Different patterns between mechanical and electrical activities: an approach to investigate gastric motility in a model of long-term diabetic rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Computational framework to support integration of biomolecular and clinical data within a translational approach

Background The use of the knowledge produced by sciences to promote human health is the main goal of translational medicine. To make it feasible we need computational methods to handle the large amount of information that arises from bench to bedside and to deal with its heterogeneity. A computational challenge that must be faced is to promote the integration of clinical, socio-demographic and biological data. In this effort, ontologies play an essential role as a powerful artifact for knowledge representation. Chado is a modular ontology-oriented database model that gained popularity due to its robustness and flexibility as a generic platform to store biological data; however it lacks supporting representation of clinical and socio-demographic information. Results We have implemented an extension of Chado – the Clinical Module - to allow the representation of this kind of information. Our approach consists of a framework for data integration through the use of a common reference ontology. The design of this framework has four levels: data level, to store the data; semantic level, to integrate and standardize the data by the use of ontologies; application level, to manage clinical databases, ontologies and data integration process; and web interface level, to allow interaction between the user and the system. The clinical module was built based on the Entity-Attribute-Value (EAV) model. We also proposed a methodology to migrate data from legacy clinical databases to the integrative framework. A Chado instance was initialized using a relational database management system. The Clinical Module was implemented and the framework was loaded using data from a factual clinical research database. Clinical and demographic data as well as biomaterial data were obtained from patients with tumors of head and neck. We implemented the IPTrans tool that is a complete environment for data migration, which comprises: the construction of a model to describe the legacy clinical data, based on an ontology; the Extraction, Transformation and Load (ETL) process to extract the data from the source clinical database and load it in the Clinical Module of Chado; the development of a web tool and a Bridge Layer to adapt the web tool to Chado, as well as other applications. Conclusions Open-source computational solutions currently available for translational science does not have a model to represent biomolecular information and also are not integrated with the existing bioinformatics tools. On the other hand, existing genomic data models do not represent clinical patient data. A framework was developed to support translational research by integrating biomolecular information coming from different “omics” technologies with patient’s clinical and socio-demographic data. This framework should present some features: flexibility, compression and robustness. The experiments accomplished from a use case demonstrated that the proposed system meets requirements of flexibility and robustness, leading to the desired integration. The Clinical Module can be accessed in http://dcm.ffclrp.usp.br/caib/pg=iptrans webcite.

