Bayesian generalized linear models for meta-analysis of diagnostic tests

With the recognition of the importance of evidence-based medicine, there is an emerging need for methods to systematically synthesize available data. Specifically, methods to provide accurate estimates of test characteristics for diagnostic tests are needed to help physicians make better clinical decisions. To provide more flexible approaches for meta-analysis of diagnostic tests, we developed three Bayesian generalized linear models. Two of these models, a bivariate normal and a binomial model, analyzed pairs of sensitivity and specificity values while incorporating the correlation between these two outcome variables. Noninformative independent uniform priors were used for the variance of sensitivity, specificity and correlation. We also applied an inverse Wishart prior to check the sensitivity of the results. The third model was a multinomial model where the test results were modeled as multinomial random variables. All three models can include specific imaging techniques as covariates in order to compare performance. Vague normal priors were assigned to the coefficients of the covariates. The computations were carried out using the 'Bayesian inference using Gibbs sampling' implementation of Markov chain Monte Carlo techniques. We investigated the properties of the three proposed models through extensive simulation studies. We also applied these models to a previously published meta-analysis dataset on cervical cancer as well as to an unpublished melanoma dataset. In general, our findings show that the point estimates of sensitivity and specificity were consistent among Bayesian and frequentist bivariate normal and binomial models. However, in the simulation studies, the estimates of the correlation coefficient from Bayesian bivariate models are not as good as those obtained from frequentist estimation regardless of which prior distribution was used for the covariance matrix. The Bayesian multinomial model consistently underestimated the sensitivity and specificity regardless of the sample size and correlation coefficient. In conclusion, the Bayesian bivariate binomial model provides the most flexible framework for future applications because of its following strengths: (1) it facilitates direct comparison between different tests; (2) it captures the variability in both sensitivity and specificity simultaneously as well as the intercorrelation between the two; and (3) it can be directly applied to sparse data without ad hoc correction. ^

Analysis of prognostic factors for the development of metastases and survival in renal cell carcinoma patients

Introduction and objective. A number of prognostic factors have been reported for predicting survival in patients with renal cell carcinoma. Yet few studies have analyzed the effects of those factors at different stages of the disease process. In this study, different stages of disease progression starting from nephrectomy to metastasis, from metastasis to death, and from evaluation to death were evaluated. ^ Methods. In this retrospective follow-up study, records of 97 deceased renal cell carcinoma (RCC) patients were reviewed between September 2006 to October 2006. Patients with TNM Stage IV disease before nephrectomy or with cancer diagnoses other than RCC were excluded leaving 64 records for analysis. Patient TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were analyzed in relation to time to metastases. Time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from metastases to death. Finally, analysis of laboratory values at time of evaluation, Eastern Cooperative Oncology Group performance status (ECOG), UCLA Integrated Staging System (UISS), time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from evaluation to death. Linear regression and Cox Proportional Hazard (univariate and multivariate) was used for testing significance. Kaplan-Meier Log-Rank test was used to detect any significance between groups at various endpoints. ^ Results. Compared to negative lymph nodes at time of nephrectomy, a single positive lymph node had significantly shorter time to metastasis (p<0.0001). Compared to other histological types, clear cell histology had significant metastasis free survival (p=0.003). Clear cell histology compared to other types (p=0.0002 univariate, p=0.038 multivariate) and time to metastasis with log conversion (p=0.028) significantly affected time from metastasis to death. A greater than one year and greater than two year metastasis free interval, compared to patients that had metastasis before one and two years, had statistically significant survival benefit (p=0.004 and p=0.0318). Time from evaluation to death was affected by greater than one year metastasis free interval (p=0.0459), alcohol consumption (p=0.044), LDH (p=0.006), ECOG performance status (p<0.001), and hemoglobin level (p=0.0092). The UISS risk stratified the patient population in a statistically significant manner for survival (p=0.001). No other factors were found to be significant. ^ Conclusion. Clear cell histology is predictive for both time to metastasis and metastasis to death. Nodal status at time of nephrectomy may predict risk of metastasis. The time interval to metastasis significantly predicts time from metastasis to death and time from evaluation to death. ECOG performance status, and hemoglobin levels predicts survival outcome at evaluation. Finally, UISS appropriately stratifies risk in our population. ^

