Response to chemotherapy, recurrence and survival in advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish BRCA mutations, compared to those without

Objectives. Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish (AJ) BRCA founder mutations, compared to sporadic ovarian cancer patients. The purpose of this study was to determine if this association exists in ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations. In addition, we sought to account for possible "survival bias" by minimizing any lead time that may exist between diagnosis and genetic testing. ^ Methods. Patients with stage III/IV ovarian, fallopian tube, or primary peritoneal cancer and a non-Ashkenazi Jewish BRCA1 or 2 mutation, seen for genetic testing January 1996-July 2007, were identified from genetics and institutional databases. Medical records were reviewed for clinical factors, including response to initial chemotherapy. Patients with sporadic (non-hereditary) ovarian, fallopian tube, or primary peritoneal cancer, without family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, year of diagnosis, and vital status at time interval to BRCA testing. When possible, 2 sporadic patients were matched to each BRCA patient. An additional group of unmatched, sporadic ovarian, fallopian tube and primary peritoneal cancer patients was included for a separate analysis. Progression-free (PFS) & overall survival (OS) were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were calculated for variables of interest. Matched pairs were treated as clusters. Stratified log rank test was used to calculate survival data for matched pairs using paired event times. Fisher's exact test, chi-square, and univariate logistic regression were also used for analysis. ^ Results. Forty five advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations, 86 sporadic-matched and 414 sporadic-unmatched patients were analyzed. Compared to the sporadic-matched and sporadic-unmatched ovarian cancer patients, non-AJ BRCA mutation carriers had longer PFS (17.9 & 13.8 mos. vs. 32.0 mos., HR 1.76 [95% CI 1.13–2.75] & 2.61 [95% CI 1.70–4.00]). In relation to the sporadic- unmatched patients, non-AJ BRCA patients had greater odds of complete response to initial chemotherapy (OR 2.25 [95% CI 1.17–5.41]) and improved OS (37.6 mos. vs. 101.4 mos., HR 2.64 [95% CI 1.49–4.67]). ^ Conclusions. This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations, confirming the previous studies in the Jewish population. Our efforts to account for "survival bias," by matching, will continue with collaborative studies. ^

Identifying and removing barriers to cycling as a viable means of transportation in Houston, Texas

The citizens of Houston, Texas, spend much time commuting. It has repeatedly been named among the “Fattest Cities” by Men’s Fitness Magazine (The fittest and fattest cities in America – Men’s Fitness. ). Obesity is one of its major public health problems as Houstonians often do not engage in enough physical activity to help them maintain their ideal weights. The use of bicycles provides a healthy and ecological alternative to commuting by driving. However, because urban cyclists must often share the roads with motorized vehicles, cyclists are often exposed to high levels of emissions. As vulnerable users of the roadways, urban cyclists also face the threat of injury. Nevertheless, there are some programs that encourage the use of bicycles. Laws and ordinances not only reveal public policy relating to bicycling but are a means to develop policy which can encourage bicycling. ^

Improving the health and well-being of women at risk for neural tube defect recurrence

There is growing interest in providing women with internatal care, a package of healthcare and ancillary services that can improve their health during the period after the termination of one pregnancy but before the conception of the next pregnancy. Women who have had a pregnancy affected by a neural tube defect can especially benefit from internatal care because they are at increased risk for recurrence and improvements to their health during the inter-pregnancy period can prevent future negative birth outcomes. The dissertation provides three papers that inform the content of internatal care for women at risk for recurrence by examining descriptive epidemiology to develop an accurate risk profile of the population, assessing whether women at risk for recurrence would benefit from a psychosocial intervention, and determining how to improve health promotion efforts targeting folic acid use.^ Paper one identifies information relevant for developing risk profiles and conducting risk assessments. A number of investigations have found that the risk for neural tube defects differs between non-Hispanic Whites and Hispanics. To understand the risk difference, the descriptive epidemiology of spina bifida and anencephaly was examined for Hispanics and non-Hispanic Whites based on data from the Texas Birth Defects Registry for the years 1999 through 2004. Crude and adjusted birth prevalence ratios and corresponding 95% confidence intervals were calculated between descriptive epidemiologic characteristics and anencephaly and spina bifida for non-Hispanic Whites and for Hispanics. In both race/ethnic groups, anencephaly expressed an inverse relationship with maternal age and a positive linear relationship with parity. Both relationships were stronger in non-Hispanic Whites. Female infants had a higher risk for anencephaly in non-Hispanic Whites. Lower maternal education was associated with increased risk for spina bifida in Hispanics.^ Paper two assesses the need for a psychosocial intervention. For mothers who have children with spina bifida, the transition to motherhood can be stressful. This qualitative study explored the process of becoming a mother to a child with spina bifida focusing particularly on stress and coping in the immediate postnatal environment. Semi-structured interviews were conducted with six mothers who have children with spina bifida. Mothers were asked about their initial emotional and problem-based coping efforts, the quality and kind of support provided by health providers, and the characteristics of their meaning-based coping efforts; questions matched Transactional Model of Stress and Coping (TMSC) constructs. Analysis of the responses revealed a number of modifiable stress and coping transactions, the most salient being: health providers are in a position to address beliefs about self-causality and prevent mothers from experiencing the repercussions that stem from maintaining these beliefs. ^ Paper three identifies considerations when creating health promotion materials targeting folic acid use. A brochure was designed using concepts from the Precaution Adoption Process Model (PAPM). Three focus groups comprising 26 mothers of children with spina bifida evaluated the brochure. One focus group was conducted in Spanish-only, the other two focus groups were conducted in English and Spanish combined. Qualitative analysis of coded transcripts revealed that a brochure is a helpful adjunct. Questions about folic acid support the inclusion of an insert with basic information. There may be a need to develop different educational material for Hispanics so the importance of folic acid is provided in a situational context. Some participants blamed themselves for their pregnancy outcome which may affect their receptivity to messages in the brochure. The women's desire for photographs that affect their perception of threat and their identification with the second role model indicate they belong to PAPM Stage 2 and 3. Participants preferred colorful envelopes, high quality paper, intimidating photographs, simple words, conversational style sentences, and positive messages.^ These papers develop the content of risk assessment, psychosocial intervention, and health promotion components of internatal care as they apply to women at risk for recurrence. The findings provided evidence for considering parity and maternal age when assessing nutritional risk. The two dissimilarities between the two race/ethnic groups, infant sex and maternal education lent support to creating separate risk profiles. Interviews with mothers of children with spina bifida revealed the existence of unmet needs-suggesting that a psychosocial intervention provided as part of internatal care can strengthen and support women's well-being. Segmenting the audience according to race/ethnicity and PAPM stage can improve the relevance of print materials promoting folic acid use.^

Determining associations and assessing methodological issues in a case-control study of hazardous air pollutants and neural tube defects

Recent studies have reported positive associations between maternal exposures to air pollutants and several adverse birth outcomes. However, there have been no assessments of the association between environmental hazardous air pollutants (HAPs) such as benzene, toluene, ethylbenzene, and xylene (BTEX) and neural tube defects (NTDs) a common and serious group of congenital malformations. Before examining this association, two important methodological questions must be addressed: (1) is maternal residential movement likely to result in exposure misclassification and (2) is it appropriate to lump defects of the neural tube, such as anencephaly and spina bifida, into a composite disease endpoint (i.e., NTDs). ^ Data from the National Birth Defects Prevention Study and Texas Birth Defects Registry were used to: (1) assess the extent to which change of residence may result in exposure misclassification when exposure is based on the address at delivery; (2) formally assess heterogeneity of the associations between known risk factors for NTDs, using polytomous logistic regression; and (3) conduct a case-control study assessing the association between ambient air levels of BTEX and the risk of NTDs among offspring. ^ Regarding maternal residential mobility, this study suggests address at delivery was not significantly different from using address at conception when assigning quartile of benzene exposure (OR 1.0, 95% CI 0.9, 1.3). On the question of effect heterogeneity among NTDs, the effect estimates for infant sex P = 0.017), maternal body mass index P = 0.016), and folate supplementation P = 0.050) were significantly different for anencephaly and spina bifida, suggesting it is often more appropriate to assess potential risk factors among subgroups of NTDs. For the main study question on the association between environmental HAPs and NTDs, mothers who have offspring with isolated spina bifida are 2.4 times likely to live in areas with the highest benzene levels (95% CI 1.1, 5.0). However, no other significant associations were observed.^ This project is the first to include not only an assessment of the relationship between environmental levels of BTEX and NTDs, but also two separate studies addressing important methodological issues associated with this question. Our results contribute to the growing body of evidence regarding air pollutant exposure and adverse birth outcomes. ^

