358 research outputs found

    State Trademark And Unfair Competition Law by The United States Trademark Association

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    \u3cem\u3eCopyright Principles, Law and Practice\u3c/em\u3e by Paul Goldstein

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    \u3cem\u3eCopyright Principles, Law and Practice\u3c/em\u3e by Paul Goldstein

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    Development and assessment of a new framework for disease surveillance, prediction, and risk adjustment: the diagnostic items classification system

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    IMPORTANCE: Current disease risk-adjustment formulas in the US rely on diagnostic classification frameworks that predate the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). OBJECTIVE: To develop an ICD-10-CM-based classification framework for predicting diverse health care payment, quality, and performance outcomes. DESIGN SETTING AND PARTICIPANTS: Physician teams mapped all ICD-10-CM diagnoses into 3 types of diagnostic items (DXIs): main effect DXIs that specify diseases; modifiers, such as laterality, timing, and acuity; and scaled variables, such as body mass index, gestational age, and birth weight. Every diagnosis was mapped to at least 1 DXI. Stepwise and weighted least-squares estimation predicted cost and utilization outcomes, and their performance was compared with models built on (1) the Agency for Healthcare Research and Quality Clinical Classifications Software Refined (CCSR) categories, and (2) the Health and Human Services Hierarchical Condition Categories (HHS-HCC) used in the Affordable Care Act Marketplace. Each model's performance was validated using R 2, mean absolute error, the Cumming prediction measure, and comparisons of actual to predicted outcomes by spending percentiles and by diagnostic frequency. The IBM MarketScan Commercial Claims and Encounters Database, 2016 to 2018, was used, which included privately insured, full- or partial-year eligible enrollees aged 0 to 64 years in plans with medical, drug, and mental health/substance use coverage. MAIN OUTCOMES AND MEASURES: Fourteen concurrent outcomes were predicted: overall and plan-paid health care spending (top-coded and not top-coded); enrollee out-of-pocket spending; hospital days and admissions; emergency department visits; and spending for 6 types of services. The primary outcome was annual health care spending top-coded at 250000.RESULTS:Atotalof65901460personyearsweresplitinto90250 000. RESULTS: A total of 65 901 460 person-years were split into 90% estimation/10% validation samples (n = 6 604 259). In all, 3223 DXIs were created: 2435 main effects, 772 modifiers, and 16 scaled items. Stepwise regressions predicting annual health care spending (mean [SD], 5821 [$17 653]) selected 76% of the main effect DXIs with no evidence of overfitting. Validated R 2 was 0.589 in the DXI model, 0.539 for CCSR, and 0.428 for HHS-HCC. Use of DXIs reduced underpayment for enrollees with rare (1-in-a-million) diagnoses by 83% relative to HHS-HCCs. CONCLUSIONS: In this diagnostic modeling study, the new DXI classification system showed improved predictions over existing diagnostic classification systems for all spending and utilization outcomes considered.Published versio

    Human Herpesvirus Replication and Abnormal CD8+ T Cell Activation and Low CD4+ T Cell Counts in Antiretroviral-Suppressed HIV-Infected Patients

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    Most HIV-infected patients receiving virologically suppressive antiretroviral therapy continue to have abnormal, generalized T cell activation. We explored whether the degree of ongoing cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) replication was associated with higher virus-specific T cell activation and the failure to achieve normal absolute CD4+ T cell counts in the face of long-term suppressive antiretroviral therapy.Longitudinally collected PBMC and saliva specimens obtained from HIV-infected patients on effective antiretroviral therapy for at least one year (plasma HIV RNA <75 copies/mL) were examined using a multiplex CMV, EBV and KSHV DNA PCR assay. Eleven cases were chosen who had CD8+ T cell CD38+HLA-DR+ expression >10% and plateau absolute CD4+ T cell counts <500 cells/microL. Five controls from the same study had CD8+ T cell CD38 expression <10% and plateau absolute CD4+ T cell counts >500 cells/microL.Among all subjects combined, 18% of PMBC samples were positive for CMV DNA, and 27%, 73% and 24% of saliva samples were positive for CMV, EBV and KSHV DNA, respectively. No significant differences or trends were observed between cases and controls in proportions of all CMV, EBV or KSHV DNA positive specimens, proportions of subjects in each group that intermittently or continuously shed CMV, EBV or KSHV DNA in saliva, or the median number of genome copies of CMV, EBV and KSHV DNA in saliva. Overall, number of genome copies in saliva were lower for KSHV than for CMV and lower for CMV than for EBV. Although replication of CMV, EBV and KSHV persists in many antiretroviral-suppressed, HIV-infected patients, we observed no evidence in this pilot case-control study that the magnitude of such human herpesvirus replication is associated with abnormally increased CD8+ T cell activation and sub-normal plateau absolute CD4+ T cell counts following virologically suppressive antiretroviral therapy

    Identification of potent, selective P2Y-purinoceptor agonists: structure-activity relationships for 2-thioether derivatives of adenosine 5'-triphosphate

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    Study of P2-purinoceptor subtypes has been difficult due to the lack of potent and selective ligands. With the goal of developing high affinity P2-purinoceptor-selective agonists, we have synthesized a series of analogues of adenine nucleotides modified on the purine ring as chain-extended 2-thioethers or as N6-methyl-substituted compounds. Chemical functionality incorporated in the thioether moiety included cyanoalkyl, nitroaromatic, amino, thiol, cycloalkyl, n-alkyl, and olefinic groups. Apparent affinity of the compounds for P2Y-purinoceptors was established by measurement of P2Y-purinoceptor-promoted phospholipase C activity in turkey erythrocyte membranes and relaxation of carbachol-contracted smooth muscle in three different preparations (guinea pig taenia coil, rabbit aorta, and rabbit mesenteric artery). Activity at P2X-purinoceptors was established by measurement of contraction of rabbit saphenous artery and of the guinea pig vas deferens and urinary bladder. All 11 of the 2-thioethers of ATP stimulated the production of inositol phosphates with K0.5 values of 1.5–770 nM, with an (aminophenyl)ethyl derivative being most potent. Two adenosine diphosphate analogues were equipotent to the corresponding ATP analogues. Adenosine monophosphate analogues were full agonists, although generally 4 orders of magnitude less potent. ATP 2-thioethers displayed pD2 values in the range of 6–8 in smooth muscle assay systems for activity at P2Y-receptors. There was a significant correlation for the 2-thioether compounds between the pK0.5 values for inositol phosphate production and the pD2 values for relaxation mediated via the P2Y-purinoceptors in the guinea pig taenia coli, but not for the vascular P2Y-receptors or for the P2X-receptors. At P2X-receptors, no activity was observed in the rabbit saphenous artery, but variable degrees of activity were observed in the guinea pig vas deferens and bladder depending on distal substituents of the thioether moiety. N6-Methyl-ATP was inactive at P2X-receptors, and approximately equipotent to ATP at taenia coli P2Y-receptors. This suggested that hybrid N6-methyl and 2-thioether ATP derivatives might be potent and selective for certain P2Y-receptors, as was shown for one such derivative, N6-methyl-2-(5-hexenylthio)-ATP

    Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts

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    Rationale: Chronic obstructive pulmonary disease exacerbations are associated with disease progression, higher healthcare cost, and increased mortality. Published predictors of future exacerbations include previous exacerbation, airflow obstruction, poor overall health, home oxygen use, and gastroesophageal reflux
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