ISLET: individual-specific reference panel recovery improves cell-type-specific inference.

We propose a statistical framework ISLET to infer individual-specific and cell-type-specific transcriptome reference panels. ISLET models the repeatedly measured bulk gene expression data, to optimize the usage of shared information within each subject. ISLET is the first available method to achieve individual-specific reference estimation in repeated samples. Using simulation studies, we show outstanding performance of ISLET in the reference estimation and downstream cell-type-specific differentially expressed genes testing. We apply ISLET to longitudinal transcriptomes profiled from blood samples in a large observational study of young children and confirm the cell-type-specific gene signatures for pancreatic islet autoantibody. ISLET is available at https://bioconductor.org/packages/ISLET .

Timing and sequencing of oro-pharyngeal swallow events in persistent dysphagia post-stroke / Momento y secuencia de los eventos de deglución orofaríngea en la disfagia persistente post-ictus

Introduction and objectives: Evidence from videofluoroscopic analysis of healthy swallowing physiology shows that typical swallowing function is not entirely ‘sequential’ but are clusters of precisely coordinated movements. It is unknown if disruption of this fine orchestra of events could be associated with persistent dysphagia in individuals post-stroke. This investigation studied the time of onset and sequencing of specific oro-pharyngeal swallowing events as seen in the modified barium swallow study in a population with airway penetration of swallowed bolus post-stroke. Materials and methods: A retrospective frame to frame analysis of 29 time points in single cued 5ml liquid barium swallows obtained from 23 individuals who satisfied inclusion criteria was conducted independently by two investigators. Relative temporal measures with reference to upper esophageal sphincter activity were calculated. Results and conclusion: Statistical analysis revealed five temporal clusters of swallowing events while the onset of oral bolus transport, soft palate elevation, upper esophageal sphincter opening, hyoid descent, and complete laryngeal closing occurred independently. A timeline of event sequences was also developed that showed multiple deviations from the known sequences reported in healthy swallowing literature. There was a delay as well as deviance from known normality in the order of swallowing events considered in this study. The findings suggested a difference in the underlying programming for a swallow in post-stroke dysphagia, that may also contribute to the airway intrusion. The study provides preliminary evidence for the inclusion of temporal measures of swallowing physiology during an instrumental assessment of swallowing function in persons with dysphagia.(AU)

Introducción y objetivos: La evidencia del análisis videofluoroscópico de la fisiología de la deglución saludable muestra que la función de la deglución típica no es completamente «secuencial», sino que son grupos de movimientos coordinados con precisión. Se desconoce si la interrupción de esta fina armonía de eventos podría asociarse con una disfagia persistente en individuos después del accidente cerebrovascular. Esta investigación estudió el tiempo de inicio y la secuenciación de eventos específicos de deglución orofaríngea, como se observa en el estudio modificado de deglución de bario en una población con penetración de las vías respiratorias del bolo ingerido después del accidente cerebrovascular. Materiales y métodos: El análisis retrospectivo paso a paso de 29 momentos de la deglución de 5ml de bario líquido analizados en 23 individuos que cumplieron con los criterios de inclusión fue realizado de forma independiente por dos investigadores. Se calcularon medidas temporales relativas a la actividad del esfínter esofágico superior. Resultados y conclusiones: El análisis estadístico reveló cinco grupos temporales de eventos de deglución, mientras que el inicio del transporte de bolo oral, la elevación del paladar blando, la apertura del esfínter esofágico superior, el descenso de hioides y el cierre laríngeo completo se produjeron de forma independiente. También se desarrolló una línea de tiempo de secuencias de eventos que mostraba múltiples desviaciones de las secuencias conocidas reportadas en la literatura de deglución saludable. Hubo un retraso, así como una desviación de la normalidad en el orden de los eventos de deglución considerados en este estudio. Los hallazgos sugirieron una diferencia en la programación subyacente para una deglución en la disfagia tras el accidente cerebrovascular, que también puede contribuir a la intrusión de las vías respiratorias.(AU)

The association between temporal measures of swallowing with penetration and aspiration in patients with dysphagia: A meta-analysis.

