The Changing Composition and Capacity of Medicare Providers, 2012-2015

Objective: Over the past decade, U.S. medical school enrollment has increased nearly 30 percent, and the growth in mid-level new graduates was even faster. Many of these new graduates are currently serving the large and growing Medicare population. Yet, little evidence so far has documented the workforce that are serving Medicare population. In the anticipation of physician supply shortages, it is important to understand who are taking care of Medicare population recently, and whether there are changes in the overall capacity and patient risk profiles of Medicare providers. Methods: Data were from 2012-2015 Medicare Physician and Other Supplier Aggregate Tables at the Centers for Medicare & Medicaid Services website, which contain information on utilization, payment, and procedures provided to more than 10 Medicare Part B beneficiaries by U.S. physicians and nurses. We identified primary care physicians (i.e., family practice, internal medicine, general practitioners, and geriatric medicine), specialists, and mid-level providers (e.g., nurse practitioners, physician assistants, etc.) based on self-reported provider type in the data. We conducted trend analysis to examine the changes in the proportion of physicians and mid-level providers over time, and also compared utilization, payment amount, and patient risk profiles of physicians and nurses between 2012 and 2015, respectively. Findings: Over the study period, the number of providers with more than 10 Medicare patients increased from 709,982 in 2012 to 782,836 in 2015. The proportion of both primary care physicians and specialists declined consistently, while in contrast, the proportion of mid-level providers increased correspondingly, from 20% in 2012 to 24% in 2015. Compared to 2012, Physicians in 2015 served fewer Medicare patients, but provided more services to beneficiaries, and had no changes in payment received than in 2015. In contrast, mid-level providers served more patients, provided more services per patient, and received higher payments in 2015 than in 2012. Both physicians and mid-level providers served more patients diagnosed with depression, asthma, chronic kidney disease, and stroke in 2015 than in 2012. Conclusion: Medicare provider composition has been changing in recent years, where mid-level providers are playing an increasing role in serving Medicare beneficiaries. State legislatures and policymakers may consider expanding scope-of-practice for mid-level providers and also weigh the importance of innovating new payment policy to better reimburse mid-level providers. Future research is needed to compare the capacity of new and existing providers and the relationship between year of practicing and capacity building to serve more Medicare patients

Rigorous Analytic Combinatorics in Several Variables in SageMath

We introduce the new sage_acsv package for the SageMath computer algebra system, allowing users to rigorously compute asymptotics for a large variety of multivariate sequences with rational generating functions. Using Sage's support for exact computations over the algebraic number field, this package provides the first rigorous implementation of algorithms from the theory of analytic combinatorics in several variables.Comment: 8 pages; Package: https://pypi.org/project/sage-acsv

The evolution of extragalactic radio sources

A model for the evolution of low-luminosity radio galaxies is presented. In the model, the lobes inflated by low-power jets are assumed to expand in near pressure-balance against the external medium. Both cases of constant external pressure and decreasing external pressure are considered. Evolution of an individual source is described by the power-size track. The source appears as its lobe is inflated and radio luminosity increases to above the detection level; the source then moves along the track and eventually disappears as its luminosity drops below the detection limit. The power-size tracks are calculated including the combined energy losses due to synchrotron radiation, adiabatic expansion, and inverse Compton scattering. It is shown that in general, the constant-pressure model predicts an excess number of luminous, small-size sources while underpredicting large-size sources in the power-size diagram. The predicted spectra are steep for most sources, which is inconsistent with observations. By comparison, the pressure-limiting model fits observations better. In this model, low-luminosity sources undergo substantial expansion losses in the initial phase and as a result, it predicts fewer luminous, small-size sources. The resultant spectra are flat for most sources except for the oldest ones, which seems consistent with observations. The power-size tracks, in contrast to that of high-luminosity radio galaxies, are characterized by a slow increase in luminosity for most of the source's life, followed by a rapid decline when the synchrotron or inverse Compton scattering losses set in.Comment: 13 pages, 8 figures, 2 tables, accepted for publication in Ap

