Inhibition of Notch Pathway Enhances Photoreceptor Commitment From Cultured Retinal Stem Cells

Purpose: Consequently to the principle that photoreceptors have to be at a very precise development stage to be successfully transplanted (MacLaren 2006), we are trying to mimic this development stage in vitro using retinal stem cells. The latter one isolated from the newborn mouse retina, derived from the radial glia population, which were previously isolated and characterized in our laboratory. We developed a protocol to commit these cells to the photoreceptor fate, but even if the percentage of cells expressing photoreceptor markers is high (30%), the differentiation process is incomplete so far (Merhi-Soussi 2006). Methods: In order to ameliorate photoreceptor differentiation, we hypothesized that the Notch pathway may interfere with this process by either promoting glia commitment, or maintaining an undifferentiated state. We are thus using a gamma-secretase inhibitor (DAPT), which inhibits Notch receptor cleavage and thus Notch activation. DAPT was used either during the whole differentiation stimulation, or only during a restricted period in two various retinal stem cell lines (RSC AA and RSC MP1). Results: RT-PCR performed during cell proliferation, showed the same positive expression in both cell lines for the following genes: Math3, Six3, Hes1, NeuroD, Pax6 and Notch1. Additionally, Mash1, Hes5, Prox1, Crx and Otx2 were detected in both cell lines but with a stronger expression in RSC MP1. Opposite results were obtained for Chx10. Nrl, Peripherin/RDS, GFAP and Math5 were detected neither in RSC AA, nor in RSC MP1. The constant presence of DAPT i) leads to a 233% (RSC AA) or 900% (RSC MP1) increase in peripherin/RDS-positive (photoreceptor marker) cells, compared to controls (no DAPT, n=3, P<0.02) along with a 68% (RSC AA) or 80% (RSC MP1) decrease in GFAP- positive cells (n=3, P<0.04), ii) modifies the ratio between uni-/bi- (23%) and multi- (77%) polar peripherin/RDS-positive cells to 45% and 55%, respectively, for both cell lines and iii) reduces by 50% the total cell number during the whole differentiation process for both cell lines. Conclusions: We are now exploring whether this reduction in total cell number is due to inhibition of cell proliferation or to cell death and whether photoreceptor differentiation is promoted instead of glial induction. We also want to confirm the results obtained with DAPT with RSCs isolated from Notch1-loxP mice. Such protocol may help to better mimic photoreceptor development, but this needs to be confirmed by genomic and proteomic profile analyses.

Involuntary Discharge from a Long-Term Facility

An involuntary discharge from a long-term care (LTC) facility occurs when the facility provides a 30-day written notice to a resident informing him/her of the need to move out of the facility. The notice must set out the reasons for the transfer or discharge as well as state the effective date, location of transfer or discharge, statement of appeal rights and the contact information (name, address and telephone number) for the Office of the State Long-Term Care Ombudsman.

Involuntary outpatient treatment for mental health problems in Switzerland: a literature review.

BACKGROUND: In 2008, the Swiss Civil Code was amended. From 1 January 2013, each Swiss canton may propose specific provisions for involuntary outpatient treatment (community treatment orders (CTOs)) for individuals with mental disorders. AIM: This review catalogues the legal provisions of the various Swiss cantons for CTOs and outlines the differences between them. It sets this in the context of variations in clinical provisions between the cantons. METHODS: Databases were searched to obtain relevant publications about CTOs in Switzerland. The Swiss Medical Association, Swiss Federal Statistical Office, Swiss Health Observatory and all the 26 Cantonal medical officers were contacted to complete the information. Conférence des cantons en matière de protection des mineurs et des adultes (COPMA), the authority which monitors guardianship legislation, and Pro Mente Sana, a patients' right association, were also approached. RESULTS: Three articles about CTOs in Switzerland were identified. Psychiatric provisions vary considerably between cantons and only a few could provide complete or even partial figures for rates of compulsion in previous years. Prior to 2013, only 6 of the 20 cantons, for which information was returned, had any provision for CTOs. Now, every canton has some form of legal basis but the level of detail is often limited. In eight cantons, the powers of the measure are not specified (for example, use of medication). In 12 cantons, the maximum duration of the CTO is not specified. German speaking cantons and rural cantons are more likely to specify the details of CTOs. CONCLUSION: Highly variable Swiss provision for CTOs is being introduced despite the absence of convincing international evidence for their effectiveness or good quality data on current coercive practice. Careful monitoring and assessment of these new cantonal provisions are essential.

Identification-commitment inventory (ICI-Model): confirmatory factor analysis and construct validity

The aim of this study is to confirm the factorial structure of the Identification-Commitment Inventory (ICI) developed within the frame of the Human System Audit (HSA) (Quijano et al. in Revist Psicol Soc Apl 10(2):27-61, 2000; Pap Psicól Revist Col Of Psicó 29:92-106, 2008). Commitment and identification are understood by the HSA at an individual level as part of the quality of human processes and resources in an organization; and therefore as antecedents of important organizational outcomes, such as personnel turnover intentions, organizational citizenship behavior, etc. (Meyer et al. in J Org Behav 27:665-683, 2006). The theoretical integrative model which underlies ICI Quijano et al. (2000) was tested in a sample (N = 625) of workers in a Spanish public hospital. Confirmatory factor analysis through structural equation modeling was performed. Elliptical least square solution was chosen as estimator procedure on account of non-normal distribution of the variables. The results confirm the goodness of fit of an integrative model, which underlies the relation between Commitment and Identification, although each one is operatively different.

Smoking behaviour, involuntary smoking, attitudes towards smoke-free legislations, and tobacco control activities in the European Union

The six most important cost-effective policies on tobacco control can be measured by the Tobacco Control Scale (TCS). The objective of our study was to describe the correlation between the TCS and smoking prevalence, self-reported exposure to secondhand smoke (SHS) and attitudes towards smoking restrictions in the 27 countries of the European Union (EU27).

A cognitive hierarchy model of behavior in the action commitment game

We apply the cognitive hierarchy model of Camerer et al. (Q J Econ 119(3):861-898, 2004)-where players have different levels of reasoning-to Huck et al. (Games Econ Behav 38:240-264, 2002) discrete version of Hamilton and Slutsky (Games Econ Behav 2:29-46, 1990) action commitment game-a duopoly with endogenous timing of entry. We show that, for an empirically reasonable average number of thinking steps, the model rules out Stackelberg equilibria, generates Cournot outcomes including delay, and outcomes where the first mover commits to a quantity higher than Cournot but lower than Stackelberg leader. We show that a cognitive hierarchy model with quantal responses can explain the most important features of the experimental data on the action commitment game in (2002). In order to gauge the success of the model in fitting the data, we compare it to a noisy Nash model. We find that the cognitive hierarchy model with quantal responses fits the data better than the noisy Nash model.

The personal research portal : web 2.0 driven individual commitment with open access for development

