A User-Level Process Package for Concurrent Computing

A lightweight user-level process(ULP) package for parallel computing is described. Each ULP has its own register context, stack, data and heap space and communication with other ULPs is performed using locally synchronous, location transparent, message passing primitives. The aim of the package is to provide support for lightweight over-decomposition, optimized local communication and transparent dynamic migration. The package supports a subset of the Parallel Virtual Machine(PVM) interface[Sun90)

Hippocampal volumes in patients with bipolar-schizophrenic spectrum disorders and their unaffected first-degree relatives

BACKGROUND: schizophrenic and bipolar disorders are complex and disabling psychiatric diseases whose classical nosography and classification are still under challenging debate aiming to overcome the traditional “Kraepelinian Dichotomy”. For the past hundred years most clinical work and research in psychiatry has proceeded under the assumption that schizophrenia and bipolar disorderaredistinctentities with separate underlying disease processes and treatments. In more recent years there has been increasing evidence for phenomenological, biological and genetic overlap between the two disorders (Potash and Bienvenu 2009). Nowadays, the categorical approach to psychiatric nosography is in contrast with the recent neurobiological, neuropsychological and genetic findings in affective and schizophrenic disorders. Further, symptoms and signs constituting bipolar and schizophrenic disorders are continuously, not dichotomously, distributed; there may be no point of “real cleavage” (Phelps et al. 2008). This recognition has led some clinicians and researchers to call for a diagnostic model that, moving to a “dimensional perspective”, formally recognizes a continuous spectrum from schizophrenic to bipolar (and recurrent depressive) disorders. Kelsoe argued that the existing data coming from various fields of research in bipolar and schizophrenic disorders may best fit a model in which different set of genes predispose to overlapping phenotypes in a continuum. Given the apparent overlap of regions of the genome implicated in bipolar disorder with those for schizophrenia (Kelsoe 1999; Berrettini 2000), the data suggest the possibility that a common polygenic background predisposes to both bipolar disorder and schizophrenia, according to the so-called “multiple threshold model” (Kelsoe 2003). As highlighted by Craddock and Owen, the recent findings are compatible with a model of functional psychosis in which susceptibility to a spectrum of clinical phenotypes is under the influence of overlapping sets of genes, which, together with environmental and epigenetic factors, determine an individual’s expression of illness (Craddock and Owen 2005). A lot of interest is focusing on brain structural abnormalities in patients suffering from schizophrenia and bipolar disorder. A huge amount of neuroimaging studies has been published so far, however the literature is heterogeneous and there is still some degree of uncertainty concerning what key regions are involved in the pathogenesis of such disorders. Schizophrenia and Bipolar Disorder have a number of overlapping symptoms and risk factors, but it is not yet clear if the disorders are characterized by similar deviations in brain morphometry or whether any such deviations reflect the impact of shared susceptibility genes on brain structure. To date there is no consensus about whether, and to what extent, gray matter loss in Schizophrenia is mirrored in Bipolar Disorder and what is the effect of medication or other confounding factors. Studies in family members of patients, who share the risk of the disease but not the confounding factors, may help elucidate whether abnormalities in brain structures are shared by both illnesses. AIM OF THE STUDY: to investigate hippocampal gray matter volume differences in a group of patients with bipolar-schizophrenic spectrum disorders, a group of their unaffected first-degree relatives, and a group of healthy control subjects. METHODS: a total of 104 subjects - 36 schizophrenic or schizoaffective (SZ), 27 bipolar (BP), 2 major depression, 8 unaffected relatives (UR), and 31 healthy controls (HC) - underwent 1,5 T MRI scanning, with volumetric T1 3D acquisition protocol, at the Neuroradiology Unit of Conegliano Hospital. We calculate bilateral hippocampal gray matter volume (HV) and total cerebral volume (TCV) in a sample of 31 SZ, 27 BP, 8 UR and 26 HC, with a stereological method using ANALYZE 10.0 software. RESULTS: we found statistically significant reductions in bilateral HV in the BP-SZ patients compared to HC; the direct comparison between patient groups identified statistically significant reduction in the right HV of SZ, but no significant differences for left HV or TCV (however statistical significance was lost after normalization); statistically significant reduction in the left HV and a trend towards statistical significance for right HV in the UR compared to HC (a trend towards statistically significant reduction in bilateral HV persisted after normalization). CONCLUSION: it might be speculated that the alterations of the gray matter volume in the hippocampus highlighted in our study could be interpreted as a possible structural “biological marker” in the schizophrenic-bipolar spectrum

The role of neuronavigation in TMS-EEG studies : Current applications and future perspectives

Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) allows measuring noninvasively the electrical response of the human cerebral cortex to a direct perturbation. Complementing TMSEEG with a structural neuronavigation tool (nTMS-EEG) is key for accurately selecting cortical areas, targeting them, and adjusting the stimulation parameters based on some relevant anatomical priors. This step, together with the employment of visualization tools designed to perform a quality check of TMS-evoked potentials (TEPs) in real-time during TMS-EEG data acquisition, is pivotal for maximizing the impact of the TMS pulse on the cortex and in ensuring highly reproducible measurements within sessions and across subjects. Moreover, storing stimulation parameters in the neumnavigation system can help in replicating the stimulation parameters within and across experimental sessions and sharing them across research centers. Finally, the systematic employment of neumnavigation in TMS-EEG studies is also critical to standardize measurements in clinical populations in search for reliable diagnostic and prognostic TMS-EEG-based biomarkers for neurological and psychiatric disorders.Peer reviewe

First-Episode Psychotic Patients Showed Longitudinal Brain Changes Using fMRI With an Emotional Auditory Paradigm

Most previous longitudinal studies of functional magnetic resonance imaging (fMRI) in first-episode psychosis (FEP) using cognitive paradigm task found an increased activation after antipsychotic medications. We designed an emotional auditory paradigm to explore brain activation during emotional and nonemotional word processing. This study aimed to analyze if longitudinal changes in brain fMRI BOLD activation is present in patients vs. healthy controls. A group of FEP patients (n = 34) received clinical assessment and had a fMRI scan at baseline and follow-up (average, 25-month interval). During the fMRI scan, both emotional and nonemotional words were presented as a block design. Results were compared with a pair of healthy control group (n = 13). Patients showed a decreased activation at follow-up fMRI in amygdala (F = 4.69; p = 0.04) and hippocampus (F = 5.03; p = 0.03) compared with controls. Middle frontal gyrus was the only area that showed a substantial increased activation in patients (F = 4.53; p = 0.04). A great heterogeneity in individual activation patterns was also found. These results support the relevance of the type of paradigm in neuroimaging for psychosis. This is, as far as we know, the first longitudinal study with an emotional auditory paradigm in FEP. Our results suggested that the amygdala and hippocampus play a key role in psychotic disease. More studies are needed to understand the heterogeneity of response at individual level

"Innovation and Growth: A Schumpeterian Model of Innovation"

Following Schumpeter we assume that innovation in specific firms, or groups of firms, can have economy-wide effects. Models based on this idea can be shown to have multiple equilibria. The idea of a positive feedback loop innovation system or POLIS is formalized by picking an appropriate sequence of equilibria over time. It is shown that POLIS has empirical relevance by applying the formal model to an actual economy. The 1997-98 financial crisis in many Asian countries, most notably South Korea, seemed to have reversed the conventional wisdom regarding the East Asian miracle". This paper applies the concept of a POLIS to the case of Taiwan to show that at least in this case, neither the view that the miracle was a mirage nor the view that the growth was a result of factor accumulation only is correct. Ultimately technological transformation - in particular the creation of a positive feedback loop innovation system is what makes the difference between sustained growth and gradual or sudden decline. Although various problems remain in both the real and the financial sectors, the successes of Taiwan in building the preconditions for an innovation system are worth examining. Upon careful examination of Taiwan's system of innovation within the above Schumpeterian model it is found that Taiwan has a fighting chance of building a POLIS in the near future. An interesting feature of the Taiwan POLIS is the modular organizational architecture of some of the high technology firms in Hsinchu science-based industrial park and other centers.

Prenatal Immune Challenge Is an Environmental Risk Factor for Brain and Behavior Change Relevant to Schizophrenia: Evidence from MRI in a Mouse Model

Objectives: Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. Method: We used an established mouse model of maternal immune activation (MIA) by the viral mimic Polyl:C administered in early (day 9) or late (day 17) gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. Results: Polyl:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4th ventricle volume but did not disrupt sensorimotor gating. Conclusions: Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life. © 2009 Li et al.published_or_final_versio

DOES DOSE-STAGGERING REDUCE METABOLIC DRUG-DRUG INTERACTION BETWEEN CLOZAPINE AND FLUVOXAMINE IN DOG?

Clozapine, an antipsychotic, and fluvoxamine, an antidepressant, are frequently coadministered in the treatment of schizophrenia. Oral coadministration of clozapine with fluvoxamine in humans results in profound increases in serum concentrations of clozapine due to reversible enzyme inhibition. Dose-staggering is a potential way to reduce drug-drug interactions with orally administered drugs. We hypothesized that staggering doses of clozapine and fluvoxamine twelve hours apart will decrease the extent of interaction between clozapine and its known inhibitor, fluvoxamine, in dog. We used the dog model due to similar metabolic profiles between humans and dogs, and for safety reasons, since doses that are well tolerated in schizophrenic patients may cause serious adverse side effects in healthy volunteers. The principle focus of this research work was to validate a computer simulation model that may predict drug-drug interaction potential. An 1-1-PLC method was developed to quantify clozapine and its two major metabolites, clozapine N-oxide and N-desmethyl clozapine in dog plasma. The pharmacokinetics of clozapine was examined for a single dose (IV and oral) and multiple doses (oral) in dog. A two-phase, crossover design was used to determine if staggering multiple oral doses of clozapine and fluvoxamine twelve hours apart could decrease the extent of this drug-drug interaction. Our HPLC method was fast, simple and demonstrated good recovery rates for clozapine and N-desmethyl clozapine. The average half-life, elimination rate constant, volume of distribution, and systemic clearance of clozapine in dog calculated from a single IV bolus dose (1 mg/kg) were 11.2 h (±2.9), 0.067 WI (±0.022), 115 L (±32), and 7.54 L/h (±2.21). The average half-life, elimination rate constant, and oral clearance of clozapine in dog calculated from a single oral dose (5 mg/kg) were 18.5 h (±14.7), 0.081 III (±0.065), and 43.51 L/h (±3.06). The average AUC TO value of clozapine between the simultaneous condition (AUC r o = 757 +181 µg x h/L) and the staggered condition (AUC To = 573 ±72 µg x h/L) approached significance (p = 0.05). Dose-staggering did not appear to decrease the extent of the drug-drug interaction between clozapine and fluvoxamine in dog. The prediction of the computer simulation model could not be confirmed