Adaptation of ACMG/AMP guidelines for clinical classification of variants in Pulmonary Arterial Hypertension resolves variants of unclear pathogenicity in ClinVar.

Purpose: Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by pathogenic variants, most frequently in the bone morphogenetic protein receptor type 2 ( ) gene. We formed a ClinGen variant curation expert panel to devise guidelines for the clinical interpretation of variants identified in PAH patients.

Methods: The general ACMG/AMP variant classification criteria were refined for PAH and adapted to following ClinGen procedures.

Defining the clinical validity of genes reported to cause pulmonary arterial hypertension.

Purpose: Pulmonary arterial hypertension (PAH) is a rare, progressive vasculopathy with significant cardiopulmonary morbidity and mortality. Genetic testing is currently recommended for adults diagnosed with heritable, idiopathic, anorexigen-, hereditary hemorrhagic telangiectasia-, and congenital heart disease-associated PAH, PAH with overt features of venous/capillary involvement, and all children diagnosed with PAH. Variants in at least 27 genes have putative evidence for PAH causality.

Persistent reshaping of cohesive sediment towards stable flocs by turbulence.

Cohesive sediment forms flocs of various sizes and structures in the natural turbulent environment. Understanding flocculation is critical in accurately predicting sediment transport and biogeochemical cycles. In addition to aggregation and breakup, turbulence also reshapes flocs toward more stable structures.

Identification and validation of a novel pathogenic variant in GDF2 (BMP9) responsible for hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular dysplasia, characterized by arteriovenous malformations (AVMs), mucocutaneous telangiectasia and nosebleeds. HHT is caused by a heterozygous null allele in ACVRL1, ENG, or SMAD4, which encode proteins mediating bone morphogenetic protein (BMP) signaling. Several missense and stop-gain variants identified in GDF2 (encoding BMP9) have been reported to cause a vascular anomaly syndrome similar to HHT, however none of these patients met diagnostic criteria for HHT.

Investigation of theoretical scaling laws using large eddy simulations for airborne spreading of viral contagion from sneezing and coughing.

Using a set of large eddy point-particle simulations, we explore the fluid dynamics of an ejected puff resulting from a cough/sneeze. The ejection contains over 61 000 potentially virus-laden droplets at an injection Reynolds number of about 46 000, comparable to an actual cough/sneeze. We observe that global puff properties, such as centroid, puff volume, momentum, and buoyancy vary little across realizations.