Le projet de recherche que j’ai suivi depuis 2015 concerne le diagnostic des troubles respiratoires du sommeil chez les enfants ayant une maladie génétique et leur prise en charge. Le projet a été développé entièrement dans l’unité de ventilation non invasive (VNI) et du sommeil de l’enfant de l’hôpital Necker Enfants malades de Paris.Dans le premier parti je me suis concentré sur le développement des nouveaux outils pour le diagnostic des troubles respiratoires du sommeil. La polysomnographie (PSG) représente l’examen de référence pour l’étude de troubles respiratoires du sommeil chez l’enfant. Néanmoins cet examen n’est pas disponible dans la plupart des centres hospitalier, est couteux et d’interprétation difficile. En plus, la qualité de l’examen est souvent réduite à cause de la perte involontaire ou à cause de l’intolérance de l’enfant aux capteurs posés. Pour cette raison, une de tache plus importante dans ce domaine c’est de développer des outils diagnostiques capables d’ameliorer la tolérance à l’examen et aussi sa performance. La première étude que j’ai suivie regarde la validation d’un particulaire capteur sous sternal pour la caractérisation des évènements respiratoires pendant une polygraphie ventilatoire. Les résultats de cette étude ont été publiés en 2016 (J Clin Sleep Med. 2016 Sep 13.). Une deuxième partie concerne la validation du même capteur pour la détection des évènements respiratoires chez l’enfant. Cette étude est actuellement en cours. Le but de ce projet est donc de démontrer la validité de ce capteur pour la détection et la caractérisation des évènements respiratoires chez l’enfant pour pouvoir permettre un ‘analyse complémentaire par rapport aux signaux dérivant des canules nasales et des bandes thoraco abdominales.La deuxième étude a analysé l’utilité de réductions de l’amplitude de l’onde de pouls pendant une polysomnographie, comme mesure des réveils corticaux liés aux évènements respiratoires. Le but de cette étude était de valider l’utilisation d’un outil simple pour remplacer l’analyse de l’EEG pour la détection des réveils corticaux associé aux évènements respiratoires. Les résultats de cette étude ont été publiés (Sleep Med. 2017 Jun;34:64-70).En ce qui concerne le deuxième parti je me suis concentré sur le traitement des troubles respiratoires du sommeil. La première étude a concerné l’efficacité du traitement par PPC dans une cohorte d’enfants ayant une séquence de Pierre Robin. Le but de cette etude etait de prouver l’efficacité de ce traitement pour eviter la tracheostomie dans ce groupe d’enfants ayant une obstruction severe des voies aeriennes superieures. Les résultats de cette étude ont été publiés en 2016 (Continuous Positive Airway Pressure for Upper Airway Obstruction in Infants with Pierre Robin Sequence (Reconstr Surg. 2016 Feb;137(2):609-12). La deuxième étude a permis d’analyser les critères de début de ventilation noninvasive (VNI) ou PPC dans une population d’enfant ayant des maladies génétiques hétérogènes. Les résultats de cette étude ont été publiés en 2016 (Sep;51(9):968-74). J’ai ensuite conclu une étude sur le début d’un traitement par PPC en ambulatoire. L’etude est actuellement en révision.J’ai aussi collaboré dans l’analyse des données et dans la rédaction des plusieurs études concernant les caractéristiques des troubles respiratoires du sommeil et de leur prise en charge chez des enfants porteurs de trisomie 21, de myasthénie congénitale et d’achondroplasie.J’ai ensuite recueilli les caractéristiques des troubles du sommeil dans une cohorte des patientes porteuses d’un syndrome de Rett. / The research project I carried out since 2015 concerns the “diagnosis and treatment of SDB in children with genetic diseases”. The entire project was developed at the NIV and sleep unit of Necker Children Hospital in Paris.The first aim of my research project is focused on the development and improvement of new tools to diagnose SDB in children. PSG remains the gold standard for the diagnosis of SDB, but this exam is expensive, time consuming, difficult to interpret and most important, not available in most paediatric centres. Moreover, PSG quality is often affected by the involuntary displacement or loss of sensors or by the intolerance of the different sensors by the child. Given these considerations, one of the main challenges in paediatric sleep medicine is the development and validation of simplified tools, capable of improving the tolerance issues while assuring high and reliable accuracy.The first project I developed concerned the validation of a suprasternal pressure sensor to characterise sleep apnoea during respiratory polygraphy. This study was published in the Journal of Clinical Sleep Medicine in December 2016. A second part of this study is currently ongoing and explores the usefulness of the same sensor for the detection of respiratory events. The aim of this two part project is to demonstrate the validity of this sensor for the detection of airflow and respiratory efforts in children, thus allowing complementary analysis to nasal cannula and thoraco abdominal belts.The second project I carried out regards the use of the variations of pulse wave amplitude (PWA) as a surrogate of cortical microarousals. This study aimed at the validation of a surrogate of cortical microarousals in order to replace the standard EEG signal for their detection and to use PWA as a simple tool for the scoring of hypopneas during respiratory polygraphy. This study was published in Sleep Medicine in June 2017.During my PhD program, I also collaborate to another study concerning the use of pulse transit time (PTT) for the characterisation of respiratory events during polygraphy. This study was published in Sleep and Breathing in March 2017.The second axe of my research concerned the treatment of SDB in children with genetic and congenital