A primer for microbiome time-series analysis

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Coenen, A. R., Hu, S. K., Luo, E., Muratore, D., & Weitz, J. S. A primer for microbiome time-series analysis. Frontiers in Genetics, 11, (2020): 310, doi:10.3389/fgene.2020.00310.Time-series can provide critical insights into the structure and function of microbial communities. The analysis of temporal data warrants statistical considerations, distinct from comparative microbiome studies, to address ecological questions. This primer identifies unique challenges and approaches for analyzing microbiome time-series. In doing so, we focus on (1) identifying compositionally similar samples, (2) inferring putative interactions among populations, and (3) detecting periodic signals. We connect theory, code and data via a series of hands-on modules with a motivating biological question centered on marine microbial ecology. The topics of the modules include characterizing shifts in community structure and activity, identifying expression levels with a diel periodic signal, and identifying putative interactions within a complex community. Modules are presented as self-contained, open-access, interactive tutorials in R and Matlab. Throughout, we highlight statistical considerations for dealing with autocorrelated and compositional data, with an eye to improving the robustness of inferences from microbiome time-series. In doing so, we hope that this primer helps to broaden the use of time-series analytic methods within the microbial ecology research community.This work was supported by the Simons Foundation (SCOPE award ID 329108) and the National Science Foundation (NSF Bio Oc 1829636)

Diversity and origins of bacterial and archaeal viruses on sinking particles reaching the abyssal ocean

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Luo, E., Leu, A. O., Eppley, J. M., Karl, D. M., & DeLong, E. F. Diversity and origins of bacterial and archaeal viruses on sinking particles reaching the abyssal ocean. ISME Journal, 16, : 1627–1635, https://doi.org/10.1038/s41396-022-01202-1.Sinking particles and particle-associated microbes influence global biogeochemistry through particulate matter export from the surface to the deep ocean. Despite ongoing studies of particle-associated microbes, viruses in these habitats remain largely unexplored. Whether, where, and which viruses might contribute to particle production and export remain open to investigation. In this study, we analyzed 857 virus population genomes associated with sinking particles collected over three years in sediment traps moored at 4000 m in the North Pacific Subtropical Gyre. Particle-associated viruses here were linked to cellular hosts through matches to bacterial and archaeal metagenome-assembled genome (MAG)-encoded prophages or CRISPR spacers, identifying novel viruses infecting presumptive deep-sea bacteria such as Colwellia, Moritella, and Shewanella. We also identified lytic viruses whose abundances correlated with particulate carbon flux and/or were exported from the photic to abyssal ocean, including cyanophages. Our data are consistent with some of the predicted outcomes of the viral shuttle hypothesis, and further suggest that viral lysis of both autotrophic and heterotrophic prokaryotes may play a role in carbon export. Our analyses revealed the diversity and origins of prevalent viruses found on deep-sea sinking particles and identified prospective viral groups for future investigation into processes that govern particle export in the open ocean.This project is funded by grants from the Simons Foundation (#329108 to EFD and DMK, #721223 to EFD, and #721252 to DMK) and the Gordon and Betty Moore Foundation (GBMF3777 to EFD and GBMF3794 to DMK). Partial support for EL was provided by the Natural Sciences and Engineering Research Council of Canada (PGSD3-487490-2016)

Microbial sources of exocellular DNA in the ocean

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Linney, M. D., Eppley, J. M., Romano, A. E., Luo, E., DeLong, E. F., & Karl, D. M. Microbial sources of exocellular DNA in the ocean. Applied and Environmental Microbiology, 88(7), (2022): e02093-21, https://doi.org/10.1128/aem.02093-21.Exocellular DNA is operationally defined as the fraction of the total DNA pool that passes through a membrane filter (0.1 μm). It is composed of DNA-containing vesicles, viruses, and free DNA and is ubiquitous in all aquatic systems, although the sources, sinks, and ecological consequences are largely unknown. Using a method that provides separation of these three fractions, we compared open ocean depth profiles of DNA associated with each fraction. Pelagibacter-like DNA dominated the vesicle fractions for all samples examined over a depth range of 75 to 500 m. Viral DNA consisted predominantly of myovirus-like and podovirus-like DNA and contained the highest proportion of unannotated sequences. Euphotic zone free DNA (75 to 125 m) contained primarily bacterial and viral sequences, with bacteria dominating samples from the mesopelagic zone (500 to 1,000 m). A high proportion of mesopelagic zone free DNA sequences appeared to originate from surface waters, including a large amount of DNA contributed by high-light Prochlorococcus ecotypes. Throughout the water column, but especially in the mesopelagic zone, the composition of free DNA sequences was not always reflective of cooccurring microbial communities that inhabit the same sampling depth. These results reveal the composition of free DNA in different regions of the water column (euphotic and mesopelagic zones), with implications for dissolved organic matter cycling and export (by way of sinking particles and/or migratory zooplankton) as a delivery mechanism.This work was supported by the Simons Collaboration on Ocean Processes and Ecology (awards 329108 to D.M.K. and E.F.D., 721252 to D.M.K., and 721223 to E.F.D.)