A comparative analysis of CHIP Perinatal policy in twelve states

The purpose of this comparative analysis of CHIP Perinatal policy (42 CFR § 457) was to provide a basis for understanding the variation in policy outputs across the twelve states that, as of June 2007, implemented the Unborn Child rule. This Department of Health and Human Services regulation expanded in 2002 the definition of “child” to include the period from conception to birth, allowing states to consider an unborn child a “targeted low-income child” and therefore eligible for SCHIP coverage. ^ Specific study aims were to (1) describe typologically the structural and contextual features of the twelve states that adopted a CHIP Perinatal policy; (2) describe and differentiate among the various designs of CHIP Perinatal policy implemented in the states; and (3) develop a conceptual model that links the structural and contextual features of the adopting states to differences in the forms the policy assumed, once it was implemented. ^ Secondary data were collected from publicly available information sources to describe characteristics of states’ political system, health system, economic system, sociodemographic context and implemented policy attributes. I posited that socio-demographic differences, political system differences and health system differences would directly account for the observed differences in policy output among the states. ^ Exploratory data analysis techniques, which included median polishing and multidimensional scaling, were employed to identify compelling patterns in the data. Scaled results across model components showed that economic system was most closely related to policy output, followed by health system. Political system and socio-demographic characteristics were shown to be weakly associated with policy output. Goodness-of-fit measures for MDS solutions implemented across states and model components, in one- and two-dimensions, were very good. ^ This comparative policy analysis of twelve states that adopted and implemented HHS Regulation 42 C.F.R. § 457 contributes to existing knowledge in three areas: CHIP Perinatal policy, public health policy and policy sciences. First, the framework allows for the identification of CHIP Perinatal program design possibilities and provides a basis for future studies that evaluate policy impact or performance. Second, studies of policy determinants are not well represented in the health policy literature. Thus, this study contributes to the development of the literature in public health policy. Finally, the conceptual framework for policy determinants developed in this study suggests new ways for policy makers and practitioners to frame policy arguments, encouraging policy change or reform. ^

Interim analysis of clinical trials: Simulation studies of fractional Brownian motion

Interim clinical trial monitoring procedures were motivated by ethical and economic considerations. Classical Brownian motion (Bm) techniques for statistical monitoring of clinical trials were widely used. Conditional power argument and α-spending function based boundary crossing probabilities are popular statistical hypothesis testing procedures under the assumption of Brownian motion. However, it is not rare that the assumptions of Brownian motion are only partially met for trial data. Therefore, I used a more generalized form of stochastic process, called fractional Brownian motion (fBm), to model the test statistics. Fractional Brownian motion does not hold Markov property and future observations depend not only on the present observations but also on the past ones. In this dissertation, we simulated a wide range of fBm data, e.g., H = 0.5 (that is, classical Bm) vs. 0.5< H <1, with treatment effects vs. without treatment effects. Then the performance of conditional power and boundary-crossing based interim analyses were compared by assuming that the data follow Bm or fBm. Our simulation study suggested that the conditional power or boundaries under fBm assumptions are generally higher than those under Bm assumptions when H > 0.5 and also matches better with the empirical results. ^

Policy analysis of Texas Senate Bill 532 and the regulation of nurse practitioners in the convenience care model

