Platelet degranulation and bleeding phenotype in a large cohort of Von Willebrand disease patients

Von Willebrand disease (VWD) is a bleeding disorder caused by quantitative (type 1 or 3) or qualitative (type 2A/2B/2M/2N) defects of circulating von Willebrand factor (VWF). Circulating VWF levels not always fully explain bleeding phenotypes, suggesting a role for alternative factors, like platelets. Here, we investigated platelet factor 4 (PF4) in a large cohort of patients with VWD. PF4 levels were lower in type 2B and current bleeding phenotype was significantly associated with higher PF4 levels, particularly in type 1 VWD. Based on our findings we speculate that platelet degranulation and cargo release may play a role across VWD subtypes

Dutch National Round Robin Trial on Plasma-Derived Circulating Cell-Free DNA Extraction Methods Routinely Used in Clinical Pathology for Molecular Tumor Profiling

BACKGROUND: Efficient recovery of circulating tumor DNA (ctDNA) depends on the quantity and quality of circulating cell-free DNA (ccfDNA). Here, we evaluated whether various ccfDNA extraction methods routinely applied in Dutch laboratories affect ccfDNA yield, ccfDNA integrity, and mutant ctDNA detection, using identical lung cancer patient-derived plasma samples. METHODS: Aliquots of 4 high-volume diagnostic leukapheresis plasma samples and one artificial reference plasma sample with predetermined tumor-derived mutations were distributed among 14 Dutch laboratories. Extractions of ccfDNA were performed according to local routine standard operating procedures and were analyzed at a central reference laboratory for mutant detection and assessment of ccfDNA quantity and integrity. RESULTS: Mutant molecule levels in extracted ccfDNA samples varied considerably between laboratories, but there was no indication of consistent above or below average performance. Compared to silica membrane-based methods, samples extracted with magnetic beads-based kits revealed an overall lower total ccfDNA yield (-29%; P < 0.0001) and recovered fewer mutant molecules (-41%; P < 0.01). The variant allelic frequency and sample integrity were similar. In samples with a higher-than-average total ccfDNA yield, an augmented recovery of mutant molecules was observed. CONCLUSIONS: In the Netherlands, we encountered diversity in preanalytical workflows with potential consequences on mutant ctDNA detection in clinical practice. Silica membrane-based methodologies resulted in the highest total ccfDNA yield and are therefore preferred to detect low copy numbers of relevant mutations. Harmonization of the extraction workflow for accurate quantification and sensitive detection is required to prevent introduction of technical divergence in the preanalytical phase and reduce interlaboratory discrepancies

Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma)

The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma and Bs0 -> phi gamma has been measured using 0.37 fb-1 of pp collisions at a centre of mass energy of sqrt(s) = 7 TeV, collected by the LHCb experiment. The value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) = 1.12 +/- 0.08 ^{+0.06}_{-0.04} ^{+0.09}_{-0.08}, where the first uncertainty is statistical, the second systematic and the third is associated to the ratio of fragmentation fractions fs/fd. Using the world average for BR(B0 -> K*0 gamma) = (4.33 +/- 0.15) x 10^{-5}, the branching fraction BR(Bs0 -> phi gamma) is measured to be (3.9 +/- 0.5) x 10^{-5}, which is the most precise measurement to date.Comment: 15 pages, 1 figure, 2 table

Search for CP violation in D+→K−K+π+D^{+} \to K^{-}K^{+}\pi^{+} decays

A model-independent search for direct CP violation in the Cabibbo suppressed decay $D^+ \to K^- K^+\pi^+$ in a sample of approximately 370,000 decays is carried out. The data were collected by the LHCb experiment in 2010 and correspond to an integrated luminosity of 35 pb$^{-1}$. The normalized Dalitz plot distributions for $D^+$ and $D^-$ are compared using four different binning schemes that are sensitive to different manifestations of CP violation. No evidence for CP asymmetry is found.Comment: 13 pages, 8 figures, submitted to Phys. Rev.

