514 research outputs found

    Measuring Monetary and Non-Monetary ROI at MMC OpEx

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    Operational Excellence (OpEx) is a data driven approach to department based continuous improvement, minimizing costs, increasing efficiencies, engaging staff in a shared quality agenda and assuming a proactive approach to maintaining facilities. The OpEx platform assists in strengthening efficiency and patient safety at Maine Medical Center (MMC) by demonstrating alignment of goals across the entire organization. A recent publication by BMC Health services “… found that the ROI concept in healthcare QI aligned with the concepts of value and benefit, both monetary and non-monetary.”2. Currently, OpEx does not have a system in place to track these values. We are looking to identify the success and impact of our department, monetary and non-monetary outcomes

    Correlations between intraplan and postplan parameters in I-125 permanent prostate brachytherapy using loose seeds or linked seeds

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    The purpose of this study was to determine the most appropriate seed arrangement by comparing two different methods (linked seeds and loose seeds). A total of sixty-one patients (28 linked seed brachytherapy cases and 33 loose seed brachytherapy cases) with clinically localized prostate cancer were treated with I-125 permanent prostate brachytherapy. Modified peripheral loading was the method used for seed placement. The parameters evaluated were as follows: prostate D90, V100, and V150; urethral D90, D10, and D5; and rectal V100 (RV100) and D2 (RD2). Coefficient parameters (r and r2) were assessed by regression analysis. Prostate V150, urethral D90, urethral D10, urethral D5, and RD2 showed significant correlations between both methods in all patients. Urethral D90, urethral D10, urethral D5, and RD2 showed significant correlations in patients who received linked seed brachytherapy. Prostate V150, urethral D90, urethral D10, urethral D5, RV100, and RD2 showed significant correlations in patients who received loose seed brachytherapy. Urethral D90, urethral D10, urethral D5, and RD2 showed significant correlations in the linked seed and loose seed brachytherapy analyses. In contrast, prostate D90 and prostate V100 showed no correlation. Parameters of normal organ damage showed good correlations between intraplan and postplan parameters. These parameters may be useful to determine normal organ damage during guided brachytherapy with two different methods (linked seeds and loose seeds).departmental bulletin pape

    Dependence of quench current level on current ramp rate in AC superconducting windings under different fixing conditions

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    Mechanical instabilities in a.c, Nb-Ti superconducting wire are theoretically investigated. We derived the expressions for the temperature rise of the SC wire due to the friction between the wire and the bobbin to estimate the quench current degradation induced by mechanical disturbances. The quench current levels were calculated for different conditions of frictional force and current ramp ratc. It is confirmed that a certain frictional force brings about the lowest quench current level. It is also found that the quench current degradation induced by mechanical disturbance may be hard to occur when the current increases rapidly.journal articl

    Dependence of quench current level of superconducting wire and cable on the winding tension

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    Mechanical instabilities in an a.c. Nb-Ti superconducting wire and cable are experimentally investigated. The quench current levels of the sample conductors were measured for different winding tensions and current increasing rates. We have developed a new type of experimental bobbin to apply the tension uniformly and to adjust it to the specified value from the outside of the cryostat. It is found that the influence of the mechanical instabilities on the quench current level decreases with an increase in the winding tension and/or the current increasing rate.journal articl

    Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC

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    Purpose: The present study compared the efficacy of sunitinib and sorafenib as first-line treatment of metastatic clear cell renal cell carcinoma (mCC-RCC) with favorable or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk. Patients and methods: Treatment-naive patients with mCC-RCC were randomized to receive open-label sunitinib followed by sorafenib (SU/SO) or sorafenib followed by sunitinib (SO/SU). The primary endpoint was first-line progression-free survival (PFS). The secondary endpoints were total PFS and overall survival (OS). Results: Of the 124 patients enrolled at 39 institutions from February 2010 to July 2012, 120 were evaluated. The median first-line PFS duration was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.42-1.08). The total PFS and OS were not significantly different between the SU/SO and SO/SU groups (27.8 and 22.6 months; HR, 0.73; 95% CI, 0.428-1.246; and 38.4 and 30.9 months; HR, 0.934; 95% CI, 0.588-1.485, respectively). The subgroup analysis revealed that the total PFS with SU/SO was superior to the total PFS with SO/SU in the patients with favorable MSKCC risk and those with Conclusions: No statistically significant differences were found in first-line PFS, total PFS, or OS between the 2 treatment arms (ClinicalTrials.gov identifier, NCT01481870)

    Eosinophils as a predictive marker of treatment-related adverse events in mRCC patients treated with first-line immune-checkpoint inhibitor combination therapy