Integrative Musterbildung kranialer Strukturen

Form und Gestalt kraniofazialer Strukturen sind primär beeinflusst durch die inhärente Integration der unterschiedlichsten Funktionssysteme und externer selektiver Einflüsse. Die Variabilität der Schädel-Morphe ist ein Indikator für solche Einflussfaktoren und damit ein idealer Gegenstand für vergleichende Analysen morphogenetischer Formbildung. Zur Ermittlung morphologisch-adaptiver Trends und Muster wurden sowohl Hypothesen zur morphologischen Differenziertheit als auch zu Korrelationen zwischen modularen Schädelkompartimenten (fazial, neurokranial, basikranial) untersucht. Zusätzlich wurden aus Schichtröntgenaufnahmen (CT) virtuelle Modelle rekonstruiert, welche die Interpretation der statistischen Befunde unterstützen sollten. Zur Berechnung der Gestaltunterschiede wurden mittels eines mechanischen Gelenkarm-Messgerätes (MicroScribe-G2) max. 85 ektokraniale Messpunkte (Landmarks) bzw. dreidimensionale Koordinaten an ca. 520 Schädeln von fünf rezenten Gattungen der Überfamilie Hominoidea (Hylobates, Pongo, Gorilla, Pan und Homo) akquiriert. Aus dem Datensatz wurden geometrische Störfaktoren (Größe, Translation, Rotation) mathematisch eliminiert und die verbleibenden Residuale bzw. ‚Gestalt-Variablen‘ diversen multivariat-statistischen Verfahren unterzogen (Faktoren, Cluster-, Regressions- und Korrelationsanalysen sowie statistische Tests). Die angewandten Methoden erhalten die geometrische Information der Untersuchungsobjekte über alle Analyseschritte hinweg und werden unter der Bezeichnung „Geometric Morphometrics (GMM)“ als aktueller Ansatz der Morphometrie zusammengefasst. Für die unterschiedlichen Fragestellungen wurden spezifische Datensätze generiert. Es konnten diverse morphologische Trends und adaptive Muster mit Hilfe der Synthese statistischer Methoden und computer-basierter Rekonstruktionen aus den generierten Datensätzen ermittelt werden. Außerdem war es möglich, präzise zu rekonstruieren, welche kranialen Strukturen innerhalb der Stichprobe miteinander wechselwirken, einzigartige Variabilitäten repräsentieren oder eher homogen gestaltet sind. Die vorliegenden Befunde lassen erkennen, dass Fazial- und Neurokranium am stärksten miteinander korrelieren, während das Basikranium geringe Abhängigkeiten in Bezug auf Gesichts- oder Hirnschädelveränderungen zeigte. Das Basikranium erweist sich zudem bei den nicht-menschlichen Hominoidea und über alle Analysen hinweg als konservative und evolutiv-persistente Struktur mit dem geringsten Veränderungs-Potential. Juvenile Individuen zeigen eine hohe Affinität zueinander und zu Formen mit einem kleinem Gesichts- und großem Hirnschädel. Während das Kranium des rezenten Menschen primär von Enkephalisation und fazialer Retraktion (Orthognathisierung) dominiert ist und somit eine einzigartige Gestalt aufweist, zeigt sich der Kauapparat als maßgeblich formbildendes Kompartiment bei den nicht-menschlichen Formen. Die Verbindung von GMM mit den interaktiven Möglichkeiten computergenerierter Modelle erwies sich als valides Werkzeug zur Erfassung der aufgeworfenen Fragestellungen. Die Interpretation der Befunde ist durch massive Interkorrelationen der untersuchten Strukturen und der statistisch-mathematischen Prozeduren als hoch komplex zu kennzeichnen. Die Studie präsentiert einen innovativen Ansatz der modernen Morphometrie, welcher für zukünftige Untersuchungen im Bereich der kraniofazialen Gestaltanalyse ausgebaut werden könnte. Dabei verspricht die Verknüpfung mit ‚klassischen’ und modernen Zugängen (z. B. Molekularbiologie) gesteigerte Erkenntnismöglichkeiten für künftige morphometrische Fragestellungen.

Monitoring pollution in river Mure , Romania, Part III: biochemical effect markers in fish and integrative reflection

Along a downstream stretch of River Mure , Romania, adult males of two feral fish species, European chub (Leuciscus cephalus) and sneep (Chondrostoma nasus) were sampled at four sites with different levels of contamination. Fish were analysed for the biochemical markers hsp70 (in liver and gills) and hepatic EROD activity, as well as several biometrical parameters (age, length, wet weight, condition factor). None of the biochemical markers correlated with any biometrical parameter, thus biomarker reactions were related to site-specific criteria. While the hepatic hsp70 level did not differ among the sites, significant elevation of the hsp70 level in the gills revealed proteotoxic damage in chub at the most upstream site, where we recorded the highest heavy metal contamination of the investigated stretch, and in both chub and sneep at the site right downstream of the city of Arad. In both species, significantly elevated hepatic EROD activity downstream of Arad indicated that fish from these sites are also exposed to organic chemicals. The results were indicative of impaired fish health at least at three of the four investigated sites. The approach to relate biomarker responses to analytical data on pollution was shown to fit well the recent EU demands on further enhanced efforts in the monitoring of Romanian water quality.

An EEG approach to the neurodevelopmental hypothesis of schizophrenia studying schizophrenics, normal controls and adolescents

