1,620 research outputs found

    Global Mutual Fund Industry Comparisons: Canada, The United Kingdom And The United States

    Get PDF
    The concept of mutual funds is older than many believe, originating in Holland over 230 years ago.  Through the years, mutual funds have evolved by allowing investors to invest their capital in various venues.  The structure of mutual funds in Canada, the United Kingdom, and the United States possess similar configurations.  The majority of funds in all three nations are invested in the equity market.  Although the structure may be the same, the size in terms of assets varies by these three countries.  This is not the only difference though; the expense ratio is greatly differentiated, dramatically affecting the amount of return that the investor will anticipate over time.  Assuming identical returns, the authors illustrate that over a hypothetical ten-year time period, your funds would grow the most in the United States, followed by the United Kingdom and finally Canada.  This analysis assumes comparable contemporary expense ratios of 1.4% for the United States, 1.63% for the United Kingdom, and 2.1% for Canada.  In addition, we make the assumption that these comparison countries are having investors procure funds in no-load mutual funds

    Lifespan extension and the doctrine of double effect

    Get PDF
    Recent developments in biogerontology—the study of the biology of ageing—suggest that it may eventually be possible to intervene in the human ageing process. This, in turn, offers the prospect of significantly postponing the onset of age-related diseases. The biogerontological project, however, has met with strong resistance, especially by deontologists. They consider the act of intervening in the ageing process impermissible on the grounds that it would (most probably) bring about an extended maximum lifespan—a state of affairs that they deem intrinsically bad. In a bid to convince their deontological opponents of the permissibility of this act, proponents of biogerontology invoke an argument which is grounded in the doctrine of double effect. Surprisingly, their argument, which we refer to as the ‘double effect argument’, has gone unnoticed. This article exposes and critically evaluates this ‘double effect argument’. To this end, we first review a series of excerpts from the ethical debate on biogerontology in order to substantiate the presence of double effect reasoning. Next, we attempt to determine the role that the ‘double effect argument’ is meant to fulfil within this debate. Finally, we assess whether the act of intervening in ageing actually can be justified using double effect reasoning

    The Arabidopsis Framework Model version 2 predicts the organism-level effects of circadian clock gene mis-regulation

    Get PDF
    Predicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate across scales. Circadian clocks are intracellular regulators that control temporal gene expression patterns and hence metabolism, physiology and behaviour. Here we explain and predict canonical phenotypes of circadian timing in a multicellular, model organism. We used diverse metabolic and physiological data to combine and extend mathematical models of rhythmic gene expression, photoperiod-dependent flowering, elongation growth and starch metabolism within a Framework Model for the vegetative growth of Arabidopsis thaliana, sharing the model and data files in a structured, public resource. The calibrated model predicted the effect of altered circadian timing upon each particular phenotype in clock-mutant plants under standard laboratory conditions. Altered night-time metabolism of stored starch accounted for most of the decrease in whole-plant biomass, as previously proposed. Mobilisation of a secondary store of malate and fumarate was also mis-regulated, accounting for any remaining biomass defect. The three candidate mechanisms tested did not explain this organic acid accumulation. Our results link genotype through specific processes to higher-level phenotypes, formalising our understanding of a subtle, pleiotropic syndrome at the whole-organism level, and validating the systems approach to understand complex traits starting from intracellular circuits

    Variations of training load, monotony, and strain and dose-response relationships with maximal aerobic speed, maximal oxygen uptake, and isokinetic strength in professional soccer players

    Get PDF
    This study aimed to identify variations in weekly training load, training monotony, and training strain across a 10-week period (during both, pre- and in-season phases); and to analyze the dose-response relationships between training markers and maximal aerobic speed (MAS), maximal oxygen uptake, and isokinetic strength. Twenty-seven professional soccer players (24.9±3.5 years old) were monitored across the 10-week period using global positioning system units. Players were also tested for maximal aerobic speed, maximal oxygen uptake, and isokinetic strength before and after 10 weeks of training. Large positive correlations were found between sum of training load and extension peak torque in the right lower limb (r = 0.57, 90%CI[0.15;0.82]) and the ratio agonist/antagonist in the right lower limb (r = 0.51, [0.06;0.78]). It was observed that loading measures fluctuated across the period of the study and that the load was meaningfully associated with changes in the fitness status of players. However, those magnitudes of correlations were small-to-large, suggesting that variations in fitness level cannot be exclusively explained by the accumulated load and loading profile

    Small-scale societies exhibit fundamental variation in the role of intentions in moral judgment

    Get PDF
    Intent and mitigating circumstances play a central role in moral and legal assessments in large-scale industrialized societies. Although these features of moral assessment are widely assumed to be universal, to date, they have only been studied in a narrow range of societies. We show that there is substantial cross-cultural variation among eight traditional small-scale societies (ranging from hunter-gatherer to pastoralist to horticulturalist) and two Western societies (one urban, one rural) in the extent to which intent and mitigating circumstances influence moral judgments. Although participants in all societies took such factors into account to some degree, they did so to very different extents, varying in both the types of considerations taken into account and the types of violations to which such considerations were applied. The particular patterns of assessment characteristic of large-scale industrialized societies may thus reflect relatively recently culturally evolved norms rather than inherent features of human moral judgment

