Balancing increased safety against detonation performance is paramount for new explosive energetic materials in the development process. Often these two requirements are in opposition to each other. Sensitivity tests to external stimuli are used to determine how safe an energetic material is to phenomena such as impact, heat, or friction. Meanwhile, detonation performance is assessed by the maximum pressure and shock velocity induced from chemical reactions. Tailoring the performance while maintaining safety of the explosive would be possible with knowledge of the chemical reactions that functional groups provide during detonation. Current knowledge of the chemical reactions that occur during detonation is limited. Several mechanisms have been suggested for first step reactions throughout the detonation process for energetic molecules; however, no single chemical pathway has been irrefutably substantiated by experiments. Alternatively, models can provide insight into the types of reactions that may transpire, but lack direct experimental comparisons. If experiments and models could be compared at the equivalent time and length scales, then measurements could guide the physics and chemistry assumptions present in models. Experiments presented in this document bridge that gap by using an ultrafast laser system to generate shocks in samples and spectroscopically probe vibrational and electronic absorption changes that occur during shock compression. A review of how to turn a benchtop chirped pulse amplifier into a shock physics and chemistry laboratory is first presented. Applications of the spectroscopic techniques developed were then applied to trinitrotoluene (TNT) and pentaerythritol tetranitrate (PETN) during shock compression. Mid-infrared absorption results for shock compressed TNT and PETN were compared to current suggestions on chemical pathways and inconsistencies were present for both materials. It is suggested that a carbon-carbon bond breaking mechanism is present for PETN, and a hydrogenic stretch like hydroxyl or amide bond formation mechanism is suggested for TNT based on the MIR absorption measurements. Recommendations for future experimental thrusts are also provided. The results provided in this document could be directly compared to simulations to refine the assumptions present in models.

Ces travaux de thèse présentés dans ce mémoire concernent l’évolution d’onde de souffle en milieu non-idéalisé. L’évolution d’une onde de souffle en champ libre peut être décrite par divers résultats empiriques disponibles dans la littérature ou par des formulations théoriques. Pourtant, dès qu’il est question d’approuver les résultats d’un code de simulation décrivant l’évolution une onde de souffle dans un milieu complexe, les connaissances sur le développement des ondes en milieu idéalisé ne suffisent plus. Dès lors, il faut acquérir de nouvelles données expérimentales afin de valider les différents outils de simulation du CEA. Les résultats de ce mémoire s’inscrivent dans ce projet. Des essais à petite échelle ont été dimensionnés afin de correspondre à un scénario avec une nature d’explosif différente de celle employée au laboratoire. La charge utilisée est gazeuse et est constituée de propane-oxygène en proportion stœchiométrique. Pour mesurer les différentes caractéristiques des ondes de souffle et d’acquérir de nouveaux résultats, deux systèmes de mesure ont été utilisées. Des capteurs de pression ont été installés au sol, couplés à un système de visualisation avec une caméra rapide dont le montage se rapproche de l’ombroscopie. Plusieurs configurations ont permis d’avoir une base solide sur les grandeurs définissant les ondes incidentes et réfléchies en champ libre. L’étude porte essentiellement sur la réflexion de Mach. Par la suite des obstacles isolés ont été installés sur le parcours d’une onde incidente ou de Mach afin de représenter des effets de surface. Les résultats ont montré une modification des caractéristiques et de la morphologie des ondes à l’aval des obstacles. / The study presented in this thesis concerns the evolution of a shock wave in a non-idealized environnment. The evolution of a free-field shock wave can be described by various empirical results found in the literature or by theoretical formulations. However, as soon as it is a question of approving the results of a simulation code describing the evolution of a shock wave in a complex environnment, knowledge about the development of waves in a free-field is no longer sufficient. Therefore, new experimental data must be acquired to validate the different simulation tools in-house. The results of this thesis are part of this project. Small-scale tests have been sized to fit a scenario with an explosive nature different from that used in the laboratory. The source used is gaseous and made of propane oxygen at a stoichiometric proportion. To measure the different characteristics of a shock wave and to acquire new results, two measurement systems were used. Pressure sensors have been installed on the ground, coupled with a visualization system with a high speed camera whose is close to shadowscopy. Several configurations allowed to have solid basis on the characteristics defining the incident and reflected shock waves in free field. The study focuses on Mach's reflection moreover on Mach stem. Subsequently isolated obstacles were installed on the path of an incident wave or Mach’s reflection to represent surface effects. The results showed a change in the characteristics and morphology of the waves downstream of the obstacles.

