The Discursive Effects of the Haiku-based SADUPA Poetry Technique in Palliative Care

International audienceThis qualitative study seeks to present the discursive effects of SADUPA, a new poetry-based technique centered on haiku, in the context of psycho-oncological treatment. The technique is used with a terminal cancer patient, Mr. A. The psychological processes involved with and the poetic writings arising from the technique are discussed. In particular, the discursive variations in Mr. A’s narrative of his illness are described as they occurred before and after his poetry writing. The authors suggest that writing workshops based on the brief poetic structures of the haiku can enable patients to produce a larger and more singular narrative about their end-of- life experiences

Network inference - with confidence - from multivariate time series

Networks - collections of interacting elements or nodes - abound in the natural and manmade worlds. For many networks, complex spatiotemporal dynamics stem from patterns of physical interactions unknown to us. To infer these interactions, it is common to include edges between those nodes whose time series exhibit sufficient functional connectivity, typically defined as a measure of coupling exceeding a pre-determined threshold. However, when uncertainty exists in the original network measurements, uncertainty in the inferred network is likely, and hence a statistical propagation-of-error is needed. In this manuscript, we describe a principled and systematic procedure for the inference of functional connectivity networks from multivariate time series data. Our procedure yields as output both the inferred network and a quantification of uncertainty of the most fundamental interest: uncertainty in the number of edges. To illustrate this approach, we apply our procedure to simulated data and electrocorticogram data recorded from a human subject during an epileptic seizure. We demonstrate that the procedure is accurate and robust in both the determination of edges and the reporting of uncertainty associated with that determination.Comment: 12 pages, 7 figures (low resolution), submitte

Identification of Yeast Transcriptional Regulation Networks Using Multivariate Random Forests

The recent availability of whole-genome scale data sets that investigate complementary and diverse aspects of transcriptional regulation has spawned an increased need for new and effective computational approaches to analyze and integrate these large scale assays. Here, we propose a novel algorithm, based on random forest methodology, to relate gene expression (as derived from expression microarrays) to sequence features residing in gene promoters (as derived from DNA motif data) and transcription factor binding to gene promoters (as derived from tiling microarrays). We extend the random forest approach to model a multivariate response as represented, for example, by time-course gene expression measures. An analysis of the multivariate random forest output reveals complex regulatory networks, which consist of cohesive, condition-dependent regulatory cliques. Each regulatory clique features homogeneous gene expression profiles and common motifs or synergistic motif groups. We apply our method to several yeast physiological processes: cell cycle, sporulation, and various stress conditions. Our technique displays excellent performance with regard to identifying known regulatory motifs, including high order interactions. In addition, we present evidence of the existence of an alternative MCB-binding pathway, which we confirm using data from two independent cell cycle studies and two other physioloigical processes. Finally, we have uncovered elaborate transcription regulation refinement mechanisms involving PAC and mRRPE motifs that govern essential rRNA processing. These include intriguing instances of differing motif dosages and differing combinatorial motif control that promote regulatory specificity in rRNA metabolism under differing physiological processes

Post hoc pattern matching: assigning significance to statistically defined expression patterns in single channel microarray data