Association of maternal sphinganine:sphingosine ratio and folate levels with neural tube defects along the South Texas border

Neural tube defects (NTDs) remain elevated in Hispanic women along the South Texas Border, despite folate supplementation and folate fortification of cereal products. Missmer et al. examined the relationships between fumonisins, a class of corn mycotoxin, and NTDs in Hispanic women who ate corn tortillas and found increased odds ratios with increasing exposure, as measured by serum sphinganine:sphingosine (sa:so) ratios. This study examined the interactions between categorized maternal serum folate levels and stratified sa:so ratios and the resultant odds ratios of NTDs, stratified by type (anencephaly and spina bifida). The hypothesis was that the above normal folate category would have lower odds ratios of NTDs at given sa:so ratio categories and that there would be a difference in odds ratio patterns for anencephaly and spina bifida. Methods. Data for 406 Hispanic women were obtained from the Missmer case-control study. Sa:so ratios were calculated and subjects were stratified into “below normal,” “normal,” and above normal range for folate. A logistic regression model was applied, controlling for BMI, serum B12, lab batch, and conception date. Results. While OR’s of NTDs increased for increasing sa:so ratios, OR’s for “above normal” folate were not decreased at any sa:so ratio and there was no statistically significant difference between OR’s of anencephaly and spina bifida. Conclusion. Folate does not appear to be protective against the potential teratogenic effect of fumonisins and did not differ in effect on OR’s of NTD by type. More research is necessary to determine the extent of fumonisin exposure in Hispanic women along the South Texas Border.^

The use of the computerized and revised vital record in conducting etiologic studies on neural tube defects

The purpose of this study was to evaluate the adequacy of computerized vital records in Texas for conducting etiologic studies on neural tube defects (NTDs), using the revised and expanded National Centers for Health Statistics vital record forms introduced in Texas in 1989.^ Cases of NTDs (anencephaly and spina bifida) among Harris County (Houston) residents were identified from the computerized birth and death records for 1989-1991. The validity of the system was then measured against cases ascertained independently through medical records and death certificates. The computerized system performed poorly in its identification of NTDs, particularly for anencephaly, where the false positive rate was 80% with little or no improvement over the 3-year period. For both NTDs the sensitivity and predictive value positive of the tapes were somewhat higher for Hispanic than non-Hispanic mothers.^ Case control studies were conducted utilizing the tape set and the independently verified data set, using controls selected from the live birth tapes. Findings varied widely between the data sets. For example, the anencephaly odds ratio for Hispanic mothers (vs. non-Hispanic) was 1.91 (CI = 1.38-2.65) for the tape file, but 3.18 (CI = 1.81-5.58) for verified records. The odds ratio for diabetes was elevated for the tape set (OR = 3.33, CI = 1.67-6.66) but not for verified cases (OR = 1.09, CI = 0.24-4.96), among whom few mothers were diabetic. It was concluded that computerized tapes should not be solely relied on for NTD studies.^ Using the verified cases, Hispanic mother was associated with spina bifida, and Hispanic mother, teen mother, and previous pregnancy terminations were associated with anencephaly. Mother's birthplace, education, parity, and diabetes were not significant for either NTD.^ Stratified analyses revealed several notable examples of statistical interaction. For anencephaly, strong interaction was observed between Hispanic origin and trimester of first prenatal care.^ The prevalence was 3.8 per 10,000 live births for anencephaly and 2.0 for spina bifida (5.8 per 10,000 births for the combined categories). ^

Endemic tuberculosis, the homeless, and public transportation: A merging of geographical information systems surveillance and the Houston Tuberculosis Initiative Surveillance project

