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Within a decade, the Repetitive Transcranial Magnetic Stimulation (rTMS) was being used to treat depression and schizophrenia. Antidepressant response has been reported in open and double-blind, sham-controlled studies of depression. Less is known about rTMS efficacy in the obsessive compulsive disorder.
The aim of the randomized, double-blind, sham controlled study was to compare the 2 and 4 week efficacy of the 10 sessions rTMS with sham rTMS in serotonin reuptake inhibitor resistant OCD patient. Thirty seven right-handed patients were randomly assigned to either active rTMS or to sham. Active rTMS with the frequency of 1 Hz at 110% of motor threshold was administered over the left dorso-lateral prefrontal cortex. The same time schedule was used for sham administration. Thirty three patients finished the study, three patients’ dropped out at the beginning. Psychopathology was assessed by CGI, HAMA, Y-BOCS and BAI before the treatment, immediately after the experimental treatment, and 2 weeks after by an independent reviewer.
Both groups improved during the study period but the treatment effect did not differ between them in any of the instruments.
Low frequency rTMS administered over the left dorso-lateral prefrontal cortex during 10 daily sessions did not differ from sham rTMS in facilitating the effect of serotonin reuptake inhibitors in OCD patients.
The Repetitive Transcranial Magnetic Stimulation (rTMS) can modulate the cortical activity. The goal of our study was to assess whether the rTMS would facilitate effect of serotonin reuptake inhibitors in patients suffering from panic disorder.
Fifteen patients suffering from panic disorder resistant to serotonin reuptake inhibitor (SRI) therapy were randomly assigned to either active or to sham rTMS. The aim of the study was to compare the 2 and 4 weeks efficacy of the 10 sessions 1 Hz rTMS with sham rTMS add on SRI therapy. We used 1 Hz, 30 minutes rTMS, 110% of motor threshold administered over the right dorso-lateral prefrontal cortex (DLPFC). The same time schedule was used for sham administration. Fifteen patients finished the study. The psychopathology was assessed using the rating scales CGI, HAMA, PDSS and BAI before the treatment, immediately after the experimental treatment and 2 weeks after the experimental treatment by an independent reviewer.
Both groups improved during the study period but the treatment effect did not differ between groups in any of the instruments.
The low frequency Repetitive Transcranial Magnetic Stimulation administered over the right dorso-lateral prefrontal cortex after 10 sessions did not differ from sham the Repetitive Transcranial Magnetic Stimulation that was add on serotonin reuptake inhibitors in patients suffering from panic disorder.
Computer programs are used in rehabilitation of cognitive deficit in schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) can directly affect cortical excitability and metabolism of prefrontal lobe and subsequently affect cognition. The objective of our study was to investigate augmentation of cognitive rehabilitation in schizophrenia with rTMS. Study subjects were stabilized patients with DSM-IV diagnosis of schizophrenia, treated with second-generation antipsychotics, except for clozapine (total N=34). Study with rTMS was double-blind, randomized, placebo-controlled, with 2 parallel arms. All subjects participated in eight-week computer-assisted cognitive training, during first 2 weeks Group 1 (N=8) received rTMS and Group 2 (N=8) inactive sham stimulation. Patients who refused stimulation participated in rehabilitation program only. Data were assessed fo the totatl study sample and for each group separately. The results showed that computer-assisted cognitive training significantly improved severity of cognitive deficit in schizophrenia in many domains, especially executive functions: attention shift – flexibility, attention control, and working memory. The output was faster, more precise, and more reliable. We did not detect to effect of rTMS on the change of cognition, there was no significant difference between active and sham stimulation. This finding can be explained by a significantly lower initial score in Raven test found in actively stimulated group or by a smaller sample size in a double-blind study. The study confirmed efficacy of computer-assisted rehabilitation in remediation of cognitive deficit in schizophrenia.
Supported by the projects IGA MZ CR NF7571-3 and MSMT CR CNS 1M0517
The goal of our study was to identify brain structures in patients with panic disorder (PD) that show changes in 18FDG PET during the treatment with cognitive behavioral therapy (CBT) or antidepressants.
Twelve patients with panic disorder were studied with [18F]-2-fluoro-deoxyglucose positron emission tomography (18FDG PET) during resting state (condition of random episodic silent thinking, REST). After PET examination patients were randomly assigned to either cognitive behavioral treatment group (6 patients) or antidepressants treatment group (6 patients). After 3 month 18FDG PET examination was repeated in both groups.
