What You Don’t Know Can Hurt You: Communicating Health Law with Vermont Physicians

Background: Physicians today need a working knowledge of pertinent medical law. With an increased focus on patients’ rights in health care, states are encouraged to set specific laws protecting patients. The additional medical legislation places a challenge on physicians to continually update their medical-legal acumen such as disease reporting, malpractice issues, and medical information access.Little research has been conducted on physicians’ knowledge of the law and medicine. In an effort to expand upon these topics and to find an efficient way to make information about the law and medicine accessible to Vermont physicians, the University of Vermont College of Medicine partnered with the Vermont Board of Medical Practice to answer the following questions: • How well do Vermont physicians understand laws that relate to the practice of medicine? • How do Vermont physicians access nformation on law and medicine? • What topics are most relevant and important to Vermont physicians? • What educational methods willbe effective and how can the Vermont Board of Medial Practice best serve such education needs?https://scholarworks.uvm.edu/comphp_gallery/1018/thumbnail.jp

Illustrating potential efficiency gains from using cost-effectiveness evidence to reallocate Medicare expenditures

This article is available open access through the publisher’s website at the linke below. Copyright @ 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).This article has been made available through the Brunel Open Access Publishing Fund.Objectives - The Centers for Medicare & Medicaid Services does not explicitly use cost-effectiveness information in national coverage determinations. The objective of this study was to illustrate potential efficiency gains from reallocating Medicare expenditures by using cost-effectiveness information, and the consequences for health gains among Medicare beneficiaries. Methods - We included national coverage determinations from 1999 through 2007. Estimates of cost-effectiveness were identified through a literature review. For coverage decisions with an associated cost-effectiveness estimate, we estimated utilization and size of the “unserved” eligible population by using a Medicare claims database (2007) and diagnostic and reimbursement codes. Technology costs originated from the cost-effectiveness literature or were estimated by using reimbursement codes. We illustrated potential aggregate health gains from increasing utilization of dominant interventions (i.e., cost saving and health increasing) and from reallocating expenditures by decreasing investment in cost-ineffective interventions and increasing investment in relatively cost-effective interventions. Results - Complete information was available for 36 interventions. Increasing investment in dominant interventions alone led to an increase of 270,000 quality-adjusted life-years (QALYs) and savings of $12.9 billion. Reallocation of a broader array of interventions yielded an additional 1.8 million QALYs, approximately 0.17 QALYs per affected Medicare beneficiary. Compared with the distribution of resources prior to reallocation, following reallocation a greater proportion was directed to oncology, diagnostic imaging/tests, and the most prevalent diseases. A smaller proportion of resources went to cardiology, treatments (including drugs, surgeries, and medical devices, as opposed to nontreatments such as preventive services), and the least prevalent diseases. Conclusions - Using cost-effectiveness information has the potential to increase the aggregate health of Medicare beneficiaries while maintaining existing spending levels.The Commonwealth Fun

Crustal shortening, exhumation, and strain localization in a collisional orogen: the Bajo Pequeño Shear Zone, Sierra de Pie de Palo, Argentina

The Bajo Pequeño Shear Zone (BPSZ) is a lower-crustal shear zone that records shortening and exhumation associated with the establishment of a new plate boundary, and its placement in a regional structural context suggests that local- to regional-scale strain localization occurred with progressive deformation. A kilometer-scale field and analytical cross section through the ~80 m thick BPSZ and its adjacent rocks indicates an early Devonian (405–400 Ma) phase of deformation on the western margin of Gondwanan continental crust. The earliest stages of the BPSZ, recorded by metamorphic and microstructural data, involved thrusting of a hotter orthogneiss over a relatively cool pelitic unit, which resulted in footwall garnet growth and reset footwall white mica 40Ar/39Ar ages in proximity to the shear zone. Later stages of BPSZ activity, as recorded by additional microstructures and quartz c-axis opening angles, were characterized by strain localization to the center of the shear zone coincident with cooling and exhumation. These and other data suggest that significant regional tectonism persisted in the Famatinian orogenic system for 60–70 million years after one microplate collision (the Precordillera) but ceased 5–10 million years prior to another (Chilenia). A survey of other synchronous structures shows that strain was accommodated on progressively narrower structures with time, indicating a regional pattern of strain localization and broad thermal relaxation as the Precordillera collision evolved.Fil: Garber, Joshua M.. University of California at Davis; Estados UnidosFil: Roeske, Sarah M.. University of California at Davis; Estados UnidosFil: Warren, Jessica. University of Stanford; Estados UnidosFil: Mulcahy, Sean R.. University of California at Berkeley; Estados UnidosFil: McClelland, William C.. University of Iowa; Estados UnidosFil: Austin, Lauren J.. University of Oregon; Estados UnidosFil: Renne, Paul R.. University of California at Berkeley; Estados UnidosFil: Vujovich, Graciela Irene. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Geología. Laboratorio de Tectónica Andina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Crustal Shortening, Exhumation, and Strain Localization in a Collisonal Orogen: the Bajo Pequeno Shear Zone, Sierra de Pie de Palo, Argentina

The Bajo Pequeño Shear Zone (BPSZ) is a lower-crustal shear zone that records shortening and exhumation associated with the establishment of a new plate boundary, and its placement in a regional structural context suggests that local- to regional-scale strain localization occurred with progressive deformation. A kilometer-scale field and analytical cross section through the ~80 m thick BPSZ and its adjacent rocks indicates an early Devonian (405–400 Ma) phase of deformation on the western margin of Gondwanan continental crust. The earliest stages of the BPSZ, recorded by metamorphic and microstructural data, involved thrusting of a hotter orthogneiss over a relatively cool pelitic unit, which resulted in footwall garnet growth and reset footwall white mica 40Ar/39Ar ages in proximity to the shear zone. Later stages of BPSZ activity, as recorded by additional microstructures and quartz c-axis opening angles, were characterized by strain localization to the center of the shear zone coincident with cooling and exhumation. These and other data suggest that significant regional tectonism persisted in the Famatinian orogenic system for 60–70 million years after one microplate collision (the Precordillera) but ceased 5–10 million years prior to another (Chilenia). A survey of other synchronous structures shows that strain was accommodated on progressively narrower structures with time, indicating a regional pattern of strain localization and broad thermal relaxation as the Precordillera collision evolved

Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis

Long noncoding RNAs (lncRNAs) comprise a diverse class of transcripts that structurally resemble mRNAs but do not encode proteins. Recent genome-wide studies in humans and the mouse have annotated lncRNAs expressed in cell lines and adult tissues, but a systematic analysis of lncRNAs expressed during vertebrate embryogenesis has been elusive. To identify lncRNAs with potential functions in vertebrate embryogenesis, we performed a time-series of RNA-seq experiments at eight stages during early zebrafish development. We reconstructed 56,535 high-confidence transcripts in 28,912 loci, recovering the vast majority of expressed RefSeq transcripts while identifying thousands of novel isoforms and expressed loci. We defined a stringent set of 1133 noncoding multi-exonic transcripts expressed during embryogenesis. These include long intergenic ncRNAs (lincRNAs), intronic overlapping lncRNAs, exonic antisense overlapping lncRNAs, and precursors for small RNAs (sRNAs). Zebrafish lncRNAs share many of the characteristics of their mammalian counterparts: relatively short length, low exon number, low expression, and conservation levels comparable to that of introns. Subsets of lncRNAs carry chromatin signatures characteristic of genes with developmental functions. The temporal expression profile of lncRNAs revealed two novel properties: lncRNAs are expressed in narrower time windows than are protein-coding genes and are specifically enriched in early-stage embryos. In addition, several lncRNAs show tissue-specific expression and distinct subcellular localization patterns. Integrative computational analyses associated individual lncRNAs with specific pathways and functions, ranging from cell cycle regulation to morphogenesis. Our study provides the first systematic identification of lncRNAs in a vertebrate embryo and forms the foundation for future genetic, genomic, and evolutionary studies.National Human Genome Research Institute (U.S.) (Grant 1RO1HG005111-01

RNA-SeQC: RNA-seq metrics for quality control and process optimization

Summary: RNA-seq, the application of next-generation sequencing to RNA, provides transcriptome-wide characterization of cellular activity. Assessment of sequencing performance and library quality is critical to the interpretation of RNA-seq data, yet few tools exist to address this issue. We introduce RNA-SeQC, a program which provides key measures of data quality. These metrics include yield, alignment and duplication rates; GC bias, rRNA content, regions of alignment (exon, intron and intragenic), continuity of coverage, 3′/5′ bias and count of detectable transcripts, among others. The software provides multi-sample evaluation of library construction protocols, input materials and other experimental parameters. The modularity of the software enables pipeline integration and the routine monitoring of key measures of data quality such as the number of alignable reads, duplication rates and rRNA contamination. RNA-SeQC allows investigators to make informed decisions about sample inclusion in downstream analysis. In summary, RNA-SeQC provides quality control measures critical to experiment design, process optimization and downstream computational analysis

Robotic Follow-Up for Human Exploration

We are studying how "robotic follow-up" can improve future planetary exploration. Robotic follow-up, which we define as augmenting human field work with subsequent robot activity, is a field exploration technique designed to increase human productivity and science return. To better understand the benefits, requirements, limitations and risks associated with this technique, we are conducting analog field tests with human and robot teams at the Haughton Crater impact structure on Devon Island, Canada. In this paper, we discuss the motivation for robotic follow-up, describe the scientific context and system design for our work, and present results and lessons learned from field testing

Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells

available in PMC 2011 November 01.Cellular RNA levels are determined by the interplay of RNA production, processing and degradation. However, because most studies of RNA regulation do not distinguish the separate contributions of these processes, little is known about how they are temporally integrated. Here we combine metabolic labeling of RNA at high temporal resolution with advanced RNA quantification and computational modeling to estimate RNA transcription and degradation rates during the response of mouse dendritic cells to lipopolysaccharide. We find that changes in transcription rates determine the majority of temporal changes in RNA levels, but that changes in degradation rates are important for shaping sharp 'peaked' responses. We used sequencing of the newly transcribed RNA population to estimate temporally constant RNA processing and degradation rates genome wide. Degradation rates vary significantly between genes and contribute to the observed differences in the dynamic response. Certain transcripts, including those encoding cytokines and transcription factors, mature faster. Our study provides a quantitative approach to study the integrative process of RNA regulation.Human Frontier Science Program (Strasbourg, France)Howard Hughes Medical InstituteBurroughs Wellcome Fund (Career Award at the Scientific Interface

Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis

Depletion of CD8+ lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8+ lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8+ lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4+ effector memory T (TEM) cells and, to a lesser extent, transitional memory T (TTrM) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4+/CCR5+ SIV “target” cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8+ lymphocytes in SIV− RMs led to a sustained increase in the number of potential CD4+ SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4+ TEM cell proliferation of CD8+ lymphocyte–depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4+ TEM and TTrM cell proliferation, it did not recapitulate the viral dynamics of CD8+ lymphocyte depletion. These data suggest that CD8+ lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection