Theoretical and experimental studies of linkage disequilibrium in human populations

Linkage disequilibrium (LD) is defined as the nonrandom association of alleles at two or more loci in a population and may be a useful tool in a diverse array of applications including disease gene mapping, elucidating the demographic history of populations, and testing hypotheses of human evolution. However, the successful application of LD-based approaches to pertinent genetic questions is hampered by a lack of understanding about the forces that mediate the genome-wide distribution of LD within and between human populations. Delineating the genomic patterns of LD is a complex task that will require interdisciplinary research that transcends traditional scientific boundaries. The research presented in this dissertation is predicated upon the need for interdisciplinary studies and both theoretical and experimental projects were pursued. In the theoretical studies, I have investigated the effect of genotyping errors and SNP identification strategies on estimates of LD. The primary importance of these two chapters is that they provide important insights and guidance for the design of future empirical LD studies. Furthermore, I analyzed the allele frequency distribution of 26,530 single nucleotide polymorphisms (SNPs) in three populations and generated the first-generation natural selection map of the human genome, which will be an important resource for explaining and understanding genomic patterns of LD. Finally, in the experimental study, I describe a novel and simple, low-cost, and high-throughput SNP genotyping method. The theoretical analyses and experimental tools developed in this dissertation will facilitate a more complete understanding of patterns of LD in human populations. ^

Economic Rights, Human Development Effort and Institutions

This paper focuses on the link between economic rights and institutions. Simple analysis of data is used to demonstrate countries' human development effort in advancing economics rights of the citizens. A country's human development effort is evaluated on the basis of the well-being of the poorest members of the society. An analysis of data reveals that there is a wide variation in countries' pro-poor stance. While it is accepted that positive rights are pro-poor, this paper argues that so too are negative economic rights and in fact the two are complements rather than substitutes. Classifying countries into human development income deficit and human development effort deficit, it is demonstrated that a large number of countries could achieve higher welfare levels for the poor if they improved on bother positive and negative economic rights. The paper attempts to explain variations in the observed commitment to economic rights by focusing on pro-poor institutions. The basic thesis advanced in the paper is that pro-poor policies are more likely to be implemented and sustained in those institutions where power is sufficiently diffused such that even the poor have leverage over policy outcomes. The paper focuses on how institutions impact on power diffusion and therefore the adoption of pro-poor growth and policies. The failure of countries to adopt pro-poor growth and policies is attributed to institutional failures manifested in concentration of power. The policy recommendations emanating from the analysis focus on institutional reforms to enhance power diffusion. These policies include enlarging the political space through democratization, strengthening institutions and capacity to fight corruption and improve transparency, and bringing the government closer to the people through appropriate design and implementation of decentralization schemes. Some recent examples of improvements in economic rights following power diffusion are provided.

The effects of proteasome inhibition on angiogenesis and autophagy in human prostate cancer cells

The proteasome degrades approximately 80% of intracellular proteins to maintain homeostasis. Proteasome inhibition is a validated therapeutic strategy, and currently, proteasome inhibitor bortezomib is FDA approved for the treatment of MM and MCL. Specific pathways affected by proteasome inhibition have been identified, but mechanisms of the anti-tumor effects of proteasome inhibition are not fully characterized and cancer cells display marked heterogeneity in terms of their sensitivity to proteasome inhibitor induced cell death. ^ The antitumor effects of proteasome inhibition involve suppression of tumor angiogenesis and vascular endothelial growth factor (VEGF) expression, but the mechanisms involved have not been clarified. In this dissertation I investigated the mechanisms underlying the effects of two proteasome inhibitors, bortezomib and NPI-0052, on VEGF expression in human prostate cancer cells. I found that proteasome inhibitors selectively downregulated hypoxia inducible factor 1alpha (HIF-1α) protein and its transcriptional activity to inhibit VEGF expression. Mechanistic studies demonstrated that proteasome inhibitors mediate the induction of the unfolded protein response (UPR) and that downregulation of HIF-1α is caused by eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and translation repression. Importantly, I showed that proteasome inhibitors activated the UPR in some cells but not in others. My observation may have implications for the design of combination regimens that are based on exploiting proteasome inhibitor-induced ER stress.^ Although proteasome inhibitors have shown modest activity on prostate cancer, there is general consensus that no single agent is likely to have significant activity in prostate cancer. In the second part of this dissertation I attempted to exploit the effects of proteasome inhibition on the UPR to design a combination therapy that would enhance cancer cell death. Autophagy is a lysosome dependent degradation pathway that functions to eliminate long-lived protein and subcellular structures. Targeting autophagy has been shown to inhibit tumors in preclinical studies. I found that inhibition of autophagy with chloroquine or 3-methyladenine enhanced proteasome inhibitor induced cell death and the effects were associated with increased intracellular stress as marked by aggresome formation. Multiple cancers appear to be resistant to proteasome inhibition treatment alone. The implications of synergy for the combined inhibition of autophagy and the proteasome would likely apply to other cancers aside from prostate cancer. ^

