session, the cold pressor test (CPT) was used to induce CPM, and the NWR thresholds, electrical pain detection thresholds and pain intensity ratings after suprathreshold electrical stimulation were assessed before and during CPT.

Current role of rufinamide in the treatment of childhood epilepsy: literature review and treatment guidelines.

Purpose: The literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes currently includes approximately 600 paediatric patients. This paper summarizes the views of a panel of experienced European epileptologists with regard to the current role of rufinamide in the treatment of childhood epilepsies.

Results: Rufinamide is effective in decreasing the seizure frequency in the Lennox-Gastaut syndrome (LGS), especially tonic and atonic seizures.

Tourette syndrome and comorbid conditions: a spectrum of different severities and complexities.

To investigate clinical correlates of Tourette syndrome and to identify the impact of comorbidities, we retrospectively recruited 92 young people affected by Tourette syndrome compared with 102 healthy controls. Neuropsychological assessment included: Youth Quality of Life-Research, Multidimensional Anxiety Scale for Children, Children's Depression Inventory, and Conner's and Child Behavior Checklist; moreover, Tourette syndrome patients completed the Yale Global Tic Severity Rating Scale and the Yale-Brown Obsessive Compulsive Scale. Four clinical subgroups were identified: pure Tourette syndrome (49.

Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain.

Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis.

Search for quantum black hole production in high-invariant-mass lepton+jet final states using pp collisions at √s=8 TeV and the ATLAS detector.

This Letter presents a search for quantum black-hole production using 20.3 fb-1 of data collected with the ATLAS detector in pp collisions at the LHC at √s = 8 TeV. The quantum black holes are assumed to decay into a final state characterized by a lepton (electron or muon) and a jet.

Search for dark matter in events with a hadronically decaying W or Z boson and missing transverse momentum in pp collisions at √s=8 TeV with the ATLAS detector.

A search is presented for dark matter pair production in association with a W or Z boson in pp collisions representing 20.3  fb(-1) of integrated luminosity at √s=8  TeV using data recorded with the ATLAS detector at the Large Hadron Collider. Events with a hadronic jet with the jet mass consistent with a W or Z boson, and with large missing transverse momentum are analyzed.

Rufinamide for the treatment of refractory epilepsy secondary to neuronal migration disorders.

Objective: To evaluate the efficacy and tolerability of add-on rufinamide in children with refractory epilepsy symptomatic of neuronal migration disorders.

Materials And Methods: We recruited 69 patients in a prospective, open-label, add-on treatment study from six Italian and one German centers for pediatric and adolescent epilepsy care according to the following criteria: age 3 or above; focal or generalized seizures refractory to at least three previous antiepileptic drugs (AEDs), alone or in combination, secondary to neuronal migration disorders; two or more seizures per month in the last 6 months; use of another AED, but no more than three, at baseline. Informed consent from parents and/or caregivers was obtained at the time of enrollment.

Headache and attention deficit and hyperactivity disorder in children: common condition with complex relation and disabling consequences.

The aim of this review was to analyze literature data on the complex association between headache and attention deficit and hyperactivity disorder (ADHD) in children, in order to explore its possible consequences on child neurological development. Headache and ADHD are two common conditions in the pediatric population. They both are disabling diseases that impact the child's quality of life and are associated with severe cognitive, emotional, and behavioral impairments.

Measurement of top quark polarization in top-antitop events from proton-proton collisions at √s=7 TeV using the ATLAS detector.

This Letter presents measurements of the polarization of the top quark in top-antitop quark pair events, using 4.7  fb(-1) of proton-proton collision data recorded with the ATLAS detector at the Large Hadron Collider at √s=7  TeV. Final states containing one or two isolated leptons (electrons or muons) and jets are considered.

Measurements of jet vetoes and azimuthal decorrelations in dijet events produced in [Formula: see text] collisions at [Formula: see text] using the ATLAS detector.

Additional jet activity in dijet events is measured using [Formula: see text] collisions at ATLAS at a centre-of-mass energy of [Formula: see text], for jets reconstructed using the [Formula: see text] algorithm with radius parameter [Formula: see text]. This is done using variables such as the fraction of dijet events without an additional jet in the rapidity interval bounded by the dijet subsystem and correlations between the azimuthal angles of the dijet s. They are presented, both with and without a veto on additional jet activity in the rapidity interval, as a function of the scalar average of the transverse momenta of the dijet s and of the rapidity interval size.

Measurement of the azimuthal angle dependence of inclusive jet yields in Pb+Pb collisions at √(sNN)=2.76 TeV with the ATLAS detector.

Measurements of the variation of inclusive jet suppression as a function of relative azimuthal angle, Δφ, with respect to the elliptic event plane provide insight into the path-length dependence of jet quenching. ATLAS has measured the Δφ dependence of jet yields in 0.14 nb(-1) of √(s(NN))=2.

Signaling intermediates (MAPK and PI3K) as therapeutic targets in NSCLC.

The RAS/RAF/MEK/ ERK and the PI3K/AKT/mTOR pathways govern fundamental physiological processes, such as cell proliferation, differentiation, metabolism, cytoskeleton reorganization and cell death and survival. Constitutive activation of these signal transduction pathways is a required hallmark of cancer and dysregulation, on either genetic or epigenetic grounds, of these pathways has been implicated in the initiation, progression and metastastic spread of lung cances. Targeting components of the MAPK and PI3K cascades is thus an attractive strategy in the development of novel therapeutic approaches to treat lung cancer, although the use of single pathway inhibitors has met with limited clinical success so far.

Probabilistic model for individual assessment of central hyperexcitability using the nociceptive withdrawal reflex: a biomarker for chronic low back and neck pain.

Background: The nociceptive withdrawal reflex (NWR) has been proven to be a valuable tool in the objective assessment of central hyperexcitability in the nociceptive system at spinal level that is present in some chronic pain disorders, particularly chronic low back and neck pain. However, most of the studies on objective assessment of central hyperexcitability focus on population differences between patients and healthy individuals and do not provide tools for individual assessment. In this study, a prediction model was developed to objectively assess central hyperexcitability in individuals.

Advances towards the design and development of personalized non-small-cell lung cancer drug therapy.

Introduction: Non-small-cell lung cancer (NSCLC) subtypes are driven by specific genetic aberrations. For reasons such as this, there is a call for treatment personalization. The ability to instigate NSCLC fragmentation poses new methodological problems, and new 'driver' molecular aberrations are being discovered at an unprecedented pace.

Reduction in retinal nerve fiber layer thickness in young adults with autism spectrum disorders.

Recent years have seen an increase in the use of retinal nerve fiber layer (RNFL) evaluation as an easy-to-use, reproducible, proxy-measure of brain structural abnormalities. Here, we evaluated RNFL thickness in a group of subjects with high functioning autism (HFA) or with Asperger Syndrome (AS) to its potential as a tool to study autism pathophysiology. All subjects underwent high-resolution spectral domain optical coherence tomography to evaluate RNFL thickness.

Ranking of tests for pain hypersensitivity according to their discriminative ability in chronic neck pain.

Background And Objectives: Quantitative sensory testing (QST) is widely used to investigate peripheral and central sensitization. However, the comparative performance of different QST for diagnostic or prognostic purposes is unclear. We explored the discriminative ability of different quantitative sensory tests in distinguishing between patients with chronic neck pain and pain-free control subjects and ranked these tests according to the extent of their association with pain hypersensitivity.