samExploreR: exploring reproducibility and robustness of RNA-seq results based on SAM files

MOTIVATION: Data from RNA-seq experiments provide us with many new possibilities to gain insights into biological and disease mechanisms of cellular functioning. However, the reproducibility and robustness of RNA-seq data analysis results is often unclear. This is in part attributed to the two counter acting goals of (a) a cost efficient and (b) an optimal experimental design leading to a compromise, e.g., in the sequencing depth of experiments.

RESULTS: We introduce an R package called samExploreR that allows the subsampling (m out of n bootstraping) of short-reads based on SAM files facilitating the investigation of sequencing depth related questions for the experimental design. Overall, this provides a systematic way for exploring the reproducibility and robustness of general RNA-seq studies. We exemplify the usage of samExploreR by studying the influence of the sequencing depth and the annotation on the identification of differentially expressed genes.

AVAILABILITY: Availability: samExploreR is available as an R package from Bioconductor (after acceptance of the paper, download link: http://www.bio-complexity.com/samExploreR_1.0.0.tar.gz).

Multiple training interventions significantly improve reproducibility of PET/CT-based lung cancer radiotherapy target volume delineation using an IAEA study protocol

BACKGROUND AND PURPOSE: To assess the impact of a standardized delineation protocol and training interventions on PET/CT-based target volume delineation (TVD) in NSCLC in a multicenter setting.

MATERIAL AND METHODS: Over a one-year period, 11 pairs, comprised each of a radiation oncologist and nuclear medicine physician with limited experience in PET/CT-based TVD for NSCLC from nine different countries took part in a training program through an International Atomic Energy Agency (IAEA) study (NCT02247713). Teams delineated gross tumor volume of the primary tumor, during and after training interventions, according to a provided delineation protocol. In-house developed software recorded the performed delineations, to allow visual inspection of strategies and to assess delineation accuracy.

RESULTS: Following the first training, overall concordance indices for 3 repetitive cases increased from 0.57±0.07 to 0.66±0.07. The overall mean surface distance between observer and expert contours decreased from -0.40±0.03 cm to -0.01±0.33 cm. After further training overall concordance indices for another 3 repetitive cases further increased from 0.64±0.06 to 0.80±0.05 (p=0.01). Mean surface distances decreased from -0.34±0.16 cm to -0.05±0.20 cm (p=0.01).

CONCLUSION: Multiple training interventions improve PET/CT-based TVD delineation accuracy in NSCLC and reduces interobserver variation.

The vertical dimension of social relations and accurate interpersonal perception: A meta-analysis

There is little consensus regarding how verticality (social power, dominance, and status) is related to accurate interpersonal perception. The relation could be either positive or negative, and there could be many causal processes at play. The present article discusses the theoretical possibilities and presents a meta-analysis of this question. In studies using a standard test of interpersonal accuracy, higher socioeconomic status (SES) predicted higher accuracy defined as accurate inference about the meanings of cues; also, higher experimentally manipulated vertical position predicted higher accuracy defined as accurate recall of others’ words. In addition, although personality dominance did not predict accurate inference overall, the type of personality dominance did, such that empathic/responsible dominance had a positive relation and egoistic/aggressive dominance had a negative relation to accuracy. In studies involving live interaction, higher experimentally manipulated vertical position produced lower accuracy defined as accurate inference about cues; however, methodological problems place this result in doubt.

"It’s just very natural" – interpersonal knowledge as a didactical device in guided classroom conversations in religious education

This article investigates how teachers in religious education (RE) think and act as professionals while working with differences in religious and philosophy of life experiences and beliefs in class and trying to do this in respectful and inclusive ways. It analyses data from two research projects that were carried out in lower secondary school in Norway. The main research question is: What is the relationship between teachers’ contextual knowledge and knowledge of the child and how do these two dimensions of professional knowledge interact when religious education teachers try to strike a good balance between inclusion and productive learning in their teaching practice? The data analysed were drawn from three different data sets featuring three Norwegian religious education-teachers. The research was part of the EU-funded "REDCo"-project and the "Religious education and diversity" - project ["ROM"] funded by the Norwegian Research Council. The interviewees emphasized the potential of the religious education subject to contribute to a wider tolerance for difference and to support individual students in their identity management. The analysis shows, however, that considerable contextual awareness - of the classroom and of the local community - is needed to realize this potential. It also shows the importance of interpersonal knowledge between the teacher and each student if contextual awareness is to be effective in terms of inclusion, participation, wellbeing and good learning outcomes for all students.

Myocardial blood flow quantification by Rb-82 cardiac PET/CT: A detailed reproducibility study between two semi-automatic analysis programs.

