SHrinkage Covariance Estimation Incorporating Prior Biological Knowledge with Applications to High-Dimensional Data

In ``-omic data'' analysis, information on the structure of covariates are broadly available either from public databases describing gene regulation processes and functional groups such as the Kyoto encyclopedia of genes and genomes (KEGG), or from statistical analyses -- for example in form of partial correlation estimators. The analysis of transcriptomic data might benefit from the incorporation of such prior knowledge. In this paper we focus on the integration of structured information into statistical analyses in which at least one major step involves the estimation of a (high-dimensional) covariance matrix. More precisely, we revisit the recently proposed ``SHrinkage Incorporating Prior'' (SHIP) covariance estimation method which takes into account the group structure of the covariates, and suggest to integrate the SHIP covariance estimator into various multivariate methods such as linear discriminant analysis (LDA), global analysis of covariance (GlobalANCOVA), and regularized generalized canonical correlation analysis (RGCCA). We demonstrate the use of the resulting new methods based on simulations and discuss the benefit of the integration of prior information through the SHIP estimator. Reproducible R codes are available at http://www.ibe.med.uni-muenchen.de/organisation/mitarbeiter/020_professuren/boulesteix/shipproject/index.html

SHrinkage Covariance Estimation Incorporating Prior Biological Knowledge with Applications to High-Dimensional Data

In ``-omic data'' analysis, information on the structure of covariates are broadly available either from public databases describing gene regulation processes and functional groups such as the Kyoto encyclopedia of genes and genomes (KEGG), or from statistical analyses -- for example in form of partial correlation estimators. The analysis of transcriptomic data might benefit from the incorporation of such prior knowledge. In this paper we focus on the integration of structured information into statistical analyses in which at least one major step involves the estimation of a (high-dimensional) covariance matrix. More precisely, we revisit the recently proposed ``SHrinkage Incorporating Prior'' (SHIP) covariance estimation method which takes into account the group structure of the covariates, and suggest to integrate the SHIP covariance estimator into various multivariate methods such as linear discriminant analysis (LDA), global analysis of covariance (GlobalANCOVA), and regularized generalized canonical correlation analysis (RGCCA). We demonstrate the use of the resulting new methods based on simulations and discuss the benefit of the integration of prior information through the SHIP estimator. Reproducible R codes are available at http://www.ibe.med.uni-muenchen.de/organisation/mitarbeiter/020_professuren/boulesteix/shipproject/index.html

Over-optimism in bioinformatics: an illustration

In statistical bioinformatics research, different optimization mechanisms potentially lead to "over-optimism" in published papers. The present empirical study illustrates these mechanisms through a concrete example from an active research field. The investigated sources of over-optimism include the optimization of the data sets, of the settings, of the competing methods and, most importantly, of the method’s characteristics. We consider a "promising" new classification algorithm that turns out to yield disappointing results in terms of error rate, namely linear discriminant analysis incorporating prior knowledge on gene functional groups through an appropriate shrinkage of the within-group covariance matrix. We quantitatively demonstrate that this disappointing method can artificially seem superior to existing approaches if we "fish for significance”. We conclude that, if the improvement of a quantitative criterion such as the error rate is the main contribution of a paper, the superiority of new algorithms should be validated using "fresh" validation data sets

Decadal prediction skill using a high-resolution climate model

The ability of a high-resolution coupled atmosphere–ocean general circulation model (with a horizontal resolution of a quarter of a degree in the ocean and of about 0.5° in the atmosphere) to predict the annual means of temperature, precipitation, sea-ice volume and extent is assessed based on initialized hindcasts over the 1993–2009 period. Significant skill in predicting sea surface temperatures is obtained, especially over the North Atlantic, the tropical Atlantic and the Indian Ocean. The Sea Ice Extent and volume are also reasonably predicted in winter (March) and summer (September). The model skill is mainly due to the external forcing associated with well-mixed greenhouse gases. A decrease in the global warming rate associated with a negative phase of the Pacific Decadal Oscillation is simulated by the model over a suite of 10-year periods when initialized from starting dates between 1999 and 2003. The model ability to predict regional change is investigated by focusing on the mid-90’s Atlantic Ocean subpolar gyre warming. The model simulates the North Atlantic warming associated with a meridional heat transport increase, a strengthening of the North Atlantic current and a deepening of the mixed layer over the Labrador Sea. The atmosphere plays a role in the warming through a modulation of the North Atlantic Oscillation: a negative sea level pressure anomaly, located south of the subpolar gyre is associated with a wind speed decrease over the subpolar gyre. This leads to a reduced oceanic heat-loss and favors a northward displacement of anomalously warm and salty subtropical water that both concur to the subpolar gyre warming. We finally conclude that the subpolar gyre warming is mainly triggered by ocean dynamics with a possible contribution of atmospheric circulation favoring its persistence

Bonds generated by homeless people in economic initiatives in Porto Alegre, Brazil

