1,538 research outputs found

    Effectiveness of denosumab for fracture prevention in real-world postmenopausal women with osteoporosis: a retrospective cohort study

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    Summary: To determine denosumab’s effectiveness for fracture prevention among postmenopausal women with osteoporosis in East Asia, the risk of fracture was compared between patients continuing denosumab therapy versus patients discontinuing denosumab after one dose. The real-world effectiveness was observed to be consistent with the efficacy demonstrated in the phase III trial. Introduction: After therapeutic efficacy is demonstrated for subjects in global clinical trials, real-world evidence may provide complementary knowledge of therapeutic effectiveness in a heterogeneous mix of patients seen in clinical practice. This retrospective cohort study was conducted to compare the fracture risk in real-world clinical care received in Taiwan and Hong Kong between a treatment cohort (patients receiving denosumab 60 mg subcutaneously every 6 months) versus an off-treatment cohort (patients discontinuing after 1 dose of denosumab, which has no known clinical benefit) among real-world postmenopausal women. Methods: This study included 38,906 and 2,835 postmenopausal women receiving denosumab in Taiwan and Hong Kong, respectively. The primary endpoint was hip fracture, and secondary endpoints were clinical vertebral and nonvertebral fractures. Propensity-score-matched analysis, adjusting for known covariates, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The robustness of findings was evaluated with a series of sensitivity and quantitative bias analyses. Results: In this study, 554 hip fractures were included in the primary Taiwan population analysis. The crude incidence rate was 0.9 per 100 person-years in the treatment cohort (n = 25,059) and 1.7 per 100 person-years in the off-treatment cohort (n = 13,847). After adjusting for prognostic differences between cohorts, denosumab reduced the risk of hip fractures by 38% (HR = 0.62, CI:0.52–0.75). Risk reductions of similar magnitude were observed for the secondary endpoints and for the analysis of the smaller Hong Kong population. Conclusion: The effectiveness of denosumab for fracture reduction among real-world postmenopausal women with osteoporosis was consistent with the efficacy demonstrated in a global clinical trial

    Observation of discrete time-crystalline order in a disordered dipolar many-body system

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    Understanding quantum dynamics away from equilibrium is an outstanding challenge in the modern physical sciences. It is well known that out-of-equilibrium systems can display a rich array of phenomena, ranging from self-organized synchronization to dynamical phase transitions. More recently, advances in the controlled manipulation of isolated many-body systems have enabled detailed studies of non-equilibrium phases in strongly interacting quantum matter. As a particularly striking example, the interplay of periodic driving, disorder, and strong interactions has recently been predicted to result in exotic "time-crystalline" phases, which spontaneously break the discrete time-translation symmetry of the underlying drive. Here, we report the experimental observation of such discrete time-crystalline order in a driven, disordered ensemble of ∼106\sim 10^6 dipolar spin impurities in diamond at room-temperature. We observe long-lived temporal correlations at integer multiples of the fundamental driving period, experimentally identify the phase boundary and find that the temporal order is protected by strong interactions; this order is remarkably stable against perturbations, even in the presence of slow thermalization. Our work opens the door to exploring dynamical phases of matter and controlling interacting, disordered many-body systems.Comment: 6 + 3 pages, 4 figure

    Dutch orthopedic thromboprophylaxis: a 5-year follow-up survey

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    Background and purpose Previous surveys in the Netherlands have revealed that guidelines regarding orthopedic thromboprophylaxis were not followed and that a wide variation in protocols exists. This survey was performed to assess the current use of thromboprophylactic modalities and to compare it with the results of a previous survey

    Cell Proliferation in the Presence of Telomerase

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    BACKGROUND: Telomerase, which is active early in development and later in stem and germline cells, is also active in the majority of human cancers. One of the known functions of telomerase is to extend the ends of linear chromosomes, countering their gradual shortening at each cell division due to the end replication problem and postreplication processing. Telomerase concentration levels vary between different cell types as well as between different tumors. In addition variable telomerase concentrations will exist in different cells in the same tumor when telomerase inhibitors are used, because of limitations of drug delivery in tissue. Telomerase extends short telomeres more frequently than long telomeres and the relation between the extension frequency and the telomere length is nonlinear. METHODOLOGY/PRINCIPAL FINDINGS: Here, the biological data of the nonlinear telomerase-telomere dynamics is incorporated in a mathematical theory to relate the proliferative potential of a cell to the telomerase concentration in that cell. The main result of the paper is that the proliferative capacity of a cell grows exponentially with the telomerase concentration. CONCLUSIONS/SIGNIFICANCE: The theory presented here suggests that long term telomerase inhibition in every cancer progenitor or cancer stem cell is needed for successful telomere targeted cancer treatment. This theory also can be used to plan and assess the results of clinical trials targeting telomerase