To reach the goals established by the Institute of Medicine (IOM) and the Centers for Disease Control's (CDC) STOP TB USA, measures must be taken to curtail a future peak in Tuberculosis (TB) incidence and speed the currently stagnant rate of TB elimination. Both efforts will require, at minimum, the consideration and understanding of the third dimension of TB transmission: the location-based spread of an airborne pathogen among persons known and unknown to each other. This consideration will require an elucidation of the areas within the U.S. that have endemic TB. The Houston Tuberculosis Initiative (HTI) was a population-based active surveillance of confirmed Houston/Harris County TB cases from 1995–2004. Strengths in this dataset include the molecular characterization of laboratory confirmed cases, the collection of geographic locations (including home addresses) frequented by cases, and the HTI time period that parallels a decline in TB incidence in the United States (U.S.). The HTI dataset was used in this secondary data analysis to implement a GIS analysis of TB cases, the locations frequented by cases, and their association with risk factors associated with TB transmission. ^ This study reports, for the first time, the incidence of TB among the homeless in Houston, Texas. The homeless are an at-risk population for TB disease, yet they are also a population whose TB incidence has been unknown and unreported due to their non-enumeration. The first section of this dissertation identifies local areas in Houston with endemic TB disease. Many Houston TB cases who reported living in these endemic areas also share the TB risk factor of current or recent homelessness. Merging the 2004–2005 Houston enumeration of the homeless with historical HTI surveillance data of TB cases in Houston enabled this first-time report of TB risk among the homeless in Houston. The homeless were more likely to be US-born, belong to a genotypic cluster, and belong to a cluster of a larger size. The calculated average incidence among homeless persons was 411/100,000, compared to 9.5/100,000 among housed. These alarming rates are not driven by a co-infection but by social determinants. The unsheltered persons were hospitalized more days and required more follow-up time by staff than those who reported a steady housing situation. The homeless are a specific example of the increased targeting of prevention dollars that could occur if TB rates were reported for specific areas with known health disparities rather than as a generalized rate normalized over a diverse population. ^ It has been estimated that 27% of Houstonians use public transportation. The city layout allows bus routes to run like veins connecting even the most diverse of populations within the metropolitan area. Secondary data analysis of frequent bus use (defined as riding a route weekly) among TB cases was assessed for its relationship with known TB risk factors. The spatial distribution of genotypic clusters associated with bus use was assessed, along with the reported routes and epidemiologic-links among cases belonging to the identified clusters. ^ TB cases who reported frequent bus use were more likely to have demographic and social risk factors associated with poverty, immune suppression and health disparities. An equal proportion of bus riders and non-bus riders were cultured for Mycobacterium tuberculosis, yet 75% of bus riders were genotypically clustered, indicating recent transmission, compared to 56% of non-bus riders (OR=2.4, 95%CI(2.0, 2.8), p<0.001). Bus riders had a mean cluster size of 50.14 vs. 28.9 (p<0.001). Second order spatial analysis of clustered fingerprint 2 (n=122), a Beijing family cluster, revealed geographic clustering among cases based on their report of bus use. Univariate and multivariate analysis of routes reported by cases belonging to these clusters found that 10 of the 14 clusters were associated with use. Individual Metro routes, including one route servicing the local hospitals, were found to be risk factors for belonging to a cluster shown to be endemic in Houston. The routes themselves geographically connect the census tracts previously identified as having endemic TB. 78% (15/23) of Houston Metro routes investigated had one or more print groups reporting frequent use for every HTI study year. We present data on three specific but clonally related print groups and show that bus-use is clustered in time by route and is the only known link between cases in one of the three prints: print 22. (Abstract shortened by UMI.)^

Indeterminate QunatiFERON-TB Gold In-Tube assay results in association with procedural specimen collection in children

