Targeting medication non-adherence behavior in selected autoimmune diseases: a systematic approach to digital health program development

Background 29 autoimmune diseases, including Rheumatoid Arthritis, gout, Crohn’s Disease, and Systematic Lupus Erythematosus affect 7.6-9.4% of the population. While effective therapy is available, many patients do not follow treatment or use medications as directed. Digital health and Web 2.0 interventions have demonstrated much promise in increasing medication and treatment adherence, but to date many Internet tools have proven disappointing. In fact, most digital interventions continue to suffer from high attrition in patient populations, are burdensome for healthcare professionals, and have relatively short life spans. Objective Digital health tools have traditionally centered on the transformation of existing interventions (such as diaries, trackers, stage-based or cognitive behavioral therapy programs, coupons, or symptom checklists) to electronic format. Advanced digital interventions have also incorporated attributes of Web 2.0 such as social networking, text messaging, and the use of video. Despite these efforts, there has not been little measurable impact in non-adherence for illnesses that require medical interventions, and research must look to other strategies or development methodologies. As a first step in investigating the feasibility of developing such a tool, the objective of the current study is to systematically rate factors of non-adherence that have been reported in past research studies. Methods Grounded Theory, recognized as a rigorous method that facilitates the emergence of new themes through systematic analysis, data collection and coding, was used to analyze quantitative, qualitative and mixed method studies addressing the following autoimmune diseases: Rheumatoid Arthritis, gout, Crohn’s Disease, Systematic Lupus Erythematosus, and inflammatory bowel disease. Studies were only included if they contained primary data addressing the relationship with non-adherence. Results Out of the 27 studies, four non-modifiable and 11 modifiable risk factors were discovered. Over one third of articles identified the following risk factors as common contributors to medication non-adherence (percent of studies reporting): patients not understanding treatment (44%), side effects (41%), age (37%), dose regimen (33%), and perceived medication ineffectiveness (33%). An unanticipated finding that emerged was the need for risk stratification tools (81%) with patient-centric approaches (67%). Conclusions This study systematically identifies and categorizes medication non-adherence risk factors in select autoimmune diseases. Findings indicate that patients understanding of their disease and the role of medication are paramount. An unexpected finding was that the majority of research articles called for the creation of tailored, patient-centric interventions that dispel personal misconceptions about disease, pharmacotherapy, and how the body responds to treatment. To our knowledge, these interventions do not yet exist in digital format. Rather than adopting a systems level approach, digital health programs should focus on cohorts with heterogeneous needs, and develop tailored interventions based on individual non-adherence patterns.

Ecological and social drivers of coffee pollination in Santander, Colombia

Bees and other insects provide pollination services that are key to determining the fruit set on coffee plantations. These pollination services are influenced by local ecology as well as human factors, both social and economic. To better understand these different factors, we assessed their effect on pollinators and coffee pollination services in Santander, Colombia. We quantified the effect of key ecological drivers on pollinator community composition, such as the method of farm management (either conventional or organic) and the surrounding landscape composition, specifically the proximity to forest. We found that ambient levels of pollination services provided by the local pollinator fauna (open pollination) accounted for a 10.5 ± 2.0% increase in final coffee fruit set, and that the various pollinators are affected differently by the differing factors. For example, our findings indicate that conventional farm management, using synthetic inputs, can promote pollinators, especially if they are in close proximity to natural forest fragments. This is particularly true for stingless bees. Honeybee visitation to coffee is also positively influenced by the conventional management of farms. Factors associated with greater numbers of stingless bees on farms include greater shade cover, lower tree densities, smaller numbers and types of trees in bloom, and younger coffee plantations. A forested landscape close to farms appears to enhance these factors, giving increased stability and resilience to the pollinating bees and insects. However we found that organic farms also support diverse pollinator communities, even if distant from forest fragments. The contribution of honeybees to pollination value (US$129.6/ha of coffee) is greater than that of stingless bees (US$16.5/ha of coffee). Since the method of farm management has a major impact on the numbers and types of pollinators attracted to farms, we have analysed the statistically significant social factors that influence farmers’ decisions on whether to adopt organic or conventional practices. These include the availability of technology, the type of landowner (whether married couples or individual owners), the number of years of farmers’ formal education, the role of institutions, membership of community organizations, farm size, coffee productivity and the number of coffee plots per farm. It is hoped that the use of our holistic approach, which combines investigation of the social as well as the ecological drivers of pollination, will help provide evidence to underpin the development of best practices for integrating the management of pollination into sustainable agricultural practices.

