Characterization of E2F1's oncogenic, apoptotic and tumor-suppressive activities utilizing the K5 mouse model

Though E2F1 is deregulated in most human cancers by mutations of the p16-cyclin D-Rb pathway, it also exhibits tumor suppressive activity. A transgenic mouse model overexpressing E2F1 under the control of the bovine keratin 5 (K5) promoter exhibits epidermal hyperplasia and spontaneously develops tumors in the skin and other epithelial tissues after one year of age. In a p53-deficient background, aberrant apoptosis in K5 E2F1 transgenic epidermis is reduced and tumorigenesis is accelerated. In sharp contrast, K5 E2F1 transgenic mice are resistant to papilloma formation in the DMBA/TPA two-stage carcinogenesis protocol. K5 E2F4 and K5 DP1 transgenic mice were also characterized and both display epidermal hyperplasia but do not develop spontaneous tumors even in cooperation with p53 deficiency. These transgenic mice do not have increased levels of apoptosis in their skin and are more susceptible to papilloma formation in the two-stage carcinogenesis model. These studies show that deregulated proliferation does not necessarily lead to tumor formation and that the ability to suppress skin carcinogenesis is unique to E2F1. E2F1 can also suppress skin carcinogenesis when okadaic acid is used as the tumor promoter and when a pre-initiated mouse model is used, demonstrating that E2F1's tumor suppressive activity is not specific for TPA and occurs at the promotion stage. E2F1 was thought to induce p53-dependent apoptosis through upregulation of p19ARF tumor suppressor, which inhibits mdm2-mediated p53 degradation. Consistent with in vitro studies, the overexpression of E2F1 in mouse skin results in the transcriptional activation of the p19ARF and the accumulation of p53. Inactivation of either p19ARF or p53 restores the sensitivity of K5 E2F1 transgenic mice to DMBA/TPA carcinogenesis, demonstrating that an intact p19ARF-p53 pathway is necessary for E2F1 to suppress carcinogenesis. Surprisingly, while p53 is required for E2F1 to induce apoptosis in mouse skin, p19ARF is not, and inactivation of p19ARF actually enhances E2F1-induced apoptosis and proliferation in transgenic epidermis. This indicates that ARF is important for E2F1-induced tumor suppression but not apoptosis. Senescence is another potential mechanism of tumor suppression that involves p53 and p19ARF. K5 E2F1 transgenic mice initiated with DMBA and treated with TPA show an increased number of senescence cells in their epidermis. These experiments demonstrate that E2F1's unique tumor suppressive activity in two-stage skin carcinogenesis can be genetically separated from E2F1-induced apoptosis and suggest that senescence utilizing the p19ARF-p53 pathway plays a role in tumor suppression by E2F1. ^

A model of factors determining levels of public support for health care policy in the United States

Public preferences for policy are formed in a little-understood process that is not adequately described by traditional economic theory of choice. In this paper I suggest that U.S. aggregate support for health reform can be modeled as tradeoffs among a small number of behavioral values and the stage of policy development. The theory underlying the model is based on Samuelson, et al.'s (1986) work and Wilke's (1991) elaboration of it as the Greed/Efficiency/Fairness (GEF) hypothesis of motivation in the management of resource dilemmas, and behavioral economics informed by Kahneman and Thaler's prospect theory. ^ The model developed in this paper employs ordered probit econometric techniques applied to data derived from U.S. polls taken from 1990 to mid-2003 that measured support for health reform proposals. Outcome data are four-tiered Likert counts; independent variables are dummies representing the presence or absence of operationalizations of each behavioral variable, along with an integer representing policy process stage. Marginal effects of each independent variable predict how support levels change on triggering that variable. Model estimation results indicate a vanishingly small likelihood that all coefficients are zero and all variables have signs expected from model theory. ^ Three hypotheses were tested: support will drain from health reform policy as it becomes increasingly well-articulated and approaches enactment; reforms appealing to fairness through universal health coverage will enjoy a higher degree of support than those targeted more narrowly; health reforms calling for government operation of the health finance system will achieve lower support than those that do not. Model results support the first and last hypotheses. Contrary to expectations, universal health care proposals did not provide incremental support beyond those targeted to “deserving” populations—children, elderly, working families. In addition, loss of autonomy (e.g. restrictions on choice of care giver) is found to be the “third rail” of health reform with significantly-reduced support. When applied to a hypothetical health reform in which an employer-mandated Medical Savings Account policy is the centerpiece, the model predicts support that may be insufficient to enactment. These results indicate that the method developed in the paper may prove valuable to health policy designers. ^

