Mathematical and empirical examinations of some epidemiological procedures

In epidemiology literature, it is often required to investigate the relationships between means where the levels of experiment are actually monotone sets forming a partition on the range of sampling values. With this need, the analysis of these group means is generally performed using classical analysis of variance (ANOVA). However, this method has never been challenged. In this dissertation, we will formulate and present our examination of its validity. First, the classical assumptions of normality and constant variance are not always true. Second, under the null hypothesis of equal means, the test statistic for the classical ANOVA technique is still valid. Third, when the hypothesis of equal means is rejected, the classical analysis techniques for hypotheses of contrasts are not valid. Fourth, under the alternative hypothesis, we can show that the monotone property of levels leads to the conclusion that the means are monotone. Fifth, we propose an appropriate method for handing the data in this situation. ^

A qualitative and quantitative assessment of cancer patients' perceptions of barriers to treatment

This study examined barriers that cancer patients experience in obtaining treatment. The principal aim of the study was to conduct a comprehensive quantitative and qualitative assessment of barriers to cancer treatment for Texas cancer patients. The three specific aims of the study were to: (1) conduct a review and critique of published and unpublished research on barriers to cancer treatment; (2) conduct focus groups for the qualitative assessment of cancer patients' perceived barriers to cancer treatment; and (3) survey a representative sample of cancer patients regarding perceived barriers to treatment. The study was guided by the Aday and Andersen access framework of predisposing, enabling, and need determinants of care-seeking.^ To address the first specific aim, a total of 732 abstracts were examined, from which 154 articles were selected for review. Of these 154 articles, 57 that related directly to research on barriers to cancer treatment were chosen for subsequent analysis. Criteria were applied to each article to evaluate the strength of the study design, sampling and measurement procedures. The major barriers that were consistently documented to influence whether or not cancer patients sought or continued required treatment included problems with communication between the patient and provider, lack of information on side effects, the cost of treatment and associated difficulties in obtaining and maintaining insurance coverage, and the absence of formal and informal networks of social support. Access barriers were generally greater for older, minority women, and patients of lower socioeconomic status.^ To address the second specific aim, a total of eight focus groups (n = 44) were conducted across the State of Texas with cancer patients identified by the Texas Community Oncology Network, American Cancer Society, and community health centers. One important finding was that cost is the greatest hurdle that patients face. Another finding was that with the health care/insurance crisis, an increasing number of physicians are working with their patients to develop individually-tailored payment plans. For people in rural areas, travel to treatment sites is a major barrier due to the travel costs as well as work time forfeited by patients and their family members. A third major finding was the patients' family and church play important roles in providing social and emotional support for cancer patients.^ To address the third aim, a total of 910 cancer patients were surveyed during October and November, 1993. Approximately 65% of the cancer patients responded to the survey. The findings showed that the major barriers to treatment included costs of medications and diagnostic tests, transportation, lack of social support, problems understanding the written information regarding their disease as well as losing coverage or having higher premiums or copayments once they were diagnosed (particularly among blacks).^ Significant differences in reported barriers were found between racial groups. The minority respondents (i.e., blacks and Hispanics) tended to experience more barriers to treatment compared to the white respondents. More specifically, Hispanics were more likely to report transportation as a barrier to treatment than both white and blacks. Future research is needed to better understand the problems that minority cancer patients experience in receiving treatment. (Abstract shortened by UMI.) ^

