Optical diode based on the chirality of guided photons

Photons are nonchiral particles: their handedness can be both left and right. However, when light is transversely confined, it can locally exhibit a transverse spin whose orientation is fixed by the propagation direction of the photons. Confined photons thus have chiral character. Here, we employ this to demonstrate nonreciprocal transmission of light at the single-photon level through a silica nanofibre in two experimental schemes. We either use an ensemble of spin-polarised atoms that is weakly coupled to the nanofibre-guided mode or a single spin-polarised atom strongly coupled to the nanofibre via a whispering-gallery-mode resonator. We simultaneously achieve high optical isolation and high forward transmission. Both are controlled by the internal atomic state. The resulting optical diode is the first example of a new class of nonreciprocal nanophotonic devices which exploit the chirality of confined photons and which are, in principle, suitable for quantum information processing and future quantum optical networks

Dimension reduction and shrinkage methods for high dimensional disease risk scores in historical data

Abstract Background Multivariable confounder adjustment in comparative studies of newly marketed drugs can be limited by small numbers of exposed patients and even fewer outcomes. Disease risk scores (DRSs) developed in historical comparator drug users before the new drug entered the market may improve adjustment. However, in a high dimensional data setting, empirical selection of hundreds of potential confounders and modeling of DRS even in the historical cohort can lead to over-fitting and reduced predictive performance in the study cohort. We propose the use of combinations of dimension reduction and shrinkage methods to overcome this problem, and compared the performances of these modeling strategies for implementing high dimensional (hd) DRSs from historical data in two empirical study examples of newly marketed drugs versus comparator drugs after the new drugs’ market entry—dabigatran versus warfarin for the outcome of major hemorrhagic events and cyclooxygenase-2 inhibitor (coxibs) versus nonselective non-steroidal anti-inflammatory drugs (nsNSAIDs) for gastrointestinal bleeds. Results Historical hdDRSs that included predefined and empirical outcome predictors with dimension reduction (principal component analysis; PCA) and shrinkage (lasso and ridge regression) approaches had higher c-statistics (0.66 for the PCA model, 0.64 for the PCA + ridge and 0.65 for the PCA + lasso models in the warfarin users) than an unreduced model (c-statistic, 0.54) in the dabigatran example. The odds ratio (OR) from PCA + lasso hdDRS-stratification [OR, 0.64; 95 % confidence interval (CI) 0.46–0.90] was closer to the benchmark estimate (0.93) from a randomized trial than the model without empirical predictors (OR, 0.58; 95 % CI 0.41–0.81). In the coxibs example, c-statistics of the hdDRSs in the nsNSAID initiators were 0.66 for the PCA model, 0.67 for the PCA + ridge model, and 0.67 for the PCA + lasso model; these were higher than for the unreduced model (c-statistic, 0.45), and comparable to the demographics + risk score model (c-statistic, 0.67). Conclusions hdDRSs using historical data with dimension reduction and shrinkage was feasible, and improved confounding adjustment in two studies of newly marketed medications

Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis

Background: Observational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture. Objectives: 1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs. Data sources Pubmed and Science Citation Index. Study eligibility criteria, participants, and interventions Studies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a “new user” design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events. Study appraisal and synthesis methods For each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference—comparing FGAs to SGAs—mediated by their difference in risk for the medical event. Results: We provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference. Conclusions: The current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs

The KB paradigm and its application to interactive configuration

The knowledge base paradigm aims to express domain knowledge in a rich formal language, and to use this domain knowledge as a knowledge base to solve various problems and tasks that arise in the domain by applying multiple forms of inference. As such, the paradigm applies a strict separation of concerns between information and problem solving. In this paper, we analyze the principles and feasibility of the knowledge base paradigm in the context of an important class of applications: interactive configuration problems. In interactive configuration problems, a configuration of interrelated objects under constraints is searched, where the system assists the user in reaching an intended configuration. It is widely recognized in industry that good software solutions for these problems are very difficult to develop. We investigate such problems from the perspective of the KB paradigm. We show that multiple functionalities in this domain can be achieved by applying different forms of logical inferences on a formal specification of the configuration domain. We report on a proof of concept of this approach in a real-life application with a banking company. To appear in Theory and Practice of Logic Programming (TPLP).Comment: To appear in Theory and Practice of Logic Programming (TPLP

