Schizophrenia remains a challenging illness to treat despite considerable progress. The heterogeneity of symptoms and variability in course, outcome, and treatment response lead to considerable ...uncertainties in treatment guidelines. One of the most challenging issues is how to determine the need for and duration of the maintenance treatment that is intended to reduce the risk of exacerbation, relapse, and hospitalization. It is clear that in large populations, antipsychotic medication is very effective in reducing those risks, however, there is likely a subpopulation of patients with diminished risk for such outcomes even when medication is discontinued. Although attempts have been made to utilize “intermittent” or “targeted” treatment, those randomized controlled trials that have been conducted show a statistically significant advantage for continuous treatment. At the same time, many patients continue to receive higher than necessary doses of antipsychotic medication and practice needs to be reevaluated in terms of dosage requirements. The challenge remains that there are no good biomarkers or predictors of who is at risk and, therefore, dosage reduction is only titrated against exacerbation or relapse. We need to proactively reconsider who requires maintenance treatment by establishing predictive biomarkers (clinical or biological) that can help us to have a more personalized approach.
Disclosure
Consultant to or receives honoraria: Alkermes, Allergan, Dainippon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen Pharmaceutical, Johnson & Johnson, LB Pharmaceuticals, Merck, Minerva, Neurocrine, Novartis Pharmaceuticals,
For normal functioning, the brain requires an adequate supply of blood. The components of normal brain vasculature are collectively referred to as the neurovascular unit. When the brain develops ...pathology, the structural and functional components of brain vasculature become compromised. This is evidenced in the case of neoplasia where the integrity of the vasculature is co-opted to further the neoplastic processes that require exponential blood resupply in order to facilitate the diffusion radius of tumor growth. Glioblastoma changes the brain vasculature in such a way that advances the tumor’s progress while making it more resistant to standard modes of treatment. While the brain vasculature is changed as a result of glioblastoma growth and progression, it is also changed to advance the invasiveness of the tumor. The diagnostic criteria for glioblastoma is correlated with advanced neovascularization processes that change the previously existing vasculature into that which is morphologically atypical and in a dysfunctional state. Advancing therapies to treat glioblastoma must understand normal brain vasculature and how it is changed as a result of tumor growth.
Control balance theory (CBT) is a control-based theory of deviant behavior When imbalances in control between an individual and their environment exist, deviant behavior can occur. However, ...sufficient violation motivation and the facilitating conditions must exist. Past research has shown that technology itself often provides the means for deviant behavior among organizational employees. Presently, research on employee deviance using technology is underdeveloped in the field of Information Systems. Further, no work has been done to explore CBT in the context of Information Systems Security Policy violations, which are often a form of technology-facilitated deviant behavior. This study examines, for the first time, Tittle's full set of proposed constructs, including fear, in the context of technology-based employee security deviance. This research uses CBT to demonstrate the importance of understanding the interplay between technology and employee deviance and the role of organizations in preventing it.
Some people are better readers than others, and this variation in comprehension ability is predicted by measures of working memory capacity (WMC). The primary goal of this study was to investigate ...the mediating role of mind-wandering experiences in the association between WMC and normal individual differences in reading comprehension, as predicted by the executive-attention theory of WMC (e.g., Engle & Kane, 2004). We used a latent-variable, structural-equation-model approach, testing skilled adult readers on 3 WMC span tasks, 7 varied reading-comprehension tasks, and 3 attention-control tasks. Mind wandering was assessed using experimenter-scheduled thought probes during 4 different tasks (2 reading, 2 attention-control). The results support the executive-attention theory of WMC. Mind wandering across the 4 tasks loaded onto a single latent factor, reflecting a stable individual difference. Most important, mind wandering was a significant mediator in the relationship between WMC and reading comprehension, suggesting that the WMC-comprehension correlation is driven, in part, by attention control over intruding thoughts. We discuss implications for theories of WMC, attention control, and reading comprehension.
Paclitaxel shows little benefit in the treatment of glioma due to poor penetration across the blood-brain barrier (BBB). Low-intensity pulsed ultrasound (LIPU) with microbubble injection transiently ...disrupts the BBB allowing for improved drug delivery to the brain. We investigated the distribution, toxicity, and efficacy of LIPU delivery of two different formulations of paclitaxel, albumin-bound paclitaxel (ABX) and paclitaxel dissolved in cremophor (CrEL-PTX), in preclinical glioma models.
The efficacy and biodistribution of ABX and CrEL-PTX were compared with and without LIPU delivery. Antiglioma activity was evaluated in nude mice bearing intracranial patient-derived glioma xenografts (PDX). Paclitaxel biodistribution was determined in sonicated and nonsonicated nude mice. Sonications were performed using a 1 MHz LIPU device (SonoCloud), and fluorescein was used to confirm and map BBB disruption. Toxicity of LIPU-delivered paclitaxel was assessed through clinical and histologic examination of treated mice.
Despite similar antiglioma activity
, ABX extended survival over CrEL-PTX and untreated control mice with orthotropic PDX. Ultrasound-mediated BBB disruption enhanced paclitaxel brain concentration by 3- to 5-fold for both formulations and further augmented the therapeutic benefit of ABX. Repeated courses of LIPU-delivered CrEL-PTX and CrEL alone were lethal in 42% and 37.5% of mice, respectively, whereas similar delivery of ABX at an equivalent dose was well tolerated.
Ultrasound delivery of paclitaxel across the BBB is a feasible and effective treatment for glioma. ABX is the preferred formulation for further investigation in the clinical setting due to its superior brain penetration and tolerability compared with CrEL-PTX.