Based on an integrative brain model which focuses on memory-driven and EEG state-dependent information processing for the organisation of behaviour, we used the developmental changes of the awake EEG to further investigate the hypothesis that neurodevelopmental abnormalities (deviations in organisation and reorganisation of cortico-cortical connectivity during development) are involved in the pathogenesis of schizophrenia. First-episode, neuroleptic-naive schizophrenics and their matched controls and three age groups of normal adolescents were studied (total: 70 subjects). 19-channel EEG delta-theta, alpha and beta spectral band centroid frequencies during resting (baseline) and after verbal stimuli were used as measure of the level of attained complexity and momentary excitability of the neuronal network (working memory). Schizophrenics compared with all control groups showed lower delta-theta activity centroids and higher alpha and beta activity centroids. Reactivity centroids (centroid after stimulus minus centroid during resting) were used as measure of update of working memory. Schizophrenics showed partial similarities in delta-theta and beta reactivity centroids with the 11-year olds and in alpha reactivity centroids with the 13-year olds. Within the framework of our model, the results suggest multifactorially elicited imbalances in the level of excitability of neuronal networks in schizophrenia, resulting in network activation at dissociated complexity levels, partially regressed and partially prematurely developed. It is hypothesised that activation of age- and/or state-inadequate representations for coping with realities becomes manifest as productive schizophrenic symptoms. Thus, the results support some aspects of the neurodevelopmental hypothesis.

Predicting Psychotherapy Dropouts: A Multilevel Approach

The role of therapeutic processes in predicting premature termination of psychotherapy has been a particular focus of recent research. The purpose of this study was to contrast outpatients who completed therapy and those who dropped out with respect to their self-reported in-session experiences of self-esteem, mastery, clarification and the therapeutic alliance. The 296 patients with mixed disorders were treated with an integrative form of cognitive–behavioural therapy without pre-determined time limit (M = 20.2 sessions). Multilevel analyses indicated that patients who did not completetreatment reported, on average, lower levels of self-esteem, mastery and clarification and lower ratings of their therapeutic alliance in treatment in contrast to patients who completed therapy. Patient-reported change in self-esteem experiences over the course of treatment turned out to be the strongest predictor of dropout from psychotherapy or successful completion. When dropout occurred before the average treatment length was reached, patients reported fewer clarifying experiences as early as the first session and their ratings of the therapeutic alliance were characterized by an absence of positive development. Both of these aspects seem to be involved in patients' decisions to leave treatment early. The findings underscore the importance of the therapeutic process in understanding the mechanisms behind treatment dropout. Copyright © 2014 John Wiley & Sons, Ltd.

INTEGRATIVE BIOMARKER IDENTIFICATION AND CLASSIFICATION USING HIGH THROUGHPUT ASSAYS

It is well accepted that tumorigenesis is a multi-step procedure involving aberrant functioning of genes regulating cell proliferation, differentiation, apoptosis, genome stability, angiogenesis and motility. To obtain a full understanding of tumorigenesis, it is necessary to collect information on all aspects of cell activity. Recent advances in high throughput technologies allow biologists to generate massive amounts of data, more than might have been imagined decades ago. These advances have made it possible to launch comprehensive projects such as (TCGA) and (ICGC) which systematically characterize the molecular fingerprints of cancer cells using gene expression, methylation, copy number, microRNA and SNP microarrays as well as next generation sequencing assays interrogating somatic mutation, insertion, deletion, translocation and structural rearrangements. Given the massive amount of data, a major challenge is to integrate information from multiple sources and formulate testable hypotheses. This thesis focuses on developing methodologies for integrative analyses of genomic assays profiled on the same set of samples. We have developed several novel methods for integrative biomarker identification and cancer classification. We introduce a regression-based approach to identify biomarkers predictive to therapy response or survival by integrating multiple assays including gene expression, methylation and copy number data through penalized regression. To identify key cancer-specific genes accounting for multiple mechanisms of regulation, we have developed the integIRTy software that provides robust and reliable inferences about gene alteration by automatically adjusting for sample heterogeneity as well as technical artifacts using Item Response Theory. To cope with the increasing need for accurate cancer diagnosis and individualized therapy, we have developed a robust and powerful algorithm called SIBER to systematically identify bimodally expressed genes using next generation RNAseq data. We have shown that prediction models built from these bimodal genes have the same accuracy as models built from all genes. Further, prediction models with dichotomized gene expression measurements based on their bimodal shapes still perform well. The effectiveness of outcome prediction using discretized signals paves the road for more accurate and interpretable cancer classification by integrating signals from multiple sources.