DETERMINING THE GENOTYPE-PHENOTYPE CONNECTION IN SYNTHETIC INDUCIBLE GENE EXPRESSION SYSTEMS

Introduction Gene expression is an important process whereby the genotype controls an individual cell’s phenotype. However, even genetically identical cells display a variety of phenotypes, which may be attributed to differences in their environment. Yet, even after controlling for these two factors, individual phenotypes still diverge due to noisy gene expression. Synthetic gene expression systems allow investigators to isolate, control, and measure the effects of noise on cell phenotypes. I used mathematical and computational methods to design, study, and predict the behavior of synthetic gene expression systems in S. cerevisiae, which were affected by noise. Methods I created probabilistic biochemical reaction models from known behaviors of the tetR and rtTA genes, gene products, and their gene architectures. I then simplified these models to account for essential behaviors of gene expression systems. Finally, I used these models to predict behaviors of modified gene expression systems, which were experimentally verified. Results Cell growth, which is often ignored when formulating chemical kinetics models, was essential for understanding gene expression behavior. Models incorporating growth effects were used to explain unexpected reductions in gene expression noise, design a set of gene expression systems with “linear” dose-responses, and quantify the speed with which cells explored their fitness landscapes due to noisy gene expression. Conclusions Models incorporating noisy gene expression and cell division were necessary to design, understand, and predict the behaviors of synthetic gene expression systems. The methods and models developed here will allow investigators to more efficiently design new gene expression systems, and infer gene expression properties of TetR based systems.

Sporomorphs and quantitative analysis of the Eocene record from IODP Hole 318-U1356A

The early Eocene epoch was characterized by extreme global warmth, which in terrestrial settings was characterized by an expansion of near-tropical vegetation belts into the high latitudes. During the middle to late Eocene, global cooling caused the retreat of tropical vegetation to lower latitudes. In high-latitude settings, near-tropical vegetation was replaced by temperate floras. This floral change has recently been traced as far south as Antarctica, where along the Wilkes Land margin paratropical forests thrived during the early Eocene and temperate Nothofagus forests developed during the middle Eocene. Here we provide both qualitative and quantitative palynological data for this floral turnover based on a sporomorph record recovered at Integrated Ocean Drilling Program (IODP) Site U1356 off the Wilkes Land margin. Following the nearest living relative concept and based on a comparison with modern vegetation types, we examine the structure and diversity patterns of the Eocene vegetation along the Wilkes Land margin. Our results indicate that the early Eocene forests along the Wilkes Land margin were characterized by a diverse canopy composed of plants that today occur in tropical settings; their richness pattern was similar to that of present-day forests from New Caledonia. The middle Eocene forests were characterized by a canopy dominated by Nothofagus and exhibited richness patterns similar to modern Nothofagus forests from New Zealand.

Pliocene-Pleistocene biostratigraphy in the Tyrrhenian Sea

The distribution of stratigraphically important calcareous nannofossils and planktonic foraminifera has been investigated in the Pliocene-Pleistocene sequences of ODP Sites 652, 653, and 654 (Tyrrhenian Sea-western Mediterranean). Semiquantitative and quantitative methods have been used, and an optimum relative sequence of bioevents based on the calcareous plankton groups has been established. About 30 bioevents in an interval of 5.0 m.y. are considered widely traceable in the area and reasonably synchronous. On the basis of those events, a correlation among the three investigated sequences is presented.

Putting prey and predator into the CO2 equation-qualitative and quantitative effects of ocean acidification on predator-prey interactions

Little is known about the impact of ocean acidification on predator-prey dynamics. Herein, we examined the effect of carbon dioxide (CO(2)) on both prey and predator by letting one predatory reef fish interact for 24 h with eight small or large juvenile damselfishes from four congeneric species. Both prey and predator were exposed to control or elevated levels of CO(2). Mortality rate and predator selectivity were compared across CO(2) treatments, prey size and species. Small juveniles of all species sustained greater mortality at high CO(2) levels, while large recruits were not affected. For large prey, the pattern of prey selectivity by predators was reversed under elevated CO(2). Our results demonstrate both quantitative and qualitative consumptive effects of CO(2) on small and larger damselfish recruits respectively, resulting from CO(2)-induced behavioural changes likely mediated by impaired neurological function. This study highlights the complexity of predicting the effects of climate change on coral reef ecosystems.

The effects of long (C20/22) and short (C18) chain omega-3 fatty acids on keel bone fractures, bone biomechanics, behavior, and egg production in free-range laying hens.

