Analysis of the first gigantic jet recorded over continental North America

[1] Two low-light cameras near Marfa, Texas, recorded a gigantic jet over northern Mexico on 13 May 2005 at approximately 0423:50 UTC. Assuming that the farthest of two candidate storm systems was its source, the bright lower channel ended in a fork at around 50–59 km height with the very dim upper branches extended to 69–80 km altitude. During the time window containing the jet, extremely low frequency magnetic field recordings show that there was no fast charge moment change larger than 50 coulomb times kilometers (C km) but there was a larger and slower charge moment change of 520 C km over 70 ms. The likely parent thunderstorm was a high-precipitation supercell cluster containing a persistent mesocyclone, with radar echo tops of at least 17 km. However, photogrammetric analysis suggests that the gigantic jet occurred over the forward flank downdraft region with echo tops of 14 km. This part of the supercell may have had an inverted-polarity charge configuration as evidenced by positive cloud-to-ground lightning flashes (+CG) dominating over negative flashes (-CG), while -CGs occurred under the downwind anvil. Four minutes before the gigantic jet, -CG activity practically ceased in this area, while +CG rates increased, culminating during the 20 s leading up to the gigantic jet with four National Lightning Detection Network–detected +CGs. A relative lull in lightning activity of both polarities was observed for up to 1.5 min after the gigantic jet. The maturing storm subsequently produced 30 sprites between 0454 and 0820 UTC, some associated with extremely large impulse charge moment change values.Peer ReviewedPostprint (published version

Patient involvement in medical decision-making and pain among elders: physician or patient-driven?

BACKGROUND: Pain is highly prevalent among older adults, but little is known about how patient involvement in medical decision-making may play a role in limiting its occurrence or severity. The purpose of this study was to evaluate whether physician-driven and patient-driven participation in decision-making were associated with the odds of frequent and severe pain. METHODS: A cross-sectional population-based survey of 3,135 persons age 65 and older was conducted in the 108-county region comprising West Texas. The survey included self-reports of frequent pain and, among those with frequent pain, the severity of pain. RESULTS: Findings from multivariate logistic regression analyses showed that higher patient-driven participation in decision-making was associated with lower odds (OR, 0.82; 95% CI, 0.75–0.89) of frequent pain, but was not significantly associated with severe pain. Physician-driven participation was not significantly associated with frequent or severe pain. CONCLUSIONS: The findings suggest that patients may need to initiate involvement in medical decision-making to reduce their chances of experiencing frequent pain. Changes to other modifiable health care characteristics, including access to a personal doctor and health insurance coverage, may be more conducive to limiting the risk of severe pain

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes

SBML Level 3: an extensible format for the exchange and reuse of biological models

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution

TBR1 regulates autism risk genes in the developing neocortex

Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with autism spectrum disorders (ASD), including TBR1, a master regulator of cortical development. We performed ChIP-seq for TBR1 during mouse cortical neurogenesis and show that TBR1-bound regions are enriched adjacent to ASD genes. ASD genes were also enriched among genes that are differentially expressed in Tbr1 knockouts, which together with the ChIP-seq data, suggests direct transcriptional regulation. Of the nine ASD genes examined, seven were misexpressed in the cortices of Tbr1 knockout mice, including six with increased expression in the deep cortical layers. ASD genes with adjacent cortical TBR1 ChIP-seq peaks also showed unusually low levels of LoF mutations in a reference human population and among Icelanders. We then leveraged TBR1 binding to identify an appealing subset of candidate ASD genes. Our findings highlight a TBR1-regulated network of ASD genes in the developing neocortex that are relatively intolerant to LoF mutations, indicating that these genes may play critical roles in normal cortical development