Identifying a core set of outcome domains to measure in clinical trials for shoulder disorders: a modified Delphi study.

OBJECTIVE: To achieve consensus on the most important outcome domains to measure across all clinical trials for shoulder disorders. METHODS: We performed an online modified Delphi study with an international, multidisciplinary and multistakeholder panel. A literature review and the OMERACT Filter 2.0 framework was used to generate a list of potential core domains, which were presented to patients, clinicians and researchers in two Delphi rounds. Participants were asked to judge the importance of each potential core domain and provide a rationale for their response. A core domain was defined a priori as a domain that at least 67% of participants considered core. RESULTS: In both rounds, 335 individuals were invited to participate (268 clinicians/researchers and 67 patients); response rates were 27% (n=91) and 29% (n=96), respectively. From a list of 41 potential core domains, four domains met our criteria for inclusion: 'pain', 'physical functioning', 'global assessment of treatment success' and 'health-related quality of life'. Two additional domains, 'sleep functioning' and 'psychological functioning', met the criteria for inclusion by some, but not all stakeholder groups. There was consensus that 'number of deaths' was not a core domain, but insufficient agreement on whether or not several other domains, including 'range of motion' and 'muscle strength', were core domains. CONCLUSIONS: Based on international consensus from patients, clinicians and researchers, 'pain', 'physical functioning', 'global assessment of treatment success' and 'health-related quality of life' were considered core outcome domains for shoulder disorder trials. The value of several other domains needs further consideration

Emergent excitations in a geometrically frustrated magnet

Frustrated systems are ubiquitous and interesting because their behavior is difficult to predict. Magnetism offers extreme examples in the form of spin lattices where all interactions between spins cannot be simultaneously satisfied. Such geometrical frustration leads to macroscopic degeneracies, and offers the possibility of qualitatively new states of matter whose nature has yet to be fully understood. Here we have discovered how novel composite spin degrees of freedom can emerge from frustrated interactions in the cubic spinel ZnCr2O4. Upon cooling, groups of six spins self-organize into weakly interacting antiferromagnetic loops whose directors, defined as the unique direction along which the spins are aligned parallel or antiparallel, govern all low temperature dynamics. The experimental evidence comes from a measurement of the magnetic form factor by inelastic neutron scattering. While the data bears no resemblance to the atomic form factor for chromium, they are perfectly consistent with the form factor for hexagonal spin loop directors. The hexagon directors are to a first approximation decoupled from each other and hence their reorientations embody the long-sought local zero energy modes for the pyrochlore lattice.Comment: 10 pages, 4 figures upon reques

Two-dimensional amine and hydroxy functionalized fused aromatic covalent organic framework

Ordered two-dimensional covalent organic frameworks (COFs) have generally been synthesized using reversible reactions. It has been difficult to synthesize a similar degree of ordered COFs using irreversible reactions. Developing COFs with a fused aromatic ring system via an irreversible reaction is highly desirable but has remained a significant challenge. Here we demonstrate a COF that can be synthesized from organic building blocks via irreversible condensation (aromatization). The as-synthesized robust fused aromatic COF (F-COF) exhibits high crystallinity. Its lattice structure is characterized by scanning tunneling microscopy and X-ray diffraction pattern. Because of its fused aromatic ring system, the F-COF structure possesses high physiochemical stability, due to the absence of hydrolysable weak covalent bonds

Quantum spin liquid states in the two dimensional kagome antiferromagnets, ZnxCu4-x(OD)6Cl2

A three-dimensional system of interacting spins typically develops static long-range order when it is cooled. If the spins are quantum (S = 1/2), however, novel quantum paramagnetic states may appear. The most highly sought state among them is the resonating valence bond (RVB) state in which every pair of neighboring quantum spins form entangled spin singlets (valence bonds) and the singlets are quantum mechanically resonating amongst all the possible highly degenerate pairing states. Here we provide experimental evidence for such quantum paramagnetic states existing in frustrated antiferromagnets, ZnxCu4-x(OD)6Cl2, where the S = 1/2 magnetic Cu2+ moments form layers of a two-dimensional kagome lattice. We find that in Cu4(OD)6Cl2, where distorted kagome planes are weakly coupled to each other, a dispersionless excitation mode appears in the magnetic excitation spectrum below ~ 20 K, whose characteristics resemble those of quantum spin singlets in a solid state, known as a valence bond solid (VBS), that breaks translational symmetry. Doping nonmagnetic Zn2+ ions reduces the distortion of the kagome lattice, and weakens the interplane coupling but also dilutes the magnetic occupancy of the kagome lattice. The VBS state is suppressed and for ZnCu3(OD)6Cl2 where the kagome planes are undistorted and 90% occupied by the Cu2+ ions, the low energy spin fluctuations in the spin liquid phase become featureless

Machine-learning of atomic-scale properties based on physical principles

We briefly summarize the kernel regression approach, as used recently in materials modelling, to fitting functions, particularly potential energy surfaces, and highlight how the linear algebra framework can be used to both predict and train from linear functionals of the potential energy, such as the total energy and atomic forces. We then give a detailed account of the Smooth Overlap of Atomic Positions (SOAP) representation and kernel, showing how it arises from an abstract representation of smooth atomic densities, and how it is related to several popular density-based representations of atomic structure. We also discuss recent generalisations that allow fine control of correlations between different atomic species, prediction and fitting of tensorial properties, and also how to construct structural kernels---applicable to comparing entire molecules or periodic systems---that go beyond an additive combination of local environments

Hidden SUSY at the LHC: the light higgsino-world scenario and the role of a lepton collider