Ki-67 and Bcl-2 Antigen Expression in Adenomatous Colorectal Polyps from Women with Breast Cancer

Background. The aim of this study was to evaluate Ki-67 and Bcl-2 antigen expression in colorectal polyps from women with breast cancer. Methods. A randomized, controlled study was carried out in 35 women, either with or without breast cancer, who had adenomatous colorectal polyps. The patients were divided into two groups: group A (without breast cancer; control group; n = 17) and group B (with breast cancer; study group; n = 18). Immunohistochemistry was performed on the colorectal polyps to evaluate Ki-67 and Bcl-2 antigen expression. Student`s t-test and the chi(2) test were used for the statistical analysis of Ki-67 and Bcl-2 expression, respectively. Statistical significance was established as P < 0.05. Results. The mean percentage of Ki-67-stained nuclei in groups A and B was 36.25 +/- 2.31 and 59.44 +/- 3.34 ( SEM), respectively (P < 0.0001), while the percentage of cases with cells expressing Bcl-2 in groups A and B was 23.5 and 77.8%, respectively (P < 0.001). Conclusions. In the present study, there was greater proliferative activity and greater expression of the antiapoptotic protein Bcl-2 in the colorectal polyps of women with breast cancer.

Analysis of Ki-67 and Bcl-2 protein expression in normal colorectal mucosa of women with breast cancer

The aim of this study was to evaluate Ki-67 and Bcl-2 protein expression in the normal colorectal mucosa adjacent to adenomatous polyps in women with breast cancer. A cross-sectional, controlled study was conducted in 35 women with and without breast cancer who had adenomatous colorectal polyps. The patients were divided into two groups: Group A (a control group of women without breast cancer, n = 18) and Group B (a study group of women with breast cancer, n = 17). A sample of normal colonic mucosa was collected at a distance of 5 cm from the polypoid lesion to evaluate immunchistochemical expression of the Ki-67 and Bcl-2 proteins. Student`s t-test and the chi-square test were used to analyse Ki-67 and Bcl-2 expression, respectively. Statistical significance was established at p < 0.05. The mean percentage of Ki-67-stained nuclei in Groups A and B was 25.12 +/- 2.08 and 41.50 +/- 1.85, respectively (p < 0.001), whereas the percentage of cases with cells expressing Bcl-2 in Groups A and B was 17.6% and 82.4%, respectively (p < 0.003). In the present study, greater proliferative activity and greater expression of the antiapoptotic protein Bcl-2 was found in the normal colorectal mucosa of women with breast cancer. (C) 2009 Elsevier Ltd. All rights reserved.

Optimization heuristic solutions, how good can they be? : With empirical applications in location problems

Combinatorial optimization problems, are one of the most important types of problems in operational research. Heuristic and metaheuristics algorithms are widely applied to find a good solution. However, a common problem is that these algorithms do not guarantee that the solution will coincide with the optimum and, hence, many solutions to real world OR-problems are afflicted with an uncertainty about the quality of the solution. The main aim of this thesis is to investigate the usability of statistical bounds to evaluate the quality of heuristic solutions applied to large combinatorial problems. The contributions of this thesis are both methodological and empirical. From a methodological point of view, the usefulness of statistical bounds on p-median problems is thoroughly investigated. The statistical bounds have good performance in providing informative quality assessment under appropriate parameter settings. Also, they outperform the commonly used Lagrangian bounds. It is demonstrated that the statistical bounds are shown to be comparable with the deterministic bounds in quadratic assignment problems. As to empirical research, environment pollution has become a worldwide problem, and transportation can cause a great amount of pollution. A new method for calculating and comparing the CO2-emissions of online and brick-and-mortar retailing is proposed. It leads to the conclusion that online retailing has significantly lesser CO2-emissions. Another problem is that the Swedish regional division is under revision and the border effect to public service accessibility is concerned of both residents and politicians. After analysis, it is shown that borders hinder the optimal location of public services and consequently the highest achievable economic and social utility may not be attained.

