Design and Performance of a High-Stability Water Vapor Radiometer

[1] The design of two new high-stability microwave water vapor radiometers is presented along with a performance evaluation. The radiometers operate next to a spacecraft tracking station at NASA's Goldstone facility in California, where they will be used to calibrate tropospheric path delay fluctuations during an upcoming gravity-wave search experiment (GWE) involving the Cassini spacecraft. Observing frequencies of the radiometers are 22.2, 23.8, and 31.4 GHz, and the antenna beam width is 1°. The instruments are room temperature Dicke radiometers with additive noise injection for gain calibration. Design highlights include: (1) a practical temperature control system capable of stabilizing the entire receiver to a few millikelvin from day to night; (2) redundant noise diode injection circuits with 30 ppm RF power stability; and (3) a voice coil actuated waveguide vane attenuator which is used as a high-performance Dicke switch. Performance of the radiometers is evaluated from intercomparisons of the two radiometers and from continuous tip curve calibrations spanning nearly 1 year. Structure function analysis of the intercomparison data indicates that the brightness temperature stability of these radiometers is better than 0.01 K on 1000-10,000 s timescales. Analysis of tip curve calibrations indicates RMS errors of $0.05 K on 30-day timescales and 0.15 K on 1-year timescales

Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues

Skeletal muscle comprises a family of diverse tissues with highly specialized functions. Many acquired diseases, including HIV and COPD, affect specific muscles while sparing others. Even monogenic muscular dystrophies selectively affect certain muscle groups. These observations suggest that factors intrinsic to muscle tissues influence their resistance to disease. Nevertheless, most studies have not addressed transcriptional diversity among skeletal muscles. Here we use RNAseq to profile mRNA expression in skeletal, smooth, and cardiac muscle tissues from mice and rats. Our data set, MuscleDB, reveals extensive transcriptional diversity, with greater than 50% of transcripts differentially expressed among skeletal muscle tissues. We detect mRNA expression of hundreds of putative myokines that may underlie the endocrine functions of skeletal muscle. We identify candidate genes that may drive tissue specialization, including Smarca4, Vegfa, and Myostatin. By demonstrating the intrinsic diversity of skeletal muscles, these data provide a resource for studying the mechanisms of tissue specialization

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Virtual Surgical Subinternships: Course Objectives and a Proposed Curriculum

BackgroundDue to the recent COVID-19 pandemic, patient care and medical education have faced many significant changes. The Association of American Medical Colleges and the American Council of Academic Plastic Surgery officially recommended halting all student rotations and interviews for the year. This change has unfortunately fallen squarely at the onset of a vital season for education and recruitment of plastic surgery subinterns. This article presents a curriculum for a single institution's virtual surgical subinternship to help inspire ideas and inspiration for programs developing their own virtual subinternships.MethodsThe goals for the virtual surgical subinternship are focused on student preparation for residency and remain similar to those outlined by the core competencies for in-person rotations. The first virtual subinternship in plastic surgery modeled after the curriculum presented was offered as a 2-week course starting May of 2020.ResultsThe components of the curriculum include a self-study syllabus, virtual case reviews, virtual suture laboratory, educational teleconferences, participation in research, and mentorship meetings. The 2-week course has approximately 25 hours of conferences and teaching, involving direct interaction with residents and faculty, and approximately 15 hours of self-directed learning.ConclusionsTo the authors' knowledge, this was the first virtual subinternship offered for rising fourth-year medical students. They strongly encourage other residency training programs to offer similar virtual learning opportunities for medical students, particularly for those without access to a home plastic surgery training program. The curriculum presented in this article is simply to provide ideas, inspiration, and a potential framework for programs wishing to create similar virtual learning opportunities

The endogenous molecular clock orchestrates the temporal separation of substrate metabolism in skeletal muscle

