991 resultados para Critical Pathways


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With salaries subjected to scrutiny more than ever, it is increasingly important that the process by which they are determined be understood and justifiable. Both public and private organisations now routinely rely on so-called job evaluation as a means of constructing an appropriate pay-scale and as such it is ever more necessary that we appreciate how this system works and that we recognise its limits. Only with such an understanding of the way in which salaries are set can we hope to have a meaningful discussion of their economic function. This paper aims to expound the details of job evaluation both in theory and in practice, and critically assess its shortcomings. In Section 1 below we describe the job evaluation system and in Section 2 we briefly outline the history and the usage of the system in both the private and the public sector. In Section 3 we theoretically analyse the often unstated but nonetheless implicit assumptions made by practitioners of the art of job evaluation. Section 4 applies the analysis of Section 3 to review a particular and important case study, namely The Senior Salaries Review of the Welsh Assembly 2004. Section 5 concludes.

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The empirical finding of an inverse U-shaped relationship between per capita income and pollution, the so-called Environmental Kuznets Curve (EKC), suggests that as countries experience economic growth, environmental deterioration decelerates and thus becomes less of an issue. Focusing on the prime example of carbon emissions, the present article provides a critical review of the new econometric techniques that have questioned the baseline polynomial specification in the EKC literature. We discuss issues related to the functional form, heterogeneity, spurious regressions and spatial dependence to address whether and to what extent the EKC can be observed. Despite these new approaches, there is still no clear-cut evidence supporting the existence of the EKC for carbon emissions. JEL classifications: C20; Q32; Q50; O13 Keywords: Environmental Kuznets Curve; Carbon emissions; Functional form; Heterogeneity; Spurious regressions; Spatial dependence.Residential satisfaction is often used as a barometer to assess the performance of public policy and programmes designed to raise individuals' well-being. However, the fact that responses elicited from residents might be biased by subjective, non-observable factors casts doubt on whether these responses can be taken as trustable indicators of the individuals' housing situation. Emotional factors such as aspirations or expectations might affect individuals' cognitions of their true residential situation. To disentangle this puzzle, we investigated whether identical residential attributes can be perceived differently depending on tenure status. Our results indicate that tenure status is crucial not only in determining the level of housing satisfaction, but also regarding how dwellers perceive their housing characteristics. Keywords: Housing satisfaction, subjective well-being, homeownership. JEL classification: D1, R2.

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Cette thse de doctorat, crite en anglais, propose la premire dition critique de Because of the Dollars , une nouvelle de l'crivain anglais Joseph Conrad publie dans le volume Within the Tides, en fvrier 1915. Outre le texte critique de la nouvelle - le seul ce jour reconstruit d'aprs une minutieuse tude des relations entre toutes les versions existantes - la prsente dition offre aussi un vaste apparat ditorial. Le texte de la prsente dition est clectique. Sa ponctuation est essentiellement base sur un texte proche du manuscrit de l'auteur, et donc non corrompu par le processus de transmission. Mais ses mots sont tirs des dernires versions rvises par l'auteur, tant donn qu'au cours de la transmission, les mots, contrairement aux marques de ponctuation, n'ont pas t contamins. Le rsultat de cette mthode est un texte refltant, tant pour les mots que pour la ponctuation, les choix de l'auteur. L'apparat ditorial sert placer la nouvelle dans la vie de Conrad, tracer l'volution du texte, et offrir au lecteur des informations historiques et culturelles qui permettront une meilleure lecture de l'oeuvre. Cet apparat est compos de quatre parties : une introduction, une tude sur les textes de la nouvelle, une collation historique de toutes les variantes, et des notes explicatives. L'introduction place l'oeuvre dans le contexte de la vie de l'crivain, en donne la rception critique de 1915 nos jours, et en claire le contexte historique (un changement de monnaie Singapour en 1903-4). L'tude sur les textes trace le dveloppement et la transmission du texte, depuis son inscription sur pages manuscrites jusqu' sa publication dans les oeuvres compltes de Conrad. La collation historique inventorie toutes les variantes textuelles entre les diffrentes versions existantes. Enfin, les notes explicatives glosent les allusions littraires, historiques, et culturelles du texte. Because of the Dollars et Within the Tides n'ayant attir que trs peu d'attention critique, les informations contenues dans cet apparat ditorial sont compltement indites, et jettent une lumire originale sur une priode peu tudie de la vie de Conrad.

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The human auditory system is comprised of specialized but interacting anatomic and functional pathways encoding object, spatial, and temporal information. We review how learning-induced plasticity manifests along these pathways and to what extent there are common mechanisms subserving such plasticity. A first series of experiments establishes a temporal hierarchy along which sounds of objects are discriminated along basic to fine-grained categorical boundaries and learned representations. A widespread network of temporal and (pre)frontal brain regions contributes to object discrimination via recursive processing. Learning-induced plasticity typically manifested as repetition suppression within a common set of brain regions. A second series considered how the temporal sequence of sound sources is represented. We show that lateralized responsiveness during the initial encoding phase of pairs of auditory spatial stimuli is critical for their accurate ordered perception. Finally, we consider how spatial representations are formed and modified through training-induced learning. A population-based model of spatial processing is supported wherein temporal and parietal structures interact in the encoding of relative and absolute spatial information over the initial ∼300ms post-stimulus onset. Collectively, these data provide insights into the functional organization of human audition and open directions for new developments in targeted diagnostic and neurorehabilitation strategies.

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When dealing with sustainability we are concerned with the biophysical as well as the monetary aspects of economic and ecological interactions. This multidimensional approach requires that special attention is given to dimensional issues in relation to curve fitting practice in economics. Unfortunately, many empirical and theoretical studies in economics, as well as in ecological economics, apply dimensional numbers in exponential or logarithmic functions. We show that it is an analytical error to put a dimensional unit x into exponential functions ( a x ) and logarithmic functions ( x a log ). Secondly, we investigate the conditions of data sets under which a particular logarithmic specification is superior to the usual regression specification. This analysis shows that logarithmic specification superiority in terms of least square norm is heavily dependent on the available data set. The last section deals with economists curve fitting fetishism. We propose that a distinction be made between curve fitting over past observations and the development of a theoretical or empirical law capable of maintaining its fitting power for any future observations. Finally we conclude this paper with several epistemological issues in relation to dimensions and curve fitting practice in economics

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Astrocytes are now considered as key players in brain information processing because of their newly discovered roles in synapse formation and plasticity, energy metabolism and blood flow regulation. However, our understanding of astrocyte function is still fragmented compared to other brain cell types. A better appreciation of the biology of astrocytes requires the development of tools to generate animal models in which astrocyte-specific proteins and pathways can be manipulated. In addition, it is becoming increasingly evident that astrocytes are also important players in many neurological disorders. Targeted modulation of protein expression in astrocytes would be critical for the development of new therapeutic strategies. Gene transfer is valuable to target a subpopulation of cells and explore their function in experimental models. In particular, viral-mediated gene transfer provides a rapid, highly flexible and cost-effective, in vivo paradigm to study the impact of genes of interest during central nervous system development or in adult animals. We will review the different strategies that led to the recent development of efficient viral vectors that can be successfully used to selectively transduce astrocytes in the mammalian brain.

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Converging evidence favors an abnormal susceptibility to oxidative stress in schizophrenia. Decreased levels of glutathione (GSH), the major cellular antioxidant and redox regulator, was observed in cerebrospinal-fluid and prefrontal cortex of patients. Importantly, abnormal GSH synthesis of genetic origin was observed: Two case-control studies showed an association with a GAG trinucleotide repeat (TNR) polymorphism in the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) catalytic subunit (GCLC) gene. The most common TNR genotype 7/7 was more frequent in controls, whereas the rarest TNR genotype 8/8 was three times more frequent in patients. The disease associated genotypes (35% of patients) correlated with decreased GCLC protein, GCL activity and GSH content. Similar GSH system anomalies were observed in early psychosis patients. Such redox dysregulation combined with environmental stressors at specific developmental stages could underlie structural and functional connectivity anomalies. In pharmacological and knock-out (KO) models, GSH deficit induces anomalies analogous to those reported in patients. (a) morphology: spine density and GABA-parvalbumine immunoreactivity (PV-I) were decreased in anterior cingulate cortex. KO mice showed delayed cortical PV-I at PD10. This effect is exacerbated in mice with increased DA from PD5-10. KO mice exhibit cortical impairment in myelin and perineuronal net known to modulate PV connectivity. (b) physiology: In cultured neurons, NMDA response are depressed by D2 activation. In hippocampus, NMDA-dependent synaptic plasticity is impaired and kainate induced g-oscillations are reduced in parallel to PV-I. (c) cognition: low GSH models show increased sensitivity to stress, hyperactivity, abnormal object recognition, olfactory integration and social behavior. In a clinical study, GSH precursor N-acetyl cysteine (NAC) as add on therapy, improves the negative symptoms and decreases the side effects of antipsychotics. In an auditory oddball paradigm, NAC improves the mismatched negativity, an evoked potential related to pre-attention and to NMDA receptors function. In summary, clinical and experimental evidence converge to demonstrate that a genetically induced dysregulation of GSH synthesis combined with environmental insults in early development represent a major risk factor contributing to the development of schizophrenia Conclusion Based on these data, we proposed a model for PSIP1 promoter activity involving a complex interplay between yet undefined regulatory elements to modulate gene expression.