Teacher’s leadership in web-based language courses in Dalarna University, Sweden

The purpose of this presentation is to discuss how teacher’s leadership can be used as a teaching method in web based language education. The environments that offer online courses provide a wide field for discussion on the contact between teacher and student. My intention is to contribute to the debate on teacher leadership in online courses. In my earlier studies on leadership, I have explored how some religious leaders affected different social movements in Brazil during the military dictatorship (1964-1985). Pruth (2004) by examining the three kinds of legitimacy described by Max Weber I aimed at seeing and analyzing how religious leaders used different teaching methods to explain their messages to ordinary citizens. Thus my research showed how educational leadership is a way to get people to reach their goals. I became interested in the subject teacher’s leadership whenI participated in a survey of the teaching methods of language courses in Dalarna University which is funded by the NGL Center of Dalarna University. In  this project, we have made interviews with the teachers, undertaken the course plans (in the language department at Dalarna University) and categorized the learning outcomes. A questionnaire was constructed based on the learning outcomes and then either sent out remotely to teachers or completed face to face through interviews. The answers provided to the questionnaires enabled the  project to identify many differences in how language teachers interact with their students but  also, the way of giving feedback, motivating and helping students, types of class activities and materials used. This made me aware of how teachers use their leadership or not in their teaching. My focus is to look at the relationship between teachers and students as an important part of the development and quality of online courses. The teacher's performance on campus is different from online courses. I want to understand how the contact between teachers and students in online courses develop and look at how students can make use of this contact and what influence the teacher's leadership has on the ability for the students to achieve the goals of their course

