Convective and absolute Eckhaus instability leading to modulated waves in a finite box

We report experimental study of the secondary modulational instability of a one-dimensional non-linear traveling wave in a long bounded channel. Two qualitatively different instability regimes involving fronts of spatio-temporal defects are linked to the convective and absolute nature of the instability. Both transitions appear to be subcritical. The spatio-temporal defects control the global mode structure.Comment: 5 pages, 7 figures (ReVTeX 4 and amsmath.sty), final versio

Schizophrenia-risk and urban birth are associated with proteomic changes in neonatal dried blood spots.

In the present study, we tested whether there were proteomic differences in blood between schizophrenia patients after the initial onset of the disorder and controls; and whether those differences were also present at birth among neonates who later developed schizophrenia compared to those without a psychiatric admission. We used multiple reaction monitoring mass spectrometry to quantify 77 proteins (147 peptides) in serum samples from 60 first-onset drug-naive schizophrenia patients and 77 controls, and 96 proteins (152 peptides) in 892 newborn blood-spot (NBS) samples collected between 1975 and 1985. Both serum and NBS studies showed significant alterations in protein levels. Serum results revealed that Haptoglobin and Plasma protease C1 inhibitor were significantly upregulated in first-onset schizophrenia patients (corrected P < 0.05). Alpha-2-antiplasmin, Complement C4-A and Antithrombin-III were increased in first-onset schizophrenia patients (uncorrected P-values 0.041, 0.036 and 0.013, respectively) and also increased in newborn babies who later develop schizophrenia (P-values 0.0058, 0.013 and 0.044, respectively). We also tested whether protein abundance at birth was associated with exposure to an urban environment during pregnancy and found highly significant proteomic differences at birth between urban and rural environments. The prediction model for urbanicity had excellent predictive performance in both discovery (area under the receiver operating characteristic curve (AUC) = 0.90) and validation (AUC = 0.89) sample sets. We hope that future biomarker studies based on stored NBS samples will identify prognostic disease indicators and targets for preventive measures for neurodevelopmental conditions, particularly those with onset during early childhood, such as autism spectrum disorder

Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis

BACKGROUND: Psychosis is a severe mental condition that is characterized by a loss of contact with reality and is typically associated with hallucinations and delusional beliefs. There are numerous psychiatric conditions that present with psychotic symptoms, most importantly schizophrenia, bipolar affective disorder, and some forms of severe depression referred to as psychotic depression. The pathological mechanisms resulting in psychotic symptoms are not understood, nor is it understood whether the various psychotic illnesses are the result of similar biochemical disturbances. The identification of biological markers (so-called biomarkers) of psychosis is a fundamental step towards a better understanding of the pathogenesis of psychosis and holds the potential for more objective testing methods. METHODS AND FINDINGS: Surface-enhanced laser desorption ionization mass spectrometry was employed to profile proteins and peptides in a total of 179 cerebrospinal fluid samples (58 schizophrenia patients, 16 patients with depression, five patients with obsessive-compulsive disorder, ten patients with Alzheimer disease, and 90 controls). Our results show a highly significant differential distribution of samples from healthy volunteers away from drug-naïve patients with first-onset paranoid schizophrenia. The key alterations were the up-regulation of a 40-amino acid VGF-derived peptide, the down-regulation of transthyretin at approximately 4 kDa, and a peptide cluster at approximately 6,800-7,300 Da (which is likely to be influenced by the doubly charged ions of the transthyretin protein cluster). These schizophrenia-specific protein/peptide changes were replicated in an independent sample set. Both experiments achieved a specificity of 95% and a sensitivity of 80% or 88% in the initial study and in a subsequent validation study, respectively. CONCLUSIONS: Our results suggest that the application of modern proteomics techniques, particularly mass spectrometric approaches, holds the potential to advance the understanding of the biochemical basis of psychiatric disorders and may in turn allow for the development of diagnostics and improved therapeutics. Further studies are required to validate the clinical effectiveness and disease specificity of the identified biomarkers