disorders. The first study concerned the use of CPAP in the treatment algorithm of a series of infants with Pierre Robin sequence. This study highlighted the usefulness of CPAP in avoiding tracheostomy in this particular group of patients with severe OSAS. This paper was published in Plastic and Reconstructive Surgery in February 2016. The second study aimed at the identification of objective criteria that lead to the initiation of CPAP or NIV in children and infants. This study was published in Pediatric Pulmonology in September 2016. I also collaborated to the conception, data analysis and draft redaction of a second manuscript regarding the criteria authorising the weaning from CPAP and NIV in children. This paper was published in Pediatric Pulmonology in September 2017. A third article concerning a programme of outpatient initiation of CPAP in children is currently under revision in the Journal of Clinical and Sleep Medicine.I also collaborated in the conception, data analysis and manuscript revision of other papers regarding the description and management of SDB in children with Down syndrome, congenital myasthenia and achondroplasia.Finally, I am the first investigator of a study concerning sleep structure and sleep related respiratory events in girls with Rett syndrome.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / This paper proposes a technological solution using a predictive analysis model to identify and reduce the level of risk for type 2 diabetes mellitus (T2DM) through a wearable device. Our proposal is based on previous models that use the auto-classification algorithm together with the addition of new risk factors, which provide a greater contribution to the results of the presumptive diagnosis of the user who wants to check his level of risk. The purpose is the primary prevention of type 2 diabetes mellitus by a non-invasive method composed of the phases: (1) Capture and storage of risk factors; (2) Predictive analysis model; (3) Presumptive results and recommendations; and (4) Preventive treatment. The main contribution is in the development of the proposed application. / Revisión por pares

I sampled the eastern portion of the Fort Apache Indian Reservation from June 19 to August 8 in 2008 and from May 6 to June 19 in 2009. I used scat detection dogs to find wolf (Canis lupus baileyi) scat on the Fort Apache Indian Reservation during 2008 and 2009. My population size estimate of the wolf population was 19 individuals (95% CI = 14 - 58; SE = 8.30) during 2008 and 2009. My study also used DNA analyses to obtain an accurate assessment of Mexican wolf diet and, compare prey remains in Mexican gray wolf scat with prey remains in two other sympatric carnivore species (coyote, C. latrans, and puma, Puma concolor). Percent biomass of prey items consumed by Mexican wolves included 89% for elk, 8% for mule deer, and 3% for coyote. Percent biomass of prey items consumed by pumas was 80% for elk, 12% for mule deer, 4% for turkey, and 4% for fox. I included an ethnographic feature to my research. My study showed evidence of shared knowledge about the wolf within Western Apache culture. My data fit the consensus model based upon the large ratio between the first and second eigenvalues. I provided a literature review of how traditional ecological knowledge has enhanced the field of conservation biology but also the challenges of collecting and incorporating it with western science. Lastly, I provide an historical perspective of wolves throughout Arizona, an assessment of their historical abundance, and document a possible mesocarnivore release. Between 1917 and 1964, 506 wolves, 117,601 coyotes, 2,608 mountain lions, 1,327 bears, 19,797 bobcats, and 21 jaguars were killed by PARC agents, bounty hunters, and ranchers as reported in U.S. Bureau of Biological Survey Annual Reports in Arizona. The relationship between the numbers of coyotes and wolves destroyed was investigated using Pearson correlation coefficient. There was a negative correlation between the numbers of wolves and coyotes destroyed in Arizona between 1917 and 1964 (r = -0.40; N = 46; p = 0.01) suggesting a possible mesopredator release of coyotes with the extirpation of the wolf in Arizona.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / To analyze the roles of CCTA, MPI, and CC to formulate a sequential clinical algorithm to use in patients with chest pain, risk factors for CAD, and an abnormal EKG. The goals of the study are to streamline and refine workup, to decrease radiation exposure to patients, and to contain costs. 39 patients underwent CCTA, MPI, and CC within 30 months of each other. CCTA was used to categorize mild, moderate, or severe CAD. MPI used SSS, SDS, TID, and formal reading to define mild, moderate, or severe physiologic ischemia. CC and coronary intervention cine films were analyzed to define and treat anatomical CAD medically or by intervention. Results: There was strong correlation between CCTA, CC, and treatment type (p<0.0001). CCTA was able to stratify all patients with mild or severe ischemia to appropriate treatment groups, and to reduce the need for MPI. With moderate ischemia from CCTA, the additional use of MPI could have reduced the need for 16/18 (89%) patients who underwent CC to undergo further testing. No patients with mild or moderate CAD by CCTA, followed by mild to moderate physiologic ischemia by MPI, needed CC or intervention. 37/39 patients (95%) could have avoided one or more tests using our algorithm. CCTA followed by MPI may be used in symptomatic patients with risk factors for CAD and an abnormal EKG to stratify mild and moderate CAD, and to thereby avoid cardiac catheterization. Our algorithm could lead to savings in healthcare expenditures, save patients from unnecessary invasive procedures, decrease radiation exposure, and total cost.

