GSuite HyperBrowser: integrative analysis of dataset collections across the genome and epigenome

Background: Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation. Findings: We here present a first principled treatment of the analysis of collections of genomic tracks. We have developed novel computational and statistical methodology to permit comparative and confirmatory analyses across multiple and disparate data sources. We delineate a set of generic questions that are useful across a broad range of investigations and discuss the implications of choosing different statistical measures and null models. Examples include contrasting analyses across different tissues or diseases. The methodology has been implemented in a comprehensive open-source software system, the GSuite HyperBrowser. To make the functionality accessible to biologists, and to facilitate reproducible analysis, we have also developed a web-based interface providing an expertly guided and customizable way of utilizing the methodology. With this system, many novel biological questions can flexibly be posed and rapidly answered. Conclusions: Through a combination of streamlined data acquisition, interoperable representation of dataset collections, and customizable statistical analysis with guided setup and interpretation, the GSuite HyperBrowser represents a first comprehensive solution for integrative analysis of track collections across the genome and epigenome. The software is available at: https://hyperbrowser.uio.no.This work was supported by the Research Council of Norway (under grant agreements 221580, 218241, and 231217/F20), by the Norwegian Cancer Society (under grant agreements 71220’PR-2006-0433 and 3485238-2013), and by the South-Eastern Norway Regional Health Authority (under grant agreement 2014041).Peer Reviewe

Assessment in Evidence-Based Practice : Psychometric Properties, Clinical Utility and Professional Co-operation from Different Perspectives of the Home Observation for Measurement of the Environment in Sweden

The overall aim of the present thesis was to explore and compare professional co-operation in child welfare investigations, explore the psychometric properties, and describe the clinical utility from different perspectives of a translated Swedish version of the standardized assessment instrument the Home Observation for Measurement of the Environment (the HOME Inventory). Social workers in Sweden, Denmark, Britain, Germany, and Texas (USA) co-operated with different professionals around a fictitious child welfare case. Differences were found between and within country-based samples, indicating an unsystematic work procedure in the social work agencies studied. The psychometric properties of the translated Early Childhood version (EC-HOME) and Middle Childhood version (MC-HOME) of the HOME Inventory were explored in terms of inter-observer reliability and by Rasch analysis. The samples were authentic Swedish child welfare cases recruited from a field setting. Inter-observer reliability was satisfactory. Results were ambiguous regarding measurement construction of the two versions studied. Because of the differentiating ability of the EC-HOME and MC-HOME, total scores could provide an indication of inadequate home environments. Experiences of social work practitioners of the clinical utility of the HOME Inventory suggested that they considered the instrument to be comprehensive and have explicit potential benefits, i.e. to be clinically useful. Correspondingly, caregivers’ overall perceptions of the HOME Inventory were positive, determining the content relevant and the format acceptable. However, certain flaws have to be rectified before the HOME Inventory is to be implemented and used successfully. Further, education and the possibility to practice administering the instrument seemed to be essential conditions for future use according to social workers. When social workers and teachers’ apprehensions about support and stimulation provided by caregivers to children in their home environments were compared, preschool teachers’ apprehensions correlated poorly with the social workers’ assessment. These results suggest that the HOME Inventory is promising but cultural adaptation and further studies of psychometric properties are necessary. Different forms of support to practitioners and agencies for successful implementation are required. Awareness of the type of information provided by different sources is important when co-operating in child welfare

Assessment in Evidence-Based Practice : Psychometric Properties, Clinical Utility and Professional Co-operation from Different Perspectives of the Home Observation for Measurement of the Environment in Sweden

The overall aim of the present thesis was to explore and compare professional co-operation in child welfare investigations, explore the psychometric properties, and describe the clinical utility from different perspectives of a translated Swedish version of the standardized assessment instrument the Home Observation for Measurement of the Environment (the HOME Inventory). Social workers in Sweden, Denmark, Britain, Germany, and Texas (USA) co-operated with different professionals around a fictitious child welfare case. Differences were found between and within country-based samples, indicating an unsystematic work procedure in the social work agencies studied. The psychometric properties of the translated Early Childhood version (EC-HOME) and Middle Childhood version (MC-HOME) of the HOME Inventory were explored in terms of inter-observer reliability and by Rasch analysis. The samples were authentic Swedish child welfare cases recruited from a field setting. Inter-observer reliability was satisfactory. Results were ambiguous regarding measurement construction of the two versions studied. Because of the differentiating ability of the EC-HOME and MC-HOME, total scores could provide an indication of inadequate home environments. Experiences of social work practitioners of the clinical utility of the HOME Inventory suggested that they considered the instrument to be comprehensive and have explicit potential benefits, i.e. to be clinically useful. Correspondingly, caregivers’ overall perceptions of the HOME Inventory were positive, determining the content relevant and the format acceptable. However, certain flaws have to be rectified before the HOME Inventory is to be implemented and used successfully. Further, education and the possibility to practice administering the instrument seemed to be essential conditions for future use according to social workers. When social workers and teachers’ apprehensions about support and stimulation provided by caregivers to children in their home environments were compared, preschool teachers’ apprehensions correlated poorly with the social workers’ assessment. These results suggest that the HOME Inventory is promising but cultural adaptation and further studies of psychometric properties are necessary. Different forms of support to practitioners and agencies for successful implementation are required. Awareness of the type of information provided by different sources is important when co-operating in child welfare