The Complex Ginzburg-Landau Equation in the Presence of Walls and Corners

We investigate the influence of walls and corners (with Dirichlet and Neumann boundary conditions) in the evolution of twodimensional autooscillating fields described by the complex Ginzburg-Landau equation. Analytical solutions are found, and arguments provided, to show that Dirichlet walls introduce strong selection mechanisms for the wave pattern. Corners between walls provide additional synchronization mechanisms and associated selection criteria. The numerical results fit well with the theoretical predictions in the parameter range studied.Comment: 10 pages, 9 figures; for related work visit http://www.nbi.dk/~martine

Plasma endocannabinoids in cocaine dependence and their relation to cerebral metabotropic glutamate receptor 5 density

Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N = 103; 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N = 92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N = 33; controls: N = 43). In an additional analysis using $^{11}$C-ABP688 positron emission tomography (PET) in a male subsample (CU: N = 18; controls: N = 16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence

CSF Metabolic and Proteomic Profiles in Patients Prodromal for Psychosis

BACKGROUND: The initial prodromal state of psychosis (IPS) is defined as an early disease stage prior to the onset of overt psychosis characterized by sub-threshold or more unspecific psychiatric symptoms. Little is known regarding the biochemical changes during this period. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the metabolic/proteomic profiles of cerebrospinal fluid (CSF) of first-onset drug naïve paranoid schizophrenia patients (n = 54) and individuals presenting with initial prodromal symptoms (n = 24), alongside healthy volunteers (n = 70) using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy and surface enhanced laser desorption ionization (SELDI) mass spectrometry, respectively. Partial least square discriminant analysis (PLS-DA) showed that 36%/29% of IPS patients displayed proteomic/metabolic profiles characteristic of first-onset, drug naïve schizophrenia, i.e., changes in levels of glucose and lactate as well as changes in a VGF-derived peptide (VGF23-62) and transthyretin protein concentrations. However, only 29% (n = 7) of the investigated IPS patients (who to date have been followed up for up to three years) have so far received a diagnosis of schizophrenia. The presence of biochemical alterations in the IPS group did not correlate with the risk to develop schizophrenia. CONCLUSIONS/SIGNIFICANCE: Our results imply that schizophrenia-related biochemical disease processes can be traced in CSF of prodromal patients. However, the biochemical disturbances identified in IPS patients, at least when measured at a single time point, may not be sufficient to predict clinical outcome

Source-Reconstruction of Event-Related Fields Reveals Hyperfunction and Hypofunction of Cortical Circuits in Antipsychotic-Naive, First-Episode Schizophrenia Patients during Mooney Face Processing

Schizophrenia is characterized by dysfunctions in neural circuits that can be investigated with electrophysiological methods, such as EEG and MEG. In the present human study, we examined event-related fields (ERFs), in a sample of medication-naive, first-episode schizophrenia (FE-ScZ) patients (n � 14) and healthy control participants (n � 17) during perception of Mooney faces to investigate the integrity of neuromagnetic responses and their experience-dependent modification. ERF responses were analyzed for M100, M170, and M250components at the sensor and source levels. In addition, we analyzed peak latency and adaptation effects due to stimulus repetition. FE-ScZ patients were characterized by significantly impaired sensory processing, as indicated by a reduced discrimination index (A�). At the sensor level, M100 and M170 responses in FE-ScZ were within the normal range, whereas the M250 response was impaired. However, source localization revealed widespread elevated activity for M100 and M170 in FE-ScZ and delayed peak latencies for the M100 and M250 responses. In addition, M170 source activity in FE-ScZ was not modulated by stimulus repetitions. The present findings suggest that neural circuits in FE-ScZ may be characterized by a disturbed balance between excitation and inhibition that could lead to a failure to gate information flow and abnormal spreading of activity, which is compatible with dysfunctional glutamatergic neurotransmission

Wound-up phase turbulence in the Complex Ginzburg-Landau equation

We consider phase turbulent regimes with nonzero winding number in the one-dimensional Complex Ginzburg-Landau equation. We find that phase turbulent states with winding number larger than a critical one are only transients and decay to states within a range of allowed winding numbers. The analogy with the Eckhaus instability for non-turbulent waves is stressed. The transition from phase to defect turbulence is interpreted as an ergodicity breaking transition which occurs when the range of allowed winding numbers vanishes. We explain the states reached at long times in terms of three basic states, namely quasiperiodic states, frozen turbulence states, and riding turbulence states. Justification and some insight into them is obtained from an analysis of a phase equation for nonzero winding number: rigidly moving solutions of this equation, which correspond to quasiperiodic and frozen turbulence states, are understood in terms of periodic and chaotic solutions of an associated system of ordinary differential equations. A short report of some of our results has been published in [Montagne et al., Phys. Rev. Lett. 77, 267 (1996)].Comment: 22 pages, 15 figures included. Uses subfigure.sty (included) and epsf.tex (not included). Related research in http://www.imedea.uib.es/Nonlinea

Transfer of manualized Short Term Psychodynamic Psychotherapy (STPP) for social phobia into clinical practice: study protocol for a cluster-randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Psychodynamic psychotherapy is frequently applied in the treatment of social phobia. Nevertheless, there has been a lack of studies on the transfer of manualized treatments to routine psychodynamic practice. Our study is the first one to examine the effects of additional training in a manualized Short Term Psychodynamic Psychotherapy (STPP) procedure on outcome in routine psychotherapy for social phobia. This study is an extension to a large multi-site RCT (N = 512) comparing the efficacy of STPP to Cognitive-Behavioral Therapy (CBT) of Social Phobia.</p> <p>Methods/Design</p> <p>The manualized treatment is designed for a time limited approach with 25 individual sessions of STPP over 6 months. Private practitioners will be randomized to training in manualized STPP vs. treatment as usual without a specific training (control condition). We plan to enrol a total of 105 patients (84 completers). Assessments will be conducted before treatment starts, after 8 and 15 weeks, after 25 treatment sessions, at the end of treatment, 6 months and 12 months after termination of treatment. The primary outcome measure is the Liebowitz Social Anxiety Scale. Remission from social phobia is defined scoring with 30 or less points on this scale.</p> <p>Discussion</p> <p>We will investigate how the treatment can be transferred from a controlled trial into the less structured setting of routine clinical care. This question represents Phase IV of psychotherapy research. It combines the benefits of randomized controlled and naturalistic research. The study is genuinely designed to promote faster and more widespread dissemination of effective interventions. It will answer the questions whether manualized STPP can be implemented into routine outpatient care, whether the new methods improve treatment courses and outcomes and whether treatment effects reached in routine psychotherapeutic treatments are comparable to those of the controlled, strictly manualized treatment of the main study.</p> <p>Trial Registration</p> <p>German Clinical Trials Register (DRKS) DRKS00000570</p

Predator Cat Odors Activate Sexual Arousal Pathways in Brains of Toxoplasma gondii Infected Rats

Cat odors induce rapid, innate and stereotyped defensive behaviors in rats at first exposure, a presumed response to the evolutionary pressures of predation. Bizarrely, rats infected with the brain parasite Toxoplasma gondii approach the cat odors they typically avoid. Since the protozoan Toxoplasma requires the cat to sexually reproduce, this change in host behavior is thought to be a remarkable example of a parasite manipulating a mammalian host for its own benefit. Toxoplasma does not influence host response to non-feline predator odor nor does it alter behavior on olfactory, social, fear or anxiety tests, arguing for specific manipulation in the processing of cat odor. We report that Toxoplasma infection alters neural activity in limbic brain areas necessary for innate defensive behavior in response to cat odor. Moreover, Toxoplasma increases activity in nearby limbic regions of sexual attraction when the rat is exposed to cat urine, compelling evidence that Toxoplasma overwhelms the innate fear response by causing, in its stead, a type of sexual attraction to the normally aversive cat odor