Anger Et Cetera: Understanding the Emotions in Ethics

This dissertation argues in part that because the ethical theory of sentimentalism is based on the mistaken belief that emotions are non-cognitive, sentimentalism cannot account for the fact of the influence of cognition in morality and moral action. Therefore sentimentalism is of little use in ethics. This work is done by going back to examine Western thinking on the emotions from its dawn in Homer\u27s writing through to contemporary philosophy and neurophysiology on the emotions. Following the development of the way emotions were thought of and how they related to ethics allows the identification of an intellectual forked path brought about by Stoic thinking on emotions and morality and calcified by the work of Ren퀌 Descartes on the emotions. I identify three `Cartesian errors\u27 that have made their way through to David Hume\u27s thought and from there to contemporary thinking on the emotions. The first Cartesian error is the belief that `mind\u27 or `mental activity\u27 is pure cognition and that `body\u27 is an unthinking machine responsive only to pleasure and pain and having nothing to do with cognition. The second Cartesian error is the irreparable separation of emotion from cognition which forces a theory into an untenable, ad hoc distinction between calm and violent passions in order to imbue some emotions with intelligence. The third Cartesian error is being unable to coherently explain how the mind and the body could have duplex communication between `mind\u27 and `body\u27. I explain how the two contemporary camps, both `cognitivists\u27 and `physicalists\u27 about emotions are compromised by the Cartesian errors. Finally, I show how experience, common sense and contemporary empirical findings in neurophysiology recommend to us a pluralist view of the emotions that avoids the Cartesian errors and fully embraces both their physiological basis and their accompanying `cognitivity\u27, as well as a fruitful cognitive ethical theory that is something of a middle ground between the sentimentalism of Shaftesbury and Hume and the rationalist positions of thinkers such as Socrates and Berkeley. This theory, which will be worked out in more detail in the future, is a synthesis of the findings of Plato, Aristotle, Lucretius, psychologist Richard Lazarus and contemporary psychophysiology

Cartographie in vivo des remaniements anatomo-fonctionnels de l'architecture des réseaux neuronaux dans le système nerveux central au cours du développement par Imagerie du Tenseur de Diffusion et Imagerie renforcée par le manganèse

L objectif de cette thèse est de développer des méthodes IRM permettant d étudier l impact d une ischémie focale transitoire sur le cerveau de rat nouveau-né. Les techniques utilisées sont l imagerie à contraste renforcé par le manganèse (MEMRI), l imagerie du tenseur de diffusion (DTI) ainsi que de façon préliminaire l imagerie Q-ball (QBI). Le MEMRI après injection intra cérébrale a été utilisé afin d étudier de manière dynamique le tractus cortico-thalamique, en parallèle le DTI a servi de marqueur de la structuration cérébrale. Les résultats ont montré une atteinte du tractus cortico-thalamique ipsi-latéral, sept et quatorze jours après ischémie. De manière générale le DTI a montré une structuration ralentie à la suite de l ischémie. A partir de ces résultats la faisabilité d une méthode d acquisition rapide et de traitement de données Q-ball a été établie puis testée sur un animal immature. Les méthodes mises en place se sont révélées efficaces dans le suivi de la maturation cérébrale dans des conditions normales ainsi que pathologiques, ouvrant des perspectives d études liées au développement cérébral.The thesis aim is to develop MRI methods to study the impact of focal transient ischemia in neonatal rat brain. The principal techniques used are MEMRI (Manganese Enhanced MRI), DTI (Diffusion Tensor Imaging) and QBI (Q-Ball Imaging). MEMRI was used to observe in a dynamic way the cortico-thalamic manganese transport combined with the structural informations extracted from the DTI experiments. Results have shown a cortico-thalamic pathway disturbance, at seven and fourteen days after ischemia. Globally DTI results have shown a slowed brain structuration. From these results, the feasibility of a fast acquisition method and the post processing steps of Q-ball protocol was established and applied in an immature rat. The different MRI protocols developed during this thesis have shown good efficiency to follow the rat brain maturation, in healthy and pathological conditions, thus opening new perspectives for brain development studies.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Efficacy of tigecycline for the treatment of complicated intraabdominal infections in real-life clinical practice from five european observational studies

Objectives: Tigecycline is a broad-spectrum antibiotic approved for the treatment of complicated intra-abdominal infections (cIAIs). The efficacy of tigecycline when administered as monotherapy or in combination with other antibacterials in the treatment of cIAIs in routine clinical practice is described. Patients and methods: Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011). Results: A total of 785 cIAI patients who received tigecycline were included (mean age 63.1+14.0 years). Of these, 56.6% were in intensive care units, 65.6% acquired their infection in hospital, 88.1% had at least one comorbidity and 65.7% had secondary peritonitis. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 16.9+7.6 (n=614) and 7.0+4.2 (n=108), respectively, indicating high disease severity. Escherichia coli (41.8%), Enterococcus faecium (40.1%) and Enterococcus faecalis (21.1%) were the most frequently isolated pathogens; 49.1% of infections were polymicrobial and 17.5% were due to resistant pathogens. Overall, 54.8% (n=430) received tigecycline as monotherapy and 45.2% (n=355) as combination therapy for a mean duration of 10.6 days. Clinical response rates at the end of treatment were 77.4% for all patients (567/733), 80.6% for patients who received tigecycline as monotherapy (329/408), 75.2% for patients with a nosocomial infection (354/471), 75.8% for patients with an APACHE II score .15 (250/330) and 54.2% (32/59) for patients with a SOFA score =7. Conclusions: In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cIAI with a high severity of illness

