Deep learning cardiac motion analysis for human survival prediction

Motion analysis is used in computer vision to understand the behaviour of moving objects in sequences of images. Optimising the interpretation of dynamic biological systems requires accurate and precise motion tracking as well as efficient representations of high-dimensional motion trajectories so that these can be used for prediction tasks. Here we use image sequences of the heart, acquired using cardiac magnetic resonance imaging, to create time-resolved three-dimensional segmentations using a fully convolutional network trained on anatomical shape priors. This dense motion model formed the input to a supervised denoising autoencoder (4Dsurvival), which is a hybrid network consisting of an autoencoder that learns a task-specific latent code representation trained on observed outcome data, yielding a latent representation optimised for survival prediction. To handle right-censored survival outcomes, our network used a Cox partial likelihood loss function. In a study of 302 patients the predictive accuracy (quantified by Harrell's C-index) was significantly higher (p < .0001) for our model C=0.73 (95$\%$ CI: 0.68 - 0.78) than the human benchmark of C=0.59 (95$\%$ CI: 0.53 - 0.65). This work demonstrates how a complex computer vision task using high-dimensional medical image data can efficiently predict human survival

Resonance bifurcations from robust homoclinic cycles

We present two calculations for a class of robust homoclinic cycles with symmetry Z_n x Z_2^n, for which the sufficient conditions for asymptotic stability given by Krupa and Melbourne are not optimal. Firstly, we compute optimal conditions for asymptotic stability using transition matrix techniques which make explicit use of the geometry of the group action. Secondly, through an explicit computation of the global parts of the Poincare map near the cycle we show that, generically, the resonance bifurcations from the cycles are supercritical: a unique branch of asymptotically stable period orbits emerges from the resonance bifurcation and exists for coefficient values where the cycle has lost stability. This calculation is the first to explicitly compute the criticality of a resonance bifurcation, and answers a conjecture of Field and Swift in a particular limiting case. Moreover, we are able to obtain an asymptotically-correct analytic expression for the period of the bifurcating orbit, with no adjustable parameters, which has not proved possible previously. We show that the asymptotic analysis compares very favourably with numerical results.Comment: 24 pages, 3 figures, submitted to Nonlinearit

Voting and the Cardinal Aggregation of Judgments

The paper elaborates the idea that voting is an instance of the aggregation of judgments, this being a more general concept than the aggregation of preferences. To aggregate judgments one must first measure them. I show that such aggregation has been unproblematic whenever it has been based on an independent and unrestricted scale. The scales analyzed in voting theory are either context dependent or subject to unreasonable restrictions. This is the real source of the diverse 'paradoxes of voting' that would better be termed 'voting pathologies'. The theory leads me to advocate what I term evaluative voting. It can also be called utilitarian voting as it is based on having voters express their cardinal preferences. The alternative that maximizes the sum wins. This proposal operationalizes, in an election context, the abstract cardinal theories of collective choice due to Fleming and Harsanyi. On pragmatic grounds, I argue for a three valued scale for general elections

Epigenome-wide profiling identifies significant differences in DNA methylation between matched-pairs of T- and B-lymphocytes from healthy individuals

Multiple reports now describe changes to the DNA methylome in rheumatoid arthritis and in many cases have analyzed methylation in mixed cell populations from whole blood. However, these approaches may preclude the identification of cell type-specific methylation, which may subsequently bias identification of disease-specific changes. To address this possibility, we conducted genome-wide DNA methylation profiling using HumanMethylation450 BeadChips to identify differences within matched pairs of T-lymphocytes and B-lymphocytes isolated from the peripheral blood of 10 healthy females. Array data were processed and differential methylation identified using NIMBL software. Validation of array data was performed by bisulfite Pyrosequencing. Genome-wide DNA methylation was initially determined by analysis of LINE-1 sequences and was higher in B-lymphocytes than matched T-lymphocytes (69.8 vs. 65.2%, p ≤ 0.01). Pairwise analysis identified 679 CpGs, representing 250 genes, which were differentially methylated between T-lymphocytes and B-lymphocytes. The majority of sites (76.6%) were hypermethylated in B-lymphocytes. Pyrosequencing of selected candidates confirmed the array data in all cases. Hierarchical clustering revealed perfect segregation of samples into two distinct clusters based on cell type. Differentially methylated genes showed enrichment for biological functions/pathways associated with leukocytes and T-lymphocytes. Our work for the first time shows that T-lymphocytes and B-lymphocytes possess intrinsic differences in DNA methylation within a restricted set of functionally-related genes. These data provide a foundation for investigating DNA methylation in diseases in which these cell types play important and distinct roles

Stability of narrow beams in bulk Kerr-type nonlinear media

We consider (2+1)-dimensional beams, whose transverse size may be comparable to or smaller than the carrier wavelength, on the basis of an extended version of the nonlinear Schr\"{o}dinger equation derived from the Maxwell`s equations. As this equation is very cumbersome, we also study, in parallel to it, its simplified version which keeps the most essential term: the term which accounts for the {\it nonlinear diffraction}. The full equation additionally includes terms generated by a deviation from the paraxial approximation and by a longitudinal electric-field component in the beam. Solitary-wave stationary solutions to both the full and simplified equations are found, treating the terms which modify the nonlinear Schr\"{o}dinger equation as perturbations. Within the framework of the perturbative approach, a conserved power of the beam is obtained in an explicit form. It is found that the nonlinear diffraction affects stationary beams much stronger than nonparaxiality and longitudinal field. Stability of the beams is directly tested by simulating the simplified equation, with initial configurations taken as predicted by the perturbation theory. The numerically generated solitary beams are always stable and never start to collapse, although they display periodic internal vibrations, whose amplitude decreases with the increase of the beam power.Comment: 7 pages, 6 figures Accepted for publication in PR

