Binary data corruption due to a Brownian agent

We introduce a model of binary data corruption induced by a Brownian agent (active random walker) on a d-dimensional lattice. A continuum formulation allows the exact calculation of several quantities related to the density of corrupted bits \rho; for example the mean of \rho, and the density-density correlation function. Excellent agreement is found with the results from numerical simulations. We also calculate the probability distribution of \rho in d=1, which is found to be log-normal, indicating that the system is governed by extreme fluctuations.Comment: 39 pages, 10 figures, RevTe

Development and Validation of Apolipoprotein AI-Associated Lipoprotein Proteome Panel for the Prediction of Cholesterol Efflux Capacity and Coronary Artery Disease

BACKGROUND: Cholesterol efflux capacity (CEC) is a measure of HDL function that, in cell-based studies, has demonstrated an inverse association with cardiovascular disease. The cell-based measure of CEC is complex and low-throughput. We hypothesized that assessment of the lipoprotein proteome would allow for precise, high-throughput CEC prediction. METHODS: After isolating lipoprotein particles from serum, we used LC-MS/MS to quantify 21 lipoprotein-associated proteins. A bioinformatic pipeline was used to identify proteins with univariate correlation to cell-based CEC measurements and generate a multivariate algorithm for CEC prediction (pCE). Using logistic regression, protein coefficients in the pCE model were reweighted to yield a new algorithm predicting coronary artery disease (pCAD). RESULTS: Discovery using targeted LC-MS/MS analysis of 105 training and test samples yielded a pCE model comprising 5 proteins (Spearman r = 0.86). Evaluation of pCE in a case-control study of 231 specimens from healthy individuals and patients with coronary artery disease revealed lower pCE in cases (P = 0.03). Derived within this same study, the pCAD model significantly improved classification (P < 0.0001). Following analytical validation of the multiplexed proteomic method, we conducted a case-control study of myocardial infarction in 137 postmenopausal women that confirmed significant separation of specimen cohorts in both the pCE (P = 0.015) and pCAD (P = 0.001) models. CONCLUSIONS: Development of a proteomic pCE provides a reproducible high-throughput alternative to traditional cell-based CEC assays. The pCAD model improves stratification of case and control cohorts and, with further studies to establish clinical validity, presents a new opportunity for the assessment of cardiovascular health

Manifesto for a European research network into Problematic Usage of the Internet

Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.Peer reviewe

Transforming ophthalmic education into virtual learning during COVID-19 pandemic : a global perspective

Objective: The coronavirus disease 2019 (COVID-19) pandemic has imposed measures of social distancing and barriers in delivery of "in person" education. Institutions, involved in training the next generation of ophthalmologists, are using alternative teaching methods to maintain the standard of education. Methods: We conducted a worldwide survey among physicians, who are actively involved in Ophthalmology-related education, between 3 and 14 April 2020. The expert survey, developed on the basis of literature search and focus group discussions, comprised 23 questions addressing the use of e-learning in Ophthalmology during the COVID-19 pandemic. Results: A total of 321 participants from both academic and non-academic institutions worldwide, with variable practice experience and expertise, completed the survey. Before the pandemic, the majority of participants used traditional training modalities, including lectures, grand rounds and journal clubs, and 48% did not use any e-learning. There was a statistically significant increase in the use of all e-learning alternatives during the pandemic (p &lt; 0.001), associated mainly with the availability of e-learning facilities (p &lt; 0.001) and the academic character of institutions (p &lt; 0.001). Zoom\uae was recognized as the mostly used platform for virtual teaching. Although theoretical teaching may take place, the surgical training of residents/fellows was dramatically reduced. The latter was significantly associated with participants' perspectives about teaching practices (p &lt; 0.001). Conclusion: COVID-19 pandemic imposed great challenges in the educational field of Ophthalmology. The experience related to virtual training in Ophthalmology, gained during the pandemic, may change the traditional teaching practices in the world and provide new educational opportunities

Integration approach to virtual-driven discrete event simulation for manufacturing systems

This is an Accepted Manuscript of an article published by Taylor & Francis in 'International Journal of Computer Integrated Manufacturing' on 11/06/2014, available online: https://doi.org/10.1080/0951192X.2014.924159.Virtual engineering (VE) environment helps to verify process and resource design through visualisation. By using VE, the impacts of re-configurability and new-process additions in the machine stops can be viewed down to the component level. On the other hand, discrete event simulation (DES) typically forecasts the system behaviour over a period of time to predict future performance. During pre-build stages of machines, DES analysis comes with uncertainties, as most of the parameters in the model are based on the assumptions. Therefore, it was aimed to use the validated and verified data, for example ‘process time’ of a machine component available from the VE-emulated systems, in the DES model. Thus, a systematic algorithm was proposed to integrate the VE tool data, with the DES. This article presents the development of a package known as ‘virtual-driven discrete event simulation’ (VDSim), used to establish an integration between the VE and DES domains. The success of this integration depends upon the quality of information and the compatibility of data flow between these independent domains. VDSim integration will help productivity planners and schedulers to get the best possible options for resource selection at stages even when the resource is not physically present

