Immunologic response to antiretroviral therapy in hepatitis C virus-coinfected adults in a population-based HIV/AIDS treatment program

BACKGROUND: We sought to characterize the impact that hepatitis C virus (HCV) infection has on CD4 cells during the first 48 weeks of antiretroviral therapy (ART) in previously ART-naive human immunodeficiency virus (HIV)-infected patients. METHODS: The HIV/AIDS Drug Treatment Programme at the British Columbia Centre for Excellence in HIV/AIDS distributes all ART in this Canadian province. Eligible individuals were those whose first-ever ART included 2 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor and who had a documented positive result for HCV antibody testing. Outcomes were binary events (time to an increase of > or = 75 CD4 cells/mm3 or an increase of > or = 10% in the percentage of CD4 cells in the total T cell population [CD4 cell fraction]) and continuous repeated measures. Statistical analyses used parametric and nonparametric methods, including multivariate mixed-effects linear regression analysis and Cox proportional hazards analysis. RESULTS: Of 1186 eligible patients, 606 (51%) were positive and 580 (49%) were negative for HCV antibodies. HCV antibody-positive patients were slower to have an absolute (P<.001) and a fraction (P = .02) CD4 cell event. In adjusted Cox proportional hazards analysis (controlling for age, sex, baseline absolute CD4 cell count, baseline pVL, type of ART initiated, AIDS diagnosis at baseline, adherence to ART regimen, and number of CD4 cell measurements), HCV antibody-positive patients were less likely to have an absolute CD4 cell event (adjusted hazard ratio [AHR], 0.84 [95% confidence interval [CI], 0.72-0.98]) and somewhat less likely to have a CD4 cell fraction event (AHR, 0.89 [95% CI, 0.70-1.14]) than HCV antibody-negative patients. In multivariate mixed-effects linear regression analysis, HCV antibody-negative patients had increases of an average of 75 cells in the absolute CD4 cell count and 4.4% in the CD4 cell fraction, compared with 20 cells and 1.1% in HCV antibody-positive patients, during the first 48 weeks of ART, after adjustment for time-updated pVL, number of CD4 cell measurements, and other factors. CONCLUSION: HCV antibody-positive HIV-infected patients may have an altered immunologic response to ART.

Modeling of transfer kinetics at the serum-cerebrospinal fluid barrier in rabbits with experimental meningitis: application to grepafloxacin

The goals of the present study were to model the population kinetics of in vivo influx and efflux processes of grepafloxacin at the serum-cerebrospinal fluid (CSF) barrier and to propose a simulation-based approach to optimize the design of dose-finding trials in the meningitis rabbit model. Twenty-nine rabbits with pneumococcal meningitis receiving grepafloxacin at 15 mg/kg of body weight (intravenous administration at 0 h), 30 mg/kg (at 0 h), or 50 mg/kg twice (at 0 and 4 h) were studied. A three-compartment population pharmacokinetic model was fit to the data with the program NONMEM (Nonlinear Mixed Effects Modeling). Passive diffusion clearance (CL(diff)) and active efflux clearance (CL(active)) are transfer kinetic modeling parameters. Influx clearance is assumed to be equal to CL(diff), and efflux clearance is the sum of CL(diff), CL(active), and bulk flow clearance (CL(bulk)). The average influx clearance for the population was 0.0055 ml/min (interindividual variability, 17%). Passive diffusion clearance was greater in rabbits receiving grepafloxacin at 15 mg/kg than in those treated with higher doses (0.0088 versus 0.0034 ml/min). Assuming a CL(bulk) of 0.01 ml/min, CL(active) was estimated to be 0.017 ml/min (11%), and clearance by total efflux was estimated to be 0.032 ml/min. The population kinetic model allows not only to quantify in vivo efflux and influx mechanisms at the serum-CSF barrier but also to analyze the effects of different dose regimens on transfer kinetic parameters in the rabbit meningitis model. The modeling-based approach also provides a tool for the simulation and prediction of various outcomes in which researchers might be interested, which is of great potential in designing dose-finding trials.

Critical evaluation of diameter increment modelling in the Great Lakes region

Simulations of forest stand dynamics in a modelling framework including Forest Vegetation Simulator (FVS) are diameter driven, thus the diameter or basal area increment model needs a special attention. This dissertation critically evaluates diameter or basal area increment models and modelling approaches in the context of the Great Lakes region of the United States and Canada. A set of related studies are presented that critically evaluate the sub-model for change in individual tree basal diameter used in the Forest Vegetation Simulator (FVS), a dominant forestry model in the Great Lakes region. Various historical implementations of the STEMS (Stand and Tree Evaluation and Modeling System) family of diameter increment models, including the current public release of the Lake States variant of FVS (LS-FVS), were tested for the 30 most common tree species using data from the Michigan Forest Inventory and Analysis (FIA) program. The results showed that current public release of the LS-FVS diameter increment model over-predicts 10-year diameter increment by 17% on average. Also the study affirms that a simple adjustment factor as a function of a single predictor, dbh (diameter at breast height) used in the past versions, provides an inadequate correction of model prediction bias. In order to re-engineer the basal diameter increment model, the historical, conceptual and philosophical differences among the individual tree increment model families and their modelling approaches were analyzed and discussed. Two underlying conceptual approaches toward diameter or basal area increment modelling have been often used: the potential-modifier (POTMOD) and composite (COMP) approaches, which are exemplified by the STEMS/TWIGS and Prognosis models, respectively. It is argued that both approaches essentially use a similar base function and neither is conceptually different from a biological perspective, even though they look different in their model forms. No matter what modelling approach is used, the base function is the foundation of an increment model. Two base functions – gamma and Box-Lucas – were identified as candidate base functions for forestry applications. The results of a comparative analysis of empirical fits showed that quality of fit is essentially similar, and both are sufficiently detailed and flexible for forestry applications. The choice of either base function in order to model diameter or basal area increment is dependent upon personal preference; however, the gamma base function may be preferred over the Box-Lucas, as it fits the periodic increment data in both a linear and nonlinear composite model form. Finally, the utility of site index as a predictor variable has been criticized, as it has been widely used in models for complex, mixed species forest stands though not well suited for this purpose. An alternative to site index in an increment model was explored, using site index and a combination of climate variables and Forest Ecosystem Classification (FEC) ecosites and data from the Province of Ontario, Canada. The results showed that a combination of climate and FEC ecosites variables can replace site index in the diameter increment model.

Training Volume and Methods of Athletes Competing at a Mixed Martial Arts Events

This study surveyed 32 athletes competing at a mixed martial arts (MMA) event held in Butte, Montana. The survey attempted to gather information regarding overall training volume, supplement use, volume change and specific exercises used. The survey return rate was 100 percent (32/32). Twenty-five of 32 athletes supplemented their training with strength training. Overall frequency of strength training ranged from one to six sessions/week, and overall frequency of fighting-specific training sessions/weel ranged from two to 10. Two of the 32 athletes used/had used anabolic-androgenic steroids. Sixteen MMA athletes performed exercises specifically for the neck musculature, and eight use the power clean within their strength-training program. Results suggested that strength and conditioning speciialists should educate the importance of, volume variation and periodization, balanced training, effective exercises, and the side effects of anabolic steroid use.

Mixed effects model in negative exponential curve

Despite many researches on development in education and psychology, not often is the methodology tested with real data. A major barrier to test the growth model is that the design of study includes repeated observations and the nature of the growth is nonlinear. The repeat measurements on a nonlinear model require sophisticated statistical methods. In this study, we present mixed effects model in a negative exponential curve to describe the development of children's reading skills. This model can describe the nature of the growth on children's reading skills and account for intra-individual and inter-individual variation. We also apply simple techniques including cross-validation, regression, and graphical methods to determine the most appropriate curve for data, to find efficient initial values of parameters, and to select potential covariates. We illustrate with an example that motivated this research: a longitudinal study of academic skills from grade 1 to grade 12 in Connecticut public schools. ^

Evaluation of the city of Houston HIV/STD prevention program in Houston Independent School District (HISD) high schools

This cross-sectional study was undertaken to evaluate the impact in terms of HIV/STD knowledge and sexual behavior that the City of Houston HIV/STD prevention program in HISD high schools has had on students who have participated in it by comparing them with their peers who have not, based on self reports. The study further evaluated the program cost-effectiveness for averting future HIV infections by computing Cost-Utility Ratios based on reported sexual behavior. ^ Mixed results were obtained, indicating a statistically significant difference in knowledge with the intervention group having scored higher (p-value 0.001) but not for any of the behaviors assessed. The knowledge score outcome's overall p-value after adjusting for each stratifying variable (age, grade, gender and ethnicity) was statistically significant. The Odds Ratio of intervention group participants aged 15 years or more scoring 70% or higher was 1.86 times; that of intervention group female participants was 2.29 times; and that of intervention group Black/African American participants was 2.47 times relative to their comparison group counterparts. The knowledge score results remained statistically significant in the logistic regression model, which controlled for age, grade level, gender and ethnicity. The Odds Ratio in this case was 1.74. ^ Three scenarios based on the difference in the risk of HIV infection between the intervention and comparison group were used for computation of Cost-Utility Ratios: Base, worst and best-case scenario. The best-case scenario yielded cost-effective results for male participants and cost-saving results for female participants when using ethnicity-adjusted HIV prevalence. The scenario remained cost-effective for female participants when using the unadjusted HIV prevalence. ^ The challenge to the program is to devise approaches that can enhance benefits for male participants. If it is a threshold problem implying that male participants require more intensive programs for behavioral change, then programs should first be piloted among boys before being implemented across the board. If it is a reflection of gender differences, then we might have to go back to the drawing board and engage boys in focus group discussions that will help formulate more effective programs. Gender-blind approaches currently in vogue do not seem to be working. ^