INTRODUCTION: Temporal features of swallowing physiology vary with age in healthy normals and have the potential to impact swallow safety and efficiency in patients with dysphagia. We conducted a meta-analysis to assess the relation between temporal features of swallowing with penetration, aspiration and residue in adult patients with dysphagia regardless of etiology. METHODS: Operational definitions of relevant terms were defined a priori. A search of 5 databases was conducted to November 2016 without restriction to language. Two independent raters reviewed abstracts and full articles, with discrepancies resolved by consensus. All accepted articles advanced to data extraction and critical appraisal according to Cochrane standards. Analysis of pooled data compared measures between groups. RESULTS: Of the 11 articles accepted, the temporal measures used in three or more studies were grouped into morphofunctional categories: bolus transit time; pharyngeal response time; laryngeal closure time; and upper esophageal opening time. Across all selected articles, definitions varied for abnormal swallow and only 4 articles reported rater blinding and reliability for measures related to timing. Pooled data identified two main findings: a. longer pharyngeal response time was associated with penetration and/or aspiration (MD = 0.40 95% CI 0.59 - 0.22), and longer upper esophageal opening duration was associated with only aspiration (PAS ≥ 6) (MD = 0.09 95% CI 0.16 - 0,02). No studies were found that related temporal measures and residue. CONCLUSION: Our pooled findings identified an association of two temporal measures with penetration and/or aspiration but none with residue. The current evidence remains limited due to the heterogeneity across studies in how swallow measures were operationalized. Future work with a standardized and reproducible approach is direly needed.

Paving the Way to Eureka-Introducing "Dira" as an Experimental Paradigm to Observe the Process of Creative Problem Solving.

"Dira" is a novel experimental paradigm to record combinations of behavioral and metacognitive measures for the creative process. This task allows assessing chronological and chronometric aspects of the creative process directly and without a detour through creative products or proxy phenomena. In a study with 124 participants we show that (a) people spend more time attending to selected vs. rejected potential solutions, (b) there is a clear connection between behavioral patterns and self-reported measures, (c) the reported intensity of Eureka experiences is a function of interaction time with potential solutions, and (d) experiences of emerging solutions can happen immediately after engaging with a problem, before participants explore all potential solutions. The conducted study exemplifies how "Dira" can be used as an instrument to narrow down the moment when solutions emerge. We conclude that the "Dira" experiment is paving the way to study the process, as opposed to the product, of creative problem solving.

Respiratory physiology during reading aloud tasks / Fisiología de la respiración en las tareas de lectura en voz alta / Fisiologia respiratória durante tarefas de leitura em voz alta

The purpose of this study was to determine the relation between speech utterance length and respiratory physiology. This experiment correlates respiratory kinematics, muscle activity and acoustic temporal measures of two utterance lengths read aloud tasks: phrase and sentence. Methods: 4 normal speakers read aloud 12 read phrases and 12 read sentences. Respiratory kinematics measures included lung volume excursion (LVE), rib cage excursion (RCE) and abdomen excursion (ABE). Respiratory muscle action included burst duration (BD) and peak amplitude (PA) of rectus abdominis (RA), pectoralis major (PM) and external oblique (EO) muscles. Acoustic temporal measures included phrase and sentence duration. For descriptive statistics means and standard deviations were used, and for inferential statistics Pearson correlation coefficient and Mann-Whitney Wilcoxon test were used. Results: All sentence mean values were greater than phrase and significance was achieved on duration, LVE and RCE means (p=.00). There was a positive correlation between duration, RCE and LVE measures (p=.00). There was a positive correlation between RCE and PA of PM and EO muscles (p=.00). Conclusions: To produce longer utterance tasks, RCE contributes greatly for the LVE needs. The RCE excursions are mostly supported by greater voluntary peak contractions of the PA and EO muscles rather than RA muscles.