<p>Abstract</p> <p>Background</p> <p>Researchers using RNA expression microarrays in experimental designs with more than two treatment groups often identify statistically significant genes with ANOVA approaches. However, the ANOVA test does not discriminate which of the multiple treatment groups differ from one another. Thus, <it>post hoc </it>tests, such as linear contrasts, template correlations, and pairwise comparisons are used. Linear contrasts and template correlations work extremely well, especially when the researcher has <it>a priori </it>information pointing to a particular pattern/template among the different treatment groups. Further, all pairwise comparisons can be used to identify particular, treatment group-dependent patterns of gene expression. However, these approaches are biased by the researcher's assumptions, and some treatment-based patterns may fail to be detected using these approaches. Finally, different patterns may have different probabilities of occurring by chance, importantly influencing researchers' conclusions about a pattern and its constituent genes.</p> <p>Results</p> <p>We developed a four step, <it>post hoc </it>pattern matching (PPM) algorithm to automate single channel gene expression pattern identification/significance. First, 1-Way Analysis of Variance (ANOVA), coupled with <it>post hoc </it>'all pairwise' comparisons are calculated for all genes. Second, for each ANOVA-significant gene, all pairwise contrast results are encoded to create unique pattern ID numbers. The # genes found in each pattern in the data is identified as that pattern's 'actual' frequency. Third, using Monte Carlo simulations, those patterns' frequencies are estimated in random data ('random' gene pattern frequency). Fourth, a Z-score for overrepresentation of the pattern is calculated ('actual' against 'random' gene pattern frequencies). We wrote a Visual Basic program (StatiGen) that automates PPM procedure, constructs an Excel workbook with standardized graphs of overrepresented patterns, and lists of the genes comprising each pattern. The visual basic code, installation files for StatiGen, and sample data are available as supplementary material.</p> <p>Conclusion</p> <p>The PPM procedure is designed to augment current microarray analysis procedures by allowing researchers to incorporate all of the information from post hoc tests to establish unique, overarching gene expression patterns in which there is no overlap in gene membership. In our hands, PPM works well for studies using from three to six treatment groups in which the researcher is interested in treatment-related patterns of gene expression. Hardware/software limitations and extreme number of theoretical expression patterns limit utility for larger numbers of treatment groups. Applied to a published microarray experiment, the StatiGen program successfully flagged patterns that had been manually assigned in prior work, and further identified other gene expression patterns that may be of interest. Thus, over a moderate range of treatment groups, PPM appears to work well. It allows researchers to assign statistical probabilities to patterns of gene expression that fit <it>a priori </it>expectations/hypotheses, it preserves the data's ability to show the researcher interesting, yet unanticipated gene expression patterns, and assigns the majority of ANOVA-significant genes to non-overlapping patterns.</p

A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1-3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas-containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities-is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions4. We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Les effets narratifs de la musique classique dans les soins palliatifs

International audienceAim: The aim of our qualitative study was to describe the narrative effects of a specific and structured protocol focused on classical music sessions, which we administered to a patient (Mrs. M, aged 60), who had experienced a metastatic cancer. Material and Methods: The protocol consists of 4 steps (Times): a preliminary exploratory interview (T1), a first moment of musical listening (T2), a second moment of musical listening (T3) and finally, a final interview (T4). We used the software T-LAB version 9.1.3, a linguistic and statistical tool for text analysis. The rationale on choosing T-LAB software is twofold: i) the multitude of instruments offered for text analysis and, ii) the possibility to use them in an integrated way and the possibility of analyzing a very large text. T-LAB works on a corpus that can be comprised of one or more texts and can be divided into different sub-sets, according to the time variables employed for describing the texts. In this research, we used co-occurrence relationship and word associations recalling moments of narrative structures, according to the humanistic/existential tradition. Findings: We showed the presence of the narrative effects before and after the listening experience. More precisely, in a first step (T2) we have identified a hedonic, sensorial and imaged effect of classical music. In a second phase (the final interview, T4) we observed a spiritual (mythological and archetypical) effect of classical music centered on the evocation of the image of the famous French singer "Barbara". Conclusion: We believe that "psychic work with classical music" cannot only distance the patient from a somatic narrative of the disease (symptoms, complaints, physical pains), but also generate pleasurable body experiences and a rich symbolic and spiritual narrative.Objectif: Cette étude qualitative vise à décrire leseffets narratifs d’un protocole d’écoute musicale (musiqueclassique) chez une patiente atteinte d’un cancer avancé, Mme M. (60 ans).Matériel et méthodes:Ils’agit d’un protocole d’écoutemusicale composé de quatre étapes (temps) : l’entretien pré-liminaire (T1), un premier moment d’écoute musicale (T2),une deuxième rencontre d’écoute musicale (T3), l’entretienfinal (T4). Nous utilisons d’abord le logiciel T-Lab 9.1.3 pour le calcul des associations de mots (cooccurrences) etensuite une interprétation du récit selon l’approche humaniste/existentielle.Résultats: Nous montrons les effets narratifs avant et aprèsl’expérience d’écoute musicale. Plus précisément, dans unpremier temps (T2), nous avons identifié un effet hédonique,sensoriel et imagé de la musique. Dans un second temps(l’entretien final, T4), nous avons observé un effet spirituel(mythologique et archétypique) de la musique classique cen-tré sur l’évocation de l’image de la célèbre chanteuse fran-çaise « Barbara ».Conclusion: Le « travail psychique avec la musique clas-sique » peut non seulement éloigner le patient d’une narra-tion somatique de la maladie (symptômes, plaintes, gènes etdouleurs physiques), mais aussi générer des expériences cor-porelles agréables et une narration riche d’éléments symbo-liques et spirituels

