86 research outputs found
Anti-amyloid antibody treatments for Alzheimer's disease
Our aim is to review the most recent evidence on novel antibody therapies for Alzheimer's disease directed against amyloid-& beta;. This is a joint statement of the European Association of Neurology and the European Psychiatric Association. After numerous unsuccessful endeavors to create a disease-modifying therapy for Alzheimer's disease, substantial and consistent evidence supporting the clinical effectiveness of monoclonal antibodies aimed at amyloid-& beta;is finally emerging. The latest trials not only achieved their primary objective of slowing the progression of the disease over several months but also demonstrated positive secondary clinical outcomes and a decrease in amyloid-& beta;levels as observed through positron emission tomography scans. Taken as a whole, these findings mark a significant breakthrough by substantiating that reducing amyloid-& beta;yields tangible clinical benefits, beyond mere changes in biomarkers. Concurrently, the regular utilization of the new generation of drugs will determine whether statistical efficacy translates into clinically meaningful improvements. This may well signify the dawning of a new era in the development of drugs for Alzheimer's disease
Effect of acceleration and deceleration distance on the walking speed of people with chronic stroke
published_or_final_versio
Fixed-parameter tractability and lower bounds for stabbing problems
We study the following general stabbing problem from a parameterized
complexity point of view: Given a set of translates of an
object in \Rd, find a set of lines with the property that every object in
is ''stabbed'' (intersected) by at least one line.
We show that when consists of axis-parallel unit squares in \Rtwo the
(decision) problem of stabbing with axis-parallel lines is W[1]-hard with
respect to (and thus, not fixed-parameter tractable unless FPT=W[1]) while
it becomes fixed-parameter tractable when the squares are disjoint. We also
show that the problem of stabbing a set of disjoint unit squares in \Rtwo
with lines of arbitrary directions is W[1]--hard with respect to . Several
generalizations to other types of objects and lines with arbitrary directions
are also presented. Finally, we show that deciding whether a set of unit balls
in \Rd can be stabbed by one line is W[1]--hard with respect to the dimension
.Comment: Based on the MSc. Thesis of Daniel Werner, Free University Berlin,
Berlin, German
The Future of Diagnosis in Clinical Neurosciences: Comparing Multiple Sclerosis and Schizophrenia
The ongoing developments of psychiatric classification systems have largely improved reliability of diagnosis, including that of schizophrenia. However, with an unknown pathophysiology and lacking biomarkers, its validity still remains low, requiring further advancements. Research has helped establish multiple sclerosis (MS) as the central nervous system (CNS) disorder with an established pathophysiology, defined biomarkers and therefore good validity and significantly improved treatment options. Before proposing next steps in research that aim to improve the diagnostic process of schizophrenia, it is imperative to recognize its clinical heterogeneity. Indeed, individuals with schizophrenia show high interindividual variability in terms of symptomatic manifestation, response to treatment, course of illness and functional outcomes. There is also a multiplicity of risk factors that contribute to the development of schizophrenia. Moreover, accumulating evidence indicates that several dimensions of psychopathology and risk factors cross current diagnostic categorizations. Schizophrenia shares a number of similarities with MS, which is a demyelinating disease of the CNS. These similarities appear in the context of age of onset, geographical distribution, involvement of immune-inflammatory processes, neurocognitive impairment and various trajectories of illness course. This article provides a critical appraisal of diagnostic process in schizophrenia, taking into consideration advancements that have been made in the diagnosis and management of MS. Based on the comparison between the two disorders, key directions for studies that aim to improve diagnostic process in schizophrenia are formulated. All of them converge on the necessity to deconstruct the psychosis spectrum and adopt dimensional approaches with deep phenotyping to refine current diagnostic boundaries
A small-molecule PI3KÎą activator for cardioprotection and neuroregeneration
Harnessing the potential beneficial effects of kinase signalling through the generation of direct kinase activators remains an underexplored area of drug development1,2,3,4,5. This also applies to the PI3K signalling pathway, which has been extensively targeted by inhibitors for conditions with PI3K overactivation, such as cancer and immune dysregulation. Here we report the discovery of UCL-TRO-1938 (referred to as 1938 hereon), a small-molecule activator of the PI3KÎą isoform, a crucial effector of growth factor signalling. 1938 allosterically activates PI3KÎą through a distinct mechanism by enhancing multiple steps of the PI3KÎą catalytic cycle and causes both local and global conformational changes in the PI3KÎą structure. This compound is selective for PI3KÎą over other PI3K isoforms and multiple protein and lipid kinases. It transiently activates PI3K signalling in all rodent and human cells tested, resulting in cellular responses such as proliferation and neurite outgrowth. In rodent models, acute treatment with 1938 provides cardioprotection from ischaemiaâreperfusion injury and, after local administration, enhances nerve regeneration following nerve crush. This study identifies a chemical tool to directly probe the PI3KÎą signalling pathway and a new approach to modulate PI3K activity, widening the therapeutic potential of targeting these enzymes through short-term activation for tissue protection and regeneration. Our findings illustrate the potential of activating kinases for therapeutic benefit, a currently largely untapped area of drug development
Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV
Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7ââfbâ1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale
Search for the associated production of the Higgs boson with a top-quark pair
Open Access. This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.A search for the standard model Higgs boson produced in association with a top-quark pair (t t ÂŻ H) is presented, using data samples corresponding to integrated luminosities of up to 5.1 fb-1 and 19.7 fb-1 collected in pp collisions at center-of-mass energies of 7 TeV and 8 TeV respectively. The search is based on the following signatures of the Higgs boson decay: H â hadrons, H â photons, and H â leptons. The results are characterized by an observed t t ÂŻ H \mathrm{t}\overline{\mathrm{t}}\mathrm{H} signal strength relative to the standard model cross section, Îź=Ď/Ď SM,under the assumption that the Higgs boson decays as expected in the standard model. The best fit value is Îź = 2.8 Âą 1.0 for a Higgs boson mass of 125.6 GeV
Search for three-jet resonances in pp collisions at âs=7 TeV
This is a Pre-Print version of the Article - Copyright @ 2011 APSA model-independent search for three-jet hadronic resonance production in pp collisions at a center-of-mass energy of 7 TeV has been conducted by the CMS Collaboration at the LHC, using a data sample corresponding to an integrated luminosity of 35 inverse picobarns. Events with high jet multiplicity and a large scalar sum of jet transverse momenta are analyzed. The number of expected standard model background events is found to be in good agreement with the observed events. Limits are set on a model describing the production of R-parity-violating supersymmetric gluino pairs, and gluino masses in the range of 200 to 280 GeV/c^2 are excluded at a 95% confidence level for the first time.This work is supported by the FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF andWCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan);
MST and MAE (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies
(Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and
NSF (USA)
Effectiveness of two web-based cognitive bias modification interventions targeting approach and attentional bias in gambling problems: study protocol for a pilot randomised controlled trial
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