The role of nitric oxide in small intestinal motility in a model of acute inflammation

Motility responses of the small intestine of iNOS deficient mice (iNOS −/−) and their wildtype littermates (iNOS+/+) to the inflammatory challenge of lipopolysaccharide (LPS) were investigated. LPS administration failed to attenuate intestinal transit in iNOS−/− mice but depressed transit in their iNOS+/+ littermates. Supporting an inhibitory role for sustained nitric oxide (NO) synthesis in the regulation of intestinal motility during inflammation, iNOS immunoreactivity was upregulated in all regions of the small intestine of iNOS+/+ mice. In contrast, neuronal NOS was barely affected. Cyclooxygenase activation was determined by prostaglandin E2 (PGE2) concentration. Following LPS challenge, PGE2 levels were elevated in all intestinal segments in both animal groups. Moreover, COX-1 and COX-2 protein levels were elevated in iNOS+/+ mice in response to LPS, while COX-2 levels were similarly increased in iNOS −/− intestine. However, no apparent relationship was observed between increased prostaglandin concentrations and attenuated intestinal transit. The presence of heme oxygenase 1 (HO-1) in the murine small intestine was also investigated. In both animal groups HO-1 immunoreactivity in the proximal intestine increased in response to treatment, while the constitutive protein levels detected in the middle and distal intestine were unresponsive to LPS administration. No apparent correlation of HO-1 to the suppression of small intestinal motility induced by LPS administration was detected. The presence of S-nitrosylated contractile proteins in the small intestine was determined. γ-smooth muscle actin was basally nitrosylated as well as in response to LPS, but myosin light chain kinase and myosin regulatory chain (MLC20) were not. In conclusion, in a model of acute intestinal inflammation, iNOS-produced NO plays a significant role in suppressing small intestinal motility while nNOS, COX-1, COX-2 and HO-1 do not participate in this event. S-nitrosylation of γ-smooth muscle actin is associated with elevated levels of nitric oxide in the smooth muscle of murine small intestine. ^

Comparing the factorial structure, invariance, and predictive validity of transtheoretical model constructs for alcohol use across restricted and unrestricted settings

With substance abuse treatment expanding in prisons and jails, understanding how behavior change interacts with a restricted setting becomes more essential. The Transtheoretical Model (TTM) has been used to understand intentional behavior change in unrestricted settings, however, evidence indicates restrictive settings can affect the measurement and structure of the TTM constructs. The present study examined data from problem drinkers at baseline and end-of-treatment from three studies: (1) Project CARE (n = 187) recruited inmates from a large county jail; (2) Project Check-In (n = 116) recruited inmates from a state prison; (3) Project MATCH, a large multi-site alcohol study had two recruitment arms, aftercare (n = 724 pre-treatment and 650 post-treatment) and outpatient (n = 912 pre-treatment and 844 post-treatment). The analyses were conducted using cross-sectional data to test for non-invariance of measures of the TTM constructs: readiness, confidence, temptation, and processes of change (Structural Equation Modeling, SEM) across restricted and unrestricted settings. Two restricted (jail and aftercare) and one unrestricted group (outpatient) entering treatment and one restricted (prison) and two unrestricted groups (aftercare and outpatient) at end-of-treatment were contrasted. In addition TTM end-of-treatment profiles were tested as predictors of 12 month drinking outcomes (Profile Analysis). Although SEM did not indicate structural differences in the overall TTM construct model across setting types, there were factor structure differences on the confidence and temptation constructs at pre-treatment and in the factor structure of the behavioral processes at the end-of-treatment. For pre-treatment temptation and confidence, differences were found in the social situations factor loadings and in the variance for the confidence and temptation latent factors. For the end-of-treatment behavioral processes, differences across the restricted and unrestricted settings were identified in the counter-conditioning and stimulus control factor loadings. The TTM end-of-treatment profiles were not predictive of drinking outcomes in the prison sample. Both pre and post-treatment differences in structure across setting types involved constructs operationalized with behaviors that are limited for those in restricted settings. These studies suggest the TTM is a viable model for explicating addictive behavior change in restricted settings but calls for modification of subscale items that refer to specific behaviors and caution in interpreting the mean differences across setting types for problem drinkers. ^

