Mixture modeling for joint analysis of survival, discrete, and continuous data

Mixture modeling is commonly used to model categorical latent variables that represent subpopulations in which population membership is unknown but can be inferred from the data. In relatively recent years, the potential of finite mixture models has been applied in time-to-event data. However, the commonly used survival mixture model assumes that the effects of the covariates involved in failure times differ across latent classes, but the covariate distribution is homogeneous. The aim of this dissertation is to develop a method to examine time-to-event data in the presence of unobserved heterogeneity under a framework of mixture modeling. A joint model is developed to incorporate the latent survival trajectory along with the observed information for the joint analysis of a time-to-event variable, its discrete and continuous covariates, and a latent class variable. It is assumed that the effects of covariates on survival times and the distribution of covariates vary across different latent classes. The unobservable survival trajectories are identified through estimating the probability that a subject belongs to a particular class based on observed information. We applied this method to a Hodgkin lymphoma study with long-term follow-up and observed four distinct latent classes in terms of long-term survival and distributions of prognostic factors. Our results from simulation studies and from the Hodgkin lymphoma study demonstrated the superiority of our joint model compared with the conventional survival model. This flexible inference method provides more accurate estimation and accommodates unobservable heterogeneity among individuals while taking involved interactions between covariates into consideration.^

An analysis of the revenue policy -making process of the Texas Legislature

The purpose of this dissertation was to develop a conceptual framework which can be used to account for policy decisions made by the House Ways and Means Committee (HW&MC) of the Texas House of Representatives. This analysis will examine the actions of the committee over a ten-year period with the goal of explaining and predicting the success of failure of certain efforts to raise revenue.^ The basis framework for modelling the revenue decision-making process includes three major components--the decision alternatives, the external factors and two competing contingency theories. The decision alternatives encompass the particular options available to increase tax revenue. The options were classified as non-innovative or innovative. The non-innovative options included the sales, franchise, property and severance taxes. The innovative options were principally the personal and corporate income taxes.^ The external factors included political and economic constraints that affected the actions of the HW&MC. Several key political constraints on committee decision-making were addressed--including public attitudes, interest groups, political party strength and tradition and precedents. The economic constraints that affected revenue decisions included court mandates, federal mandates and the fiscal condition of the nation and the state.^ The third component of the revenue decision-making framework included two alternative contingency theories. The first alternative theory postulated that the committee structure, including the individual member roles and the overall committee style, resulted in distinctive revenue decisions. This theory will be favored if evidence points to the committee acting autonomously with less concern for the policies of the Speaker of the House. The Speaker assignment theory, postulated that the assignment of committee members shaped or changed the course of committee decision-making. This theory will be favored if there was evidence that the committee was strictly a vehicle for the Speaker to institute his preferred tax policies.^ The ultimate goal of this analysis is to develop an explanation for legislative decision-making about tax policy. This explanation will be based on the linkages across various tax options, political and economic constraints, member roles and committee style and the patterns of committee assignment. ^

Cloning and molecular analysis of paraxis: A {\it trans\/}-acting factor required for somite maturation

During vertebrate embryogenesis, cells from the paraxial mesoderm coalesce in a rostral-to-caudal progression to form the somites. Subsequent compartmentalization of the somites yields the sclerotome, myotome and dermatome, which give rise to the axial skeleton, axial musculature, and dermis, respectively. Recently, we cloned a novel basic-Helix-Loop-Helix (bHLH) protein, called scleraxis, which is expressed in the sclerotome, in mesenchymal precursors of bone and cartilage, and in connective tissues. This dissertation focuses on the cloning, expression and functional analysis of a bHLH protein termed paraxis, which is nearly identical to scleraxis within the bHLH region but diverges in both its amino and carboxyl termini. During the process of mouse embryogenesis, paraxis transcripts are first detected at about day 7.5 post coitum within the primitive mesoderm lying posterior to the head and heart primordia. Subsequently, paraxis expression progresses caudally through the paraxial mesoderm, immediately preceding somite formation. Paraxis is expressed at high levels in newly formed somites before the first detectable expression of the myogenic bHLH genes, and as the somite becomes compartmentalized, paraxis becomes downregulated within the myotome.^ To determine the function of paraxis during mammalian embryogenesis, mice were generated with a null mutation in the paraxis locus. Paraxis null mice survived until birth, but exhibited severe foreshortening along the anteroposterior axis due to the absence of vertebrae caudal to the midthoracic region. The phenotype also included axial skeletal defects, particularly shortened bifurcated ribs which were detached from the vertebral column, fused vertebrae and extensive truncation and disorganization caudal to the hindlimbs. Mutant neonates also lacked normal levels of trunk muscle and exhibited defects in the dermis as well as the stratification of the epidermis. Analysis of paraxis -/- mutant embryos has revealed a failure of the somites to both properly epithelialize and compartmentalize, resulting in defects in somite-derived cell lineages. These results suggest that paraxis is an essential component of the genetic pathway regulating somitogenesis. ^

Fulminant hepatic and multiple organ failure following acute viral tonsillitis: a case report.