Scores of psychopathology rating scales (CGI, HAMA, PDSS) decreased in both groups. Changes of 18FDG uptake in pharmacotherapy group: decreases were found in a priori hypothesized regions in right hemisphere, in superior, middle, medial and inferior frontal gyrus, superior and middle temporal gyrus, and increases were detected in a priori hypothesized regions, mainly in left hemisphere in medial and middle frontal gyrus, superior, middle and transverse temporal gyrus. Changes of 18FDG uptake in CBT group: decreases were found in a priori hypothesized regions of right hemisphere in inferior temporal gyrus, superior and inferior frontal gyrus, and increases were detected in a priori hypothesized region, mostly in left hemisphere: inferior frontal gyrus, middle temporal gyrus and insula.
Changes in brain metabolism after treatment either with CBT or with antidepressants were similar in number of brain areas, with prominent right-left difference.
Most clinicians tend to believe that the occurrence of the anxiety disorder in tandem with a personality disorder often leads to longer treatment, worsens the prognosis, and thus increasing treatment costs.
We compare the efficacy of 6weeks therapeutic program and 6weeks follow up in patients suffering with panic disorder and/or agoraphobia and comorbid personality disorder (29 patients) and panic disorder and/or agoraphobia without comorbid personality disorder (31 patients). Patients were treated with CBT and psychopharmacs. They were regularly assessed in week 0, 2, 4, 6 and 12 on the CGI, PDSS, HAMA, SDS, HDRS, BAI and BDI.
A combination of CBT and pharmacotherapy proved to be the effective treatment of patients suffering with panic disorder and/or agoraphobia with or without comorbid personality disorder. The 12th week treatment efficacy in the patients with panic disorder without personality disorder had been showed significantly better compared with the group with panic disorder comorbid with personality disorder in CGI and specific inventory for panic disorder - PDSS. Also the scores in depression inventories HDRS and BDI showed significantly higher decrease during the treatment comparing with group without personality disorder. But the treatment effect between groups did not differ in objective anxiety scale HAMA, and subjective anxiety scale BAI.
We consider interactions between surface and interfacial waves in a two-layer system. Our approach is based on the Hamiltonian structure of the equations of motion, and includes the general procedure for diagonalization of the quadratic part of the Hamiltonian. Such diagonalization allows us to derive the interaction cross-section between surface and interfacial waves and to derive the coupled kinetic equations describing spectral energy transfers in this system. Our kinetic equation allows resonant and near-resonant interactions. We find that the energy transfers are dominated by the class III resonances of Alam (J. Fluid Mech., vol. 691, 2012, pp. 267–278). We apply our formalism to calculate the rate of growth for interfacial waves for different values of wind velocity. Using our kinetic equation, we also consider the energy transfer from wind-generated surface waves to interfacial waves for the case when the spectrum of the surface waves is given by the JONSWAP spectrum and interfacial waves are initially absent. We find that such energy transfer can occur along a time scale of hours; there is a range of wind speeds for the most effective energy transfer at approximately the wind speed corresponding to white capping of the sea. Furthermore, interfacial waves oblique to the direction of the wind are also generated.
In schizophrenia, relative stability in the magnitude of cognitive deficits across age and illness duration is inconsistent with the evidence of accelerated deterioration in brain regions known to support these functions. These discrepant brain–cognition outcomes may be explained by variability in cognitive reserve (CR), which in neurological disorders has been shown to buffer against brain pathology and minimize its impact on cognitive or clinical indicators of illness.
Age-related change in fluid reasoning, working memory and frontal brain volume, area and thickness were mapped using regression analysis in 214 individuals with schizophrenia or schizoaffective disorder and 168 healthy controls. In patients, these changes were modelled as a function of CR.
Patients showed exaggerated age-related decline in brain structure, but not fluid reasoning compared to controls. In the patient group, no moderation of age-related brain structural change by CR was evident. However, age-related cognitive change was moderated by CR, such that only patients with low CR showed evidence of exaggerated fluid reasoning decline that paralleled the exaggerated age-related deterioration of underpinning brain structures seen in all patients.