While the SUSY flavor, CP and gravitino problems seem to favor a very heavy spectrum of matter scalars, fine-tuning in the electroweak sector prefers low values of superpotential mass \mu. In the limit of low \mu, the two lightest neutralinos and light chargino are higgsino-like. The light charginos and neutralinos may have large production cross sections at LHC, but since they are nearly mass degenerate, there is only small energy release in three-body sparticle decays. Possible dilepton and trilepton signatures are difficult to observe after mild cuts due to the very soft p_T spectrum of the final state isolated leptons. Thus, the higgsino-world scenario can easily elude standard SUSY searches at the LHC. It should motivate experimental searches to focus on dimuon and trimuon production at the very lowest p_T(\mu) values possible. If the neutralino relic abundance is enhanced via non-standard cosmological dark matter production, then there exist excellent prospects for direct or indirect detection of higgsino-like WIMPs. While the higgsino-world scenario may easily hide from LHC SUSY searches, a linear e^+e^- collider or a muon collider operating in the \sqrt{s}\sim 0.5-1 TeV range would be able to easily access the chargino and neutralino pair production reactions.Comment: 20 pages including 12 .eps figure

Nanodiamonds as Carriers for Address Delivery of Biologically Active Substances

Surface of detonation nanodiamonds was functionalized for the covalent attachment of immunoglobulin, and simultaneously bovine serum albumin and Rabbit Anti-Mouse Antibody. The nanodiamond-IgGI125 and RAM-nanodiamond-BSAI125 complexes are stable in blood serum and the immobilized proteins retain their biological activity. It was shown that the RAM-nanodiamond-BSAI125 complex is able to bind to the target antigen immobilized on the Sepharose 6B matrix through antibody–antigen interaction. The idea can be extended to use nanodiamonds as carriers for delivery of bioactive substances (i.e., drugs) to various targets in vivo

Multiple targets for flecainide action: implications for cardiac arrhythmogenesis

Flecainide suppresses cardiac tachyarrhythmias including paroxysmal atrial fibrillation, supraventricular tachycardia and arrhythmic long QT syndromes (LQTS), as well as the Ca(2+) -mediated, catecholaminergic polymorphic ventricular tachycardia (CPVT). However, flecainide can also exert pro-arrhythmic effects most notably following myocardial infarction and when used to diagnose Brugada syndrome (BrS). These divergent actions result from its physiological and pharmacological actions at multiple, interacting levels of cellular organization. These were studied in murine genetic models with modified Nav channel or intracellular ryanodine receptor (RyR2)-Ca(2+) channel function. Flecainide accesses its transmembrane Nav 1.5 channel binding site during activated, open, states producing a use-dependent antagonism. Closing either activation or inactivation gates traps flecainide within the pore. An early peak INa related to activation of Nav channels followed by rapid de-activation, drives action potential (AP) upstrokes and their propagation. This is diminished in pro-arrhythmic conditions reflecting loss of function of Nav 1.5 channels, such as BrS, accordingly exacerbated by flecainide challenge. Contrastingly, pro-arrhythmic effects attributed to prolonged AP recovery by abnormal late INaL following gain-of-function modifications of Nav 1.5 channels in LQTS3 are reduced by flecainide. Anti-arrhythmic effects of flecainide that reduce triggering in CPVT models mediated by sarcoplasmic reticular Ca(2+) release could arise from its primary actions on Nav channels indirectly decreasing [Ca(2+) ]i through a reduced [Na(+) ]i and/or direct open-state RyR2-Ca(2+) channel antagonism. The consequent [Ca(2+) ]i alterations could also modify AP propagation velocity and therefore arrhythmic substrate through its actions on Nav 1.5 channel function. This is consistent with the paradoxical differences between flecainide actions upon Na(+) currents, AP conduction and arrhythmogenesis under circumstances of normal and increased RyR2 function.S.C.S. and A.P.J. are funded by the British Heart Foundation (PG/14/79/31102). K.J. is funded by the Fundamental Research Grant Scheme (FRGS/2/2014/SKK01/PERDANA/ 02/1), Ministry of Education, Malaysia and the Research Support Fund, Faculty of Health and Medical Science, University of Surrey. A.F.D. is funded by the National Health and Medical Research Council (NHMRC) of Australia (APP1126201). A.J.T. is funded by the British Heart Foundation (PG/13/39/3029). C.L.H.H. is funded by the Medical Research Council (MR/M001288/1), Wellcome Trust (105727/Z/14/Z), British Heart Foundation (PG/14/79/ 31102), the McVeigh Benefaction and SADS UK

A photonic quantum information interface

Quantum communication is the art of transferring quantum states, or quantum bits of information (qubits), from one place to another. On the fundamental side, this allows one to distribute entanglement and demonstrate quantum nonlocality over significant distances. On the more applied side, quantum cryptography offers, for the first time in human history, a provably secure way to establish a confidential key between distant partners. Photons represent the natural flying qubit carriers for quantum communication, and the presence of telecom optical fibres makes the wavelengths of 1310 and 1550 nm particulary suitable for distribution over long distances. However, to store and process quantum information, qubits could be encoded into alkaline atoms that absorb and emit at around 800 nm wavelength. Hence, future quantum information networks made of telecom channels and alkaline memories will demand interfaces able to achieve qubit transfers between these useful wavelengths while preserving quantum coherence and entanglement. Here we report on a qubit transfer between photons at 1310 and 710 nm via a nonlinear up-conversion process with a success probability greater than 5%. In the event of a successful qubit transfer, we observe strong two-photon interference between the 710 nm photon and a third photon at 1550 nm, initially entangled with the 1310 nm photon, although they never directly interacted. The corresponding fidelity is higher than 98%.Comment: 7 pages, 3 figure