BACKGROUND Pyogenic tonsillitis may often be observed in the general Western population. In severe cases, it may require antibiotic treatment or even hospitalization and often a prompt clinical response will be noted. Here we present an unusual case of progressive multiple organ failure including fulminant liver failure following acute tonsillitis initially mistaken for "classic" pyogenic (that is bacterial) tonsillitis. CASE PRESENTATION A 68-year-old previously healthy white man was referred with suspicion of pyogenic angina. After tonsillectomy, he developed acute liver failure and consecutive multiple organ failure including acute hemodynamic, pulmonary and dialysis-dependent renal failure. Immunohistopathological analysis of his tonsils and liver as well as serum polymerase chain reaction analyses revealed herpes simplex virus-2 to be the causative pathogen. Treatment included high-dose acyclovir and multiorgan supportive intensive care therapy. His final outcome was favorable. CONCLUSIONS Fulminant herpes simplex virus-2-induced multiple organ failure is rarely observed in the Western hemisphere and should be considered a potential diagnosis in patients with tonsillitis and multiple organ failure including acute liver failure. From a clinical perspective, it seems important to note that fulminant herpes simplex virus-2 infection may masquerade as "routine" bacterial severe sepsis/septic shock. This persevering condition should be diagnosed early and treated goal-oriented in order to gain control of this life-threatening condition.

An investigation of the performance of a new Mechanical thrombectomy device using Bond Graph modelling: application to the extraction of blood clots in the middle cerebral artery

A number of thrombectomy devices using a variety of methods have now been developed to facilitate clot removal. We present research involving one such experimental device recently developed in the UK, called a ‘GP’ Thrombus Aspiration Device (GPTAD). This device has the potential to bring about the extraction of a thrombus. Although the device is at a relatively early stage of development, the results look encouraging. In this work, we present an analysis and modeling of the GPTAD by means of the bond graph technique; it seems to be a highly effective method of simulating the device under a variety of conditions. Such modeling is useful in optimizing the GPTAD and predicting the result of clot extraction. The aim of this simulation model is to obtain the minimum pressure necessary to extract the clot and to verify that both the pressure and the time required to complete the clot extraction are realistic for use in clinical situations, and are consistent with any experimentally obtained data. We therefore consider aspects of rheology and mechanics in our modeling.

Analysis of the Fracture of Reinforced Concrete Flat Elements Subjected to Explosions. Experimental Procedure and Numerical Validation

Many of the material models most frequently used for the numerical simulation of the behavior of concrete when subjected to high strain rates have been originally developed for the simulation of ballistic impact. Therefore, they are plasticity-based models in which the compressive behavior is modeled in a complex way, while their tensile failure criterion is of a rather simpler nature. As concrete elements usually fail in tensión when subjected to blast loading, available concrete material models for high strain rates may not represent accurately their real behavior. In this research work an experimental program of reinforced concrete fíat elements subjected to blast load is presented. Altogether four detonation tests are conducted, in which 12 slabs of two different concrete types are subjected to the same blast load. The results of the experimental program are then used for the development and adjustment of numerical tools needed in the modeling of concrete elements subjected to blast.

Simulation of a mechanical thrombectomy device based in the use of self-expandable stents for the blood clots extraction

Recently, we have presented some studies concerning the analysis, design and optimization of one experimental device developed in the UK - GPTAD - which has been designed to remove blood clots without the need to make contact with the clot itself, thereby potentially reducing the risk of problems such as downstream embolisation. Based on the idea of a modification of the previous device, in this work, we present a model based in the use of stents like the SolitaireTM FR, which is in contact with the clot itself. In the case of such devices, the stent is self-expandable and the extraction of the blood clot is faciliatated by the stent, which must be inside the clot. Such stents are generally inserted in position by using the guidewire inserted into the catheter. This type of modeling could potentially be useful in showing how the blood clot is moved by the various different forces involved. The modelling has been undertaken by analyzing the resistances, compliances and inertances effects. We model an artery and blood clot for range of forces for the guidewire. In each case we determine the interaction between blood clot, stent and artery.

