Transport and turbulence studies in the linear ohmic confinement regime in Alcator C-Mod

Transport in ohmically heated plasmas in Alcator C-Mod was studied in both the linear (LOC) and saturated (SOC) ohmic L-mode confinement regimes and the importance of turbulent transport in the region r/a = 0.5–0.8 was established. After an extensive analysis with TGLF and GYRO, it is found that using an effective impurity ion species with Z[subscript i] = 8, and moderately high Z[subscript eff] (2.0–5.6), in the LOC regime electron transport becomes dominant due to TEM turbulence. The key ingredient in the present results is the observation that dilution of the main ion species (deuterium) by impurity species of moderate charge state reduces dominant ITG turbulence, in contrast to the SOC regime with little, if any dilution. The turbulent spectrum measured with the phase contrast imaging (PCI) diagnostic is in qualitative agreement with predictions of a synthetic PCI diagnostic adopted to Global GYRO. The toroidal rotation in the low-density LOC regime is in the co-current direction but as the density is raised in the SOC regime the rotation reverses to the counter current drive direction. The impurity content of the plasma was measured recently and an effective Z[subscript i] of 9 was deduced.United States. Dept. of Energy (Grant DE-FC02-99ER54512-CMOD

Developing and testing an instrument for identifying performance incentives in the Greek health care sector

BACKGROUND: In the era of cost containment, managers are constantly pursuing increased organizational performance and productivity by aiming at the obvious target, i.e. the workforce. The health care sector, in which production processes are more complicated compared to other industries, is not an exception. In light of recent legislation in Greece in which efficiency improvement and achievement of specific performance targets are identified as undisputable health system goals, the purpose of this study was to develop a reliable and valid instrument for investigating the attitudes of Greek physicians, nurses and administrative personnel towards job-related aspects, and the extent to which these motivate them to improve performance and increase productivity. METHODS: A methodological exploratory design was employed in three phases: a) content development and assessment, which resulted in a 28-item instrument, b) pilot testing (N = 74) and c) field testing (N = 353). Internal consistency reliability was tested via Cronbach's alpha coefficient and factor analysis was used to identify the underlying constructs. Tests of scaling assumptions, according to the Multitrait-Multimethod Matrix, were used to confirm the hypothesized component structure. RESULTS: Four components, referring to intrinsic individual needs and external job-related aspects, were revealed and explain 59.61% of the variability. They were subsequently labeled: job attributes, remuneration, co-workers and achievement. Nine items not meeting item-scale criteria were removed, resulting in a 19-item instrument. Scale reliability ranged from 0.782 to 0.901 and internal item consistency and discriminant validity criteria were satisfied. CONCLUSION: Overall, the instrument appears to be a promising tool for hospital administrations in their attempt to identify job-related factors, which motivate their employees. The psychometric properties were good and warrant administration to a larger sample of employees in the Greek healthcare system

Somatically ill persons’ self-nominated quality of life domains: review of the literature and guidelines for future studies

OBJECTIVE: To review which domains somatically ill persons nominate as constituting their QoL. Specific objective is to examine whether the method of enquiry affect these domains. METHODS: We conducted two literature searches in the databases PubMed/Medline, CINAHL and Psychinfo for qualitative studies examining patients' self-defined QoL domains using (1) SEIQoL and (2) study-specific questions. For each database, two researchers independently assessed the eligibility of the retrieved abstracts and three researchers subsequently classified all QoL domains. RESULTS: Thirty-six eligible papers were identified: 27 studies using the SEIQoL, and nine presenting data derived from study-specific questions. The influence of the method of enquiry on patients' self-nominated QoL domains appears limited: most domains were presented in both types of studies, albeit with different frequencies. CONCLUSIONS: This review provides a comprehensive overview of somatically ill persons' self-nominated QoL domains. However, limitations inherent to reviewing qualitative studies (e.g., the varying level of abstraction of patients' self-defined QoL domains), limitations of the included studies and limitations inherent to the review process, hinder cross-study comparisons. Therefore, we provide guidelines to address shortcomings of qualitative reports amenable to improvement and to stimulate further improvement of conducting and reporting qualitative research aimed at exploring respondents' self-nominated QoL domains

VX-659-Tezacaftor-Ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles

Background The next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659–tezacaftor–ivacaftor), was developed to restore the function of Phe508del CFTR protein in patients with cystic fibrosis. Methods We evaluated the effects of VX-659–tezacaftor–ivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659–tezacaftor–ivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508del–MF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508del–Phe508del genotype). The primary end points were safety and the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1). Results VX-659–tezacaftor–ivacaftor significantly improved the processing and trafficking of Phe508del CFTR protein as well as chloride transport in vitro. In patients, VX-659–tezacaftor–ivacaftor had an acceptable safety and side-effect profile. Most adverse events were mild or moderate. VX-659–tezacaftor–ivacaftor resulted in significant mean increases in the percentage of predicted FEV1 through day 29 (P<0.001) of up to 13.3 points in patients with Phe508del–MF genotypes; in patients with the Phe508del–Phe508del genotype already receiving tezacaftor–ivacaftor, adding VX-659 resulted in a further 9.7-point increase in the percentage of predicted FEV1. The sweat chloride concentrations and scores on the respiratory domain of the Cystic Fibrosis Questionnaire–Revised improved in both patient populations. Conclusions Robust in vitro activity of VX-659–tezacaftor–ivacaftor targeting Phe508del CFTR protein translated into improvements for patients with Phe508del–MF or Phe508del–Phe508del genotypes. VX-659 triple-combination regimens have the potential to treat the underlying cause of disease in approximately 90% of patients with cystic fibrosis. (Funded by Vertex Pharmaceuticals; VX16-659-101 and VX16-659-001 ClinicalTrials.gov numbers, NCT03224351 and NCT03029455.