Objetivo: O objetivo deste estudo foi determinar a relação entre a duração da produção de fala e a fisiologia respiratória. Este estudo correlaciona a cinemática respiratória, a atividade muscular e a medida acústico-temporal de duas tarefas fonatórias de leitura-em-voz-alta de diferentes durações: oração e frase. Métodos: 4 normofalantes leram em voz alta 12 orações e 12 frases. Medidas cinemáticas respiratórias incluíram expansão do volume pulmonar (EVP), expansão da caixa torácica (ECT) e expansão do abdómen (EAB). A ação muscular respiratória incluiu a duração da contração (DC) e pico de amplitude da contração (AP) dos músculos reto abdominal (RA), peitoral maior (PM) e oblíquo externo (OE). Medidas acústicotemporais incluíram duração da oração e da frase. Para uma estatística descritiva foram utilizadas médias e desvios-padrão. Para a estatística inferencial foi utilizado o coeficiente de correlação de Pearson e o teste de Mann-WhitneyWilcoxon. Resultados: Todas as médias das medidas da frase foram maiores do que das orações, sendo que as médias de duração, EVP e ECT atingiram significância (p=.00). As medidas de EVP e ECT correlacionaram-se positivamente (p=.00). As medidas de ECT correlacionaramse positivamente com PA dos músculos PM e OE (p=.00). Conclusão: As tarefas fonatórias mais longas apresentaram maiores amplitudes de EVP e com maiores contribuições de ECT, comparativamente com as de EAB. Por último, as amplitudes de ECT foram suportadas pelos músculos PA e OE, que apresentaram contrações significativamente mais longas e intensas, comparativamente com o RA.

Objetivo: Se buscó determinar la relación entre la duración de producción del habla y la fisiología respiratoria. Este estudio correlaciona la cinemática de la respiración, la actividad muscular y la medida acústico temporal de dos tareas de fonación de lectura en voz alta: oración y frase. Métodos: Cuatro hablantes normales leyeron doce frases y doce oraciones. Las medidas cinemáticas respiratorias incluían: expansión de volumen pulmonar (EVP), expansión de caja torácica (ECT) y expansión de abdomen (EAB). La acción de los músculos respiratorios incluyó la duración de la contracción (DC) y el pico de amplitud de la contracción (AP) de los músculos del recto abdominal (RA), los pectorales mayores (PM) y el oblicuo externo (OE). Las medidas acústico temporales incluyeron la duración de la oración y de la frase. Para la estadística descriptiva se utilizó desviaciones media y estándar, y para la inferencial se usó el coeficiente de correlación de Pearson y la prueba de Mann-Whitney Wilcoxon. Resultados: Todos los valores medios de las frases fueron mayores que los de las oraciones; las medias de duración EVP y ECT alcanzaron significancia (p = .00). Las medidas de ECT se correlacionaron positivamente con el AP de los músculos PM y OE (p = .00). Conclusión: Las tareas de fonación más largas presentaron mayores amplitudes EVP y mayores contribuciones de ECT, comparado a la EAB. Finalmente, las amplitudes de ECT fueron soportadas por los músculos de AP y OE, que presentaron contracciones significativamente más largas e intensas, comparados con los músculos del RA.

Influence of handwriting skills during spelling in primary and lower secondary grades.

We sought to identify, the impact of handwriting skills on the efficiency and temporal course of word spelling across Grades 2-9. Eighty-four students, drawn from primary and lower secondary schools, were asked to perform a dictation task to assess their word spelling. They also had to write out the letters of the alphabet, as well as their firstnames and surnames, from memory to assess their handwriting skills. Handwriting kinematics were recorded using a digitizing tablet and a computer running Eye and Pen software. Results revealed that graphomotor skills (as assessed by the name writing task) influenced the success and temporal course of spelling, but only in primary grades, whereas the influence of orthographic knowledge (as assessed by the alphabet task) could still be observed in the lower secondary grades, even if it ceased to influence the temporal course and only affected errors. We discuss what these findings tell us about changes in transcription processes over the course of child development.