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Sepsis is among the leading causes of death worldwide and its incidence is increasing. Defined as the host response to infection, sepsis is a clinical syndrome considered to be the expression of a dysregulated immune reaction induced by danger signals that may lead to organ failure and death. Remarkable progresses have been made in our understanding of the molecular basis of host defenses in recent years. The host defense response is initiated by innate immune sensors of danger signals designated under the collective name of pattern-recognition receptors. Members of the family of microbial sensors include the complement system, the Toll-like receptors, the nucleotide-binding oligomerization domainlike receptors, the RIG-I-like helicases and the C-type lectin receptors. Ligand-activated pattern-recognition receptors kick off a cascade of intracellular events resulting in the expression of co-stimulatory molecules and release of effector molecules playing a fundamental role in the initiation of the innate and adaptive immune responses. Fine tuning of proinflammatory and anti-inflammatory reactions is critical for keeping the innate immune response in check. Overwhelming or dysregulated responses induced by infectious stimuli may have dramatic consequences for the host as shown by the profound derangements observed in sepsis. Unfortunately, translational research approaches aimed at the development of therapies targeting newly identified innate immune pathways have not held their promises. Indeed, all recent clinical investigations of adjunctive anti-sepsis treatments had little, if any, impact on morbidity and all-cause mortality of sepsis. Dissecting the mechanisms underlying the transition from infection to sepsis is essential for solving the sepsis enigma. Important components of the puzzle have already been identified, but the hunt must go on in the laboratory and at the bedside.

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The epidemiological methods have become useful tools for the assessment of the effectiveness and safety of health care technologies. The experimental methods, namely the randomized controlled trials (RCT), give the best evidence of the effect of a technology. However, the ethical issues and the very nature of the intervention under study sometimes make it difficult to carry out an RCT. Therefore, quasi-experimental and non-experimental study designs are also applied. The critical issues concerning these designs are discussed. The results of evaluative studies are of importance for decision-makers in health policy. The measurements of the impact of a medical technology should go beyond a statement of its effectiveness, because the essential outcome of an intervention or programme is the health status and quality of life of the individuals and populations concerned.

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A first episode of depression after 65years of age has long been associated with both severe macrovascular and small microvascular pathology. Among the three more frequent forms of depression in old age, post-stroke depression has been associated with an abrupt damage of cortical circuits involved in monoamine production and mood regulation. Late-onset depression (LOD) in the absence of stroke has been related to lacunes and white matter lesions that invade both the neocortex and subcortical nuclei. Recurrent late-life depression is thought to induce neuronal loss in the hippocampal formation and white matter lesions that affect limbic pathways. Despite an impressive number of magnetic resonance imaging (MRI) studies in this field, the presence of a causal relationship between structural changes in the human brain and LOD is still controversial. The present article provides a critical overview of the contribution of neuropathology in post-stroke, late-onset, and late-life recurrent depression. Recent autopsy findings challenge the role of stroke location in the occurrence of post-stroke depression by pointing to the deleterious effect of subcortical lacunes. Despite the lines of evidences supporting the association between MRI-assessed white matter changes and mood dysregulation, lacunes, periventricular and deep white matter demyelination are all unrelated to the occurrence of LOD. In the same line, neuropathological data show that early-onset depression is not associated with an acceleration of aging-related neurodegenerative changes in the human brain. However, they also provide data in favor of the neurotoxic theory of depression by showing that neuronal loss occurs in the hippocampus of chronically depressed patients. These three paradigms are discussed in the light of the complex relationships between psychosocial determinants and biological vulnerability in affective disorders.

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Critical limb ischemia is a major public health problem in our western countries due to the epidemia of (diabesity). The outcome of patients suffering from critical limb ischemia reains poor with an amputation free survival rate at one year of about 50%. The treatment should be multidiciplinary and done in emergency in specialized centers to ensure the limb salvage: this management should be centered aroud 3 axis: the screening of the cardiovascular risk factors, the best medical treatment and the invasive approaches. Due to multiple endovascular technical innovations, more frail patients with com plex diseases can be treated with good results. Therefore, the endovascular treatment is essential in the management of such patients by vascular surgeons.

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The intraerythrocytic malarial parasite is involved in an extremely intensive anabolic activity while it resides in its metabolically quiescent host cell. The necessary fast uptake of nutrients and the discharge of waste product, are guaranteed by parasite-induced alterations of the constitutive transporters of the host cell and the production of new parallel pathways. The membrane of the host cell thus becomes permeable to phospholipids, purine bases and nucleosides, small non-electrolytes, anions and cations. When the new pathways are quantitatively unimportant, classical inhibitors of native transporters can be used to inhibit parasite growth. Several compounds were found to effectively inhibit the new pathways and consequently, parasite growth. The pathways have also been used to introduce cytotoxic agents. The parasitophorous membrane consists of channels which are highly permeable to small solutes and display no ion selectivity. Transport of some cations and anions across the parasite membrane is rapid and insensitive to classical inhibitors, and in some cases it is mediated by specific antiporters which respond to their respective inhibitors. Macromolecules have been shown to reach the parasitophorous space through a duct contiguous with the host cell membrane, and subsequently to be endocytosed at the parasite membrane. The simultaneous presence of the parasitophorous membrane channels and the duct, however, is incompatible with experimental evidences. No specific inhibitors were found as yet that would efficiently inhibit transport through the channels or the duct.