Common pathways in idiopathic pulmonary fibrosis and cancer

Idiopathic pulmonary fibrosis (IPF) is marked by a very disappointing survival rate and still represents a clinical dilemma. According to the current pathogenic hypothesis, chronic damage of the alveolar epithelium is followed by abnormal tissue repair and impairment of the alveolar structure. This process is driven by pathogenic events very similar to cancer, including epigenetic and genetic changes, altered response to regulatory signals, abnormal expression of microRNAs and activation of specific signalling pathways. IPF also resembles cancer with regard to its poor response to medical treatment and prognosis, which is very often worse than many cancers. We have hypothesised that IPF might be assimilated to a neoproliferative disorder of the lung. Viewing IPF as a cancer-like disease may satisfy the need for a better understanding of the pathogenesis of IPF by exploiting the large amount of knowledge that cancer biology evokes. The recognition of common pathogenic pathways between the two diseases may stimulate new clinical trials with cancer drugs, different drug combinations and different lines of drugs, as already experimented in oncology. Moreover, the concept of IPF as a cancer-like disorder may improve the attention given to this dreadful disease on a public, political and healthcare level

When to start and when to stop antifibrotic therapies

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive changes of the lung architecture causing cough and dyspnoea and ultimately leading to lung failure and death. Today, for the first time, two drugs that may reduce the inexorable progression of the disease are available, suggesting that treatment with specific drugs for IPF should be started as soon as diagnosis is made. This applies to any disease and particularly to IPF, which is marked by a 5-year survival comparable or even worse than many cancers. However, despite common sense and even worse, in spite of scientific data coming from clinical trials, post hoc analysis, long-term safety studies and real-life experiences, the question of when to start and when to stop treatment with antifibrotics is still debated. In IPF, particularly when the disease is diagnosed at an early stage, "wait and watch" behaviour is not rare to observe. This is largely due to the lack of awareness of both patients and clinicians regarding the progression of the disease and its prognosis. Another important issue is when treatment should be stopped. In general, there are two main reasons to stop a therapy: unbearable side-effects and/or lack of efficacy. According to current (although preliminary) evidence, antifibrotic drugs should not be discontinued except for safety issues

Bayesian principles or Gestalt perception for clinical judgment

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Coronary prevention in two European areas with different risk levels, Stockholm and Sicily : doctors' risk judgments and statin utilization

Introduction International guidelines on the primary prevention of cardiovascular disease recommend that preventive measures should be based on the doctors’ quantitative total risk assessment of the patient. Treatment is recommended when the patient’s risk is above a certain threshold. Risk scoring systems have been developed to assist clinicians with risk estimates. However, in clinical practice this estimation is usually made subjectively. This implies that factors unrelated to the true risk of the patients may influence the doctors’ risk estimates and decisions about treatment. Aim We aimed to study coronary preventive care in two areas with different coronary risk levels, with special reference to doctors’ attitudes in investigating risk factors, and their risk assessments and decisions about treatment. In accordance with the different levels of cardiovascular risk in the areas studied, we also aimed to test the hypothesis that the same set of risk factors may be perceived as indicating higher risk in a high-risk country, than in a low-risk country. Methods The studies were performed in two European areas, one with a high and the other with a low level of population cardiovascular risk, Stockholm county and Sicily, respectively. Questionnaires on doctors’ clinical practice (Study I) and written patient cases (Studies II-IV) were presented to random samples of doctors in Stockholm and in Sicily. The cases were constructed according to the Framingham scoring system, ranging from very high- to very low-risk cases. Differences in the use of statins and coronary mortality in the populations (Study V) were studied by collecting official data from the health care systems in both areas. Results and Discussion There were differences in the management of hyperlipidaemia (Study I). More doctors in Stockholm investigated lipids in patients with other cardiovascular risk factors. The cholesterol level at which doctors started lipid-lowering treatment was higher in Stockholm than in Sicily. In Study II, General Practitioners (GPs) were asked to evaluate nine written patient cases. Their coronary risk estimates showed large variability, especially in high-risk cases, and in general the risk was underestimated compared to the risk calculated according to the Framingham equations. Contrary to the hypothesis, GPs in Stockholm made lower estimates and less often decided to start lipid-lowering treatment than was the case in Sicily. A possible reason for this is that a high background risk level of the population tends to suppress the risk estimate of an individual with a certain set of risk factors, and vice versa if the population risk is low. Support to such line of thinking was found comparing risk estimates and decisions about treatment between doctors who usually deal with coronary preventive care: GPs, cardiologists and internists (Study III). Compared to the other specialists, cardiologists, who usually deal with high-risk patients, showed lower risk estimates when assessing the same set of patient cases. In study IV we found that the task of risk rating and the task of making decisions about treatment did not mutually influence each other. Female GPs and GPs with shorter clinical experience were more likely to make correct decisions. The differences in coronary risk ratings and decisions about treatment observed in the two areas with different population coronary risk levels may be related to the use of statins in the whole population of the respective area. Study V investigated the time trends in the relations between population coronary risk levels, expressed as coronary mortality, and use of statins, in the period 2001-2011. In both areas there was a reduction in coronary mortality and an increase in statin utilization. A larger reduction in coronary mortality was observed in Stockholm compared to Sicily, whereas the statin utilization increased more in Sicily than in Stockholm. Thus, the changes over time in statin utilization seem inversely associated with the changes in coronary mortality. However, the influence of other variables that are independent of the population coronary risk, such as cost containment policies, socioeconomic gradients in the use of statins, and drug discontinuation rate, must be taken into account. Conclusions There are several differences in primary coronary prevention between the two European areas with different population cardiovascular risk profiles. Doctors’ quantitative risk estimates and decisions about treatment are influenced by factors not directly related to the actual risk of the patients, and seem tentatively to be inversely related to the background cardiovascular risk in the population. The differences in primary coronary prevention may contribute to an increase in statin utilization that is not justified by changes in population coronary risk. The results of the thesis may help in the development of decision tools and recommendations for primary coronary prevention