Environmental sustainability and the human element: Decision making in National Cancer Institute-designated cancer centers and Practice Greenhealth subscribing institutions

Background. Various aspects of sustainability have taken root in the hospital environment; however, decisions to pursue sustainable practices within the framework of a master plan are not fully developed in National Cancer Institute (NCI) -designated cancer centers and subscribing institutions to the Practice Greenhealth (PGH) listserv.^ Methods. This cross sectional study was designed to identify the organizational characteristics each study group pursed to implement sustainability practices, describe the barriers they encountered and reasons behind their choices for undertaking certain sustainability practices. A web-based questionnaire was pilot tested, and then sent out to 64 NCI-designated cancer centers and 1638 subscribing institutions to the PGH listserv.^ Results. Complete responses were received from 39 NCI-designated cancer centers and 58 subscribing institutions to the PGH listserv. NCI-designated cancer centers reported greater progress in integrating sustainability criteria into design and construction projects than hospitals of institutions subscribing to the PHG listserv (p-value = <0.05). Statistically significant differences were also identified between these two study groups in undertaking work life options, conducting energy usage assessments, developing energy conservation and optimization plans, implementing solid waste and hazardous waste minimization programs, using energy efficient vehicles and reporting sustainability progress to external stakeholders. NCI-designated cancer centers were further along in implementing these programs (p-value = <0.05). In comparing the self-identified NCI-designated cancer centers to centers that indicated they were both and NCI and PGH, the later had made greater progress in using their collective buying power to pursue sustainable purchasing practices within the medical community (p-value = <0.05). In both study groups, recycling programs were well developed.^ Conclusions. Employee involvement was viewed as the most important reason for both study groups to pursue recycling initiatives and incorporated environmental criteria into purchasing decisions. A written sustainability commitment did not readily translate into a high percentage that had developed a sustainability master plan. Coordination of sustainability programs through a designated sustainability professional was not being undertaken by a large number of institutions within each study group. This may be due to the current economic downturn or management's attention to the emerging health care legislation being debated in congress. ^ Lifecycle assessments, an element of a carbon footprint, are seen as emerging areas of opportunity for health care institutions that can be used to evaluate the total lifecycle costs of products and services.^

Houston Rescue and Restore Coalition human trafficking needs assessment

Background. Human trafficking, or "modern day slavery", is a complex public health issue that we must understand more fully before it can be effectively tackled. There have been very few empirical studies on human trafficking and estimates of global and national human trafficking victims vary widely. Free the Slaves, a non-profit organization, estimates that there are at least 27 million people in the world at any given time that can be classified as victims of human trafficking. Houston, Texas has been identified as a place where human trafficking may be more likely to exist due to its close proximity to Mexico and due to economic and population factors. Houston Rescue and Restore Coalition (HRRC) is a local organization that exists to raise awareness of human trafficking in Houston, Texas. To better serve victims of human trafficking, HRRC commissioned a community assessment of the services available to victims of human trafficking in the greater Houston metropolitan area.^ Purpose. The current study assessed the capacity of organizations and agencies within the greater Houston metropolitan area to deal with human trafficking issues; in particular, knowledge regarding human trafficking issues among these organizations and agencies was evaluated.^ Methods. A cross-sectional study design was used to conduct surveys with key informants/stakeholders from organizations and agencies within the greater Houston metropolitan area. The survey instrument included 41 items in three parts, and consisted of multiple choice questions, open-ended essay questions, and closed-ended 5 point Likert questions.^ Results. The findings from this study indicate that efforts must be made to increase comprehensive awareness of the issue of human trafficking, including the federal and state laws that have been enacted to combat this problem. The data also indicate that there are limited services provided to human trafficking victims within the greater Houston metropolitan area.^ Conclusion. The results of the survey will provide Houston Rescue and Restore Coalition with information that will assist them in targeting their efforts to combat human trafficking in Houston, Texas.^

A comprehensive review of the environmental impacts and human health risks associated with the occurrence of waste pharmaceuticals in water sources of the United States, and policy implications

