Heterogeneity in susceptibility dictates the order of epidemiological models

The fundamental models of epidemiology describe the progression of an infectious disease through a population using compartmentalized differential equations, but do not incorporate population-level heterogeneity in infection susceptibility. We show that variation strongly influences the rate of infection, while the infection process simultaneously sculpts the susceptibility distribution. These joint dynamics influence the force of infection and are, in turn, influenced by the shape of the initial variability. Intriguingly, we find that certain susceptibility distributions (the exponential and the gamma) are unchanged through the course of the outbreak, and lead naturally to power-law behavior in the force of infection; other distributions often tend towards these "eigen-distributions" through the process of contagion. The power-law behavior fundamentally alters predictions of the long-term infection rate, and suggests that first-order epidemic models that are parameterized in the exponential-like phase may systematically and significantly over-estimate the final severity of the outbreak

Non-idealities in lab-scale kinetic testing: a theoretical study of a modular Temkin reactor

The Temkin reactor can be applied for industrial relevant catalyst testing with unmodified catalyst particles. It was assumed in the literature that this reactor behaves as a cascade of continuously stirred tank reactors (CSTR). However, this assumption was based only on outlet gas composition or inert residence time distribution measurements. The present work theoretically investigates the catalytic CO2 methanation as a test case on different catalyst geometries, a sphere, and a ring, inside a single Temkin reaction chamber under isothermal conditions. Axial gas-phase species profiles from detailed computational fluid dynamics (CFD) are compared with a CSTR and 1D plug-flow reactor (PFR) model using a sophisticated microkinetic model. In addition, a 1D chemical reactor network (CRN) model was developed, and model parameters were adjusted based on the CFD simulations. Whereas the ideal reactor models overpredict the axial product concentrations, the CRN model results agree well with the CFD simulations, especially under low to medium flow rates. This study shows that complex flow patterns greatly influence species fields inside the Temkin reactor. Although residence time measurements suggest CSTR-like behavior, the reactive flow cannot be described by either a CSTR or PFR model but with the developed CRN model

Predicting combustion properties of hydrocarbon fuel mixtures

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 189-201).In this thesis, I applied computational quantum chemistry to improve the accuracy of kinetic mechanisms that are used to model combustion chemistry. I performed transition state theory calculations for several reactions that are critical in combustion, including a detailed analysis of the pressure dependence of these rate coefficients. I developed a new method for rapidly estimating the vibrational modes and hindered rotor parameters for molecules. This new method has been implemented in an automatic reaction mechanism generation software, RMG, and has improved the accuracy of the density of states computed in RMG, which in turn has improved RMG's ability to predict the pressure-dependence of rate coefficients for complex reaction networks. I used statistical mechanics to compute the thermochemistry for over 170 of the most important species in combustion. These calculations form a new library of thermodynamic parameters, and this library will improve the accuracy of kinetic models, particularly for fuel lean conditions. I measured reaction rate coefficients using both laser flash-photolysis absorption spectroscopy in a slow-flow reactor and time-of-flight mass spectrometry and laser Schlieren densitometry in a shock tube. Based upon these experimental projects, I helped design a one-of-a-kind instrument for measuring rate coefficients for combustion-relevant reactions. The new reactor combines photoionization time-of-flight mass spectrometry with multi-pass absorption spectroscopy in a laser-flash photolysis cell. The cumulative effect of these efforts should advance our understanding of combustion chemistry and allow us to make more accurate predictions of how hydrocarbons burn.by Claude Franklin Goldsmith, III.Ph.D

Role of parathyroid hormone in the phosphaturia of extracellular fluid volume expansion

