Autonomic function and prothrombotic activity in women after an acute coronary event

BACKGROUND: The link between decreased heart rate variability (HRV) and atherosclerosis progression is elusive. We hypothesized that reduced HRV relates to increased levels of prothrombotic factors previously shown to predict coronary risk. METHODS: We studied 257 women (aged 56 +/- 7 years) between 3 and 6 months after an acute coronary event and obtained very low frequency (VLF), low frequency (LF), and high frequency (HF) power, and LF/HF ratio from 24-hour ambulatory ECG recordings. Plasma levels of activated clotting factor VII (FVIIa), fibrinogen, von Willebrand factor antigen (VWF:Ag), and plasminogen activator inhibitor-1 (PAI-1) activity were determined, and their levels were aggregated into a standardized composite index of prothrombotic activity. RESULTS: In bivariate analyses, all HRV indices were inversely correlated with the prothrombotic index explaining between 6% and 14% of the variance (p < 0.001). After controlling for sociodemographic factors, index event, menopausal status, cardiac medication, lifestyle factors, self-rated health, metabolic variables, and heart rate, VLF power, LF power, and HF power explained 2%, 5%, and 3%, respectively, of the variance in the prothrombotic index (p < 0.012). There were also independent relationships between VLF power and PAI-1 activity, between LF power and fibrinogen, VWF:Ag, and PAI-1 activity, between HF power and FVIIa and fibrinogen, and between the LF/HF power ratio and PAI-1 activity, explaining between 2% and 3% of the respective variances (p < 0.05). CONCLUSIONS: Decreased HRV was associated with prothrombotic changes partially independent of covariates. Alteration in autonomic function might contribute to prothrombotic activity in women with coronary artery disease (CAD).

Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep.

Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36 years) completed FMD testing and the Pittsburgh Sleep Quality Index, along with a polysomnography assessment to obtain the following measures: slow wave sleep, percentage rapid eye movement (REM) sleep, REM sleep latency, total arousal index, total sleep time, wake after sleep onset, sleep efficiency and apnea-hypopnea index. Bivariate correlations and follow-up multiple regressions examined how FMD related to subjective (i.e., Pittsburgh Sleep Quality Index scores) and objective (i.e., polysomnography-derived) indicators of sleep quality. After FMD showed bivariate correlations with Pittsburgh Sleep Quality Index scores, percentage REM sleep and REM latency, further examination with separate regression models indicated that these associations remained significant after adjustments for sex, age, race, hypertension, body mass index, apnea-hypopnea index, smoking and income (Ps < 0.05). Specifically, as FMD decreased, scores on the Pittsburgh Sleep Quality Index increased (indicating decreased subjective sleep quality) and percentage REM sleep decreased, while REM sleep latency increased (Ps < 0.05). Poorer subjective sleep quality and adverse changes in REM sleep were associated with diminished vasodilation, which could link sleep disturbances to cardiovascular disease.

Effects of informative censoring on the hazard function: Application to the proportional hazards regression model

The standard analyses of survival data involve the assumption that survival and censoring are independent. When censoring and survival are related, the phenomenon is known as informative censoring. This paper examines the effects of an informative censoring assumption on the hazard function and the estimated hazard ratio provided by the Cox model.^ The limiting factor in all analyses of informative censoring is the problem of non-identifiability. Non-identifiability implies that it is impossible to distinguish a situation in which censoring and death are independent from one in which there is dependence. However, it is possible that informative censoring occurs. Examination of the literature indicates how others have approached the problem and covers the relevant theoretical background.^ Three models are examined in detail. The first model uses conditionally independent marginal hazards to obtain the unconditional survival function and hazards. The second model is based on the Gumbel Type A method for combining independent marginal distributions into bivariate distributions using a dependency parameter. Finally, a formulation based on a compartmental model is presented and its results described. For the latter two approaches, the resulting hazard is used in the Cox model in a simulation study.^ The unconditional survival distribution formed from the first model involves dependency, but the crude hazard resulting from this unconditional distribution is identical to the marginal hazard, and inferences based on the hazard are valid. The hazard ratios formed from two distributions following the Gumbel Type A model are biased by a factor dependent on the amount of censoring in the two populations and the strength of the dependency of death and censoring in the two populations. The Cox model estimates this biased hazard ratio. In general, the hazard resulting from the compartmental model is not constant, even if the individual marginal hazards are constant, unless censoring is non-informative. The hazard ratio tends to a specific limit.^ Methods of evaluating situations in which informative censoring is present are described, and the relative utility of the three models examined is discussed. ^