Development and evaluation of a nutrition education program designed to increase fruit and vegetable consumption in girls, ages 9--12

The purpose of this study is to evaluate the theory-based Eat 5 nutrition badge. It is designed to increase fruit and vegetable (F&V) intake in 4th-6th grade junior Girl Scouts. Twenty-two troops were recruited and randomized by grade level (4th, 5th, 6th, or mixed) into either the intervention or control conditions. The leaders in the intervention condition received a brief training and the materials and conducted the program with their troops during four meetings. The Girl Scouts in the intervention condition completed 1-day Food Frequency Questionnaires and Nutrition Questionnaires both before and after completing the Eat 5 badge, and a third measurement of F&V intake three months after the posttest. Girl Scouts in the control condition were only evaluated at the three time periods.^ The primary hypotheses were that the Girl Scouts in the intervention condition would increase their daily intake of fruits and vegetables at both the posttest and three months later, compared to the Girl Scouts in the control condition. Other study questions investigated the impact of the Eat 5 program on intervening variables such as knowledge, self-efficacy, barriers, norms, F&V preference, and F&V selection and preparation skills.^ A nested ANOVA, with troop as the unit of analysis nested within condition, was used to assess the effects of the program. Pretest F&V intake and grade level were used as covariates. Pretest mean F&V intake for the total sample of 210 girls was 2.50 servings per day; 3.0 for the intervention group (n = 101). Significant increases in F&V intake (to 3.4 servings per day), knowledge, and fruit and vegetable preference were found for the intervention condition troops compared to the troops in the control condition. Three months later, the mean F&V intake had returned to pretest levels.^ This study indicates that social groups such as Girl Scouts can provide a channel for nutrition education. Long term effects were not sustained by the intervention; a possible cause was the lack of change in self-efficacy. Therefore, additional interventions are recommended such as booster lessons to maintain increased F&V intake by Girl Scouts. ^

NONLINEAR TIME SERIES/SYSTEM ANALYSIS (STATE-SPACE, DYNAMICS, INTERVENTION, RESILIENCE, KALMAN)

A discussion of nonlinear dynamics, demonstrated by the familiar automobile, is followed by the development of a systematic method of analysis of a possibly nonlinear time series using difference equations in the general state-space format. This format allows recursive state-dependent parameter estimation after each observation thereby revealing the dynamics inherent in the system in combination with random external perturbations.^ The one-step ahead prediction errors at each time period, transformed to have constant variance, and the estimated parametric sequences provide the information to (1) formally test whether time series observations y(,t) are some linear function of random errors (ELEM)(,s), for some t and s, or whether the series would more appropriately be described by a nonlinear model such as bilinear, exponential, threshold, etc., (2) formally test whether a statistically significant change has occurred in structure/level either historically or as it occurs, (3) forecast nonlinear system with a new and innovative (but very old numerical) technique utilizing rational functions to extrapolate individual parameters as smooth functions of time which are then combined to obtain the forecast of y and (4) suggest a measure of resilience, i.e. how much perturbation a structure/level can tolerate, whether internal or external to the system, and remain statistically unchanged. Although similar to one-step control, this provides a less rigid way to think about changes affecting social systems.^ Applications consisting of the analysis of some familiar and some simulated series demonstrate the procedure. Empirical results suggest that this state-space or modified augmented Kalman filter may provide interesting ways to identify particular kinds of nonlinearities as they occur in structural change via the state trajectory.^ A computational flow-chart detailing computations and software input and output is provided in the body of the text. IBM Advanced BASIC program listings to accomplish most of the analysis are provided in the appendix. ^

Health outcomes, quality improvement and cost-effectiveness of the Community Diabetes Education (CoDE) program: Results of a randomized controlled trial

The objectives of this dissertation were to evaluate health outcomes, quality improvement measures, and the long-term cost-effectiveness and impact on diabetes-related microvascular and macrovascular complications of a community health worker-led culturally tailored diabetes education and management intervention provided to uninsured Mexican Americans in an urban faith-based clinic. A prospective, randomized controlled repeated measures design was employed to compare the intervention effects between: (1) an intervention group (n=90) that participated in the Community Diabetes Education (CoDE) program along with usual medical care; and (2) a wait-listed comparison group (n=90) that received only usual medical care. Changes in hemoglobin A1c (HbA1c) and secondary outcomes (lipid status, blood pressure and body mass index) were assessed using linear mixed-models and an intention-to-treat approach. The CoDE group experienced greater reduction in HbA1c (-1.6%, p<.001) than the control group (-.9%, p<.001) over the 12 month study period. After adjusting for group-by-time interaction, antidiabetic medication use at baseline, changes made to the antidiabetic regime over the study period, duration of diabetes and baseline HbA1c, a statistically significant intervention effect on HbA1c (-.7%, p=.02) was observed for CoDE participants. Process and outcome quality measures were evaluated using multiple mixed-effects logistic regression models. Assessment of quality indicators revealed that the CoDE intervention group was significantly more likely to have received a dilated retinal examination than the control group, and 53% achieved a HbA1c below 7% compared with 38% of control group subjects. Long-term cost-effectiveness and impact on diabetes-related health outcomes were estimated through simulation modeling using the rigorously validated Archimedes Model. Over a 20 year time horizon, CoDE participants were forecasted to have less proliferative diabetic retinopathy, fewer foot ulcers, and reduced numbers of foot amputations than control group subjects who received usual medical care. An incremental cost-effectiveness ratio of $355 per quality-adjusted life-year gained was estimated for CoDE intervention participants over the same time period. The results from the three areas of program evaluation: impact on short-term health outcomes, quantification of improvement in quality of diabetes care, and projection of long-term cost-effectiveness and impact on diabetes-related health outcomes provide evidence that a community health worker can be a valuable resource to reduce diabetes disparities for uninsured Mexican Americans. This evidence supports formal integration of community health workers as members of the diabetes care team.^

Abundance of mesozooplankton in the western part of the Black Sea in 1995 during the Cooperative Marine Science Program for the Black Sea (CoMSBlack)

The "CoMSBlack-95" dataset is based on samples collected in the summer of 1995. The whole dataset is composed of 81 samples (28 stations) with data of zooplankton species composition, abundance and biomass. Samples were collected in discrete layers 0-10, 0-20, 0-50, 10-25, 25-50, 50-100 and from bottom up to the surface at depths depending on water column stratification and the thermocline depth. Zooplankton samples were collected with vertical closing Juday net,diameter - 36 cm, mesh size 150 µm. Tows were performed from surface down to bottom meters depths in discrete layers. Samples were preserved by a 4% formaldehyde sea water buffered solution. Sampling volume was estimated by multiplying the mouth area with the wire length. Mesozooplankton abundance: The collected material was analysed using the method of Domov (1959). Samples were brought to volume of 25-30 ml depending upon zooplankton density and mixed intensively until all organisms were distributed randomly in the sample volume. After that 5 ml of sample was taken and poured in the counting chamber which is a rectangle form for taxomomic identification and count. Large (> 1 mm body length) and not abundant species were calculated in whole sample. Counting and measuring of organisms were made in the Dimov chamber under the stereomicroscope to the lowest taxon possible. Taxonomic identification was done at the Institute of Oceanology by Asen Konsulov and Lyudmila Kamburska using the relevant taxonomic literature (Mordukhay-Boltovskoy, F.D. (Ed.). 1968, 1969,1972). Taxon-specific abundance: The collected material was analysed using the method of Domov (1959). Samples were brought to volume of 25-30 ml depending upon zooplankton density and mixed intensively until all organisms were distributed randomly in the sample volume. After that 5 ml of sample was taken and poured in the counting chamber which is a rectangle form for taxomomic identification and count. Copepods and Cladoceras were identified and enumerated; the other mesozooplankters were identified and enumerated at higher taxonomic level (commonly named as mesozooplankton groups). Large (> 1 mm body length) and not abundant species were calculated in whole sample. Counting and measuring of organisms were made in the Dimov chamber under the stereomicroscope to the lowest taxon possible. Taxonomic identification was done at the Institute of Oceanology by Asen Konsulov and Lyudmila Kamburska using the relevant taxonomic literature (Mordukhay-Boltovskoy, F.D. (Ed.). 1968, 1969,1972).