In schizophrenia-spectrum illness, CR may negate ageing effects on fluid reasoning by buffering against pathologically exaggerated structural brain deterioration through some form of compensation. CR may represent an important modifier that could explain inconsistencies in brain structure – cognition outcomes in the extant literature.
The two-phase mixing layer formed between parallel gas and liquid streams is an important fundamental problem in turbulent multiphase flows. The problem is relevant to many industrial applications and natural phenomena, such as air-blast atomizers in fuel injection systems and breaking waves in the ocean. The velocity difference between the gas and liquid streams triggers an interfacial instability which can be convective or absolute depending on the stream properties and injection parameters. In the present study, a direct numerical simulation of a two-phase gas–liquid mixing layer that lie in the absolute instability regime is conducted. A dominant frequency is observed in the simulation and the numerical result agrees well with the prediction from viscous stability theory. As the interfacial wave plays a critical role in turbulence transition and development, the temporal evolution of turbulent fluctuations (such as the enstrophy) also exhibits a similar frequency. To investigate the statistical response of the multiphase turbulence flow, the simulation has been run for a long physical time so that time-averaging can be performed to yield the statistically converged results for Reynolds stresses and the turbulent kinetic energy (TKE) budget. An extensive mesh refinement study using from 8 million to about 4 billions cells has been performed. The turbulent dissipation is shown to be highly demanding on mesh resolution compared with other terms in TKE budget. The results obtained with the finest mesh are shown to be close to converged results of turbulent dissipation which allow us to obtain estimations of the Kolmogorov and Hinze scales. The estimated Kolmogorov scale is found to be similar to the cell size of the finest mesh used here. The computed Hinze scale is significantly larger than the size of droplets observed and does not seem to be a relevant length scale to describe the smallest size of droplets formed in atomization.
OBJECTIVES/SPECIFIC AIMS: Background: Annually, 2.5 million traumatic brain injuries (TBI) occur with nearly 75% classified as mild TBI (mTBI), also known as a concussion. Mild TBI can be subtle and detection requires a high index of suspicion and a regimented evaluation process. This study was done to define the proportion of patients with a possible mTBI evaluated for concussion at a high volume urban trauma center. METHODS/STUDY POPULATION: Methods: A prospective cohort of patients was identified using a 3-question screen at the time of triage: did an injury occur; was the mechanism consistent with mTBI; was there a period of altered mental status. Patients who screened positive were thought to meet a minimum threshold for the evaluation of mTBI. Information about mTBI specific evaluation, management, and education was obtained from the patient’s charts. RESULTS/ANTICIPATED RESULTS: Results: 38,484 patients were screened over 16 weeks, of whom 453 (1.18%) screened positive for a possible mTBI and did not meet exclusion criteria. In total, 198 patients had documented loss of consciousness, 101 were diagnosed with mTBI, and 49 received mTBI discharge instructions. Overall, 32.5% of included patients had mTBI listed in the differential or as a diagnosis and 32.3% with loss of consciousness received a mTBI diagnosis. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Many patients with a possible mTBI were not evaluated, managed, or educated for their potential injury. Changes in physicians’ approach to mTBI must occur to increase the proportion of patients receiving appropriate evaluation, management, and education. These results define the current reality of mTBI treatment in the Emergency Department and show the need for further experimental studies targeted at physician decision support interventions to improve mTBI care.
Childhood-onset attention-deficit hyperactivity disorder (ADHD) in adults is clinically heterogeneous and commonly presents with different patterns of cognitive deficits. It is unclear if this clinical heterogeneity expresses a dimensional or categorical difference in ADHD.
We first studied differences in functional connectivity in multi-echo resting-state functional magnetic resonance imaging (rs-fMRI) acquired from 80 medication-naïve adults with ADHD and 123 matched healthy controls. We then used canonical correlation analysis (CCA) to identify latent relationships between symptoms and patterns of altered functional connectivity (dimensional biotype) in patients. Clustering methods were implemented to test if the individual associations between resting-state brain connectivity and symptoms reflected a non-overlapping categorical biotype.
Adults with ADHD showed stronger functional connectivity compared to healthy controls, predominantly between the default-mode, cingulo-opercular and subcortical networks. CCA identified a single mode of brain–symptom co-variation, corresponding to an ADHD dimensional biotype. This dimensional biotype is characterized by a unique combination of altered connectivity correlating with symptoms of hyperactivity-impulsivity, inattention, and intelligence. Clustering analyses did not support the existence of distinct categorical biotypes of adult ADHD.
