Development of automated image analysis tools for verification of radiotherapy field accuracy with an electronic portal imaging device

The successful management of cancer with radiation relies on the accurate deposition of a prescribed dose to a prescribed anatomical volume within the patient. Treatment set-up errors are inevitable because the alignment of field shaping devices with the patient must be repeated daily up to eighty times during the course of a fractionated radiotherapy treatment. With the invention of electronic portal imaging devices (EPIDs), patient's portal images can be visualized daily in real-time after only a small fraction of the radiation dose has been delivered to each treatment field. However, the accuracy of human visual evaluation of low-contrast portal images has been found to be inadequate. The goal of this research is to develop automated image analysis tools to detect both treatment field shape errors and patient anatomy placement errors with an EPID. A moments method has been developed to align treatment field images to compensate for lack of repositioning precision of the image detector. A figure of merit has also been established to verify the shape and rotation of the treatment fields. Following proper alignment of treatment field boundaries, a cross-correlation method has been developed to detect shifts of the patient's anatomy relative to the treatment field boundary. Phantom studies showed that the moments method aligned the radiation fields to within 0.5mm of translation and 0.5$\sp\circ$ of rotation and that the cross-correlation method aligned anatomical structures inside the radiation field to within 1 mm of translation and 1$\sp\circ$ of rotation. A new procedure of generating and using digitally reconstructed radiographs (DRRs) at megavoltage energies as reference images was also investigated. The procedure allowed a direct comparison between a designed treatment portal and the actual patient setup positions detected by an EPID. Phantom studies confirmed the feasibility of the methodology. Both the moments method and the cross-correlation technique were implemented within an experimental radiotherapy picture archival and communication system (RT-PACS) and were used clinically to evaluate the setup variability of two groups of cancer patients treated with and without an alpha-cradle immobilization aid. The tools developed in this project have proven to be very effective and have played an important role in detecting patient alignment errors and field-shape errors in treatment fields formed by a multileaf collimator (MLC). ^

HUMAN PROPHASE CHROMOSOME UNIQUE BAND SEQUENCES; DEFINITION, CHARACTERIZATION, AND APPLICATION (CYTOGENETICS, IMAGE PROCESSING)

Extensive experience with the analysis of human prophase chromosomes and studies into the complexity of prophase GTG-banding patterns have suggested that at least some prophase chromosomal segments can be accurately identified and characterized independently of the morphology of the chromosome as a whole. In this dissertation the feasibility of identifying and analyzing specified prophase chromosome segments was thus investigated as an alternative approach to prophase chromosome analysis based on whole chromosome recognition. Through the use of prophase idiograms at the 850-band-stage (FRANCKE, 1981) and a comparison system based on the calculation of cross-correlation coefficients between idiogram profiles, we have demonstrated that it is possible to divide the 24 human prophase idiograms into a set of 94 unique band sequences. Each unique band sequence has a banding pattern that is recognizable and distinct from any other non-homologous chromosome portion.^ Using chromosomes 11p and 16 thru 22 to demonstrate unique band sequence integrity at the chromosome level, we found that prophase chromosome banding pattern variation can be compensated for and that a set of unique band sequences very similar to those at the idiogram level can be identified on actual chromosomes.^ The use of a unique band sequence approach in prophase chromosome analysis is expected to increase efficiency and sensitivity through more effective use of available banding information. The use of a unique band sequence approach to prophase chromosome analysis is discussed both at the routine level by cytogeneticists and at an image processing level with a semi-automated approach to prophase chromosome analysis. ^

