The geometry of the Landmark Task

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Development of the Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database and the Rett Evaluation of Symptoms and Treatments (REST) Questionnaire

Introduction Rett syndrome (RTT) is a pervasive neurodevelopmental disorder that presents with deficits in brain functioning leading to language and learning regression, characteristic hand stereotypies and developmental delay. Different mutations in the gene implicated in RTT-methyl-CpG-binding protein 2 (MECP2) establishes RTT as a disorder with divergent symptomatology ranging from individuals with severe to milder phenotypes. A reliable and single multidimensional questionnaire is needed that can embrace all symptoms, and the relationships between them, and can map clinically meaningful data to symptomatology across the lifespan in patients with RTT. As part of the HealthTracker-based Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database, the Rett Evaluation of Symptoms and Treatments (REST) Questionnaire will be able to marry with the physiological aspects of the disease obtained using wearable sensor technology, along with genetic and psychosocial data to stratify patients. Taken together, the web-based TRIAL database will empower clinicians and researchers with the confidence to delineate between different aspects of disorder symptomatology to streamline care pathways for individuals or for those patients entering clinical trials. This protocol describes the anticipated development of the REST questionnaire and the TRIAL database which links with the outcomes of the wearable sensor technology, and will serve as a barometer for longitudinal patient monitoring in patients with RTT. Methods and analysis The US Food and Drug Administration Guidance for Patient-Reported Outcome Measures will be used as a template to inform the methodology of the study. It will follow an iterative framework that will include item/concept identification, item/concept elicitation in parent/carer-mediated focus groups, expert clinician feedback, web-based presentation of questionnaires, initial scale development, instrument refinement and instrument validation. Ethics and dissemination The study has received favourable opinion from the National Health Service (NHS) Research Ethics Committee (REC): NHS Research Ethics Committee (REC)-London, Bromley Research Ethics Committee (reference: 15/LO/1772).</p

Online change point detection for weighted and directed random dot product graphs

Given a sequence of random (directed and weighted) graphs, we address the problem of online monitoring and detection of changes in the underlying data distribution. Our idea is to endow sequential change-point detection (CPD) techniques with a graph representation learning substrate based on the versatile Random Dot Product Graph (RDPG) model. We consider efficient, online updates of a judicious monitoring function, which quantifies the discrepancy between the streaming graph observations and the nominal RDPG. This reference distribution is inferred via spectral embeddings of the first few graphs in the sequence. We characterize the distribution of this running statistic to select thresholds that guarantee error-rate control, and under simplifying approximations we offer insights on the algorithm’s detection resolution and delay. The end result is a lightweight online CPD algorithm, that is also explainable by virtue of the well-appreciated interpretability of RDPG embeddings. This is in stark contrast with most existing graph CPD approaches, which either rely on extensive computation, or they store and process the entire observed time series. An apparent limitation of the RDPG model is its suitability for undirected and unweighted graphs only, a gap we aim to close here to broaden the scope of the CPD framework. Unlike previous proposals, our non-parametric RDPG model for weighted graphs does not require a priori specification of the weights’ distribution to perform inference and estimation. This network modeling contribution is of independent interest beyond CPD. We offer an open-source implementation of the novel online CPD algorithm for weighted and direct graphs, whose effectiveness and efficiency are demonstrated via (reproducible) synthetic and real network data experimentsWork in this paper is supported in part by ANII (grant FMV 3 2018 1 148149) and the NSF (awards CCF-1750428, CCF-1934962 and ECCS-1809356). Part of the results in this paper were submitted to the 2021 EUSIPCO and Asilomar Conference

Decoupling between SARS-CoV-2 transmissibility and population mobility associated with increasing immunity from vaccination and infection in South America

All South American countries from the Southern cone (Argentina, Brazil, Chile, Paraguay and Uruguay) experienced severe COVID-19 epidemic waves during early 2021 driven by the expansion of variants Gamma and Lambda, however, there was an improvement in different epidemic indicators since June 2021. To investigate the impact of national vaccination programs and natural infection on viral transmission in those South American countries, we analyzed the coupling between population mobility and the viral effective reproduction number Rt. Our analyses reveal that population mobility was highly correlated with viral Rt from January to May 2021 in all countries analyzed; but a clear decoupling occurred since May–June 2021, when the rate of viral spread started to be lower than expected from the levels of social interactions. These findings support that populations from the South American Southern cone probably achieved the conditional herd immunity threshold to contain the spread of regional SARS-CoV-2 variants circulating at that time

Opioid Peptide Gene Expression in the Primary Hereditary Cardiomyopathy of the Syrian Hamster I. REGULATION OF PRODYNORPHIN GENE EXPRESSION BY NUCLEAR PROTEIN KINASE C