The occurrence of waste pharmaceuticals has been identified and well documented in water sources throughout North America and Europe. Many studies have been conducted which identify the occurrence of various pharmaceutical compounds in these waters. This project is an extensive review of the documented evidence of this occurrence published in the scientific literature. This review was performed to determine if this occurrence has a significant impact on the environment and public health. This project and review found that pharmaceuticals such as sex hormone drugs, antibiotic drugs and antineoplastic/cytostatic agents as well as their metabolites have been found to occur in water sources throughout the United States at levels high enough to have noticeable impacts on human health and the environment. It was determined that the primary sources of this occurrence of pharmaceuticals were waste water effluent and solid wastes from sewage treatment plants, pharmaceutical manufacturing plants, healthcare and biomedical research facilities, as well as runoff from veterinary medicine applications (including aquaculture). ^ In addition, current public policies of US governmental agencies such as the Environmental Protection Agency (EPA), Food and Drug Administration (FDA), and Drug Enforcement Agency (DEA) have been evaluated to see if they are doing a sufficient job at controlling this issue. Specific recommendations for developing these EPA, FDA, and DEA policies have been made to mitigate, prevent, or eliminate this issue.^ Other possible interventions such as implementing engineering controls were also evaluated in order to mitigate, prevent and eliminate this issue. These engineering controls include implementing improved current treatment technologies such as the advancement and improvement of waste water treatment processes utilized by conventional sewage treatment and pharmaceutical manufacturing plants. In addition, administrative controls such as the use of “green chemistry” in drug synthesis and design were also explored and evaluated as possible alternatives to mitigate, prevent, or eliminate this issue. Specific recommendations for incorporating these engineering and administrative controls into the applicable EPA, FDA, and DEA policies have also been made.^

An evaluation of sleep hypnotic and stimulant effect on human performance using a computerized psychological test battery

This study evaluated the administration-time-dependent effects of a stimulant (Dexedrine 5-mg), a sleep-inducer (Halcion 0.25-mg) and placebo (control) on human performance. The investigation was conducted on 12 diurnally active (0700-2300) male adults (23-38 yrs) using a double-blind, randomized sixway-crossover three-treatment, two-timepoint (0830 vs 2030) design. Performance tests were conducted hourly during sleepless 13-hour studies using a computer generated, controlled and scored multi-task cognitive performance assessment battery (PAB) developed at the Walter Reed Army Institute of Research. Specific tests were Simple and Choice Reaction Time, Serial Addition/Subtraction, Spatial Orientation, Logical Reasoning, Time Estimation, Response Timing and the Stanford Sleepiness Scale. The major index of performance was "Throughput", a combined measure of speed and accuracy.^ For the Placebo condition, Single and Group Cosinor Analysis documented circadian rhythms in cognitive performance for the majority of tests, both for individuals and for the group. Performance was best around 1830-2030 and most variable around 0530-0700 when sleepiness was greatest (0300).^ Morning Dexedrine dosing marginally enhanced performance an average of 3% with reference to the corresponding in time control level. Dexedrine AM also increased alertness by 10% over the AM control. Dexedrine PM failed to improve performance with reference to the corresponding PM control baseline. With regard to AM and PM Dexedrine administrations, AM performance was 6% better with subjects 25% more alert.^ Morning Halcion administration caused a 7% performance decrement and 16% increase in sleepiness and a 13% decrement and 10% increase in sleepiness when administered in the evening compared to corresponding in time control data. Performance was 9% worse and sleepiness 24% greater after evening versus morning Halcion administration.^ These results suggest that for evening Halcion dosing, the overnight sleep deprivation occurring in coincidence with the nadir in performance due to circadian rhythmicity together with the CNS depressant effects combine to produce performance degradation. For Dexedrine, morning administration resulted in only marginal performance enhancement; Dexedrine in the evening was less effective, suggesting the 5-mg dose level may be too low to counteract the partial sleep deprivation and nocturnal nadir in performance. ^

Design of long-term animal bioassay for low-dose extrapolation using a multistage model

Conventional designs of animal bioassays allocate the same number of animals into control and dose groups to explore the spontaneous and induced tumor incidence rates, respectively. The purpose of such bioassays are (a) to determine whether or not the substance exhibits carcinogenic properties, and (b) if so, to estimate the human response at relatively low doses. In this study, it has been found that the optimal allocation to the experimental groups which, in some sense, minimize the error of the estimated response for low dose extrapolation is associated with the dose level and tumor risk. The number of dose levels has been investigated at the affordable experimental cost. The pattern of the administered dose, 1 MTD, 1/2 MTD, 1/4 MTD,....., etc. plus control, gives the most reasonable arrangement for the low dose extrapolation purpose. The arrangement of five dose groups may make the highest dose trivial. A four-dose design can circumvent this problem and has also one degree of freedom for testing the goodness-of-fit of the response model.^ An example using the data on liver tumors induced in mice in a lifetime study of feeding dieldrin (Walker et al., 1973) is implemented with the methodology. The results are compared with conclusions drawn from other studies. ^

The SanaViz: Human Centered Geovisualization to facilitate visual exploration of Public Health data

These three manuscripts are presented as a PhD dissertation for the study of using GeoVis application to evaluate telehealth programs. The primary reason of this research was to understand how the GeoVis applications can be designed and developed using combined approaches of HC approach and cognitive fit theory and in terms utilized to evaluate telehealth program in Brazil. First manuscript The first manuscript in this dissertation presented a background about the use of GeoVisualization to facilitate visual exploration of public health data. The manuscript covered the existing challenges that were associated with an adoption of existing GeoVis applications. The manuscript combines the principles of Human Centered approach and Cognitive Fit Theory and a framework using a combination of these approaches is developed that lays the foundation of this research. The framework is then utilized to propose the design, development and evaluation of “the SanaViz” to evaluate telehealth data in Brazil, as a proof of concept. Second manuscript The second manuscript is a methods paper that describes the approaches that can be employed to design and develop “the SanaViz” based on the proposed framework. By defining the various elements of the HC approach and CFT, a mixed methods approach is utilized for the card sorting and sketching techniques. A representative sample of 20 study participants currently involved in the telehealth program at the NUTES telehealth center at UFPE, Recife, Brazil was enrolled. The findings of this manuscript helped us understand the needs of the diverse group of telehealth users, the tasks that they perform and helped us determine the essential features that might be necessary to be included in the proposed GeoVis application “the SanaViz”. Third manuscript The third manuscript involved mix- methods approach to compare the effectiveness and usefulness of the HC GeoVis application “the SanaViz” against a conventional GeoVis application “Instant Atlas”. The same group of 20 study participants who had earlier participated during Aim 2 was enrolled and a combination of quantitative and qualitative assessments was done. Effectiveness was gauged by the time that the participants took to complete the tasks using both the GeoVis applications, the ease with which they completed the tasks and the number of attempts that were taken to complete each task. Usefulness was assessed by System Usability Scale (SUS), a validated questionnaire tested in prior studies. In-depth interviews were conducted to gather opinions about both the GeoVis applications. This manuscript helped us in the demonstration of the usefulness and effectiveness of HC GeoVis applications to facilitate visual exploration of telehealth data, as a proof of concept. Together, these three manuscripts represent challenges of combining principles of Human Centered approach, Cognitive Fit Theory to design and develop GeoVis applications as a method to evaluate Telehealth data. To our knowledge, this is the first study to explore the usefulness and effectiveness of GeoVis to facilitate visual exploration of telehealth data. The results of the research enabled us to develop a framework for the design and development of GeoVis applications related to the areas of public health and especially telehealth. The results of our study showed that the varied users were involved with the telehealth program and the tasks that they performed. Further it enabled us to identify the components that might be essential to be included in these GeoVis applications. The results of our research answered the following questions; (a) Telehealth users vary in their level of understanding about GeoVis (b) Interaction features such as zooming, sorting, and linking and multiple views and representation features such as bar chart and choropleth maps were considered the most essential features of the GeoVis applications. (c) Comparing and sorting were two important tasks that the telehealth users would perform for exploratory data analysis. (d) A HC GeoVis prototype application is more effective and useful for exploration of telehealth data than a conventional GeoVis application. Future studies should be done to incorporate the proposed HC GeoVis framework to enable comprehensive assessment of the users and the tasks they perform to identify the features that might be necessary to be a part of the GeoVis applications. The results of this study demonstrate a novel approach to comprehensively and systematically enhance the evaluation of telehealth programs using the proposed GeoVis Framework.