Spirituality and Cancer: a Qualitative Study

International audienceAims: Patients suffering from cancer are often confronted with an awareness of their own finiteness and with the fact that their life is now ruled by the cancer. This existential upheaval can be accompanied by spiritual “work” which contributes to the adjustment to the disease and to the conditions of the end of life. Spirituality can be defined as a process through which individuals seek for and give meaning to their life, feel connected to the self, to others, at the present moment and in what is sacred. Few studies in France have studied spirituality in the context of cancer. So, the aim of our research was to identify and to study the role of spiritual components in the experience of cancer.Procedure: We carried out 15 semi-directed interviews with patients at the medical oncology and palliative care department at the CHU in Timone (Marseille). A double analysis was performed: 1) a lexicographical analysis and 2) a thematic content analysis of the most typical interviews from the lexicographical analysis.Results: The lexicographical analysis highlighted three lexical classes. Class 1 represented the illness of cancer as a personal transformation (40.5%), Class 2 concerned the biographical disruption experience (13.4%) and Class 3 corresponded to daily life with the illness (46.1%). Moreover, the thematic content analysis revealed different themes testifying to spirituality in the lived experience of cancer, in particular the experience of and the relationship with the sacred, the relationship with transcendence and the role of spirituality in the lived experience of patients who are suffering from cancer.Conclusion: The two analyses of the interviews allowed us to identify the expression of spirituality. Spirituality was expressed as a resource, an “invisible spring,” allowing people to adjust to the extreme experience of the disease of cancer. Both “secular” and “central” dimensions of spirituality: the transcendence and the relationship with the sacred open perspectives for the integration of spirituality into the care of patients suffering from cancer, without threatening the principle of secularism in French hospitals.Contexte : Les malades du cancer sont souvent confrontés à une prise de conscience de leur propre finitude et au fait de composer avec une vie désormais rythmée par le cancer. Ce bouleversement existentiel peut s’accompagner d’un « travail » spirituel qui contribue à l’ajustement à la maladie et aux conditions de la fin de la vie. La spiritualité peut être définie comme un processus par lequel les individus cherchent et donnent du sens à leur vie, se sentent connectés à soi, aux autres, au moment présent et à ce qui est sacré. Très peu d’études en France s’intéressent à la spiritualité dans le contexte du cancer. Ainsi, l’objectif de notre étude était d’identifier et d’étudier le rôle des composantes spirituelles dans le vécu de la maladie cancéreuse.Méthodologie : Nous avons réalisé 15 entretiens semidirectifs auprès de patients du service d’oncologie médicale et de soins palliatifs du CHU de la Timone (Marseille). Une double analyse a été réalisée : 1) une analyse lexicographique et 2) une analyse thématique ciblée sur les entretiens les plus typiques issus de l’analyse lexicographique.Résultats : L’analyse lexicographique a mis en évidence trois classes lexicales. La classe 1 renvoie à l’expérience vécue du cancer ainsi qu’aux transformations et réaménagements internes (40,5 %), la classe 2 est relative à la rupture biographique constitutive du vécu expérientiel du cancer (13,4 %) et la classe 3 correspond à la description du vécu quotidien du cancer (46,1 %). En complément, l’analyse thématique fait apparaître différents thèmes témoignant de la spiritualité dans l’expérience vécue du cancer, notamment l’expérimentation et la relation au sacré, la relation à la transcendance et le rôle de la spiritualité dans le vécu expérientiel des patients.Conclusion : L’analyse des entretiens a permis d’identifier l’expression de composantes spirituelles. Elles s’expriment comme une ressource, un « ressort invisible » afin de permettre l’ajustement à l’expérience extrême de la maladie cancéreuse. Les deux dimensions centrales « laïques » de la spiritualité : la transcendance et la relation au sacré ouvrent des perspectives pour l’intégration de la spiritualité dans la prise en charge des patients atteints de cancer, sans remettre en cause le principe de laïcité des hôpitaux français