Role of parathyroid hormone in the phosphaturia of extracellular fluid volume expansion. Acute expansion of the extracellular fluid volume increases the urinary excretion of phosphate. The present study examined the importance of increased plasma parathyroid hormone concentration in the phosphaturia accompanying acute extracellular fluid volume expansion (ECVE). Infusion of a calcium-free Ringer's solution into dogs was associated with increased urinary phosphate excretion and serum immunoreactive parathyroid hormone concentration (iPTH), the latter being significantly correlated with a decrease in plasma ionized calcium concentration. Prevention of the fall in plasma ionized calcium concentration by infusion of a calcium containing Ringer's solution prevented the increase in serum iPTH but the magnitude of the phosphaturia was not affected. The phosphaturia associated with ECVE was also not affected in thyroparathyroidectomized (TPTX) dogs which received a maintenance infusion of bovine PTH. In contrast, in acutely TPTX dogs which did not receive a maintenance infusion of PTH, the phosphaturic response to ECVE was significantly depressed. These data indicate that 1) the increase in serum iPTH concentration following ECVE is the result of a fall in plasma ionized calcium concentration, 2) the increase in phosphate excretion accompanying ECVE is not dependent on an increase in serum iPTH concentration and 3) in the presence of a low or falling serum PTH concentration, the increase in phosphate excretion can be significantly blunted.Rôle de l'hormone parathyroïdienne dans la phosphaturie consécutive à l'expansion extracellulaire. L'expansion aiguë du volume extracellulaire augmente l'excrétion urinaire du phosphate. Ce travail examine le rôle de l'augmentation de la concentration d'hormone parathyroïdienne dans la phosphaturie qui accompagne l'expansion du volume extracellulaire (ECVE). L'administration à des chiens d'une solution de Ringer sans calcium est associée à une augmentation de l'excrétion urinaire de phosphate et à une augmentation de la concentration d'hormone parathyroïdienne immunoréactive du plasma (iPTH). Cette dernière est significativement corrélée à la diminution de la concentration plasmatique du calcium ionisé. L'empêchement de la diminution de la concentration plasmatique du calcium ionisé par l'administration d'une solution de Ringer contenant du calcium évite l'augmentation de iPTH dans le plasma mais n'affecte pas l'importance de la phosphaturie. La phosphaturie associée à ECVE n'est pas non plus modifiée chez des chiens thyroparathyroïdectomisés (TPTX) qui reçoivent une perfusion de PTH bovine. Au contraire chez des chiens TPTX aigus qui ne reçoivent pas de perfusion de PTX la réponse à ECVE est significativement diminuée. Ces résultats indiquent que 1) L'augmentation de iPTH du plasma après ECVE est la conséquence d'une diminution de la concentration plasmatique du calcium ionisé, 2) l'augmentation de l'excrétion du phosphate qui accompagne ECVE ne dépend pas de l'augmentation de iPTH du plasma et 3) quand la concentration plasmatique de PTH est faible ou en voie de diminution, l'augmentation de l'excrétion de phosphate peut être significativement masquée

Automated Generation of Microkinetics for Heterogeneously Catalyzed Reactions Considering Correlated Uncertainties

The study presents an ab-initio based framework for the automated construction of microkinetic mechanisms considering correlated uncertainties in all energetic parameters and estimation routines. 2000 unique microkinetic models were generated within the uncertainty space of the BEEF-vdW functional for the oxidation reactions of representative exhaust gas emissions from stoichiometric combustion engines over Pt(111) and compared to experiments through multiscale modeling. The ensemble of simulations stresses the importance of considering uncertainties. Within this set of first-principles-based models, it is possible to identify a microkinetic mechanism that agrees with experimental data. This mechanism can be traced back to a single exchange-correlation functional, and it suggests that Pt(111) could be the active site for the oxidation of light hydrocarbons. The study provides a universal framework for the automated construction of reaction mechanisms with correlated uncertainty quantification, enabling a DFT-constrained microkinetic model optimization for other heterogeneously catalyzed systems

Factors influencing referrals for ultrasound-diagnosed complications during prenatal care in five low and middle income countries

