Modeling survival and the development of second primary tumors among Hodgkin's disease patients

Hodgkin's disease (HD) is a cancer of the lymphatic system. Survivors of HD face varieties of consequent adverse effects, in which secondary primary tumors (SPT) is one of the most serious consequences. This dissertation is aimed to model time-to-SPT in the presence of death and HD relapses during follow-up.^ The model is designed to handle a mixture phenomenon of SPT and the influence of death. Relapses of HD are adjusted as a covariate. Proportional hazards framework is used to define SPT intensity function, which includes an exponential term to estimate explanatory variables. Death as a competing risk is considered according to different scenarios, depending on which terminal event comes first. Newton-Raphson method is used to estimate the parameter estimates in the end.^ The proposed method is applied to a real data set containing a group of HD patients. Several risk factors for the development of SPT are identified and the findings are noteworthy in the development of healthcare guidelines that may lead to the early detection or prevention of SPT.^

Probiotics and the prevention of necrotizing enterocolitis in preterm infants: A systematic review of the literature

Necrotizing enterocolitis is a common gastrointestinal disease associated with high mortality and morbidity among preterm infants. This was a systematic literature review that evaluated whether the administration of probiotic supplements is of benefit in the prevention of NEC. The search was narrowed to randomized clinical trials identified through The Cochrane Central Register of Controlled Trials, U.S. National Institute of Health clinical trials registry database, Pub Med and OVID MEDLINE databases. Inclusion criteria were: prospective, randomized clinical trials that administered probiotics as a preventive measure against NEC for infants of early gestational age (<35 wks) and/or low birth weight (<1500g), maintained NEC as the primary measured outcome, used Bell’s classification for NEC diagnosis with reports of stage 2 NEC or higher, and began probiotic administration within 10 days of life. Trials were excluded if participant enrollment was fewer than 100 infants, published before the year 2000, or probiotic supplementation was discontinued after less than seven consecutive days. Based on specific study characteristics, each resulting article was then judged by two authors for study quality. The search was further narrowed to studies of either high or moderate quality, which were then summarized in a set of tables based on study characteristics and results. From an initial set of 20 identified studies, five clinical trials met all criteria; each was discussed thoroughly based on trial limitations, strengths and comparisons to other included publications. Based on this review, the weight of evidence appears to support the use of probiotic supplementation in preterm infants as a preventive measure against NEC. Recommendations for future research were also provided.^

Process evaluation of intervention program for prevention of early sexual activity and alcohol use among Hispanic teenagers

Hispanic teens are a high-risk population for initiation of early sexual activity and alcohol use which in turn has numerous social and health consequences. One strategy to address prevention of these behaviors is to implement a capacity building intervention that promotes parent child communication, encompasses their cultural values and community participation. This study describes the process evaluation of a pilot intervention program amongst Hispanic teens and their families living along the Texas-Mexico border. “Girls Lets Talk” is a small group intervention with 10-14 year old teens and their female adult family members that involves education regarding effects of alcohol use and sexual activity as well as activities for monitoring and refusal skills to prevent risky behaviors. Two waves of the program each consisting of at least seven mother daughter dyads were conducted. During the designing process, community advisory board meetings and focus groups were held to review course materials and ensure they were appropriate to the Mexican American culture. Parent and adolescent surveys were administered at the beginning and end of the intervention to assess for psychosocial outcome variables. All sessions received high mean satisfactory scores (mean of 4.00 or better on a five point scale) for both adult and adolescent participants. Qualitative feedback was obtained via debriefing sessions to evaluate experience as well as alter recruitment strategies. A Wilcoxon Sign Rank analysis of the pre and post intervention surveys was done that showed significant changes in some outcome variables such as intentions and confidence for monitoring behaviors for adults and beliefs regarding sexual activity. “Girls Lets Talk” is a promising example of how a process evaluation plan can help develop a theory based health promotion program using the community based participatory research approach. The intervention may also be effective in altering intentions and enhancing self-efficacy among parents and teens in order to decrease risky behaviors such as early sexual activity and alcohol use.^

THE RELATIONSHIP BETWEEN SERUM CHOLESTEROL AND CANCER INCIDENCE IN THE POPULATION OF THE HYPERTENSION DETECTION AND FOLLOW-UP PROGRAM

