131 research outputs found

    Static and dynamic behavior of multiplex networks under interlink strength variation

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    It has recently been suggested \cite{Radicchi2013} that in a two-level multiplex network, a gradual change in the value of the "interlayer" strength pp can provoke an abrupt structural transition. The critical point p∗p^* at which this happens is system-dependent. In this article, we show in a similar way as in \cite{Garrahan2014} that this is a consequence of the graph Laplacian formalism used in \cite{Radicchi2013}. We calculate the evolution of p∗p^{*} as a function of system size for ER and RR networks. We investigate the behavior of structural measures and dynamical processes of a two-level system as a function of pp, by Monte-Carlo simulations, for simple particle diffusion and for reaction-diffusion systems. We find that as pp increases there is a smooth transition from two separate networks to a single one. We cannot find any abrupt change in static or dynamic behavior of the underlying system.Comment: 8 pages, 5 figure

    Explosive Percolation: Unusual Transitions of a Simple Model

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    In this paper we review the recent advances on explosive percolation, a very sharp phase transition first observed by Achlioptas et al. (Science, 2009). There a simple model was proposed, which changed slightly the classical percolation process so that the emergence of the spanning cluster is delayed. This slight modification turns out to have a great impact on the percolation phase transition. The resulting transition is so sharp that it was termed explosive, and it was at first considered to be discontinuous. This surprising fact stimulated considerable interest in "Achlioptas processes". Later work, however, showed that the transition is continuous (at least for Achlioptas processes on Erdos networks), but with very unusual finite size scaling. We present a review of the field, indicate open "problems" and propose directions for future research.Comment: 27 pages, 4 figures, Review pape

    Therapeutic targeting of ALS pathways: refocusing an incomplete picture

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    © 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Numerous potential amyotrophic lateral sclerosis (ALS)-relevant pathways have been hypothesized and studied preclinically, with subsequent translation to clinical trial. However, few successes have been observed with only modest effects. Along with an improved but incomplete understanding of ALS as a neurodegenerative disease is the evolution of more sophisticated and diverse in vitro and in vivo preclinical modeling platforms, as well as clinical trial designs. We highlight proposed pathological pathways that have been major therapeutic targets for investigational compounds. It is likely that the failures of so many of these therapeutic compounds may not have occurred because of lack of efficacy but rather because of a lack of preclinical modeling that would help define an appropriate disease pathway, as well as a failure to establish target engagement. These challenges are compounded by shortcomings in clinical trial design, including lack of biomarkers that could predict clinical success and studies that are underpowered. Although research investments have provided abundant insights into new ALS-relevant pathways, most have not yet been developed more fully to result in clinical study. In this review, we detail some of the important, well-established pathways, the therapeutics targeting them, and the subsequent clinical design. With an understanding of some of the shortcomings in translational efforts over the last three decades of ALS investigation, we propose that scientists and clinicians may choose to revisit some of these therapeutic pathways reviewed here with an eye toward improving preclinical modeling, biomarker development, and the investment in more sophisticated clinical trial designs.Research funding: Cytokinetics National Institutes of Health, USA. Grant Number: 5R01NS117604-03info:eu-repo/semantics/publishedVersio

    Two-photon ionization of Helium studied with the multiconfigurational time-dependent Hartree-Fock method

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    The multiconfigurational time-dependent Hartree-Fock method (MCTDHF) is applied for simulations of the two-photon ionization of Helium. We present results for the single- and double ionization from the groundstate for photon energies in the non-sequential regime, and compare them to direct solutions of the Schr\"odinger equation using the time-dependent (full) Configuration Interaction method (TDCI). We find that the single-ionization is accurately reproduced by MCTDHF, whereas the double ionization results correctly capture the main trends of TDCI

    The use of live attenuated influenza vaccine (LAIV) in healthcare personnel (HCP): Guidance from the society for healthcare epidemiology of America (SHEA)

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    Because of the live viral backbone of live attenuated influenza vaccine (LAIV), questions have arisen regarding infection control precautions and restrictions surrounding its use in healthcare personnel (HCP). This document provides guidance from the Society for Healthcare Epidemiology of America regarding use of LAIV in HCP and the infection control precautions that are recommended with its use in this population. Infect Control Hosp Epidemiol 2012;33(10):981-98