Keel fractures in the laying hen are the most critical animal welfare issue facing the egg production industry, particularly with the increased use of extensive systems in response to the 2012 EU directive banning conventional battery cages. The current study is aimed at assessing the effects of 2 omega-3 (n3) enhanced diets on bone health, production endpoints, and behavior in free-range laying hens. Data was collected from 2 experiments over 2 laying cycles, each of which compared a (n3) supplemented diet with a control diet. Experiment 1 employed a diet supplemented with a 60:40 fish oil-linseed mixture (n3:n6 to 1.35) compared with a control diet (n3:n6 to 0.11), whereas the n3 diet in Experiment 2 was supplemented with a 40:60 fish oil-linseed (n3:n6 to 0.77) compared to the control diet (n3:n6 to 0.11). The n3 enhanced diet of Experiment 1 had a higher n3:n6 ratio, and a greater proportion of n3 in the long chain (C20/22) form (0.41 LC:SC) than that of Experiment 2 (0.12 LC:SC). Although dietary treatment was successful in reducing the frequency of fractures by approximately 27% in Experiment 2, data from Experiment 1 indicated the diet actually induced a greater likelihood of fracture (odds ratio: 1.2) and had substantial production detriment. Reduced keel breakage during Experiment 2 could be related to changes in bone health as n3-supplemented birds demonstrated greater load at failure of the keel, and tibiae and humeri that were more flexible. These results support previous findings that n3-supplemented diets can reduce fracture likely by increasing bone strength, and that this can be achieved without detriment to production. However, our findings suggest diets with excessive quantities of n3, or very high levels of C20/22, may experience health and production detriments. Further research is needed to optimize the quantity and type of n3 in terms of bone health and production variables and investigate the potential associated mechanisms.

Refining predictions of iberian plant distribution: lessons from p. nigra and p. sylvestris palaeoecological-based habitat suitability models

In recent years, challenged by the climate scenarios put forward by the IPCC and its potential impact on plant distribution, numerous predictive techniques -including the so called habitat suitability models (HSM)- have been developed. Yet, as the output of the different methods produces different distribution areas, developing validation tools are strong needs to reduce uncertainties. Focused in the Iberian Peninsula, we propose a palaeo-based method to increase the robustness of the HSM, by developing an ecological approach to understand the mismatches between the palaeoecological information and the projections of the HSMs. Here, we present the result of (1) investigating causal relationships between environmental variables and presence of Pinus sylvestris L. and P. nigra Arn. available from the 3rd Spanish Forest Inventory, (2) developing present and past presence-predictions through the MaxEnt model for 6 and 21 kyr BP, and (3) assessing these models through comparisons with biomized palaeoecological data available from the European Pollen Database for the Iberian Peninsula.

Metodología de evaluación de la seguridad vial en intersecciones basada en el análisis cuantitativo de conflictos entre vehículos