Orexinergic Input to Dopaminergic Neurons of the Human Ventral Tegmental Area

The mesolimbic reward pathway arising from dopaminergic (DA) neurons of the ventral tegmental area (VTA) has been strongly implicated in reward processing and drug abuse. In rodents, behaviors associated with this projection are profoundly influenced by an orexinergic input from the lateral hypothalamus to the VTA. Because the existence and significance of an analogous orexigenic regulatory mechanism acting in the human VTA have been elusive, here we addressed the possibility that orexinergic neurons provide direct input to DA neurons of the human VTA. Dual-label immunohistochemistry was used and orexinergic projections to the VTA and to DA neurons of the neighboring substantia nigra (SN) were analyzed comparatively in adult male humans and rats. Orexin B-immunoreactive (IR) axons apposed to tyrosine hydroxylase (TH)-IR DA and to non-DA neurons were scarce in the VTA and SN of both species. In the VTA, 15.062.8% of TH-IR perikarya in humans and 3.260.3% in rats received orexin B-IR afferent contacts. On average, 0.2460.05 and 0.0560.005 orexinergic appositions per TH-IR perikaryon were detected in humans and rats, respectively. The majority(86–88%) of randomly encountered orexinergic contacts targeted the dendritic compartment of DA neurons. Finally, DA neurons of the SN also received orexinergic innervation in both species. Based on the observation of five times heavierorexinergic input to TH-IR neurons of the human, compared with the rat, VTA, we propose that orexinergic mechanism acting in the VTA may play just as important roles in reward processing and drug abuse in humans, as already established well in rodents

Tailoring hyper-heuristics to specific instances of a scheduling problem using affinity and competence functions

Hyper-heuristics are high level heuristics which coordinate lower level ones to solve a given problem. Low level heuristics, however, are not all as competent/good as each other at solving the given problem and some do not work together as well as others. Hence the idea of measuring how good they are (competence) at solving the problem and how well they work together (their affinity). Models of the affinity and competence properties are suggested and evaluated using previous information on the performance of the simple low level heuristics. The resulting model values are used to improve the performance of the hyper-heuristic by tailoring it not only to the specific problem but the specific instance being solved. The test case is a hard combinatorial problem, namely the Hybrid Flow Shop scheduling problem. Numerical results on randomly generated as well as real-world instances are included

Heart rate variability and target organ damage in hypertensive patients

Background: We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD). Methods: A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index. Results: Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors. Conclusions: Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Mutation screening of retinal dystrophy patients by targeted capture from tagged pooled DNAs and next generation sequencing.

Purpose: Retinal dystrophies are genetically heterogeneous, resulting from mutations in over 200 genes. Prior to the development of massively parallel sequencing, comprehensive genetic screening was unobtainable for most patients. Identifying the causative genetic mutation facilitates genetic counselling, carrier testing and prenatal/pre-implantation diagnosis, and often leads to a clearer prognosis. In addition, in a proportion of cases, when the mutation is known treatment can be optimised and patients are eligible for enrolment into clinical trials for gene-specific therapies. Methods: Patient genomic DNA was sheared, tagged and pooled in batches of four samples, prior to targeted capture and next generation sequencing. The enrichment reagent was designed against genes listed on the RetNet database (July 2010). Sequence data were aligned to the human genome and variants were filtered to identify potential pathogenic mutations. These were confirmed by Sanger sequencing. Results: Molecular analysis of 20 DNAs from retinal dystrophy patients identified likely pathogenic mutations in 12 cases, many of them known and/or confirmed by segregation. These included previously described mutations in ABCA4 (c.6088C>T,p.R2030*; c.5882G>A,p.G1961E), BBS2 (c.1895G>C,p.R632P), GUCY2D (c.2512C>T,p.R838C), PROM1 (c.1117C>T,p.R373C), RDH12 (c.601T>C,p.C201R; c.506G>A,p.R169Q), RPGRIP1 (c.3565C>T,p.R1189*) and SPATA7 (c.253C>T,p.R85*) and new mutations in ABCA4 (c.3328+1G>C), CRB1 (c.2832_2842+23del), RP2 (c.884-1G>T) and USH2A (c.12874A>G,p.N4292D). Conclusions: Tagging and pooling DNA prior to targeted capture of known retinal dystrophy genes identified mutations in 60% of cases. This relatively high success rate may reflect enrichment for consanguineous cases in the local Yorkshire population, and the use of multiplex families. Nevertheless this is a promising high throughput approach to retinal dystrophy diagnostics