Active safety monitoring of newly marketed medications in a distributed data network: application of a semi-automated monitoring system

We developed a semi-automated active monitoring system that uses sequential matched-cohort analyses to assess drug safety across a distributed network of longitudinal electronic healthcare data. In a retrospective analysis, we showed that the system would have identified cerivastatin-induced rhabdomyolysis. In this study, we evaluated whether the system would generate alerts for three drug-outcome pairs: rosuvastatin and rhabdomyolysis (known null association), rosuvastatin and diabetes mellitus, and telithromycin and hepatotoxicity (two examples for which alerting would be questionable). During >5 years of monitoring, rate differences (RDs) comparing rosuvastatin to atorvastatin were -0.1 cases of rhabdomyolysis per 1,000 person-years (95% CI, -0.4, 0.1) and -2.2 diabetes cases per 1,000 person-years (95% CI, -6.0, 1.6). The RD for hepatotoxicity comparing telithromycin to azithromycin was 0.3 cases per 1,000 person-years (95% CI, -0.5, 1.0). In a setting in which false positivity is a major concern, the system did not generate alerts for three drug-outcome pairs

Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study

Objective To assess risks of mortality associated with use of individual antipsychotic drugs in elderly residents in nursing homes

Scattering and absorption of ultracold atoms by nanotubes

We investigate theoretically how cold atoms, including Bose-Einstein condensates, are scattered from, or absorbed by nanotubes with a view to analysing recent experiments. In particular we consider the role of potential strength, quantum reflection, atomic interactions and tube vibrations on atom loss rates. Lifshitz theory calculations deliver a significantly stronger scattering potential than that found in experiment and we discuss possible reasons for this. We find that the scattering potential for dielectric tubes can be calculated to a good approximation using a modified pairwise summation approach, which is efficient and easily extendable to arbitrary geometries. Quantum reflection of atoms from a nanotube may become a significant factor at low temperatures, especially for non-metallic tubes. Interatomic interactions are shown to increase the rate at which atoms are lost to the nanotube and lead to non-trivial dynamics. Thermal nanotube vibrations do not significantly increase loss rates or reduce condensate fractions, but lower frequency oscillations can dramatically heat the cloud.Comment: 7 pages, 4 figure

Next-generation sequencing reveals the impact of repetitive DNA in phylogenetically closely related genomes of Orobanchaceae

We used next-generation sequencing to characterize the genomes of nine species of Orobanchaceae of known phylogenetic relationships, different life forms, and including a polyploid species. The study species are the autotrophic, nonparasitic Lindenbergia philippensis, the hemiparasitic Schwalbea americana, and seven nonphotosynthetic parasitic species of Orobanche (Orobanche crenata, Orobanche cumana, Orobanche gracilis (tetraploid), and Orobanche pancicii) and Phelipanche (Phelipanche lavandulacea, Phelipanche purpurea, and Phelipanche ramosa). Ty3/Gypsy elements comprise 1.93%–28.34% of the nine genomes and Ty1/Copia elements comprise 8.09%–22.83%. When compared with L. philippensis and S. americana, the nonphotosynthetic species contain higher proportions of repetitive DNA sequences, perhaps reflecting relaxed selection on genome size in parasitic organisms. Among the parasitic species, those in the genus Orobanche have smaller genomes but higher proportions of repetitive DNA than those in Phelipanche, mostly due to a diversification of repeats and an accumulation of Ty3/ Gypsy elements. Genome downsizing in the tetraploid O. gracilis probably led to sequence loss across most repeat types