Biomass of mesozooplankton in the western part of the Black Sea in 1997 during the Cooperative Marine Science Program for the Black Sea (CoMSBlack)

The "15BO1997001" dataset is based on samples collected in the spring of 1997. The whole dataset is composed of 66 samples (from 27 stations of National Monitoring Sampling Grid) with data of zooplankton species composition, abundance and biomass. Samples were collected in discrete layers 0-10, 0-20, 0-50, 10-25, 25-50, 50-100 and from bottom up to the surface at depths depending on water column stratification and the thermocline depth. The collected material was analysed using the method of Dimov (1959). Samples were brought to volume of 25-30 ml depending upon zooplankton density and mixed intensively until all organisms were distributed randomly in the sample volume. After that 5 ml of sample was taken and poured in the counting chamber which is a rectangle form for taxomomic identification and count. Large (> 1 mm body length) and not abundant species were calculated in whole sample. Counting and measuring of organisms were made in the Dimov chamber under the stereomicroscope to the lowest taxon possible. Taxonomic identification was done at the Institute of Oceanology by Asen Konsulov using the relevant taxonomic literature (Mordukhay-Boltovskoy, F.D. (Ed.). 1968, 1969,1972 ). The biomass was estimated as wet weight by Petipa, 1959 (based on species specific wet weight). Wet weight values were transformed to dry weight using the equation DW=0.16*WW as suggested by Vinogradov & Shushkina, 1987. The collected material was analysed using the method of Dimov (1959). Samples were brought to volume of 25-30 ml depending upon zooplankton density and mixed intensively until all organisms were distributed randomly in the sample volume. After that 5 ml of sample was taken and poured in the counting chamber which is a rectangle form for taxomomic identification and count. Copepods and Cladoceras were identified and enumerated; the other mesozooplankters were identified and enumerated at higher taxonomic level (commonly named as mesozooplankton groups). Large (> 1 mm body length) and not abundant species were calculated in whole sample. Counting and measuring of organisms were made in the Dimov chamber under the stereomicroscope to the lowest taxon possible. Taxonomic identification was done at the Institute of Oceanology by Asen Konsulov using the relevant taxonomic literature (Mordukhay-Boltovskoy, F.D. (Ed.). 1968, 1969,1972 ). The biomass was estimated as wet weight by Petipa, 1959 ussing standard average weight of each species in mg/m3. WW were converted to DW by equation DW=0.16*WW (Vinogradov ME, Sushkina EA, 1987).

Biomass of mesozooplankton in the western part of the Black Sea in 1992 during the Cooperative Marine Science Program for the Black Sea (CoMSBlack)

The "CoMSBlack92" dataset is based on samples collected in the summer of 1992 along the Bulgarian coast including coastal and open sea areas. The whole dataset is composed of 79 samples (28 stations) with data of zooplankton species composition, abundance and biomass. Sampling for zooplankton was performed from bottom up to the surface at standard depths depending on water column stratification and the thermocline depth. Zooplankton samples were collected with vertical closing Juday net,diameter - 36cm, mesh size 150 ?m. Tows were performed from surface down to bottom meters depths in discrete layers. Samples were preserved by a 4% formaldehyde sea water buffered solution. Sampling volume was estimated by multiplying the mouth area with the wire length. Sampling volume was estimated by multiplying the mouth area with the wire length. The collected material was analysed using the method of Domov (1959). Samples were brought to volume of 25-30 ml depending upon zooplankton density and mixed intensively until all organisms were distributed randomly in the sample volume. After that 5 ml of sample was taken and poured in the counting chamber which is a rectangle form for taxomomic identification and count. Large (> 1 mm body length) and not abundant species were calculated in whole sample. Counting and measuring of organisms were made in the Dimov chamber under the stereomicroscope to the lowest taxon possible. Taxonomic identification was done at the Institute of Oceanology by Asen Konsulov using the relevant taxonomic literature (Mordukhay-Boltovskoy, F.D. (Ed.). 1968, 1969,1972 ). The biomass was estimated as wet weight by Petipa, 1959 (based on species specific wet weight). Wet weight values were transformed to dry weight using the equation DW=0.16*WW as suggested by Vinogradov & Shushkina, 1987. Copepods and Cladoceras were identified and enumerated; the other mesozooplankters were identified and enumerated at higher taxonomic level (commonly named as mesozooplankton groups). Large (> 1 mm body length) and not abundant species were calculated in whole sample. The biomass was estimated as wet weight by Petipa, 1959 ussing standard average weight of each species in mg/m**3.