Evaluation of a Command-line Parser-based Order Entry Pathway for the Department of Veterans Affairs Electronic Patient Record

Objective: To improve and simplify electronic order entry in an existing electronic patient record, the authors developed an alternative system for entering orders, which is based on a command- interface using robust and simple natural-language techniques. Design: The authors conducted a randomized evaluation of the new entry pathway, measuring time to complete a standard set of orders, and users' satisfaction measured by questionnaire. A group of 16 physician volunteers from the staff of the Department of Veterans Affairs Puget Sound Health Care System-Seattle Division participated in the evaluation. Results: Thirteen of the 16 physicians (81%) were able to enter medical orders more quickly using the natural-language-based entry system than the standard graphical user interface that uses menus and dialogs (mean time spared, 16.06 ± 4.52 minutes; P=0.029). Compared with the graphical user interface, the command--based pathway was perceived as easier to learn (P<0.01), was considered easier to use and faster (P<0.01), and was rated better overall (P<0.05). Conclusion: Physicians found the command- interface easier to learn and faster to use than the usual menu-driven system. The major advantage of the system is that it combines an intuitive graphical user interface with the power and speed of a natural-language analyze

A focused telephonic nursing intervention delivers improved adherence to A1c testing

Compliance with hemoglobin A1c (A1c) testing is suboptimal despite the clear national recommendations and guidelines established for care of patients with diabetes. Recent studies have demonstrated a relationship between participation in a diabetes disease management (DM) program and improved adherence to A1c testing. A focused intervention study was initiated to investigate the ability of a DM program to drive improvement in A1c testing. A cohort of 36,327 members experienced a statistically significant increase (29%) in A1c testing while participating in the 6-month focused intervention. This finding demonstrated that a focused DM intervention is able to deliver improvement in a clinical process metric critical for managing patients with diabetes, thereby reducing their risk of disease exacerbation

Optical modeling and polarization calibration for CMB measurements with ACTPol and Advanced ACTPol

The Atacama Cosmology Telescope Polarimeter (ACTPol) is a polarization sensitive upgrade to the Atacama Cosmology Telescope. Located at an elevation of 5190 m, ACTPol measures the Cosmic Microwave Background (CMB) temperature and polarization with arcminute-scale angular resolution. Calibration of the detector angles is a critical step in producing maps of the CMB polarization. Polarization angle offsets in the detector calibration can cause leakage in polarization from E to B modes and induce a spurious signal in the EB and TB cross correlations, which eliminates our ability to measure potential cosmological sources of EB and TB signals, such as cosmic birefringence. We present our optical modeling and measurements associated with calibrating the detector angles in ACTPol.Comment: 12 pages, 8 figures, conference proceedings submitted to Proceedings of SPIE; added reference in section 2 and merged repeated referenc

Macrophages sense and kill bacteria through carbon monoxide-dependent inflammasome activation

Microbial clearance by eukaryotes relies on complex and coordinated processes that remain poorly understood. The gasotransmitter carbon monoxide (CO) is generated by the stress-responsive enzyme heme oxygenase-1 (HO-1, encoded by Hmox1), which is highly induced in macrophages in response to bacterial infection. HO-1 deficiency results in inadequate pathogen clearance, exaggerated tissue damage, and increased mortality. Here, we determined that macrophage-generated CO promotes ATP production and release by bacteria, which then activates the Nacht, LRR, and PYD domains-containing protein 3 (NALP3) inflammasome, intensifying bacterial killing. Bacterial killing defects in HO-1-deficient murine macrophages were restored by administration of CO. Moreover, increased CO levels enhanced the bacterial clearance capacity of human macrophages and WT murine macrophages. CO-dependent bacterial clearance required the NALP3 inflammasome, as CO did not increase bacterial killing in macrophages isolated from NALP3-deficient or caspase-1-deficient mice. IL-1β cleavage and secretion were impaired in HO-1-deficient macrophages, and CO-dependent processing of IL-1β required the presence of bacteria-derived ATP. We found that bacteria remained viable to generate and release ATP in response to CO. The ATP then bound to macrophage nucleotide P2 receptors, resulting in activation of the NALP3/IL-1β inflammasome to amplify bacterial phagocytosis by macrophages. Taken together, our results indicate that macrophage-derived CO permits efficient and coordinated regulation of the host innate response to invading microbes.NIH grants: (HL-071797, HL-076167, HL-106227), American Heart Association grants: (10SDG2640091 and NIH R21CA169904-01), Julie Henry Fund, Transplant Center of the BIDMC, FCT grants: (SFRH/BPD/25436/2005, PTDC/BIO/70815/2006, PTDC/BIA-BCM/101311/2008, PTDC/SAU-FCF/100762/2008), the European Community, 6th Framework grant LSH-2005-1.2.5-1 and ERC-2011-AdG, Howard Hughes Medical Institute

