Solar Intranetwork Magnetic Elements: bipolar flux appearance

The current study aims to quantify characteristic features of bipolar flux appearance of solar intranetwork (IN) magnetic elements. To attack such a problem, we use the Narrow-band Filter Imager (NFI) magnetograms from the Solar Optical Telescope (SOT) on board \emph{Hinode}; these data are from quiet and an enhanced network areas. Cluster emergence of mixed polarities and IN ephemeral regions (ERs) are the most conspicuous forms of bipolar flux appearance within the network. Each of the clusters is characterized by a few well-developed ERs that are partially or fully co-aligned in magnetic axis orientation. On average, the sampled IN ERs have total maximum unsigned flux of several 10^{17} Mx, separation of 3-4 arcsec, and a lifetime of 10-15 minutes. The smallest IN ERs have a maximum unsigned flux of several 10^{16} Mx, separations less than 1 arcsec, and lifetimes as short as 5 minutes. Most IN ERs exhibit a rotation of their magnetic axis of more than 10 degrees during flux emergence. Peculiar flux appearance, e.g., bipole shrinkage followed by growth or the reverse, is not unusual. A few examples show repeated shrinkage-growth or growth-shrinkage, like magnetic floats in the dynamic photosphere. The observed bipolar behavior seems to carry rich information on magneto-convection in the sub-photospheric layer.Comment: 26 pages, 14 figure

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

A new algorithm for epilepsy seizure onset detection and spread estimation from EEG signals

International audienceAppropriate diagnosis and treatment of epilepsy is a main public health issue. Patients suffering from this disease often exhibit different physical characterizations, which result from the synchronous and excessive discharge of a group of neurons in the cerebral cortex. Extracting this information using EEG signals is an important problem in biomedical signal processing. In this work we propose a new algorithm for seizure onset detection and spread estimation in epilepsy patients. The algorithm is based on a multilevel 1-D wavelet decomposition that captures the physiological brain frequency signals coupled with a generalized gaussian model. Preliminary experiments with signals from 30 epilepsy crisis and 11 subjects, suggest that the proposed methodology is a powerful tool for detecting the onset of epilepsy seizures with his spread across the brain

Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement

Background: Jeune asphyxiating thoracic dystrophy (JATD) is a rare, often lethal, recessively inherited chondrodysplasia characterised by shortened ribs and long bones, sometimes accompanied by polydactyly, and renal, liver and retinal disease. Mutations in intraflagellar transport (IFT) genes cause JATD, including the IFT dynein-2 motor subunit gene DYNC2H1. Genetic heterogeneity and the large DYNC2H1 gene size have hindered JATD genetic diagnosis.Aims and methods: to determine the contribution to JATD we screened DYNC2H1 in 71 JATD patients JATD patients combining SNP mapping, Sanger sequencing and exome sequencing.Results and conclusions: we detected 34 DYNC2H1 mutations in 29/71 (41%) patients from 19/57 families (33%), showing it as a major cause of JATD especially in Northern European patients. This included 13 early protein termination mutations (nonsense/frameshift, deletion, splice site) but no patients carried these in combination, suggesting the human phenotype is at least partly hypomorphic. In addition, 21 missense mutations were distributed across DYNC2H1 and these showed some clustering to functional domains, especially the ATP motor domain. DYNC2H1 patients largely lacked significant extra-skeletal involvement, demonstrating an important genotype–phenotype correlation in JATD. Significant variability exists in the course and severity of the thoracic phenotype, both between affected siblings with identical DYNC2H1 alleles and among individuals with different alleles, which suggests the DYNC2H1 phenotype might be subject to modifier alleles, non-genetic or epigenetic factors. Assessment of fibroblasts from patients showed accumulation of anterograde IFT proteins in the ciliary tips, confirming defects similar to patients with other retrograde IFT machinery mutations, which may be of undervalued potential for diagnostic purpose

The effect of pre-exercise carbohydrate feedings on the intensity that elicits maximal fat oxidation

Type 2 collagen disorders encompass a diverse group of skeletal dysplasias that are commonly associated with orthopedic, ocular, and hearing problems. However, the frequency of many clinical features has never been determined. We retrospectively investigated the clinical, radiological, and genotypic data in a group of 93 patients with molecularly confirmed SEDC or a related disorder. The majority of the patients (80/93) had short stature, with radiological features of SEDC (n = 64), others having SEMD (n = 5), Kniest dysplasia (n = 7), spondyloperipheral dysplasia (n = 2), or Torrance-like dysplasia (n = 2). The remaining 13 patients had normal stature with mild SED, Stickler-like syndrome or multiple epiphyseal dysplasia. Over 50% of the patients had undergone orthopedic surgery, usually for scoliosis, femoral osteotomy or hip replacement. Odontoid hypoplasia was present in 56% (95% CI 38-74) and a correlation between odontoid hypoplasia and short stature was observed. Atlanto-axial instability, was observed in 5 of the 18 patients (28%, 95% CI 10-54) in whom flexion-extension films of the cervical spine were available; however, it was rarely accompanied by myelopathy. Myopia was found in 45% (95% CI 35-56), and retinal detachment had occurred in 12% (95% CI 6-21; median age 14 years; youngest age 3.5 years). Thirty-two patients complained of hearing loss (37%, 95% CI 27-48) of whom 17 required hearing aids. The ophthalmological features and possibly also hearing loss are often relatively frequent and severe in patients with splicing mutations. Based on clinical findings, age at onset and genotype-phenotype correlations in this cohort, we propose guidelines for the management and follow-up in this group of disorders