Abnormalities in the processing of emotional prosody from single words in schizophrenia

Background: Abnormalities in emotional prosody processing have been consistently reported in schizophrenia and are related to poor social outcomes. However, the role of stimulus complexity in abnormal emotional prosody processing is still unclear. Method: We recorded event-related potentials in 16 patients with chronic schizophrenia and 16 healthy controls to investigate: 1) the temporal course of emotional prosody processing; and 2) the relative contribution of prosodic and semantic cues in emotional prosody processing. Stimuli were prosodic single words presented in two conditions: with intelligible (semantic content condition—SCC) and unintelligible semantic content (pure prosody condition—PPC). Results: Relative to healthy controls, schizophrenia patients showed reduced P50 for happy PPC words, and reduced N100 for both neutral and emotional SCC words and for neutral PPC stimuli. Also, increased P200 was observed in schizophrenia for happy prosody in SCC only. Behavioral results revealed higher error rates in schizophrenia for angry prosody in SCC and for happy prosody in PPC. Conclusions: Together, these data further demonstrate the interactions between abnormal sensory processes and higher-order processes in bringing about emotional prosody processing dysfunction in schizophrenia. They further suggest that impaired emotional prosody processing is dependent on stimulus complexity.

Prognostic value of technetium-99m-labeled single-photon emission computerized tomography in the follow-up of patients after their first myocardial revascularization surgery

OBJECTIVE: To assess the prognostic value of Technetium-99m-labeled single-photon emission computerized tomography (SPECT) in the follow-up of patients who had undergone their first myocardial revascularization. METHODS: We carried out a retrospective study of 280 revascularized patients undergoing myocardial scintigraphy under stress (exercise or pharmacological stress with dipyridamole) and at rest according to a 2-day protocol. A set of clinical, stress electrocardiographic and scintigraphic variables was assessed. Cardiac events were classified as "major" (death, infarction, unstable angina) and "any" (major event or coronary angioplasty or new myocardial revascularization surgery). RESULTS: Thirty-six major events occurred as follows: 3 deaths, 11 infarctions, and 22 unstable anginas. In regard to any event, 22 angioplasties and 7 new surgeries occurred in addition to major events, resulting a total of 65 events. The sensitivity of scintigraphy in prognosticating a major event or any event was, respectively, 55% and 58%, showing a negative predictive value of 90% and 83%, respectively. Diabetes mellitus, inconclusive stress electrocardiography, and a scintigraphic visualization of left ventricular enlargement were significant variables for the occurrence of a major event. On multivariate analysis, abnormal myocardial scintigraphy was a predictor of any event. CONCLUSION: Myocardial perfusion tomography with Technetium-99m may be used to identify high-risk patients after their first myocardial revascularization surgery.

Comparison of immediate results and follow-up of patients with single-vessel and multivessel coronary artery disease younger than 50 years of age undergoing coronary stent implantation

OBJECTIVE: To assess the in-hospital results and clinical follow-up of young patients (< 50 years) with multivessel coronary artery disease undergoing stent implantation in native coronary arteries and to compare their results with those of patients with single-vessel coronary artery disease. METHODS: We retrospectively studied 462 patients undergoing coronary stent implantation. Patients were divided into 2 groups: group I (G-I) - 388 (84%) patients with single-vessel coronary artery disease; and group II (G-II) - 74 (16%) patients with multivessel coronary artery disease. RESULTS: The mean age of the patients was 45±4.9 years, and the clinical findings at presentation and demographic data were similar in both groups. The rate of clinical success was 95% in G-I and 95.8% in G-II (P=0.96), with no difference in regard to in-hospital evolution between the groups. Death, acute myocardial infarction, and the need for myocardial revascularization during clinical follow-up occurred in 10.1% and 11.2% (P=0.92) in G-I and G-II, respectively. By the end of 24 months, the actuarial analysis showed an event-free survival of 84.6 % in G-I and 81.1% in G-II (P=0.57). CONCLUSION: Percutaneous treatment with coronary stent implantation in young patients with multivessel disease may be safe with a high rate of clinical success, a low incidence of in-hospital complications, and a favorable evolution in clinical follow-up.

The role of the right parietal cortex in sound localization: a chronometric single pulse transcranial magnetic stimulation study.