Early Growth Response Gene 1–mediated Apoptosis Is Essential for Transforming Growth Factor β1–induced Pulmonary Fibrosis

Fibrosis and apoptosis are juxtaposed in pulmonary disorders such as asthma and the interstitial diseases, and transforming growth factor (TGF)-β1 has been implicated in the pathogenesis of these responses. However, the in vivo effector functions of TGF-β1 in the lung and its roles in the pathogenesis of these responses are not completely understood. In addition, the relationships between apoptosis and other TGF-β1–induced responses have not been defined. To address these issues, we targeted bioactive TGF-β1 to the murine lung using a novel externally regulatable, triple transgenic system. TGF-β1 produced a transient wave of epithelial apoptosis that was followed by mononuclear-rich inflammation, tissue fibrosis, myofibroblast and myocyte hyperplasia, and septal rupture with honeycombing. Studies of these mice highlighted the reversibility of this fibrotic response. They also demonstrated that a null mutation of early growth response gene (Egr)-1 or caspase inhibition blocked TGF-β1–induced apoptosis. Interestingly, both interventions markedly ameliorated TGF-β1–induced fibrosis and alveolar remodeling. These studies illustrate the complex effects of TGF-β1 in vivo and define the critical role of Egr-1 in the TGF-β1 phenotype. They also demonstrate that Egr-1–mediated apoptosis is a prerequisite for TGF-β1–induced fibrosis and remodeling

Outcomes of rare patients with a primary cutaneous CD30(+) lymphoproliferative disorder developing extracutaneous disease

Contains fulltext : 218224.pdf (Publisher’s version ) (Open Access

Cell-of-origin classification using the Hans and Lymph2Cx algorithms in primary cutaneous large B-cell lymphomas

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma with a diffuse population of large cells (PCFCL-LC) are both primary cutaneous B-cell lymphomas with large-cell morphology (CLBCL) but with different clinical characteristics and behavior. In systemic diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), gene-expression profiling (GEP) revealed two molecular subgroups based on their cell-of-origin (COO) with prognostic significance: the germinal center B-cell-like (GCB) subtype and the activated B-cell-like (ABC) subtype. This study investigated whether COO classification is a useful tool for classification of CLBCL. For this retrospective study, 51 patients with PCDLBCL-LT and 15 patients with PCFCL-LC were analyzed for their COO according to the immunohistochemistry-based Hans algorithm and the NanoString GEP-based Lymph2Cx algorithm. In PCFCL-LC, all cases (100%) classified as GCB by both Hans and Lymph2Cx. In contrast, COO classification in PCDLBCL-LT was heterogeneous. Using Hans, 75% of the PCDLBCL-LT patients classified as non-GCB and 25% as GCB, while Lymph2Cx classified only 18% as ABC, 43% as unclassified/intermediate, and 39% as GCB. These COO subgroups did not differ in the expression of BCL2 and IgM, mutations in MYD88 and/or CD79B, loss of CDKN2A, or survival. In conclusion, PCFCL-LC uniformly classified as GCB, while PCDLBCL-LT classified along the COO spectrum of DLBCL-NOS using the Hans and Lymph2Cx algorithms. In contrast to DLBCL-NOS, the clinical relevance of COO classification in CLBCL using these algorithms has limitations and cannot be used as an alternative for the current multiparameter approach in differentiation of PCDLBCL-LT and PCFCL-LC