Internal audit - an Asia-Pacific profile and the level of compliance with internal auditing standards

Purpose &ndash; The purpose of this paper is to provide an overview of the profile of internal audit in five Asia-Pacific countries and investigate the usage and compliance with the Institute of Internal Auditors (IIA) International Standards for the Professional Practices of Internal Auditing (Standards) by organizations\u27 internal audit activities (IAAs). This paper shows the differences between Australia, China, Japan, New Zealand and Taiwan. It also discusses part of the results of the Common Body of Knowledge 2006 global study conducted by the IIA. Design/methodology/approach &ndash; The paper reports the results of a questionnaire survey sent to the global membership of the IIA in September 2006 on various aspects of internal audit practices. Findings &ndash; The profile of internal audit differs amongst the countries with much older organizations exist in Australia, Japan and New Zealand. Respondents in New Zealand, Japan, Chinese Taiwan, China and Australia all report to have a reasonably high level of usage of Standards. However, Australia has the highest number of respondents who report that they are in full compliance of the Standards. Originality/value &ndash; This is the first global study of internal auditors\u27 compliance with the IIA Standards.<br /

Hypertrophic cardiomyopathy in myosin-binding protein C (MYBPC3) Icelandic founder mutation carriers

Objective: The myosin-binding protein C (MYBPC3) c.927-2A>G founder mutation accounts for >90% of sarcomeric hypertrophic cardiomyopathy (HCM) in Iceland. This cross-sectional observational study explored the penetrance and phenotypic burden among carriers of this single, prevalent founder mutation. Methods: We studied 60 probands with HCM caused by MYBPC3 c.927-2A>G and 225 first-degree relatives. All participants underwent comprehensive clinical evaluation and relatives were genotyped. Results: Genetic and clinical evaluation of relatives identified 49 genotype-positive (G+) relatives with left ventricular hypertrophy (G+/LVH+), 59 G+without LVH (G+/LVH−) and 117 genotype-negative relatives (unaffected). Compared with HCM probands, G+/ LVH+ relatives were older at HCM diagnosis, had less LVH, a less prevalent diastolic dysfunction, fewer ECG abnormalities, lower serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I levels, and fewer symptoms. The penetrance of HCM was influenced by age and sex; specifically, LVH was present in 39% of G+males but only 9% of G+females under age 40 years (p=0.015), versus 86% and 83%, respectively, after age 60 (p=0.89). G+/LVH− subjects had normal wall thicknesses, diastolic function and NT-proBNP levels, but subtle changes in LV geometry and more ECG abnormalities than their unaffected relatives. Conclusions: Phenotypic expression of the Icelandic MYBPC3 founder mutation varies by age, sex and proband status. Men are more likely to have LVH at a younger age, and disease manifestations were more prominent in probands than in relatives identified via family screening. G+/LVH− individuals had subtle clinical differences from unaffected relatives well into adulthood, indicating subclinical phenotypic expression of the pathogenic mutation

Robust statistics towards detection of the 21 cm signal from the Epoch of Reionization

© 2019 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. We explore methods for robust estimation of the 21 cm signal from the Epoch of Reionization (EoR). A Kernel Density Estimator (KDE) is introduced for measuring the spatial temperature fluctuation power spectrum from the EoR. The KDE estimates the underlying probability distribution function of fluctuations as a function of spatial scale, and contains different systematic biases and errors to the typical approach to estimating the fluctuation power spectrum. Extraction of histograms of visibilities allows moments analysis to be used to discriminate foregrounds from 21 cm signal and thermal noise. We use the information available in the histograms, along with the statistical dis-similarity of foregrounds from two independent observing fields, to robustly separate foregrounds from cosmological signal, while making no assumptions about the Gaussianity of the signal. Using two independent observing fields to robustly discriminate signal from foregrounds is crucial for the analysis presented in this paper. We apply the techniques to 13 h of Murchison Widefield Array EoR data over two observing fields. We compare the output to that obtained with a comparative power spectrum estimation method, and demonstrate the reduced foreground contamination using this approach. Using the second moment obtained directly from the KDE distribution functions yields a factor of 2-3 improvement in power for k < 0.3 h Mpc-1 compared with a matched delay space power estimator, while weighting data by additional statistics does not offer significant improvement beyond that available for thermal noise-only weights

Underlying molecular mechanisms of DIO2 susceptibility in symptomatic osteoarthritis

Objectives: To investigate how the genetic susceptibility gene DIO2 confers risk to osteoarthritis (OA) onset in humans and to explore whether counteracting the deleterious effect could contribute to novel therapeutic approaches. Methods: Epigenetically regulated expression of DIO2 was explored by assessing methylation of positional CpG-dinucleotides and the respective DIO2 expression in OA-affected and macroscopically preserved articular cartilage from end-stage OA patients. In a human in vitro chondrogenesis model, we measured the effects when thyroid signalling during culturing was either enhanced (excess T3 or lentiviral induced DIO2 overexpression) or decreased (iopanoic acid). Results: OA-related changes in methylation at a specific CpG dinucleotide upstream of DIO2 caused significant upregulation of its expression (ß=4.96; p=0.0016). This effect was enhanced and appeared driven specifically by DIO2 rs225014 risk allele carriers (ß=5.58, p=0.0006). During in vitro chondrogenesis, DIO2 overexpression resulted in a significant reduced capacity of chondrocytes to deposit extracellular matrix (ECM) components, concurrent with significant induction of ECM degrading enzymes (ADAMTS5, MMP13) and markers of mineralisation (ALPL, COL1A1). Given their concurrent and significant upregulation of expression, this process is likely mediated via HIF-2a/RUNX2 signalling. In contrast, we showed that inhibiting deiodinases during in vitro chondrogenesis contributed to prolonged cartilage homeostasis as reflected by significant increased deposition of ECM components and attenuated upregulation of matrix degrading enzymes. Conclusions: Our findings show how genetic variation at DIO2 could confer risk to OA and raised the possibility that counteracting thyroid signalling may be a novel therapeutic approach

Diverse Lifestyles and Strategies of Plant Pathogenesis Encoded in the Genomes of Eighteen Dothideomycetes Fungi

The class Dothideomycetes is one of the largest groups of fungi with a high level of ecological diversity including many plant pathogens infecting a broad range of hosts. Here, we compare genome features of 18 members of this class, including 6 necrotrophs, 9 (hemi)biotrophs and 3 saprotrophs, to analyze genome structure, evolution, and the diverse strategies of pathogenesis. The Dothideomycetes most likely evolved from a common ancestor more than 280 million years ago. The 18 genome sequences differ dramatically in size due to variation in repetitive content, but show much less variation in number of (core) genes. Gene order appears to have been rearranged mostly within chromosomal boundaries by multiple inversions, in extant genomes frequently demarcated by adjacent simple repeats. Several Dothideomycetes contain one or more gene-poor, transposable element (TE)-rich putatively dispensable chromosomes of unknown function. The 18 Dothideomycetes offer an extensive catalogue of genes involved in cellulose degradation, proteolysis, secondary metabolism, and cysteine-rich small secreted proteins. Ancestors of the two major orders of plant pathogens in the Dothideomycetes, the Capnodiales and Pleosporales, may have had different modes of pathogenesis, with the former having fewer of these genes than the latter. Many of these genes are enriched in proximity to transposable elements, suggesting faster evolution because of the effects of repeat induced point (RIP) mutations. A syntenic block of genes, including oxidoreductases, is conserved in most Dothideomycetes and upregulated during infection in L. maculans, suggesting a possible function in response to oxidative stress