A simulation study of the standard design, the rolling six design, the CRM, and the modified CRM in Phase I clinical trials

The Phase I clinical trial is considered the "first in human" study in medical research to examine the toxicity of a new agent. It determines the maximum tolerable dose (MTD) of a new agent, i.e., the highest dose in which toxicity is still acceptable. Several phase I clinical trial designs have been proposed in the past 30 years. The well known standard method, so called the 3+3 design, is widely accepted by clinicians since it is the easiest to implement and it does not need a statistical calculation. Continual reassessment method (CRM), a design uses Bayesian method, has been rising in popularity in the last two decades. Several variants of the CRM design have also been suggested in numerous statistical literatures. Rolling six is a new method introduced in pediatric oncology in 2008, which claims to shorten the trial duration as compared to the 3+3 design. The goal of the present research was to simulate clinical trials and compare these phase I clinical trial designs. Patient population was created by discrete event simulation (DES) method. The characteristics of the patients were generated by several distributions with the parameters derived from a historical phase I clinical trial data review. Patients were then selected and enrolled in clinical trials, each of which uses the 3+3 design, the rolling six, or the CRM design. Five scenarios of dose-toxicity relationship were used to compare the performance of the phase I clinical trial designs. One thousand trials were simulated per phase I clinical trial design per dose-toxicity scenario. The results showed the rolling six design was not superior to the 3+3 design in terms of trial duration. The time to trial completion was comparable between the rolling six and the 3+3 design. However, they both shorten the duration as compared to the two CRM designs. Both CRMs were superior to the 3+3 design and the rolling six in accuracy of MTD estimation. The 3+3 design and rolling six tended to assign more patients to undesired lower dose levels. The toxicities were slightly greater in the CRMs.^

Software Design Guidelines for Usability

For years, the Human Computer Interaction (HCI) community has crafted usability guidelines that clearly define what characteristics a software system should have in order to be easy to use. However, in the Software Engineering (SE) community keep falling short of successfully incorporating these recommendations into software projects. From a SE perspective, the process of incorporating usability features into software is not always straightforward, as a large number of these features have heavy implications in the underlying software architecture. For example, successfully including an “undo” feature in an application requires the design and implementation of many complex interrelated data structures and functionalities. Our work is focused upon providing developers with a set of software design patterns to assist them in the process of designing more usable software. This would contribute to the proper inclusion of specific usability features with high impact on the software design. Preliminary validation data show that usage of the guidelines also has positive effects on development time and overall software design quality.

Using the Journalistic Metaphor to Design User Interfaces That Explain Sensor Data

Facilitating general access to data from sensor networks (including traffic, hydrology and other domains) increases their utility. In this paper we argue that the journalistic metaphor can be effectively used to automatically generate multimedia presentations that help non-expert users analyze and understand sensor data. The journalistic layout and style are familiar to most users. Furthermore, the journalistic approach of ordering information from most general to most specific helps users obtain a high-level understanding while providing them the freedom to choose the depth of analysis to which they want to go. We describe the general characteristics and architectural requirements for an interactive intelligent user interface for exploring sensor data that uses the journalistic metaphor. We also describe our experience in developing this interface in real-world domains (e.g., hydrology).

On the biomimetic design of agile-robot legs

The development of functional legged robots has encountered its limits in human-made actuation technology. This paper describes research on the biomimetic design of legs for agile quadrupeds. A biomimetic leg concept that extracts key principles from horse legs which are responsible for the agile and powerful locomotion of these animals is presented. The proposed biomimetic leg model defines the effective leg length, leg kinematics, limb mass distribution, actuator power, and elastic energy recovery as determinants of agile locomotion, and values for these five key elements are given. The transfer of the extracted principles to technological instantiations is analyzed in detail, considering the availability of current materials, structures and actuators. A real leg prototype has been developed following the biomimetic leg concept proposed. The actuation system is based on the hybrid use of series elasticity and magneto-rheological dampers which provides variable compliance for natural motion. From the experimental evaluation of this prototype, conclusions on the current technological barriers to achieve real functional legged robots to walk dynamically in agile locomotion are presented.

Contributions to the contextualization of human-machine spoken interaction systems

