Image Texture Characterization Using the Discrete Orthonormal S-Transform

We present a new efficient approach for characterizing image texture based on a recently published discrete, orthonormal space-frequency transform known as the DOST. We develop a frequency-domain implementation of the DOST in two dimensions for the case of dyadic frequency sampling. Then, we describe a rapid and efficient approach to obtain local spatial frequency information for an image and show that this information can be used to characterize the horizontal and vertical frequency patterns in synthetic images. Finally, we demonstrate that DOST components can be combined to obtain a rotationally invariant set of texture features that can accurately classify a series of texture patterns. The DOST provides the computational efficiency and multi-scale information of wavelet transforms, while providing texture features in terms of Fourier frequencies. It outperforms leading wavelet-based texture analysis methods

Genomic and protein structural maps of adaptive evolution of human influenza a virus to increased virulence in the mouse

Adaptive evolution is characterized by positive and parallel, or repeated selection of mutations. Mouse adaptation of influenza A virus (IAV) produces virulent mutants that demonstrate positive and parallel evolution of mutations in the hemagglutinin (HA) receptor and non-structural protein 1 (NS1) interferon antagonist genes. We now present a genomic analysis of all 11 genes of 39 mouse adapted IAV variants from 10 replicate adaptation experiments. Mutations were mapped on the primary and structural maps of each protein and specific mutations were validated with respect to virulence, replication, and RNA polymerase activity. Mouse adapted (MA) variants obtained after 12 or 20-21 serial infections acquired on average 5.8 and 7.9 nonsynonymous mutations per genome of 11 genes, respectively. Among a total of 115 nonsynonymous mutations, 51 demonstrated properties of natural selection including 27 parallel mutations. The greatest degree of parallel evolution occurred in the HA receptor and ribonucleocapsid components, polymerase subunits (PB1, PB2, PA) and NP. Mutations occurred in host nuclear trafficking factor binding sites as well as sites of virus-virus protein subunit interaction for NP, NS1, HA and NA proteins. Adaptive regions included cap binding and endonuclease domains in the PB2 and PA polymerase subunits. Four mutations in NS1 resulted in loss of binding to the host cleavage and polyadenylation specificity factor (CPSF30) suggesting that a reduction in inhibition of host gene expression was being selected. The most prevalent mutations in PB2 and NP were shown to increase virulence but differed in their ability to enhance replication and demonstrated epistatic effects. Several positively selected RNA polymerase mutations demonstrated increased virulence associated with >300% enhanced polymerase activity. Adaptive mutations that control host range and virulence were identified by their repeated selection to comprise a defined model for studying IAV evolution to increased virulence in the mouse

Is alcohol consumption a risk factor for prostate cancer? A systematic review and meta-analysis.

Background: Research on a possible causal association between alcohol consumption and risk of prostate cancer is inconclusive. Recent studies on associations between alcohol consumption and other health outcomes suggest these are influenced by drinker misclassification errors and other study quality characteristics. The influence of these factors on estimates of the relationship between alcohol consumption and prostate cancer has not been previously investigated. Methods: PubMed and Web of Science searches were made for case–control and cohort studies of alcohol consumption and prostate cancer morbidity and mortality (ICD–10: C61) up to December 2014. Studies were coded for drinker misclassification errors, quality of alcohol measures, extent of control for confounding and other study characteristics. Mixed models were used to estimate relative risk (RR) of morbidity or mortality from prostate cancer due to alcohol consumption with study level controls for selection bias and confounding. Results: A total of 340 studies were identified of which 27 satisfied inclusion criteria providing 126 estimates for different alcohol exposures. Adjusted RR estimates indicated a significantly increased risk of prostate cancer among low (RR = 1.08, P 1.3, <24 g per day). This relationship is stronger in the relatively few studies free of former drinker misclassification error. Given the high prevalence of prostate cancer in the developed world, the public health implications of these findings are significant. Prostate cancer may need to be incorporated into future estimates of the burden of disease alongside other cancers (e.g. breast, oesophagus, colon, liver) and be integrated into public health strategies for reducing alcohol related disease

Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas.