Phraseological features in conversational routines: An integrative model of autonomy

This paper deals with the analysis of routine formulas according to their degree of independence in discourse, with the aim of establishing a gradual line which restructures Sphere III (Corpas 1996, Alvarado 2015) — where phraseological utterances belong. The system developed by Briz and the Val.Es.Co. Group (2003, 2014) will help us segment conversation and check that phraseological utterances show various degrees of independence, both in Peninsular Spanish and in Latin American Spanish, which will make it possible to restructure Sphere III. The methodology utilized corresponds to the phraseological and pragmatic approach, and the examples were extracted from the Corpus de Conversaciones Coloquiales of Briz and the Val.Es.Co. Group (2002), and from the Corpus Preseea (2014).

Hurt feelings in couple relationships: Towards integrative models of the negative effects of hurtful events

Previous research suggests that hurt feelings can have powerful effects on individual and relational outcomes. This study examined a typology of hurtful events in couple relationships, together with integrative models predicting ongoing effects on victims and relationships. Participants were 224 students from introductory and third-year psychology classes, who completed open-ended and structured measures concerning an event in which a partner had hurt their feelings. By tailoring Leary et al.'s (1998) typology to the context of romantic relationships, five categories of hurtful events were proposed: active disassociation, passive disassociation, criticism, infidelity, and deception. Analyses assessing similarities and differences among the categories confirmed the utility of the typology. Structural equation modeling showed that longer-term effects on the victim were predicted by relationship anxiety and by the victim's immediate reactions to the event (negative emotions and self-perceptions; feelings of rejection and powerlessness). In contrast, ongoing effects on the relationship were predicted by avoidance, the victim's attributions and perceptions of offender remorse, and the victim's own behavior. The results highlight the utility of an integrated approach to hurt, incorporating emotional, cognitive, and behavioral responses, and dimensions of attachment security.

Towards an integrative theory of religion and politics

In the social sciences, debate on the relationship between religion and politics is mainly the subject of analysis in the sociology of religion and the theory of international relations. While each of these fields promotes different approaches to study their interdependency. The individual's perception of religion and politics is neglected by current research. The faithful, who participates in religious ceremonies, listening and behaving according to specific religious teachings, actively engaging in the liturgical life of the institutional form of his religion, has a specific way of understanding the relationship between religion and politics. I argue that this aspect is under-researched and misrepresented in the literature of sociology and international relations. However, a more complex analysis is offered by the study of nationalism, and especially by its ethnosymbolic approach, which includes at the micro and macro societal level the presence of myths and symbols as part of the individual's and the nation's life. An integrative theory analysing the connection between religion and politics takes into account the role of myths and symbols from the perspectives of both individuals and ethnic communities.

Managing diversity in organizations:an integrative model and agenda for future research

The literature on policies, procedures, and practices of diversity management in organizations is currently fragmented and often contradictory in highlighting what is effective diversity management, and which organizational and societal factors facilitate or hinder its implementation. In order to provide a comprehensive and cohesive view of diversity management in organizations, we develop a multilevel model informed by the social identity approach that explains, on the basis of a work motivation logic, the processes by, and the conditions under which employee dissimilarity within diverse work groups is related to innovation, effectiveness, and well-being. Building on this new model, we then identify those work group factors (e.g., climate for inclusion and supervisory leadership), organizational factors (e.g., diversity management policies and procedures, and top management's diversity beliefs), and societal factors (e.g., legislation, socioeconomic situation, and culture) that are likely to contribute to the effective management of diversity in organizations. In our discussion of the theoretical implications of the proposed model, we offer a set of propositions to serve as a guide for future research. We conclude with a discussion of possible limitations of the model and practical implications for managing diversity in organizations. © 2014 Taylor & Francis.