Background. Retail clinics, also called convenience care clinics, have become a rapidly growing trend since their initial development in 2000. These clinics are coupled within a larger retail operation and are generally located in "big-box" discount stores such as Wal-mart or Target, grocery stores such as Publix or H-E-B, or in retail pharmacies such as CVS or Walgreen's (Deloitte Center for Health Solutions, 2008). Care is typically provided by nurse practitioners. Research indicates that this new health care delivery system reduces cost, raises quality, and provides a means of access to the uninsured population (e.g., Deloitte Center for Health Solutions, 2008; Convenient Care Association, 2008a, 2008b, 2008c; Hansen-Turton, Miller, Nash, Ryan, Counts, 2007; Salinsky, 2009; Scott, 2006; Ahmed & Fincham, 2010). Some healthcare analysts even suggest that retail clinics offer a feasible solution to the shortage of primary care physicians facing the nation (AHRQ Health Care Innovations Exchange, 2010). ^ The development and performance of retail clinics is heavily dependent upon individual state policies regulating NPs. Texas currently has one of the most highly regulated practice environments for NPs (Stout & Elton, 2007; Hammonds, 2008). In September 2009, Texas passed Senate Bill 532 addressing the scope of practice of nurse practitioners in the convenience care model. In comparison to other states, this law still heavily regulates nurse practitioners. However, little research has been conducted to evaluate the impact of state laws regulating nurse practitioners on the development and performance of retail clinics. ^ Objectives. (1). To describe the potential impact that SB 532 has on retail clinic performance. (2). To discuss the effectiveness, efficiency, and equity of the convenience care model. (3). To describe possible alternatives to Texas' nurse practitioner scope of practice guidelines as delineated in Texas Senate Bill 532. (4). To describe the type of nurse practitioner state regulation (i.e. independent, light, moderate, or heavy) that best promotes the convenience care model. ^ Methods. State regulations governing nurse practitioners can be characterized as independent, light, moderate, and heavy. Four state NP regulatory types and retail clinic performance were compared and contrasted to that of Texas regulations using Dunn and Aday's theoretical models for conducting policy analysis and evaluating healthcare systems. Criteria for measurement included effectiveness, efficiency, and equity. Comparison states were Arizona (Independent), Minnesota (Light), Massachusetts (Moderate), and Florida (Heavy). ^ Results. A comparative states analysis of Texas SB 532 and alternative NP scope of practice guidelines among the four states: Arizona, Florida, Massachusetts, and Minnesota, indicated that SB 532 has minimal potential to affect the shortage of primary care providers in the state. Although SB 532 may increase the number of NPs a physician may supervise, NPs are still heavily restricted in their scope of practice and limited in their ability to act as primary care providers. Arizona's example of independent NP practice provided the best alternative to affect the shortage of PCPs in Texas as evidenced by a lower uninsured rate and less ED visits per 1,000 population. A survey of comparison states suggests that retail clinics thrive in states that more heavily restrict NP scope of practice as opposed to those that are more permissive, with the exception of Arizona. An analysis of effectiveness, efficiency, and equity of the convenience care model indicates that retail clinics perform well in the areas of effectiveness and efficiency; but, fall short in the area of equity. ^ Conclusion. Texas Senate 532 represents an incremental step towards addressing the problem of a shortage of PCPs in the state. A comparative policy analysis of the other four states with varying degrees of NP scope of practice indicate that a more aggressive policy allowing for independent NP practice will be needed to achieve positive changes in health outcomes. Retail clinics pose a temporary solution to the shortage of PCPs and will need to expand their locations to poorer regions and incorporate some chronic care to obtain measurable health outcomes. ^

A comparative analysis of Texas and Louisiana Oil-field NORM Waste Policy

NORM (Naturally Occurring Radioactive Material) Waste Policies for the nation's oil and gas producing states have been in existence since the 1980's, when Louisiana was the first state to develop a NORM regulatory program in 1989. Since that time, expectations for NORM Waste Policies have evolved, as Health, Safety, Environment, and Social responsibility (HSE & SR) grows increasingly important to the public. Therefore, the oil and gas industry's safety and environmental performance record will face challenges in the future, about its best practices for managing the co-production of NORM wastes. ^ Within the United States, NORM is not federally regulated. The U.S. EPA claims it regulates NORM under CERCLA (superfund) and the Clean Water Act. Though, there are no universally applicable regulations for radium-based NORM waste. Therefore, individual states have taken responsibility for developing NORM regulatory programs, because of the potential radiological risk it can pose to man (bone and lung cancer) and his environment. This has led to inconsistencies in NORM Waste Policies as well as a NORM management gap in both state and federal regulatory structures. ^ Fourteen different NORM regulations and guidelines were compared between Louisiana and Texas, the nation's top two petroleum producing states. Louisiana is the country's top crude oil producer when production from its Federal offshore waters are included, and fourth in crude oil production, behind Texas, Alaska, and California when Federal offshore areas are excluded. Louisiana produces more petroleum products than any state but Texas. For these reasons, a comparative analysis between Louisiana and Texas was undertaken to identify differences in their NORM regulations and guidelines for managing, handling and disposing NORM wastes. Moreover, this analysis was undertaken because Texas is the most explored and drilled worldwide and yet appears to lag behind its neighboring state in terms of its NORM Waste Policy and developing an industry standard for handling, managing and disposing NORM. As a result of this analysis, fourteen recommendations were identified.^

Improved Techniques for Acquisition and Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Detecting Vascular Permeability in the Central Nervous System