UA Open Access Publishing Fund / Background: Noninvasive positive-pressure ventilation (NIPPV) use has increased in the treatment of patients with respiratory failure. However, despite decreasing the need for intubation in some patients, there are no data regarding the risk of intubation-related complications associated with delayed intubation in adult patients who fail NIPPV. The objective of this study is to evaluate the odds of a composite complication of intubation following failed NIPPV compared to patients intubated primarily in the medical intensive care unit (ICU). Methods: This is a single-center retrospective cohort study of 235 patients intubated between 1 January 2012 and 30 June 2013 in a medical ICU of a university medical center. A total of 125 patients were intubated after failing NIPPV, 110 patients were intubated without a trial of NIPPV. Intubation-related data were collected prospectively through a continuous quality improvement (CQI) program and retrospectively extracted from the medical record on all patients intubated on the medical ICU. A propensity adjustment for the factors expected to affect the decision to initially use NIPPV was used, and the adjusted multivariate regression analysis was performed to evaluate the odds of a composite complication (desaturation, hypotension, or aspiration) with intubation following failed NIPPV versus primary intubation. Results: A propensity-adjusted multivariate regression analysis revealed that the odds of a composite complication of intubation in patients who fail NIPPV was 2.20 (CI 1.14 to 4.25), when corrected for the presence of pneumonia or acute respiratory distress syndrome (ARDS), and adjusted for factors known to increase complications of intubation (total attempts and operator experience). When a composite complication occurred, the unadjusted odds of death in the ICU were 1.79 (95% CI 1.03 to 3.12). Conclusions: After controlling for potential confounders, this propensity-adjusted analysis demonstrates an increased odds of a composite complication with intubation following failed NIPPV. Further, the presence of a composite complication during intubation is associated with an increased odds of death in the ICU.

ABSTRACT Patients with respiratory failure secondary to acute asthma exacerbation (AAE) frequently present at emergency units. Some patients may develop respiratory muscle fatigue. Current guidelines for the treatment of an AAE center on pharmacological treatment and invasive mechanical ventilation. Noninvasive positive pressure ventilation (NPPV) has an established role in COPD exacerbations. The role it can play in an AAE remains unanswered although it is frequently used in the clinical setting. Aims: The present study proposed to investigate if the early use of NPPV in the forms of continuous positive airway pressure (CPAP) or bilevel positive pressure ventilation (BPPV) together with standard medical therapy in AAE can decrease time of response to therapy compared to standard medical therapy alone. We further tested the effect of BPPV against CPAP. Methods: Asthmatic patients who presented with a severe AAE (PEFR % predicted < 60 %) at the emergency unit were randomized to either standard medical therapy (ST), ST and CPAP or ST and BPPV. Thirty patients fulfilled the inclusion criteria for the study. Groups presented similar baseline characteristics. The mean age for the group was 42.1 ± 12.6 years. Mean baseline PEFR % predicted was 35.2 ± 10.7 % (ST), 30.5 ± 11.7 % (ST + CPAP) and 33.5 ±13.8 % (ST + BPPV). Results: Hourly improvement (Δ) in respiratory rate and sensation of breathlessness was significantly better in the BPPV intervention group. Improvement (Δ) from baseline to end of treatment in respiratory rate and sensation of breathlessness was significant for both CPAP and BPPV (p = 0.0463; p = 0.0132 respectively) compared to ST alone. Lung function was significantly improved in the CPAP intervention group hourly and from baseline to end of treatment (p = 0.0403 for PEFR and p = 0.0293 for PEFR % predicted) compared to ST + BPPV and ST alone. The mean shift (Δ) in PEFR from baseline to 3 hours of treatment was 67.4, 123.5 and 86.8 L/min (p = 0.0445) for ST, ST + CPAP and ST + BPPV respectively. This corresponded to a 38.1, 80.8 and 51.7 % improvement in lung function respectively. Discussion: The effect of BPPV on the reduction of respiratory rate and sensation of breathlessness could be related to the inspiratory assistance provided by BPPV. The significant improvement in lung function in the CPAP group could be related to its intrinsic effect on the airway smooth muscle and / or on the airway smooth muscle load. Conclusion: The present results suggest that adding NPPV to standard treatment for an AAE not only improves clinical signs faster but also improves lung function faster. CPAP seems to have an intrinsic effect on the airway smooth muscle so rendering it more effective in ameliorating lung function.