    Mechanisms Models and Biomarkers in Amyotrophic Lateral Sclerosis

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    The last 30 years have seen a major advance in the understanding of the clinical and pathological heterogeneity of amyotrophic lateral sclerosis (ALS), and its overlap with frontotemporal dementia. Multiple, seemingly disparate biochemical pathways converge on a common clinical syndrome characterized by progressive loss of upper and lower motor neurons. Pathogenic themes in ALS include excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation, altered energy metabolism, and most recently RNA mis-processing. The transgenic rodent, overexpressing mutant superoxide dismutase-1, is now only one of several models of ALS pathogenesis. The nematode, fruit fly and zebrafish all offer fresh insight, and the development of induced pluripotent stem cell-derived motor neurons holds promise for the screening of candidate therapeutics. The lack of useful biomarkers in ALS contributes to diagnostic delay, and the inability to stratify patients by prognosis may be an important factor in the failure of therapeutic trials. Biomarkers sensitive to disease activity might lessen reliance on clinical measures and survival as trial endpoints and reduce study length. Emerging proteomic markers of neuronal loss and glial activity in cerebrospinal fluid, a cortical signature derived from advanced structural and functional MRI, and the development of more sensitive measurements of lower motor neuron physiology are leading a new phase of biomarker-driven therapeutic discovery

    Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection: A Case Series From a 12-Month Longitudinal Occupational Cohort

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    Findings are described in 7 patients with severe acute respiratory syndrome coronavirus 2 reinfection from the National Basketball Association 2020-2021 occupational testing cohort, including clinical details, antibody test results, genomic sequencing, and longitudinal reverse-transcription polymerase chain reaction results. Reinfections were infrequent and varied in clinical presentation, viral dynamics, and immune response

    Eradication of multidrug-resistant Acinetobacter baumannii in a female patient with total hip arthroplasty, with debridement and retention: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Multidrug-resistant <it>Acinetobacter baumannii </it>has become a significant cause of healthcare-associated infections, but few reports have addressed <it>Acinetobacter baumannii </it>infections associated with orthopedic devices. The current recommended treatment for complicated infections due to orthopedic devices, including resistant gram-negative rods, consists of antimicrobial therapy with debridement and removal of implants.</p> <p>Case presentation</p> <p>The patient, a 47-year-old woman, had previously had a prior total hip arthroplasty at 16 years of age for a complex femoral neck fracture, and multiple subsequent revisions. This time, she underwent a fifth revision secondary to pain. Surgery was complicated by hypotension resulting in transfer to the intensive care unit and prolonged respiratory failure. She received peri-operative cefazolin but postoperatively developed surgical wound drainage requiring debridement of a hematoma. Cultures of this grew ampicillin-sensitive <it>Enterococcus </it>and <it>Acinetobacter baumannii </it>(sensitive only to amikacin and imipenem). The patient was started on imipenem. Removal of the total hip arthroplasty was not recommended because of the recent surgical complications, and the patient was eventually discharged home. She was seen weekly for laboratory tests and examinations and, after 4 months of therapy, the imipenem was discontinued. She did well clinically for 7 months before recurrent pain led to removal of the total hip arthroplasty. Intra-operative cultures grew ampicillin-sensitive <it>Enterococcus </it>and coagulase-negative <it>Staphylococcus </it>but no multidrug-resistant <it>Acinetobacter baumannii</it>. The patient received ampicillin for 8 weeks and had not had recurrent infection at the time of writing, 37 months after discontinuing imipenem.</p> <p>Conclusion</p> <p>We describe the successful treatment of an acute infection from multidrug-resistant <it>Acinetobacter baumannii </it>with debridement and retention of the total hip arthroplasty, using monotherapy with imipenem. This case challenges the general assumption that all orthopedic-device infections due to multidrug-resistant gram-negative organisms will require hardware removal. Further studies are needed to determine if organisms such as multidrug-resistant <it>Acinetobacter baumannii </it>are amenable to treatment with hardware retention.</p
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