    Proteomic signatures improve risk prediction for common and rare diseases

    Get PDF
    For many diseases there are delays in diagnosis due to a lack of objective biomarkers for disease onset. Here, in 41,931 individuals from the United Kingdom Biobank Pharma Proteomics Project, we integrated measurements of ~3,000 plasma proteins with clinical information to derive sparse prediction models for the 10-year incidence of 218 common and rare diseases (81–6,038 cases). We then compared prediction models developed using proteomic data with models developed using either basic clinical information alone or clinical information combined with data from 37 clinical assays. The predictive performance of sparse models including as few as 5 to 20 proteins was superior to the performance of models developed using basic clinical information for 67 pathologically diverse diseases (median delta C-index = 0.07; range = 0.02–0.31). Sparse protein models further outperformed models developed using basic information combined with clinical assay data for 52 diseases, including multiple myeloma, non-Hodgkin lymphoma, motor neuron disease, pulmonary fibrosis and dilated cardiomyopathy. For multiple myeloma, single-cell RNA sequencing from bone marrow in newly diagnosed patients showed that four of the five predictor proteins were expressed specifically in plasma cells, consistent with the strong predictive power of these proteins. External replication of sparse protein models in the EPIC-Norfolk study showed good generalizability for prediction of the six diseases tested. These findings show that sparse plasma protein signatures, including both disease-specific proteins and protein predictors shared across several diseases, offer clinically useful prediction of common and rare diseases

    Intermittent control models of human standing: similarities and differences

    Get PDF
    Two architectures of intermittent control are compared and contrasted in the context of the single inverted pendulum model often used for describing standing in humans. The architectures are similar insofar as they use periods of open-loop control punctuated by switching events when crossing a switching surface to keep the system state trajectories close to trajectories leading to equilibrium. The architectures differ in two significant ways. Firstly, in one case, the open-loop control trajectory is generated by a system-matched hold, and in the other case, the open-loop control signal is zero. Secondly, prediction is used in one case but not the other. The former difference is examined in this paper. The zero control alternative leads to periodic oscillations associated with limit cycles; whereas the system-matched control alternative gives trajectories (including homoclinic orbits) which contain the equilibrium point and do not have oscillatory behaviour. Despite this difference in behaviour, it is further shown that behaviour can appear similar when either the system is perturbed by additive noise or the system-matched trajectory generation is perturbed. The purpose of the research is to come to a common approach for understanding the theoretical properties of the two alternatives with the twin aims of choosing which provides the best explanation of current experimental data (which may not, by itself, distinguish beween the two alternatives) and suggesting future experiments to distinguish between the two alternatives

    Responsiveness of SF-36 Health Survey and Patient Generated Index in people with chronic knee pain commenced on oral analgesia: analysis of data from a randomised controlled clinical trial

    Get PDF
    Purpose. (1) to assess the responsiveness of the Short Form 36 Health Survey (SF-36) and Patient Generated Index (PGI) in people with knee pain who were given oral analgesics; and (2) to perform content analysis of the SF-36 and PGI aiming to identify differences between the instruments and causes of different responsiveness. Methods. An observational study nested within a randomised controlled trial comparing oral paracetamol, ibuprofen or a combination of the two in 884 community-derived people with chronic knee pain. Each participant was given the SF-36 and PGI questionnaires to fill out at baseline, day 10, week 7 and week 13 after commencement on analgesia. Responsiveness was measured as a standardised response mean from baseline and contents of the instruments were analysed. Results. The PGI showed the greater responsiveness to analgesics than the SF-36 throughout the study period. Only the Bodily Pain Score of the SF-36 showed comparable responsiveness to the PGI. The standardised response mean of the PGI at 13 weeks was 0.61 (95% confidence interval 0.51 to 0.72), and that of the Bodily Pain Score of the SF-36 was 0.49 (95% confidence interval 0.39 to 0.58). Content analysis of the PGI identified multiple areas which are not represented in the SF-36 which may help explain its performance. Conclusions. Overall the PGI is more responsive than the SF-36 to commonly used oral analgesics taken for knee pain. The PGI is able to elicit areas of individualised health related quality of life which are not captured by the SF-36

    Simplified Models for LHC New Physics Searches

    Get PDF
    This document proposes a collection of simplified models relevant to the design of new-physics searches at the LHC and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the "Topologies for Early LHC Searches" workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first ~50-500 pb-1 of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results from "Topologies for Early LHC Searches" workshop (SLAC, September 2010). Supplementary material can be found at http://lhcnewphysics.or
    • 

    corecore