OBJETIVO: Describir las características clínicas y epidemiológicas en los pacientes que ingresaron a la Unidad de Shock Trauma del Hospital Nacional Dos de Mayo durante los años Enero 2001- Diciembre 2002. DISEÑO: Es un estudio retrospectivo descriptivo, tipo serie de casos, realizado mediante la revisión de historias clínicas, lo cual nos permitió analizar las características de los pacientes que ingresaron a esta Unidad durante este periodo. MATERIALES Y MÉTODOS: Se revisaron los libros de registro y las historias clínicas de los pacientes que ingresaron a esta Unidad durante el periodo ya establecido, los datos se llenaron en fichas prefabricadas. En ellos se registraron 1549 pacientes de los cuales, cumplieron con los criterios de inclusión 1424, 724 pacientes del 2001 y 700 pacientes del 2002. RESULTADOS: Del estudio descriptivo se obtuvo que el 67,7% de pacientes fueron varones, existiendo una relación hombres a mujeres de 2:1, y el 54,1% de pacientes tenían entre 18 y 60 años. El 82,5% de pacientes ingresaron al servicio de shock trauma por el servicio de Emergencia. Se realizaron 1694 procedimientos de los cuales el 36,1% fueron Intubaciones Endotraqueales. En este periodo se realizaron 1742 Exámenes Auxiliares de los cuales el 15% fueron TAC cerebrales. La causa más frecuente de ingreso a la Unidad de Shock Trauma es el Traumatismo (27,3%), siendo el Traumatismo Encéfalo Craneano el más importante, seguido por la Insuficiencia Respiratoria Aguda. La principal causa de mortalidad fue la Insuficiencia Respiratoria Aguda con un 21%. El 41,57% de pacientes permaneció en la Unidad por un periodo comprendido entre 1 y 6 horas. El 42,71% de pacientes queda en hospitalización. En el análisis estadístico se encontró relación estadísticamente significativa entre el diagnóstico de traumatismo con la edad (p = 0,004) y con el sexo masculino; relación entre la Insuficiencia Respiratoria Aguda y la edad (p = 0.045). CONCLUSIONES: La Unidad de Shock Trauma atendió en este periodo el 1,7% de la población que acudió a la Emergencia del Hospital, el traumatismo y la insuficiencia respiratoria fueron las causas más frecuentes. / Tesis de segunda especialidad

Orientador: Maria Regina Bentlin / Resumo: Introdução: A sepse e choque séptico são importantes causas de morbimortalidade no período neonatal. A implantação de protocolos permite uma condução sequencial e rápida na sepse/ choque, o que pode melhorar o prognóstico desses pacientes. Objetivo: Investigar nos prematuros de muito baixo peso (PT-MBP) se o quadro séptico está sendo conduzido de forma sistematizada de acordo com o protocolo e se essa sistematização melhorou o prognóstico em curto prazo. Métodos: Estudo retrospectivo, do tipo coorte realizado na UTI Neonatal do Hospital das Clinicas da Faculdade de Medicina de Botucatu no período de janeiro de 2013 a dezembro de 2015, após aprovação do CEP. Foram selecionados todos os recém-nascidos (RN) prematuros com peso ao nascer inferior a 1500g (muito baixo peso), internados na UTI, nascidos ou não no Serviço, que sobreviveram por mais de 72 horas de vida. Foram incluídos todos os prematuros menores de 34 semanas e que apresentaram diagnóstico de sepse / choque séptico na Unidade. Não foram incluídos aqueles com malformações múltiplas e infecções congênitas. Variáveis estudadas: maternas, gestacionais, neonatais e variáveis do protocolo de choque da Unidade. Os recém-nascidos (RN) foram comparados inicialmente em dois grupos: sepse e choque séptico; para a avaliação do protocolo foram estudados apenas os que evoluíram para choque: com protocolo VS sem protocolo. Desfechos: displasia broncopulmonar (DBP), hemorragia periintraventricular (HPIV) grave, retinopatia da prema... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Orientador: Maria Regina Bentlin / Resumo: Introdução: O choque séptico é uma importante causa de morbimortalidade em recém-nascidos prematuros. O lactato vem sendo estudado como marcador diagnóstico e prognóstico do choque, mas os estudos no período neonatal são escassos. Objetivo: Investigar se os níveis séricos de lactato podem predizer o risco de morte em prematuros com choque séptico. Métodos: Estudo retrospectivo, longitudinal, realizado na UTI Neonatal do Hospital das Clinicas da Faculdade de Medicina de Botucatu no período de janeiro de 2014 a dezembro de 2016, após aprovação do CEP. Foram incluídos todos os prematuros menores que 37 semanas, internados na UTI, com mais de 72 horas de vida, que apresentaram diagnóstico de choque séptico e dosagem do lactato sérico nas primeiras 48 horas do choque. Foram excluídos aqueles com malformações múltiplas, infecções congênitas e erros inatos do metabolismo. Variáveis estudadas: maternas, gestacionais, neonatais, agente etiológico e dosagem do lactato. Os prematuros foram comparados em dois grupos: sobrevida e óbito. Desfecho: óbito. Análise estatística: testes paramétricos e não paramétricos com significância estatística se p<0.05. Acurácia do lactato: sensibilidade, especificidade, valor preditivo positivo e negativo. Resultados: Dentre os 456 prematuros sobreviventes por mais de 72 horas, 130 apresentaram sepse tardia (28,5%) e destes, 36 choque séptico (28%). A mortalidade no choque foi de 42%. A positividade em hemocultura foi de 36% com predomínio de Gram-positiv... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Septic shock is an important cause of morbidity and mortality in premature infants. Lactate has been studied as a diagnostic and prognostic marker of shock, but studies in the neonatal period are scarce. Objective: To investigate if serum lactate levels can predict the risk of death in preterm infants with septic shock. Methods: Retrospective, longitudinal study performed at the Neonatal Intensive Care Unit (NICU) of the Clinics Hospital – Botucatu School of Medicine, from January 2014 to December 2016, after approval of the Ethics Committee. All preterm infants less than 37 weeks gestational age, with more than 72 hours of life, admitted at the NICU with diagnosis of septic shock and serum lactate dosage in the first 48 hours of shock were included. Those with multiple malformations, congenital infections and inborn errors of metabolism were excluded. Variables studied: maternal, gestational, neonatal, etiologic agent and lactate dosage. The preterm infants were compared in two groups: survival and death. Outcome: death. Statistical analysis: parametric and non-parametric tests with statistical significance if p<0.05. Lactate accuracy: sensitivity, specificity, positive and negative predictive value. Results: Among the 456 preterm infants who survived for more than 72 hours, 130 had late onset sepsis (28.5%) and of these 36 septic shock (28%). The shock mortality was 42%. The positivity in blood cultures was 36%, with a predominance of Gram-positive in the surv... (Complete abstract click electronic access below) / Mestre

Microscopic polyangiitis (MPA) is a rare condition characterized by nonspecific symptoms of fatigue, fever, or loss of appetite and additional symptoms related to areas of involvement. The rarity of the disease and its variable presentation can delay its diagnosis in the acute setting, potentially leading to delay in effective treatment and poor outcomes. This is a case report of a 68-year-old man, who presented to the hospital after being found poorly responsive at home. He was sedated and intubated in the field and brought to the ER. He was found to be hypotensive. History revealed abdominal aortic aneurysm, but no known history of GI bleed or use of blood-thinners. Physical exam revealed rhonchi throughout both lung fields, a soft, nondistended abdomen with normoactive bowel sounds, and cool extremities with weak palpable pulses. CBC was suggestive of anemia. BUN and creatinine were elevated indicating kidney injury. CT abdomen showed no acute pathology and an intact abdominal aortic aneurysm. CT chest revealed left lower lobe atelectasis and bilateral pulmonary edema. CT head was consistent with watershed infarction. Numerous blood transfusions were given. However, slow decline in hemoglobin continued to