Flood frequency analysis by a bivariate model based on copulas

La adecuada estimación de avenidas de diseño asociadas a altos periodos de retorno es necesaria para el diseño y gestión de estructuras hidráulicas como presas. En la práctica, la estimación de estos cuantiles se realiza normalmente a través de análisis de frecuencia univariados, basados en su mayoría en el estudio de caudales punta. Sin embargo, la naturaleza de las avenidas es multivariada, siendo esencial tener en cuenta características representativas de las avenidas, tales como caudal punta, volumen y duración del hidrograma, con el fin de llevar a cabo un análisis apropiado; especialmente cuando el caudal de entrada se transforma en un caudal de salida diferente durante el proceso de laminación en un embalse o llanura de inundación. Los análisis de frecuencia de avenidas multivariados han sido tradicionalmente llevados a cabo mediante el uso de distribuciones bivariadas estándar con el fin de modelar variables correlacionadas. Sin embargo, su uso conlleva limitaciones como la necesidad de usar el mismo tipo de distribuciones marginales para todas las variables y la existencia de una relación de dependencia lineal entre ellas. Recientemente, el uso de cópulas se ha extendido en hidrología debido a sus beneficios en relación al contexto multivariado, permitiendo superar los inconvenientes de las técnicas tradicionales. Una copula es una función que representa la estructura de dependencia de las variables de estudio, y permite obtener la distribución de frecuencia multivariada de dichas variables mediante sus distribuciones marginales, sin importar el tipo de distribución marginal utilizada. La estimación de periodos de retorno multivariados, y por lo tanto, de cuantiles multivariados, también se facilita debido a la manera en la que las cópulas están formuladas. La presente tesis doctoral busca proporcionar metodologías que mejoren las técnicas tradicionales usadas por profesionales para estimar cuantiles de avenida más adecuados para el diseño y la gestión de presas, así como para la evaluación del riesgo de avenida, mediante análisis de frecuencia de avenidas bivariados basados en cópulas. Las variables consideradas para ello son el caudal punta y el volumen del hidrograma. Con el objetivo de llevar a cabo un estudio completo, la presente investigación abarca: (i) el análisis de frecuencia de avenidas local bivariado centrado en examinar y comparar los periodos de retorno teóricos basados en la probabilidad natural de ocurrencia de una avenida, con el periodo de retorno asociado al riesgo de sobrevertido de la presa bajo análisis, con el fin de proporcionar cuantiles en una estación de aforo determinada; (ii) la extensión del enfoque local al regional, proporcionando un procedimiento completo para llevar a cabo un análisis de frecuencia de avenidas regional bivariado para proporcionar cuantiles en estaciones sin aforar o para mejorar la estimación de dichos cuantiles en estaciones aforadas; (iii) el uso de cópulas para investigar tendencias bivariadas en avenidas debido al aumento de los niveles de urbanización en una cuenca; y (iv) la extensión de series de avenida observadas mediante la combinación de los beneficios de un modelo basado en cópulas y de un modelo hidrometeorológico. Accurate design flood estimates associated with high return periods are necessary to design and manage hydraulic structures such as dams. In practice, the estimate of such quantiles is usually done via univariate flood frequency analyses, mostly based on the study of peak flows. Nevertheless, the nature of floods is multivariate, being essential to consider representative flood characteristics, such as flood peak, hydrograph volume and hydrograph duration to carry out an appropriate analysis; especially when the inflow peak is transformed into a different outflow peak during the routing process in a reservoir or floodplain. Multivariate flood frequency analyses have been traditionally performed by using standard bivariate distributions to model correlated variables, yet they entail some shortcomings such as the need of using the same kind of marginal distribution for all variables and the assumption of a linear dependence relation between them. Recently, the use of copulas has been extended in hydrology because of their benefits regarding dealing with the multivariate context, as they overcome the drawbacks of the traditional approach. A copula is a function that represents the dependence structure of the studied variables, and allows obtaining the multivariate frequency distribution of them by using their marginal distributions, regardless of the kind of marginal distributions considered. The estimate of multivariate return periods, and therefore multivariate quantiles, is also facilitated by the way in which copulas are formulated. The present doctoral thesis seeks to provide methodologies that improve traditional techniques used by practitioners, in order to estimate more appropriate flood quantiles for dam design, dam management and flood risk assessment, through bivariate flood frequency analyses based on the copula approach. The flood variables considered for that goal are peak flow and hydrograph volume. In order to accomplish a complete study, the present research addresses: (i) a bivariate local flood frequency analysis focused on examining and comparing theoretical return periods based on the natural probability of occurrence of a flood, with the return period associated with the risk of dam overtopping, to estimate quantiles at a given gauged site; (ii) the extension of the local to the regional approach, supplying a complete procedure for performing a bivariate regional flood frequency analysis to either estimate quantiles at ungauged sites or improve at-site estimates at gauged sites; (iii) the use of copulas to investigate bivariate flood trends due to increasing urbanisation levels in a catchment; and (iv) the extension of observed flood series by combining the benefits of a copula-based model and a hydro-meteorological model.

