The Business Case for Community Paramedicine: Lessons from Commonwealth Care Alliance's Pilot Program

Mobile integrated health care and community paramedicine (MIH-CP) programs expand the role of traditional emergency medical services personnel to address non-emergency needs and bring outpatient primary and urgent care into patients' homes. These programs offer potential for reducing health care costs, eliminating unecessary emergency department use, and shifting service back to community-based and home settings. Between 2014 and 2015, the Massachusetts-based Commonwealth Care Alliance (CCA) piloted a community paramedicine prgoram, Acute Community Care (ACC), to serve its members in the Greater Boston area.This brief summarizes ACC's business case assessment, which showed that increasing patient volume after the pilot period would reuslt in net savings given the progam's success in averting unnecessary emergency care. By illustrating cost considerations for an expansion of MIH-CP services, this brief may inform the design and sustainability planning of other MIH-CP programs. The business case assessment was conducted by Mathematica Policy Research through support from the Center for Health Care Strategies' Complex Care Innovation Lab, a Kaiser Permanente Community Benefit-funded initiative

Pan-urologic cancer genomic subtypes that transcend tissue of origin

AbstractUrologic cancers include cancers of the bladder, kidney, prostate, and testes, with common molecular features spanning different types. Here, we show that 1954 urologic cancers can be classified into nine major genomic subtypes, on the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy number, and RNA and protein expression). Tissue dominant effects are first removed computationally in order to define these subtypes, which reveal common processes—reflecting in part tumor microenvironmental influences—driving cellular behavior across tumor lineages. Six of the subtypes feature a mixture of represented cancer types as defined by tissue or cell of origin. Differences in patient survival and in the manifestation of specific pathways—including hypoxia, metabolism, NRF2-ARE, Hippo, and immune checkpoint—can further distinguish the subtypes. Immune checkpoint markers and molecular signatures of macrophages and T cell infiltrates are relatively high within distinct subsets of each cancer type studied. The pan-urologic cancer genomic subtypes would facilitate information sharing involving therapeutic implications between tissue-oriented domains.</jats:p

New Molecular Mechanism for Ullrich Congenital Muscular Dystrophy: A Heterozygous In-Frame Deletion in the COL6A1 Gene Causes a Severe Phenotype

Recessive mutations in two of the three collagen VI genes, COL6A2 and COL6A3, have recently been shown to cause Ullrich congenital muscular dystrophy (UCMD), a frequently severe disorder characterized by congenital muscle weakness with joint contractures and coexisting distal joint hyperlaxity. Dominant mutations in all three collagen VI genes had previously been associated with the considerably milder Bethlem myopathy. Here we report that a de novo heterozygous deletion of the COL6A1 gene can also result in a severe phenotype of classical UCMD precluding ambulation. The internal gene deletion occurs near a minisatellite DNA sequence in intron 8 that removes 1.1 kb of genomic DNA encompassing exons 9 and 10. The resulting mutant chain contains a 33–amino acid deletion near the amino-terminus of the triple-helical domain but preserves a unique cysteine in the triple-helical domain important for dimer formation prior to secretion. Thus, dimer formation and secretion of abnormal tetramers can occur and exert a strong dominant negative effect on microfibrillar assembly, leading to a loss of normal localization of collagen VI in the basement membrane surrounding muscle fibers. Consistent with this mechanism was our analysis of a patient with a much milder phenotype, in whom we identified a previously described Bethlem myopathy heterozygous in-frame deletion of 18 amino acids somewhat downstream in the triple-helical domain, a result of exon 14 skipping in the COL6A1 gene. This deletion removes the crucial cysteine, so that dimer formation cannot occur and the abnormal molecule is not secreted, preventing the strong dominant negative effect. Our studies provide a biochemical insight into genotype-phenotype correlations in this group of disorders and establish that UCMD can be caused by dominantly acting mutations

Fate of methoprene in temperate salt marsh ditches following aerial applications

Aerial applications of liquid methoprene are used in salt marshes to control mosquitoes by preventing adult emergence. Despite concern about toxicity to non-target organisms, little is known about environmental concentrations after applications, nor methoprene\u27s persistence in salt marsh environments. Aqueous and sediment samples were collected from two marshes receiving weekly applications. Aqueous samples were collected as early as 30 minutes after applications and as long as nine days afterwards; sediment samples were taken within hours of application and as long as 19 days post-application. Use of time-of-flight liquid chromatography – mass spectral analysis allowed for ultra low detection limits (0.5 ng/L) in water samples. The data show loss of nearly all methoprene from 1 m deep marsh ditches within 1 day and presence but not accumulation of methoprene in marsh sediments despite repeated applications. Methoprene concentrations observed in salt-marsh mosquito ditches were below those found to be of toxicological significance in other studies