BACKGROUND: Several analysis software packages for myocardial blood flow (MBF) quantification from cardiac PET studies exist, but they have not been compared using concordance analysis, which can characterize precision and bias separately. Reproducible measurements are needed for quantification to fully develop its clinical potential. METHODS: Fifty-one patients underwent dynamic Rb-82 PET at rest and during adenosine stress. Data were processed with PMOD and FlowQuant (Lortie model). MBF and myocardial flow reserve (MFR) polar maps were quantified and analyzed using a 17-segment model. Comparisons used Pearson's correlation ρ (measuring precision), Bland and Altman limit-of-agreement and Lin's concordance correlation ρc = ρ·C b (C b measuring systematic bias). RESULTS: Lin's concordance and Pearson's correlation values were very similar, suggesting no systematic bias between software packages with an excellent precision ρ for MBF (ρ = 0.97, ρc = 0.96, C b = 0.99) and good precision for MFR (ρ = 0.83, ρc = 0.76, C b = 0.92). On a per-segment basis, no mean bias was observed on Bland-Altman plots, although PMOD provided slightly higher values than FlowQuant at higher MBF and MFR values (P < .0001). CONCLUSIONS: Concordance between software packages was excellent for MBF and MFR, despite higher values by PMOD at higher MBF values. Both software packages can be used interchangeably for quantification in daily practice of Rb-82 cardiac PET.

Structured Approaches for Exploring Interpersonal Relationships in Natural Language Text

Human relationships have long been studied by scientists from domains like sociology, psychology, literature, etc. for understanding people's desires, goals, actions and expected behaviors. In this dissertation we study inter-personal relationships as expressed in natural language text. Modeling inter-personal relationships from text finds application in general natural language understanding, as well as real-world domains such as social networks, discussion forums, intelligent virtual agents, etc. We propose that the study of relationships should incorporate not only linguistic cues in text, but also the contexts in which these cues appear. Our investigations, backed by empirical evaluation, support this thesis, and demonstrate that the task benefits from using structured models that incorporate both types of information. We present such structured models to address the task of modeling the nature of relationships between any two given characters from a narrative. To begin with, we assume that relationships are of two types: cooperative and non-cooperative. We first describe an approach to jointly infer relationships between all characters in the narrative, and demonstrate how the task of characterizing the relationship between two characters can benefit from including information about their relationships with other characters in the narrative. We next formulate the relationship-modeling problem as a sequence prediction task to acknowledge the evolving nature of human relationships, and demonstrate the need to model the history of a relationship in predicting its evolution. Thereafter, we present a data-driven method to automatically discover various types of relationships such as familial, romantic, hostile, etc. Like before, we address the task of modeling evolving relationships but don't restrict ourselves to two types of relationships. We also demonstrate the need to incorporate not only local historical but also global context while solving this problem. Lastly, we demonstrate a practical application of modeling inter-personal relationships in the domain of online educational discussion forums. Such forums offer opportunities for its users to interact and form deeper relationships. With this view, we address the task of identifying initiation of such deeper relationships between a student and the instructor. Specifically, we analyze contents of the forums to automatically suggest threads to the instructors that require their intervention. By highlighting scenarios that need direct instructor-student interactions, we alleviate the need for the instructor to manually peruse all threads of the forum and also assist students who have limited avenues for communicating with instructors. We do this by incorporating the discourse structure of the thread through latent variables that abstractly represent contents of individual posts and model the flow of information in the thread. Such latent structured models that incorporate the linguistic cues without losing their context can be helpful in other related natural language understanding tasks as well. We demonstrate this by using the model for a very different task: identifying if a stated desire has been fulfilled by the end of a story.

DEVELOPMENT AND REPRODUCIBILITY OF THE INSTRUMENTO DE AVALIAÇÃO DA PROMOÇÃO DA SAÚDE NA UNIVERSIDADE - IAPSU (ASSESSMENT TOOL FOR HEALTH PROMOTION AT THE UNIVERSITY)

Objective: To present the Instrumento de Avaliação da Promoção da Saúde na Universidade – IAPSU (Assessment Tool for Health Promotion at the University) and its reproducibility assessment process. Methods: Cross-sectional study conducted between May and July 2014 with 50 students from a university of Fortaleza, Ceará, which developed the IAPSU through the analysis of government documents and a systematic review of the literature on a potentially healthy university. The tool has 41 questions divided into five domains: physical activity, diet, environmental factors, psychosocial factors and alcohol and drug use, integrative and complementary practices. To assess the inter-examiner reproducibility, the students answered the IAPSU twice, applied by two different examiners; to assess the intraexaminer reproducibility, another application of the instrument was performed after seven days. Results: The study comprised 40 Nursing students and 10 Physical Therapy students, with a mean age of 25 ± 5.4 years; 88% were women and white individuals were predominant. In the reproducibility assessment, strong intraclass, intra- and inter-examiner correlation coefficients - above 0.8 - were observed in all the domains. Conclusion: The IAPSU is a reproducible and reliable instrument for assessing health promotion at the university.

The interpersonal and mental health implications of the coherence of coming out narratives for a sample of gay men in committed romantic relationships

The coming out process has been conceptualized as a developmental imperative for those who will eventually accept their same-sex attractions. It is widely accepted that homophobia, heterosexism, and homonegativity are cultural realities that may complicate this developmental process for gay men. The current study views coming out as an extra-developmental life task that is at best a stressful event, and at worst traumatic when coming out results in the rupture of salient relationships with parents, siblings, and/or close friends. To date, the minority stress model (Meyer, 1995; 2003) has been utilized as an organizing framework for how to empirically examine external stressors and mental health disparities for lesbians, gay men, and bisexual individuals in the United States. The current study builds on this literature by focusing on the influence of how gay men make sense of and represent the coming out process in a semi-structured interview, more specifically, by examining the legacy of the coming out process on indicators of wellness. In a two-part process, this study first employs the framework well articulated in the adult attachment literature of coherence of narratives to explore both variation and implications of the coming out experience for a sample of gay men (n = 60) in romantic relationships (n = 30). In particular, this study employed constructs identified in the adult attachment literature, namely Preoccupied and Dismissing current state of mind, to code a Coming Out Interview (COI). In the present study current state of mind refers to the degree of coherent discourse produced about coming out experiences as relayed during the COI. Multilevel analyses tested the extent to which these COI dimensions, as revealed through an analysis of coming out narratives in the COI, were associated with relationship quality, including self-reported satisfaction and observed emotional tone in a standard laboratory interaction task and self-reported symptoms of psychopathology. In addition, multilevel analyses also assessed the Acceptance by primary relationship figures at the time of disclosure, as well as the degree of Outness at the time of the study. Results revealed that participant’s narratives on the COI varied with regard to Preoccupied and Dismissing current state of mind, suggesting that the AAI coding system provides a viable organizing framework for extracting meaning from coming out narratives as related to attachment relevant constructs. Multilevel modeling revealed construct validity of the attachment dimensions assessed via the COI; attachment (i.e., Preoccupied and Dismissing current state of mind) as assessed via the Adult Attachment Interview (AAI) was significantly correlated with the corresponding COI variables. These finding suggest both methodological and conceptual convergence between these two measures. However, with one exception, COI Preoccupied and Dismissing current state of mind did not predict relationship outcomes or self-reported internalizing and externalizing symptoms. However, further analyses revealed that the degree to which one is out to others moderated the relationship between COI Preoccupied and internalizing. Specifically, for those who were less out to others, there was a significant and positive relationship between Preoccupied current state of mind towards coming out and internalizing symptoms. In addition, the degree of perceived acceptance of sexual orientation by salient relationship figures at the time of disclosure emerged as a predictor of mental health. In particular, Acceptance was significantly negatively related to internalizing symptoms. Overall, the results offer preliminary support that gay men’s narratives do reflect variation as assessed by attachment dimensions and highlights the role of Acceptance by salient relationship figures at the time of disclosure. Still, for the most part, current state of mind towards coming out in this study was not associated with relationship quality and self-reported indicators of mental health. This finding may be a function of low statistical power given the modest sample size. However, the relationship between Preoccupied current state of mind and mental health (i.e., internalizing) appears to depend on degree of Outness. In addition, the response of primary relationships figures to coming out may be a relevant factor in shaping mental health outcomes for gay men. Limitations and suggestions for future research and clinical intervention are offered.

Development Of Interpersonal Relationships in Global Virtual Teams

This study investigates the development of relationships in same global virtual team working on different projects. The purpose is to explore how do interpersonal relationships develop in terms of characteristics of virtuality and if there is any influence of project lifespan on the development of these relationships. Since relationships are dynamic in nature and are influenced by multiple levels of variables including individual, group and organizational level, therefore characteristics of virtuality have been considered from all these aspects so as to study their influence on development of relationships. In this study, relationships have been studied at two different levels. At first, dyadic relationships between two members of a GVT have been analyzed and thereafter, focus has been on the development of relationships among the team, based on these dyads. Characteristics having influence on development of relationships include trust, physical distance, time zone difference, cultural and language differences, level of formalization in the organization and means of communication used by team members. Level of formalization and means of communication are two characteristics which emerged after empirical study and are found to have direct influence on development of relationships. Remaining characteristics have been identified through literature review. In order to conduct the study, qualitative methodology has been applied. Empirical data has been collected based on a single case study while using semi-structured interviews as data gathering technique. Data analysis has been performed by applying thematic analysis along with the utilization of company documents such as work sheets, minutes of meetings and recordings of conferences. Findings of the study indicate that development of relationships, both at dyadic level and team level, is influenced by different events taking place among different members of GVT. These events have either positive or negative influence on the characteristics of virtuality, which leads to development of the relationships. It has been found that, trust, among all factors plays a greater role in development of these relations. Contrary to the belief that most conflicts arise among members of different cultures, they are equally likely to happen among the members from same culture in GVT environment. Study suggests that relationship development is not a smooth process but it fluctuates based on different events in teams. For further research, teams within large firms shall be studied along these lines. This study is an early attempt towards bringing different characteristics of virtuality together which previously, have been studied individually. It is therefore plausible to conduct similar studies so as to generalize the findings of this study which has provided a starting point.