The relationship between serum cholesterol and cancer incidence was investigated in the population of the Hypertension Detection and Follow-up Program (HDFP). The HDFP was a multi-center trial designed to test the effectiveness of a stepped program of medication in reducing mortality associated with hypertension. Over 10,000 participants, ages 30-69, were followed with clinic and home visits for a minimum of five years. Cancer incidence was ascertained from existing study documents, which included hospitalization records, autopsy reports and death certificates. During the five years of follow-up, 286 new cancer cases were documented. The distribution of sites and total number of cases were similar to those predicted using rates from the Third National Cancer Survey. A non-fasting baseline serum cholesterol level was available for most participants. Age, sex, and race specific five-year cancer incidence rates were computed for each cholesterol quartile. Rates were also computed by smoking status, education status, and percent ideal weight quartiles. In addition, these and other factors were investigated with the use of the multiple logistic model.^ For all cancers combined, a significant inverse relationship existed between baseline serum cholesterol levels and cancer incidence. Previously documented associations between smoking, education and cancer were also demonstrated but did not account for the relationship between serum cholesterol and cancer. The relationship was more evident in males than females but this was felt to represent the different distribution of occurrence of specific cancer sites in the two sexes. The inverse relationship existed for all specific sites investigated (except breast) although a level of statistical significance was reached only for prostate carcinoma. Analyses after exclusion of cases diagnosed during the first two years of follow-up still yielded an inverse relationship. Life table analysis indicated that competing risks during the period of follow-up did not account for the existence of an inverse relationship. It is concluded that a weak inverse relationship does exist between serum cholesterol for many but not all cancer sites. This relationship is not due to confounding by other known cancer risk factors, competing risks or persons entering the study with undiagnosed cancer. Not enough information is available at the present time to determine whether this relationship is causal and further research is suggested. ^

THE RELATIONSHIP BETWEEN DEGREE OF BLOOD PRESSURE REDUCTION AND MORTALITY AMONG HYPERTENSIVES IN THE HYPERTENSION DETECTION AND FOLLOW-UP PROGRAM

The relationship between degree of diastolic blood pressure (DBP) reduction and mortality was examined among hypertensives, ages 30-69, in the Hypertension Detection and Follow-up Program (HDFP). The HDFP was a multi-center community-based trial, which followed 10,940 hypertensive participants for five years. One-year survival was required for inclusion in this investigation since the one-year annual visit was the first occasion where change in blood pressure could be measured on all participants. During the subsequent four years of follow-up on 10,052 participants, 568 deaths occurred. For levels of change in DBP and for categories of variables related to mortality, the crude mortality rate was calculated. Time-dependent life tables were also calculated so as to utilize available blood pressure data over time. In addition, the Cox life table regression model, extended to take into account both time-constant and time-dependent covariates, was used to examine the relationship change in blood pressure over time and mortality.^ The results of the time-dependent life table and time-dependent Cox life table regression analyses supported the existence of a quadratic function which modeled the relationship between DBP reduction and mortality, even after adjusting for other risk factors. The minimum mortality hazard ratio, based on a particular model, occurred at a DBP reduction of 22.6 mm Hg (standard error = 10.6) in the whole population and 8.5 mm Hg (standard error = 4.6) in the baseline DBP stratum 90-104. After this reduction, there was a small increase in the risk of death. There was not evidence of the quadratic function after fitting the same model using systolic blood pressure. Methodologic issues involved in studying a particular degree of blood pressure reduction were considered. The confidence interval around the change corresponding to the minimum hazard ratio was wide and the obtained blood pressure level should not be interpreted as a goal for treatment. Blood pressure reduction was attributed, not only to pharmacologic therapy, but also to regression to the mean, and to other unknown factors unrelated to treatment. Therefore, the surprising results of this study do not provide direct implications for treatment, but strongly suggest replication in other populations. ^

Development and evaluation of a video-based modeling strategy for the dissemination phase of a school health tobacco -use prevention program