A survey of the implementation status of environmental management systems in U.S. colleges and universities, and, An environmental management system implementation model for U.S. colleges and universities

A census of 925 U.S. colleges and universities offering masters and doctorate degrees was conducted in order to study the number of elements of an environmental management system as defined by ISO 14001 possessed by small, medium and large institutions. A 30% response rate was received with 273 responses included in the final data analysis. Overall, the number of ISO 14001 elements implemented among the 273 institutions ranged from 0 to 16, with a median of 12. There was no significant association between the number of elements implemented among institutions and the size of the institution (p = 0.18; Kruskal-Wallis test) or among USEPA regions (p = 0.12; Kruskal-Wallis test). The proportion of U.S. colleges and universities that reported having implemented a structured, comprehensive environmental management system, defined by answering yes to all 16 elements, was 10% (95% C.I. 6.6%–14.1%); however 38% (95% C.I. 32.0%–43.8%) reported that they had implemented a structured, comprehensive environmental management system, while 30.0% (95% C.I. 24.7%–35.9%) are planning to implement a comprehensive environmental management system within the next five years. Stratified analyses were performed by institution size, Carnegie Classification and job title. ^ The Osnabruck model, and another under development by the South Carolina Sustainable Universities Initiative, are the only two environmental management system models that have been proposed specifically for colleges and universities, although several guides are now available. The Environmental Management System Implementation Model for U.S. Colleges and Universities developed is an adaptation of the ISO 14001 standard and USEPA recommendations and has been tailored to U.S. colleges and universities for use in streamlining the implementation process. In using this implementation model created for the U.S. research and academic setting, it is hoped that these highly specialized institutions will be provided with a clearer and more cost-effective path towards the implementation of an EMS and greater compliance with local, state and federal environmental legislation. ^

A physiological role of cytochromes P450 4Fs: Mouse model

Cytochromes P450 4Fs (CYP4F) are a subfamily of enzymes involved in arachidonic acid metabolism with highest catalytic activity towards leukotriene B 4 (LTB4), a potent chemoattractant involved in prompting inflammation. CYP4F-mediated metabolism of LTB4 leads to inactive ω-hydroxy products incapable of initiating chemotaxis and the inflammatory stimuli that result in the influx of inflammatory cells. Our hypothesis is based on the catalytic ability of CYP4Fs to inactivate pro-inflammatory LTB4 which assures these enzymes a pivotal role in the process of inflammation resolution. ^ To test this hypothesis and evaluate the changes in CYP4F expression under complex inflammatory conditions, we designed two mouse models, one challenged with lipopolysaccharide (LPS) as a sterile model of sepsis and the other challenged with a systemic live bacterial infection of Citrobacter rodentium, an equivalent of the human enterobacterium E. coli pathogen invasion. Based on the evidence that Peroxisome Proliferator Activated Receptors (PPARs) play an active role in inflammation regulation, we also examined PPARs as a regulation mechanism in CYP4F expression during inflammation using PPARα knockout mice under LPS challenge. Using the Citrobacter rodentium model of inflammation, we studied CYP4F levels to compare them to those in LPS challenged animals. LPS-triggered inflammation signal is mediated by Toll-like 4 (TLR4) receptors which specifically respond to LPS in association with several other proteins. Using TLR4 knockout mice challenged with Citrobacter rodentium we addressed possible mediation of CYP4F expression regulation via these receptors. ^ Our results show isoform- and tissue-specific CYP4F expression in all the tissues examined. The Citrobacter rodentium inflammation model revealed significant reduction in liver expression of CYP4F14 and CYP4F15 and an up-regulation of gene expression of CYP4F16 and CYP4F18. TLR4 knockout studies showed that the decrease in hepatic CYP4F15 expression is TLR4-dependent. CYP4F expression in kidney shows down-regulation of CYP4F14 and CYP4F15 and up-regulation of CYP4F18 expression. In the LPS inflammation model, we showed similar patterns of CYP4F changes as in Citrobacter rodentium -infected mice. The renal profile of CYP4Fs in PPARα knockout mice with LPS challenge showed CYP4F15 down-regulation to be PPARα dependent. Our study confirmed tissue- and isoform-specific regulation of CYP4F isoforms in the course of inflammation. ^