Auditory spatial functions, including the ability to discriminate between the positions of nearby sound sources, are subserved by a large temporo-parieto-frontal network. With the aim of determining whether and when the parietal contribution is critical for auditory spatial discrimination, we applied single pulse transcranial magnetic stimulation on the right parietal cortex 20, 80, 90 and 150 ms post-stimulus onset while participants completed a two-alternative forced choice auditory spatial discrimination task in the left or right hemispace. Our results reveal that transient TMS disruption of right parietal activity impairs spatial discrimination when applied at 20 ms post-stimulus onset for sounds presented in the left (controlateral) hemispace and at 80 ms for sounds presented in the right hemispace. We interpret our finding in terms of a critical role for controlateral temporo-parietal cortices over initial stages of the building-up of auditory spatial representation and for a right hemispheric specialization in integrating the whole auditory space over subsequent, higher-order processing stages.

Analyzing the effects of transient faults into applications

As computer chips implementation technologies evolve to obtain more performance, those computer chips are using smaller components, with bigger density of transistors and working with lower power voltages. All these factors turn the computer chips less robust and increase the probability of a transient fault. Transient faults may occur once and never more happen the same way in a computer system lifetime. There are distinct consequences when a transient fault occurs: the operating system might abort the execution if the change produced by the fault is detected by bad behavior of the application, but the biggest risk is that the fault produces an undetected data corruption that modifies the application final result without warnings (for example a bit flip in some crucial data). With the objective of researching transient faults in computer system’s processor registers and memory we have developed an extension of HP’s and AMD joint full system simulation environment, named COTSon. This extension allows the injection of faults that change a single bit in processor registers and memory of the simulated computer. The developed fault injection system makes it possible to: evaluate the effects of single bit flip transient faults in an application, analyze an application robustness against single bit flip transient faults and validate fault detection mechanism and strategies.

Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort.

BACKGROUND: Superinfection with drug resistant HIV strains could potentially contribute to compromised therapy in patients initially infected with drug-sensitive virus and receiving antiretroviral therapy. To investigate the importance of this potential route to drug resistance, we developed a bioinformatics pipeline to detect superinfection from routinely collected genotyping data, and assessed whether superinfection contributed to increased drug resistance in a large European cohort of viremic, drug treated patients. METHODS: We used sequence data from routine genotypic tests spanning the protease and partial reverse transcriptase regions in the Virolab and EuResist databases that collated data from five European countries. Superinfection was indicated when sequences of a patient failed to cluster together in phylogenetic trees constructed with selected sets of control sequences. A subset of the indicated cases was validated by re-sequencing pol and env regions from the original samples. RESULTS: 4425 patients had at least two sequences in the database, with a total of 13816 distinct sequence entries (of which 86% belonged to subtype B). We identified 107 patients with phylogenetic evidence for superinfection. In 14 of these cases, we analyzed newly amplified sequences from the original samples for validation purposes: only 2 cases were verified as superinfections in the repeated analyses, the other 12 cases turned out to involve sample or sequence misidentification. Resistance to drugs used at the time of strain replacement did not change in these two patients. A third case could not be validated by re-sequencing, but was supported as superinfection by an intermediate sequence with high degenerate base pair count within the time frame of strain switching. Drug resistance increased in this single patient. CONCLUSIONS: Routine genotyping data are informative for the detection of HIV superinfection; however, most cases of non-monophyletic clustering in patient phylogenies arise from sample or sequence mix-up rather than from superinfection, which emphasizes the importance of validation. Non-transient superinfection was rare in our mainly treatment experienced cohort, and we found a single case of possible transmitted drug resistance by this route. We therefore conclude that in our large cohort, superinfection with drug resistant HIV did not compromise the efficiency of antiretroviral treatment.

Variability of North Atlantic hurricanes: seasonal versus individual-event features

Tropical cyclones are affected by a large number of climatic factors, which translates into complex patterns of occurrence. The variability of annual metrics of tropical-cyclone activity has been intensively studied, in particular since the sudden activation of the North Atlantic in the mid 1990’s. We provide first a swift overview on previous work by diverse authors about these annual metrics for the North-Atlantic basin, where the natural variability of the phenomenon, the existence of trends, the drawbacks of the records, and the influence of global warming have been the subject of interesting debates. Next, we present an alternative approach that does not focus on seasonal features but on the characteristics of single events [Corral et al., Nature Phys. 6, 693 (2010)]. It is argued that the individual-storm power dissipation index (PDI) constitutes a natural way to describe each event, and further, that the PDI statistics yields a robust law for the occurrence of tropical cyclones in terms of a power law. In this context, methods of fitting these distributions are discussed. As an important extension to this work we introduce a distribution function that models the whole range of the PDI density (excluding incompleteness effects at the smallest values), the gamma distribution, consisting in a powerlaw with an exponential decay at the tail. The characteristic scale of this decay, represented by the cutoff parameter, provides very valuable information on the finiteness size of the basin, via the largest values of the PDIs that the basin can sustain. We use the gamma fit to evaluate the influence of sea surface temperature (SST) on the occurrence of extreme PDI values, for which we find an increase around 50 % in the values of these basin-wide events for a 0.49 C SST average difference. Similar findings are observed for the effects of the positive phase of the Atlantic multidecadal oscillation and the number of hurricanes in a season on the PDI distribution. In the case of the El Niño Southern oscillation (ENSO), positive and negative values of the multivariate ENSO index do not have a significant effect on the PDI distribution; however, when only extreme values of the index are used, it is found that the presence of El Niño decreases the PDI of the most extreme hurricanes.

Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98.

PURPOSE: We report the long-term results of a randomized clinical trial comparing induction therapy with once per week for 4 weeks single-agent rituximab alone versus induction followed by 4 cycles of maintenance therapy every 2 months in patients with follicular lymphoma. PATIENTS AND METHODS: Patients (prior chemotherapy 138; chemotherapy-naive 64) received single-agent rituximab and if nonprogressive, were randomly assigned to no further treatment (observation) or four additional doses of rituximab given at 2-month intervals (prolonged exposure). RESULTS: At a median follow-up of 9.5 years and with all living patients having been observed for at least 5 years, the median event-free survival (EFS) was 13 months for the observation and 24 months for the prolonged exposure arm (P < .001). In the observation arm, patients without events at 8 years were 5%, while in the prolonged exposure arm they were 27%. Of previously untreated patients receiving prolonged treatment after responding to rituximab induction, at 8 years 45% were still without event. The only favorable prognostic factor for EFS in a multivariate Cox regression was the prolonged rituximab schedule (hazard ratio, 0.59; 95% CI, 0.39 to 0.88; P = .009), whereas being chemotherapy naive, presenting with stage lower than IV, and showing a VV phenotype at position 158 of the Fc-gamma RIIIA receptor were not of independent prognostic value. No long-term toxicity potentially due to rituximab was observed. CONCLUSION: An important proportion of patients experienced long-term remission after prolonged exposure to rituximab, particularly if they had no prior treatment and responded to rituximab induction.

Long-term follow-up of follicular lymphoma (FL) patients receiving single agent rituximab at two different schedules in trial SAKK 35/98

Background: In FL, Rituximab as a single agent delivered in the standard schedule (4 times weekly) may induce a response rate of 50−70% with an event-free survival (EFS) of 1−3 years according to patients' characteristics. Prolonged Rituximab exposure seems to improve EFS at least in responding patients and to increase the rate of longterm responders. Here we report long-term results of a clinical trial comparing single agent Rituximab delivered in the standard schedule versus prolonged exposure, with focus on the proportion of long-term responders and their characteristics. Material and Methods: Between 1998 and 2002, chemotherapy na¨ıve (n = 64) or pre-treated (n = 138) FL patients received Rituximab in the standard schedule. Those responding or with stable disease were randomized to no further treatment (observation, n = 78) or 4 additional doses of Rituximab given at 2-month intervals (prolonged exposure, n = 73). EFS was calculated from the first dose of standard schedule until progression, relapse, second tumor or death. Results: At a median follow up of 9.4 years and with all living patients having been followed for at least 5 years, the median EFS is 13 months for the observation and 24 months for the prolonged exposure arm (p = 0.0007). In the observation arm 13% had no event at 5-years and only 4% at 8 years, while in the prolonged exposure arm it was 27% at 5 years and remained 21% at 8 years. The only significant prognostic factor for EFS in a multivariate Cox regression was the prolonged Rituximab schedule (hazard ratio 0.58, CI 0.39−0.86, p = 0.007), whereas being chemotherapy na¨ıve, presenting with stage

Genotyping of human parvovirus B19 in clinical samples from Brazil and Paraguay using heteroduplex mobility assay, single-stranded conformation polymorphism and nucleotide sequencing

Heteroduplex mobility assay, single-stranded conformation polymorphism and nucleotide sequencing were utilised to genotype human parvovirus B19 samples from Brazil and Paraguay. Ninety-seven serum samples were collected from individuals presenting with abortion or erythema infectiosum, arthropathies, severe anaemia and transient aplastic crisis; two additional skin samples were collected by biopsy. After the procedure, all clinical samples were classified as genotype 1.