Prodynorphin gene expression was investigated in adult ventricular myocytes isolated from normal (F1B) or cardiomyopathic (BIO 14.6) hamsters. Prodynorphin mRNA levels were higher in cardiomyopathic than in control myocytes and were stimulated by treatment of control cells with the protein kinase C (PKC) activator 1, 2-dioctanoyl-sn-glycerol. Both chelerythrine and calphostin C, two PKC inhibitors, abolished the stimulatory effect of the diglyceride and significantly reduced prodynorphin gene expression in cardiomyopathic myocytes. Nuclear run-off experiments indicated that the prodynorphin gene was regulated at the transcriptional level and that treatment of nuclei isolated from control cells with 1, 2-dioctanoyl-sn-glycerol increased prodynorphin gene transcription, whereas chelerythrine or calphostin C abolished this transcriptional effect. Direct exposure of nuclei isolated from cardiomyopathic myocytes to these inhibitors markedly down-regulated the rate of gene transcription. The expression of PKC-alpha, -delta, and -epsilon, as well as PKC activity, were increased in nuclei of cardiomyopathic myocytes compared with nuclei from control cells. The levels of both intracellular and secreted dynorphin B, a biologically active product of the gene, were higher in cardiomyopathic than in control cells and were stimulated or inhibited by cell treatment with 1,2-dioctanoyl-sn-glycerol or PKC inhibitors, respectively

Relación entre movilidad y tasa de reproducción.

En este documento se analiza la correlación entre índices de movilidad con datos de Google y el número de reproducción R, calculado a partir de datos públicos de fecha de test. Como el fenómeno biológico tiene ciertos tiempos intrínsecos, una variación significativa en el comportamiento de la población podría generar cambios en la tasa de reproducción cierta cantidad de días después. Para analizar este corrimiento temporal se busca la cantidad de días que hay que desplazar las series temporales de movilidad y R para maximizar la correlación. Finalmente, teniendo en cuenta estos desplazamientos, se compara la movilidad trasladada en el tiempo con el número de reproducción, para visualizar la relación entre las tendencias de ambos. Se observa una correlación significativa entre la movilidad y la tasa de reproducción, en escenarios epidemiológicos de alta transmisión comunitaria como el que enfrentamos en Uruguay desde fines de 2020. Además, se realizan estudios similares para Chile e Israel

Tactile distance illusions reflect a coherent stretch of tactile space

Illusions of the perception of distance between two touches on the skin have been described since the classic work of Weber in the 19th century. The perceptual mechanisms underlying such spatial distortions, however, remain poorly understood. One potential interpretation is that the representational space of touch is related to the true structure of the skin by a geometrically simple stretch. If distortions of tactile distance perception reflect a simple stretch of tactile space, perceived distance should vary predictably as a function of the orientation of the stimulus on the skin, showing a sinusoidal pattern. Here, we tested this prediction by obtained judgments of perceived tactile distance for pairs of touches aligned with eight orientations on the skin. Across four experiments, the results were highly consistent with this prediction, showing no apparent deviation from a model of simple stretch of tactile space. Similar results were apparent on both the dorsum and palm of the hand, as well as the forehead. These results show that spatial distortions of touch are well characterized by a geometrically simple stretch of tactile space

Linee guida per lo sviluppo di modelli numerici di flusso in acquiferi porosi: Una proposta IRSA-ISPRA

A livello nazionale, nell'ambito dei procedimenti di bonifica dei siti contaminati, disciplinati dalla parte Quarta – Titolo V del decreto legislativo 152 del 2006, l'implementazione di modelli matematici di flusso e di trasporto dei contaminanti è uno strumento che ha acquisito con il tempo sempre maggiore importanza, soprattutto ai fini della definizione e progettazione degli interventi di messa in sicurezza e bonifica delle acque di falda. Modelli matematici sono utilizzati anche a scala di bacino o sottobacino per la caratterizzazione e la gestione delle risorse idriche sotterranee [...]

Eventos de supercontagio.

Los eventos de supercontagio, aquellos donde se produce una transmisión de la enfermedad a un número de personas mucho mayor al promedio para esa misma enfermedad, presentan un riesgo importante para el manejo de la pandemia de COVID-19 en los próximos meses. En esta nota intentamos avanzar en la caracterización, a partir de un repaso de la literatura existente, de los eventos de supercontagio, entender su relevancia en el marco de la COVID-19, y presentar algunas posibles acciones que, a través del control de este tipo de eventos, podrían ser útiles para el manejo general de la pandemia, en especial en el caso de Uruguay