Analysis of the Mechanical Properties of Multicrystalline and Monocrystalline Silicon Wafers Manufactured by Casting Methods

Quasi-monocrystalline silicon wafers have appeared as a critical innovation in the PV industry, joining the most favourable characteristics of the conventional substrates: the higher solar cell efficiencies of monocrystalline Czochralski-Si (Cz-Si) wafers and the lower cost and the full square-shape of the multicrystalline ones. However, the quasi-mono ingot growth can lead to a different defect structure than the typical Cz-Si process. Thus, the properties of the brand-new quasi-mono wafers, from a mechanical point of view, have been for the first time studied, comparing their strength with that of both Cz-Si mono and typical multicrystalline materials. The study has been carried out employing the four line bending test and simulating them by means of FE models. For the analysis, failure stresses were fitted to a three-parameter Weibull distribution. High mechanical strength was found in all the cases. The low quality quasi-mono wafers, interestingly, did not exhibit critical strength values for the PV industry, despite their noticeable density of extended defects.

Upper Limb Portable Motion Analysis System Based on Inertial Technology for Neurorehabilitation Purposes

Here an inertial sensor-based monitoring system for measuring and analyzing upper limb movements is presented. The final goal is the integration of this motion-tracking device within a portable rehabilitation system for brain injury patients. A set of four inertial sensors mounted on a special garment worn by the patient provides the quaternions representing the patient upper limb’s orientation in space. A kinematic model is built to estimate 3D upper limb motion for accurate therapeutic evaluation. The human upper limb is represented as a kinematic chain of rigid bodies with three joints and six degrees of freedom. Validation of the system has been performed by co-registration of movements with a commercial optoelectronic tracking system. Successful results are shown that exhibit a high correlation among signals provided by both devices and obtained at the Institut Guttmann Neurorehabilitation Hospital.

Program analysis, debugging and optimization using the ciao system preprocessor

We present a tutorial overview of Ciaopp, the Ciao system preprocessor. Ciao is a public-domain, next-generation logic programming system, which subsumes ISO-Prolog and is specifically designed to a) be highly extensible via librarles and b) support modular program analysis, debugging, and optimization. The latter tasks are performed in an integrated fashion by Ciaopp. Ciaopp uses modular, incremental abstract interpretation to infer properties of program predicates and literals, including types, variable instantiation properties (including modes), non-failure, determinacy, bounds on computational cost, bounds on sizes of terms in the program, etc. Using such analysis information, Ciaopp can find errors at compile-time in programs and/or perform partial verification. Ciaopp checks how programs cali system librarles and also any assertions present in the program or in other modules used by the program. These assertions are also used to genérate documentation automatically. Ciaopp also uses analysis information to perform program transformations and optimizations such as múltiple abstract specialization, parallelization (including granularity control), and optimization of run-time tests for properties which cannot be checked completely at compile-time. We illustrate "hands-on" the use of Ciaopp in all these tasks. By design, Ciaopp is a generic tool, which can be easily tailored to perform these and other tasks for different LP and CLP dialects.

Using global analysis, partial specifications, and an extensible assertion language for program validation and debugging

We discuss a framework for the application of abstract interpretation as an aid during program development, rather than in the more traditional application of program optimization. Program validation and detection of errors is first performed statically by comparing (partial) specifications written in terms of assertions against information obtained from (global) static analysis of the program. The results of this process are expressed in the user assertion language. Assertions (or parts of assertions) which cannot be checked statically are translated into run-time tests. The framework allows the use of assertions to be optional. It also allows using very general properties in assertions, beyond the predefined set understandable by the static analyzer and including properties defined by user programs. We also report briefly on an implementation of the framework. The resulting tool generates and checks assertions for Prolog, CLP(R), and CHIP/CLP(fd) programs, and integrates compile-time and run-time checking in a uniform way. The tool allows using properties such as types, modes, non-failure, determinacy, and computational cost, and can treat modules separately, performing incremental analysis.

Using global analysis, partial specifications, and an extensible assertion language for program validation and debugging

We present a framework for the application of abstract interpretation as an aid during program development, rather than in the more traditional application of program optimization. Program validation and detection of errors is first performed statically by comparing (partial) specifications written in terms of assertions against information obtained from static analysis of the program. The results of this process are expressed in the user assertion language. Assertions (or parts of assertions) which cannot be verified statically are translated into run-time tests. The framework allows the use of assertions to be optional. It also allows using very general properties in assertions, beyond the predefined set understandable by the static analyzer and including properties defined by means of user programs. We also report briefly on an implementation of the framework. The resulting tool generates and checks assertions for Prolog, CLP(R), and CHIP/CLP(fd) programs, and integrates compile-time and run-time checking in a uniform way. The tool allows using properties such as types, modes, non-failure, determinacy, and computational cost, and can treat modules separately, performing incremental analysis. In practice, this modularity allows detecting statically bugs in user programs even if they do not contain any assertions.