BACKGROUND: Skeletal muscle is a major contributor to whole-body metabolism as it serves as a depot for both glucose and amino acids, and is a highly metabolically active tissue. Within skeletal muscle exists an intrinsic molecular clock mechanism that regulates the timing of physiological processes. A key function of the clock is to regulate the timing of metabolic processes to anticipate time of day changes in environmental conditions. The purpose of this study was to identify metabolic genes that are expressed in a circadian manner and determine if these genes are regulated downstream of the intrinsic molecular clock by assaying gene expression in an inducible skeletal muscle-specific Bmal1 knockout mouse model (iMS-Bmal1-/- ). METHODS: We used circadian statistics to analyze a publicly available, high-resolution time-course skeletal muscle expression dataset. Gene ontology analysis was utilized to identify enriched biological processes in the skeletal muscle circadian transcriptome. We generated a tamoxifen-inducible skeletal muscle-specific Bmal1 knockout mouse model and performed a time-course microarray experiment to identify gene expression changes downstream of the molecular clock. Wheel activity monitoring was used to assess circadian behavioral rhythms in iMS-Bmal1-/- and control iMS-Bmal1+/+ mice. RESULTS: The skeletal muscle circadian transcriptome was highly enriched for metabolic processes. Acrophase analysis of circadian metabolic genes revealed a temporal separation of genes involved in substrate utilization and storage over a 24-h period. A number of circadian metabolic genes were differentially expressed in the skeletal muscle of the iMS-Bmal1-/- mice. The iMS-Bmal1-/- mice displayed circadian behavioral rhythms indistinguishable from iMS-Bmal1+/+ mice. We also observed a gene signature indicative of a fast to slow fiber-type shift and a more oxidative skeletal muscle in the iMS-Bmal1-/- model. CONCLUSIONS: These data provide evidence that the intrinsic molecular clock in skeletal muscle temporally regulates genes involved in the utilization and storage of substrates independent of circadian activity. Disruption of this mechanism caused by phase shifts (that is, social jetlag) or night eating may ultimately diminish skeletal muscle\u27s ability to efficiently maintain metabolic homeostasis over a 24-h period

Validating a Comprehensive Model of Environmental Concern Cross-Nationally: A U.S.-Canadian Comparison

The dimensionality of "environmental concern" remains ambiguous despite decades of research on environmental attitudes and beliefs. We attempt to provide insight into this issue by using the belief systems perspective and confirmatory factor analysis (CFA) to test a comprehensive conceptualization of environmental concern. Copyright (c) 2007 Southwestern Social Science Association.

Psychiatric Risk Factors for HIV Disease Progression: The Role of Inconsistent Patterns of Antiretroviral Therapy Utilization

BACKGROUND: In the era of anti-retroviral therapy (ART), depression and substance use predict hastened HIV disease progression but the underlying biological or behavioral mechanisms that explain these effects are not fully understood. METHODS: Using outcome data from 603 participants enrolled in a randomized controlled trial of a behavioral intervention, binary logistic and linear regression were employed to examine whether inconsistent patterns of ART utilization partially mediated the effects of depression and substance use on higher HIV viral load over a 25-month follow-up. RESULTS: Elevated affective symptoms of depression independently predicted ART discontinuation (Adjusted OR [AOR] = 1.39, 95% CI = 1.08 – 1.78), and use of stimulants at least weekly independently predicted intermittent ART utilization (AOR = 2.62, 95% CI = 1.45 – 4.73). After controlling for the average self-reported percentage of ART doses taken and baseline T-helper (CD4+) count, elevated depressive symptoms predicted a 50% higher mean viral load, and weekly stimulant use predicted a 137% higher mean viral load. These effects became non-significant after accounting for inconsistent patterns of ART utilization, providing evidence of partial mediation. CONCLUSIONS: Inconsistent patterns of ART utilization may partially explain the effects of depression and stimulant use on hastened HIV disease progression

Psychiatric Risk Factors for HIV Disease Progression: The Role of Inconsistent Patterns of Antiretroviral Therapy Utilization

BACKGROUND: In the era of anti-retroviral therapy (ART), depression and substance use predict hastened HIV disease progression but the underlying biological or behavioral mechanisms that explain these effects are not fully understood. METHODS: Using outcome data from 603 participants enrolled in a randomized controlled trial of a behavioral intervention, binary logistic and linear regression were employed to examine whether inconsistent patterns of ART utilization partially mediated the effects of depression and substance use on higher HIV viral load over a 25-month follow-up. RESULTS: Elevated affective symptoms of depression independently predicted ART discontinuation (Adjusted OR [AOR] = 1.39, 95% CI = 1.08 – 1.78), and use of stimulants at least weekly independently predicted intermittent ART utilization (AOR = 2.62, 95% CI = 1.45 – 4.73). After controlling for the average self-reported percentage of ART doses taken and baseline T-helper (CD4+) count, elevated depressive symptoms predicted a 50% higher mean viral load, and weekly stimulant use predicted a 137% higher mean viral load. These effects became non-significant after accounting for inconsistent patterns of ART utilization, providing evidence of partial mediation. CONCLUSIONS: Inconsistent patterns of ART utilization may partially explain the effects of depression and stimulant use on hastened HIV disease progression