The design and development of spoken interaction systems has been a thoroughly studied research scope for the last decades. The aim is to obtain systems with the ability to interact with human agents with a high degree of naturalness and efficiency, allowing them to carry out the actions they desire using speech, as it is the most natural means of communication between humans. To achieve that degree of naturalness, it is not enough to endow systems with the ability to accurately understand the user’s utterances and to properly react to them, even considering the information provided by the user in his or her previous interactions. The system has also to be aware of the evolution of the conditions under which the interaction takes place, in order to act the most coherent way as possible at each moment. Consequently, one of the most important features of the system is that it has to be context-aware. This context awareness of the system can be reflected in the modification of the behaviour of the system taking into account the current situation of the interaction. For instance, the system should decide which action it has to carry out, or the way to perform it, depending on the user that requests it, on the way that the user addresses the system, on the characteristics of the environment in which the interaction takes place, and so on. In other words, the system has to adapt its behaviour to these evolving elements of the interaction. Moreover that adaptation has to be carried out, if possible, in such a way that the user: i) does not perceive that the system has to make any additional effort, or to devote interaction time to perform tasks other than carrying out the requested actions, and ii) does not have to provide the system with any additional information to carry out the adaptation, which could imply a lesser efficiency of the interaction, since users should devote several interactions only to allow the system to become adapted. In the state-of-the-art spoken dialogue systems, researchers have proposed several disparate strategies to adapt the elements of the system to different conditions of the interaction (such as the acoustic characteristics of a specific user’s speech, the actions previously requested, and so on). Nevertheless, to our knowledge there is not any consensus on the procedures to carry out these adaptation. The approaches are to an extent unrelated from one another, in the sense that each one considers different pieces of information, and the treatment of that information is different taking into account the adaptation carried out. In this regard, the main contributions of this Thesis are the following ones: Definition of a contextualization framework. We propose a unified approach that can cover any strategy to adapt the behaviour of a dialogue system to the conditions of the interaction (i.e. the context). In our theoretical definition of the contextualization framework we consider the system’s context as all the sources of variability present at any time of the interaction, either those ones related to the environment in which the interaction takes place, or to the human agent that addresses the system at each moment. Our proposal relies on three aspects that any contextualization approach should fulfill: plasticity (i.e. the system has to be able to modify its behaviour in the most proactive way taking into account the conditions under which the interaction takes place), adaptivity (i.e. the system has also to be able to consider the most appropriate sources of information at each moment, both environmental and user- and dialogue-dependent, to effectively adapt to the conditions aforementioned), and transparency (i.e. the system has to carry out the contextualizaton-related tasks in such a way that the user neither perceives them nor has to do any effort in providing the system with any information that it needs to perform that contextualization). Additionally, we could include a generality aspect to our proposed framework: the main features of the framework should be easy to adopt in any dialogue system, regardless of the solution proposed to manage the dialogue. Once we define the theoretical basis of our contextualization framework, we propose two cases of study on its application in a spoken dialogue system. We focus on two aspects of the interaction: the contextualization of the speech recognition models, and the incorporation of user-specific information into the dialogue flow. One of the modules of a dialogue system that is more prone to be contextualized is the speech recognition system. This module makes use of several models to emit a recognition hypothesis from the user’s speech signal. Generally speaking, a recognition system considers two types of models: an acoustic one (that models each of the phonemes that the recognition system has to consider) and a linguistic one (that models the sequences of words that make sense for the system). In this work we contextualize the language model of the recognition system in such a way that it takes into account the information provided by the user in both his or her current utterance and in the previous ones. These utterances convey information useful to help the system in the recognition of the next utterance. The contextualization approach that we propose consists of a dynamic adaptation of the language model that is used by the recognition system. We carry out this adaptation by means of a linear interpolation between several models. Instead of training the best interpolation weights, we make them dependent on the conditions of the dialogue. In our approach, the system itself will obtain these weights as a function of the reliability of the different elements of information available, such as the semantic concepts extracted from the user’s utterance, the actions that he or she wants to carry out, the information provided in the previous interactions, and so on. One of the aspects more frequently addressed in Human-Computer Interaction research is the inclusion of user specific characteristics into the information structures managed by the system. The idea is to take