Intensive care noise and mean arterial blood pressure in ELBW neonates

Objective. Loud noises in neonatal intensive care units (NICUs) may impede growth and development for extremely low birthweight (ELBW, < 1000 grams) newborns. The objective of this study was to measure the association between NICU sound levels and ELBW neonates' arterial blood pressure to determine whether these newborns experience noise-induced stress. ^ Methods. Noise and arterial blood pressure recordings were collected for 9 ELBW neonates during the first week of life. Sound levels were measured inside the incubator, and each subject's arterial blood pressures were simultaneously recorded for 15 minutes (at 1 sec intervals). Time series cross-correlation functions were calculated for NICU noise and mean arterial blood pressure (MABP) recordings for each subject. The grand mean noise-MABP cross-correlation was calculated for all subjects and for lower and higher birthweight groups for comparison. ^ Results. The grand mean noise-MABP cross-correlation for all subjects was mostly negative (through 300 sec lag time) and nearly reached significance at the 95% level at 111 sec lag (mean r = -0.062). Lower birthweight newborns (454-709 g) experienced significant decreases in blood pressure with increasing NICU noise after 145 sec lag (peak r = -0.074). Higher birthweight newborns had an immediate negative correlation with NICU sound levels (at 3 sec lag, r = -0.071), but arterial blood pressures increased to a positive correlation with noise levels at 197 sec lag (r = 0.075). ^ Conclusions. ELBW newborns' arterial blood pressure was influenced by NICU noise levels during the first week of life. Lower birthweight newborns may have experienced an orienting reflex to NICU sounds. Higher birthweight newborns experienced an immediate orienting reflex to increasing sound levels, but arterial blood pressure increased approximately 3 minutes after increases in noise levels. Increases in arterial blood pressure following increased NICU sound levels may result from a stress response to noise. ^

Correlates of tobacco cessation counseling among Hispanic physicians in the US: a cross-sectional survey study.

BACKGROUND: Physician advice is an important motivator for attempting to stop smoking. However, physicians' lack of intervention with smokers has only modestly improved in the last decade. Although the literature includes extensive research in the area of the smoking intervention practices of clinicians, few studies have focused on Hispanic physicians. The purpose of this study was to explore the correlates of tobacco cessation counseling practices among Hispanic physicians in the US. METHODS: Data were collected through a validated survey instrument among a cross-sectional sample of self-reported Hispanic physicians practicing in New Mexico, and who were members of the New Mexico Hispanic Medical Society in the year 2001. Domains of interest included counseling practices, self-efficacy, attitudes/responsibility, and knowledge/skills. Returned surveys were analyzed to obtain frequencies and descriptive statistics for each survey item. Other analyses included: bivariate Pearson's correlation, factorial ANOVAs, and multiple linear regressions. RESULTS: Respondents (n = 45) reported a low level of compliance with tobacco control guidelines and recommendations. Results indicate that physicians' familiarity with standard cessation protocols has a significant effect on their tobacco-related practices (r = .35, variance shared = 12%). Self-efficacy and gender were both significantly correlated to tobacco related practices (r = .42, variance shared = 17%). A significant correlation was also found between self-efficacy and knowledge/skills (r = .60, variance shared = 36%). Attitudes/responsibility was not significantly correlated with any of the other measures. CONCLUSION: More resources should be dedicated to training Hispanic physicians in tobacco intervention. Training may facilitate practice by increasing knowledge, developing skills and, ultimately, enhancing feelings of self-efficacy.

Correlation between dental care utilization and oral cavity cancer in a large sample of community-based United States residents

Cancer of the oral cavity and pharynx remains one of the ten leading causes of cancer death in the United States (US). Besides smoking and alcohol consumption, there are no well established risk factors. While poor dental care had been implicated, it is unknown if the lack of dental care, implying poor dental hygiene predisposes to oral cavity cancer. This study aimed to assess the relationship between dental care utilization during the past twelve months and the prevalence of oral cavity cancer. A cross-sectional design of the National Health Interview Survey of adult, non-institutionalized US residents (n=30,475) was used to assess the association between dental care utilization and self reported diagnosis of oral cavity cancer. Chi square statistic was used to examine the crude association between the predictor variable, dental care utilization and other covariates, while unconditional logistic regression was used to assess the relationship between oral cavity cancer and dental care utilization. There were statistically significant differences between those who utilized dental care during the past twelve months and those who did not with respect to education, income, age, marital status, and gender (p < 0.05), but not health insurance coverage (p = 0.53). Also, those who utilized dental care relative to those who did not were 65% less likely to present with oral cavity cancer, prevalence odds ratio (POR), 0.35, 95% Confidence Interval (CI), 0.12–0.98. Further, higher income advanced age, people of African heritage, and unmarried status were statistically significantly associated with oral cavity cancer, (p < 0.05), but health insurance coverage, alcohol use and smoking were not, p > 0.05. However, after simultaneously controlling for the relevant covariates, the association between dental care and oral cavity cancer did not attenuate nor persist. Thus, compared with those who did not use dental care, those who did wee 62% less likely to present with oral cavity cancer adjusted POR, 0.38, 95% CI, 0.13-1.10. Among US adults residing in community settings, use of dental care during the past twelve months did not significantly reduce the predisposition to oral cavity cancer. However, due to the nature of the data used in this study, which restricts temporal sequence, a large sample prospective study that may identify modifiable factors associated with oral cancer development namely poor dental care, is needed. ^