Diel cycling of the cosmopolitan abundant Pelagibacter virus 37‐F6: one of the most abundant viruses on earth

The spatiotemporal dynamics for marine viral populations has only recently been explored. However, nothing is known about temporal activities of the uncultured Pelagibacter virus vSAG 37‐F6, which was discovered by single‐virus genomics as potentially the most abundant marine virus. Here, we investigate the diel cycling of 37‐F6 virus and the putative SAR11 host using coastal and oceanic transcriptomic and viromic time‐series data from Osaka Bay and North Pacific Subtropical Gyre. Virus 37‐F6 and relatives displayed diel cycling of transcriptional activities synchronized with its putative host. In both virus and host, the lowest transcription rates were observed at 14:00–15:00, coinciding roughly with maximum solar irradiance, while higher transcriptional rates were detected during the night/early morning and afternoon. Diel abundance of free viruses of 37‐F6 in seawater roughly mirrored the transcriptional activities of both virus and host. In Osaka Bay, among viral relatives (genus level), virus 37‐F6 specifically showed the highest ratio of transcriptional activity to virome abundance, a proxy for viral transcriptional activity relative to free viral particle abundance. This high ratio suggests high infection rate efficiencies in vSAG 37‐F6 virus compared to viral relatives. Thus, time‐series data revealed temporal transcript activities in one of the most abundant viruses in Earth.This work has been supported by Spanish Ministry of Economy and Competitiveness to MMG (Ref. RTI2018-094248-B-100), Generalitat Valenciana to FMH (ACIF/2015/332), and Gordon and Betty Moore Foundation to MMG (grant 5334). Gordon and Betty Moore Foundation to EFD (3777) and Simons Foundation Grant #329108 (to EFD)

Berberine Inhibits HIV Protease Inhibitor-Induced Inflammatory Response by Modulating ER Stress Signaling Pathways in Murine Macrophages

Background HIV protease inhibitor (PI)-induced inflammatory response plays an important role in HIV PI-associated dyslipidemia and cardiovascular complications. This study examined the effect of berberine, a traditional herb medicine, on HIV PI-induced inflammatory response and further investigated the underlying cellular/molecular mechanisms in macrophages. Methodology and Principal Findings Cultured mouse J774A.1 macrophages and primary mouse macrophages were used in this study. The expression of TNF-α and IL-6 were detected by real-time RT-PCR and ELISA. Activations of ER stress and ERK signaling pathways were determined by Western blot analysis. Immunofluorescent staining was used to determine the intracellular localization of RNA binding protein HuR. RNA-pull down assay was used to determine the association of HuR with endogenous TNF-α and IL-6. Berberine significantly inhibited HIV PI-induced TNF-α and IL-6 expression by modulating ER stress signaling pathways and subsequent ERK activation, in turn preventing the accumulation of the RNA binding protein HuR in cytosol and inhibiting the binding of HuR to the 3′-UTRs of TNF-α and IL-6 in macrophages. Conclusions and Significance Inhibition of ER stress represents a key mechanism by which berberine prevents HIV PI-induced inflammatory response. Our findings provide a new insight into the molecular mechanisms of berberine and show the potential application of berberine as a complimentary therapeutic agent for HIV infection

mRNA Display Design of Fibronectin-based Intrabodies That Detect and Inhibit Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein

The nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) coronavirus plays important roles in both viral replication and modulation of host cell processes. New ligands that target the N protein may thus provide tools to track the protein inside cells, detect interaction hot spots on the protein surface, and discover sites that could be used to develop new anti-SARS therapies. Using mRNA display selection and directed evolution, we designed novel antibody-like protein affinity reagents that target SARS N protein with high affinity and selectivity. Our libraries were based on an 88-residue variant of the 10th fibronectin type III domain from human fibronectin (10Fn3). This selection resulted in eight independent 10Fn3 intrabodies, two that require the N-terminal domain for binding and six that recognize the C terminus, one with K_d = 1.7 nM. 10Fn3 intrabodies are well expressed in mammalian cells and are relocalized by N in SARS-infected cells. Seven of the selected intrabodies tested do not perturb cellular function when expressed singly in vivo and inhibit virus replication from 11- to 5900-fold when expressed in cells prior to infection. Targeting two sites on SARS-N simultaneously using two distinct 10Fn3s results in synergistic inhibition of virus replication