Altered resting-state EEG source functional connectivity in schizophrenia:the effect of illness duration

Despite the increasing body of evidence supporting the hypothesis of schizophrenia as a disconnection syndrome, studies of resting-state EEG Source Functional Connectivity (EEG-SFC) in people affected by schizophrenia are sparse. The aim of the present study was to investigate resting-state EEG-SFC in 77 stable, medicated patients with schizophrenia (SCZ) compared to 78 healthy volunteers (HV). In order to study the effect of illness duration, SCZ were divided in those with a short duration of disease (SDD; n = 25) and those with a long duration of disease (LDD; n = 52). Resting-state EEG recordings in eyes closed condition were analyzed and lagged phase synchronization (LPS) indices were calculated for each ROI pair in the source-space EEG data. In delta and theta bands, SCZ had greater EEG-SFC than HV; a higher theta band connectivity in frontal regions was observed in LDD compared with SDD. In the alpha band, SCZ showed lower frontal EEG-SFC compared with HV whereas no differences were found between LDD and SDD. In the beta1 band, SCZ had greater EEG-SFC compared with HVs and in the beta2 band, LDD presented lower frontal and parieto-temporal EEG-SFC compared with HV. In the gamma band, SDD had greater connectivity values compared with LDD and HV. This study suggests that resting state brain network connectivity is abnormally organized in schizophrenia, with different patterns for the different EEG frequency components and that EEG can be a powerful tool to further elucidate the complexity of such disordered connectivity.

Approximate Model Checking of Real-Time Systems for Linear Duration Invariants

Real-time systems are usually modelled with timed automata and real-time requirements relating to the state durations of the system are often specifiable using Linear Duration Invariants, which is a decidable subclass of Duration Calculus formulas. Various algorithms have been developed to check timed automata or real-time automata for linear duration invariants, but each needs complicated preprocessing and exponential calculation. To the best of our knowledge, these algorithms have not been implemented. In this paper, we present an approximate model checking technique based on a genetic algorithm to check real-time automata for linear durration invariants in reasonable times. Genetic algorithm is a good optimization method when a problem needs massive computation and it works particularly well in our case because the fitness function which is derived from the linear duration invariant is linear. ACM Computing Classification System (1998): D.2.4, C.3.

Spectral width and pulse duration tuning in Yb+ modelocked fiber laser with birefringent Lyot filter

A method of pulse duration and spectral width control in all-fiber Ytterbium modelocked laser with SWCNT is presented. It is shown that PM-fiber can also serve as a spectrally selective filter. © 2012 OSA.

Neural activity during object perception in schizophrenia patients is associated with illness duration and affective symptoms

Background - Abnormalities in visual processes have been observed in schizophrenia patients and have been associated with alteration of the lateral occipital complex and visual cortex. However, the relationship of these abnormalities with clinical symptomatology is largely unknown. Methods - We investigated the brain activity associated with object perception in schizophrenia. Pictures of common objects were presented to 26 healthy participants (age = 36.9; 11 females) and 20 schizophrenia patients (age = 39.9; 8 females) in an fMRI study. Results - In the healthy sample the presentation of pictures yielded significant activation (pFWE (cluster) < 0.001) of the bilateral fusiform gyrus, bilateral lingual gyrus, and bilateral middle occipital gyrus. In patients, the bilateral fusiform gyrus and bilateral lingual gyrus were significantly activated (pFWE (cluster) < 0.001), but not so the middle occipital gyrus. However, significant bilateral activation of the middle occipital gyrus (pFWE (cluster) < 0.05) was revealed when illness duration was controlled for. Depression was significantly associated with increased activation, and anxiety with decreased activation, of the right middle occipital gyrus and several other brain areas in the patient group. No association with positive or negative symptoms was revealed. Conclusions - Illness duration accounts for the weak activation of the middle occipital gyrus in patients during picture presentation. Affective symptoms, but not positive or negative symptoms, influence the activation of the right middle occipital gyrus and other brain areas.

Duration of a flood along a plant diversity gradient in the Jena Experiment (Main Experiment, June 2013)

The Jena Biodiversity Experiment is located on a Central European mesophilic floodplain on the banks of the Saale River (see further details below). In the main experiment, 82 grassland plots of 20 x 20 m were established from a pool of 60 species belonging to four functional groups (grasses, legumes, tall and small herbs). In May 2002, varying numbers of plant species from this species pool were sown in the plots to create a gradient of plant species richness (1, 2, 4, 8, 16 and 60 species) and functional richness (1, 2, 3, or 4 functional groups). Plots were maintained by bi-annual weeding and mowing. In June 2013, a natural 200-year flood event occurred at the field site. Rainfall in May 2013 in Jena was ~150mm, constituting >25% of annual precipitation at the site that year. Overall the flood affected the entire Elbe River Basin and much of Europe and was one of the largest natural flooding events in the past two centuries. The flood lasted for a total of 24 days at the site (30 May-24 June) and led to anaerobic soil conditions. Due to small topographical differences among the plots in the experiment (<1m), there was variation in the duration of flooding and the proportion of each plot that was flooded. This variation was well-distributed across the diversity gradient. To assess the importance of flood severity, the proportion of each plot that was flooded was estimated by eye (using five classes: 0 completely dry, 0.25 up to a quarter under water, 0.5 half, 0.75 up to three quarters under water, and 1 more than three quarters under water up to completely submerged). These values, for each of the 24 days that the flood lasted, were summed up to calculate a flooding index. The resulting flooding index is given for each plot of the Main Experiment.