Control ejecutivo y fluidez verbal en población infantil: Medidas cuantitativas, cualitativas y temporales / Executive control and verbal fluency in child population: Quantitative, qualitative and temporal measures

Para evaluar la evocación de palabras asociadas bajo una consigna de prueba de fluidez verbal (PFV) se tienen en cuenta la cantidad de palabras producidas, las asociaciones categoriales y fonológicas entre ellas y el tiempo en que son evocadas. A continuación se presenta un estudio que se realizó aplicando PFV semánticas y fonológicas en una población infantil (8 - 12 años) de la ciudad de Granada (España), que tuvo por objetivos: (1) revisar las tradicionales medidas en PFV, (2) actualizar los índices temporales de medición y (3) presentar combinaciones de éstas con el fin de establecer con mayor precisión la participación del control ejecutivo en PFV. Se encontraron resultados significativos entre los que se destaca que la combinación entre la medida temporal de evocación de palabras conjuntas y la cualitativa de palabras en relación cluster podría aislar con mayor fiabilidad el compromiso de funciones ejecutivas como el control inhibitorio y la flexibilidad cognitiva. Esto se determinó empleando medidas de regresión, ingresando como variables independientes funciones ejecutivas y como variables dependientes cada una de las medidas de Fluidez Verbal. Para la mencionada combinación de palabras conjuntas - palabras en relación cluster (PFV fonológica letra P) se halló un R² de .41 (p = .000) ingresando como variables predictoras el Trail Making B y la parte Color - Palabra de la versión Trenerry del paradigma Stroop (Lezak, 1995). Se describen también otras posibilidades de medición temporales - cualitativas y su posible utilidad clínica y de investigación.

Verbal fluency tests (VFTs) are considered semantic cognitive tasks. They demand the retrieval of words under different semantic, phonologic, and grammatical conditions. The measures most commonly used to assess word recall in VFTs are: (1) the number of words produced, (2) categorical and phonological association between words, (3) switching between clusters, and (4) the time at which the words are evoked. These measures involve quantitative (1), qualitative (2 and 3), and temporal (4) analyses. In this study, semantic and phonological VFTs were administered to a child population (8-12 years) in Granada (Spain), in order to: (1) review traditional VFT measures, (2) update temporal indices, and (3) introduce combinations, in an effort to more precisely establish the role of executive control. Topics widely-discussed in the literature include two crucial cognitive processes that underlie VFT performance: semantic processing and executive control, which have been associated with activity in temporal and frontal brain regions, respectively. One of the major challenges in the study of these processes is to distinguish between their separate contributions to VFT execution using obtained data. Measures of switching and clustering have traditionally been used to this end, however they do not take into account the time at which the words are evoked. These measures have also been criticized because their final scores are interrelated and exposed to biases difficult to control. Considering temporal measures important, we evaluated the role of five executive control variables (attentional control, cognitive flexibility, inhibitory control, switching, and sustained control) and their relationship with combined quantitative, qualitative and temporal measures. Time variables were included by placing each word evoked on a sixtysecond timeline of verbal production. This way we were able to simultaneously calculate the clustering and switching of words, and their temporal positions. All of these results were associated with executive measures using predictive association statistical techniques. Significant results were found among those measures that emphasized the combination of temporary and qualitative cluster measures. We were also able to reliably isolate the participation of executive functions such as inhibitory control and cognitive flexibility in the combination of spurts and clusters words. This was determined with Multiple Regression Analysis scores, entering the executive functions as independent variables and each of the verbal fluency measures as dependent variables. For example, an R² of .41 (.000) was obtained for the abovementioned combination of spurted -clustered words in the phonological VFT letter P, entering Trail Making B and Trenerry's Color-Word version of the Stroop task (Lezak, 1995) as predictor variables. When compared, these values clearly exceed those obtained with traditional quantitative and qualitative measures. We discussed these results in relation to the possibility of developing a more precise executive control index for VFTs, specifically for the rapid transition from one word to another related word. As far as we know, only switching (shifting between clusters of words) has been considered an executive control index in VFTs. Here we propose the combination measures described. Possible cognitive mechanisms related to these findings are discussed. Future research must contemplate: (1) a greater sample size, because only 61 participants were studied here, (2) using other technical measures to determine clustering and switching, (3) improving the executive function measures, (4) including other VFTs, such as letter exclusion or action fluency, and (5) extending the procedure to an adult population.