El modo tradicional de estimar el nivel de seguridad vial es el registro de accidentes de tráfico, sin embargo son altamente variables, aleatorios y necesitan un periodo de registro de al menos 3 años. Existen metodologías preventivas en las cuales no es necesario que ocurra un accidente para determinar el nivel de seguridad de una intersección, como lo es la técnica de los conflictos de tráfico, que introduce las mediciones alternativas de seguridad como cuantificadoras del riesgo de accidente. El objetivo general de la tesis es establecer una metodología que permita clasificar el riesgo en intersecciones interurbanas, en función del análisis de conflictos entre vehículos, realizado mediante las variables alternativas o indirectas de seguridad vial. La metodología para el análisis y evaluación temprana de la seguridad en una intersección, estará basada en dos medidas alternativas de seguridad: el tiempo hasta la colisión y el tiempo posterior a la invasión de la trayectoria. El desarrollo experimental se realizó mediante estudios de campo, para la parte exploratoria de la investigación, se seleccionaron 3 intersecciones interurbanas en forma de T donde se obtuvieron las variables que caracterizan los conflictos entre vehículos; luego mediante técnicas de análisis multivariante, se obtuvo los modelos de clasificación del riesgo cualitativo y cuantitativo. Para la homologación y el estudio final de concordancia entre el índice propuesto y el modelo de clasificación, se desarrollaron nuevos estudios de campo en 6 intersecciones interurbanas en forma de T. El índice de riesgo obtenido resulta una herramienta muy útil para realizar evaluaciones rápidas conducentes a estimar la peligrosidad de una intersección en T, debido a lo simple y económico que resulta obtener los registros de datos en campo, por medio de una rápida capacitación a operarios; la elaboración del informe de resultados debe ser por un especialista. Los índices de riesgo obtenidos muestran que las variables originales más influyentes son las mediciones de tiempo. Se pudo determinar que los valores más altos del índice de riesgo están relacionados a un mayor riesgo de que un conflicto termine en accidente. Dentro de este índice, la única variable cuyo aporte es proporcionalmente directo es la velocidad de aproximación, lo que concuerda con lo que sucede en un conflicto, pues una velocidad excesiva se manifiesta como un claro factor de riesgo ya que potencia todos los fallos humanos en la conducción. Una de las principales aportaciones de esta tesis doctoral a la ingeniería de carreteras, es la posibilidad de aplicación de la metodología por parte de administraciones de carreteras locales, las cuales muchas veces cuentan con recursos de inversión limitados para efectuar estudios preventivos, sobretodo en países en vías de desarrollo. La evaluación del riesgo de una intersección luego de una mejora en cuanto a infraestructura y/o dispositivos de control de tráfico, al igual que un análisis antes – después, pero sin realizar una comparación mediante la ocurrencia de accidentes, sino que por medio de la técnica de conflictos de tráfico, se puede convertir en una aplicación directa y económica. Además, se pudo comprobar que el análisis de componentes principales utilizado en la creación del índice de riesgo de la intersección, es una herramienta útil para resumir todo el conjunto de mediciones que son posibles de obtener con la técnica de conflictos de tráfico y que permiten el diagnóstico del riesgo de accidentalidad en una intersección. En cuanto a la metodología para la homologación de los modelos, se pudo establecer la validez y confiabilidad al conjunto de respuestas entregadas por los observadores en el registro de datos en campo, ya que los resultados de la validación establecen que la medición de concordancia de las respuestas entregadas por los modelos y lo observado, son significativas y sugieren una alta coincidencia entre ellos. ABSTRACT The traditional way of estimating road safety level is the record of occurrence of traffic accidents; however, they are highly variable, random, and require a recording period of at least three years. There are preventive methods which do not need an accident to determine the road safety level of an intersection, such as traffic conflict technique, which introduces surrogate safety measures as parameters for the evaluation of accident risks. The general objective of the thesis is to establish a methodology that will allow the classification of risk at interurban intersections as a function of the analysis of conflicts between vehicles performed by means of surrogate road safety variables. The proposal of a methodology for the analysis and early evaluation of safety at an intersection will be based on two surrogate safety measures: the time to collision and the post encroachment time. On the other hand, the experimental development has taken place by means of field studies in which the exploratory part of the investigation selected three interurban T-intersections where the application of the traffic conflict technique gave variables that characterize the conflicts between vehicles; then, using multivariate analysis techniques, the models for the classification of qualitative and quantitative risk were obtained. With the models new field studies were carried out at six interurban Tintersections with the purpose of developing the homologation and the final study of the agreement between the proposed index and the classification model. The risk index obtained is a very useful tool for making rapid evaluations to estimate the hazard of a T-intersection, as well as for getting simply and economically the field data records after a fast training of the workers and then preparing the report of results by a specialist. The risk indices obtained show that the most influential original variables are the measurements of time. It was determined that the highest risk index values are related with greater risk of a conflict resulting in an accident. Within this index, the only variable whose contribution is proportionally direct is the approach speed, in agreement with what happens in a conflict, because excessive speed appears as a clear risk factor at an intersection because it intensifies all the human driving faults. One of the main contributions of this doctoral thesis to road engineering is the possibility of applying the methodology by local road administrations, which very often have limited investment resources to carry out these kinds of preventive studies, particularly in developing countries. The evaluation of the risk at an intersection after an improvement in terms of infrastructure and/or traffic control devices, the same as a before/after analysis, without comparison of accident occurrence but by means of the traffic conflict technique, can become a direct and economical application. It is also shown that main components analysis used for producing the risk index of the intersection is a useful tool for summarizing the whole set of measurements that can be obtained with the traffic conflict technique and allow diagnosing accident risk at an intersection. As to the methodology for the homologation of the models, the validity and reliability of the set of responses delivered by the observers recording the field data could be established, because the results of the validation show that agreement between the observations and the responses delivered by the models is significant and highly coincident.