Made available in DSpace on 2017-07-21T14:13:05Z (GMT). No. of bitstreams: 1 Leandro Aparecido Ravski.pdf: 4617218 bytes, checksum: e0fe68e5c3e65a36aaefc7a187e57e8b (MD5) Previous issue date: 2016-02-22 / Pneumonia is an acute disease characterized by inflammation of the lung parenchyma tissue.It is a respiratory disease with the highest incidence in the world. There are approximately 150 million cases in children under 5 years each year, and approximately 2 million result in death. In pneumonia, the damage to the lung tissue occurs due to the release of reactive oxygen species, causing increased oxidative stress due to the formation of free radicals. In the search for new alternatives to assist in the diagnosis of pneumonia, the assessment of possible variations in intracranial pressure (ICP) compared to pulmonary infection can be of great importance. Researchers have developed a new ICP measurement system completely noninvasive,which changed the course of history of neuroscience. This work aims to bring new data to the scientific community, characterizing normal PIC waves to a group of healthy children and investigating possible changes in children diagnosed with pneumonia. This study included 96 volunteers, divided into two groups: Test (hospitalized children diagnosed with pneumonia) and control (healthy children). There was the realization of the following laboratory tests: blood count, biochemical tests, inflammatory markers, serum total antioxidant capacity and catalase activity. In addition to the completion of the ICP monitoring with the use of new non-invasive technology. There was a significant increase in blood glucose, the inflammatory parameters in hematological parameters (total leukocytes, neutrophils, rods and targeted) and total serum antioxidant capacity of the test group. Urea, creatinine, total protein, albumin, total cholesterol, HDL, LDL, hemoglobin and hematocrit were significantly decreased in the test group. Although there was no statistical difference between the groups in terms of PIC. Our study showed the PIC's behavior in children, identifying changes in both groups, showing no direct relationship with pneumonia. This study served to introduce this innovative monitoring unit pic completely non-invasive, which has revolutionized the neuromedicina without the need for trepanation of the skull, can now be studied without any population risks to volunteer study. / A pneumonia é uma doença aguda, caracterizada pela inflamação do parênquima do tecido pulmonar. É a doença respiratória de maior incidência no mundo. Ocorrem aproximadamente 150 milhões de casos em crianças menores de 5 anos a cada ano, e aproximadamente 2 milhões resultam em morte. Na pneumonia, o dano ao tecido pulmonar ocorre devido à liberação das espécies reativas do oxigênio, causando aumento do estresse oxidativo, devido à formação de radicais livres. Na busca de novas alternativas para auxiliar no diagnóstico da pneumonia, a avaliação de possíveis variações na pressão intracraniana (PIC) frente à infecção pulmonar pode ter grande importância. Pesquisadores desenvolveram um novo sistema de aferição da PIC totalmente não invasivo, que alterou o curso da história da neurociência. Este trabalho tem o objetivo de trazer novos dados à comunidade científica, caracterizando ondas de PIC normais para um grupo de crianças sadias e investigando possíveis alterações em crianças diagnosticadas com pneumonia. Este estudo incluiu 96 voluntários, divididos em dois grupos: Teste (crianças internadas diagnosticadas com pneumonia) e Controle (crianças saudáveis). Houve a realização dos seguintes exames laboratoriais: hemograma, dosagens bioquímicas, marcadores inflamatórios, capacidade antioxidante total do soro e atividade da catalase. Além da realização do monitoramento da PIC com a utilização da nova tecnologia não invasiva. Ocorreu aumento significativo na glicemia, nos parâmetros inflamatórios, nos parâmetros hematológicos (leucócitos totais, neutrófilos, bastonetes e segmentados) e na capacidade antioxidante total do soro para o grupo Teste. Uréia, creatinina, proteínas totais, albumina, colesterol total, HDL, LDL,hemoglobina e hematócrito foram significativamente diminuídos no grupo Teste. Ainda houve diferença estatística entre os grupos na análise da PIC. Nosso estudo mostrou o comportamento da PIC em crianças, identificando alterações nos dois grupos estudados, não demonstrando relação direta com a pneumonia. Este estudo serviu para introduzir este inovador aparelho de monitoramento da PIC, totalmente não invasivo, que vem revolucionando a neuromedicina, sem a necessidade de trepanação do crânio, podendo agora, qualquer população ser estudada sem riscos ao voluntário do estudo.

Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering; and, (B.S.)--Massachusetts Institute of Technology, Dept. of Mathematics, 1982. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING / Includes bibliographical references and index. / by Richard J. Tello. / B.S.

Quantifying physiological stress may aid in a better understanding of how animals survive various environmental conditions. One noninvasive technique for assessing physiological stress in animals is to extract steroid hormones from fecal samples. This technique has the potential to aid in wildlife conservation by providing a better understanding of behavior and welfare for a variety of species. The objectives of the study were to (1) determine responses in plasma and fecal steroid hormone concentrations for coyotes (Canis latrans), (2) determine which steroid hormone (cortisol or corticosterone) was better for examining physiological stress responses for coyotes, and (3) determine the amount of time steroid hormone metabolites can be found in coyote scats during 2 different seasons. We first conducted an adrenocorticotropic hormone (ACTH) challenge in 16 coyotes and examined both plasma and fecal steroid hormone concentrations. An ACTH challenge is when there is an externally derived hormone (ACTH) injected into a subjects blood stream, which causes an increase in the subject’s circulating steroid hormones associated with physiological stress. We injected 16 treatment animals with ACTH and 16 control animals with a saline solution. We collected blood and fecal samples pre- and post-injection to measure steroid hormone concentrations. Radioimmunoassay, a laboratory method used to measure substances, was used to measure concentrations of steroid hormones in coyote blood and feces. To evaluate if steroid hormone concentrations remained in feces for an extended period of time we collected samples from 6 captive coyotes and left the samples in natural environmental conditions for 13 days. Each day a sub-sample was collected, and hormones were extracted and run through radioimmunoassay. We found increased steroid hormone concentrations after an ACTH challenge in both blood and feces, validating the use of fecal steroid hormone concentrations as a tool to measure physiological stress in coyotes. We also found there were no differences in levels of steroid hormone concentrations over 13 days. Our study provides validation for use of fecal steroid hormone concentrations in coyotes to quantify stress levels and confirms that steroid hormone metabolites are viable up to 13 days post deposition in coyote scat. This noninvasive tool can aid in the evaluation of the abilities of coyotes to adapt and exist in a variety of habitats.

BACKGROUND: Older individuals suffer from higher rates of pulmonary infections than younger individuals. In addition, older individuals have increased morbidity and mortality due to pulmonary infections when compared to younger individuals. The physiological and immunological reasons for these aforementioned differences are not clear. Recently, non-invasive markers of the lung's physiologic and immunologic status have been recognized. This study employs one of these non-invasive markers, exhaled nitric oxide, in an attempt to determine how the airways may change with age, predisposing older individuals to pulmonary diseases and poorer outcomes as compared to younger individuals. METHODS: Exhaled nitric oxide measurements were obtained from a group of 25 older subjects (61 to 79 years old, median 72 years old) and a group of 23 younger subjects (21 to 30 years old, median 24 years old) that were non-smokers with no history of pulmonary disease, no recent respiratory infections, and no history of environmental allergies. A focused history and physical exam along with spirometry were used to confirm the normal pulmonary status of each subject. Exhaled nitric oxide was measured following the American Thoracic Society recommendations using the Sievers Nitric Oxide Analyzer 280i. The exhaled nitric oxide values for the old and young groups were compared using the Wilcoxon Rank Sum test. RESULTS: For the older subjects, the median exhaled NO concentration was 36.9 ppb. For the younger subjects, the median exhaled NO concentration was 18.7 ppb. These exhaled NO concentrations are significantly different (p = 0.0011). CONCLUSIONS: The exhaled NO concentrations are significantly higher in older individuals than in younger individuals. The reasons for this difference along with the significance are unclear and further studies will be necessary to further evaluate these issues.