Mutual Information for Testing Gene-Environment Interaction

Despite current enthusiasm for investigation of gene-gene interactions and gene-environment interactions, the essential issue of how to define and detect gene-environment interactions remains unresolved. In this report, we define gene-environment interactions as a stochastic dependence in the context of the effects of the genetic and environmental risk factors on the cause of phenotypic variation among individuals. We use mutual information that is widely used in communication and complex system analysis to measure gene-environment interactions. We investigate how gene-environment interactions generate the large difference in the information measure of gene-environment interactions between the general population and a diseased population, which motives us to develop mutual information-based statistics for testing gene-environment interactions. We validated the null distribution and calculated the type 1 error rates for the mutual information-based statistics to test gene-environment interactions using extensive simulation studies. We found that the new test statistics were more powerful than the traditional logistic regression under several disease models. Finally, in order to further evaluate the performance of our new method, we applied the mutual information-based statistics to three real examples. Our results showed that P-values for the mutual information-based statistics were much smaller than that obtained by other approaches including logistic regression models.

Tracking the Flow of Information through the Hippocampal Formation in the Rat

The hippocampus receives input from upper levels of the association cortex and is implicated in many mnemonic processes, but the exact mechanisms by which it codes and stores information is an unresolved topic. This work examines the flow of information through the hippocampal formation while attempting to determine the computations that each of the hippocampal subfields performs in learning and memory. The formation, storage, and recall of hippocampal-dependent memories theoretically utilize an autoassociative attractor network that functions by implementing two competitive, yet complementary, processes. Pattern separation, hypothesized to occur in the dentate gyrus (DG), refers to the ability to decrease the similarity among incoming information by producing output patterns that overlap less than the inputs. In contrast, pattern completion, hypothesized to occur in the CA3 region, refers to the ability to reproduce a previously stored output pattern from a partial or degraded input pattern. Prior to addressing the functional role of the DG and CA3 subfields, the spatial firing properties of neurons in the dentate gyrus were examined. The principal cell of the dentate gyrus, the granule cell, has spatially selective place fields; however, the behavioral correlates of another excitatory cell, the mossy cell of the dentate polymorphic layer, are unknown. This report shows that putative mossy cells have spatially selective firing that consists of multiple fields similar to previously reported properties of granule cells. Other cells recorded from the DG had single place fields. Compared to cells with multiple fields, cells with single fields fired at a lower rate during sleep, were less likely to burst, and were more likely to be recorded simultaneously with a large population of neurons that were active during sleep and silent during behavior. These data suggest that single-field and multiple-field cells constitute at least two distinct cell classes in the DG. Based on these characteristics, we propose that putative mossy cells tend to fire in multiple, distinct locations in an environment, whereas putative granule cells tend to fire in single locations, similar to place fields of the CA1 and CA3 regions. Experimental evidence supporting the theories of pattern separation and pattern completion comes from both behavioral and electrophysiological tests. These studies specifically focused on the function of each subregion and made implicit assumptions about how environmental manipulations changed the representations encoded by the hippocampal inputs. However, the cell populations that provided these inputs were in most cases not directly examined. We conducted a series of studies to investigate the neural activity in the entorhinal cortex, dentate gyrus, and CA3 in the same experimental conditions, which allowed a direct comparison between the input and output representations. The results show that the dentate gyrus representation changes between the familiar and cue altered environments more than its input representations, whereas the CA3 representation changes less than its input representations. These findings are consistent with longstanding computational models proposing that (1) CA3 is an associative memory system performing pattern completion in order to recall previous memories from partial inputs, and (2) the dentate gyrus performs pattern separation to help store different memories in ways that reduce interference when the memories are subsequently recalled.

Environmental and behavioral risk factors for moderate or severe rotavirus diarrhea in children less than 24 months

On a global basis rotaviruses are the most important agents involved in childhood diarrhea. In developing countries they account for 6% of all diarrheas and 20% of all diarrhea related deaths of children under 5 years of age, with over 1 billion episodes and over 4 million deaths annually. Given the disease burden, there is a need for better understanding the risk factors involved in rotavirus disease, to identify areas of intervention. In order to provide this information, two areas were developed: a review of the literature, examining the causal evidence for rotavirus diarrhea and a case comparison study. The case comparison study analyzed two areas: identifying climate factors and, identifying environmental and behavioral risk factors. The literature review showed that few analytical studies have identified specific risk factors such as home environment, and a winter seasonal trend for temperate areas, but in key areas evidence is contradictory. The case comparison study for climate factors demonstrated that seasonality occurs in a tropical country like Venezuela and that a complex interplay between weather conditions contribute to the seasonal pattern. A positive association between rain fall (OR 4.1); dew point (OR 2.3) and temperature differential during the day (OR 1.4) and, an inverse association with temperature (OR 0.5) and relative humidity (OR 0.8) was found. This information is useful in understanding the seasonal pattern of rotavirus and for planning health care needs. The second analysis demonstrated that environmental variables such as crowding (OR 14.3), contact with someone with an infectious disease (OR 4.9) and animal ownership (OR 2.3) were important. Restricting the analysis to animal owners demonstrated that living In a rural settling (OR 13.8), defecating in inappropriate places (OR 7.2), crowding(4.2) and indoor animals (4.0) are of importance. Behavioral variables identified were: lack of breast feeding (OR 4.0) and visiting when someone was sick (OR 3.4). Biological and demographic variables of importance were: age, with a dose response relationship; undernurishment (OR 11.3) and household per capita monthly income less than US $ 16.30 (OR 8.5). Using a diarrhea compeer group we found that, although some of the previous variables were of importance, no major differences were found. These findings are important in identifying paths for prevention and further research. ^

Toxics Release Inventory facilities and childhood cancer: Geographic information systems based approach

Purpose. To examine the association between living in proximity to Toxics Release Inventory (TRI) facilities and the incidence of childhood cancer in the State of Texas. ^ Design. This is a secondary data analysis utilizing the publicly available Toxics release inventory (TRI), maintained by the U.S. Environmental protection agency that lists the facilities that release any of the 650 TRI chemicals. Total childhood cancer cases and childhood cancer rate (age 0-14 years) by county, for the years 1995-2003 were used from the Texas cancer registry, available at the Texas department of State Health Services website. Setting: This study was limited to the children population of the State of Texas. ^ Method. Analysis was done using Stata version 9 and SPSS version 15.0. Satscan was used for geographical spatial clustering of childhood cancer cases based on county centroids using the Poisson clustering algorithm which adjusts for population density. Pictorial maps were created using MapInfo professional version 8.0. ^ Results. One hundred and twenty five counties had no TRI facilities in their region, while 129 facilities had at least one TRI facility. An increasing trend for number of facilities and total disposal was observed except for the highest category based on cancer rate quartiles. Linear regression analysis using log transformation for number of facilities and total disposal in predicting cancer rates was computed, however both these variables were not found to be significant predictors. Seven significant geographical spatial clusters of counties for high childhood cancer rates (p<0.05) were indicated. Binomial logistic regression by categorizing the cancer rate in to two groups (<=150 and >150) indicated an odds ratio of 1.58 (CI 1.127, 2.222) for the natural log of number of facilities. ^ Conclusion. We have used a unique methodology by combining GIS and spatial clustering techniques with existing statistical approaches in examining the association between living in proximity to TRI facilities and the incidence of childhood cancer in the State of Texas. Although a concrete association was not indicated, further studies are required examining specific TRI chemicals. Use of this information can enable the researchers and public to identify potential concerns, gain a better understanding of potential risks, and work with industry and government to reduce toxic chemical use, disposal or other releases and the risks associated with them. TRI data, in conjunction with other information, can be used as a starting point in evaluating exposures and risks. ^

Smoke free restaurant ordinance, compliance with the regulation to reduce exposure to environmental tobacco smoke while dining at local restaurants in San Antonio, Texas

This study is a secondary analysis of a survey developed by Dr. Jimmy Perkins and administered by San Antonio/Bexar County Metropolitan Health District. The survey was developed subsequent to the implementation of the city smoking ordinance effective January 1, 2004. The survey had a multi-purpose plan to establish the number of restaurants having smoke free status prior to and following the ordinance, determine compliance as it relates to a necessary smoking section and proper signage, and expose the rationale for restaurants to become smoke free. The data resulting from the survey was presented to the San Antonio/Bexar County Metropolitan Health District. The summary presented the types of establishments surveyed, smoking status of the establishment, reasons for the establishment becoming smoke free, compliance with smoking sections, compliance with signage requirements, awareness of ordinance, and chain status of the establishment. ^ The results of this study display the relationships among the variables previously mentioned. The following relationships have been examined and the outcomes have determined whether each is significant. After careful analysis, knowledge translates into compliance with signage regulations, which then translate into ordinance compliance. Size does matter as it relates to an establishment's number of employees and seating capacity. The smaller the establishment the more likely the establishment is to have become smoke free before the ordinance went into effect. Restaurants, rather than fast food establishments most commonly cited their reason for becoming smoke free was to comply with the ordinance and only ten percent of restaurants gave policy as the main reason for becoming smoke free. ^ This study is important for public health because the negative health effects of environmental tobacco smoke (ETS) are still an overwhelming problem in the United States (3). ETS is a Known Human Group A Carcinogen (5). The Environmental Protection Agency (EPA) has estimated that around 3,000 non-smoking Americans die every year from lung cancer caused by ETS (6). This information illustrates the importance of providing smoke free establishments, especially to non-smoking patrons. ^

