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Sökning: WFRF:(Sriram S)

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1.
  • 2021
  • swepub:Mat__t
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  • Glasbey, JC, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Thomas, HS, et al. (författare)
  • 2019
  • swepub:Mat__t
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  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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9.
  • de Erausquin, Gabriel A, et al. (författare)
  • Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium.
  • 2022
  • Ingår i: Alzheimer's & dementia (New York, N. Y.). - : Wiley. - 2352-8737. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term.This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions.Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe.The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection.The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease.We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic.The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.
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  • Deka, Shankar, 1993-, et al. (författare)
  • Path-Integral Formula for Computing Koopman Eigenfunctions
  • 2023
  • Ingår i: 2023 62nd IEEE Conference on Decision and Control, CDC 2023. - : Institute of Electrical and Electronics Engineers Inc.. ; , s. 6641-6646
  • Konferensbidrag (refereegranskat)abstract
    • The paper is about the computation of the principal spectrum of the Koopman operator (i.e., eigenvalues and eigenfunctions). The principal eigenfunctions of the Koopman operator are the ones with the corresponding eigenvalues equal to the eigenvalues of the linearization of the nonlinear system at an equilibrium point. The main contribution of this paper is to provide a novel approach for computing the principal eigenfunctions using a path-integral formula. Furthermore, we provide conditions based on the stability property of the dynamical system and the eigenvalues of the linearization towards computing the principal eigenfunction using the path-integral formula. Further, we provide a Deep Neural Network framework that utilizes our proposed path-integral approach for eigenfunction computation in high-dimension systems. Finally, we present simulation results for the computation of principal eigenfunction and demonstrate their application for determining the stable and unstable manifolds and constructing the Lyapunov function.
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11.
  • Zhou, Weihua, et al. (författare)
  • Purine metabolism regulates DNA repair and therapy resistance in glioblastoma
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Intratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming therapy resistance. Treatments that are effective independent of genotype are urgently needed. By correlating intracellular metabolite levels with radiation resistance across dozens of genomically-distinct models of GBM, we find that purine metabolites, especially guanylates, strongly correlate with radiation resistance. Inhibiting GTP synthesis radiosensitizes GBM cells and patient-derived neurospheres by impairing DNA repair. Likewise, administration of exogenous purine nucleosides protects sensitive GBM models from radiation by promoting DNA repair. Neither modulating pyrimidine metabolism nor purine salvage has similar effects. An FDA-approved inhibitor of GTP synthesis potentiates the effects of radiation in flank and orthotopic patient-derived xenograft models of GBM. High expression of the rate-limiting enzyme of de novo GTP synthesis is associated with shorter survival in GBM patients. These findings indicate that inhibiting purine synthesis may be a promising strategy to overcome therapy resistance in this genomically heterogeneous disease.
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  • Easwar, Vijayalakshmi, et al. (författare)
  • Audiological Practice in India: An Internet-Based Survey of Audiologists
  • 2013
  • Ingår i: INDIAN JOURNAL OF OTOLARYNGOLOGY AND HEAD and NECK SURGERY. - : Springer Verlag (Germany). - 2231-3796 .- 0973-7707. ; 65, s. S636-S644
  • Tidskriftsartikel (refereegranskat)abstract
    • The field of Audiology in India has expanded exponentially in recent years. Audiologists practice in a variety of work places. However, little is known about the practice trends across these several work places. An Internet-based survey probing into Audiology practice was conducted between June and September 2012. The survey focused on four domains, namely, demography, assessment, hearing aid (HA) fitting and protocol usage. A total of 199 audiologists completed the survey. A large proportion of these audiologists were from Southern India. Majority of the respondents provide hearing assessment and HA services for children and adults. Results indicate diverse practice among respondents, even in essential procedures such as otoscopy. Although a large proportion of audiologists reported performing HA fitting in children as well as adults, less than 12 % of them performed real ear or simulated real ear verification during any HA fitting. Implications for the development of preferred practice guidelines in India have been discussed.
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  • Kang, Evan S. H., et al. (författare)
  • Organic Anisotropic Excitonic Optical Nanoantennas
  • 2022
  • Ingår i: Advanced Science. - : Wiley. - 2198-3844 .- 2198-3844. ; 9:23
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical nanoantennas provide control of light at the nanoscale, which makes them important for diverse areas ranging from photocatalysis and flat metaoptics to sensors and biomolecular tweezing. They have traditionally been limited to metallic and dielectric nanostructures that sustain plasmonic and Mie resonances, respectively. More recently, nanostructures of organic J-aggregate excitonic materials have been proposed capable of also supporting nanooptical resonances, although their advance has been hampered from difficulty in nanostructuring. Here, the authors present the realization of organic J-aggregate excitonic nanostructures, using nanocylinder arrays as model system. Extinction spectra show that they can sustain both plasmon-like resonances and dielectric resonances, owing to the material providing negative and large positive permittivity regions at the different sides of its exciton resonance. Furthermore, it is found that the material is highly anisotropic, leading to hyperbolic and elliptic permittivity regions. Nearfield analysis using optical simulation reveals that the nanostructures therefore support hyperbolic localized surface exciton resonances and elliptic Mie resonances, neither of which has been previously demonstrated for this type of material. The anisotropic nanostructures form a new type of optical nanoantennas, which combined with the presented fabrication process opens up for applications such as fully organic excitonic metasurfaces.