    The Quantum Internet

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    Quantum networks offer a unifying set of opportunities and challenges across exciting intellectual and technical frontiers, including for quantum computation, communication, and metrology. The realization of quantum networks composed of many nodes and channels requires new scientific capabilities for the generation and characterization of quantum coherence and entanglement. Fundamental to this endeavor are quantum interconnects that convert quantum states from one physical system to those of another in a reversible fashion. Such quantum connectivity for networks can be achieved by optical interactions of single photons and atoms, thereby enabling entanglement distribution and quantum teleportation between nodes.Comment: 15 pages, 6 figures Higher resolution versions of the figures can be downloaded from the following link: http://www.its.caltech.edu/~hjkimble/QNet-figures-high-resolutio

    An empirical study of software reuse by experts in object-oriented design

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    This paper presents an empirical study of the software reuse activity by expert designers in the context of object-oriented design. Our study focuses on the three following aspects of reuse : (1) the interaction between some design processes, e.g. constructing a problem representation, searching for and evaluating solutions, and reuse processes, i.e. retrieving and using previous solutions, (2) the mental processes involved in reuse, e.g. example-based retrieval or bottom-up versus top-down expanding of the solution, and (3) the mental representations constructed throughout the reuse activity, e.g. dynamic versus static representations. Some implications of these results for the specification of software reuse support environments are discussed

    GLOBAL STABILITY AND BIFURCATIONS ANALYSIS OF AN EPIDEMIC MODEL WITH CONSTANT REMOVAL RATE OF THE INFECTIVE

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    In this thesis we consider an epidemic model with a constant removal rate of infective individuals is proposed to understand the effect of limited resources for treatment of infective on the disease spread. It is found that it is unnecessary to take such a large treatment capacity that endemic equilibria disappear to eradicate the disease. It is shown that the outcome of disease spread may depend on the position of the initial states for certain range of parameters. It is also shown that the model undergoes a sequence of bifurcations including saddle-node bifurcation, subcritical Hopf bifurcation. Keyword: Epidemic model, nonlinear incidence rate, basic reproduction number, local and global stabilit

    Factorization at Subleading Power and Irreducible Uncertainties in Bˉ→Xsγ\bar B\to X_s\gamma Decay

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    Using methods from soft-collinear and heavy-quark effective theory, a systematic factorization analysis is performed for the Bˉ→Xsγ\bar B\to X_s\gamma photon spectrum in the endpoint region mb−2Eγ=O(ΛQCD)m_b-2E_\gamma={\cal O}(\Lambda_{\rm QCD}). It is proposed that, to all orders in 1/mb1/m_b, the spectrum obeys a novel factorization formula, which besides terms with the structure H J⊗SH\,J\otimes S familiar from inclusive Bˉ→Xul νˉ\bar B\to X_u l\,\bar\nu decay distributions contains "resolved photon" contributions of the form H J⊗S⊗JˉH\,J\otimes S\otimes\bar J and H J⊗S⊗Jˉ⊗JˉH\,J\otimes S\otimes\bar J\otimes\bar J. Here SS and Jˉ\bar J are new soft and jet functions, whose form is derived. These contributions arise whenever the photon couples to light partons instead of coupling directly to the effective weak interaction. The new contributions appear first at order 1/mb1/m_b and are related to operators other than Q7γQ_{7\gamma} in the effective weak Hamiltonian. They give rise to non-vanishing 1/mb1/m_b corrections to the total decay rate, which cannot be described using a local operator product expansion. A systematic analysis of these effects is performed at tree level in hard and hard-collinear interactions. The resulting uncertainty on the decay rate defined with a cut Eγ>1.6E_\gamma>1.6 GeV is estimated to be approximately ±5\pm 5%. It could be reduced by an improved measurement of the isospin asymmetry Δ0−\Delta_{0-} to the level of ±4\pm 4%. We see no possibility to reduce this uncertainty further using reliable theoretical methods.Comment: 63 pages, 11 Figures, Journal Versio
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