Blockade of the action of nitric oxide in human septic shock increases systemic vascular resistance and has detrimental effects on pulmonary function after a short infusion of methylene blue

To investigate the role of nitric oxide in human sepsis, ten patients with severe septic shock requiring vasoactive drug therapy and mechanical ventilation were enrolled in a prospective, open, non-randomized clinical trial to study the acute effects of methylene blue, an inhibitor of guanylate cyclase. Hemodynamic and metabolic variables were measured before and 20, 40, 60, and 120 min after the start of a 1-h intravenous infusion of 4 mg/kg of methylene blue. Methylene blue administration caused a progressive increase in mean arterial pressure (60 [55-70] to 70 [65-100] mmHg, median [25-75th percentiles]; P<0.05), systemic vascular resistance index (649 [479-1084] to 1066 [585-1356] dyne s-1 cm-5 m-2; P<0.05) and the left ventricular stroke work index (35 [27-47] to 38 [32-56] g m-1 m-2; P<0.05) from baseline to 60 min. The pulmonary vascular resistance index increased from 150 [83-207] to 186 [121-367] dyne s-1 cm-5 m-2 after 20 min (P<0.05). Mixed venous saturation decreased from 65 [56-76] to 63 [55-69]% (P<0.05) after 60 min. The PaO2/FiO2 ratio decreased from 168 [131-215] to 132 [109-156] mmHg (P<0.05) after 40 min. Arterial lactate concentration decreased from 5.1 ± 2.9 to 4.5 ± 2.1 mmol/l, mean ± SD (P<0.05) after 60 min. Heart rate, cardiac filling pressures, cardiac output, oxygen delivery and consumption did not change. Methylene blue administration was safe and no adverse effect was observed. In severe human septic shock, a short infusion of methylene blue increases systemic vascular resistance and may improve myocardial function. Although there was a reduction in blood lactate concentration, this was not explained by an improvement in tissue oxygenation, since overall oxygen availability did not change. However, there was a significant increase in pulmonary vascular tone and a deterioration in gas exchange. Further studies are needed to demonstrate if nitric oxide blockade with methylene blue can be safe for patients with septic shock and, particularly, if it has an effect on pulmonary function.

Classificações de signos de C.S.Peirce: de ‘On the Logic of Science’ ao ‘Syllabus of Certain Topics of Logic’

As classificações dos signos de C.S.Peirce começam a ser desenvolvidas em 1865 e se estendem a até, pelo menos, 1909. Vou apresentar o período que tem início em 1865, e possui dois momentos de intensa produção - "On a New List of Categories" e "On the Algebra of Logic: a contribution to the philosophy of notation". Em seguida apresento as dez classes de signos, uma morfologia que aparece no "Syllabus of Certain Topics of Logic", e é desenvolvida a partir de 1903. Meu propósito aqui é familiarizar o leitor com as intrincadas classificações sígnicas de Peirce.

An exploratory study of nurses' perceptions of their action learning experience /

Each year, the College of Nurses of Ontario (CNO) requires all registered nurses and registered practical nurses in Ontario to complete a Reflective Practice learning activity. In doing so, nurses are expected to perform a self- assessment, identify a practice problem or issue, create and implement a personal learning plan, and evaluate the learning and outcomes accomplished. The process and components of CNO's Reflective Practice program are very similar to an Action Learning activity. The purpose of this qualitative research was to explore the perceptions of 1 1 nurses who completed at least 1 Action Learning activity. Data analysis of their comments provided insight into their perceptions of the Action Learning experience, perceptions of the negative and positive characteristics of various activities within the Action Learning process, and perceptions of barriers or challenges within this experience. The author concluded that participants perceived their Action Learning activities to be a positive experience because the process focused on practice problems and issues, enhanced thinking about practice problems, and achieved practice-relevant outcomes. However, the results indicated that self-directed learning and journal writing were difficult activities for some participants, and some experienced negative emotional responses during reflection. The research concluded that barriers to implementation of Action Learning include a lack of understanding of the process and a perceived lack of support from employers.

