Search results
Found 16089 matches for
Nature of Glutamate Alterations in Schizophrenia: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies.
IMPORTANCE: Alterations in glutamatergic neurotransmission may be fundamental to the pathophysiology of schizophrenia, and the glutamatergic system is a target for novel therapeutic interventions in the disorder. OBJECTIVE: To investigate the nature of brain glutamate alterations in schizophrenia by conducting a meta-analysis of glutamate proton magnetic resonance (MRS) spectroscopy studies. DATA SOURCES: The MEDLINE database was searched for studies published from January 1, 1980, to April 1, 2015. Search terms included magnetic resonance spectroscopy, schizophrenia, psychosis, clinical or genetic high risk, and schizoaffective. Inclusion criteria were single voxel 1H-MRS studies reporting glutamate, glutamine or Glx values for a patient or risk group in comparison to a healthy volunteer group. STUDY SELECTION: Fifty-nine studies were identified, which included 1686 patients and 1451 healthy individuals serving as controls. DATA EXTRACTION AND SYNTHESIS: A random-effects, inverse-weighted variance model was used to calculate the pooled effect size. Mean values were extracted and verified independently. Effect sizes were determined for glutamate, glutamine, and Glx in brain regions that had been examined in at least 3 different studies. A secondary analysis grouped studies into those examining patients at different stages of illness (high risk, first-episode psychosis, or chronic schizophrenia). Effects of age, antipsychotic dose, and symptom severity were determined using meta-regression. RESULTS: In schizophrenia, there were significant elevations in glutamate in the basal ganglia (Hedges g = 0.63; 95% CI, 0.15-1.11), glutamine in the thalamus (g = 0.56; 95% CI, 0.02-1.09), and Glx in the basal ganglia (g = 0.39; 95% CI, 0.09-0.70) and medial temporal lobe (g = 0.32; 95% CI, 0.12-0.52). No region showed a reduction in glutamate metabolites in schizophrenia. Secondary analyses revealed that elevated medial frontal Glx levels were evident in individuals at high risk for schizophrenia (g = 0.26; 95% CI, 0.05-0.46) but not in those with first-episode psychosis or chronic schizophrenia, whereas elevated Glx in the medial temporal lobe was seen with chronic schizophrenia (g = 0.40; 95% CI, 0.08-0.71) but not in the high-risk or first-episode groups. Meta-regression found no association with age, symptom severity, or antipsychotic dose. CONCLUSIONS AND RELEVANCE: Schizophrenia is associated with elevations in glutamatergic metabolites across several brain regions. This finding supports the hypothesis that schizophrenia is associated with excess glutamatergic neurotransmission in several limbic areas and further indicates that compounds that reduce glutamatergic transmission may have therapeutic potential.
Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia: A Systematic Review and Meta-analysis.
Importance: Ketamine hydrochloride is increasingly used to treat depression and other psychiatric disorders but can induce schizophrenia-like or psychotomimetic symptoms. Despite this risk, the consistency and magnitude of symptoms induced by ketamine or what factors are associated with these symptoms remain unknown. Objective: To conduct a meta-analysis of the psychopathological outcomes associated with ketamine in healthy volunteers and patients with schizophrenia and the experimental factors associated with these outcomes. Data Sources: MEDLINE, Embase, and PsychINFO databases were searched for within-participant, placebo-controlled studies reporting symptoms using the Brief Psychiatric Rating Scale (BPRS) or the Positive and Negative Syndrome Scale (PANSS) in response to an acute ketamine challenge in healthy participants or patients with schizophrenia. Study Selection: Of 8464 citations retrieved, 36 studies involving healthy participants were included. Inclusion criteria were studies (1) including healthy participants; (2) reporting symptoms occurring in response to acute administration of subanesthetic doses of ketamine (racemic ketamine, s-ketamine, r-ketamine) intravenously; (3) containing a placebo condition with a within-subject, crossover design; (4) measuring total positive or negative symptoms using BPRS or PANSS; and (5) providing data allowing the estimation of the mean difference and deviation between the ketamine and placebo condition. Data Extraction and Synthesis: Two independent investigators extracted study-level data for a random-effects meta-analysis. Total, positive, and negative BPRS and PANSS scores were extracted. Subgroup analyses were conducted examining the effects of blinding status, ketamine preparation, infusion method, and time between ketamine and placebo conditions. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Main Outcomes and Measures: Standardized mean differences (SMDs) were used as effect sizes for individual studies. Standardized mean differences between ketamine and placebo conditions were calculated for total, positive, and negative BPRS and PANSS scores. Results: The overall sample included 725 healthy volunteers (mean [SD] age, 28.3 [3.6] years; 533 [73.6%] male) exposed to the ketamine and placebo conditions. Racemic ketamine or S-ketamine was associated with a statistically significant increase in transient psychopathology in healthy participants for total (SMD = 1.50 [95% CI, 1.23-1.77]; P < .001), positive (SMD = 1.55 [95% CI, 1.29-1.81]; P < .001), and negative (SMD = 1.16 [95% CI, 0.96-1.35]; P < .001) symptom ratings relative to the placebo condition. The effect size for this association was significantly greater for positive than negative symptoms of psychosis (estimate, 0.36 [95% CI, 0.12-0.61]; P = .004). There was significant inconsistency in outcomes between studies (I2 range, 77%-83%). Bolus followed by constant infusion increased ketamine's association with positive symptoms relative to infusion alone (effect size, 1.63 [95% CI, 1.36-1.90] vs 0.84 [95% CI, 0.35-1.33]; P = .006). Single-day study design increased ketamine's ability to generate total symptoms (effect size, 2.29 [95% CI, 1.69-2.89] vs 1.39 [95% CI, 1.12-1.66]; P = .007), but age and sex did not moderate outcomes. Insufficient studies were available for meta-analysis of studies in schizophrenia. Of these studies, 2 found a statistically significant increase in symptoms with ketamine administration in total and positive symptoms. Only 1 study found an increase in negative symptom severity with ketamine. Conclusions and Relevance: This study found that acute ketamine administration was associated with schizophrenia-like or psychotomimetic symptoms with large effect sizes, but there was a greater increase in positive than negative symptoms and when a bolus was used. These findings suggest that bolus doses should be avoided in the therapeutic use of ketamine to minimize the risk of inducing transient positive (psychotic) symptoms.
BFKL approach and 2→5 maximally helicity violating amplitude in N=4 super-Yang-Mills theory
We study maximally helicity violating amplitude for the 2→5 scattering in the multi-Regge kinematics. The Mandelstam cut correction to the Bern-Dixon-Smirnov amplitude is calculated in the leading logarithmic approximation and the corresponding remainder function is given to any loop order in a closed integral form. We show that the leading logarithmic approximation remainder function at two loops for 2→5 amplitude can be written as a sum of two 2→4 remainder functions due to recursive properties of the leading order impact factors. We also make some generalizations for the maximally helicity violating amplitudes with more external particles. The results of the present study are in agreement with the all leg two-loop symbol derived by Caron-Huot as shown in a parallel paper of one of the authors with collaborators. © 2012 American Physical Society.
Multiparticle production in the mean field approximation of high density QCD
The generating functional is suggested for multiparticle generation processes. In mean field approximation of high density QCD two equations for new generating functional are derived: linear functional equation for an arbitrary initial condition and non-linear one for a specific initial condition. The non-linear equation has the form of Kovchegov-Levin equation for diffraction production and gives its generalization on the processes with fixed multiplicities of produced particles. © 2008 Elsevier B.V. All rights reserved.
On the nuclear modification factor at RHIC and LHC
We show that pQCD factorization incorporated with pre-hadronization energy-loss effect naturally leads to flatness of the nuclear modification factor RAA for produced hadrons at high transverse momentum pT. We consider two possible scenarios for the pre-hadronization: In scenario 1, the produced gluon propagates through dense QCD medium and loses energy. In scenario 2, all gluons first decay to quark-antiquark pairs and then each pair loses energy as propagating through the medium. We show that the estimates of the energy-loss in these two different models lead to very close values and is able to explain the suppression of high-pT hadrons in nucleus-nucleus collisions at RHIC. We show that the onset of the flatness of RAA for the produced hadron in central collisions at midrapidity is about pT≈15 and 25 GeV at RHIC and the LHC energies, respectively. We show that the smallness (RAA<0.5) and the high-pT flatness of RAA obtained from the kT factorization supplemented with the Balitsky-Kovchegov (BK) equation is rather generic and it does not strongly depend on the details of the BK solutions. We show that energy-loss effect reduces the nuclear modification factor obtained from the kT factorization about 30-50% at moderate pT. © 2011 Elsevier B.V.