into account the features that make each user different from the others in order to offer to each particular user different services (or the same service, but in a different way). We could consider this approach as a user-dependent contextualization of the system. In our work we propose the definition of a user model that contains all the information of each user that could be potentially useful to the system at a given moment of the interaction. In particular we will analyze the actions that each user carries out throughout his or her interaction. The objective is to determine which of these actions become the preferences of that user. We represent the specific information of each user as a feature vector. Each of the characteristics that the system will take into account has a confidence score associated. With these elements, we propose a probabilistic definition of a user preference, as the action whose likelihood of being addressed by the user is greater than the one for the rest of actions. To include the user dependent information into the dialogue flow, we modify the information structures on which the dialogue manager relies to retrieve information that could be needed to solve the actions addressed by the user. Usage preferences become another source of contextual information that will be considered by the system towards a more efficient interaction (since the new information source will help to decrease the need of the system to ask users for additional information, thus reducing the number of turns needed to carry out a specific action). To test the benefits of the contextualization framework that we propose, we carry out an evaluation of the two strategies aforementioned. We gather several performance metrics, both objective and subjective, that allow us to compare the improvements of a contextualized system against the baseline one. We will also gather the user’s opinions as regards their perceptions on the behaviour of the system, and its degree of adaptation to the specific features of each interaction. Resumen El diseño y el desarrollo de sistemas de interacción hablada ha sido objeto de profundo estudio durante las pasadas décadas. El propósito es la consecución de sistemas con la capacidad de interactuar con agentes humanos con un alto grado de eficiencia y naturalidad. De esta manera, los usuarios pueden desempeñar las tareas que deseen empleando la voz, que es el medio de comunicación más natural para los humanos. A fin de alcanzar el grado de naturalidad deseado, no basta con dotar a los sistemas de la abilidad de comprender las intervenciones de los usuarios y reaccionar a ellas de manera apropiada (teniendo en consideración, incluso, la información proporcionada en previas interacciones). Adicionalmente, el sistema ha de ser consciente de las condiciones bajo las cuales transcurre la interacción, así como de la evolución de las mismas, de tal manera que pueda actuar de la manera más coherente en cada instante de la interacción. En consecuencia, una de las características primordiales del sistema es que debe ser sensible al contexto. Esta capacidad del sistema de conocer y emplear el contexto de la interacción puede verse reflejada en la modificación de su comportamiento debida a las características actuales de la interacción. Por ejemplo, el sistema debería decidir cuál es la acción más apropiada, o la mejor manera de llevarla a término, dependiendo del usuario que la solicita, del modo en el que lo hace, etcétera. En otras palabras, el sistema ha de adaptar su comportamiento a tales elementos mutables (o dinámicos) de la interacción. Dos características adicionales son requeridas a dicha adaptación: i) el usuario no ha de percibir que el sistema dedica recursos (temporales o computacionales) a realizar tareas distintas a las que aquél le solicita, y ii) el usuario no ha de dedicar esfuerzo alguno a proporcionar al sistema información adicional para llevar a cabo la interacción. Esto último implicaría una menor eficiencia de la interacción, puesto que los usuarios deberían dedicar parte de la misma a proporcionar información al sistema para su adaptación, sin ningún beneficio inmediato. En los sistemas de diálogo hablado propuestos en la literatura, se han propuesto diferentes estrategias para llevar a cabo la adaptación de los elementos del sistema a las diferentes condiciones de la interacción (tales como las características acústicas del habla de un usuario particular, o a las acciones a las que se ha referido con anterioridad). Sin embargo, no existe una estrategia fija para proceder a dicha adaptación, sino que las mismas no suelen guardar una relación entre sí. En este sentido, cada una de ellas tiene en cuenta distintas fuentes de información, la cual es tratada de manera diferente en función de las características de la adaptación buscada. Teniendo en cuenta lo anterior, las contribuciones principales de esta Tesis son las siguientes: Definición de un marco de contextualización. Proponemos un criterio unificador que pueda cubrir cualquier estrategia de adaptación del comportamiento de un sistema de diálogo a las condiciones de la interacción (esto es, el contexto de la misma). En nuestra definición teórica del marco de contextualización consideramos el contexto del sistema como todas aquellas fuentes de variabilidad presentes en cualquier instante de la interacción, ya estén relacionadas con el entorno en el que tiene lugar la interacción, ya dependan del agente humano que se dirige al sistema en cada momento. Nuestra propuesta se basa en tres aspectos que cualquier estrategia de contextualización debería cumplir: plasticidad (es decir, el sistema ha de ser capaz de modificar su comportamiento de la manera más proactiva posible, teniendo en cuenta las condiciones en las que tiene lugar la interacción), adaptabilidad (esto es, el sistema ha de ser capaz de considerar la información oportuna en cada instante, ya dependa del entorno o del usuario, de tal manera que adecúe su comportamiento de manera eficaz a las condiciones mencionadas), y transparencia (que implica que el sistema ha de desarrollar las tareas