BACKGROUND. The development of interferon-gamma release assays (IGRA) has introduced powerful tools in diagnosing latent tuberculosis infection (LTBI) and may play a critical role in the future of tuberculosis diagnosis. However, there have been reports of high indeterminate results in young patient populations (0-18 years). This study investigated results of the QunatiFERON-TB Gold In-Tube (QFT-GIT) IGRA in a population of children (0-18 years) at Texas Children's Hospital in association with specimen collection procedures using surrogate variables. ^ METHODS. A retrospective case-control study design was used for this investigation. Cases were defined as having QFT-GIT indeterminate results. Controls were defined as having either positive or negative results (determinates). Patients' admission status, staff performing specimen collection, and specific nurse performing specimen collection were used as surrogates to measure specimen collection procedures. ^ To minimize potential confounding, abstraction of patients' electronic medical records was performed. Abstracted data included patients' medications and evaluation at the time of QFT-GIT specimen collection in addition to their medical history. QFT-GIT related data was also abstracted. Cases and controls were characterized using chi-squared tests or Fisher's exact tests across categorical variables. Continuous variables were analyzed using one-way ANOVA and t-tests for continuous variables. A multivariate model was constructed by backward stepwise removal of statistically significant variables from univariate analysis. ^ RESULTS. Patient data was abstracted from 182 individuals aged 0-18 years from July 2010 to August 2011 at Texas Children's Hospital. 56 cases (indeterminates) and 126 controls (determinates) were enrolled. Cancer was found to be an effect modifier with subsequent stratification resulting in a cancer patient population too small to analyze (n=13). Subsequent analyses excluded these patients. ^ The exclusion of cancer patients resulted in a population of 169 patients with 49 indeterminates (28.99%) and 120 determinates (71.01%), with mean ages of 9.73 (95% CI: 8.03, 11.43) years and 11.66 (95% CI: 10.75, 12.56) years (p = 0.033), respectively. Median age of patients who were indeterminates and determinates were 12.37 and 12.87 years, respectively. Lack of data for our specific nurse surrogate (QFTNurse) resulted in its exclusion from analysis. The final model included only our remaining surrogate variables (QFTStaff and QFTInpatientOutpatient). The staff collecting surrogate (QFTStaff) was found to be modestly associated with indeterminates when nurses collected the specimen (OR = 1.54, 95% CI: 0.51, 4.64, p = 0.439) in the final model. Inpatients were found to have a strong and statistically significant association with indeterminates (OR = 11.65, 95% CI: 3.89, 34.9, p < 0.001) in the final model. ^ CONCLUSION. Inpatient status was used as a surrogate for indication of nurse drawn blood specimens. Nurses have had little to no training regarding shaking of tubes versus phlebotomists regarding QFT-GIT testing procedures. This was also measured by two other surrogates; specifically a medical note stating whether a nurse or phlebotomist collected the specimen (QFTStaff) and the name and title of the specific nurse if collection was performed by a nurse (QFTNurse). Results indicated that inpatient status was a strong and statistically significant factor for indeterminates, however, nurse collected specimens and indeterminate results had no statistically significant association in non-cancer patients. The lack of data denoting the specific nurse performing specimen collection excluded the QFTNurse surrogate in our analysis. ^ Findings suggests training of staff personnel in specimen procedures may have little effect on the number of indeterminates while inpatient status and thus possibly illness severity may be the most important factor for indeterminate results in this population. The lack of congruence between our surrogate measures may imply that our inpatient surrogate gauged illness severity rather than collection procedures as intended. ^ Despite the lack of clear findings, our analysis indicated that more than half of indeterminates were found in specimens drawn by nurses and as such staff training may be explored. Future studies may explore methods in measuring modifiable variables during pre-analytical QFT-GIT procedures that can be discerned and controlled. Identification of such measures may provide insight into ways to lowering indeterminate QFT-GIT rates in children.^

Fluid pressure actuated net weighing device with pneumatic taring

The weighing device comprises a tension load cell including an upper liquid chamber and a lower air chamber which has a volume much greater than the volume of the liquid chamber. The weight of a suspended load and the load supporting structure on the load cell are applied on both chambers. A gauge reads the liquid pressure in the upper chamber and a valve unit connectible to a source of air under pressure is connected to the air chamber. The load cell is tared by initially adjusting the air pressure in the lower chamber to produce a zero reading on the gauge. When a load is applied on the device, the volume displacement of the air chamber is small relative to the volume displacement of the liquid in the upper chamber. The volume of the air chamber thus remains substantially constant so that the gauge indicates directly the net weight of the applied load.

Framework for risk assessment for maritime transportation systems

Maritime accidents involving ships carrying passengers may pose a high risk with respect to human casualties. For effective risk mitigation, an insight into the process of risk escalation is needed. This requires a proactive approach when it comes to risk modelling for maritime transportation systems. Most of the existing models are based on historical data on maritime accidents, and thus they can be considered reactive instead of proactive. This paper introduces a systematic, transferable and proactive framework estimating the risk for maritime transportation systems, meeting the requirements stemming from the adopted formal definition of risk. The framework focuses on ship-ship collisions in the open sea, with a RoRo/Passenger ship (RoPax) being considered as the struck ship. First, it covers an identification of the events that follow a collision between two ships in the open sea, and, second, it evaluates the probabilities of these events, concluding by determining the severity of a collision. The risk framework is developed with the use of Bayesian Belief Networks and utilizes a set of analytical methods for the estimation of the risk model parameters. The model can be run with the use of GeNIe software package. Finally, a case study is presented, in which the risk framework developed here is applied to a maritime transportation system operating in the Gulf of Finland (GoF). The results obtained are compared to the historical data and available models, in which a RoPax was involved in a collision, and good agreement with the available records is found.