Overweight duration in older adults and cancer risk: a study of cohorts in Europe and the United States

Recent studies have shown that cancer risk related to overweight and obesity is mediated by time and might be better approximated by using life years lived with excess weight. In this study we aimed to assess the impact of overweight duration and intensity in older adults on the risk of developing different forms of cancer. Study participants from seven European and one US cohort study with two or more weight assessments during follow-up were included (n = 329,576). Trajectories of body mass index (BMI) across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25) and cumulative weighted overweight years were calculated. In multivariate Cox models and random effects analyses, a longer duration of overweight was significantly associated with the incidence of obesity-related cancer [overall hazard ratio (HR) per 10-year increment: 1.36; 95 % CI 1.12-1.60], but also increased the risk of postmenopausal breast and colorectal cancer. Additionally accounting for the degree of overweight further increased the risk of obesity-related cancer. Risks associated with a longer overweight duration were higher in men than in women and were attenuated by smoking. For postmenopausal breast cancer, increased risks were confined to women who never used hormone therapy. Overall, 8.4 % of all obesity-related cancers could be attributed to overweight at any age. These findings provide further insights into the role of overweight duration in the etiology of cancer and indicate that weight control is relevant at all ages. This knowledge is vital for the development of effective and targeted cancer prevention strategies.

Functional analysis of the ATM-p53-p21 pathway in the LRF CLL4 trial: blockade at the level of p21 is associated with short response duration.

PURPOSE: This study sought to establish whether functional analysis of the ATM-p53-p21 pathway adds to the information provided by currently available prognostic factors in patients with chronic lymphocytic leukemia (CLL) requiring frontline chemotherapy. EXPERIMENTAL DESIGN: Cryopreserved blood mononuclear cells from 278 patients entering the LRF CLL4 trial comparing chlorambucil, fludarabine, and fludarabine plus cyclophosphamide were analyzed for ATM-p53-p21 pathway defects using an ex vivo functional assay that uses ionizing radiation to activate ATM and flow cytometry to measure upregulation of p53 and p21 proteins. Clinical endpoints were compared between groups of patients defined by their pathway status. RESULTS: ATM-p53-p21 pathway defects of four different types (A, B, C, and D) were identified in 194 of 278 (70%) samples. The type A defect (high constitutive p53 expression combined with impaired p21 upregulation) and the type C defect (impaired p21 upregulation despite an intact p53 response) were each associated with short progression-free survival. The type A defect was associated with chemoresistance, whereas the type C defect was associated with early relapse. As expected, the type A defect was strongly associated with TP53 deletion/mutation. In contrast, the type C defect was not associated with any of the other prognostic factors examined, including TP53/ATM deletion, TP53 mutation, and IGHV mutational status. Detection of the type C defect added to the prognostic information provided by TP53/ATM deletion, TP53 mutation, and IGHV status. CONCLUSION: Our findings implicate blockade of the ATM-p53-p21 pathway at the level of p21 as a hitherto unrecognized determinant of early disease recurrence following successful cytoreduction.

Compared with specialist registrars, experienced staff nurses shorten the duration of weaning neonates from mechanical ventilation

OBJECTIVE: To compare the overall performance of specially trained neonatal nurses acting autonomously, unsupervised, and without a protocol with specialist registrars when weaning neonates from mechanical ventilation.

DESIGN: Prospective, randomized, controlled trial.

SETTING: A single neonatal intensive care unit.

PATIENTS: Neonates requiring conventional mechanical ventilation (n = 50).

INTERVENTIONS: Infants on conventional ventilation were randomly assigned to receive either nurse-led (n = 25) or registrar-led (n = 23) weaning. A total of 48 infants completed the study (two infants in the registrar group were excluded when their parents withdrew consent).

MEASUREMENTS AND MAIN RESULTS: The main outcome measure, median weaning time, was 1200 mins (95% confidence interval [CI], 621-1779 mins) in the nurse group and 3015 mins (95% CI, 2650-3380 mins) in the registrar group (p = .0458). The median time from treatment assignment to the first ventilator change was 60 mins (95% CI, 52-68 mins) in the nurse group and 120 mins (95% CI, 103-137 mins) in the registrar group (p = .35). On average, the nurses made ventilator changes every 4.5 hrs (95% CI, 2.9-6 hrs) and the registrars every 7.2 hrs (95% CI, 5.4-9 hrs; p = .003). The median number (range) of backward steps taken per infant was 0 (0-5 steps) in the nurse group and 1 (0-5 steps) in the registrar group (p = .019).

CONCLUSIONS: The findings of this study suggest that additional domains of neonatal critical care could be reviewed for their potential transfer to appropriately prepared nurses.

Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU):A randomised, double-blind, placebo-controlled trial

Background: Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. Methods: We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5 mg or 0·9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings: 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0·53). The most common adverse events were oversedation (11 patients in the haloperidol group vs six in the placebo group) and QTc prolongation (seven patients in the haloperidol group vs six in the placebo group). No patient had a serious adverse event related to the study drug. Interpretation: These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for short-term management of acute agitation. Funding: National Institute for Health Research. © 2013 Elsevier Ltd.