Facebook3d

INTRODUCTION With the advent of Web 2.0, social networking websites like Facebook, MySpace and LinkedIn have become hugely popular. According to (Nilsen, 2009), social networking websites have global1 figures of almost 250 millions unique users among the top five2, with the time people spend on those networks increasing 63% between 2007 and 2008. Facebook alone saw a massive growth of 566% in number of minutes in the same period of time. Furthermore their appeal is clear, they enable users to easily form persistent networks of friends with whom they can interact and share content. Users then use those networks to keep in touch with their current friends and to reconnect with old friends. However, online social network services have rapidly evolved into highly complex systems which contain a large amount of personally salient information derived from large networks of friends. Since that information varies from simple links to music, photos and videos, users not only have to deal with the huge amount of data generated by them and their friends but also with the fact that it‟s composed of many different media forms. Users are presented with increasing challenges, especially as the number of friends on Facebook rises. An example of a problem is when a user performs a simple task like finding a specific friend in a group of 100 or more friends. In that case he would most likely have to go through several pages and make several clicks till he finds the one he is looking for. Another example is a user with more than 100 friends in which his friends make a status update or another action per day, resulting in 10 updates per hour to keep up. That is plausible, especially since the change in direction of Facebook to rival with Twitter, by encouraging users to update their status as they do on Twitter. As a result, to better present the web of information connected to a user the use of better visualizations is essential. The visualizations used nowadays on social networking sites haven‟t gone through major changes during their lifetimes. They have added more functionality and gave more tools to their users, but still the core of their visualization hasn‟t changed. The information is still presented in a flat way in lists/groups of text and images which can‟t show the extra connections pieces of information. Those extra connections can give new meaning and insights to the user, allowing him to more easily see if that content is important to him and the information related to it. However showing extra connections of information but still allowing the user to easily navigate through it and get the needed information with a quick glance is difficult. The use of color coding, clusters and shapes becomes then essential to attain that objective. But taking into consideration the advances in computer hardware in the last decade and the software platforms available today, there is the opportunity to take advantage of 3D. That opportunity comes in because we are at a phase were the hardware and the software available is ready for the use of 3D in the web. With the use of the extra dimension brought by 3D, visualizations can be constructed to show the content and its related information to the user at the same screen and in a clear way. Also it would allow a great deal of interactivity. Another opportunity to create better information‟s visualization presents itself in the form of the open APIs, specifically the ones made available by the social networking sites. Those APIs allow any developers to create their own applications or sites taking advantage of the huge amount of information there is on those networks. Specifically to this case, they open the door for the creation of new social network visualizations. Nevertheless, the third dimension is by itself not enough to create a better interface for a social networking website, there are some challenges to overcome. One of those challenges is to make the user understand what the system is doing during the interaction with the user. Even though that is important in 2D visualizations, it becomes essential in 3D due to the extra dimension. To overcome that challenge it‟s necessary the use of the principles of animations defined by the artists at Walt Disney Studios (Johnston, et al., 1995). By applying those principles in the development of the interface, the actions of the system in response to the user inputs became clear and understandable. Furthermore, a user study needs to be performed so the users‟ main goals and motivations, while navigating the social network, are revealed. Their goals and motivations are important in the construction of an interface that reflects the user expectations for the interface, but also helps in the development of appropriate metaphors. Those metaphors have an important role in the interface, because if correctly chosen they help the user understand the elements of the interface instead of making him memorize it. The last challenge is the use of 3D visualization on the web, since there have been several attempts to bring 3D into it, mainly with the various versions of VRML which were destined to failure due to the hardware limitations at the time. However, in the last couple of years there has been a movement to make the necessary tools to finally allow developers to use 3D in a useful way, using X3D or OpenGL but especially flash. This thesis argues that there is a need for a better social network visualization that shows all the dimensions of the information connected to the user and that allows him to move through it. But there are several characteristics the new visualization has to possess in order for it to present a real gain in usability to Facebook‟s users. The first quality is to have the friends at the core of its design, and the second to make use of the metaphor of circles of friends to separate users in groups taking into consideration the order of friendship. To achieve that several methods have to be used, from the use of 3D to get an extra dimension for presenting relevant information, to the use of direct manipulation to make the interface comprehensible, predictable and controllable. Moreover animation has to be use to make all the action on the screen perceptible to the user. Additionally, with the opportunity given by the 3D enabled hardware, the flash platform, through the use of the flash engine Papervision3D and the Facebook platform, all is in place to make the visualization possible. But even though it‟s all in place, there are challenges to overcome like making the system actions in 3D understandable to the user and creating correct metaphors that would allow the user to understand the information and options available to him. This thesis document is divided in six chapters, with Chapter 2 reviewing the literature relevant to the work described in this thesis. In Chapter 3 the design stage that resulted in the application presented in this thesis is described. In Chapter 4, the development stage, describing the architecture and the components that compose the application. In Chapter 5 the usability test process is explained and the results obtained through it are presented and analyzed. To finish, Chapter 6 presents the conclusions that were arrived in this thesis.

Prognostic significance of beta-2 adrenergic receptor in oral squamous cell carcinoma

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A framework for monitoring and runtime recovery of web service-based applications

Service provisioning is a challenging research area for the design and implementation of autonomic service-oriented software systems. It includes automated QoS management for such systems and their applications. Monitoring, Diagnosis and Repair are three key features of QoS management. This work presents a self-healing Web service-based framework that manages QoS degradation at runtime. Our approach is based on proxies. Proxies act on meta-level communications and extend the HTTP envelope of the exchanged messages with QoS-related parameter values. QoS Data are filtered over time and analysed using statistical functions and the Hidden Markov Model. Detected QoS degradations are handled with proxies. We experienced our framework using an orchestrated electronic shop application (FoodShop).

Reduced pancreatic β-cell mass is associated with decreased FoxO1 and Erk1/2 protein phosphorylation in low-protein malnourished rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Increased pancreatic islet mass is accompanied by activation of the insulin receptor substrate-2/serine-threonine kinase pathway and augmented cyclin D(2) protein levels in insulin-resistant rats

