801 research outputs found
Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer
Background
Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer.
Methods
Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA.
Results
Ninety patients overall received treatment. The maximum tolerated dose was refametinib 50 mg twice daily plus standard gemcitabine (1000 mg/m2 weekly). The combination was well tolerated, with no pharmacokinetic interaction. Treatment-emergent toxicities included thrombocytopenia, fatigue, anemia, and edema. The objective response rate was 23% and the disease control rate was 73%. Overall response rate, disease control rate, progression-free survival, and overall survival were higher in patients without detectable KRAS mutations (48% vs. 28%, 81% vs. 69%, 8.8 vs. 5.3 months, and 18.2 vs. 6.6 months, respectively).
Conclusion
Refametinib plus gemcitabine was well tolerated, with a promising objective response rate, and had an acceptable safety profile and no pharmacokinetic interaction. There was a trend towards improved outcomes in patients without detectable KRAS mutations that deserves future investigation
Acute haemoabdomen associated with Angiostrongylus vasorum infection in a dog: a case report
A one-year-old intact female, Danish shorthaired pointer was referred to the emergency service with a history of acute collapse and pale mucous membranes after a month of reduced activity but with no other clinical signs. An ultrasound examination of the abdomen indicated the presence of a large amount of free fluid with no obvious cause such as neoplasia or splenic rupture. Fluid analysis had the macroscopic appearance of blood with no signs of infection or neoplasia. Multiple Angiostrongylus vasorum L1 larvae were revealed on a direct rectal faecal smear. The dog was treated with fenbendazole 25 mg/kg orally once daily for 20 days and given supportive treatment. The dog was stabilised on this treatment. Haemoabdomen is a clinical sign where surgical intervention is often considered an integral part of the diagnostic investigation (i.e., laparotomy) or treatment. Failing to make the diagnosis of canine angiostrongylosis before performing surgery may have a serious adverse affect on the outcome. Consequently, in areas where A. vasorum is enzootic, a Baermann test and a direct faecal smear should be included in the initial diagnostic investigation of all dogs presenting with bleeding disorders of unknown origin
The social cost of chronic kidney disease in Italy
This study aims to estimate the mean annual social cost per patient with chronic kidney disease (CKD) by stages 4 and 5 pre-dialyses and cost components in Italy. The multicenter cross-sectional study included all adult outpatients in charge of the 14 main Nephrology Centers of Tuscany Region during 7 weeks from 2012 to 2013. Direct medical costs have been estimated using tariffs for laboratory tests, diagnostic exams, visits, hospitalization and prices for drugs. Non-medical costs included expenses of low-protein special foods, travel, and formal and informal care. Patients' and caregivers' losses of productivity have been estimated as indirect costs using the human capital approach. Costs have been expressed in Euros (2016). Totals of 279 patients in stage 4 and 205 patients in stage 5 have been enrolled. The estimated mean annual social cost of a patient with CKD were a,notsign7422 (+/- a,notsign6255) for stage 4 and a,notsign8971 (+/- a,notsign6503) for stage 5 (p < 0.05). Direct medical costs were higher in stage 5 as compared to stage 4; direct non-medical costs and indirect costs accounted, respectively, for 41 and 5 % of the total social cost of CKD stage 4 and for 33 and 9 % of CKD stage 5. In Italy, the overall annual social cost of CKD was a,notsign1,809,552,398 representing 0.11 % of the Gross Domestic Product. Direct non-medical costs and indirect costs were weighted on the social cost of CKD almost as much as the direct medical cost. Patients, their families and the productivity system sustain the burden of the disease almost as much as the healthcare system. © 2016, The Author(s)
Evidence for t\bar{t}\gamma Production and Measurement of \sigma_t\bar{t}\gamma / \sigma_t\bar{t}
Using data corresponding to 6.0/fb of ppbar collisions at sqrt(s) = 1.96 TeV
collected by the CDF II detector, we present a cross section measurement of
top-quark pair production with an additional radiated photon. The events are
selected by looking for a lepton, a photon, significant transverse momentum
imbalance, large total transverse energy, and three or more jets, with at least
one identified as containing a b quark. The ttbar+photon sample requires the
photon to have 10 GeV or more of transverse energy, and to be in the central
region. Using an event selection optimized for the ttbar+photon candidate
sample we measure the production cross section of, and the ratio of cross
sections of the two samples. Control samples in the dilepton+photon and
lepton+photon+\met, channels are constructed to aid in decay product
identification and background measurements. We observe 30 ttbar+photon
candidate events compared to the standard model expectation of 26.9 +/- 3.4
events. We measure the ttbar+photon cross section to be 0.18+0.08 pb, and the
ratio of the cross section of ttbar+photon to ttbar to be 0.024 +/- 0.009.
Assuming no ttbar+photon production, we observe a probability of 0.0015 of the
background events alone producing 30 events or more, corresponding to 3.0
standard deviations.Comment: 9 pages, 3 figure
A search for resonant production of pairs in $4.8\ \rm{fb}^{-1}p\bar{p}\sqrt{s}=1.96\ \rm{TeV}$
We search for resonant production of tt pairs in 4.8 fb^{-1} integrated
luminosity of ppbar collision data at sqrt{s}=1.96 TeV in the lepton+jets decay
channel, where one top quark decays leptonically and the other hadronically. A
matrix element reconstruction technique is used; for each event a probability
density function (pdf) of the ttbar candidate invariant mass is sampled. These
pdfs are used to construct a likelihood function, whereby the cross section for
resonant ttbar production is estimated, given a hypothetical resonance mass and
width. The data indicate no evidence of resonant production of ttbar pairs. A
benchmark model of leptophobic Z \rightarrow ttbar is excluded with m_{Z'} <
900 GeV at 95% confidence level.Comment: accepted for publication in Physical Review D Sep 21, 201
Measurement of the CKM angle γ from a combination of B±→Dh± analyses
A combination of three LHCb measurements of the CKM angle γ is presented. The decays B±→D K± and
B±→Dπ± are used, where D denotes an admixture of D0 and D0 mesons, decaying into K+K−, π+π−, K±π∓, K±π∓π±π∓, K0Sπ+π−, or K0S K+K− final states. All measurements use a dataset corresponding to 1.0 fb−1 of integrated luminosity. Combining results from B±→D K± decays alone a best-fit value of
γ =72.0◦ is found, and confidence intervals are set
γ ∈ [56.4,86.7]◦ at 68% CL,
γ ∈ [42.6,99.6]◦ at 95% CL.
The best-fit value of γ found from a combination of results from B±→Dπ± decays alone, is γ =18.9◦,
and the confidence intervals
γ ∈ [7.4,99.2]◦ ∪ [167.9,176.4]◦ at 68% CL
are set, without constraint at 95% CL. The combination of results from B± → D K± and B± → Dπ±
decays gives a best-fit value of γ =72.6◦ and the confidence intervals
γ ∈ [55.4,82.3]◦ at 68% CL,
γ ∈ [40.2,92.7]◦ at 95% CL
are set. All values are expressed modulo 180◦, and are obtained taking into account the effect of D0–D0
mixing
Precision Top-Quark Mass Measurements at CDF
We present a precision measurement of the top-quark mass using the full
sample of Tevatron TeV proton-antiproton collisions collected
by the CDF II detector, corresponding to an integrated luminosity of 8.7
. Using a sample of candidate events decaying into the
lepton+jets channel, we obtain distributions of the top-quark masses and the
invariant mass of two jets from the boson decays from data. We then compare
these distributions to templates derived from signal and background samples to
extract the top-quark mass and the energy scale of the calorimeter jets with
{\it in situ} calibration. The likelihood fit of the templates from signal and
background events to the data yields the single most-precise measurement of the
top-quark mass, \mtop = 172.85 \pm\pmComment: submitted to Phys. Rev. Let
Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-
We report the first observation of the baryonic flavor-changing neutral
current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a
statistical significance of 5.8 Gaussian standard deviations. This measurement
uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV
collected by the CDF II detector at the Tevatron collider. The total and
differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We
find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}.
We also report the first measurement of the differential branching ratio of B_s
-> phi mu+ mu- using 49 signal events. In addition, we report branching ratios
for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let
Combined search for the standard model Higgs boson decaying to a bb pair using the full CDF data set
We combine the results of searches for the standard model Higgs boson based
on the full CDF Run II data set obtained from sqrt(s) = 1.96 TeV p-pbar
collisions at the Fermilab Tevatron corresponding to an integrated luminosity
of 9.45/fb. The searches are conducted for Higgs bosons that are produced in
association with a W or Z boson, have masses in the range 90-150 GeV/c^2, and
decay into bb pairs. An excess of data is present that is inconsistent with the
background prediction at the level of 2.5 standard deviations (the most
significant local excess is 2.7 standard deviations).Comment: To be published in Phys. Rev. Lett (v2 contains minor updates based
on comments from PRL
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