Time series irreversibility: a visibility graph approach

We propose a method to measure real-valued time series irreversibility which combines two differ- ent tools: the horizontal visibility algorithm and the Kullback-Leibler divergence. This method maps a time series to a directed network according to a geometric criterion. The degree of irreversibility of the series is then estimated by the Kullback-Leibler divergence (i.e. the distinguishability) between the in and out degree distributions of the associated graph. The method is computationally effi- cient, does not require any ad hoc symbolization process, and naturally takes into account multiple scales. We find that the method correctly distinguishes between reversible and irreversible station- ary time series, including analytical and numerical studies of its performance for: (i) reversible stochastic processes (uncorrelated and Gaussian linearly correlated), (ii) irreversible stochastic pro- cesses (a discrete flashing ratchet in an asymmetric potential), (iii) reversible (conservative) and irreversible (dissipative) chaotic maps, and (iv) dissipative chaotic maps in the presence of noise. Two alternative graph functionals, the degree and the degree-degree distributions, can be used as the Kullback-Leibler divergence argument. The former is simpler and more intuitive and can be used as a benchmark, but in the case of an irreversible process with null net current, the degree-degree distribution has to be considered to identifiy the irreversible nature of the series.Comment: submitted for publicatio

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Liquido cefalorraqueano no récem-nascido pré-termo sadio

Estudo da composição do LCR de 54 recém-nascidos prematuros sadios no segundo dia de vida. Os prematuros estudados precediam de gestações sem inter-corrências com parto não-traumático, apresentavam Apgar entre 6 e 9 aos 5 minutos de vida e não apresentavam anormalidades quanto ao exame clínico, neurológico, hematimétrico e gasométrico. Da composição do LCR foram estu-dades a citometria e as concentrações de proteínas totais, glicose, bilirrubina e hemoglobina. As estimativas encontradas permitem aceitar como limites das variações fisiológicas da composição do LCR do RN-PT os seguintes valores: leucócitos até 16 por mm ³; hemácias até 1.280 por mm3; proteínas totais até 300 mg/100 ml; bilirrubina de 10 a 80 µM/l; hemoglobina até 8 µM/l; glicose: cerca de 2/3 da concentração no sangue. Em relação à composição do LCR de 79 recém-nascidos normais a termo, avaliada mediante os mesmos métodos e no mesmo laboratório, são significativamente maiores as concentrações de proteínas totais e de bilirrubina, bem como estar presente a hemoglobina, pigmento não demonstrado no recém-nascido a termo. É discutida a importância da imaturidade da barreira hêmato-liquórica quanto às características do LCR apontadas, considerando-se encontrar-se ela ainda menos diferenciada no recém-nascido prematuro que no recém-nascido a termo

Autistic Perspectives on the Future of Clinical Autism Research

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