PAI-1 and functional blockade of SNAI1 in breast cancer cell migration

12 pages, 5 figures.-- PMID: 19055748 [PubMed].-- et al.[Introduction]: Snail, a family of transcriptional repressors implicated in cell movement, has been correlated with tumour invasion. The Plasminogen Activation (PA) system, including urokinase plasminogen activator (uPA), its receptor and its inhibitor, plasminogen activator inhibitor type 1(PAI-1), also plays a key role in cancer invasion and metastasis, either through proteolytic degradation or by non-proteolytic modulation of cell adhesion and migration. Thus, Snail and the PA system are both over-expressed in cancer and influence this process. In this study we aimed to determine if the activity of SNAI1 (a member of the Snail family) is correlated with expression of the PA system components and how this correlation can influence tumoural cell migration.[Methods]: We compared the invasive breast cancer cell-line MDA-MB-231 expressing SNAI1 (MDA-mock) with its derived clone expressing a dominant-negative form of SNAI1 (SNAI1-DN). Expression of PA system mRNAs was analysed by cDNA microarrays and real-time quantitative RT-PCR. Wound healing assays were used to determine cell migration. PAI-1 distribution was assessed by immunostaining.[Results]: We demonstrated by both cDNA microarrays and realtime quantitative RT-PCR that the functional blockade of SNAI1 induces a significant decrease of PAI-1 and uPA transcripts. After performing an in vitro wound-healing assay, we observed that SNAI1-DN cells migrate more slowly than MDA-mock cells and in a more collective manner. The blockade of SNAI1 activity resulted in the redistribution of PAI-1 in SNAI1-DN cells decorating large lamellipodia, which are commonly found structures in these cells.[Conclusions]: In the absence of functional SNAI1, the expression of PAI-1 transcripts is decreased, although the protein is redistributed at the leading edge of migrating cells in a manner comparable with that seen in normal epithelial cells.This work was supported by the CNRS ACI Program "Complexité du vivant" (grant # 050009DR11) and by the Evry Genopole grant "Aide à l'acquisition d'équipement semi-lourd" 2007 and 2008.Peer reviewe

Comprehensive review:Computational modelling of Schizophrenia

Computational modelling has been used to address: (1) the variety of symptoms observed in schizophrenia using abstract models of behavior (e.g. Bayesian models - top-down descriptive models of psychopathology); (2) the causes of these symptoms using biologically realistic models involving abnormal neuromodulation and/or receptor imbalance (e.g. connectionist and neural networks - bottom-up realistic models of neural processes). These different levels of analysis have been used to answer different questions (i.e. understanding behavioral vs. neurobiological anomalies) about the nature of the disorder. As such, these computational studies have mostly supported diverging hypotheses of schizophrenia's pathophysiology, resulting in a literature that is not always expanding coherently. Some of these hypotheses are however ripe for revision using novel empirical evidence.Here we present a review that first synthesizes the literature of computational modelling for schizophrenia and psychotic symptoms into categories supporting the dopamine, glutamate, GABA, dysconnection and Bayesian inference hypotheses respectively. Secondly, we compare model predictions against the accumulated empirical evidence and finally we identify specific hypotheses that have been left relatively under-investigated

Insects as Stem Engineers: Interactions Mediated by the Twig-Girdler Oncideres albomarginata chamela Enhance Arthropod Diversity

Background: Ecosystem engineering may influence community structure and biodiversity by controlling the availability of resources and/or habitats used by other organisms. Insect herbivores may act as ecosystem engineers but there is still poor understanding of the role of these insects structuring arthropod communities. Methodology/Principal Findings: We evaluated the effect of ecosystem engineering by the stem-borer Oncideres albomarginata chamela on the arthropod community of a tropical dry forest for three consecutive years. The results showed that ecosystem engineering by O. albomarginata chamela had strong positive effects on the colonization, abundance, species richness and composition of the associated arthropod community, and it occurred mainly through the creation of a habitat with high availability of oviposition sites for secondary colonizers. These effects cascade upward to higher trophic levels. Overall, ecosystem engineering by O. albomarginata chamela was responsible for nearly 95 % of the abundance of secondary colonizers and 82 % of the species richness. Conclusions/Significance: Our results suggest that ecosystem engineering by O. albomarginata chamela is a keystone process structuring an arthropod community composed by xylovores, predators and parasitoids. This study is the first to empirically demonstrate the effect of the ecosystem engineering by stem-boring insects on important attributes o

A transatlantic perspective on 20 emerging issues in biological engineering

Advances in biological engineering are likely to have substantial impacts on global society. To explore these potential impacts we ran a horizon scanning exercise to capture a range of perspectives on the opportunities and risks presented by biological engineering. We first identified 70 potential issues, and then used an iterative process to prioritise 20 issues that we considered to be emerging, to have potential global impact, and to be relatively unknown outside the field of biological engineering. The issues identified may be of interest to researchers, businesses and policy makers in sectors such as health, energy, agriculture and the environment