Asymmetries of Influence: Differential Effects of Body Postures on Perceptions of Emotional Facial Expressions

The accuracy and speed with which emotional facial expressions are identified is influenced by body postures. Two influential models predict that these congruency effects will be largest when the emotion displayed in the face is similar to that displayed in the body: the emotional seed model and the dimensional model. These models differ in whether similarity is based on physical characteristics or underlying dimensions of valence and arousal. Using a 3- alternative forced-choice task in which stimuli were presented briefly (Exp 1a) or for an unlimited time (Exp 1b) we provide evidence that congruency effects are more complex than either model predicts; the effects are asymmetrical and cannot be accounted for by similarity alone. Fearful postures are especially influential when paired with facial expressions, but not when presented in a flanker task (Exp 2). We suggest refinements to each model that may account for our results and suggest that additional studies be conducted prior to drawing strong theoretical conclusions.

Methodology in Economics: the Logic of Appraisal

This Paper Intends to Develop a Coherent Methodological Framework Concerned with the Appraisal of Scientific Theories in Economics, and Which Is Based on a Postulated Aim of Science. We First Define the Scope of a Methodological Inquiry (Precise Definition of What Is Meant by the Logic of Appraisal of Scientific Theories) and Review the Work of Popper and Lakatos in the Philosophy of Science. We Then Use Their Results to Develop a Rational Structure of Scientific Activity. We Identify and Analyse Both a Micro and Macro Framework for the Process of Appraisal and Single Out the Importance of So-Called 'Fundamental Assumptions' in Creating Externalities in the Appraisal Process Which Forces Us to Adop a Multi-Level Analysis. Special Attention Is Given to the Role and Significance of the Abstraction Process and the Use of Assumptions in General. the Proposed Structure of Scientific Activity Is Illustrated with Examples From Economics.

STUDY OF INFLUENCE OF SAFETY ENGINEERING AND MANAGEMENT PRACTICES IN SELECTED INDUSTRIES IN KERALA

In the twentieth century, as technology grew with it. This resulted in collective efforts and thinking in the direction of controlling work related hazards and accidents. Thus, safety management developed and became an important part of industrial management. While considerable research has been reported on the topic of safety management in industries from various parts of the world, there is scarcity of literature from India. It is logical to think that a clear understanding of the critical safety management practices and their relationships with accident rates and management system certifications would help in the development and implementation of safety management systems. In the first phase of research, a set of six critical safety management practices has been identified based on a thorough review of the prescriptive, practitioner, conceptual and empirical literature. An instrument for measuring the level of practice of these safety conduction a survey using questionnaire in chemical/process industry. The instrument has been empirically validated using Confirmatory Factor Analysis (CFA) approach. As the second step. Predictive validity of safety management practices and the relationship between safety management practices and self-reported accident rates and management system certifications have been investigated using ANOVA. Results of the ANOVA tests show that there is significant difference in the identified safety management practices and the determinants of safety performance have been investigated using Multiple Regression Analysis. The inter-relationships between safety management practices, determinants of safety performance and components of safety performance have been investigated with the help of structural equation modeling. Further investigations into engineering and construction industries reveal that safety climate factors are not stable across industries. However, some factors are found to be common in industries irrespective of the type of industry. This study identifies the critical safety management practices in major accident hazard chemical/process industry from the perspective of employees and the findings empirically support the necessity for obtaining safety specific management system certifications

Publicness of goods and violent conflict : evidence from Colombia

How the degree of publicness of goods affect violent conflict? Based on the theoretical model in Esteban and Ray (2001) we find that the effect of the degree of publicness depends on the group size. When the group is small (large), the degree of publicness increases (decreases) the likelihood of conflict. This opens an empirical question that we tackle using microdata from the Colombian conflict at the municipality level. We use three goods with different publicness degree to identify the sign of the effect of publicness on conflict. These goods are coca crops (private good), road density (public good subject to congestion) and average education quality (a purer public good). After dealing with endogeneity issues using an IV approach, we find that the degree of publicness reduces the likelihood of both paramilitary and guerrilla attacks. Moreover, coca production exacerbates conflict and the provision of both public goods mitigates conflict. These results are robust to size, geographical, and welfare controls. Policies that improve public goods provision will help to fight the onset of conflict.

La política comercial de Estados Unidos en el marco de la Organización Mundial del Comercio. Discurso vs. comportamiento con relación a prácticas anticompetitivas

El objetivo principal de esta monografía es identificar cuáles son las razones que justifican las contradicciones entre el discurso y el comportamiento de Estados Unidos en el marco de la Organización Mundial del Comercio, particularmente con relación a prácticas anticompetitivas derivadas del programa de protección a la agricultura del país. Para ello se analizan el interés nacional y los elementos de la seguridad nacional a partir de los cuales éste se ha construido. También se evalúan los procesos de formulación de política comercial y las interacciones entre los representantes políticos, las asociaciones de productores y el sector privado para mostrar como este comportamiento contradictorio corresponde a la legitimización de un interés particular.

