Strengthening the Reporting of Observational Studies in Epidemiology for respondent-driven sampling studies: "STROBE-RDS" statement.

OBJECTIVES Respondent-driven sampling (RDS) is a new data collection methodology used to estimate characteristics of hard-to-reach groups, such as the HIV prevalence in drug users. Many national public health systems and international organizations rely on RDS data. However, RDS reporting quality and available reporting guidelines are inadequate. We carried out a systematic review of RDS studies and present Strengthening the Reporting of Observational Studies in Epidemiology for RDS Studies (STROBE-RDS), a checklist of essential items to present in RDS publications, justified by an explanation and elaboration document. STUDY DESIGN AND SETTING We searched the MEDLINE (1970-2013), EMBASE (1974-2013), and Global Health (1910-2013) databases to assess the number and geographical distribution of published RDS studies. STROBE-RDS was developed based on STROBE guidelines, following Guidance for Developers of Health Research Reporting Guidelines. RESULTS RDS has been used in over 460 studies from 69 countries, including the USA (151 studies), China (70), and India (32). STROBE-RDS includes modifications to 12 of the 22 items on the STROBE checklist. The two key areas that required modification concerned the selection of participants and statistical analysis of the sample. CONCLUSION STROBE-RDS seeks to enhance the transparency and utility of research using RDS. If widely adopted, STROBE-RDS should improve global infectious diseases public health decision making.

Service level agreements-driven management of distributed applications in cloud computing environments

Advancements in cloud computing have enabled the proliferation of distributed applications, which require management and control of multiple services. However, without an efficient mechanism for scaling services in response to changing workload conditions, such as number of connected users, application performance might suffer, leading to violations of Service Level Agreements (SLA) and possible inefficient use of hardware resources. Combining dynamic application requirements with the increased use of virtualised computing resources creates a challenging resource Management context for application and cloud-infrastructure owners. In such complex environments, business entities use SLAs as a means for specifying quantitative and qualitative requirements of services. There are several challenges in running distributed enterprise applications in cloud environments, ranging from the instantiation of service VMs in the correct order using an adequate quantity of computing resources, to adapting the number of running services in response to varying external loads, such as number of users. The application owner is interested in finding the optimum amount of computing and network resources to use for ensuring that the performance requirements of all her/his applications are met. She/he is also interested in appropriately scaling the distributed services so that application performance guarantees are maintained even under dynamic workload conditions. Similarly, the infrastructure Providers are interested in optimally provisioning the virtual resources onto the available physical infrastructure so that her/his operational costs are minimized, while maximizing the performance of tenants’ applications. Motivated by the complexities associated with the management and scaling of distributed applications, while satisfying multiple objectives (related to both consumers and providers of cloud resources), this thesis proposes a cloud resource management platform able to dynamically provision and coordinate the various lifecycle actions on both virtual and physical cloud resources using semantically enriched SLAs. The system focuses on dynamic sizing (scaling) of virtual infrastructures composed of virtual machines (VM) bounded application services. We describe several algorithms for adapting the number of VMs allocated to the distributed application in response to changing workload conditions, based on SLA-defined performance guarantees. We also present a framework for dynamic composition of scaling rules for distributed service, which used benchmark-generated application Monitoring traces. We show how these scaling rules can be combined and included into semantic SLAs for controlling allocation of services. We also provide a detailed description of the multi-objective infrastructure resource allocation problem and various approaches to satisfying this problem. We present a resource management system based on a genetic algorithm, which performs allocation of virtual resources, while considering the optimization of multiple criteria. We prove that our approach significantly outperforms reactive VM-scaling algorithms as well as heuristic-based VM-allocation approaches.

Biomechanical evaluation of different angle-stable locking plate systems for mandibular surgery

PURPOSE To compare the initial stability and stability after fatigue of three different locking systems (Synthes(®), Stryker(®) and Medartis(®)) for mandibular fixation and reconstruction. METHOD Standard mandible locking plates with identical profile height (1,5 mm), comparable length and screws with identical diameter (2,0 mm) were used. Plates were fixed with six screws according a preparation protocol. Four point bending tests were then performed using artificial bone material to compare their initial stability and failure limit under realistic loading conditions. Loading of the plates was performed using of a servo hydraulic driven testing machine. The stiffness of the implant/bone construct was calculated using a linear regression on the experimental data included in a range of applied moment between 2 Nm and 6 Nm. RESULTS No statistical difference in the elastic stiffness was visible between the three types of plate. However, differences were observed between the systems concerning the maximal load supported. The Stryker and Synthes systems were able to support a significantly higher moment. CONCLUSION For clinical application all systems show good and reliable results. Practical aspects such as handling, possible angulation of screw fixation, possibility of screw/plate removal, etc. may favour one or the other plating system.

Binary recombinase systems for high-resolution conditional mutagenesis.

Conditional mutagenesis using Cre recombinase expressed from tissue specific promoters facilitates analyses of gene function and cell lineage tracing. Here, we describe two novel dual-promoter-driven conditional mutagenesis systems designed for greater accuracy and optimal efficiency of recombination. Co-Driver employs a recombinase cascade of Dre and Dre-respondent Cre, which processes loxP-flanked alleles only when both recombinases are expressed in a predetermined temporal sequence. This unique property makes Co-Driver ideal for sequential lineage tracing studies aimed at unraveling the relationships between cellular precursors and mature cell types. Co-InCre was designed for highly efficient intersectional conditional transgenesis. It relies on highly active trans-splicing inteins and promoters with simultaneous transcriptional activity to reconstitute Cre recombinase from two inactive precursor fragments. By generating native Cre, Co-InCre attains recombination rates that exceed all other binary SSR systems evaluated in this study. Both Co-Driver and Co-InCre significantly extend the utility of existing Cre-responsive alleles.

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

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

Systems Biology Approaches to Probe Gene Regulation in Bacteria

Mechanisms that allow pathogens to colonize the host are not the product of isolated genes, but instead emerge from the concerted operation of regulatory networks. Therefore, identifying components and the systemic behavior of networks is necessary to a better understanding of gene regulation and pathogenesis. To this end, I have developed systems biology approaches to study transcriptional and post-transcriptional gene regulation in bacteria, with an emphasis in the human pathogen Mycobacterium tuberculosis (Mtb). First, I developed a network response method to identify parts of the Mtb global transcriptional regulatory network utilized by the pathogen to counteract phagosomal stresses and survive within resting macrophages. As a result, the method unveiled transcriptional regulators and associated regulons utilized by Mtb to establish a successful infection of macrophages throughout the first 14 days of infection. Additionally, this network-based analysis identified the production of Fe-S proteins coupled to lipid metabolism through the alkane hydroxylase complex as a possible strategy employed by Mtb to survive in the host. Second, I developed a network inference method to infer the small non-coding RNA (sRNA) regulatory network in Mtb. The method identifies sRNA-mRNA interactions by integrating a priori knowledge of possible binding sites with structure-driven identification of binding sites. The reconstructed network was useful to predict functional roles for the multitude of sRNAs recently discovered in the pathogen, being that several sRNAs were postulated to be involved in virulence-related processes. Finally, I applied a combined experimental and computational approach to study post-transcriptional repression mediated by small non-coding RNAs in bacteria. Specifically, a probabilistic ranking methodology termed rank-conciliation was developed to infer sRNA-mRNA interactions based on multiple types of data. The method was shown to improve target prediction in Escherichia coli, and therefore is useful to prioritize candidate targets for experimental validation.

Pathway Semantics: An Algebraic Data Driven Algorithm to Generate Hypotheses about Molecular Patterns Underlying Disease Progression

The overarching goal of the Pathway Semantics Algorithm (PSA) is to improve the in silico identification of clinically useful hypotheses about molecular patterns in disease progression. By framing biomedical questions within a variety of matrix representations, PSA has the flexibility to analyze combined quantitative and qualitative data over a wide range of stratifications. The resulting hypothetical answers can then move to in vitro and in vivo verification, research assay optimization, clinical validation, and commercialization. Herein PSA is shown to generate novel hypotheses about the significant biological pathways in two disease domains: shock / trauma and hemophilia A, and validated experimentally in the latter. The PSA matrix algebra approach identified differential molecular patterns in biological networks over time and outcome that would not be easily found through direct assays, literature or database searches. In this dissertation, Chapter 1 provides a broad overview of the background and motivation for the study, followed by Chapter 2 with a literature review of relevant computational methods. Chapters 3 and 4 describe PSA for node and edge analysis respectively, and apply the method to disease progression in shock / trauma. Chapter 5 demonstrates the application of PSA to hemophilia A and the validation with experimental results. The work is summarized in Chapter 6, followed by extensive references and an Appendix with additional material.