Hamilton-Jacobi Equations for Nonlinear Descriptor Systems

Optimal control problems for nonlinear descriptor systems are considered. Anapproach where the descriptor system is conceptually reduced to a state spaceform is compared to an approach where the Hamilton-Jacobi equation is directly formulated for the descriptor system. The two approaches are shown to give essentially the same systems of equations to be solved. A certain unknown function is present only in the second approach but is shown to be computable from the quantities common to both approches

Power Series Solution of the Hamilton-Jacobi-Bellman Equation for Time-Varying Differential-Algebraic Equations

Optimal control problems for a class of nonlinear time-varying differential-algebraic equations are considered. It is shown that they possess a well-defined feedback solution in a neighborhood of the origin. Explicit formulas for the series expansions of the cost function and control law are given

Computing the Controllability Function for Nonlinear Descriptor Systems

The computation of the controllability function for nonlinear descriptor systems is considered. Three different methods are derived. The first method is based on the necessary conditions for optimality from the Hamilton-Jacobi-Bellman theory for descriptor systems. The second method uses completion of squares to find the solution. The third method gives a series expansion solution, which with a finite number of terms can serve as an approximate solution

The middle manager's complex work condition/situation/role at organizational level : A qualitative study focusing on the interpretation of the middle manager role

Mellanchefens organisatoriska roll har transformerats sedan Burns först utforskade mellanchefsrollen och sedan slutet av 1900-talet har rollen förändrats och tilldelats fleråtaganden än tidigare. En studie från Previa belyser mellanchefsrollens ökade sjukskrivningar och vittnar om att positionen i mitten av organisationer har blivit en utsatt arbetsbefattning att disponera över i dagens moderna samhälle. Följande kvalitativa studie syftar till att utforska hur mellanchefsrollen upplevs av olika chefspositioner inom organisationer och belysa problematiken kring rollkonflikterna som uppstår på mellanchefspositioner ur ett nytt perspektiv. Studiens empiriska material utgår frånelva chefsintervjuer från tre matrisorganisationer. För att bearbeta studiens material har vi använt oss av en abduktiv metod där vi under studiens gång har arbetat genom hermeneutiken och pendlat mellan empiri och teori för att skapa förståelse. I studien försöker vi inte definiera mellanchefsrollen ur några exakta riktlinjer utan studien utforskar rollen i en föränderlig praktik. Vi har inte som avsikt med studien att presentera någon form av absolut sanning gällande mellanchefsrollen utan vi vill snarare förmedla olika poänger om mellanchefsrollens arbetssituation som förhoppningsvis leder till en djupare reflektion tills studiens läsare. I studien bearbetar vi fram mellanchefsrollens komplexitetgenom differentierade chefers kunskaper, perspektiv och berättelser om det vardagligaarbetet. Studiens resultat framhäver att mellanchefsrollen upplevs olika beroende på vilken chefsposition rollen upplevs av. Framförallt skiljer sig övre chefers perspektiv gentemot linjechefernas perspektiv på vad rollen finns till för i organisationer och vilka interna intressenter som mellanchefsrollen ska tillfredsställa. The organizational role of the middle manager has been transformed since Burns first explored the role of middle manager, since the end of the 20th century the role continues to change and increasingly more tasks than before have been added to its role. A study from Previa highlights the middle managers role's increased sick leave and indicates that the organization's mid-level position has become a vulnerable job role to command of, in today's modern society. The following qualitative study aims to explore how the role of middle manager is experienced by different managerial positions within organizations hierarchy and from a new perspective shed light on the problems surrounding the role conflicts that arise in middle manager positions. The empirical data is based on eleven conducted managerial semistructured interviews from three organizations. To process the study's material, we’ve applied an abductive method where we throughout the course of the study worked through hermeneutics and thus altered between empiricism and theory to produce an understanding. In this study we don’t aim to define the middle manager role from any exact guidelines, but the study explores the role in a changing practice. Furthermore, this study doesn’t intend to present any form of absolute truth regarding the middle manager role, but rather we want to convey different perspectives about the middle manager role's work situation. Hopefully this will subsequently lead to a deeper reflection for the readers. Through the differentiated managers' knowledge, perspectives and stories about everyday work we managed to understand and process the complexity of the middle manager role. In conclusion, the results concludes that the perception of the middle manager's role varies, depending on which managerial position is being addressed. Above all, there is a conspicuous difference between the senior executives’ perspectives and the line managers' perspectives on the middle managers function within the organization and which internal stakeholders the middle manager role ought to satisfy.

Power Series Solution of the Hamilton-Jacobi-Bellman Equation for Descriptor Systems

Optimal control problems for a class of nonlinear descriptor systems are considered. It is shown that they possess a well-defined analytical feedback solution in a neighborhood of the origin, provided stabilizability and some other regularity conditions are satisfied. Explicit formulas for the series expansions of the cost function and control law are given