Patient centred diagnosis: sharing diagnostic decisions with patients in clinical practice.

Patient centred diagnosis is best practised through shared decision making; an iterative dialogue between doctor and patient, whichrespects a patient’s needs, values, preferences, and circumstances. Shared decision making for diagnostic situations differs fundamentally from that for treatment decisions. This has important implications when considering its practical application. The nature of dialogue should be tailored to the specific diagnostic decision; scenarios with higher stakes or uncertainty usually require more detailed conversation

Sextupole correction magnets for the Large Hadron Collider

About 2500 superconducting sextupole corrector magnets (MCS) are needed for the Large Hadron Collider (LHC) at CERN to compensate persistent current sextupole fields of the main dipoles. The MCS is a cold bore magnet with iron yoke. The coils are made from a NbTi conductor, which is cooled to 1.9 K. In the original CERN design 6 individual sub-coils, made from a monolithic composite conductor, are assembled and spliced together to form the sextupole. The coils are individually wound around precision-machined central islands and stabilized with matching saddle pieces at both ends. The Advanced Magnet Lab, Inc. (AML) has produced an alternative design, which gives improved performance and reliability at reduced manufacturing cost. In the AML design, the magnet consists of three splice-free sub-coils, which are placed with an automated winding process into pockets of prefabricated G-11 support cylinders. Any assembly process of sub-coils with potential misalignment is eliminated. The AML magnet uses a Kapton-wrapped mini-cable, which allows helium penetration into the vicinity of the conductor, increasing its cryogenic stability. Eliminating all internal splices from the magnet significantly reduces heat loads and the risk of magnet failure during operation. A tested prototype reached the critical current limit of the conductor in the first quench. (3 refs)

Actinin BioID reveals sarcomere crosstalk with oxidative metabolism through interactions with IGF2BP2.

Actinins are strain-sensing actin cross-linkers that are ubiquitously expressed and harbor mutations in human diseases. We utilize CRISPR, pluripotent stem cells, and BioID to study actinin interactomes in human cardiomyocytes. We identify 324 actinin proximity partners, including those that are dependent on sarcomere assembly. We confirm 19 known interactors and identify a network of RNA-binding proteins, including those with RNA localization functions. In vivo and biochemical interaction studies support that IGF2BP2 localizes electron transport chain transcripts to actinin neighborhoods through interactions between its K homology (KH) domain and actinin\u27s rod domain. We combine alanine scanning mutagenesis and metabolic assays to disrupt and functionally interrogate actinin-IGF2BP2 interactions, which reveal an essential role in metabolic responses to pathological sarcomere activation using a hypertrophic cardiomyopathy model. This study expands our functional knowledge of actinin, uncovers sarcomere interaction partners, and reveals sarcomere crosstalk with IGF2BP2 for metabolic adaptation relevant to human disease

A Contraction Stress Model of Hypertrophic Cardiomyopathy due to Sarcomere Mutations.

Thick-filament sarcomere mutations are a common cause of hypertrophic cardiomyopathy (HCM), a disorder of heart muscle thickening associated with sudden cardiac death and heart failure, with unclear mechanisms. We engineered four isogenic induced pluripotent stem cell (iPSC) models of β-myosin heavy chain and myosin-binding protein C3 mutations, and studied iPSC-derived cardiomyocytes in cardiac microtissue assays that resemble cardiac architecture and biomechanics. All HCM mutations resulted in hypercontractility with prolonged relaxation kinetics in proportion to mutation pathogenicity, but not changes in calcium handling. RNA sequencing and expression studies of HCM models identified p53 activation, oxidative stress, and cytotoxicity induced by metabolic stress that can be reversed by p53 genetic ablation. Our findings implicate hypercontractility as a direct consequence of thick-filament mutations, irrespective of mutation localization, and the p53 pathway as a molecular marker of contraction stress and candidate therapeutic target for HCM patients

Further Search for the Two-Photon Production of the Glueball Candidate fJ(2220)f_{J}(2220)