COX-2 expression in operable triple negative breast cancer: A hospital based cross-sectional study

Objectives. Triple Negative Breast Cancer (TNBC) lack expression of estrogen receptors (ER), progesterone receptors (PR), and absence of Her2 gene amplification. Current literature has identified TNBC and over-expression of cyclo-oxygenase-2 (COX-2) protein in primary breast cancer to be independent markers of poor prognosis in terms of overall and distant disease free survival. The purpose of this study was to compare COX-2 over-expression in TNBC patients to those patients who expressed one or more of the three tumor markers (i.e. ER, and/or PR, and/or Her2).^ Methods. Using a secondary data analysis, a cross-sectional design was implemented to examine the association of interest. Data collected from two ongoing protocols titled "LAB04-0657: a model for COX-2 mediated bone metastasis (Specific aim 3)" and "LAB04-0698: correlation of circulating tumor cells and COX-2 expression in primary breast cancer metastasis" was used for analysis. A sample of 125 female patients was analyzed using Chi-square tests and logistic regression models. ^ Results. COX-2 over-expression was present in 33% (41/125) and 28% (35/124) patients were identified as having TNBC. TNBC status was associated with elevated COX-2 expression (OR= 3.34; 95% CI= 1.40–8.22) and high tumor grade (OR= 4.09; 95% CI= 1.58–10.82). In a multivariable analysis, TNBC status was an important predictor of COX-2 expression after adjusting for age, menopausal status, BMI, and lymph node status (OR= 3.31; 95% CI: 1.26–8.67; p=0.01).^ Conclusion. TNBC is associated with COX-2 expression—a known marker of poor prognosis in patients with operable breast cancer. Replication of these results in a study with a larger sample size, or a future randomized clinical trial demonstrating an improved prognosis with COX-2 suppression in these patients would support this hypothesis.^

Selection bias and the cross-validation of regression models for prediction

Strategies are compared for the development of a linear regression model with stochastic (multivariate normal) regressor variables and the subsequent assessment of its predictive ability. Bias and mean squared error of four estimators of predictive performance are evaluated in simulated samples of 32 population correlation matrices. Models including all of the available predictors are compared with those obtained using selected subsets. The subset selection procedures investigated include two stopping rules, C$\sb{\rm p}$ and S$\sb{\rm p}$, each combined with an 'all possible subsets' or 'forward selection' of variables. The estimators of performance utilized include parametric (MSEP$\sb{\rm m}$) and non-parametric (PRESS) assessments in the entire sample, and two data splitting estimates restricted to a random or balanced (Snee's DUPLEX) 'validation' half sample. The simulations were performed as a designed experiment, with population correlation matrices representing a broad range of data structures.^ The techniques examined for subset selection do not generally result in improved predictions relative to the full model. Approaches using 'forward selection' result in slightly smaller prediction errors and less biased estimators of predictive accuracy than 'all possible subsets' approaches but no differences are detected between the performances of C$\sb{\rm p}$ and S$\sb{\rm p}$. In every case, prediction errors of models obtained by subset selection in either of the half splits exceed those obtained using all predictors and the entire sample.^ Only the random split estimator is conditionally (on $\\beta$) unbiased, however MSEP$\sb{\rm m}$ is unbiased on average and PRESS is nearly so in unselected (fixed form) models. When subset selection techniques are used, MSEP$\sb{\rm m}$ and PRESS always underestimate prediction errors, by as much as 27 percent (on average) in small samples. Despite their bias, the mean squared errors (MSE) of these estimators are at least 30 percent less than that of the unbiased random split estimator. The DUPLEX split estimator suffers from large MSE as well as bias, and seems of little value within the context of stochastic regressor variables.^ To maximize predictive accuracy while retaining a reliable estimate of that accuracy, it is recommended that the entire sample be used for model development, and a leave-one-out statistic (e.g. PRESS) be used for assessment. ^

Total cholesterol and anthropometric measurements distributions in a cross-sectional study of school children