Refutations and the Logic of Practice. 'Refutaciones y la Lógica de la Práctica'.

Resumen basado en el de la publicación

MEASUREMENT AND MODELING OF THE TOXICITY OF BINARY MIXTURES IN THE NEMATODE CAENORHABDITIS ELEGANS-A TEST OF INDEPENDENT ACTION

Ecological risk assessments must increasingly consider the effects of chemical mixtures on the environment as anthropogenic pollution continues to grow in complexity. Yet testing every possible mixture combination is impractical and unfeasible; thus, there is an urgent need for models that can accurately predict mixture toxicity from single-compound data. Currently, two models are frequently used to predict mixture toxicity from single-compound data: Concentration addition and independent action (IA). The accuracy of the predictions generated by these models is currently debated and needs to be resolved before their use in risk assessments can be fully justified. The present study addresses this issue by determining whether the IA model adequately described the toxicity of binary mixtures of five pesticides and other environmental contaminants (cadmium, chlorpyrifos, diuron, nickel, and prochloraz) each with dissimilar modes of action on the reproduction of the nematode Caenorhabditis elegans. In three out of 10 cases, the IA model failed to describe mixture toxicity adequately with significant or antagonism being observed. In a further three cases, there was an indication of synergy, antagonism, and effect-level-dependent deviations, respectively, but these were not statistically significant. The extent of the significant deviations that were found varied, but all were such that the predicted percentage effect seen on reproductive output would have been wrong by 18 to 35% (i.e., the effect concentration expected to cause a 50% effect led to an 85% effect). The presence of such a high number and variety of deviations has important implications for the use of existing mixture toxicity models for risk assessments, especially where all or part of the deviation is synergistic.

Identifying and understanding factors influencing the uptake of new technologies on dairy farms in SW England using the theory of reasoned action

Whilst much is known of new technology adopters, little research has addressed the role of their attitudes in adoption decisions; particularly, for technologies with evident economic potential that have not been taken up by farmers. This paper presents recent research that has used a new approach which examines the role that adopters' attitudes play in identifying the drivers of and barriers to adoption. The study was concerned with technologies for livestock farming systems in SW England, specifically oestrus detection, nitrogen supply management, and, inclusion of white clover. The adoption behaviour is analysed using the social-psychology theory of reasoned action to identify factors that affect the adoption of technologies, which are confirmed using principal components analysis. The results presented here relate to the specific adoption behaviour regarding the Milk Development Council's recommended observation times for heat detection. The factors that affect the adoption of this technology are: cost effectiveness, improved detection and conception rates as the main drivers, whilst the threat to demean the personal knowledge and skills of a farmer in 'knowing' their cows is a barrier. This research shows clearly that promotion of a technology and transfer of knowledge for a farming system need to take account of the beliefs and attitudes of potential adopters. (C) 2006 Elsevier Ltd. All rights reserved.

Use of global gene expression patterns in mechanistic studies of oestrogen action in MCF7 human breast cancer cells

Over the years, the MCF7 human breast cancer cell line has provided a model system for the study of cellular and molecular mechanisms in oestrogen regulation of cell proliferation and in progression to oestrogen and antioestrogen independent growth. Global gene expression profiling has shown that oestrogen action in MCF7 cells involves the coordinated regulation of hundreds of genes across a wide range of functional groupings and that more genes are down regulated than upregulated. Adaptation to long-term oestrogen deprivation, which results in loss of oestrogen-responsive growth, involves alterations to gene patterns not only at early time points (0-4 weeks) but continuing through to later times (20-55 weeks), and even involves alterations to patterns of oestrogen-regulated gene expression. Only 48% of the genes which were regulated >= 2-fold by oestradiol in oestrogen-responsive cells retained this responsiveness after long-term oestrogen deprivation but other genes developed de novo oestrogen regulation. Long-term exposure to fulvestrant, which resulted in loss of growth inhibition by the antioestrogen, resulted in some very large fold changes in gene expression up to 10,000-fold. Comparison of gene profiles produced by environmental chemicals with oestrogenic properties showed that each ligand gave its own unique expression profile which suggests that environmental oestrogens entering the human breast may give rise to a more complex web of interference in cell function than simply mimicking oestrogen action at inappropriate times. (C) 2009 Elsevier Ltd. All rights reserved.