BACKGROUND: Ultrasound during antenatal care (ANC) is proposed as a strategy for increasing hospital deliveries for complicated pregnancies and improving maternal, fetal, and neonatal outcomes. The First Look study was a cluster-randomized trial conducted in the Democratic Republic of Congo, Guatemala, Kenya, Pakistan and Zambia to evaluate the impact of ANC-ultrasound on these outcomes. An additional survey was conducted to identify factors influencing women with complicated pregnancies to attend referrals for additional care. METHODS: Women who received referral due to ANC ultrasound findings participated in structured interviews to characterize their experiences. Cochran-Mantel-Haenszel statistics were used to examine differences between women who attended the referral and women who did not. Sonographers\u27 exam findings were compared to referred women\u27s recall. RESULTS: Among 700 referred women, 510 (71%) attended the referral. Among referred women, 97% received a referral card to present at the hospital, 91% were told where to go in the hospital, and 64% were told that the hospital was expecting them. The referred women who were told who to see at the hospital (88% vs 66%), where to go (94% vs 82%), or what should happen, were more likely to attend their referral (68% vs 56%). Barriers to attending referrals were cost, transportation, and distance. Barriers after reaching the hospital were substantial. These included not connecting with an appropriate provider, not knowing where to go, and being told to return later. These barriers at the hospital often led to an unsuccessful referral. CONCLUSIONS: Our study found that ultrasound screening at ANC alone does not adequately address barriers to referrals. Better communication between the sonographer and the patient increases the likelihood of a completed referral. These types of communication include describing the ultrasound findings, including the reason for the referral, to the mother and staff; providing a referral card; describing where to go in the hospital; and explaining the procedures at the hospital. Thus, there are three levels of communication that need to be addressed to increase completion of appropriate referrals-communication between the sonographer and the woman, the sonographer and the clinic staff, and the sonographer and the hospital

Distribution of Water Vapor in Molecular Clouds

We report the results of a large-area study of water vapor along the Orion Molecular Cloud ridge, the purpose of which was to determine the depth-dependent distribution of gas-phase water in dense molecular clouds. We find that the water vapor measured toward 77 spatial positions along the face-on Orion ridge, excluding positions surrounding the outflow associated with BN/KL and IRc2, display integrated intensities that correlate strongly with known cloud surface tracers such as CN, C2H, 13CO J =5-4, and HCN, and less well with the volume tracer N2H+. Moreover, at total column densities corresponding to Av < 15 mag., the ratio of H2O to C18O integrated intensities shows a clear rise approaching the cloud surface. We show that this behavior cannot be accounted for by either optical depth or excitation effects, but suggests that gas-phase water abundances fall at large Av. These results are important as they affect measures of the true water-vapor abundance in molecular clouds by highlighting the limitations of comparing measured water vapor column densities with such traditional cloud tracers as 13CO or C18O. These results also support cloud models that incorporate freeze-out of molecules as a critical component in determining the depth-dependent abundance of water vapor

Imaging Inflammation in a Patient with Epilepsy Due to Focal Cortical Dysplasia

BACKGROUND AND PURPOSE Evidence from animal models and examination of human epilepsy surgery specimens indicates that inflammation plays an important role in epilepsy. Positron emission tomography (PET) using [C11]PK11195, a marker of activated microglia, provides a means to visualize neuroinflammation in vivo in humans. We hypothesize that in patients with active epilepsy, [C11]PK11195 PET (PK-PET) may be able to identify areas of focally increased inflammation corresponding to the seizure onset zone. METHODS A young woman with intractable epilepsy underwent PK-PET as part of an approved research study. PK-PET results were compared with results from other clinical studies. RESULTS PK-PET revealed an area of focally increased radiotracer uptake in the right frontal lobe corresponding to this patient’s seizure focus as identified by ictal and interictal 18Ffluorodeoxyglucose (FDG)-PET and EEG. Routine brain magnetic resonance imaging (MRI) was initially considered normal, though high-resolution studies showed possible subtle dysplasia of the right frontal lobe. The patient underwent a right frontal lobe resection, and pathological evaluation showed focal cortical dysplasia with activated microglia. CONCLUSIONS PK-PET can identify neuroinflammation associated with subtle focal cortical dysplasia, and may therefore have a clinical role in guiding epilepsy surgery for patients with difficult-to-localize seizure foci