Cross-sectional age and sex specific distributions of serum total cholesterol were described for 1091 children age 6-18 years, in The Woodlands, Texas. Associations of serum total cholesterol with five anthropometric measurements (weight, height, body mass index, arm circumference, and triceps skinfold thickness) were examined by correlation and regression analyses. Examination of serum total cholesterol distributions showed lower levels in boys than in girls for most of the age groups studied. Mean levels of total cholesterol peaked at age 9 for boys and 8 for girls. Serum total cholesterol leveled off until age 14 for boys and 11 for girls, and then dropped through age 18 for both boys and girls. These results support the hypothesis that serum total cholesterol concentration drops at pre-adolescence.^ Age adjusted correlations were observed between serum total cholesterol and triceps skinfold thickness for both boys and girls. This association was stronger in boys. Triceps skinfold thickness and arm circumference were consistently the strongest correlates for serum total cholesterol in boys. Weight and arm circumference were consistently the strongest correlates for serum total cholesterol in girls. ^

Cross-culture perspectives on fear of HIV disease and AIDS in health care workers

Health care workers have been known to carry into the workplace a variety of judgmental and negative attitudes towards their patients. In no other area of patient care has this issue been more pronounced as in the management of patients with AIDS. Health care workers have refused to treat or manage patients with AIDS and have often treated them more harshly than identically described leukemia patients. Some health care institutions have simply refused to admit patients with AIDS and even recent applicants to medical colleges and schools of nursing have indicated a preference for schools in areas with low prevalence of HIV disease. Since the attitudes of health care workers do have significant consequences on patient management, this study was carried out to determine the differences in clinical practice in Nigeria and the United States of America as it relates to knowledge of a patient's HIV status, determine HIV prevalence and culture in each of the study sites and how they impact on infection control practices, determine the relationship between infection control practices and fear of AIDS, and also determine the predictors of safe infection control practices in each of the study sites.^ The study utilized the 38-item fear of AIDS scale and the measure of infection control questionnaire for its data. Questionnaires were administered to health care workers at the university teaching hospital sites of Houston, Texas and Calabar in Nigeria. Data was analyzed using a chi-square test, and where appropriate, a student t-tests to establish the demographic variables for each country. Factor analysis was done using principal components analysis followed by varimax rotation to simple structure. The subscale scores for each study site were compared using t-tests (separate variance estimates) and utilizing Bonferroni adjustments for number of tests. Finally, correlations were carried out between infection control procedures and fear of AIDS in each study site using Pearson-product moment correlation coefficients.^ The study revealed that there were five dimensions of the fear of AIDS in health care workers, namely fear of loss of control, fear of sex, fear of HIV infection through blood and illness, fear of death and medical interventions and fear of contact with out-groups. Fear of loss of control was the primary area of concern in the Nigerian health care workers whereas fear of HIV infection through blood and illness was the most important area of AIDS related feats in United States health care workers. The study also revealed that infection control precautions and practices in Nigeria were based more on normative and social pressures whereas it was based on knowledge of disease transmission, supervision and employee discipline in the United States, and thus stresses the need for focused educational programs in health care settings that emphasize universal precautions at all times and that are sensitive to the cultural nuances of that particular environment. ^

The Relationship of Provincial Economic Level and Child Injury Mortality in Thailand: A Cross-Sectional Analysis in a Middle Income Country

The objective of this cross-sectional study was to examine the relationship of provincial economic development indices with incidences of child injury mortality in Thailand from 1999 - 2001. All injury deaths among children age 1-14 years were included. The independent variables included gross provincial product per capita (GPP/c), poverty and inequality indices, material and social deprivation indices, population in rural/ urban areas, and migration. Due to multicollinearity of such variables, the 76 provinces were categorized by GPP/c quartile, and means of overall injury, drowning, and transport-related mortality rates were compared among quartile groups. Spearman’s rho correlation between GPP/c and injury mortality rates was also performed. Finally, factor analysis was employed to create a set of factors to be treated as uncorrelated variables and stepwise multiple regression was carried out for the effects of the factors on injury mortality rates. A significant direct relationship was observed between GPP/c and overall injury mortality among children age 1-4 years, and 10-14 year-olds of both genders. Drowning was the main cause of this relationship among children age 1-4 years, and transport-related injury was the principle cause among children age 10-14 years. Conversely, provinces with lower GPP/c experienced higher injury mortality rates among school-age children 5-9 years old for both genders, mostly due to drowning. Factor analysis, and multiple regression results confirmed the relationships between economic development and injury mortality rates. These findings revealed that economic development had an adverse impact on injury-related mortality among children 1 to 4 and 10 to14 in Thailand.