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique for quantitative assessment of the integrity of blood-brain barrier and blood-spinal cord barrier (BSCB) in the presence of central nervous system pathologies. However, the results of DCE-MRI show substantial variability. The high variability can be caused by a number of factors including inaccurate T1 estimation, insufficient temporal resolution and poor contrast-to-noise ratio. My thesis work is to develop improved methods to reduce the variability of DCE-MRI results. To obtain fast and accurate T1 map, the Look-Locker acquisition technique was implemented with a novel and truly centric k-space segmentation scheme. In addition, an original multi-step curve fitting procedure was developed to increase the accuracy of T1 estimation. A view sharing acquisition method was implemented to increase temporal resolution, and a novel normalization method was introduced to reduce image artifacts. Finally, a new clustering algorithm was developed to reduce apparent noise in the DCE-MRI data. The performance of these proposed methods was verified by simulations and phantom studies. As part of this work, the proposed techniques were applied to an in vivo DCE-MRI study of experimental spinal cord injury (SCI). These methods have shown robust results and allow quantitative assessment of regions with very low vascular permeability. In conclusion, applications of the improved DCE-MRI acquisition and analysis methods developed in this thesis work can improve the accuracy of the DCE-MRI results.

A comparative analysis of hospital -based physician monitoring systems

The purpose of the multiple case-study was to determine how hospital subsystems (such as physician monitoring and credentialing; quality assurance; risk management; and peer review) were supporting the monitoring of physicians? Three large metropolitan hospitals in Texas were studied and designated as hospitals #1, #2, and #3. Realizing that hospital subsystems are a unique entity and part of a larger system, conclusions were made on the premises of a quality control system, in relation to the tools of government (particularly the Health Care Quality Improvement Act (HCQIA)), and in relation to itself as a tool of a hospital.^ Three major analytical assessments were performed. First, the subsystems were analyzed as to their "completeness"; secondly, the subsystems were analyzed for "performance"; and thirdly, the subsystems were analyzed in reference to the interaction of completeness and performance.^ The physician credentialing and monitoring and the peer review subsystems as quality control systems were most complete, efficient, and effective in hospitals #1 and #3. The HCQIA did not seem to be an influencing factor in the completeness of the subsystem in hospital #1. The quality assurance and risk management subsystem in hospital #2 was not representative of completeness and performance and the HCQIA was not an influencing factor in the completeness of the Q.A. or R.M. systems in any hospital. The efficiency (computerization) of the physician credentialing, quality assurance and peer review subsystems in hospitals #1 and #3 seemed to contribute to their effectiveness (system-wide effect).^ The results indicated that the more complete, effective, and efficient subsystems were characterized by (1) all defined activities being met, (2) the HCQIA being an influencing factor, (3) a decentralized administrative structure, (4) computerization an important element, and (5) staff was sophisticated in subsystem operations. However, other variables were identified which deserve further research as to their effect on completeness and performance of subsystems. They include (1) medical staff affiliations, (2) system funding levels, (3) the system's administrative structure, and (4) the physician staff "cultural" characteristics. Perhaps by understanding other influencing factors, health care administrators may plan subsystems that will be compatible with legislative requirements and administrative objectives. ^

Whole Genome Analysis of Pinkeye Scores in Angus Cattle

Infectious Bovine Keratoconjunctivitis (IBK), known as pinkeye, is a common infectious disease affecting the eyes of cattle. It is characterized by excessive tearing, inflammation of the conjunctiva, and ulceration of the cornea. Although pinkeye is non-fatal, it has a marked economic impact on the cattle industry, due to the decreased performance of infected individuals. Genetic effects on the susceptibility of IBK have been studied and Hereford, Jersey, and Holstein breeds were found to be more susceptible to IBK than Bos Indicus breeds. The objectives of our study were: 1) to estimate genetic parameters of IBK scored in different categories by using genomic threshold model, and 2) to detect markers in linkage disequilibrium with quantitative tract loci (QTL) associated with IBK.