The Politicization of the European Union

What are the consequences of EU politicization for the EU and European societies? This book shifts the analytical focus from EU politicization processes to their empirical and normative research on the effects of politicization on public opinion, public discourses, policymaking and European integration

Toxoplasmosis in transplant recipients, Europe, 2010-2014

Transplantation activity is increasing, leading to a growing number of patients at risk for toxoplasmosis. We reviewed toxoplasmosis prevention practices, prevalence, and outcomes for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT; heart, kidney, or liver) patients in Europe. We collected electronic data on the transplant population and prevention guidelines/regulations and clinical data on toxoplasmosis cases diagnosed during 2010-2014. Serologic pretransplant screening of allo-hematopoietic stem cell donors was performed in 80% of countries, screening of organ donors in 100%. SOT recipients were systematically screened in 6 countries. Targeted anti-Toxoplasma chemoprophylaxis was heterogeneous. A total of 87 toxoplasmosis cases were recorded (58 allo-HSCTs, 29 SOTs). The 6-month survival rate was lower among Toxoplasma-seropositive recipients and among allo-hematopoietic stem cell and liver recipients. Chemoprophylaxis improved outcomes for SOT recipients. Toxoplasmosis remains associated with high mortality rates among transplant recipients. Guidelines are urgently needed to standardize prophylactic regimens and optimize patient management

Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders.

Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called episignatures ). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight their key features as they are related to genetic heterogeneity, dosage effect, unaffected carrier status, and incomplete penetrance. We demonstrate the necessity of multiclass modeling for accurate genetic variant classification and show how disease classification using a single episignature at a time can sometimes lead to classification errors in closely related episignatures. We demonstrate the utility of this tool in resolving ambiguous clinical cases and identification of previously undiagnosed cases through mass screening of a large cohort of subjects with developmental delays and congenital anomalies. This study more than doubles the number of published syndromes with DNA methylation episignatures and, most significantly, opens new avenues for accurate diagnosis and clinical assessment in individuals affected by these disorders

The Impact of Different Antibiotic Regimens on the Emergence of Antimicrobial-Resistant Bacteria

Backgroud: The emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address. Methods/Principal Findings: A model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains. Conclusions/Significance: The principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance

Relevance of platelet desialylation and thrombocytopenia in type 2B von Willebrand disease: preclinical and clinical evidence

Patients with type 2B von Willebrand disease (vWD) (caused by gain-of-function mutations in the gene coding for von Willebrand factor) display bleeding to a variable extent and, in some cases, thrombocytopenia. There are several underlying causes of thrombocytopenia in type 2B vWD. It was recently suggested that desialylation-mediated platelet clearance leads to thrombocytopenia in this disease. However, this hypothesis has not been tested in vivo. The relationship between platelet desialylation and the platelet count was probed in 36 patients with type 2B von Willebrand disease (p.R1306Q, p.R1341Q, and p.V1316M mutations) and in a mouse model carrying the severe p.V1316M mutation (the 2B mouse). We observed abnormally high elevated levels of platelet desialylation in both patients with the p.V1316M mutation and the 2B mice. In vitro, we demonstrated that 2B p.V1316M/von Willebrand factor induced more desialylation of normal platelets than wild-type von Willebrand factor did. Furthermore, we found that N-glycans were desialylated and we identified αIIb and β3 as desialylation targets. Treatment of 2B mice with sialidase inhibitors (which correct platelet desialylation) was not associated with the recovery of a normal platelet count. Lastly, we demonstrated that a critical platelet desialylation threshold (not achieved in either 2B patients or 2B mice) was required to induce thrombocytopenia in vivo. In conclusion, in type 2B vWD, platelet desialylation has a minor role and is not sufficient to mediate thrombocytopenia

The Politicization of the European Union

What are the consequences of EU politicization for the EU and European societies? This book shifts the analytical focus from EU politicization processes to their empirical and normative research on the effects of politicization on public opinion, public discourses, policymaking and European integration

Effects of macromolecular crowding on intracellular diffusion from a single particle perspective

Compared to biochemical reactions taking place in relatively well-defined aqueous solutions in vitro, the corresponding reactions happening in vivo occur in extremely complex environments containing only 60–70% water by volume, with the remainder consisting of an undefined array of bio-molecules. In a biological setting, such extremely complex and volume-occupied solution environments are termed ‘crowded’. Through a range of intermolecular forces and pseudo-forces, this complex background environment may cause biochemical reactions to behave differently to their in vitro counterparts. In this review, we seek to highlight how the complex background environment of the cell can affect the diffusion of substances within it. Engaging the subject from the perspective of a single particle’s motion, we place the focus of our review on two areas: (1) experimental procedures for conducting single particle tracking experiments within cells along with methods for extracting information from these experiments; (2) theoretical factors affecting the translational diffusion of single molecules within crowded two-dimensional membrane and three-dimensional solution environments. We conclude by discussing a number of recent publications relating to intracellular diffusion in light of the reviewed material