Hospital and environmental variation in Texas nonprofit hospital organizational policies regarding charity care

The 2005 Annual Statement of Community Benefits Standard (ASCBS) and the annual report of the Community Benefits Plan, Summary of Current Hospital Charity Care Policy and Community Benefits, were used to identify various environmental and policy relationships with regard to eligibility for charity care requirements, a component for meeting the nonprofit requirements established by the Texas Legislature for nonprofit tax exemption (Texas Health and Safety Code, §311.04610). ^ Charity care policies are established by the individual hospital (or systems) and are generally defined as rules concerning care provided by the institution without the expectation of payment. This study has been undertaken to provide specific information about the charity care eligibility requirement policies of nonprofit hospitals. These hospitals are the part of the safety net for those persons who are indigent, low-income and uninsured. This study examines nonprofit hospitals by physical location, bed size, religious affiliation, trauma level, disproportionate share, and teaching designations. County information includes population, percentage of residents eligible for Medicaid benefits, ethnic makeup of county residents, poverty level, designation of a hospital district or operators of a public hospital, and the number of nonprofit and for-profit hospitals located in the county. Although this information has been collected by the Texas Department of State Health Services (DSHS), no other analysis has been conducted. ^

The relationship between hospital financial performance and information technology integration strategy selection

In light of the new healthcare regulations, hospitals are increasingly reevaluating their IT integration strategies to meet expanded healthcare information exchange requirements. Nevertheless, hospital executives do not have all the information they need to differentiate between the available strategies and recognize what may better fit their organizational needs. ^ In the interest of providing the desired information, this study explored the relationships between hospital financial performance, integration strategy selection, and strategy change. The integration strategies examined – applied as binary logistic regression dependent variables and in the order from most to least integrated – were Single-Vendor (SV), Best-of-Suite (BoS), and Best-of-Breed (BoB). In addition, the financial measurements adopted as independent variables for the models were two administrative labor efficiency and six industry standard financial ratios designed to provide a broad proxy of hospital financial performance. Furthermore, descriptive statistical analyses were carried out to evaluate recent trends in hospital integration strategy change. Overall six research questions were proposed for this study. ^ The first research question sought to answer if financial performance was related to the selection of integration strategies. The next questions, however, explored whether hospitals were more likely to change strategies or remain the same when there was no external stimulus to change, and if they did change, they would prefer strategies closer to the existing ones. These were followed by a question that inquired if financial performance was also related to strategy change. Nevertheless, rounding up the questions, the last two probed if the new Health Information Technology for Economic and Clinical Health (HITECH) Act had any impact on the frequency and direction of strategy change. ^ The results confirmed that financial performance is related to both IT integration strategy selection and strategy change, while concurred with prior studies that suggested hospital and environmental characteristics are associated factors as well. Specifically this study noted that the most integrated SV strategy is related to increased administrative labor efficiency and the hybrid BoS strategy is associated with improved financial health (based on operating margin and equity financing ratios). On the other hand, no financial indicators were found to be related to the least integrated BoB strategy, except for short-term liquidity (current ratio) when involving strategy change. ^ Ultimately, this study concluded that when making IT integration strategy decisions hospitals closely follow the resource dependence view of minimizing uncertainty. As each integration strategy may favor certain organizational characteristics, hospitals traditionally preferred not to make strategy changes and when they did, they selected strategies that were more closely related to the existing ones. However, as new regulations further heighten revenue uncertainty while require increased information integration, moving forward, as evidence already suggests a growing trend of organizations shifting towards more integrated strategies, hospitals may be more limited in their strategy selection choices.^