Even the best school health education programs will be unsuccessful if they are not disseminated effectively in a manner that encourages classroom adoption and implementation. This study involved two components: (1) the development of a videotape intervention to be used in the dissemination phase of a 4-year, NCI-funded diffusion study and (2) the evaluation of that videotape intervention strategy in comparison with a print (information transfer) strategy. Conceptualization has been guided by Social Learning Theory, Diffusion Theory, and communication theory. Additionally, the PRECEDE Framework has been used. Seventh and 8th grade classroom teachers from Spring Branch Independent School District in west Houston participated in the evaluation of the videotape and print interventions using a 57-item preadoption survey instrument developed by the UT Center for Health Promotion Research and Development. Two-way ANOVA was used to study individual score differences for five outcome variables: Total Scale Score (comprised of 57 predisposing, enabling, and reinforcing items), Adoption Characteristics Subscale, Attitude Toward Innovation Subscale, Receptivity Toward Innovation, and Reinforcement Subscale. The aim of the study is to compare the effect upon score differences of video and print interventions alone and in combination. Seventy-three 7th and 8th grade classroom teachers completed the study providing baseline and post-intervention measures on factors related to the adoption and implementation of tobacco-use prevention programs. Two-way ANOVA, in relation to the study questions, found significant scoring differences for those exposed to the videotape intervention alone for both the Attitude Toward Innovation Subscale and the Receptivity to Adopt Subscale. No significant results were found to suggest that print alone influences favorable scoring differences between baseline and post-intervention testing. One interaction effect was found suggesting video and print combined are more effective for influencing favorable scoring differences for the Reinforcement for the Adoption Subscale.^ This research is unique in that it represents a newly emerging field in health promotion communications research with implications for Social Learning Theory, Diffusion Theory, and communication science that are applicable to the development of improved school health interventions. ^

Prevention and Management of Postpartum Hemorrhage

Este video de formación clínica ofrece orientación sobre el manejo activo de la tercera etapa del parto, el tratamiento de la hemorragia posparto y la hemorragia excesiva

Achievements of the FIGO Initiative for the Prevention of Unsafe Abortion and its Consequences in South-Southeast Asia.

Since 2008, the FIGO Initiative for the Prevention of Unsafe Abortion and its Consequences has contributed to ensuring the substitution of sharp curettage by manual vacuum aspiration (MVA) and medical abortion in selected hospitals in participating countries of South-Southeast Asia. This initiative facilitated the registration of misoprostol in Pakistan and Bangladesh, and the approval of mifepristone for "menstrual regulation" in Bangladesh. The Pakistan Nursing Council agreed to include MVA and medical abortion in the midwifery curriculum. The Bangladesh Government has approved the training of nurses and paramedics in the use of MVA to treat incomplete abortion in selected cases. The Sri Lanka College of Obstetricians and Gynaecologists, in collaboration with partners, has presented a draft petition to the relevant authorities appealing for them to liberalize the abortion law in cases of rape and incest or when lethal congenital abnormalities are present. Significantly, the initiative has introduced or strengthened the provision of postabortion contraception.

Design, implementation and evaluation of an unconstrained and contactless biometric system based on hand geometry and stress detection

