Perturbations of Markov Chains

This thesis is concerned with studying the hitting time of an absorbing state on Markov chain models that have a countable state space. For many models it is challenging to study the hitting time directly; I present a perturbative approach that allows one to uniformly bound the difference between the hitting time moment generating functions of two Markov chains in a neighbourhood of the origin. I demonstrate how this result can be applied to both discrete and continuous time Markov chains. The motivation for this work came from the field of biology, namely DNA damage and repair. Biophysicists have highlighted that the repair process can lead to Double Strand Breaks; due to the serious nature of such an eventuality it is important to understand the hitting time of this event. There is a phase transition in the model that I consider. In the regime of parameters where the process reaches quasi-stationarity before being absorbed I am able to apply my perturbative technique in order to further understand this hitting time

Paradigme éclectique, modèle Uppsala… Quoi de neuf pour analyser les décisions et modes d’investissement à l’international ?

International audienc

Patients’ and Carers’ Perspectives of Psychopharmacological Interventions Targeting Anorexia Nervosa Symptoms

In clinical practice, patients with anorexia nervosa (AN), their carers and clinicians often disagree about psychopharmacological treatment. We developed two corresponding questionnaires to survey the perspectives of patients with AN and their carers on psychopharmacological treatment. These questionnaires were distributed to 36 patients and 37 carers as a quality improvement project on a specialist unit for eating disorders at the South London and Maudsley NHS Foundation Trust. Although most patients did not believe that medication could help with AN, the majority thought that medication for AN should help with anxiety (61.1%), concentration (52.8%), sleep problems (52.8%) and anorexic thoughts (55.6%). Most of the carers shared the view that drug treatment for AN should help with anxiety (54%) and anorexic thoughts (64.8%). Most patients had concerns about potential weight gain, increased appetite, changes in body shape and metabolism during psychopharmacological treatment. By contrast, the majority of carers were not concerned about these specific side effects. Some of the concerns expressed by the patients seem to be AN-related. However, their desire for help with anxiety and anorexic thoughts, which is shared by their carers, should be taken seriously by clinicians when choosing a medication or planning psychopharmacological studies

Continuous renal replacement therapy for the critically ill patient

Since its introduction in 1977, continuous renal replacement therapy has advanced considerably and is now widely used in the management of renal insufficiency in critical illness. Acute kidney injury affects 3.2–18.3% of hospitalized patients, and 35% of critically ill patients (Palevsky et al, 2008; Selby et al, 2012). Whatever the underlying cause, acute kidney injury is associated with increased mortality and is a frequent reason for escalation to critical care for renal replacement therapy

Serra da Estrela Jogável

O objeto do projeto consiste num videojogo de esqui cujo cenário jogável é a estância de desportos de inverno localizada na serra da Estrela. Os modos de jogo compreendem a exploração do cenário, corrida contra o tempo ou prática de acrobacias no local do cenário apropriado para o efeito. O mundo virtual é enriquecido por alterações ambientais e climatéricas dinâmicas e o cenário contém marcadores com fotos panorâmicas reais do local onde estes se encontram. A interação é feita através do detetor de movimentos Leap Motion, que a partir dos movimentos das mãos do utilizador controla o deslocamento da personagem; a interação é auxiliada por uns óculos de Realidade Virtual que imergem o público no mundo digital através de um abrangente campo de visão estereoscópica. A principal motivação é a concretização pessoal e reconhecimento académico, o projeto prova que é possível criar novas experiências imersivas vídeo jogáveis para o público em geral com recursos atualmente disponíveis.The object of the project is a videogame whose playable scenario is the winter sports resort located at serra da Estrela. The game modes range from exploring the scenario, race against the clock or perform tricks in the snow park. The virtual world is enriched with environmental and climatic changes, and the scenario has markers with the respective panoramic photos of the real place. The interaction is done through the Leap Motion tracker that uses the user hands movement to control the character motion; the interaction is reinforced with a Virtual Reality headset that emerge the public inside the virtual world with a large stereoscopic field of vision. The main motivations range from personal and academic recognition, and the project is also a proof of concept that it is possible to create new immersive playable experiences for the general public with available resources

Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring

Objectives.This study compared the effects of amlodipine, atenolol and their combination on ischemia during treadmill testing and 48-h ambulatory monitoring.Background.It is not known whether anti-ischemic drugs exert similar effects on ischemia during ambulatory monitoring and exercise treadmill testing.Methods.Patients with stable coronary artery disease and ischemia during treadmill testing and ambulatory monitoring were randomized to receive amlodipine (n = 51) or atenolol (n = 49). Each group underwent a counterbalanced, crossover evaluation of single drug and placebo, followed by evaluation of the combination.Results.Amlodipine and the combination prolonged exercise time to 0.1-mV ST segment depression by 29% and 34%, respectively (p < 0.001) versus 3% for atenolol (p = NS). During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p = 0.083 [NS]), by 57% with atenolol (p < 0.001) and by 72% with the combination (p < 0.05 vs. both single drugs; p < 0.001 vs. placebo). Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina. Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.005 vs. placebo, atenolol and amlodipine). In patients with angina, total exercise time improved by 16% with amlodipine (p < 0.001), by 4% with atenolol (p = NS) and by 19% with the combination (p < 0.05 vs. placebo and either single drug). In those patients without angina, no therapy significantly improved total exercise time.Conclusions.Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination was more effective than either single drug in both settings

Effects of Short-Term Exposure to Inhalable Particulate Matter on Telomere Length, Telomerase Expression, and Telomerase Methylation in Steel Workers

Shortened leukocyte telomere length (LTL) is a marker of cardiovascular risk that has been recently associated with long-term exposure to ambient particulate matter (PM). However, LTL is increased during acute inflammation and allows for rapid proliferation of inflammatory cells. Whether short-term exposure to proinflammatory exposures such as PM increases LTL has never been evaluated.We investigated the effects of acute exposure to metal-rich PM on blood LTL, as well as molecular mechanisms contributing to LTL regulation in a group of steel workers with high PM exposure.We measured LTL, as well as mRNA expression and promoter DNA methylation of the telomerase catalytic enzyme gene [human telomerase reverse transcriptase (hTERT)] in blood samples obtained from 63 steel workers on the first day of a workweek (baseline) and after 3 days of work (postexposure).LTL was significantly increased in postexposure (mean \ub1 SD, 1.43 \ub1 0.51) compared with baseline samples (1.23 \ub1 0.28, p-value < 0.001). Postexposure LTL was positively associated with PM\u2081\u2080 (\u3b2 = 0.30, p-value = 0.002 for 90th vs. 10th percentile exposure) and PM\u2081 (\u3b2 = 0.29, p-value = 0.042) exposure levels in regression models adjusting for multiple covariates. hTERT expression was lower in postexposure samples (1.31 \ub1 0.75) than at baseline (1.68 \ub1 0.86, p-value < 0.001), but the decrease in hTERT expression did not show a dose-response relationship with PM. We found no exposure-related differences in the methylation of any of the CpG sites investigated in the hTERT promoter.Short-term exposure to PM caused a rapid increase in blood LTL. The LTL increase did not appear to be mediated by PM-related changes in hTERT expression and methylation

Regulation of NMDA Receptor Signaling at Single Synapses by Human Anti-NMDA Receptor Antibodies

The NMDA receptor (NMDAR) subunit GluN1 is critical for receptor function and plays a pivotal role in synaptic plasticity. Mounting evidence has shown that pathogenic autoantibody targeting of the GluN1 subunit of NMDARs, as in anti-NMDAR encephalitis, leads to altered NMDAR trafficking and synaptic localization. However, the underlying signaling pathways affected by antibodies targeting the NMDAR remain to be fully delineated. It remains unclear whether patient antibodies influence synaptic transmission via direct effects on NMDAR channel function. Here, we show using short-term incubation that GluN1 antibodies derived from patients with anti-NMDAR encephalitis label synapses in mature hippocampal primary neuron culture. Miniature spontaneous calcium transients (mSCaTs) mediated via NMDARs at synaptic spines are not altered in pathogenic GluN1 antibody exposed conditions. Unexpectedly, spine-based and cell-based analyses yielded distinct results. In addition, we show that calcium does not accumulate in neuronal spines following brief exposure to pathogenic GluN1 antibodies. Together, these findings show that pathogenic antibodies targeting NMDARs, under these specific conditions, do not alter synaptic calcium influx following neurotransmitter release. This represents a novel investigation of the molecular effects of anti-NMDAR antibodies associated with autoimmune encephalitis