occur. Colonoscopy was considered for possible identification of the source of bleeding, however was not performed due to the family’s wish for conservative management. Bronchoscopy was performed, revealing extensive mucus plugging and bloody plugs. He was eventually weaned off sedation but remained largely unresponsive, occasionally opening his eyes to stimuli. On hospital day 7, necrotic lesions were noted on the patient’s ear and fingers. These findings prompted serologic studies for vasculitis that resulted in positive p-ANCA and myeloperoxidase antibodies, consistent with MPA. He was started on pulse dose IV steroids resulting in modest improvement in renal parameters and hemoglobin, but no discernible change in neurological status. The patient was transitioned to comfort care and palliative extubation was performed. Four days later, the patient expired. This case illustrates the potential for hypovolemic shock as a consequence of undiagnosed vasculitis. In this case, a definite diagnosis was not made, due to inability to perform a lung biopsy because of patient being on comfort measures. However, given that he was p-ANCA and myeloperoxidase positive, along with visualized blood on bronchoscopy, a presumptive diagnosis of MPA can be made. Although this patient may not have recovered even with early immunosuppressive treatment, vasculitis should be considered as a differential diagnosis in patients presenting in hypovolemic shock, especially if history, exam and noninvasive testing are unrevealing.

Crackle is a perceptual feature of supersonic jet noise that is related to the presence of acoustic shocks. The skewness of the time-derivative of the pressure waveform, or derivative skewness, is used as a metric indicative of crackle perception. The three main objectives of this work are: 1) Determine the potential spatial origin of crackle-related events in the near field of a high-performance military aircraft via an event-based beamforming method. 2) Investigate the potential for nonlinear, irregular shock reflections occurring along the near-field ground array and their implications on derivative skewness. 3) Relate the near-field, crackle-related events to far-field crackle perception by comparing nonlinearly propagated waveforms with measured far-field data. The event-based beamforming method used to determine source and far-field relationship of shock-like events utilizes the cross correlation between adjacent microphone waveform segments to determine the angle of propagation for an ensemble of crackle-related events within the waveform. The angle of propagation is traced towards the source for each event to find its apparent origin along the jet lipline. Beamforming results indicate that crackle-related events appear to originate anywhere from 2 to 14.5 m downstream along the jet lipline, with distributions that shift downstream and broaden with increasing engine power. The shock reflection classification method builds on the event-based beamforming method to calculate angle of incidence relative to the ground for an ensemble of shock events. The combination of angles of incidence and the measured shock strengths of the events reveal that irregular reflections are likely to occur over the majority of the array, which likely elevates the derivative skewness values due to steeper shocks with greater peak-to-peak pressures relative to off-ground measurements. Near-field, crackle-related events are extrapolated to the far field using a nonlinear propagation model to determine their prevalence in the far field. Cross-correlation coefficients of waveform segments centered about the propagated events indicates that for farther aft angles, near-field events are more related to far-field measurements. Waveform observations show that shock-like events in the near field that are more spiked in nature tend not propagate into the far field. However, near-field, large-derivative events with broader, high-pressure peaks nonlinearly steepen and form shocks in the far field that are likely contribute to crackle perception.

