Exploring the impact of the reclassification of a hereditary cancer syndrome gene variant: emerging themes from a qualitative study

The complexity of genetic variant interpretation means that a proportion of individuals who undergo genetic testing for a hereditary cancer syndrome will have their test result reclassified over time. Such a reclassification may involve a clinically significant upgrade or downgrade in pathogenicity, which may have significant implications for medical management. To date, few studies have examined the psychosocial impact of a reclassification in a hereditary cancer syndrome context. To address this gap, semi-structured telephone interviews were performed with eighteen individuals who had a BRCA1, BRCA2 or Lynch syndrome-related (MLH1, MSH2, MSH6 or PMS2) gene variant reclassified. The interviews were analysed utilising an inductive, qualitative approach and emergent themes were identified by thematic analysis. Variable levels of recall amongst participants were found. Common motivations for initial testing included a significant personal and/or family history of cancer and a desire to “find an answer”. No individual whose uncertain result was upgraded reported negative psychosocial outcomes; most reported adapting to their reclassified result and appraised their genetic testing experience positively. However, individuals whose likely pathogenic/pathogenic results were downgraded reported feelings of anger, shock and sadness post reclassification, highlighting that additional psychosocial support may be required for some. Genetic counselling issues and recommendations for clinical practice are outlined

Prevalence of Community-Associated Methicillin-Resistant Staphylococcus aureus in Patients with Cystic Fibrosis

We prospectively determined the prevalence of community-associated Staphylococcus aureus in a large cystic fibrosis (CF) center between October 2005 and October 2007. We found that 2.7% (19/707) of the CF patients who had cultures during the study period were infected with this organism, representing 14% of the total methicillin-resistant Staphylococcus aureus strains (n = 140) recovered from the patient population during the study period

Evidence for direct CP violation in the decay B->D(*)K, D->KsPi+Pi- and measurement of the CKM phase phi3

We present a new measurement of the unitarity triangle angle phi3 using a Dalitz plot analysis of the KsPi+Pi- decay of the neutral D meson produced in B->D(*)K decays. The method exploits the interference between D0 and D0bar to extract the angle phi3, strong phase delta and the ratio r of suppressed and allowed amplitudes. We apply this method to a 605 fb-1 data sample collected by the Belle experiment. The analysis uses three decays: B->DK, and B->D*K with D*->DPi0 and D*->Dgamma, as well as the corresponding charge-conjugate modes. From a combined maximum likelihood fit to the three modes, we obtain phi3 = 78.4^+10.8_-11.6 +- 3.6 (syst) +- 8.9 (model) degrees. CP conservation in this process is ruled out at the confidence level (1-CL)=5x10^-4, or 3.5 standard deviations.Comment: 10 pages, 5 figures, 4 tables. Replaced by version published in Phys. Rev.

Observation of Bs->Ds(*)+Ds(*)- using e+e- collisions and a determination of the Bs-Bsbar width difference \Delta\Gamma_s

We have made the first observation of Bs->Ds(*)+Ds(*)- decays using 23.6 fb-1 of data recorded by the Belle experiment running on the Upsilon(5S) resonance. The branching fractions are measured to be B(B^0_s\ra D^+_s D^-_s) = (1.0\,^{+0.4}_{-0.3}\,^{+0.3}_{-0.2})%, B(B^0_s\ra D^{*\pm}_s D^{\mp}_s) = (2.8\,^{+0.8}_{-0.7}\,\pm 0.7)%, and B(B^0_s\ra D^{*+}_s D^{*-}_s) = (3.1\,^{+1.2}_{-1.0}\,\pm 0.8)%; the sum is B(B^0_s\ra D^{(*)+}_s D^{(*)-}_s) = (6.9\,^{+1.5}_{-1.3}\,\pm 1.9)%. Assuming Bs->Ds(*)+Ds(*)- saturates decays to CP-even final states, the branching fraction determines the ratio \Delta\Gamma_s/cos(\phi), where \Delta\Gamma_s is the difference in widths between the two Bs-Bsbar mass eigenstates, and \phi is a CP-violating weak phase. Taking CP violation to be negligibly small, we obtain \Delta\Gamma_s/\Gamma_s = 0.147^{+0.036}_{-0.030}(stat.)^{+0.044}_{-0.042}(syst.), where \Gamma_s is the mean decay width.Comment: 13 pages, 2 figures, 2 tables. v2: text added for clarification, version published in Phys. Rev. Letter

Evidence for a new resonance and search for the Y(4140) in γγ→ϕJ/ψ\gamma \gamma \to \phi J/\psi