Measurements of the branching fractions of B+→ppK+ decays

The branching fractions of the decay B+ → pp̄K+ for different intermediate states are measured using data, corresponding to an integrated luminosity of 1.0 fb-1, collected by the LHCb experiment. The total branching fraction, its charmless component Mpp̄ < 2.85 GeV/c2 and the branching fractions via the resonant cc̄ states η c(1S) and ψ(2S) relative to the decay via a J/ψ intermediate state are [Equation not available: see fulltext.] Upper limits on the B + branching fractions into the η c(2S) meson and into the charmonium-like states X(3872) and X(3915) are also obtained

Observation of excited Lambda_b0 baryons

Using pp collision data corresponding to 1.0 fb-1 integrated luminosity collected by the LHCb detector, two narrow states are observed in the Lambda_b0pi+pi- spectrum with masses 5911.97 +- 0.12(stat) +- 0.02(syst) +- 0.66(Lambda_b0 mass) MeV/c^2 and 5919.77 +- 0.08(stat) +- 0.02(syst) +- 0.66(Lambda_b0 mass) MeV/c^2. The significances of the observations are 5.2 and 10.2 standard deviations, respectively. These states are interpreted as the orbitally-excited Lambda_b0 baryons, Lambda_b*0(5912) and Lambda_b*0(5920).Comment: Replaced by version published in Phys. Rev. Lett, modified fit with better mass resolution treatmen

Opposite-side flavour tagging of B mesons at the LHCb experiment

The calibration and performance of the oppositeside flavour tagging algorithms used for the measurements of time-dependent asymmetries at the LHCb experiment are described. The algorithms have been developed using simulated events and optimized and calibrated with B + →J/ψK +, B0 →J/ψK ∗0 and B0 →D ∗− μ + νμ decay modes with 0.37 fb−1 of data collected in pp collisions at √ s = 7 TeV during the 2011 physics run. The oppositeside tagging power is determined in the B + → J/ψK + channel to be (2.10 ± 0.08 ± 0.24) %, where the first uncertainty is statistical and the second is systematic

Strong constraints on the rare decays Bs -> mu+ mu- and B0 -> mu+ mu-

A search for Bs -> mu+ mu- and B0 -> mu+ mu- decays is performed using 1.0 fb^-1 of pp collision data collected at \sqrt{s}=7 TeV with the LHCb experiment at the Large Hadron Collider. For both decays the number of observed events is consistent with expectation from background and Standard Model signal predictions. Upper limits on the branching fractions are determined to be BR(Bs -> mu+ mu-) mu+ mu-) < 1.0 (0.81) x 10^-9 at 95% (90%) confidence level.Comment: 2+6 pages; 4 figures; Accepted for publication in Physical Review Letter

Measurement of the CP-violating phase phi_s in the decay Bs->J/psi phi

We present a measurement of the time-dependent CP-violating asymmetry in B_s -> J/psi phi decays, using data collected with the LHCb detector at the LHC. The decay time distribution of B_s -> J/psi phi is characterized by the decay widths Gamma_H and Gamma_L of the heavy and light mass eigenstates of the B_s-B_s-bar system and by a CP-violating phase phi_s. In a sample of about 8500 B_s -> J/psi phi events isolated from 0.37 fb^-1 of pp collisions at sqrt(s)=7 TeV we measure phi_s = 0.15 +/- 0.18 (stat) +/- 0.06 (syst) rad. We also find an average B_s decay width Gamma_s == (Gamma_L + Gamma_H)/2 = 0.657 +/- 0.009 (stat) +/- 0.008 (syst) ps^-1 and a decay width difference Delta Gamma_s == Gamma_L - Gamma_H} = 0.123 +/- 0.029 (stat) +/- 0.011 (syst) ps^-1. Our measurement is insensitive to the transformation (phi_s,DeltaGamma_s --> pi - phi_s, - Delta Gamma_s.Comment: 9 pages, 3 figure