Em Porto Alegre, pessoas em situação ou com trajetória de rua se organizam em frentes que contradizem sua representação negativa na mídia e desafiam o conhecimento acadêmico consolidado sobre eles. Esse artigo analisa o vínculo estabelecido por elas com duas iniciativas econômicas coletivas da cidade, e verificar como contribuem tais vínculos para a satisfação das necessidades materiais e subjetivas dessas pessoas, em direção ao seu fortalecimento enquanto sujeitos éticos. Articulam-se categorias da proposta de uma economia para a vida, que situam e colocam em evidência a relação entre economia e ética. Realizou-se uma pesquisa qualitativa, com observação participante inspirada na técnica dos grupos operativos, de onde os dados levantados relacionaram-se com o referencial teórico em razão de sua intertextualidade. Dentre os resultados encontrados, se destaca que somar-se a uma iniciativa econômica coletiva pode fortalecer vínculos sociais entre pessoas em situação ou com trajetória de ruas; os consensos e acordos entre os integrantes produzem uma nova institucionalidade, pautada na solidariedade, na submissão da produção às suas necessidades materiais e na responsabilidade mútua.In Porto Alegre, homeless people or those with homeless background organize themselves in fronts that contradict their negative representation in the media and challenge the consolidated academic knowledge about them. This article analyzes the bond established by these people with two collective economic initiatives of the city, and how this contributes to the satisfaction of their material and subjective needs, and to their strengthening as ethical subjects. We articulate categories of the proposal for an economy for life, which situate and highlight the relationship between economy and ethics. A qualitative research with participant observation was carried out, inspired by the technique of the operative groups, the data collected was related to the theoretical reference due to its intertextuality. Among the findings, it is worth mentioning that joining a collective economic initiative can strengthen social bonds between homeless people or with homeless background; consensus and agreements between the members produce a new institutionality, based on solidarity, subordination of production to their material needs and mutual responsibility

Bureaucracy and the challenges of coordination in service delivery : a comparative study of Kabulonga and Kamanga primary schools in Lusaka City, 2010- 2014

Masters in Public Administration - MPAThe study Bureaucracy and the challenges of coordination in service delivery: A comparative study of Kamanga and Kabulonga Primary Schools in Lusaka City 2010- 2014 had the main aim of finding out the challenges encountered in the coordination of primary education within Lusaka City. The study was attempting to draw lessons and understand why schools within the same district and level (primary) were performing differently. There are many reasons as to why the study is important. To begin with, the information derived from this study is important in the post MDG implementation period after the end of the implementation period in 2015. Second, no research has been done on organizational design and development in the context of Africa and Zambia. While some scholars have published on education management, the aspect of bureaucratic coordination has not been adequately addressed. The study took a comparative approach to research. Qualitative research was deployed as means of carrying out the study. Both primary and secondary data were used. Primary data was collected from two schools which were sampled purposively. The researcher approached the District education office to recommend two schools (one performing well and another underperforming one). The two schools recommended are Kabulonga Primary and Kamanga Primary respectively. A sample of seven experts was then extracted including two teachers from each school, a school manager for each school and the district planning officer at district level. Data was collected using semi structured interview guides between December 2015 and January 2016. Data was collected through a recorder, transcribed and analyzed using thematic analysis. On the other hand, secondary data was obtained from policy, legal, government and internal documents. Among the major findings was that the school's locations or environments have a major impact on how they function. For instance Kabulonga performed better than Kamanga because the latter is in an area where majority are low earning poor households. Further, internally, the ability of Kabulonga to plan in a long term manner enabled the school to match resources with specific priorities, something Kamanga did not do. Furthermore, the avenues used for communication in the district have got poor information feedback mechanisms. The study thus recommended that the government should distribute resources to schools with a connotation of giving an extra financial bell out to those schools operating in poverty stricken areas since such schools cannot find other means of survival

Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force

Background: Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). Objective: To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods: Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. Results: Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient's status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9-10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions: The task force defined the treatment target as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research. These recommendations can inform the various stakeholders about expert opinion that aims for reaching optimal outcomes of SpA

Le théâtre de Dumas père, entre héritage et renouvellement

Ce livre part d'un constat : malgré une abondante production, étalée sur près de cinquante ans, le théâtre de Dumas subit aujourd'hui une indéniable éclipse. Or, son auteur a joué un rôle de premier plan dans la « bataille » romantique ; il a continué sans interruption d'écrire pour la scène jusqu'à sa mort ; refusant l'exclusive, il a pratiqué tous les genres. Il laisse un corpus officiel de soixante-six pièces, en réalité plus de cent si l'on comptabilise les textes non signés mais où sa collaboration est attestée. Cette œuvre s'inscrit dans un héritage, revendiqué ou implicite, de l'Antiquité à la production contemporaine : tragédie classique et néo-classique, comédie d'intrigue et de caractère, scène historique, drame bourgeois, vaudeville, mélodrame, proverbe… Elle en fait un usage complexe, entre emprunts, variations et détournements, en jouant de la contamination entre modèles « nobles » et modèles « mineurs ». Parcouru par un double processus d'assimilation et de transformation, le théâtre de Dumas fonctionne comme un creuset dramatique ; il fait évoluer les genres, modernise les enjeux et renouvelle le spectaculaire, marquant ainsi un repère capital pour les générations suivantes. Travail collectif d'une équipe de chercheurs engagés dans la publication du Théâtre complet de Dumas, ce volume veut rendre hommage à la richesse et à la diversité d'une œuvre qui résume un demi-siècle de vie dramatique

Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force

Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field