The process \gamma \gamma \to \phi \jpsi is measured for \phi \jpsi masses between threshold and 5 GeV/${\it c}^2$, using a data sample of 825 fb$^{-1}$ collected with the Belle detector. A narrow peak of $8.8^{+4.2}_{-3.2}$ events, with a significance of 3.2 standard deviations including systematic uncertainty, is observed. The mass and natural width of the structure (named X(4350)) are measured to be $(4350.6^{+4.6}_{-5.1}(\rm{stat})\pm 0.7(\rm{syst})) \hbox{MeV}/{\it c}^2$ and $(13^{+18}_{-9}(\rm{stat})\pm 4(\rm{syst})) \hbox{MeV}$, respectively. The product of its two-photon decay width and branching fraction to \phi\jpsi is $(6.7^{+3.2}_{-2.4}(\rm{stat}) \pm 1.1(\rm{syst})) \hbox{eV}$ for $J^P=0^+$, or $(1.5^{+0.7}_{-0.6}(\rm{stat}) \pm 0.3(\rm{syst})) \hbox{eV}$ for $J^P=2^+$. No signal for the Y(4140)\to \phi \jpsi structure reported by the CDF Collaboration in B\to K^+ \phi \jpsi decays is observed, and limits of \Gamma_{\gamma \gamma}(Y(4140)) \BR(Y(4140)\to\phi \jpsi)<41 \hbox{eV} for $J^P=0^+$ or $<6.0 \hbox{eV}$ for $J^P=2^+$ are determined at the 90% C.L. This disfavors the scenario in which the Y(4140) is a $D_{s}^{\ast+} {D}_{s}^{\ast-}$ molecule.Comment: 9 pages, 3 figures, publication in Phys. Rev. Lett. 104, 112004, 201

Search for the X(1812) in B±→K±ωϕB^{\pm} \to K^{\pm} \omega \phi

We report on a search for the X(1812) state in the decay $B^{\pm} \to K^{\pm} \omega \phi$ with a data sample of $657\times10^6$ $B\bar{B}$ pairs collected with the Belle detector at the KEKB $e^+e^-$ collider. No significant signal is observed. An upper limit ${\cal B}(B^{\pm} \to K^{\pm} X(1812),X(1812) \to \omega \phi)<3.2\times 10^{-7}$ (90% C.L.) is determined. We also constrain the three-body decay branching fraction to be ${\cal B}(B^{\pm} \to K^{\pm} \omega \phi)$ $<$ 1.9 $\times 10^{-6}$ (90% C.L.).Comment: 5pages,2 figures(3 figure files). submitted to PRD(RC

Measurement of CP violating asymmetries in B^0 -> K^+K^- K^0_S decays with a time-dependent Dalitz approach

We report a measurement of $CP$ violating asymmetries in $B^0(\overline{B}^0) \to K^+ K^- K^0_S$ decays with a time-dependent Dalitz approach. This analysis is based on a data sample of $657\times 10^6$ $B\overline{B}$ pairs accumulated at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. As the result of an unbinned maximum likelihood fit to the selected candidates, the mixing-induced and direct $CP$ violation parameters, $\phi^{\rm eff}_1$ and ${\cal A}_{CP}$ are obtained for $B^0 \to \phi(1020) K^0_S$, $B^0 \to f_0(980) K^0_S$ and other $B^0 \to K^+ K^- K^0_S$ decays. We find four solutions that describe the data. There are \{eqnarray*} \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (32.2 \pm 9.0 \pm 2.6 \pm 1.4)^{\circ}; \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (26.2 \pm 8.8 \pm 2.7 \pm 1.2)^{\circ};\\ \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (27.3 \pm 8.6 \pm 2.8 \pm 1.3)^{\circ}\; {\rm and}\\ \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (24.3 \pm 8.0 \pm 2.9 \pm 5.2)^{\circ}.{eqnarray*}\ The values for the $CP$ violating phase in $B^0\to \phi(1020) K^0_S$ are similar but other properties of the Dalitz plot are quite different for the four solutions. These four solutions have consistent $\phi^{\rm eff}_1$ values for all three $B$ meson decay channels and none of them deviates significantly from the values measured in $B \to (c\bar{c}) K^0$ decays with the currently available statistics. In addition, we find no significant direct $CP$ violation.Comment: submitted to PR

Measurement Of |V_ub| From Inclusive Charmless Semileptonic B Decays

We present the partial branching fraction for inclusive charmless semileptonic B decays and the corresponding value of the CKM matrix element |Vub|, using a multivariate analysis method to access ~90% of the B -> Xu l nu phase space. This approach dramatically reduces the theoretical uncertainties from the b-quark mass and non-perturbative QCD compared to all previous inclusive measurements. The results are based on a sample of 657 million B -Bbar pairs collected with the Belle detector. We find that Delta BR(B -> Xu l nu; p^*B_l>1.0 GeV/c=1.963 x (1 +/- 0.088(stat.) +/- 0.081(sys.)) x 10^-3. Corresponding values of |Vub| are extracted using several theoretical calculations.Comment: 9 pages, 1 figure, 2 tables. Published in PR

Evidence for B- -> tau- nu_bar with a Semileptonic Tagging Method

We present a measurement of the decay B- -> tau- nu_bar using a data sample containing 657 million BB_bar pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. A sample of BB_bar pairs are tagged by reconstructing one B meson decaying semileptonically. We detect the B- -> tau- nu_bar candidate in the recoil. We obtain a signal with a significance of 3.6 standard deviations including systematic uncertainties, and measure the branching fraction to be Br(B- -> tau- nu_bar) = [1.54+0.38-0.37(stat)+0.29-0.31(syst)]*10^-4. This result confirms the evidence for B- -> tau- nu_bar obtained in a previous Belle measurement that used a hadronic B tagging method.Comment: 7 pages, 3 figures, corrected references, to appear in PRD-R