The CLEOII detector at the Cornell e+ e- storage ring CESR has been used to search for the two-photon production of the $f_J(2220)$ decaying into pi+ pi-. No evidence for a signal is found in data corresponding to an integrated luminosity of 4.77/fb and a 95% CL upper limit on $\Gamma_{two-photon} * BR{pi+ pi-}$ of 2.5 eV is set. If this result is combined with the BES Collaboration's measurement of $f_J(2220) -> pi+ pi-$ in radiative $J/\psi$ decay, a 95% CL lower limit on the stickiness of the $f_J(2220)$ of 73 is obtained. If the recent CLEO result for \Gamma_{two-photon} * BR{\K_S K_S} is combined with the present result, the stickiness of the $f_J(2220)$ is found to be larger than 102 at the 95% CL. These results for the stickiness (the ratio of the probabilities for two-gluon coupling and two-photon coupling) provide further support for a substantial neutral parton content in the $f_J(2220)$.Comment: 8 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Measurement of the Bˉ→Dℓνˉ\bar{B}\to D\ell\bar{\nu} Partila Width and Form Factor Parameters

We have studied the decay $\bar{B} \to D\ell\bar{\nu}$, where $\ell=e or \mu$. From a fit to the differential decay rate $d\Gamma/dw$ we measure the rate normalization ${\cal F}_D(1)|V_{cb}|$ and form factor slope $\hat{\rho}^2_D$, and, using measured values of $\tau_B$, find $\Gamma(\bar{B} \to D\ell\bar{\nu}) = (12.0 \pm 0.9 \pm 2.1) ns^{-1}$. The resulting branching fractions are ${\cal B}(\bar{B}^0 \to D^+\ell^-\bar{\nu})=(1.87 \pm 0.15 \pm 0.32)$ and ${\cal B}(B^- \to D^0\ell^-\bar{\nu})=(1.94 \pm 0.15 \pm 0.34)$. The form factor parameters are in agreement with those measured in $\bar{B} \to D^*\ell\bar{\nu}$ decays, as predicted by heavy quark effective theory.Comment: 11 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Search for Exclusive Charmless Hadronic B Decays

We have searched for two-body charmless hadronic decays of $B$ mesons. Final states include $\pi\pi$, $K \pi$, and $KK$ with both charged and neutral kaons and pions; $\pi\rho$, $K \rho$, and $K^*\pi$; and $K\phi$, $K^*\phi$, and $\phi\phi$. The data used in this analysis consist of 2.6~million $B\bar{B}$~pairs produced at the $\Upsilon(4S)$ taken with the CLEO-II detector at the Cornell Electron Storage Ring (CESR). We measure the branching fraction of the sum of $B^0 \rightarrow \pi^+\pi^-$ and $B^0 \rightarrow K^+\pi^-$ to be $(1.8^{+0.6+0.2}_{-0.5-0.3}\pm0.2) \times 10^{-5}$. In addition, we place upper limits on individual branching fractions in the range from $10^{-4}$ to $10^{-6}$.Comment: 33 page LATEX file, uses REVTEX and psfig, 14 figures in a separate uuencoded postscript file, postscript version also available through http://w4.lns.cornell.edu/public/CLN

Observation of the Isospin-Violating Decay Ds∗+→Ds+π0D_s^{*+}\to D_s^+\pi^0

Using data collected with the CLEO~II detector, we have observed the isospin-violating decay $D_s^{*+}\to D_s^+\pi^0$. The decay rate for this mode, relative to the dominant radiative decay, is found to be $\Gamma(D_s^{*+}\to D_s^+\pi^0)/\Gamma(D_s^{*+}\to D_s^+\gamma)= 0.062^{+0.020}_{-0.018}\pm0.022$.Comment: 8 page uuencoded postscript file, also available through http://w4.lns.cornell.edu/public/CLN

Limit on the Two-Photon Production of the Glueball Candidate fJ(2220)f_{J}(2220) at CLEO

We use the CLEO detector at the Cornell electron-positron storage ring, CESR, to search for the two-photon production of the glueball candidate f_J(2220) in its decay to K_s K_s. We present a restrictive upper limit on the product of the two-photon partial width and the K_s K_s branching fraction. We use this limit to calculate a lower limit on the stickiness, which is a measure of the two-gluon coupling relative to the two-photon coupling. This limit on stickiness indicates that the f_J(2220) has substantial glueball content.Comment: 9 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN