108,364 research outputs found

    Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial

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    Oral capecitabine (Xeloda<sup>®</sup>) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings £3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings £1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK

    Branching fraction and CP asymmetry of the decays B+→K0Sπ+ and B+→K0SK+

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    An analysis of B+ → K0 Sπ+ and B+ → K0 S K+ decays is performed with the LHCb experiment. The pp collision data used correspond to integrated luminosities of 1 fb−1 and 2 fb−1 collected at centre-ofmass energies of √ s = 7 TeV and √ s = 8 TeV, respectively. The ratio of branching fractions and the direct CP asymmetries are measured to be B(B+ → K0 S K+ )/B(B+ → K0 Sπ+ ) = 0.064 ± 0.009 (stat.) ± 0.004 (syst.), ACP(B+ → K0 Sπ+ ) = −0.022 ± 0.025 (stat.) ± 0.010 (syst.) and ACP(B+ → K0 S K+ ) = −0.21 ± 0.14 (stat.) ± 0.01 (syst.). The data sample taken at √ s = 7 TeV is used to search for B+ c → K0 S K+ decays and results in the upper limit ( fc · B(B+ c → K0 S K+ ))/( fu · B(B+ → K0 Sπ+ )) < 5.8 × 10−2 at 90% confidence level, where fc and fu denote the hadronisation fractions of a ¯b quark into a B+ c or a B+ meson, respectively

    Mutation frequencies following the 5-FU-, 4NQO-, and CPT-treatment.

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    A), C), and E) The frequencies of overall Lys+ mutations following treatments with 5-FU (10 μM), CPT (100 μM), or 4NQO (0.2 μg/mL), respectively, for 24 hrs. B), D), and F) The frequencies of the uracil-dependent A>C and T>G mutations following treatments with 5-FU, CPT and 4NQO, respectively. Error bars indicate 95% confidence intervals. The number of cultures used to determine the frequencies of mutations and the numerical values of the median mutation frequencies and the confidence intervals represented as graphs in this figure are listed in S4 Table.</p

    Measurement of the ratio of prompt χ c to J / ψ production in pp collisions at √s = 7 TeV

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    The prompt production of charmonium χ c and J / ψ states is studied in proton-proton collisions at a centre-of-mass energy of √s = 7 TeV at the Large Hadron Collider. The χ c and J / ψ mesons are identified through their decays χ c → J / ψ γ and J / ψ → μ + μ - using 36 pb - 1 of data collected by the LHCb detector in 2010. The ratio of the prompt production cross-sections for χ c and J / ψ, σ (χ c → J / ψ γ) / σ (J / ψ), is determined as a function of the J / ψ transverse momentum in the range 2 < p T J / ψ < 15 GeV / c. The results are in excellent agreement with next-to-leading order non-relativistic expectations and show a significant discrepancy compared with the colour singlet model prediction at leading order, especially in the low p T J / ψ region

    Massachusetts Institute of Technology: The Fu Research Group

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    The Massachusetts Institute of Technology (MIT) publicizes the Fu Research Group&#039;s four main chemistry project areas: asymmetric nucleophilic catalysis with planar-chiral heterocycles; new chiral ligands for transition metal-catalyzed reactions; palladium-catalyzed coupling reactions; and chemistry of boron heterocycles. For each project link, visitors can find concise descriptions with helpful diagrams and selected publications in pdf format. Visitors can also view images of the Group&#039;s laboratory facilities

    Prompt charm production in pp collisions at &#8730;<span style="text-decoration:overline">s</span>=7 TeV

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    Charm production at the LHC in pp collisions at s√=7 TeV is studied with the LHCb detector. The decays D0→K−π+, D+→K−π+π+, D⁎+→D0(K−π+)π+, D+s→ϕ(K−K+)π+, Λ+c→pK−π+, and their charge conjugates are analysed in a data set corresponding to an integrated luminosity of 15 nb−1. Differential cross-sections dσ/dpT are measured for prompt production of the five charmed hadron species in bins of transverse momentum and rapidity in the region 0&#60;pT&#60;8 GeV/c and 2.0&#60;y&#60;4.5. Theoretical predictions are compared to the measured differential cross-sections. The integrated cross-sections of the charm hadrons are computed in the above pT-y range, and their ratios are reported. A combination of the five integrated cross-section measurements gives σ(cc¯)pT&#60;8 GeV/c,2.0&#60;y&#60;4.5=1419±12(stat)±116(syst)±65(frag) μb, where the uncertainties are statistical, systematic, and due to the fragmentation functions

    Nickel-Catalyzed Coupling Reactions of Alkyl Electrophiles, Including Unactivated Tertiary Halides, To Generate Carbon–Boron Bonds

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    Through the use of a catalyst formed in situ from NiBr[subscript 2]·diglyme and a pybox ligand (both of which are commercially available), we have achieved our first examples of coupling reactions of unactivated tertiary alkyl electrophiles, as well as our first success with nickel-catalyzed couplings that generate bonds other than C–C bonds. Specifically, we have determined that this catalyst accomplishes Miyaura-type borylations of unactivated tertiary, secondary, and primary alkyl halides with diboron reagents to furnish alkylboronates, a family of compounds with substantial (and expanding) utility, under mild conditions; indeed, the umpolung borylation of a tertiary alkyl bromide can be achieved at a temperature as low as −10 °C. The method exhibits good functional-group compatibility and is regiospecific, both of which can be issues with traditional approaches to the synthesis of alkylboronates. In contrast to seemingly related nickel-catalyzed C–C bond-forming processes, tertiary halides are more reactive than secondary or primary halides in this nickel-catalyzed C–B bond-forming reaction; this divergence is particularly noteworthy in view of the likelihood that both transformations follow an inner-sphere electron-transfer pathway for oxidative addition.National Institute of General Medical Sciences (U.S.) (Grant R01-GM62871

    Gemcitabine: Progress in the treatment of pancreatic cancer

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    Unresectable pancreatic cancer has a dismal prognosis with a median survival of 3-5 months in untreated disease. Since the introduction of gemcitabine, pancreatic cancer may no longer be regarded a chemotherapy-resistant tumor. Treatment with single-agent gemcitabine achieved clinical benefit and symptoms improvement in 20-30% of patients. While 1-year survival was observed in 2% of 5-fluorouracil (5-FU)-treated patients, it was raised to 18% by single-agent gemcitabine. Good treatment tolerability and low incidence of side effects are clear advantages of single-agent gemcitabine. Improvement of efficacy is, however, expected from combination treatment. Gemcitabine and cisplatin given as first-line treatment in three studies achieved a median survival of 7.4-8.3 months. One-year survival was raised to 28% as reported in one study. Comparable activity was obtained by a combination of gemcitabine with 5-FU. Nine studies using gemcitabine in combination with standard-dose or high-dose 5-FU reported a median survival ranging from 5.5 to 13 months. Notwithstanding these promising results, recommendations regarding palliative chemotherapy of pancreatic cancer remain tentative and still need confirmation by presently ongoing phase III trials. Inclusion of pancreatic cancer patients into clinical trials should be a major goal. Outside clinical trials, patients should present with an adequate PS (Karnofsky-performance index greater than or equal to 70) to qualify for chemotherapy. Copyright (C) 2001 S. Karger AG, Basel
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