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15.
  • Karami, Nahid, 1959, et al. (författare)
  • Identity of bla ctx-m carrying plasmids in sequential esbl-e. Coli isolates from patients with recurrent urinary tract infections
  • 2021
  • Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasmid-mediated multidrug resistance in E. coli is becoming increasingly prevalent. Considering this global threat to human health, it is important to understand how plasmid-mediated resistance spreads. From a cohort of 123 patients with recurrent urinary tract infections (RUTI) due to extended spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL E. coli), only five events with a change of ESBL E. coli strain between RUTI episodes were identified. Their blaCTX-M encoding plasmids were compared within each pair of isolates using optical DNA mapping (ODM) and PCR-based replicon typing. Despite similar blaCTX-M genes and replicon types, ODM detected only one case with identical plasmids in the sequential ESBL E. coli strains, indicating that plasmid transfer could have occurred. For comparison, plasmids from seven patients with the same ESBL E. coli strain reoccurring in both episodes were analyzed. These plasmids (encoding blaCTX-M-3, blaCTX-M-14, and blaCTX-M-15 ) were unaltered for up to six months between recurrent infections. Thus, transmission of blaCTX-M plasmids appears to be a rare event during the course of RUTI. Despite the limited number (n = 23) of plasmids investigated, similar blaCTX-M-15 plasmids in unrelated isolates from different patients were detected, suggesting that some successful plasmids could be associated with specific strains, or are more easily transmitted.
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  • Kesarimangalam, Sriram, 1983, et al. (författare)
  • A parallelized nanofluidic device for high-throughput optical dna mapping of bacterial plasmids
  • 2021
  • Ingår i: Micromachines. - : MDPI AG. - 2072-666X. ; 12:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical DNA mapping (ODM) has developed into an important technique for DNA anal-ysis, where single DNA molecules are sequence-specifically labeled and stretched, for example, in nanofluidic channels. We have developed an ODM assay to analyze bacterial plasmids—circular extrachromosomal DNA that often carry genes that make bacteria resistant to antibiotics. As for most techniques, the next important step is to increase throughput and automation. In this work, we designed and fabricated a nanofluidic device that, together with a simple automation routine, allows parallel analysis of up to 10 samples at the same time. Using plasmids encoding extended-spectrum beta-lactamases (ESBL), isolated from Escherichia coli and Klebsiella pneumoniae, we demon-strate the multiplexing capabilities of the device when it comes to both many samples in parallel and different resistance genes. As a final example, we combined the device with a novel protocol for rapid cultivation and extraction of plasmids from fecal samples collected from patients. This combined protocol will make it possible to analyze many patient samples in one device already on the day the sample is collected, which is an important step forward for the ODM analysis of plas-mids in clinical diagnostics.
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  • Kesarimangalam, Sriram, 1983, et al. (författare)
  • Identification and characterization of plasmids carrying the mobile colistin resistance gene mcr-1 using optical DNA mapping
  • 2023
  • Ingår i: JAC-Antimicrobial Resistance. - : Oxford University Press (OUP). - 2632-1823. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Colistin is a last-resort antibiotic, but there has been a rapid increase in colistin resistance, threatening its use in the treatment of infections with carbapenem-resistant Enterobacterales (CRE). Plasmid-mediated colistin resistance, in particular the mcr-1 gene, has been identified and WGS is the go-to method in identifying plasmids carrying mcr-1 genes. The goal of this study is to demonstrate the use of optical DNA mapping (ODM), a fast, efficient and amplification-free technique, to characterize plasmids carrying mcr-1. Methods ODM is a single-molecule technique, which we have demonstrated can be used for identifying plasmids harbouring antibiotic resistance genes. We here applied the technique to plasmids isolated from 12 clinical Enterobacterales isolates from patients at a major hospital in Thailand and verified our results using Nanopore long-read sequencing. Results We successfully identified plasmids encoding the mcr-1 gene and, for the first time, demonstrated the ability of ODM to identify resistance gene sites in small (similar to 30 kb) plasmids. We further identified bla(CTX-M) genes in different plasmids than the ones encoding mcr-1 in three of the isolates studied. Finally, we propose a cut-and-stretch assay, based on similar principles, but performed using surface-functionalized cover slips for DNA immobilization and an inexpensive microscope with basic functionalities, to identify the mcr-1 gene in a plasmid sample. Conclusions Both ODM and the cut-and-stretch assay developed could be very useful in identifying plasmids encoding antibiotic resistance in hospitals and healthcare facilities. The cut-and-stretch assay is particularly useful in low- and middle-income countries, where existing techniques are limited.
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  • Kesarimangalam, