2,541 research outputs found

    Near-Optimal Computation of Runs over General Alphabet via Non-Crossing LCE Queries

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    Longest common extension queries (LCE queries) and runs are ubiquitous in algorithmic stringology. Linear-time algorithms computing runs and preprocessing for constant-time LCE queries have been known for over a decade. However, these algorithms assume a linearly-sortable integer alphabet. A recent breakthrough paper by Bannai et.\ al.\ (SODA 2015) showed a link between the two notions: all the runs in a string can be computed via a linear number of LCE queries. The first to consider these problems over a general ordered alphabet was Kosolobov (\emph{Inf.\ Process.\ Lett.}, 2016), who presented an O(n(logn)2/3)O(n (\log n)^{2/3})-time algorithm for answering O(n)O(n) LCE queries. This result was improved by Gawrychowski et.\ al.\ (accepted to CPM 2016) to O(nloglogn)O(n \log \log n) time. In this work we note a special \emph{non-crossing} property of LCE queries asked in the runs computation. We show that any nn such non-crossing queries can be answered on-line in O(nα(n))O(n \alpha(n)) time, which yields an O(nα(n))O(n \alpha(n))-time algorithm for computing runs

    Myotoxicity of telbivudine in pre-existing muscle damage

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    <p>Abstract</p> <p>Objectives</p> <p>It is unknown if telbivudine causes muscle damage only in patients with pre-existing muscle pathology.</p> <p>Case report</p> <p>A 27 yo male of African origin received telbivudine for hepatitis B during 3 months. Three weeks after initiation of the drug he developed myalgia, and tiredness. Creatine-kinase increased from 278 U/l (n, <170 U/l) at baseline to 3243 U/l. Shortly after discontinuation of telbivudine muscle symptoms and hyper-CK-emia disappeared. The findings suggest that pre-existing muscle damage favored the myotoxic effect of telbivudine.</p> <p>Conclusions</p> <p>Telbivudine appears to cause accelerated muscle toxicity if given to patients who already have muscle damage. Patients under telbivudine should be closely monitored for muscular side effects and those with pre-existing muscle damage should not receive the drug.</p

    Neuromodulation and the role of electrodiagnostic techniques

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    Electrodiagnostic techniques have been utilized in surgery since the early 1960s. These techniques have been primarily used in neurosurgery; however, with the introduction of neuromodulation for voiding dysfunction, these techniques have now found their way into the field of female pelvic medicine. This article will review techniques applicable to evaluate pelvic floor function as it relates to neuromodulation. It will also review the literature describing how these techniques are used to help determine appropriate candidates as well as improve surgical outcomes. A PubMed search was conducted using the terms neuromodulation, Interstim, electrodiagnosis, electrodiagnostic techniques, electromyography with limits to the pelvic floor, and voiding dysfunction. Eight articles and three abstracts were found that directly related to the use of electrodiagnostic techniques as they apply to neuromodulation. Electrodiagnostic techniques may play a role in helping predict appropriate candidates for neuromodulation as well as improve surgical outcomes

    Effect of Dietary Components on Larval Life History Characteristics in the Medfly (Ceratitis capitata: Diptera, Tephritidae)

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    Background: The ability to respond to heterogenous nutritional resources is an important factor in the adaptive radiation of insects such as the highly polyphagous Medfly. Here we examined the breadth of the Medfly’s capacity to respond to different developmental conditions, by experimentally altering diet components as a proxy for host quality and novelty. Methodology/Principal Findings: We tested responses of larval life history to diets containing protein and carbohydrate components found in and outside the natural host range of this species. A 40% reduction in the quantity of protein caused a significant increase in egg to adult mortality by 26.5%±6% in comparison to the standard baseline diet. Proteins and carbohydrates had differential effects on larval versus pupal development and survival. Addition of a novel protein source, casein (i.e. milk protein), to the diet increased larval mortality by 19.4%±3% and also lengthened the duration of larval development by 1.93±0.5 days in comparison to the standard diet. Alteration of dietary carbohydrate, by replacing the baseline starch with simple sugars, increased mortality specifically within the pupal stage (by 28.2%±8% and 26.2%±9% for glucose and maltose diets, respectively). Development in the presence of the novel carbohydrate lactose (milk sugar) was successful, though on this diet there was a decrease of 29.8±1.6 µg in mean pupal weight in comparison to pupae reared on the baseline diet. Conclusions: The results confirm that laboratory reared Medfly retain the ability to survive development through a wide range of fluctuations in the nutritional environment. We highlight new facets of the responses of different stages of holometabolous life histories to key dietary components. The results are relevant to colonisation scenarios and key to the biology of this highly invasive species