Venezuelan equine encephalitis (VEE) complex alphaviruses are important re-emerging arboviruses that cause life-threatening disease in equids during epizootics as well as spillover human infections. We conducted a comprehensive analysis of VEE complex alphaviruses by sequencing the genomes of 94 strains and performing phylogenetic analyses of 130 isolates using complete open reading frames for the nonstructural and structural polyproteins. Our analyses confirmed purifying selection as a major mechanism influencing the evolution of these viruses as well as a confounding factor in molecular clock dating of ancestors. Times to most recent common ancestors (tMRCAs) could be robustly estimated only for the more recently diverged subtypes; the tMRCA of the ID/IAB/IC/II and IE clades of VEE virus (VEEV) were estimated at ca. 149–973 years ago. Evolution of the IE subtype has been characterized by a significant evolutionary shift from the rest of the VEEV complex, with an increase in structural protein substitutions that are unique to this group, possibly reflecting adaptation to its unique enzootic mosquito vector Culex (Melanoconion) taeniopus. Our inferred tree topologies suggest that VEEV is maintained primarily in situ, with only occasional spread to neighboring countries, probably reflecting the limited mobility of rodent hosts and mosquito vectors

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability

Chemical combination effects predict connectivity in biological systems

Efforts to construct therapeutically useful models of biological systems require large and diverse sets of data on functional connections between their components. Here we show that cellular responses to combinations of chemicals reveal how their biological targets are connected. Simulations of pathways with pairs of inhibitors at varying doses predict distinct response surface shapes that are reproduced in a yeast experiment, with further support from a larger screen using human tumour cells. The response morphology yields detailed connectivity constraints between nearby targets, and synergy profiles across many combinations show relatedness between targets in the whole network. Constraints from chemical combinations complement genetic studies, because they probe different cellular components and can be applied to disease models that are not amenable to mutagenesis. Chemical probes also offer increased flexibility, as they can be continuously dosed, temporally controlled, and readily combined. After extending this initial study to cover a wider range of combination effects and pathway topologies, chemical combinations may be used to refine network models or to identify novel targets. This response surface methodology may even apply to non-biological systems where responses to targeted perturbations can be measured

The effective rate of influenza reassortment is limited during human infection

We characterise the evolutionary dynamics of influenza infection described by viral sequence data collected from two challenge studies conducted in human hosts. Viral sequence data were collected at regular intervals from infected hosts. Changes in the sequence data observed across time show that the within-host evolution of the virus was driven by the reversion of variants acquired during previous passaging of the virus. Treatment of some patients with oseltamivir on the first day of infection did not lead to the emergence of drug resistance variants in patients. Using an evolutionary model, we inferred the effective rate of reassortment between viral segments, measuring the extent to which randomly chosen viruses within the host exchange genetic material. We find strong evidence that the rate of effective reassortment is low, such that genetic associations between polymorphic loci in different segments are preserved during the course of an infection in a manner not compatible with epistasis. Combining our evidence with that of previous studies we suggest that spatial heterogeneity in the viral population may reduce the extent to which reassortment is observed. Our results do not contradict previous findings of high rates of viral reassortment in vitro and in small animal studies, but indicate that in human hosts the effective rate of reassortment may be substantially more limited.CJRI is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 101239/Z/13/Z) and received support from the National Science Foundation Research Coordination Network on Infectious Disease Evolution Across Scales. KK, ASL, CWW, and MTM were funded by NIGMS U54-GM111274, the MIDAS Center for Inference and Dynamics of Infectious Disease. ASL acknowledges support from the MSTP training grant number T32 GM007171. GJDS was supported by the Duke-NUS Signature Research Programme funded by the Ministry of Health, Singapore and by contract HHSN272201400006C from the National Institute of Allergy and Infectious Disease, National Institutes of Health, Department of Health and Human Services, USA. DEW, RAH, XL, AR, TBS, SRD and also the influenza whole genome sequencing were supported with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract HHSN272200900007C. GSG was funded by the Defense Advanced Research Projects Agency under grant number DARPA-N66001-07-C-2024. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Evolution Across Scales. KK, ASL, CWW, and MTM were funded by NIGMS U54- GM111274, the MIDAS Center for Inference and Dynamics of Infectious Disease. DEW, RAH, XL, AR, TBS, and SRD were supported with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract HHSN272200900007C. GSG was funded by the Defense Advanced Research Projects Agency under grant number DARPA-N66001-07-C-2024. This work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council

Early prediction of cardiac resynchronization therapy response by non-invasive electrocardiogram markers