Peer-reviewed

Commitment to military service among Finnish conscripts

This research establishes the primary components, predictors, and consequences of organizational commitment in the military context. Specifically, the research examines commitment to the military service among Finnish conscripts and whether initial affective commitment prior to service predicts later commitment, attitudes, behavior, and performance, and, furthermore, analyzes the changes in commitment and its possible outcomes. The data were collected from records as well as by surveys from 1,387 rank and file soldiers, immediately after they reported for duty, near the end of basic training, and near the end of 6 to 12 months of service. The data covered a wide array of predictor variables, including background items, attitudes toward conscription, mental and physical health, sociability, training quality, and leadership. Moreover, the archival data included such items as rank, criminal record, performance ratings, and the number of medical examines and exemptions. The measures were further refined based on the results of factor analysis and reliability tests. The results indicated that initial commitment significantly corresponded with expected adjustment, intentions to stay in the military, and acceptance of authority. Moreover, initial commitment moderately related to personal growth, perceived performance, and the number of effective service days at the end of service. During basic training, affective commitment was mostly influenced by challenging training, adjustment experiences, regimentation, and unit climate. At the end of service, committed soldiers demonstrated more personal growth and development in service, had higher-level expected performance, and less malingering during their service. Additionally, they had significantly more positive attitudes toward national defense. The results suggest that affective commitment requires adequate personal adjustment, experiences of personal growth and development, and satisfaction with unit dynamics and training. This research contributes to the theoretical discussion on organizational commitment and the will to defend the nation and advances developing models to support and manage conscript training, education, leadership, and personnel policy. This is achieved by determining the main factors and variables, including their relative strength, that affect commitment to the military service. These findings may also facilitate in designing programs aimed at reducing unwanted discharges and inadequate performance. In particular, these results provide tools for improving conscripts’ overall attachment to and identification with the military service.

System-wide approaches to uncover Th2 cell lineage commitment

T helper (Th) cells are vital regulators of the adaptive immune system. When activated by presentation of cognate antigen, Th cells demonstrate capacity to differentiate into functionally distinct effector cell subsets. The Th2 subset is required for protection against extracellular parasites, such as helminths, but is also closely linked to pathogenesis of asthma and allergies. The intracellular molecular signal transduction pathways regulating T helper cell subset differentiation are still incompletely known. Moreover, great majority of studies regarding Th2 differentiation have been conducted with mice models, while studies with human cells have been fewer in comparison. The goal of this thesis was to characterize molecular mechanisms promoting the development of Th2 phenotype, focusing specifically on human umbilical cord blood T cells as an experimental model. These primary cells, activated and differentiated to Th2 cells in vitro, were investigated by complementary system-wide approaches, targeting levels of mRNA, proteins, and lipid molecules. Specifically, the results indicated IL4-regulated recruitment of nuclear protein, and described novel components of the Th2-promoting STAT6 enhanceosome complex. Furthermore, the development of the activated effector cell phenotype was found to correlate with remodeling of the cellular lipidome. These findings will hopefully advance the understanding of human Th2 cell lineage commitment and development of Th2-associated disease states.

De-escalation of commitment management strategy in IT project management methodology: case of ERP implementation project by IT consulting company

According to several surveys and observations, the percentage of successfully conducted IT projects without over-budgeting and delays in time schedule are extremely low. Many projects also are evaluated as failures in terms of delivered functionality. Nuldén (1996) compares IT projects with bad movies; after watching for 2 hours, one still tries to finish it even though one understands that it is a complete waste of time. The argument for that is 'I've already invested too much time to terminate it now'. The same happens with IT projects: sometimes the company continues wasting money on these projects for a long time, even though there are no expected benefits from these projects. Eventually these projects are terminated anyway, but until this moment, the company spends a lot. The situation described above is a consequence of “escalation of commitment” - project continuation even after a manager receives negative feedback of the project’s success probability. According to Keil and Mähring (2010), even though escalation can occur in any type of project, it is more common among complex technological projects, such as IT projects. Escalation of commitment very often results in runaway projects. In order to avoid it, managers use de-escalation strategies, which allow the resources to be used in more effective. These strategies lead to project termination or turning around, which stops the flow of wasted investments. Numbers of researches explore escalation of commitment phenomena based on experiments and business cases. Moreover, during the last decade several frameworks were proposed for de-escalation strategy. However, there is no evidence of successful implementation of the de-escalation of commitment strategy in the literature. In addition, despite that fact that IT project management methodologies are widely used in the companies, none of them cover the topic of escalation of commitment risks. At the same time, there are no researches proposing the way to implement de-escalation of commitment strategy into the existing project management methodology The research is focused on a single case of large ERP implementation project by the consulting company. Hence, the main deliverables of the study include suggestions of improvement in de-escalation methods and techniques in the project and in the company. Moreover, the way to implement these methods into existing project management methodology and into the company general policies is found.