New Bivariate Lifetime Distributions Based on Bath-Tub Shaped Failure Rate

A class of lifetime distributions which has received considerable attention in modelling and analysis of lifetime data is the class of lifetime distributions with bath-tub shaped failure rate functions because of their extensive applications. The purpose of this thesis was to introduce a new class of bivariate lifetime distributions with bath-tub shaped failure rates (BTFRFs). In this research, first we reviewed univariate lifetime distributions with bath-tub shaped failure rates, and several multivariate extensions of a univariate failure rate function. Then we introduced a new class of bivariate distributions with bath-tub shaped failure rates (hazard gradients). Specifically, the new class of bivariate lifetime distributions were developed using the method of Morgenstern’s method of defining bivariate class of distributions with given marginals. The computer simulations and numerical computations were used to investigate the properties of these distributions.

Application of a Bivariate Probit Model to Investigate the Intended Evacuation from Hurricane

With evidence of increasing hurricane risks in Georgia Coastal Area (GCA) and Virginia in the U.S. Southeast and elsewhere, understanding intended evacuation behavior is becoming more and more important for community planners. My research investigates intended evacuation behavior due to hurricane risks, a behavioral survey of the six counties in GCA under the direction of two social scientists with extensive experience in survey research related to citizen and household response to emergencies and disasters. Respondents gave answers whether they would evacuate under both voluntary and mandatory evacuation orders. Bivariate probit models are used to investigate the subjective belief structure of whether or not the respondents are concerned about the hurricane, and the intended probability of evacuating as a function of risk perception, and a lot of demographic and socioeconomic variables (e.g., gender, military, age, length of residence, owning vehicles).

An approximate method for the solution of an influence function foil rolling model

Fleck and Johnson (Int. J. Mech. Sci. 29 (1987) 507) and Fleck et al. (Proc. Inst. Mech. Eng. 206 (1992) 119) have developed foil rolling models which allow for large deformations in the roll profile, including the possibility that the rolls flatten completely. However, these models require computationally expensive iterative solution techniques. A new approach to the approximate solution of the Fleck et al. (1992) Influence Function Model has been developed using both analytic and approximation techniques. The numerical difficulties arising from solving an integral equation in the flattened region have been reduced by applying an Inverse Hilbert Transform to get an analytic expression for the pressure. The method described in this paper is applicable to cases where there is or there is not a flat region.

Smoothing a Discrete Hazard Function for the Number of Patients Colonized with Methicillin-Resistance Staphylococcus Aureus in an Intensive Care Unit

A new method for estimating the time to colonization of Methicillin-resistant Staphylococcus Aureus (MRSA) patients is developed in this paper. The time to colonization of MRSA is modelled using a Bayesian smoothing approach for the hazard function. There are two prior models discussed in this paper: the first difference prior and the second difference prior. The second difference prior model gives smoother estimates of the hazard functions and, when applied to data from an intensive care unit (ICU), clearly shows increasing hazard up to day 13, then a decreasing hazard. The results clearly demonstrate that the hazard is not constant and provide a useful quantification of the effect of length of stay on the risk of MRSA colonization which provides useful insight.