A global seasonal surface ocean climatology of phytoplankton types based on CHEMTAX analysis of HPLC pigments

Much advancement has been made in recent years in field data assimilation, remote sensing and ecosystem modeling, yet our global view of phytoplankton biogeography beyond chlorophyll biomass is still a cursory taxonomic picture with vast areas of the open ocean requiring field validations. High performance liquid chromatography (HPLC) pigment data combined with inverse methods offer an advantage over many other phytoplankton quantification measures by way of providing an immediate perspective of the whole phytoplankton community in a sample as a function of chlorophyll biomass. Historically, such chemotaxonomic analysis has been conducted mainly at local spatial and temporal scales in the ocean. Here, we apply a widely tested inverse approach, CHEMTAX, to a global climatology of pigment observations from HPLC. This study marks the first systematic and objective global application of CHEMTAX, yielding a seasonal climatology comprised of ~1500 1°x1° global grid points of the major phytoplankton pigment types in the ocean characterizing cyanobacteria, haptophytes, chlorophytes, cryptophytes, dinoflagellates, and diatoms, with results validated against prior regional studies where possible. Key findings from this new global view of specific phytoplankton abundances from pigments are a) the large global proportion of marine haptophytes (comprising 32 ± 5% of total chlorophyll), whose biogeochemical functional roles are relatively unknown, and b) the contrasting spatial scales of complexity in global community structure that can be explained in part by regional oceanographic conditions. These publicly accessible results will guide future parameterizations of marine ecosystem models exploring the link between phytoplankton community structure and marine biogeochemical cycles.

Field analysis of solar PV-based collective systems for rural electrification.

This article analyses the long-term performance of collective off-grid photovoltaic (PV) systems in rural areas. The use of collective PV systems for the electrification of small medium-size villages in developing countries has increased in the recent years. They are basically set up as stand-alone installations (diesel hybrid or pure PV) with no connection with other electrical grids. Their particular conditions (isolated) and usual installation places (far from commercial/industrial centers) require an autonomous and reliable technology. Different but related factors affect their performance and the energy supply; some of them are strictly technical but others depend on external issues like the solar energy resource and users’ energy and power consumption. The work presented is based on field operation of twelve collective PV installations supplying the electricity to off-grid villages located in the province of Jujuy, Argentina. Five of them have PV generators as unique power source while other seven include the support of diesel groups. Load demand evolution, energy productivity and fuel consumption are analyzed. Besides, energy generation strategies (PV/diesel) are also discussed.

Ion Beam Analysis of He-implanted fusion solid breedes

Introduction Lithium-based ceramics (silicates, titanates, ?) possess a series of advantages as alternative over liquid lithium and lithium-lead alloys for fusion breeders. They have a sufficient lithium atomic density (up to 540 kg*m-3), high temperature stability (up to 1300 K), and good chemical compatibility with structural materials. Nevertheless, few research is made on the diffusion behavior of He and H isotopes through polycrystalline structures of porous ceramics which is crucial in order to understand the mobility of gas coolants as well as, the release of tritium. Moreover, in the operating conditions of actual breeder blanket concepts, the extraction rate of the helium produced during lithium transmutation can be affected by the composition and the structure of the near surface region modifying the performance of BB materials

A robust numerical framework for the analysis of material failure of fibre reinforced soft tissue

In this work, robustness and stability of continuum damage models applied to material failure in soft tissues are addressed. In the implicit damage models equipped with softening, the presence of negative eigenvalues in the tangent elemental matrix degrades the condition number of the global matrix, leading to a reduction of the computational performance of the numerical model. Two strategies have been adapted from literature to improve the aforementioned computational performance degradation: the IMPL-EX integration scheme [Oliver,2006], which renders the elemental matrix contribution definite positive, and arclength-type continuation methods [Carrera,1994], which allow to capture the unstable softening branch in brittle ruptures. The IMPL-EX integration scheme has as a major drawback the need to use small time steps to keep numerical error below an acceptable value. A convergence study, limiting the maximum allowed increment of internal variables in the damage model, is presented. Finally, numerical simulation of failure problems with fibre reinforced materials illustrates the performance of the adopted methodology.

Dynamic Analysis of high Speed Railway Traffic Loads on Ballasted Track

This paper reports the studies carried out to develop and calibrate the optimal models for the objectives of this work. In particular, quarter bogie model for vehicle, rail-wheel contact with Lagrangian multiplier method, 2D spatial discretization were selected as the optimal decisions. Furthermore, the 3D model of coupled vehicle-track also has been developed to contrast the results obtained in the 2D model. The calculations were carried out in the time domain and envelopes of relevant results were obtained for several track profiles and speed ranges. Distributed elevation irregularities were generated based on power spectral density (PSD) distributions. The results obtained include the wheel-rail contact forces, forces transmitted to the bogie by primary suspension. The latter loads are relevant for the purpose of evaluating the performance of the infrastructure