Metastatic lung cancer in a new mouse model inheriting p53 and latent K-ras mutations

Lung cancer is a devastating disease with very poor prognosis. The design of better treatments for patients would be greatly aided by mouse models that closely resemble the human disease. The most common type of human lung cancer is adenocarcinoma with frequent metastasis. Unfortunately, current models for this tumor are inadequate due to the absence of metastasis. Based on the molecular findings in human lung cancer and metastatic potential of osteosarcomas in mutant p53 mouse models, I hypothesized that mice with both K-ras and p53 missense mutations might develop metastatic lung adenocarcinomas. Therefore, I incorporated both K-rasLA1 and p53RI72HΔg alleles into mouse lung cells to establish a more faithful model for human lung adenocarcinoma and for translational and mechanistic studies. Mice with both mutations ( K-rasLA1/+ p53R172HΔg/+) developed advanced lung adenocarcinomas with similar histopathology to human tumors. These lung adenocarcinomas were highly aggressive and metastasized to multiple intrathoracic and extrathoracic sites in a pattern similar to that seen in lung cancer patients. This mouse model also showed gender differences in cancer related death and developed pleural mesotheliomas in 23.2% of them. In a preclinical study, the new drug Erlotinib (Tarceva) decreased the number and size of lung lesions in this model. These data demonstrate that this mouse model most closely mimics human metastatic lung adenocarcinoma and provides an invaluable system for translational studies. ^ To screen for important genes for metastasis, gene expression profiles of primary lung adenocarcinomas and metastases were analyzed. Microarray data showed that these two groups were segregated in gene expression and had 79 highly differentially expressed genes (more than 2.5 fold changes and p<0.001). Microarray data of Bub1b, Vimentin and CCAM1 were validated in tumors by quantitative real-time PCR (QPCR). Bub1b , a mitotic checkpoint gene, was overexpressed in metastases and this correlated with more chromosomal abnormalities in metastatic cells. Vimentin, a marker of epithelial-mesenchymal transition (EMT), was also highly expressed in metastases. Interestingly, Twist, a key EMT inducer, was also highly upregulated in metastases by QPCR, and this significantly correlated with the overexpression of Vimentin in the same tumors. These data suggest EMT occurs in lung adenocarcinomas and is a key mechanism for the development of metastasis in K-ras LA1/+ p53R172HΔg/+ mice. Thus, this mouse model provides a unique system to further probe the molecular basis of metastatic lung cancer.^