An integrative case study of positive youth development in a recreational community sport program

Participation in organized activities is associated with many markers of positive youth development (PYD) such as improved self-esteem, social competence, and academic achievement (Mahoney et al., 2009). Sport is an extra-curricular activity that is particularly popular among youth, as nearly three quarters of Canadian children and adolescents are engaged in organized sport or physical activity (CFLRI, 2012). Much of the research in this area has examined sport programs which are explicitly structured to promote life skills or PYD outcomes; however, the sustainability of such programs has recently been called into question (Turnnidge, Hancock, & Côté, 2014). The purpose of this program of research was to conduct an in-depth case study of a successful, sustainable community youth basketball league. Study 1 was a qualitative descriptive exploration of coaches’ perceptions of the basketball league. This study provided a general overview of the structure and perceived benefits of the league, from the perspective of current coaches. Coaches highlighted the unique emphasis that the league places on fun and positive immediate sport experiences. Study 2 expanded on selected themes from Study 1, namely, the salience of the league’s culture and tendency for former players to return to the league as volunteers. This study used an ethnographic approach wherein the first author volunteered as an assistant coach on a basketball team over the course of a six-month season. This approach enabled him to gain considerable first hand insight into the organizational culture of the basketball league. The third and final study adopted a quantitative approach using both systematic observation and questionnaires to investigate the relationship between PYD outcomes and observed athlete behaviour during basketball games. A cluster analysis revealed the presence of two distinct groups of athletes characterized by relatively high and low perceptions of PYD outcomes, which were also associated with varying behavioural characteristics during competition. The results of these three studies provide a detailed blueprint of a successful youth sport program that has been sustained over 60 years. While not without limitations, many characteristics of the league should prove useful in structuring youth sport programs in other contexts.

Providing a ‘whole-of-family’ approach to care: family-focused practices in mental health services

Introduction: Family members including children are all impacted by a family member’s mental illness. Although mental health services are increasingly encouraged to engage in family-focused practice, this is not a well-understood concept or practice in mental health care. Methods: An integrative review using systematic methods was conducted with international literature, with the aim of identifying concepts and practices of family-focused practice in child and youth and adult mental health services. Results: Findings from 40 peer-reviewed literature identified a range of understandings and applications of family-focused practice, including who comprises the ‘family’, whether the focus is family of origin or family of procreation or choice, and whether the context of practice is child and youth or adult. ‘Family’ as defined by its members forms the foundation for practice that aims to provide a whole-of-family approach to care. Six core practices comprise a family focus to care: assessment; psychoeducation; family care planning and goal-setting; liaison between families and services; instrumental, emotional and social support; and a coordinated system of care between families and services. Conclusion: By incorporating key principles and the core family-focused practices into their care delivery, clinicians can facilitate a whole-of-family approach to care and strengthen family members’ wellbeing and resilience, and their individual and collective health outcomes.

Mental health nurses’ attitudes, behaviour, experience and knowledge regarding adults with a diagnosis of borderline personality disorder: systematic, integrative literature review

Aims and objectives To establish whether mental health nurses responses to people with borderline personality disorder are problematic and, if so, to inform solutions to support change. Background There is some evidence that people diagnosed with borderline personality disorder are unpopular among mental health nurses who respond to them in ways which could be counter-therapeutic. Interventions to improve nurses’ attitudes have had limited success. Design Systematic, integrative literature review. Methods Computerised databases were searched from inception to April 2015 for papers describing primary research focused on mental health nurses’ attitudes, behaviour, experience, and knowledge regarding adults diagnosed with borderline personality disorder. Analysis of qualitative studies employed metasynthesis; analysis of quantitative studies was informed by the theory of planned behaviour. Results Forty studies were included. Only one used direct observation of clinical practice. Nurses’ knowledge and experiences vary widely. They find the group very challenging to work with, report having many training needs, and, objectively, their attitudes are poorer than other professionals’ and poorer than towards other diagnostic groups. Nurses say they need a coherent therapeutic framework to guide their practice, and their experience of caregiving seems improved where this exists. Conclusions Mental health nurses’ responses to people with borderline personality disorder are sometimes counter-therapeutic. As interventions to change them have had limited success there is a need for fresh thinking. Observational research to better understand the link between attitudes and clinical practice is required. Evidence-based education about borderline personality disorder is necessary, but developing nurses to lead in the design, implementation and teaching of coherent therapeutic frameworks may have greater benefits. Relevance to clinical practice There should be greater focus on development and implementation of a team-wide approach, with nurses as equal partners, when working with patients with borderline personality disorder.

An Integrative Case Study of Positive Youth Development in a Recreational Community Sport Program

Thesis (Ph.D, Kinesiology & Health Studies) -- Queen's University, 2016-07-21 14:22:50.954