Long-term prognostic value of single-photon emission computed tomography myocardial perfusion imaging in diabetic patients with and without coronary artery disease

Keywords Diabetes mellitus; coronary artery disease; myocardial ischemia; prognostic value; single-photon emission computed tomography myocardial perfusion imaging Summary Aim: To determine the long-term prognostic value of SPECT myocardial perfusion imaging (MPI) for the occurrence of cardiovascular events in diabetic patients. Methods: SPECT MPI of 210 consecutive Caucasian diabetic patients were analysed using Kaplan-Meier event-free survival curves and independent predictors were determined by Cox multivariate analyses. Results: Follow-up was complete in 200 (95%) patients with a median period of 3.0 years (0.8-5.0). The population was composed of 114 (57%) men, age 65±10 years, 181 (90.5%) type 2 diabetes mellitus, 50 (25%) with a history of coronary artery disease (CAD) and 98 (49%) presenting chest pain prior to MPI. The prevalence of abnormal MPI was 58%. Patients with a normal MPI had neither cardiac death, nor myocardial infarction, independently of a history of coronary artery disease or chest pain. Among the independent predictors of cardiac death and myocardial infarction, the strongest was abnormal MPI (p<.0001), followed by history of CAD (Hazard Ratio (HR)= t 5.9, p=0.0001), diabetic retinopathy (HR=10.0, p=0.001) and inability to exercise (HR=7.7, p=0.02). Patients with normal 1VIPI had a low revascularisation rate of 2.4% during the follow-up period. Compared to normal MPI, cardiovascular events increased 5.2 fold for reversible defects, 8.5 fold for fixed defects and 20.1 fold for the association of both defects. Conclusion: Diabetic patients with normal MPI had an excellent prognosis independently of history of CAD. On the opposite, an abnormal MPI led to a > 5 fold increase in cardiovascular events. This emphasizes the value of SPECT MPI in predicting and risk-stratifying cardiovascular events in diabetic patients. Mots-Clés Diabète; maladie coronarienne; ischémie myocardique; valeur pronostique; tomoscintigraphie myocardique de perfusion par émission monophotonique Résumé Objectifs: Déterminer la valeur pronostique à long terme de la tomoscintigraphie myocardique de perfusion (TSMP) chez les patients diabétiques pour prédire les événements cardiovasculaires (ECV). Méthodes: Etude de 210 diabétiques caucasiens consécutifs référés pour une TSMP. Les courbes de survie ont été déterminées par Kaplan-Meier et les facteurs prédictifs indépendants par analyses multivariées de type Cox. Résultats: Le suivi a été complet chez 200 (95%) patients avec une durée médiane de 3.0 ans (0.8-50). La population était composée de 114 (57%) hommes, âge moyen 65±10 ans, avec 181 (90.5%) diabète de type 2, 50 (25%) antécédents de maladie coronarienne (AMC) et 98 (49%) patients connus pour un angor avant la TSMP. La prévalence de TSMP anormales était de 58%. Aucun décès d'origine cardiaque ou infarctus du myocarde n'est survenu chez les patients avec une TSMP normale, ceci indépendamment de leurs AMC et des douleurs thoraciques. Les facteurs prédictifs indépendants pour les ECV sont une TSMP anormale (p<.0001), les AMC (Hazard Ratio (HR)=15.9, p-0.0001), suivi de la rétinopathie diabétique (HR-10.0, p=0.001) et de l'incapacité à effectuer un exercice (HR=7.7, p=0.02). Les patients avec une TSMP normale ont présenté un taux de revascularisations de 2.4%. La présence de défauts mixtes accroît le risque d'ECV de 20.1 fois, les défauts fixes de 8.5 fois et les défauts réversibles de 5.2 fois comparés aux sujets avec une TSMP normale. Conclusion: Les patients diabétiques, coronariens ou non, avec une tomoscintigraphie myocardique de perfusion normale ont un excellent pronostique. A l'opposé, une TSMP anormale est associée à une augmentation du risque d'ECV de plus de 5 fois. Ceci confirme l'utilité de la TSMP dans la stratification du risque chez les patients diabétiques.