relacionadas con la contextualización de tal manera que el usuario no perciba la manera en que dichas tareas se llevan a cabo, ni tampoco deba proporcionar al sistema con información adicional alguna). De manera adicional, incluiremos en el marco propuesto el aspecto de la generalidad: las características del marco de contextualización han de ser portables a cualquier sistema de diálogo, con independencia de la solución propuesta en los mismos para gestionar el diálogo. Una vez hemos definido las características de alto nivel de nuestro marco de contextualización, proponemos dos estrategias de aplicación del mismo a un sistema de diálogo hablado. Nos centraremos en dos aspectos de la interacción a adaptar: los modelos empleados en el reconocimiento de habla, y la incorporación de información específica de cada usuario en el flujo de diálogo. Uno de los módulos de un sistema de diálogo más susceptible de ser contextualizado es el sistema de reconocimiento de habla. Este módulo hace uso de varios modelos para generar una hipótesis de reconocimiento a partir de la señal de habla. En general, un sistema de reconocimiento emplea dos tipos de modelos: uno acústico (que modela cada uno de los fonemas considerados por el reconocedor) y uno lingüístico (que modela las secuencias de palabras que tienen sentido desde el punto de vista de la interacción). En este trabajo contextualizamos el modelo lingüístico del reconocedor de habla, de tal manera que tenga en cuenta la información proporcionada por el usuario, tanto en su intervención actual como en las previas. Estas intervenciones contienen información (semántica y/o discursiva) que puede contribuir a un mejor reconocimiento de las subsiguientes intervenciones del usuario. La estrategia de contextualización propuesta consiste en una adaptación dinámica del modelo de lenguaje empleado en el reconocedor de habla. Dicha adaptación se lleva a cabo mediante una interpolación lineal entre diferentes modelos. En lugar de entrenar los mejores pesos de interpolación, proponemos hacer los mismos dependientes de las condiciones actuales de cada diálogo. El propio sistema obtendrá estos pesos como función de la disponibilidad y relevancia de las diferentes fuentes de información disponibles, tales como los conceptos semánticos extraídos a partir de la intervención del usuario, o las acciones que el mismo desea ejecutar. Uno de los aspectos más comúnmente analizados en la investigación de la Interacción Persona-Máquina es la inclusión de las características específicas de cada usuario en las estructuras de información empleadas por el sistema. El objetivo es tener en cuenta los aspectos que diferencian a cada usuario, de tal manera que el sistema pueda ofrecer a cada uno de ellos el servicio más apropiado (o un mismo servicio, pero de la manera más adecuada a cada usuario). Podemos considerar esta estrategia como una contextualización dependiente del usuario. En este trabajo proponemos la definición de un modelo de usuario que contenga toda la información relativa a cada usuario, que pueda ser potencialmente utilizada por el sistema en un momento determinado de la interacción. En particular, analizaremos aquellas acciones que cada usuario decide ejecutar a lo largo de sus diálogos con el sistema. Nuestro objetivo es determinar cuáles de dichas acciones se convierten en las preferencias de cada usuario. La información de cada usuario quedará representada mediante un vector de características, cada una de las cuales tendrá asociado un valor de confianza. Con ambos elementos proponemos una definición probabilística de una preferencia de uso, como aquella acción cuya verosimilitud es mayor que la del resto de acciones solicitadas por el usuario. A fin de incluir la información dependiente de usuario en el flujo de diálogo, llevamos a cabo una modificación de las estructuras de información en las que se apoya el gestor de diálogo para recuperar información necesaria para resolver ciertos diálogos. En dicha modificación las preferencias de cada usuario pasarán a ser una fuente adicional de información contextual, que será tenida en cuenta por el sistema en aras de una interacción más eficiente (puesto que la nueva fuente de información contribuirá a reducir la necesidad del sistema de solicitar al usuario información adicional, dando lugar en consecuencia a una reducción del número de intervenciones necesarias para llevar a cabo una acción determinada). Para determinar los beneficios de las aplicaciones del marco de contextualización propuesto, llevamos a cabo una evaluación de un sistema de diálogo que incluye las estrategias mencionadas. Hemos recogido diversas métricas, tanto objetivas como subjetivas, que nos permiten determinar las mejoras aportadas por un sistema contextualizado en comparación con el sistema sin contextualizar. De igual manera, hemos recogido las opiniones de los participantes en la evaluación acerca de su percepción del comportamiento del sistema, y de su capacidad de adaptación a las condiciones concretas de cada interacción.

Analysis and design of multiagent systems using MAS-CommonKADS

This article proposes an agent-oriented methodology called MAS-CommonKADS and develops a case study. This methodology extends the knowledge engineering methodology CommonKADSwith techniquesfrom objectoriented and protocol engineering methodologies. The methodology consists of the development of seven models: Agent Model, that describes the characteristics of each agent; Task Model, that describes the tasks that the agents carry out; Expertise Model, that describes the knowledge needed by the agents to achieve their goals; Organisation Model, that describes the structural relationships between agents (software agents and/or human agents); Coordination Model, that describes the dynamic relationships between software agents; Communication Model, that describes the dynamic relationships between human agents and their respective personal assistant software agents; and Design Model, that refines the previous models and determines the most suitable agent architecture for each agent, and the requirements of the agent network.