1,721,022 research outputs found
GENOME-WIDE ANALYSIS OF TRANSCRIPTION FACTOR NETWORKS IN MYELOID DIFFERENTIATION AND ACUTE MYELOID LEUKAEMIA
No full textOne of the most frequent genetic abnormalities underlying the pathogenesis of acute myeloid leukaemia (AML) is a reciprocal translocation between chromosomes 8 and 21 which results in the generation of a chimeric gene that encodes for the AML1/ETO fusion protein. AML1/ETO has the capacity to block myeloid differentiation, thus leading to the accumulation of immature precursor cells. The fusion protein functions as an aberrant DNA binding transcription factor, therefore altering the normal gene expression profile of the cell. Moreover, it interacts with a number of other transcription factors involved in myeloid differentiation.
In this thesis, a murine haematopoietic stem/precursor cell line was exploited to study AML1/ETO functions. The binding pattern of AML1/ETO was investigated by ChIP-sequencing and correlated to the binding profiles of AML1, PU.1 and C/EBPα transcription factors. The distribution of three histone marks (H3K4me1, H3K4me3 and H3K27ac) upon expression of AML1/ETO was also analysed. The results showed that AML1/ETO expression is associated with modifications in the binding profile of the three transcription factors and in the distribution of chromatin marks, that changes in gene expression are associated with such modifications, and more rarely, with AML1/ETO binding. High-throughput profiling of miRNAs expression revealed the presence of two miRNAs up-regulated by AML1/ETO, miR-322* and miR-351, which are likely candidates for having a role in the block of differentiation, since their inhibition restores the ability of AML1/ETO-expressing cells to differentiate. Analysis of the AML1/ETO-associated gene expression profile predicted a modulation of the cell motility and cell localization. To further explore these functions, in vitro migration assays and in vivo homing experiments were performed. These assays confirmed that AML1/ETO endows the cell with an enhanced motility and an impaired homing of cells to haematopoietic organs.
Bioinformatics analysis of AML1/ETO target genes and their regulatory regions revealed that a modification in the intensity of AML1, PU.1 and C/EBPα binding correlates with changes in gene expression. Sequence analysis showed that STAT6 and other STAT factors could synergize with AML1/ETO in the regulation of gene expression.
Taken together, these results describe how AML1/ETO expression influences its target genes and how the three transcription factors included in the study, chromatin modifications, microRNAs, and putative co-regulators are involved in such regulation. In addition, alterations in cell motility and localization, functions not yet described for AML1/ETO, were identified
The four phases of UCD with associated rules.
No full textDashed lines represent feedback in the iterative process. UCD, user-centered design. Figure adapted by Sierra N. Young and Sheila M. Saia from [27].</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
LA SEGNALAZIONE DEGLI EVENTI SENTINELLA NELLA REGIONE VENETO
No full textINTRODUZIONE: Con il Decreto Ministeriale del 11 dicembre 2009 “Istituzione del sistema informativo per il monitoraggio degli errori in sanità” è stato istituito il cosiddetto flusso SIMES, finalizzato alla raccolta delle informazioni relative agli eventi sentinella (EVS) ed alla denuncia dei sinistri, e tale decreto ha previsto come Regioni e Province Autonome dovessero mettere a disposizione le informazioni relative agli eventi sentinella verificatesi dal 1 Gennaio 2009 ed alle denunce dei sinistri presentate a far data dal 1 luglio 2009, adempimento ricompreso tra quelli cui le regioni devono ottemperare per l'accesso al finanziamento integrativo a carico dello Stato, ai sensi dell'Intesa sancita dalla Conferenza Stato-Regioni il 23 marzo 2005 e successive integrazioni e modifiche.
Allo scopo di dimensionare il ricorso alla segnalazione degli EVS è stata condotta nella regione Veneto, dimensionando il fenomeno nel primo quinquennio di applicazione e indagando la tipologia di eventi segnalati e le relative cause/fattori di rischio. MATERIALI E METODI: Dall’analisi del flusso SIMES relativamente al quinquennio 2009-2013, sono stati considerati tutti gli EVS comprensivi della scheda B e validati a livello regionale segnalati dalle strutture sanitarie operanti nella Regione Veneto, sia pubbliche che private accreditate, presso la quale operano n. 21 Az. ULSS, n. 2 Az. Ospedaliere, n. 1 IRCCS oncologico; n. 28 strutture private accreditate. RISULTATI: Sono stati segnalati complessivamente 363 EVS, mediamente 72,6/anno, con il dato relativo al primo anno dell’analisi presumibilmente sottodimensionato (n. 35) in considerazione dell’imputazione a posteriori.
Per quanto concerne le segnalazioni, ognuna delle 16 tipologie di EVS proposte è stata segnalata e alle segnalazioni hanno contribuito tutte le 24 strutture pubbliche e 23 delle 28 private accreditate, con un range di segnalazioni piuttosto ampio (1-83) e non rapportabile alla tipologia e ai volumi di prestazioni erogate.
L’evento “morte o grave danno per caduta di paziente”, con 137 segnalazioni pari al 38%, rappresenta l’EVS più frequentemente segnalato, seguito da “ogni altro evento avverso che causa morte o grave danno al paziente” con 50 (14%), e dal “suicidio o tentato suicidio di paziente in ospedale” con 34 (9%).
Da riportare come la letalità degli EVS segnalati si sia attestata al 21%, con un picco del 43% riferito al primo anno, e come l’esito più frequentemente riportato sia stato, come atteso in virtù della tipologia di EVS segnalati, il “trauma maggiore conseguente a caduta di paziente” nel 27% dei casi, con la tipologia di EVS relativo alla caduta dei pazienti che nel 71% dei casi ha esitato in un trauma maggior e nel 11% nel decesso.
Per quanto concerne le aree di accadimento, la maggior parte degli EVS segnalati erano appannaggio dell’area medica (43%), seguita dalla chirurgica (20%) e dalla materno infantile (10%), e, dall’analisi per luogo di accadimento, emerge come quasi la metà degli EVS si sia verificata presso le unità di degenza (48%), con la sala operatoria a rappresentare il secondo luogo in termini di frequenza assoluta (16%) e il principale luogo di accadimento per le unità operative dell’area chirurgica (55%).
Di rilievo come dall’analisi delle cause e fattori contribuenti, riportati nelle segnalazioni, l’accadimento degli EVS, oltre a carenze formative e comunicative (33%), fosse principalmente riconducibile a inadeguatezza, violazioni o assenza di linee guida, istruzioni operative o protocolli interni (51%).
Contenuto infine l’impatto delle segnalazioni relative a errori nella terapia farmacologica (5%) e di rilievo invece come le segnalazioni siano pervenute anche da strutture extraospedaliere (4%). CONCLUSIONI: Quanto emerso, oltre a confermare la problematicità della sottonotifica delle segnalazioni, testimoniata dall’elevatissima letalità degli EVS segnalati, pari al 21%, a rappresentazione di un contesto comunque gravato dall’effetto paradosso secondo il quale le istituzioni con un numero maggiore di segnalazioni rappresentano le realtà più attente e sensibili alle politiche della sicurezza e qualità delle cure, conferma la tipologia degli EVS riportati nella letteratura maggiormente accreditata
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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