(Table S1) Diatom abundance in coastal upwelling systems

Coastal upwelling systems account for approximately half of global ocean primary production and contribute disproportionately to biologically driven carbon sequestration. Diatoms, silica-precipitating microalgae, constitute the dominant phytoplankton in these productive regions, and their abundance and assemblage composition in the sedimentary record is considered one of the best proxies for primary production. The study of the sedimentary diatom abundance (SDA) and total organic carbon content (TOC) in the five most important coastal upwelling systems of the modern ocean (Iberia-Canary, Benguela, Peru-Humboldt, California and Somalia-Oman) reveals a global-scale positive relationship between diatom production and organic carbon burial. The analysis of SDA in conjunction with environmental variables of coastal upwelling systems such as upwelling strength, satellite-derived net primary production and surface water nutrient concentrations shows different relations between SDA and primary production on the regional scale. At the global-scale, SDA appears modulated by the capacity of diatoms to take up silicic acid, which ultimately sets an upper limit to global export production in these ocean regions.

Communication: Transition State Theory for dissipative systems without a dividing surface

Transition state theory is a central cornerstone in reaction dynamics. Its key step is the identification of a dividing surface that is crossed only once by all reactive trajectories. This assumption is often badly violated, especially when the reactive system is coupled to an environment. The calculations made in this way then overestimate the reaction rate and the results depend critically on the choice of the dividing surface. In this Communication, we study the phase space of a stochastically driven system close to an energetic barrier in order to identify the geometric structure unambiguously determining the reactive trajectories, which is then incorporated in a simple rate formula for reactions in condensed phase that is both independent of the dividing surface and exact.

Adaptive fuzzy knowledge-based systems for control metabots' mobility on virtual environments

The confluence of three-dimensional (3D) virtual worlds with social networks imposes on software agents, in addition to conversational functions, the same behaviours as those common to human-driven avatars. In this paper, we explore the possibilities of the use of metabots (metaverse robots) with motion capabilities in complex virtual 3D worlds and we put forward a learning model based on the techniques used in evolutionary computation for optimizing the fuzzy controllers which will subsequently be used by metabots for moving around a virtual environment.

A policy-driven architecture for supporting joint degrees through e-learning services

En un mercado de educación superior cada vez más competitivo, la colaboración entre universidades es una efectiva estrategia para acceder al mercado global. El desarrollo de titulaciones conjuntas es un importante mecanismo para fortalecer las colaboraciones académicas y diversificar los conocimientos. Las titulaciones conjuntas están siendo cada vez más implementadas en las universidades de todo el mundo. En Europa, el proceso de Bolonia y el programa Erasmus, están fomentado el reconocimiento de titulaciones conjuntas y dobles y promoviendo la colaboración entre las instituciones académicas. En el imparable proceso de la globalización y convergencia educativa, el uso de sistemas de e-learning para soportar cursos tanto semipresencial como online es una tendencia en crecimiento. Dado que los sistemas de e-learning soportan una amplia variedad de cursos, es necesario encontrar una solución adecuada que permita a las universidades soportar y gestionar las titulaciones conjuntas a través de sus sistemas de e-learning en conformidad con los acuerdos de colaboración establecidos por las universidades participantes. Esta tesis doctoral abordará las siguientes preguntas de investigación: 1. ¿Qué factores deben tenerse en cuenta en la implementación y gestión de titulaciones conjuntas? 2. ¿Cómo pueden los sistemas actuales de e-learning soportar el desarrollo de titulaciones conjuntas? 3. ¿Qué otros servicios y sistemas necesitan ser adaptados por las universidades interesadas en participar en una titulación conjunta a través de sus sistemas de e-learning? La implementación de titulaciones conjuntas a través de sistemas de e-learning es compleja e implica retos técnicos, administrativos, culturales, financieros, jurídicos y de seguridad. Esta tesis doctoral propone una serie de contribuciones que pueden ayudar a resolver algunos de los retos identificados. En primer lugar se ha elaborado un modelo conceptual que incluye la información del contexto de las titulaciones conjuntas que es relevante para la implementación de estas titulaciones en los sistemas de e-learning. Después de definir el modelo conceptual, se ha propuesto una arquitectura basada en políticas para la implementación de titulaciones interinstitucionales a través de sistemas de e-learning de acuerdo a los términos estipulados en los acuerdos de colaboración que son firmados por las universidades participantes. El autor se ha centrado en el componente de gestión de flujos de trabajo de esta arquitectura. Por último y con el fin de permitir la interoperabilidad de repositorios de objetos educativos, los componentes básicos a implementar han sido identificados y validados. El uso de servicios multimedia en educación es una tendencia creciente, proporcionando servicios de e-learning que permiten mejorar la comunicación y la interacción entre profesores y alumnos. Dentro de estos servicios, nos hemos centrado en el uso de la videoconferencia y la grabación de clases como servicios adecuados para el desarrollo de cursos impartidos en escenarios de educación colaborativos. Las contribuciones han sido validadas en proyectos de investigación de ámbito nacional y europeo en los que el autor ha participado. Abstract In an increasingly competitive higher education market, collaboration between universities is an effective strategy for gaining access to the global market. The development of joint degrees is an important mechanism for strengthening academic research collaborations and diversifying knowledge. Joint degrees are becoming increasingly implemented in universities around the world. In Europe, the Bologna process and the Erasmus programme have encouraged both the global recognition of joint and double degrees and promoted close collaboration between academic institutions. In the unstoppable process of globalization and educational convergence, the use of e-learning systems for supporting both blended and online courses is becoming a growing trend. Since e-learning systems covers a wide range of courses, it becomes necessary to find a suitable solution that enables universities to support and manage joint degrees through their e-learning systems in accordance with the collaboration agreements established by the universities involved. This dissertation will address the following research questions: 1. What factors need to be considered in the implementation and management of joint degrees? 2. How can the current e-learning systems support the development of joint degrees? 3. What other services and systems need to be adapted by universities interested in participating in a joint degree through their e-learning systems? The implementation of joint degrees using e-learning systems is complex and involves technical, administrative, security, cultural, financial and legal challenges. This dissertation proposes a series of contributions to help solve some of the identified challenges. One of the cornerstones of this proposal is a conceptual model of all the relevant issues related to the support of joint degrees by means of e-learning systems. After defining the conceptual model, this dissertation proposes a policy-driven architecture for implementing inter-institutional degree collaborations through e-learning systems as stipulated by a collaboration agreement signed by two universities. The author has focused on the workflow management component of this architecture. Finally, the building blocks for achieving interoperability of learning object repositories have been identified and validated. The use of multimedia services in education is a growing trend, providing rich e-learning services that improve the communication and interaction between teachers and students. Within these e-learning services, we have focused on the use of videoconferencing and lecture recording as the best-suited services to support collaborative learning scenarios. The contributions have been validated within national and European research projects that the author has been involved in.

Autonomous vehicle control systems for safe crossroads

This article presents a cooperative manoeuvre among three dual mode cars – vehicles equipped with sensors and actuators, and that can be driven either manually or autonomously. One vehicle is driven autonomously and the other two are driven manually. The main objective is to test two decision algorithms for priority conflict resolution at intersections so that a vehicle autonomously driven can take their own decision about crossing an intersection mingling with manually driven cars without the need for infrastructure modifications. To do this, the system needs the position, speeds, and turning intentions of the rest of the cars involved in the manoeuvre. This information is acquired via communications, but other methods are also viable, such as artificial vision. The idea of the experiments was to adjust the speed of the manually driven vehicles to force a situation where all three vehicles arrive at an intersection at the same time.

Implementation of an event driven scheme for visualizing parallel execution of logic programs

This article presents in an informal way some early results on the design of a series of paradigms for visualization of the parallel execution of logic programs. The results presented here refer to the visualization of or-parallelism, as in MUSE and Aurora, deterministic dependent and-parallelism, as in Andorra-I, and independent and-parallelism as in &-Prolog. A tool has been implemented for this purpose and has been interfaced with these systems. Results are presented showing the visualization of executions from these systems and the usefulness of the resulting tool is briefly discussed.

Towards data-aware cost-driven adaptation for service orchestrations.

Several activities in service oriented computing, such as automatic composition, monitoring, and adaptation, can benefit from knowing properties of a given service composition before executing them. Among these properties we will focus on those related to execution cost and resource usage, in a wide sense, as they can be linked to QoS characteristics. In order to attain more accuracy, we formulate execution costs / resource usage as functions on input data (or appropriate abstractions thereof) and show how these functions can be used to make better, more informed decisions when performing composition, adaptation, and proactive monitoring. We present an approach to, on one hand, synthesizing these functions in an automatic fashion from the definition of the different orchestrations taking part in a system and, on the other hand, to effectively using them to reduce the overall costs of non-trivial service-based systems featuring sensitivity to data and possibility of failure. We validate our approach by means of simulations of scenarios needing runtime selection of services and adaptation due to service failure. A number of rebinding strategies, including the use of cost functions, are compared.