Chimpanzee: A predictive model for the human cytochrome P450 3A subfamily

The human cytochrome P450 3A (CYP3A) subfamily is responsible for most of the metabolism of therapeutic drugs; however, an adequate in vivo model has yet to be discovered. This study begins with an investigation of a controversial topic surrounding the human CYP3As--estrogen regulation. A novel approach to this topic was used by defining expression in the estrogen-responsive endometrium. This study shows that estrogen down-regulates CYP3A4 expression in the endometrium. On the other hand, analogous studies showed an increase in CYP3A expression as age increases in liver tissue. Following the discussion of estrogen regulation, is an investigation of the cross-species relationships among all of the CYP3As was completed. The study compares isoforms from piscines, avians, rodents, canines, ovines, bovines, and primates. Using the traditional phylogenetic analyses and employing a novel approach using exon and intron lengths, the results show that only another primate could be the best animal model for analysis of the regulation of the expression of the human CYP3As. This analysis also demonstrated that the chimpanzee seems to be the best available human model. Moreover, the study showed the presence and similarities of one additional isoform in the chimpanzee genome that is absent in humans. Based on these results, initial characterization of the chimpanzee CYP3A subfamily was begun. While the human genome contains four isoforms--CYP3A4, CYP3A5, CYP3A7, and CYP3A43--the chimpanzee genome has five, the four previously mentioned and CYP3A67. Both species express CYP3A4, CYP3A5, and CYP3A43, but humans express CYP3A7 while chimpanzees express CYP3A67. In humans, CYP3A4 is expressed at higher levels than the other isoforms, but some chimpanzee individuals express CYP3A67 at higher levels than CYP3A4. Such a difference is expected to alter significantly the total CYP3A metabolism. On the other hand, any study considering individual isoforms would still constitute a valid method of study for the human CYP3A4, CYP3A5, and CYP3A43 isoforms. ^

High-resolution microarray analysis of chromosome 20q in human colon cancer metastasis model systems

Amplification of human chromosome 20q DNA is the most frequently occurring chromosomal abnormality detected in sporadic colorectal carcinomas and shows significant correlation with liver metastases. Through comprehensive high-resolution microarray comparative genomic hybridization and microarray gene expression profiling, we have characterized chromosome 20q amplicon genes associated with human colorectal cancer metastasis in two in vitro metastasis model systems. The results revealed increasing complexity of the 20q genomic profile from the primary tumor-derived cell lines to the lymph node and liver metastasis derived cell lines. Expression analysis of chromosome 20q revealed a subset of over expressed genes residing within the regions of genomic copy number gain in all the tumor cell lines, suggesting these are Chromosome 20q copy number responsive genes. Bases on their preferential expression levels in the model system cell lines and known biological function, four of the over expressed genes mapping to the common intervals of genomic copy gain were considered the most promising candidate colorectal metastasis-associated genes. Validation of genomic copy number and expression array data was carried out on these genes, with one gene, DNMT3B, standing out as expressed at a relatively higher levels in the metastasis-derived cell lines compared with their primary-derived counterparts in both the models systems analyzed. The data provide evidence for the role of chromosome 20q genes with low copy gain and elevated expression in the clonal evolution of metastatic cells and suggests that such genes may serve as early biomarkers of metastatic potential. The data also support the utility of the combined microarray comparative genomic hybridization and expression array analysis for identifying copy number responsive genes in areas of low DNA copy gain in cancer cells. ^

Adaptation and maladaptation of heart and skeletal muscle to different diets in a rodent model of human obesity

Obesity and diabetes are metabolic disorders associated with fatty acid availability in excess of the tissues' capacity for fatty acid oxidation. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in skeletal muscle insulin resistance. My dissertation will present work to test the overall hypothesis that "western" and high fat diets differentially affect cardiac and skeletal muscle fatty acid oxidation, the expression of fatty acid responsive genes, and cardiac contractile function. Wistar rats were fed a low fat, "western," or high fat (10%, 45%, or 60% calories from fat, respectively) diet for acute (1 day to 1 week), short (4 to 8 weeks), intermediate (16 to 24 weeks), or long (32 to 48 weeks) term. With high fat diet, cardiac oleate oxidation increased at all time points investigated. In contrast, with western diet cardiac oleate oxidation increased in the acute, short and intermediate term, but not in the long term. Consistent with a maladaptation of fatty acid oxidation, cardiac power (measured ex vivo) decreased with long term western diet only. In contrast to the heart, soleus muscle oleate oxidation increased only in the acute and short term with either western or high fat feeding. Transcript analysis revealed that several fatty acid responsive genes, including pyruvate dehydrogenase kinase 4, uncoupling protein 3, mitochondrial thioesterase 1, and cytosolic thioesterase 1 increased in heart and soleus muscle to a greater extent with high fat diet, versus western diet, feeding. In conclusion, the data implicate inadequate induction of a cassette of fatty acid responsive genes in both the heart and skeletal muscle by western diet resulting in impaired activation of fatty acid oxidation, and the development of cardiac dysfunction. ^

Federally regulated institutional review boards: The aspects of a "model" IRB---Is the current system in need of a tune up or complete overhaul?