In this comment, we contrast different conceptions of mind wandering that were presented in 2 recent theoretical reviews:
Smallwood and Schooler (2006)
and
Watkins (2008)
. We also introduce a new ...perspective on the role of executive control in mind wandering by integrating empirical evidence presented in Smallwood and Schooler with 2 theoretical frameworks: Watkins's elaborated control theory and
Klinger's (1971
,
2009
) current concerns theory. In contrast to the Smallwood-Schooler claim that mind wandering recruits executive resources, we argue that mind wandering represents a failure of executive control and that it is dually determined by the presence of automatically generated thoughts in response to environmental and mental cues and the ability of the executive-control system to deal with this interference. We present empirical support for this view from experimental, neuroimaging, and individual-differences research.
Time series models can play an important role in disease prediction. Incidence data can be used to predict the future occurrence of disease events. Developments in modeling approaches provide an ...opportunity to compare different time series models for predictive power.
We applied ARIMA and Random Forest time series models to incidence data of outbreaks of highly pathogenic avian influenza (H5N1) in Egypt, available through the online EMPRES-I system. We found that the Random Forest model outperformed the ARIMA model in predictive ability. Furthermore, we found that the Random Forest model is effective for predicting outbreaks of H5N1 in Egypt.
Random Forest time series modeling provides enhanced predictive ability over existing time series models for the prediction of infectious disease outbreaks. This result, along with those showing the concordance between bird and human outbreaks (Rabinowitz et al. 2012), provides a new approach to predicting these dangerous outbreaks in bird populations based on existing, freely available data. Our analysis uncovers the time-series structure of outbreak severity for highly pathogenic avain influenza (H5N1) in Egypt.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
People’s ability to think creatively is a primary means of technological and cultural progress, yet the neural architecture of the highly creative brain remains largely undefined. Here, we employed a ...recently developed method in functional brain imaging analysis—connectome-based predictive modeling—to identify a brain network associated with high-creative ability, using functional magnetic resonance imaging (fMRI) data acquired from 163 participants engaged in a classic divergent thinking task. At the behavioral level, we found a strong correlation between creative thinking ability and self-reported creative behavior and accomplishment in the arts and sciences (r = 0.54). At the neural level, we found a pattern of functional brain connectivity related to high-creative thinking ability consisting of frontal and parietal regions within default, salience, and executive brain systems. In a leave-one-out cross-validation analysis, we show that this neural model can reliably predict the creative quality of ideas generated by novel participants within the sample. Furthermore, in a series of external validation analyses using data from two independent task fMRI samples and a large task-free resting-state fMRI sample, we demonstrate robust prediction of individual creative thinking ability from the same pattern of brain connectivity. The findings thus reveal a whole-brain network associated with high-creative ability comprised of cortical hubs within default, salience, and executive systems—intrinsic functional networks that tend to work in opposition—suggesting that highly creative people are characterized by the ability to simultaneously engage these large-scale brain networks.
Ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists (NMDAR antagonists) recently demonstrated antidepressant efficacy for the treatment of refractory depression, but effect sizes, ...trajectories and possible class effects are unclear.
We searched PubMed/PsycINFO/Web of Science/clinicaltrials.gov until 25 August 2015. Parallel-group or cross-over randomized controlled trials (RCTs) comparing single intravenous infusion of ketamine or a non-ketamine NMDAR antagonist v. placebo/pseudo-placebo in patients with major depressive disorder (MDD) and/or bipolar depression (BD) were included in the analyses. Hedges' g and risk ratios and their 95% confidence intervals (CIs) were calculated using a random-effects model. The primary outcome was depressive symptom change. Secondary outcomes included response, remission, all-cause discontinuation and adverse effects.
A total of 14 RCTs (nine ketamine studies: n = 234; five non-ketamine NMDAR antagonist studies: n = 354; MDD = 554, BD = 34), lasting 10.0 ± 8.8 days, were meta-analysed. Ketamine reduced depression significantly more than placebo/pseudo-placebo beginning at 40 min, peaking at day 1 (Hedges' g = -1.00, 95% CI -1.28 to -0.73, p < 0.001), and loosing superiority by days 10-12. Non-ketamine NMDAR antagonists were superior to placebo only on days 5-8 (Hedges' g = -0.37, 95% CI -0.66 to -0.09, p = 0.01). Compared with placebo/pseudo-placebo, ketamine led to significantly greater response (40 min to day 7) and remission (80 min to days 3-5). Non-ketamine NMDAR antagonists achieved greater response at day 2 and days 3-5. All-cause discontinuation was similar between ketamine (p = 0.34) or non-ketamine NMDAR antagonists (p = 0.94) and placebo. Although some adverse effects were more common with ketamine/NMDAR antagonists than placebo, these were transient and clinically insignificant.
A single infusion of ketamine, but less so of non-ketamine NMDAR antagonists, has ultra-rapid efficacy for MDD and BD, lasting for up to 1 week. Development of easy-to-administer, repeatedly given NMDAR antagonists without risk of brain toxicity is of critical importance.
Nitrile groups in the polymer of intrinsic microporosity PIM-1 were reduced to primary amines using borane complexes. In adsorption experiments, the novel amine–PIM-1 showed higher CO2 uptake and ...higher CO2/N2 sorption selectivity than the parent polymer, with very evident dual-mode sorption behavior. In gas permeation with six light gases, the individual contributions of solubility and diffusion to the overall permeability was determined via time-lag analysis. The high CO2 affinity drastically restricts diffusion at low pressures and lowers CO2 permeability compared to the parent PIM-1. Furthermore, the size-sieving properties of the polymer are increased, which can be attributed to a higher stiffness of the system arising from hydrogen bonding of the amine groups. Thus, for the H2/CO2 gas pair, whereas PIM-1 favors CO2, amine–PIM-1 shows permselectivity toward H2, breaking the Robeson 2008 upper bound.
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