Mathematical and Numerical Modeling in Maritime Geomechanics

A theoretical and numerical framework to model the foundation of marine offshore structures is presented. The theoretical model is composed by a system of partial differential equations describing coupling between seabed solid skeleton and pore fluids (water, air, oil,…) combined with a system of ordinary differential equations describing the specific constitutive relation of the seabed soil skeleton. Once the theoretical model is described, the finite element numerical procedure to achieve an approximate solution of the governing equations is outlined. In order to validate the proposed theoretical and numerical framework the seaward tilt mechanism induced by the action of breaking waves over a vertical breakwater is numerically reproduced. The results numerically attained are in agreement with the main conclusions drawn from the literature associated with this failure mechanism

De los proyectos al programa en el ámbito público: nuevo modelo de evaluación del empleo en la Comunidad de Madrid.

Regarding different programmes belonging to the public sphere, it is essential to have proper tools able to quickly provide accurate data related to impacts generated by its projects. This aspect, along with the actual use of this data is essential for proper planning. This communication presents the system designed for project-based evaluation of the employment programs in the Community of Madrid. This system aims to provide fast and reliable information by relying on a combination of qualitative and quantitative methods from existing information and structures. Another contribution of the designed system is the implementation of the Empowerment Evaluation as a tool to encourage the incorporation of evaluation results to the planning processes in a systematic way.

Mechanical and chemical unfolding of a single protein: A comparison

Is the mechanical unraveling of protein domains by atomic force microscopy (AFM) just a technological feat or a true measurement of their unfolding? By engineering a protein made of tandem repeats of identical Ig modules, we were able to get explicit AFM data on the unfolding rate of a single protein domain that can be accurately extrapolated to zero force. We compare this with chemical unfolding rates for untethered modules extrapolated to 0 M denaturant. The unfolding rates obtained by the two methods are the same. Furthermore, the transition state for unfolding appears at the same position on the folding pathway when assessed by either method. These results indicate that mechanical unfolding of a single protein by AFM does indeed reflect the same event that is observed in traditional unfolding experiments. The way is now open for the extensive use of AFM to measure folding reactions at the single-molecule level. Single-molecule AFM recordings have the added advantage that they define the reaction coordinate and expose rare unfolding events that cannot be observed in the absence of chemical denaturants.

Dynamic and quantitative Ca2+ measurements using improved cameleons

Cameleons are genetically-encoded fluorescent indicators for Ca2+ based on green fluorescent protein variants and calmodulin (CaM). Because cameleons can be targeted genetically and imaged by one- or two-photon excitation microscopy, they offer great promise for monitoring Ca2+ in whole organisms, tissues, organelles, and submicroscopic environments in which measurements were previously impossible. However, the original cameleons suffered from significant pH interference, and their Ca2+-buffering and cross-reactivity with endogenous CaM signaling pathways was uncharacterized. We have now greatly reduced the pH-sensitivity of the cameleons by introducing mutations V68L and Q69K into the acceptor yellow green fluorescent protein. The resulting new cameleons permit Ca2+ measurements despite significant cytosolic acidification. When Ca2+ is elevated, the CaM and CaM-binding peptide fused together in a cameleon predominantly interact with each other rather than with free CaM and CaM-dependent enzymes. Therefore, if cameleons are overexpressed, the primary effect is likely to be the unavoidable increase in Ca2+ buffering rather than specific perturbation of CaM-dependent signaling.