Institutional Review Boards (IRBs) are the primary gatekeepers for the protection of ethical standards of federally regulated research on human subjects in this country. This paper focuses on what general, broad measures that may be instituted or enhanced to exemplify a "model IRB". This is done by examining the current regulatory standards of federally regulated IRBs, not private or commercial boards, and how many of those standards have been found either inadequate or not generally understood or followed. The analysis includes suggestions on how to bring about changes in order to make the IRB process more efficient, less subject to litigation, and create standardized educational protocols for members. The paper also considers how to include better oversight for multi-center research, increased centralization of IRBs, utilization of Data Safety Monitoring Boards when necessary, payment for research protocol review, voluntary accreditation, and the institution of evaluation/quality assurance programs. ^ This is a policy study utilizing secondary analysis of publicly available data. Therefore, the research for this paper focuses on scholarly medical/legal journals, web information from the Department of Health and Human Services, Federal Drug Administration, and the Office of the Inspector General, Accreditation Programs, law review articles, and current regulations applicable to the relevant portions of the paper. ^ Two issues are found to be consistently cited by the literature as major concerns. One is a need for basic, standardized educational requirements across all IRBs and its members, and secondly, much stricter and more informed management of continuing research. There is no federally regulated formal education system currently in place for IRB members, except for certain NIH-based trials. Also, IRBs are not keeping up with research once a study has begun, and although regulated to do so, it does not appear to be a great priority. This is the area most in danger of increased litigation. Other issues such as voluntary accreditation and outcomes evaluation are slowing gaining steam as the processes are becoming more available and more sought after, such as JCAHO accrediting of hospitals. ^ Adopting the principles discussed in this paper should promote better use of a local IRBs time, money, and expertise for protecting the vulnerable population in their care. Without further improvements to the system, there is concern that private and commercial IRBs will attempt to create a monopoly on much of the clinical research in the future as they are not as heavily regulated and can therefore offer companies quicker and more convenient reviews. IRBs need to consider the advantages of charging for their unique and important services as a cost of doing business. More importantly, there must be a minimum standard of education for all IRB members in the area of the ethical standards of human research and a greater emphasis placed on the follow-up of ongoing research as this is the most critical time for study participants and may soon lead to the largest area for litigation. Additionally, there should be a centralized IRB for multi-site trials or a study website with important information affecting the trial in real time. There needs to be development of standards and metrics to assess the performance of the IRBs for quality assurance and outcome evaluations. The boards should not be content to run the business of human subjects' research without determining how well that function is actually being carried out. It is important that federally regulated IRBs provide excellence in human research and promote those values most important to the public at large.^

Simulation study of joint transition and Weibull survival model with shared parameters

This study investigates a theoretical model where a longitudinal process, that is a stationary Markov-Chain, and a Weibull survival process share a bivariate random effect. Furthermore, a Quality-of-Life adjusted survival is calculated as the weighted sum of survival time. Theoretical values of population mean adjusted survival of the described model are computed numerically. The parameters of the bivariate random effect do significantly affect theoretical values of population mean. Maximum-Likelihood and Bayesian methods are applied on simulated data to estimate the model parameters. Based on the parameter estimates, predicated population mean adjusted survival can then be calculated numerically and compared with the theoretical values. Bayesian method and Maximum-Likelihood method provide parameter estimations and population mean prediction with comparable accuracy; however Bayesian method suffers from poor convergence due to autocorrelation and inter-variable correlation. ^

Assessing residents' readiness to screen for domestic violence: Utilizing the transtheoretical model - stages of change, decisional balance and self-efficacy