Development of system design information for carbon dioxide using an amine type sorber

Development work on system design information for amine type carbon dioxide sorber is reported. Amberlite IR-45, an aminated styrene divinyl benzene matrix, was investigated to determine the influence of design parameters of sorber particle size, process flow rate, CO2 partial pressure, total pressure, and bed designs. CO2 capacity and energy requirements for a 4-man size system were related mathematically to important operational parameters. Some fundamental studies in CO2 sorber capacity, energy requirements, and process operation were also performed

Exploring Educators’ Decisions During the Era of New Professionalism : Teachers and Administrators Dialoguing Together in a Performance-Based Pay School District

The purpose of this action research study was to examine how teachers embedded in cultures of accountability, performance, and rewards, attempted to maintain integrity and professionalism in their instructional choices, with administrators as supportive partners. In addition, I aimed to explore how teachers and administrators balance power relations while negotiating this terrain. The research questions that guided this dissertation study were: 1. When given a supportive space for ongoing dialogue in the current era of new professionalism and neoliberalism, how do we as teachers and administrators describe our educational decisions while functioning in evaluation systems? 2. What kinds of actions might teachers recommend or consider taking regarding how administrators can best support their instructional decision-making in this era of heightened accountability? Teacher accountability policies since 2001 have changed the landscape of education in the United States, with a heightened emphasis on the yearly evaluation scores of educators. Hence, this study took place within the new era of heightened accountability and rewards cultures that prevailed in education. I conducted a participatory action research (PAR) study consisting of eight participants (seven teachers and myself, an administrator) who met weekly in a professional learning community (PLC) and journaled online about these sessions, as well as their everyday experiences. These findings add to research regarding the effects of new professionalism on both teachers and administrators and how an in-depth look at the daily interactions between these groups can inform future legislation and local decisions regarding educator practice and evaluation systems

Development of a regenerable carbon dioxide removal system Final report, Jun. 1965 - Jan. 1968

Design criteria for regenerative carbon dioxide removal system for manned spacecraf

Chapitre VI. Le moment Canudo

L’art ou la condition historique du cinéma Le cinéma ne devient pas un art parce qu’il réussit l’examen de son habilitation esthétique ou parce qu’il est enfin devenu capable de satisfaire aux critères que lui adresse la critique et que lui inspire l’Académie. Non, il n’y parvient qu’au terme d’un conflit artistique aux multiples rameaux, qui s’est soldé par un coup de force théorique dont le succès a eu pour conséquence de bloquer l’histoire du cinéma en solidarisant le nom de cinéma et le m..

Chapitre II. Théories du cinéma

La littérature théorique qui s’est saisie du cinéma a fait valoir une puissance de droit du discours qui a largement déterminé son évolution. En se demandant si le cinéma pouvait être un art, les théories ne nous ont donc pas seulement renseignés sur le désir de légitimation artistique qui s’est emparé d’une époque, elles nous ont plus volontiers prévenus de la révolution esthétique que l’art engageait sur lui-même. L’un ne va pas sans l’autre. Le parcours théorique qui va suivre devrait nous..