Development and validation of the ACE tool: Assessing medical trainees' competency in evidence based medicine

BACKGROUND: While a variety of instruments have been developed to assess knowledge and skills in evidence based medicine (EBM), few assess all aspects of EBM - including knowledge, skills attitudes and behaviour - or have been psychometrically evaluated. The aim of this study was to develop and validate an instrument that evaluates medical trainees’ competency in EBM across knowledge, skills and attitude. METHODS: The ‘Assessing Competency in EBM’ (ACE) tool was developed by the authors, with content and face validity assessed by expert opinion. A cross-sectional sample of 342 medical trainees representing ‘novice’, ‘intermediate’ and ‘advanced’ EBM trainees were recruited to complete the ACE tool. Construct validity, item difficulty, internal reliability and item discrimination were analysed. RESULTS: We recruited 98 EBM-novice, 108 EBM-intermediate and 136 EBM-advanced participants. A statistically significant difference in the total ACE score was observed and corresponded to the level of training: on a 0-15-point test, the mean ACE scores were 8.6 for EBM-novice; 9.5 for EBM-intermediate; and 10.4 for EBM-advanced (p < 0.0001). Individual item discrimination was excellent (Item Discrimination Index ranging from 0.37 to 0.84), with internal reliability consistent across all but three items (Item Total Correlations were all positive ranging from 0.14 to 0.20). CONCLUSION: The 15-item ACE tool is a reliable and valid instrument to assess medical trainees’ competency in EBM. The ACE tool provides a novel assessment that measures user performance across the four main steps of EBM. To provide a complete suite of instruments to assess EBM competency across various patient scenarios, future refinement of the ACE instrument should include further scenarios across harm, diagnosis and prognosis

Evanescent light-matter Interactions in Atomic Cladding Wave Guides

Alkali vapors, and in particular rubidium, are being used extensively in several important fields of research such as slow and stored light non-linear optics3 and quantum computation. Additionally, the technology of alkali vapors plays a major role in realizing myriad industrial applications including for example atomic clocks magentometers8 and optical frequency stabilization. Lately, there is a growing effort towards miniaturizing traditional centimeter-size alkali vapor cells. Owing to the significant reduction in device dimensions, light matter interactions are greatly enhanced, enabling new functionalities due to the low power threshold needed for non-linear interactions. Here, taking advantage of the mature Complimentary Metal-Oxide-Semiconductor (CMOS) compatible platform of silicon photonics, we construct an efficient and flexible platform for tailored light vapor interactions on a chip. Specifically, we demonstrate light matter interactions in an atomic cladding wave guide (ACWG), consisting of CMOS compatible silicon nitride nano wave-guide core with a Rubidium (Rb) vapor cladding. We observe the highly efficient interaction of the electromagnetic guided mode with the thermal Rb cladding. The nature of such interactions is explained by a model which predicts the transmission spectrum of the system taking into account Doppler and transit time broadening. We show, that due to the high confinement of the optical mode (with a mode area of 0.3{\lambda}2), the Rb absorption saturates at powers in the nW regime.Comment: 10 Pages 4 Figures. 1 Supplementar

Social Preferences and the Efficiency of Bilateral Exchange

Under what conditions do social preferences, such as altruism or a concern for fair outcomes, generate efficient trade? I analyze theoretically a simple bilateral exchange game: Each player sequentially takes an action that reduces his own material payoff but increases the other player’s. Each player’s preferences may depend on both his/her own material payoff and the other player’s. I identify necessary conditions and sufficient conditions on the players’ preferences for the outcome of their interaction to be Pareto efficient. The results have implications for interpreting the rotten kid theorem, gift exchange in the laboratory, and gift exchange in the field

Evidence-based practice educational intervention studies: A systematic review of what is taught and how it is measured

Abstract Background Despite the established interest in evidence-based practice (EBP) as a core competence for clinicians, evidence for how best to teach and evaluate EBP remains weak. We sought to systematically assess coverage of the five EBP steps, review the outcome domains measured, and assess the properties of the instruments used in studies evaluating EBP educational interventions. Methods We conducted a systematic review of controlled studies (i.e. studies with a separate control group) which had investigated the effect of EBP educational interventions. We used citation analysis technique and tracked the forward and backward citations of the index articles (i.e. the systematic reviews and primary studies included in an overview of the effect of EBP teaching) using Web of Science until May 2017. We extracted information on intervention content (grouped into the five EBP steps), and the outcome domains assessed. We also searched the literature for published reliability and validity data of the EBP instruments used. Results Of 1831 records identified, 302 full-text articles were screened, and 85 included. Of these, 46 (54%) studies were randomised trials, 51 (60%) included postgraduate level participants, and 63 (75%) taught medical professionals. EBP Step 3 (critical appraisal) was the most frequently taught step (63 studies; 74%). Only 10 (12%) of the studies taught content which addressed all five EBP steps. Of the 85 studies, 52 (61%) evaluated EBP skills, 39 (46%) knowledge, 35 (41%) attitudes, 19 (22%) behaviours, 15 (18%) self-efficacy, and 7 (8%) measured reactions to EBP teaching delivery. Of the 24 instruments used in the included studies, 6 were high-quality (achieved ≥3 types of established validity evidence) and these were used in 14 (29%) of the 52 studies that measured EBP skills; 14 (41%) of the 39 studies that measured EBP knowledge; and 8 (26%) of the 35 studies that measured EBP attitude. Conclusions Most EBP educational interventions which have been evaluated in controlled studies focus on teaching only some of the EBP steps (predominantly critically appraisal of evidence) and did not use high-quality instruments to measure outcomes. Educational packages and instruments which address all EBP steps are needed to improve EBP teaching