Overall, our data advance a novel finding that the reduced functional segregation between default-mode and cognitive control networks supports a clinically important dimensional biotype of childhood-onset adult ADHD. Despite the heterogeneity of its presentation, our work suggests that childhood-onset adult ADHD is a single disorder characterized by dimensional brain–symptom mediators.
Multi-analyte assays with algorithmic analyses (MAAAs) use combinations of circulating and clinical markers including omics-based sources for diagnostic and/or prognostic purposes. Assessing MAAAs is challenging under existing health technology assessment (HTA) methods or practices. We undertook a scoping review to explore the HTA methods used for MAAAs to identify the criteria used for clinical research and reimbursement purposes.
This review included only non-companion (stand-alone) tests that are actionable and that have been evaluated by leading HTA or insurer/reimbursement bodies up to September 2017.
Twenty-five reports and articles evaluating seventeen MAAAs were examined, most of which have been developed in oncology. The two main models used were the EUnetHTA Core model and the Evaluation of Genomic Applications in Practice and Prevention ACCE framework. Clinical validity and utility criteria were used, as were economic, ethical, legal, and social aspects. Economic evidence on MAAAs was scarce, and there is no consensus on whether the perspectives used are sufficiently broad to include all relevant stakeholders.
Clinical utility and efficiency were the most used criteria, with stronger evidence needed linking the use of the algorithm with the clinical outcomes in real-life practice. HTA bodies must as well consider questions related to the analytical validity of MAAAs or with organizational aspects. The two main models, the EUnetHTA Core model and the ACCE framework, could be adapted to the assessment of MAAAs.
We investigate droplet impact on a solid substrate in order to understand the influence of the gas in the splashing dynamics. We use numerical simulations where both the liquid and the gas phases are considered incompressible in order to focus on the gas inertial and viscous contributions. We first confirm that the dominant gas effect on the dynamics is due to its viscosity through the cushioning of the gas layer beneath the droplet. We then describe an additional inertial effect that is directly related to the gas density. The two different splashing mechanisms initially suggested theoretically are observed numerically, depending on whether a jet is created before or after the impacting droplet wets the substrate. Finally, we provide a phase diagram of the drop impact outputs as the gas viscosity and density vary, emphasizing the dominant effect of the gas viscosity with a small correction due to the gas density. Our results also suggest that gas inertia influences the splashing formation through a Kelvin–Helmholtz-like instability of the surface of the impacting droplet, in agreement with former theoretical works.
We consider the problem of gas–liquid flow with phase transition in a porous medium, governed by the buoyancy force. Free gas releases due to continuous pressure decrease. We take into account the gas expansion and the dissolution of chemical components in both phases controlled by the local phase equilibrium. We have developed an asymptotic model of flow for low pressure gradients in the form of a nonlinear hyperbolic system of first order with respect to the liquid saturation and the total flow velocity, which is the extended non-homogeneous Buckley–Leverett model. In two asymptotic cases determined by two different ratios between the characteristic times, this model is completely decoupled from pressure, i.e. the pressure enters in this model as a parameter determined through an independent formula. The segregation problem with phase transition in a bounded domain is solved for two cases of boundary conditions. The saturation behaviour is described in terms of nonlinear kinematic waves, whose evolution follows a complex segregation scenario, which includes the wave reflection and formation of shocks. The macroscopic gas–liquid interfaces are described in terms of shock waves. The comparison with numerical simulations shows satisfactory results.
Two single-nucleotide polymorphisms (SNPs) (rs4281084 and rs12155594) within the neuregulin-1 (NRG1) gene have been associated with psychosis transition. However, the neurobiological changes associated with these SNPs remain unclear. We aimed to determine what relationship these two SNPs have on lateral ventricular volume and white matter integrity, as abnormalities in these brain structures are some of the most consistent in schizophrenia.
Structural (n = 370) and diffusion (n = 465) magnetic resonance imaging data were obtained from affected and unaffected individuals predominantly of European descent. The SNPs rs4281084, rs12155594, and their combined allelic load were examined for their effects on lateral ventricular volume, fractional anisotropy (FA) as well as axial (AD) and radial (RD) diffusivity. Additional exploratory analyses assessed NRG1 effects on gray matter volume, cortical thickness, and surface area throughout the brain.
Individuals with a schizophrenia age of onset ⩽25 and a combined allelic load ⩾3 NRG1 risk alleles had significantly larger right (up to 50%, padj = 0.01) and left (up to 45%, padj = 0.05) lateral ventricle volumes compared with those with allelic loads of less than three. Furthermore, carriers of three or more risk alleles, regardless of age of onset and case status, had significantly reduced FA and elevated RD but stable AD in the frontal cortex compared with those carrying fewer than three risk alleles.
Our findings build on a growing body of research supporting the functional importance of genetic variation within the NRG1 gene and complement previous findings implicating the rs4281084 and rs12155594 SNPs as markers for psychosis transition.
White matter disruptions in schizophrenia have been widely reported, but it remains unclear whether these abnormalities differ between illness stages. We mapped the connectome in patients with recently diagnosed and chronic schizophrenia and investigated the extent and overlap of white matter connectivity disruptions between these illness stages.
Diffusion-weighted magnetic resonance images were acquired in recent-onset (n = 19) and chronic patients (n = 45) with schizophrenia, as well as age-matched controls (n = 87). Whole-brain fiber tracking was performed to quantify the strength of white matter connections. Connections were tested for significant streamline count reductions in recent-onset and chronic groups, relative to separate age-matched controls. Permutation tests were used to assess whether disrupted connections significantly overlapped between chronic and recent-onset patients. Linear regression was performed to test whether connectivity was strongest in controls, weakest in chronic patients, and midway between these extremities in recent-onset patients (controls > recent-onset > chronic).
Compared with controls, chronic patients displayed a widespread network of connectivity disruptions (p < 0.01). In contrast, connectivity reductions were circumscribed to the anterior fibers of the corpus callosum in recent-onset patients (p < 0.01). A significant proportion of disrupted connections in recent-onset patients (86%) coincided with disrupted connections in chronic patients (p < 0.01). Linear regression revealed that chronic patients displayed reduced connectivity relative to controls, while recent-onset patients showed an intermediate reduction compared with chronic patients (p < 0.01).
Connectome pathology in recent-onset patients with schizophrenia is confined to select tracts within a more extensive network of white matter connectivity disruptions found in chronic illness. These findings may suggest a trajectory of progressive deterioration of connectivity in schizophrenia.
We investigate the dynamics of drop impact on a thin liquid film at short times in order to identify the mechanisms of splash formation. Using numerical simulations and scaling analysis, we show that it depends both on the inertial dynamics of the liquid and the cushioning of the gas. Two asymptotic regimes are identified, characterized by a new dimensionless number
: when the gas cushioning is weak, the jet is formed after a sequence of bubbles are entrapped and the jet speed is mostly selected by the Reynolds number of the impact. On the other hand, when the air cushioning is important, the lubrication of the gas beneath the drop and the liquid film controls the dynamics, leading to a single bubble entrapment and a weaker jet velocity.
This article investigates the appearance of instabilities in two planar coflowing fluid sheets with different densities and viscosities via experiments, numerical simulation and linear stability analysis. At low dynamic pressure ratios a convective instability is shown to appear for which the frequency of the waves in the primary atomization region is influenced by both liquid and gas velocities. For large dynamic pressure ratios an asymptotic regime is obtained in which frequency is solely controlled by gas velocity and the instability becomes absolute. The transition from convective to absolute is shown to be influenced by the velocity defect induced by the presence of the separator plate. We show that in this regime the splitter plate thickness can also affect the nature of the instability if it is larger than the gas vorticity thickness. Computational and experimental results are in agreement with the predictions of a spatio-temporal stability analysis.
The present work investigates the influence of bubble clustering on the propagation of shock waves in bubbly liquids. A continuum model is developed to describe the macroscopic response of a bubbly liquid with a cluster structure, using a two-step homogenization technique. The proposed methodology allows us to simulate shock wave propagation over long distances with a small computation time and to study the effect of bubble clustering on the shock structure. It is shown that the typical length of the shock profile is related to the global response of the clusters instead of the single-bubble dynamics, as in homogeneous bubbly flows. The accuracy of the proposed modelling is assessed through comparisons with axisymmetric simulations, in which clusters are directly specified, with given positions and sizes, and with experimental data.