    Decision-making in percutaneous coronary intervention: a survey

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    <p>Abstract</p> <p>Background</p> <p>Few researchers have examined the perceptions of physicians referring cases for angiography regarding the degree to which collaboration occurs during percutaneous coronary intervention (PCI) decision-making. We sought to determine perceptions of physicians concerning their involvement in PCI decisions in cases they had referred to the cardiac catheterization laboratory at a major academic medical center.</p> <p>Methods</p> <p>An anonymous survey was mailed to internal medicine faculty members at a major academic medical center. The survey elicited whether responders perceived that they were included in decision-making regarding PCI, and whether they considered such collaboration to be the best process of decision-making.</p> <p>Results</p> <p>Of the 378 surveys mailed, 35% (133) were returned. Among responding non-cardiologists, 89% indicated that in most cases, PCI decisions were made solely by the interventionalist at the time of the angiogram. Among cardiologists, 92% indicated that they discussed the findings with the interventionalist prior to any PCI decisions. When asked what they considered the best process by which PCI decisions are made, 66% of non-cardiologists answered that they would prefer collaboration between either themselves or a non-interventional cardiologist and the interventionalist. Among cardiologists, 95% agreed that a collaborative approach is best.</p> <p>Conclusion</p> <p>Both non-cardiologists and cardiologists felt that involving another decision-maker, either the referring physician or a non-interventional cardiologist, would be the best way to make PCI decisions. Among cardiologists, there was more concordance between what they believed was the best process for making decisions regarding PCI and what they perceived to be the actual process.</p

    The Epidemiology of Otosclerosis in a British Cohort

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    OBJECTIVE: To analyse the epidemiology of otosclerosis in a British cohort collected between 2011 and 2017. DESIGN: Retrospective cohort study. SETTING: Five UK ENT Departments. PATIENTS: Patients with surgically confirmed otosclerosis. MAIN OUTCOME MEASURES: Questionnaire data documented family history of otosclerosis, age of onset, medical history, and information on associated risk factors for 657 patients. Pre and post-surgical pure-tone audiometry was collected for 154 of these patients. RESULTS: The age of onset, incidence of bilateral disease, tinnitus and vertigo, a higher prevalence of women (65%) than men (35%) are similar to those reported previously for otosclerosis cohorts. No association with measles infection was detected. Patients with a family history (40%) have an earlier age of onset and a higher incidence of bilateral disease and vertigo than non-familial subjects. Pedigree analysis is consistent with an autosomal dominant inheritance with reduced penetrance being apparent in 44/91 pedigrees studied. Women who associate their hearing loss with pregnancy have an earlier age of onset than those that do not (p = 6 × 10). CONCLUSIONS: This study confirms that otosclerosis is an early adult onset disease that is more prevalent in women than men with a large minority of patients having a family history of otosclerosis. We report new evidence to support a relationship between pregnancy and otosclerosis progression in a proportion of women. In addition, this is the first study to identify differences in severity between familial and non-familial cases of otosclerosis, highlighting the possibility that more than one etiology may be involved

    Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

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    Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

    Crystal Structure of a Charge Engineered Human Lysozyme Having Enhanced Bactericidal Activity

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    Human lysozyme is a key component of the innate immune system, and recombinant forms of the enzyme represent promising leads in the search for therapeutic agents able to treat drug-resistant infections. The wild type protein, however, fails to participate effectively in clearance of certain infections due to inherent functional limitations. For example, wild type lysozymes are subject to electrostatic sequestration and inactivation by anionic biopolymers in the infected airway. A charge engineered variant of human lysozyme has recently been shown to possess improved antibacterial activity in the presence of disease associated inhibitory molecules. Here, the 2.04 Å crystal structure of this variant is presented along with an analysis that provides molecular level insights into the origins of the protein's enhanced performance. The charge engineered variant's two mutated amino acids exhibit stabilizing interactions with adjacent native residues, and from a global perspective, the mutations cause no gross structural perturbations or loss of stability. Importantly, the two substitutions dramatically expand the negative electrostatic potential that, in the wild type enzyme, is restricted to a small region near the catalytic residues. The net result is a reduction in the overall strength of the engineered enzyme's electrostatic potential field, and it appears that the specific nature of this remodeled field underlies the variant's reduced susceptibility to inhibition by anionic biopolymers
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