Imputation in data fusion of heterogeneous data sets a model-based numerical experiment

Given the very large amount of data obtained everyday through population surveys, much of the new research again could use this information instead of collecting new samples. Unfortunately, relevant data are often disseminated into different files obtained through different sampling designs. Data fusion is a set of methods used to combine information from different sources into a single dataset. In this article, we are interested in a specific problem: the fusion of two data files, one of which being quite small. We propose a model-based procedure combining a logistic regression with an Expectation-Maximization algorithm. Results show that despite the lack of data, this procedure can perform better than standard matching procedures.

Real-life versus package insert: a post-marketing study on adverse-event rates of the virosomal hepatitis A vaccine Epaxal® in healthy travellers.

There are various methods to collect adverse events (AEs) in clinical trials. The methods how AEs are collected in vaccine trials is of special interest: solicited reporting can lead to over-reporting events that have little or no biological relationship to the vaccine. We assessed the rate of AEs listed in the package insert for the virosomal hepatitis A vaccine Epaxal(®), comparing data collected by solicited or unsolicited self-reporting. In an open, multi-centre post-marketing study, 2675 healthy travellers received single doses of vaccine administered intramuscularly. AEs were recorded based on solicited and unsolicited questioning during a four-day period after vaccination. A total of 2541 questionnaires could be evaluated (95.0% return rate). Solicited self-reporting resulted in significantly higher (p<0.0001) rates of subjects with AEs than unsolicited reporting, both at baseline (18.9% solicited versus 2.1% unsolicited systemic AEs) and following immunization (29.6% versus 19.3% local AEs; 33.8% versus 18.2% systemic AEs). This could indicate that actual reporting rates of AEs with Epaxal(®) may be substantially lower than described in the package insert. The distribution of AEs differed significantly between the applied methods of collecting AEs. The most common AEs listed in the package insert were reported almost exclusively with solicited questioning. The reporting of local AEs was more likely than that of systemic AEs to be influenced by subjects' sex, age and study centre. Women reported higher rates of AEs than men. The results highlight the need for detailing the methods how vaccine tolerability was reported and assessed.

A phase 1b study of humanized KS-interleukin-2 (huKS-IL2) immunocytokine with cyclophosphamide in patients with EpCAM-positive advanced solid tumors.

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent. METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated. RESULTS: Twenty-seven patients were treated for up to 6 cycles; 26 were evaluable for response. The MTD of huKS-IL2 in combination with 300 mg/m2 cyclophosphamide was 3.0 mg/m2. At higher doses, myelosuppression was dose-limiting. Transient lymphopenia was the most common grade 3/4 adverse event (AE). Other significant AEs included hypotension, hypophosphatemia, and increase in serum creatinine. All patients recovered from these AEs. The huKS-IL2 exposure was dose-dependent, but not dose-proportional, accumulation was negligible, and elimination half-life and systemic clearance were independent of dose and time. Most patients had a transient immune response to huKS-IL2. Immunologic activity was observed at all doses. Ten patients (38%) had stable disease as best response, lasting for ≥ 4 cycles in 3 patients. CONCLUSION: The combination of huKS-IL2 with low-dose cyclophosphamide was well tolerated. Although no objective responses were observed, the combination showed evidence of immunologic activity and 3 patients showed stable disease for ≥ 4 cycles. TRIAL REGISTRATION: http://NCT00132522.

Fusion of data sets in multivariate linear regression with errors-in-variables

We consider the application of normal theory methods to the estimation and testing of a general type of multivariate regressionmodels with errors--in--variables, in the case where various data setsare merged into a single analysis and the observable variables deviatepossibly from normality. The various samples to be merged can differ on the set of observable variables available. We show that there is a convenient way to parameterize the model so that, despite the possiblenon--normality of the data, normal--theory methods yield correct inferencesfor the parameters of interest and for the goodness--of--fit test. Thetheory described encompasses both the functional and structural modelcases, and can be implemented using standard software for structuralequations models, such as LISREL, EQS, LISCOMP, among others. An illustration with Monte Carlo data is presented.