Domestic violence is a major public health problem, yet most physicians do not effectively identify patients at risk. Medical students and residents are not routinely educated on this topic and little is known about the factors that influence their decisions to include screening for domestic violence in their subsequent practice. In order to assess the readiness of primary care residents to screen all patients for domestic violence, this study utilized a survey incorporating constructs from the Transtheoretical Model, including Stages of Change, Decisional Balance (Pros and Cons) and Self-Efficacy. The survey was distributed to residents at the University of Texas Health Science Center Medical School in Houston in: Internal Medicine, Medicine/Pediatrics, Pediatrics, Family Medicine, and Obstetrics and Gynecology. Data from the survey was analyzed to test the hypothesis that residents in the earlier Stages of Change report more costs and fewer benefits with regards to screening for domestic violence, and that those in the later stages exhibit higher Self-Efficacy scores. The findings from this study were consistent with the model in that benefits to screening (Pros) and Self-Efficacy were correlated with later Stages of Change, however reporting fewer costs (Cons) was not. Very few residents were ready to screen all of their patients.^

Effect of a lifestyle physical activity intervention on transtheoretical model variables

Purpose. To determine the effect a stage-based, lifestyle physical activity intervention has on Transtheoretical Model variables in a population of breast cancer survivors. ^ Methods. Sedentary breast cancer survivors (N=60) were randomized to either a standard care study condition or to a 6-month, 21-session intervention. The Transtheoretical Model variables stage of change, self-efficacy, decisional balance (pros and cons to exercise), and processes of change were measured at baseline, 3 months, and 6 months. ^ Results. Women in the lifestyle group had significantly higher self-efficacy than women in the standard care group (F=9.55, p=0.003). Although there was not a significant difference between the two groups for perceived pros of exercise, there was a significant difference between the groups for perceived cons of exercise. Women in the lifestyle group perceived significantly fewer cons of exercise at both 3 and 6 months compared with women in the standard care condition (F=5.416, p=0.025). Between baseline and the 6 month assessment, the intervention also had an effect on three of the processes of change, while seven of the processes were not significantly affected by the intervention. ^ Conclusions. Data from the pilot study suggest that a stage-based, lifestyle physical activity intervention has an effect on Transtheoretical Model variables, which have been shown to facilitate exercise adoption, and should be tested in a larger trial. ^

A model for use by local public health departments to evaluate pandemic influenza plans

The events of the 1990's and early 2000's demonstrated the need for effective planning and response to natural and man-made disasters. One of those potential natural disasters is pandemic flu. Once defined, the CDC stated that program, or plan, effectiveness is improved through the process of program evaluation. (Centers for Disease Control and Prevention, 1999) Program evaluation should be accomplished not only periodically, but in the course of routine administration of the program. (Centers for Disease Control and Prevention, 1999) Accomplishing this task for a "rare, but significant event" is challenging. (Herbold, John R., PhD., 2008) To address this challenge, the RAND Corporation (under contract to the CDC) developed the "Facilitated Look-Backs" approach that was tested and validated at the state level. (Aledort et al., 2006).^ Nevertheless, no comprehensive and generally applicable pandemic influenza program evaluation tool or model is readily found for use at the local public health department level. This project developed such a model based on the "Facilitated Look-Backs" approach developed by RAND Corporation. (Aledort et al., 2006) Modifications to the RAND model included stakeholder additions, inclusion of all six CDC program evaluation steps, and suggestions for incorporating pandemic flu response plans in seasonal flu management implementation. Feedback on the model was then obtained from three LPHD's—one rural, one suburban, and one urban. These recommendations were incorporated into the final model. Feedback from the sites also supported the assumption that this model promotes the effective and efficient evaluation of both pandemic flu and seasonal flu response by reducing redundant evaluations of pandemic flu plans, seasonal flu plans, and funding requirement accountability. Site feedback also demonstrated that the model is comprehensive and flexible, so it can be adapted and applied to different LPHD needs and settings. It also stimulates evaluation of the major issues associated with pandemic flu planning. ^ The next phase in evaluating this model should be to apply it in a program evaluation of one or more LPHD's seasonal flu response that incorporates pandemic flu response plans.^