Esta tesis propone un sistema biométrico de geometría de mano orientado a entornos sin contacto junto con un sistema de detección de estrés capaz de decir qué grado de estrés tiene una determinada persona en base a señales fisiológicas Con respecto al sistema biométrico, esta tesis contribuye con el diseño y la implementación de un sistema biométrico de geometría de mano, donde la adquisición se realiza sin ningún tipo de contacto, y el patrón del usuario se crea considerando únicamente datos del propio individuo. Además, esta tesis propone un algoritmo de segmentación multiescala para solucionar los problemas que conlleva la adquisición de manos en entornos reales. Por otro lado, respecto a la extracción de características y su posterior comparación esta tesis tiene una contribución específica, proponiendo esquemas adecuados para llevar a cabo tales tareas con un coste computacional bajo pero con una alta precisión en el reconocimiento de personas. Por último, este sistema es evaluado acorde a la norma estándar ISO/IEC 19795 considerando seis bases de datos públicas. En relación al método de detección de estrés, esta tesis propone un sistema basado en dos señales fisiológicas, concretamente la tasa cardiaca y la conductancia de la piel, así como la creación de un innovador patrón de estrés que recoge el comportamiento de ambas señales bajo las situaciones de estrés y no-estrés. Además, este sistema está basado en lógica difusa para decidir el grado de estrés de un individuo. En general, este sistema es capaz de detectar estrés de forma precisa y en tiempo real, proporcionando una solución adecuada para sistemas biométricos actuales, donde la aplicación del sistema de detección de estrés es directa para evitar situaciónes donde los individuos sean forzados a proporcionar sus datos biométricos. Finalmente, esta tesis incluye un estudio de aceptabilidad del usuario, donde se evalúa cuál es la aceptación del usuario con respecto a la técnica biométrica propuesta por un total de 250 usuarios. Además se incluye un prototipo implementado en un dispositivo móvil y su evaluación. ABSTRACT: This thesis proposes a hand biometric system oriented to unconstrained and contactless scenarios together with a stress detection method able to elucidate to what extent an individual is under stress based on physiological signals. Concerning the biometric system, this thesis contributes with the design and implementation of a hand-based biometric system, where the acquisition is carried out without contact and the template is created only requiring information from a single individual. In addition, this thesis proposes an algorithm based on multiscale aggregation in order to tackle with the problem of segmentation in real unconstrained environments. Furthermore, feature extraction and matching are also a specific contributions of this thesis, providing adequate schemes to carry out both actions with low computational cost but with certain recognition accuracy. Finally, this system is evaluated according to international standard ISO/IEC 19795 considering six public databases. In relation to the stress detection method, this thesis proposes a system based on two physiological signals, namely heart rate and galvanic skin response, with the creation of an innovative stress detection template which gathers the behaviour of both physiological signals under both stressing and non-stressing situations. Besides, this system is based on fuzzy logic to elucidate the level of stress of an individual. As an overview, this system is able to detect stress accurately and in real-time, providing an adequate solution for current biometric systems, where the application of a stress detection system is direct to avoid situations where individuals are forced to provide the biometric data. Finally, this thesis includes a user acceptability evaluation, where the acceptance of the proposed biometric technique is assessed by a total of 250 individuals. In addition, this thesis includes a mobile implementation prototype and its evaluation.

Detection and selective dissociation of intact ribosomes in a mass spectrometer

Intact Escherichia coli ribosomes have been projected into the gas phase of a mass spectrometer by means of nanoflow electrospray techniques. Species with mass/charge ratios in excess of 20,000 were detected at the level of individual ions by using time-of-flight analysis. Once in the gas phase the stability of intact ribosomes was investigated and found to increase as a result of cross-linking ribosomal proteins to the rRNA. By lowering the Mg2+ concentration in solutions containing ribosomes the particles were found to dissociate into 30S and 50S subunits. The resolution of the charge states in the spectrum of the 30S subunit enabled its mass to be determined as 852,187 ± 3,918 Da, a value within 0.6% of that calculated from the individual proteins and the 16S RNA. Further dissociation into smaller macromolecular complexes and then individual proteins could be induced by subjecting the particles to increasingly energetic gas phase collisions. The ease with which proteins dissociated from the intact species was found to be related to their known interactions in the ribosome particle. The results show that emerging mass spectrometric techniques can be used to characterize a fully functional biological assembly as well as its isolated components.

Chemical chaperones mediate increased secretion of mutant α1-antitrypsin (α1-AT) Z: A potential pharmacological strategy for prevention of liver injury and emphysema in α1-AT deficiency

In α1-AT deficiency, a misfolded but functionally active mutant α1-ATZ (α1-ATZ) molecule is retained in the endoplasmic reticulum of liver cells rather than secreted into the blood and body fluids. Emphysema is thought to be caused by the lack of circulating α1-AT to inhibit neutrophil elastase in the lung. Liver injury is thought to be caused by the hepatotoxic effects of the retained α1-ATZ. In this study, we show that several “chemical chaperones,” which have been shown to reverse the cellular mislocalization or misfolding of other mutant plasma membrane, nuclear, and cytoplasmic proteins, mediate increased secretion of α1-ATZ. In particular, 4-phenylbutyric acid (PBA) mediated a marked increase in secretion of functionally active α1-ATZ in a model cell culture system. Moreover, oral administration of PBA was well tolerated by PiZ mice (transgenic for the human α1-ATZ gene) and consistently mediated an increase in blood levels of human α1-AT reaching 20–50% of the levels present in PiM mice and normal humans. Because clinical studies have suggested that only partial correction is needed for prevention of both liver and lung injury in α1-AT deficiency and PBA has been used safely in humans, it constitutes an excellent candidate for chemoprophylaxis of target organ injury in α1-AT deficiency.