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    Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade ≥ 3 TRAEs in mRCC patients undergoing ICI combination therapy. In this retrospective analysis across 21 hospitals in Japan, we examined 180 patients treated with ICI/ICI therapy and 216 patients treated with ICI/tyrosine kinase inhibitor (TKI) therapy. Grade ≥ 3 TRAEs occurred in 39.4% and 31.9% of patients in the ICI/ICI and ICI/TKI groups, respectively. An elevated eosinophil proportion of ≥ 2.0% (odds ratio [OR]: 2.36; 95% CI [confidence interval] 1.23–4.54, p = 0.01) and a low neutrophil/eosinophil ratio (NER) of ≤ 40.0 (OR: 2.78, 95% CI 1.39–5.53, p = 0.004) were significant predictors of severe TRAEs in the ICI/ICI group. However, no significant associations were found in the ICI/TKI group. These findings may help identify patients who suffer from grade ≥ 3 TRAEs and help determine individualized treatment strategies in patients with mRCC

    Thymic development beyond β-selection requires phosphatidylinositol 3-kinase activation by CXCR4

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    T cell development requires phosphatidylinositol 3-kinase (PI3K) signaling with contributions from both the class IA, p110δ, and class IB, p110γ catalytic subunits. However, the receptors on immature T cells by which each of these PI3Ks are activated have not been identified, nor has the mechanism behind their functional redundancy in the thymus. Here, we show that PI3K signaling from the preTCR requires p110δ, but not p110γ. Mice deficient for the class IB regulatory subunit p101 demonstrated the requirement for p101 in T cell development, implicating G protein–coupled receptor signaling in β-selection. We found evidence of a role for CXCR4 using small molecule antagonists in an in vitro model of β-selection and demonstrated a requirement for CXCR4 during thymic development in CXCR4-deficient embryos. Finally, we demonstrate that CXCL12, the ligand for CXCR4, allows for Notch-dependent differentiation of DN3 thymocytes in the absence of supporting stromal cells. These findings establish a role for CXCR4-mediated PI3K signaling that, together with signals from Notch and the preTCR, contributes to continued T cell development beyond β-selection

    Deletion of PKBalpha/Akt1 affects thymic development

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    BACKGROUND: The thymus constitutes the primary lymphoid organ for the majority of T cells. The phosphatidyl-inositol 3 kinase (PI3K) signaling pathway is involved in lymphoid development. Defects in single components of this pathway prevent thymocytes from progressing beyond early T cell developmental stages. Protein kinase B (PKB) is the main effector of the PI3K pathway. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether PKB mediates PI3K signaling in the thymus, we characterized PKB knockout thymi. Our results reveal a significant thymic hypocellularity in PKBalpha(-/-) neonates and an accumulation of early thymocyte subsets in PKBalpha(-/-) adult mice. Using thymic grafting and fetal liver cell transfer experiments, the latter finding was specifically attributed to the lack of PKBalpha within the lymphoid component of the thymus. Microarray analyses show that the absence of PKBalpha in early thymocyte subsets modifies the expression of genes known to be involved in pre-TCR signaling, in T cell activation, and in the transduction of interferon-mediated signals. CONCLUSIONS/SIGNIFICANCE: This report highlights the specific requirements of PKBalpha for thymic development and opens up new prospects as to the mechanism downstream of PKBalpha in early thymocytes

    A Single Nucleotide in Stem Loop II of 5′-Untranslated Region Contributes to Virulence of Enterovirus 71 in Mice

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    BACKGROUND: Enterovirus 71 (EV71) has emerged as a neuroinvasive virus responsible for several large outbreaks in the Asia-Pacific region while virulence determinant remains unexplored. PRINCIPAL FINDINGS: In this report, we investigated increased virulence of unadapted EV71 clinical isolate 237 as compared with isolate 4643 in mice. A fragment 12 nucleotides in length in stem loop (SL) II of 237 5'-untranslated region (UTR) visibly reduced survival time and rate in mice was identified by constructing a series of infectious clones harboring chimeric 5'-UTR. In cells transfected with bicistronic plasmids, and replicon RNAs, the 12-nt fragment of isolate 237 enhanced translational activities and accelerated replication of subgenomic EV71. Finally, single nucleotide change from cytosine to uridine at base 158 in this short fragment of 5'-UTR was proven to reduce viral translation and EV71 virulence in mice. Results collectively indicated a pivotal role of novel virulence determinant C158 on virus translation in vitro and EV71 virulence in vivo. CONCLUSIONS: These results presented the first reported virulence determinant in EV71 5'-UTR and first position discovered from unadapted isolates
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