A QCD motivated model for soft processes
In this talk we give a brief description of a QCD motivated model for both hard and soft interactions at high energies. In this model the long distance behaviour of the scattering amplitude is determined by the dipole scattering amplitude in the saturation domain. © 2009 American Institute of Physics.
Analytic structure of the n=7 scattering amplitude in N=4 SYM theory in the multi-Regge kinematics: Conformal Regge pole contribution
We investigate the analytic structure of the 2→5 production amplitude in the planar limit of N=4 SYM in the multi-Regge kinematics in all physical regions. We demonstrate the close connection between Regge pole and Regge cut contributions: in a selected class of kinematic regions (Mandelstam regions), the usual factorizing Regge pole formula develops unphysical singularities that have to be absorbed and compensated by Regge cut contributions. This leads, in the corrections to the Bern-Dixon-Smirnov formula, to conformal invariant "renormalized" Regge pole expressions in the remainder function. We compute these renormalized Regge poles for the 2→5 production amplitude. © 2014 American Physical Society.
Analytic structure of the n=7 scattering amplitude in N=4 SYM theory in multi-Regge kinematics: Conformal Regge cut contribution
© 2015 American Physical Society. In this second part of our investigation [1] of the analytic structure of the 2→5 scattering amplitude in the planar limit of N=4 super Yang-Mills theory in multi-Regge kinematics we compute, in all kinematic regions, the Regge-cut contributions at leading order. The results are infrared finite and conformally invariant.
Geometric scaling behavior of the scattering amplitude for DIS with nuclei
The main question, that we answer in this paper, is whether the initial condition can influence on the geometric scaling behavior of the amplitude for DIS at high energy. We re-write the non-linear Balitsky-Kovchegov equation in the form which is useful for treating the interaction with nuclei. Using the simplified BFKL kernel, we find the analytical solution to this equation with the initial condition given by the McLerran-Venugopalan formula. This solution does not show the geometric scaling behavior of the amplitude deeply in the saturation region. On the other hand, the BFKL Pomeron calculus with the initial condition at xA=1/mRA given by the solution to Balitsky-Kovchegov equation, leads to the geometric scaling behavior. The McLerran-Venugopalan formula is the natural initial condition for the Color Glass Condensate (CGC) approach. Therefore, our result gives a possibility to check experimentally which approach: CGC or BFKL Pomeron calculus, is more satisfactory. © 2011 Elsevier B.V.
QCD motivated approach to soft interactions at high energies: Nucleus-nucleus and hadron-nucleus collisions
In this paper we consider nucleus-nucleus and hadron-nucleus reactions in the kinematic region: gA1/3G3Pexp(ΔPY)≥1 and G3P2exp(ΔPY)<1, where G3P is the triple Pomeron coupling, g is the vertex of Pomeron nucleon interaction, and 1+ΔP denotes the Pomeron intercept. We find that in this kinematic region the traditional Glauber-Gribov eikonal approach is inadequate. We show that it is necessary to take into account inelastic Glauber corrections, which cannot be expressed in terms of the nucleon-nucleon scattering amplitudes. We derive the nucleus-nucleus scattering amplitude in the wide range of energies where αP'Y≪RA2, where this amplitude does not depend on the details of the nucleon-nucleon interaction at high energy. In the formalism we present, the only (correlated) parameters that are required to describe the data are ΔP, G3P and g. These parameters were taken from our description of the nucleon-nucleon data at high energies Gotsman et al. (2008) [1]. The predicted nucleus modification factor is compared with RHIC Au-Au data at W=200 GeV. Estimates for LHC energies are presented and discussed. © 2010 Elsevier B.V.
Survival probabilities for high mass diffraction
Based on the calculation of survival probabilities, we suggest a procedure to assess the value of G3P, the triple pomeron 'bare' coupling constant, by comparing the large rapidity gap single high mass diffraction data in proton-proton scattering and J/Ψ photo and DIS production. For p-p scattering the calculation in a three amplitude rescattering eikonal model predicts the survival probability to be an order of magnitude smaller than for the two amplitude case. The calculations of the survival probabilities for photo and DIS J/Ψ production are made in a dedicated model. In this process we show that, even though its survival probability is considerably larger than in p-p scattering, its value is below unity and cannot be neglected in the data analysis. We argue that, regardless of the uncertainties in the suggested procedures, the outcome is important, both with regards to a realistic estimate of G3P and to the survival probabilities relevant to LHC experiments. © 2007 Springer-Verlag / Società Italiana di Fisica.
High density QCD and nucleus-nucleus scattering deeply in the saturation region
In this paper we solve the equations that describe nucleus-nucleus scattering, in high density QCD, in the framework of the BFKL Pomeron Calculus. We found that (i) the contribution of short distances to the opacity for nucleus-nucleus scattering dies at high energies, (ii) the opacity tends to unity at high energy, and (iii) the main contribution that survives comes from soft (long distance) processes for large values of the impact parameter. The corrections to the opacity Ω(Y,b)=1 were calculated and it turns out that they have a completely different form, namely (1-Ω→exp(-Const√Y)) than the opacity that stems from the Balitsky-Kovchegov equation, which is (1-Ω→exp(-ConstY2)). We reproduce the formula for the nucleus-nucleus cross section that is commonly used in the description of nucleus-nucleus scattering, and there is no reason why it should be correct in the Glauber-Gribov approach. © 2011 Elsevier B.V.
Non-linear equation: Energy conservation and impact parameter dependence
In this paper we address two questions: how energy conservation affects the solution to the non-linear equation, and how impact parameter dependence influences the inclusive production. Answering the first question we solve the modified BK equation which takes into account energy conservation. In spite of the fact that we used the simplified kernel, we believe that the main result of the paper: the small (≤40%) suppression of the inclusive production due to energy conservation, reflects a general feature. This result leads us to believe that the small value of the nuclear modification factor is of a non-perturbative nature. In the solution a new scale appears Qfr=Qsexp(-1/(2αS)) and the production of dipoles with the size larger than 2/Qfr is suppressed. Therefore, we can expect that the typical temperature for hadron production is about Qfr (T≈Qfr). The simplified equation allows us to obtain a solution to Balitsky-Kovchegov equation taking into account the impact parameter dependence. We show that the impact parameter (b) dependence can be absorbed into the non-perturbative b dependence of the saturation scale. The solution of the BK equation, as well as of the modified BK equation without b dependence, is only accurate up to ±25%. © 2010 Elsevier B.V.
Utilization of the Signature Method to Identify the Early Onset of Sepsis From Multivariate Physiological Time Series in Critical Care Monitoring.
OBJECTIVES: Patients in an ICU are particularly vulnerable to sepsis. It is therefore important to detect its onset as early as possible. This study focuses on the development and validation of a new signature-based regression model, augmented with a particular choice of the handcrafted features, to identify a patient's risk of sepsis based on physiologic data streams. The model makes a positive or negative prediction of sepsis for every time interval since admission to the ICU. DESIGN: The data were sourced from the PhysioNet/Computing in Cardiology Challenge 2019 on the "Early Prediction of Sepsis from Clinical Data." It consisted of ICU patient data from three separate hospital systems. Algorithms were scored against a specially designed utility function that rewards early predictions in the most clinically relevant region around sepsis onset and penalizes late predictions and false positives. SETTING: The work was completed as part of the PhysioNet 2019 Challenge alongside 104 other teams. PATIENTS: PhysioNet sourced over 60,000 ICU patients with up to 40 clinical variables for each hour of a patient's ICU stay. The Sepsis-3 criteria was used to define the onset of sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The algorithm yielded a utility function score which was the first placed entry in the official phase of the challenge.
Named entity recognition in electronic health records using transfer learning bootstrapped Neural Networks.
Neural networks (NNs) have become the state of the art in many machine learning applications, such as image, sound (LeCun et al., 2015) and natural language processing (Young et al., 2017; Linggard et al., 2012). However, the success of NNs remains dependent on the availability of large labelled datasets, such as in the case of electronic health records (EHRs). With scarce data, NNs are unlikely to be able to extract this hidden information with practical accuracy. In this study, we develop an approach that solves these problems for named entity recognition, obtaining 94.6 F1 score in I2B2 2009 Medical Extraction Challenge (Uzuner et al., 2010), 4.3 above the architecture that won the competition. To achieve this, we bootstrap our NN models through transfer learning by pretraining word embeddings on a secondary task performed on a large pool of unannotated EHRs and using the output embeddings as a foundation of a range of NN architectures. Beyond the official I2B2 challenge, we further achieve 82.4 F1 on extracting relationships between medical terms using attention-based seq2seq models bootstrapped in the same manner.