The atomization of a liquid by an air stream has been an item of much concern in the past, and there have been numerous experimental studies of the process made in an effort to correlate liquid and air- stream physical properties into a general model which will predict the degree of and the time required for atomization for a given physical situation. The breakup of liquid drops, a major portion of the atomization process, finds application in the field of meteorology, where the formation, breakup, and shape of raindrops is an item of much concern; in the field of internal combustion engines, where the carburization of a fuel is of major importance; in the industrial field, where the atomization of paint and plant insecticides and spray drying processes are oft-mentioned objects of concern; in the chemical industries, where the emulsification of liquid- liquid systems, the formation of froths, the production of aerosols, and dispersion processes in general are most important considerations; and in the science of rheology, wherein the motion and dispersion of liquids, gases, and solids must take into consideration various breakup mechanisms. Despite the oft-mentioned importance of such liquid atomization processes, there has been little theoretical work done in .an effort to mathematically correlate the important variables and parameters common to all breakup and dispersion processes in general.

Preignition is an ignition event that happens before it is expected to happen and, many times, where it is not expected to happen. Understanding this phenomenon is of great importance as it influences the design and operation of modern downsized boosted internal combustion engines. To gain a fundamental understanding of preignition, homogeneous reactors like shock tubes and rapid compression machines may be used to decipher the influence of fuel chemical structure, temperature, pressure, equivalence ratio and bath gas on preignition. In this thesis, a comprehensive study of the preignition tendency of various chemical systems is presented. Firstly, renewable fuels like ethanol, methanol and a surrogate of conventional fuels, n-hexane, are characterized by traditional shock tube techniques, such as the measurements of ignition delay times and pressure-time histories, to identify thermodynamic conditions which promote non-ideal ignition behavior. Preignition pressure rise and the expedition of measured ignition delay times are identified as the indicators of non-homogeneous combustion. It is shown that preignition effects are more likely to be observed in mixtures containing higher fuel concentration and that preignition energy release is more pronounced at lower temperatures. High-speed imaging was implemented to visualize the combustion process taking place inside the shock tube. End-wall imaging showed that low-temperature ignition may be initiated from an individual hot spot that grows gradually, while high-temperatures ignition starts from many spots simultaneously which consume the reactive mixture almost homogeneously. Simultaneous lateral and endwall imaging was implemented in both low- and high-pressure shock tube facilities. All tested fuels exhibited localized ignition at low temperatures, and methanol showed a higher propensity than ethanol to ignite far from the endwall. Imaging experiments were also performed in a rapid compression machine to understand preignition at lower temperatures. Herein, ethanol showed non-homogeneous ignition while iso-octane and diethyl ether exhibited homogeneous ignition at the low-temperature conditions. Various criteria for the onset of preignition were tested against experimental observations to propose an adequate predictor of non-ideal ignition phenomena in practical applications. A non-dimensional number, relating the ignition delay sensitivity and laminar flame speed of the mixtures, was found to be the best criterion to elucidate ignition regimes.

Lung tumor progression is regulated by proangiogenic factors. Heat shock protein A12B (HSPA12B) is a recently identified regulator of expression of proangiogenic factors. However, whether HSPA12B plays a role in lung tumor growth is unknown. To address this question, transgenic mice overexpressing HSPA12B (Tg) and wildtype littermates (WT) were implanted with Lewis lung cancer cells to induce lung tumorigenesis. Tg mice showed significantly higher number and bigger size of tumors than WT mice. Tg tumors exhibited increased angiogenesis and proliferation while reduced apoptosis compared with WT tumors. Interestingly, a significantly enhanced upregulation of Cox-2 was detected in Tg tumors than in WT tumors. Also, Tg tumors demonstrated upregulation of VEGF and angiopoietin-1, downregulation of AKAP12, and increased eNOS phosphorylation compared with WT tumors. Celecoxib, a selective Cox-2 inhibitor, suppressed the HSPA12B-induced increase in lung tumor burden. Moreover, celecoxib decreased angiogenesis and proliferation whereas increased apoptosis in Tg tumors. Additionally, celecoxib reduced angiopoietin-1 expression and eNOS phosphorylation but increased AKAP12 levels in Tg tumors. Our results indicate that HSPA12B stimulates lung tumor growth via a Cox-2-dependent mechanism. The present study identified HSPA12B as a novel facilitator of lung tumor growth and a potential therapeutic target for the treatment of lung cancer.