It is well known that glucocorticoids induce peripheral insulin resistance in rodents and humans. Here, we investigated the structural and ultrastructural modifications, as well as the proteins involved in beta-cell function and proliferation, in islets from insulin-resistant rats. Adult male Wistar rats were made insulin resistant by daily administration of dexamethasone (DEX; 1mg/kg, i.p.) for five consecutive days, whilst control (CTL) rats received saline alone. Structure analyses showed a marked hypertrophy of DEX islets with an increase of 1.7-fold in islet mass and of 1.6-fold in islet density compared with CTL islets (P < 0.05). Ultrastructural evaluation of islets revealed an increased amount of secreting organelles, such as endoplasmic reticulum and Golgi apparatus in DEX islets. Mitotic figures were observed in DEX islets at structural and ultrastructural levels. Beta-cell proliferation, evaluated at the immunohistochemical level using anti-PCNA (proliferating cell nuclear antigen), showed an increase in pancreatic beta-cell proliferation of 6.4-fold in DEX islets compared with CTL islets (P < 0.0001). Increases in insulin receptor substrate-2 (IRS-2), phosphorylated-serine-threonine kinase AKT (p-AKT), cyclin D(2) and a decrease in retinoblastoma protein (pRb) levels were observed in DEX islets compared with CTL islets (P < 0.05). Therefore, during the development of insulin resistance, the endocrine pancreas adapts itself increasing beta-cell mass and proliferation, resulting in an amelioration of the functions. The potential mechanisms that underlie these events involve the activation of the IRS-2/AKT pathway and activation of the cell cycle, mediated by cyclin D(2). These adaptations permit the maintenance of glycaemia at near-physiological ranges.

A Methodology for Building Service-Oriented Applications in the Presence of Non-Functional Properties

This thesis presents ⇡SOD-M (Policy-based Service Oriented Development Methodology), a methodology for modeling reliable service-based applications using policies. It proposes a model driven method with: (i) a set of meta-models for representing non-functional constraints associated to service-based applications, starting from an use case model until a service composition model; (ii) a platform providing guidelines for expressing the composition and the policies; (iii) model-to-model and model-to-text transformation rules for semi-automatizing the implementation of reliable service-based applications; and (iv) an environment that implements these meta-models and rules, and enables the application of ⇡SOD-M. This thesis also presents a classification and nomenclature for non-functional requirements for developing service-oriented applications. Our approach is intended to add value to the development of service-oriented applications that have quality requirements needs. This work uses concepts from the service-oriented development, non-functional requirements design and model-driven delevopment areas to propose a solution that minimizes the problem of reliable service modeling. Some examples are developed as proof of concepts

Direito autoral e tecnologias de informação e comunicação no contexto da produção, uso e disseminação de informação: um olhar para as Licenças Creative Commons

The development of information and communication technologies, in particular, Internet, and its Web 2.0 information environment has led to significant changes in contemporary society as to the ways of producing informational content. Collaboration and remix, favored by the new services and applications resulting from the development of the Web, are practices which contribute for the exponential growth of information producers. An important part of humanity ceases to be a mere consumer of symbolic goods and becomes a member in a society that sees in the collaboration and remix a new form of creation, use and dissemination of intellectual content. However, as such practices involve the production and use of information intelectual content, and are ruled by a legisltion which determine determines under what conditions the author and the user must produce and use the intellectual work. This legislation established for a context prior to the develompment of the Web has created an imbalance in the context of Web 2.0 which needs to be solved in some way so as to provide the required rebalance for the flow of information. This study explores the collaborative Web environment, the scope of copyright law in Web enviroment and the Creative Commons licenses as an alternative for producers and users of information to create, recreate, share, use, reuse and disseminate legally the intellectual production for the benefit of the construction of knowledge.

JCircus 2.0: Uma extensão da ferramenta de tradução de Circus para Java

This dissertation aims at extending the JCircus tool, a translator of formal specifications into code that receives a Circus specification as input, and translates the specification into Java code. Circus is a formal language whose syntax is based on Z s and CSP s syntax. JCircus generated code uses JCSP, which is a Java API that implements CSP primitives. As JCSP does not implement all CSP s primitives, the translation strategy from Circus to Java is not trivial. Some CSP primitives, like parallelism, external choice, communication and multi-synchronization are partially implemented. As an aditional scope, this dissertation will also develop a tool for testing JCSP programs, called JCSPUnit, which will also be included in JCircus new version. The extended version of JCircus will be called JCircus 2.0.