Fragmentation production of doubly heavy baryons

Baryons with a single heavy quark are being studied experimentally at present. Baryons with two units of heavy flavor will be abundantly produced not only at future colliders, but also at existing facilities. In this paper we study the production via heavy quark fragmentation of baryons containing two heavy quarks at the Tevatron, the LHC, HERA, and the NLC. The production rate is woefully small at HERA and at the NLC, but significant at $pp$ and $p\bar{p}$ machines. We present distributions in various kinematical variables in addition to the integrated cross sections at hadron colliders.Comment: 13 pages, macro package epsfig needed, 6 .eps figure files in a separate uuencoded, compressed and tarred file; complete paper available at http://www.physics.carleton.ca/~mad/papers/paper.p

5-Androstene-3β,7β,17β-triol (β-AET) Slows Thermal Injury Induced Osteopenia in Mice: Relation to Aging and Osteoporosis

5-androstene-3β,7β,17β-triol (β-AET), an active metabolite of dehydroepiandrosterone (DHEA), reversed glucocorticoid (GC)-induced suppression of IL-6, IL-8 and osteoprotegerin production by human osteoblast-like MG-63 cells and promoted osteoblast differentiation of human mesenchymal stem cells (MSCs). In a murine thermal injury model that includes glucocorticoid-induced osteopenia, β-AET significantly (p<0.05) preserved bone mineral content, restored whole body bone mineral content and endochondral growth, suggesting reversal of GC-mediated decreases in chondrocyte proliferation, maturation and osteogenesis in the growth plate. In men and women, levels of β-AET decline with age, consistent with a role for β-AET relevant to diseases associated with aging. β-AET, related compounds or synthetic derivatives may be part of effective therapeutic strategies to accelerate tissue regeneration and prevent or treat diseases associated with aging such as osteoporosis

Charmed quark component of the photon wave function

We determine the c-anti-c component of the photon wave function on the basis of (i) the data on the transitions e+ e- -> J/psi(3096), psi(3686), psi(4040), psi(4415), (ii) partial widths of the two-photon decays eta_{c0}(2979), chi_{c0}(3415), chi_{c2}(3556) -> gamma-gamma, and (iii) wave functions of the charmonium states obtained by solving the Bethe-Salpeter equation for the c-anti-c system. Using the obtained c-anti-c component of the photon wave function we calculate the gamma-gamma decay partial widths for radial excitation 2S state, eta_{c0}(3594) -> gamma-gamma, and 2P states chi_{c0}(3849), chi_{c2}(3950) -> gamma-gamma.Comment: 20 pages, 8 figure

HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression

<p>Abstract</p> <p>Background</p> <p>17α-Ethynyl-5-androsten-3β, 7β, 17β-triol (HE3286) is a synthetic derivative of an endogenous steroid androstenetriol (β-AET), a metabolite of the abundant adrenal steroid deyhdroepiandrosterone (DHEA), with broad anti-inflammatory activities. We tested the ability of this novel synthetic steroid with improved pharmacological properties to limit non-productive lung inflammation in rodents and attempted to gauge its immunological impact.</p> <p>Methods and Results</p> <p>In mice, oral treatment with HE3286 (40 mg/kg) significantly (<it>p </it>< 0.05) decreased neutrophil counts and exudate volumes (~50%) in carrageenan-induced pleurisy, and myeloperoxidase in lipopolysaccharide-induced lung injury. HE3286 (40 mg/kg) was not found to be profoundly immune suppressive in any of the classical animal models of immune function, including those used to evaluate antigen specific immune responses <it>in vivo </it>(ovalbumin immunization). When mice treated for two weeks with HE3286 were challenged with <it>K. pneumoniae</it>, nearly identical survival kinetics were observed in vehicle-treated, HE3286-treated and untreated groups.</p> <p>Conclusions</p> <p>HE3286 represents a novel, first-in-class anti-inflammatory agent that may translate certain benefits of β-AET observed in rodents into treatments for chronic inflammatory pulmonary disease.</p

The Baculovirus Uses a Captured Host Phosphatase to Induce Enhanced Locomotory Activity in Host Caterpillars

The baculovirus is a classic example of a parasite that alters the behavior or physiology of its host so that progeny transmission is maximized. Baculoviruses do this by inducing enhanced locomotory activity (ELA) that causes the host caterpillars to climb to the upper foliage of plants. We previously reported that this behavior is not induced in silkworms that are infected with a mutant baculovirus lacking its protein tyrosine phosphatase (ptp) gene, a gene likely captured from an ancestral host. Here we show that the product of the ptp gene, PTP, associates with baculovirus ORF1629 as a virion structural protein, but surprisingly phosphatase activity associated with PTP was not required for the induction of ELA. Interestingly, the ptp knockout baculovirus showed significantly reduced infectivity of larval brain tissues. Collectively, we show that the modern baculovirus uses the host-derived phosphatase to establish adequate infection for ELA as a virion-associated structural protein rather than as an enzyme