[EN] Cardiac resynchronization therapy (CRT) is an effective treatment for those patients with severe heart failure. Regrettably, there are about one third of CRT "non-responders", i.e. patients who have undergone this form of device therapy but do not respond to it, which adversely affects the utility and cost-effectiveness of CRT. In this paper, we assess the ability of a novel surface ECG marker to predict CRT response. We performed a retrospective exploratory study of the ECG previous to CRT implantation in 43 consecutive patients with ischemic (17) or non-ischemic (26) cardiomyopathy. We extracted the QRST complexes (consisting of the QRS complex, the S-T segment, and the T wave) and obtained a measure of their energy by means of spectral analysis. This ECG marker showed statistically significant lower values for non-responder patients and, joint with the duration of QRS complexes (the current gold-standard to predict CRT response), the following performances: 86% accuracy, 88% sensitivity, and 80% specificity. In this manner, the proposed ECG marker may help clinicians to predict positive response to CRT in a non-invasive way, in order to minimize unsuccessful procedures.This work was supported by MINECO under grants MTM2013-43540-P and MTM2016-76647-P.Ortigosa, N.; Pérez-Roselló, V.; Donoso, V.; Osca Asensi, J.; Martínez-Dolz, L.; Fernández Rosell, C.; Galbis Verdu, A. (2018). Early prediction of cardiac resynchronization therapy response by non-invasive electrocardiogram markers. Medical & Biological Engineering & Computing. 56(4):611-621. https://doi.org/10.1007/s11517-017-1711-1S611621564Boggiatto P, Fernández C, Galbis A (2009) A group representation related to the stockwell transform. Indiana University Mathematics Journal 58(5):2277–2296Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G et al (2013) 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy. Europace 15:1070–1118Brown RA, Lauzon ML, Frayne R (2010) A general description of linear time-frequency transforms and formulation of a fast, invertible transform that samples the continuous s-transform spectrum nonredundantly. IEEE Trans Signal Process 58(1): 281–290Carità P, Corrado E, Pontone G, Curnis A, Bontempi L et al (2016) Non-responders to cardiac resynchronization therapy: insights from multimodality imaging and electrocardiography. A brief review. Int J Cardiol 225:402–407Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C et al (2001) Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 344:873–880Chang CC, Lin CJ (2011) LIBSVM: a library for support vector machines. 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Heart Rhythm 12(5):1071–1079Goldenberg I, Kutyifa V, Klein HU, Cannom DS, Brown MW et al (2014) Survival with cardiac-resynchronization therapy in mild heart failure. N Engl J Med 370:1694–1701He H, Bai Y, Garcia EA, Li S (2008) ADASYN: adaptive synthetic sampling approach for imbalanced learning. In: International joint conference on neural networks, pp 1322–1328Jacobsson J, Borgguist R, Reitan C, Ghafoori E, Chatterjee NA et al (2016) Usefulness of the sum absolute QRST integral to predict outcomes in patients receiving cardiac resynchronization therapy. J Cardiovasc Electrophysiol 118(3):389–395McMurray JJ (2010) Clinical practice. Systolic heart failure. N Engl J Med 3623:228–238Meyer CR, Keiser HN (1977) Electrocardiogram baseline noise estimation and removal using cubic splines and state-space computation techniques. Comput Biomed Res 10:459–470Ortigosa N, Giménez VM (2014) Raw data extraction from electrocardiograms with portable document format. 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Genome-wide DNA methylation map of human neutrophils reveals widespread inter-individual epigenetic variation

The extent of variation in DNA methylation patterns in healthy individuals is not yet well documented. Identification of inter-individual epigenetic variation is important for understanding phenotypic variation and disease susceptibility. Using neutrophils from a cohort of healthy individuals, we generated base-resolution DNA methylation maps to document inter-individual epigenetic variation. We identified 12851 autosomal inter-individual variably methylated fragments (iVMFs). Gene promoters were the least variable, whereas gene body and upstream regions showed higher variation in DNA methylation. The iVMFs were relatively enriched in repetitive elements compared to non-iVMFs, and were associated with genome regulation and chromatin function elements. Further, variably methylated genes were disproportionately associated with regulation of transcription, responsive function and signal transduction pathways. Transcriptome analysis indicates that iVMF methylation at differentially expressed exons has a positive correlation and local effect on the inclusion of that exon in the mRNA transcript

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death