2,012 research outputs found

    Stable isotopic analysis of atmospheric methane by infrared spectroscopy by use of diode laser difference-frequency generation

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    An infrared absorption spectrometer has been constructed to measure the stable isotopic composition of atmospheric methane samples. The spectrometer employs periodically poled lithium niobate to generate 15 μW of tunable difference-frequency radiation from two near-infrared diode lasers that probe the ν3 rotational-vibrational band of methane at 3.4 μm. To enhance the signal, methane is extracted from 25 l of air by use of a cryogenic chromatographic column and is expanded into the multipass cell for analysis. A measurement precision of 12‰ is demonstrated for both δ13C and δD

    Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

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    BackgroundCurrent treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.MethodsWe performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG).ResultsRituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of 16,298,correspondingtoanincrementalcosteffectivenessratioof16,298, corresponding to an incremental cost-effectiveness ratio of 61,984 (95% CI 34,08734,087-135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was 100,000/LYG.Thecosteffectivenessratiowasmostfavourableforpatientslessthan60yearsold(100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old (31,800/LYG) but increased to 80,600/LYGforpatients6079yearsoldand80,600/LYG for patients 60-79 years old and 110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age.ConclusionsOur results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug

    High efficacy and low toxicity of weekly docetaxel given as first-line treatment for metastatic breast cancer

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    Background: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer. Patients and Methods: All patients received docetaxel, 35 mg/m(2) weekly for 6 weeks, followed by 2 weeks of rest. Subsequent cycles ( 3 weeks of treatment, 2 weeks of rest) were given until a maximum of 5 cycles or disease progression. Premedication consisted of 8 mg dexamethasone intravenously 30 min prior to the infusion of docetaxel. Results: Fifty-four patients at a median age of 58 years with previously untreated MBC were included in the study. A median of 10 doses ( median cumulative dose 339 mg/m(2)) was administered ( range: 2 - 18). The overall response rate was 48.1% ( 95% CI: 34 - 61%, intent-to-treat). Median survival was 15.8 months and median time to progression was 5.9 months ( intent-to-treat). Hematological toxicity was mild with absence of neutropenia-related complications. Grade 3 neutropenia was observed in 3.7% of patients and grade 3 and 4 anemia was observed in 5.6 and 1.9% of patients, respectively. Conclusion: The weekly administration of docetaxel is highly efficient and safe as first-line treatment for MBC and may serve as an important treatment option specifically in elderly patients and patients with a reduced performance status. Copyright (C) 2005 S. Karger AG, Basel

    Fourier and Gegenbauer expansions for a fundamental solution of the Laplacian in the hyperboloid model of hyperbolic geometry

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    Due to the isotropy dd-dimensional hyperbolic space, there exist a spherically symmetric fundamental solution for its corresponding Laplace-Beltrami operator. On the RR-radius hyperboloid model of dd-dimensional hyperbolic geometry with R>0R>0 and d2d\ge 2, we compute azimuthal Fourier expansions for a fundamental solution of Laplace's equation. For d2d\ge 2, we compute a Gegenbauer polynomial expansion in geodesic polar coordinates for a fundamental solution of Laplace's equation on this negative-constant sectional curvature Riemannian manifold. In three-dimensions, an addition theorem for the azimuthal Fourier coefficients of a fundamental solution for Laplace's equation is obtained through comparison with its corresponding Gegenbauer expansion.Comment: arXiv admin note: substantial text overlap with arXiv:1201.440

    A 7-year follow-up of sacral anterior root stimulation for bladder control in patients with a spinal cord injury: quality of life and users' experiences\ud

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    Study design: Cross-sectional descriptive study.\ud \ud Objectives: To assess long-term effects and quality of life (QoL) of using sacral anterior root stimulation (SARS) in spinal cord injured patients.\ud \ud Setting: Neurosurgical and Urological Departments of a large teaching hospital and a large rehabilitation centre in the Netherlands.\ud \ud Methods: In all, 42 patients with complete spinal cord injury (SCI) implanted between 1987 and 2000 were included. A questionnaire was constructed to determine complications, technical failures and personal experiences of the patients. The Qualiveen questionnaire was used and the outcome was compared with data obtained from a reference group of 400 SCI patients with neurogenic bladder problems not using the bladder controller. The Qualiveen questionnaire measures disease-specific aspects in four domains with respect to limitations, constraints, fears and feelings and general QoL aspects, suitable for use in SCI patients with urinary disorders.\ud \ud Results: The results of 37 patients are presented. Our results with the bladder controller with respect to medical and technical complications and infection rates are similar to the results presented by others. From users' experiences, the most important advantages reported were a decreased infection rate (68%), improved social life (54%) and continence (54%). Comparison of the obtained results of our patient group with the Qualiveen questionnaire with a reference group not using the bladder controller indicates that the specific impact of urinary disorders in the four domains on QoL is reduced and that general QoL is improved.\ud \ud Conclusion: SARS is effective and safe for neurogenic bladder management in patients with complete SCI. Users' experiences are positive. Furthermore, this therapy seems to reduce the effects of urinary-disorder-specific QoL aspects, and to increase the QoL in general\u

    How does gender influence the recognition of cardiovascular risk and adherence to self-care recommendations? : a study in polish primary care

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    Background: Studies have shown a correlation between gender and an ability to change lifestyle to reduce the risk of disease. However, the results of these studies are ambiguous, especially where a healthy lifestyle is concerned. Additionally, health behaviors are strongly modified by culture and the environment. Psychological factors also substantially affect engagement with disease-related lifestyle interventions. This study aimed to examine whether there are differences between men and women in the frequency of health care behavior for the purpose of reducing cardiovascular risk (CVR), as well as cognitive appraisal of this type of risk. We also aimed to identify the psychological predictors of engaging in recommended behavior for reducing the risk of cardiovascular disease after providing information about this risk in men and women. Methods: A total of 134 consecutive eligible patients in a family practice entered a longitudinal study. At initial consultation, the individual’s CVR and associated health burden was examined, and preventive measures were recommended by the physician. Self-care behavior, cognitive appraisal of risk, and coping styles were then assessed using psychological questionnaires. Six months after the initial data collection, the frequency of subjects’ self-care behavior was examined. Results: We found an increase in health care behavior after providing information regarding the rate of CVR in both sexes; this increase was greater for women than for men. Women followed self-care guidelines more often than men, particularly for preventive measures and dietary advice. Women were more inclined to recognize their CVR as a challenge. Coping style, cognitive appraisal, age, level of health behaviors at baseline and CVR values accounted for 48% of the variance in adherence to self-care guidelines in women and it was 52% in men. In women, total risk of CVD values were most important, while in men, cognitive appraisal of harm/loss was most important. Conclusions: Different predictors of acquisition of health behavior are encountered in men and women. Our results suggest that gender-adjusted motivation models influencing the recognition process need to be considered to optimize compliance in patients with CVR

    Secretoneurin stimulates the production and release of luteinizing hormone in mouse L beta T2 gonadotropin cells

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    Secretoneurin (SN) is a functional secretogranin II (SgII)-derived peptide that stimulates luteinizing hormone (LH) production and its release in the goldfish. However, the effects of SN on the pituitary of mammalian species and the underlying mechanisms remain poorly understood. To study SN in mammals, we adopted the mouse LβT2 gonadotropin cell line that has characteristics consistent with normal pituitary gonadotrophs. Using radioimmunoassay and real-time RT-PCR, we demonstrated that static treatment with SN induced a significant increment of LH release and production in LβT2 cells in vitro. We found that GnRH increased cellular SgII mRNA level and total SN-immunoreactive protein release into the culture medium. We also report that SN activated the extracellular signal-regulated kinases (ERK) in either 10-min acute stimulation or 3-h chronic treatment. The SN-induced ERK activation was significantly blocked by pharmacological inhibition of MAPK kinase (MEK) with PD-98059 and protein kinase C (PKC) with bisindolylmaleimide. SN also increased the total cyclic adenosine monophosphate (cAMP) levels similarly to GnRH. However, SN did not activate the GnRH receptor. These data indicate that SN activates the protein kinase A (PKA) and cAMP-induced ERK signaling pathways in the LH-secreting mouse LβT2 pituitary cell line

    A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer

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    This multi-center Phase II study evaluated lapatinib, pazopanib, and the combination in patients with relapsed HER2+ inflammatory breast cancer. In Cohort 1, 76 patients were randomized 1:1 to receive lapatinib 1,500 mg + placebo or lapatinib 1,500 mg + pazopanib 800 mg (double-blind) once daily until disease progression, unacceptable toxicity, or death. Due to high-grade diarrhea observed with this dose combination in another study (VEG20007), Cohort 1 was closed. The protocol was amended such that an additional 88 patients (Cohort 2) were randomized in a 5:5:2 ratio to receive daily monotherapy lapatinib 1,500 mg, lapatinib 1,000 mg + pazopanib 400 mg, or monotherapy pazopanib 800 mg, respectively. The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response, progression-free survival (PFS), overall survival, and safety. In Cohort 1, ORR for the lapatinib (n = 38) and combination (n = 38) arms was 29 and 45 %, respectively; median PFS was 16.1 and 14.3 weeks, respectively. Grade ≥3 adverse events (AEs) were more frequent in the combination arm (71 %) than in the lapatinib arm (24 %). Dose reductions and interruptions due to AEs were also more frequent in the combination arm (45 and 53 %, respectively) than in the lapatinib monotherapy arm (0 and 11 %, respectively). In Cohort 2, ORR for patients treated with lapatinib (n = 36), lapatinib + pazopanib (n = 38), and pazopanib (n = 13) was 47, 58, and 31 %, respectively; median PFS was 16.0, 16.0, and 11.4 weeks, respectively. In the lapatinib, combination, and pazopanib therapy arms, grade ≥3 AEs were reported for 17, 50, and 46 % of patients, respectively, and the incidence of discontinuations due to AEs was 0, 24, and 23 %, respectively. The lapatinib–pazopanib combination was associated with a numerically higher ORR but no increase in PFS compared to lapatinib alone. The combination also had increased toxicity resulting in more dose reductions, modifications, and treatment delays. Activity with single-agent lapatinib was confirmed in this population
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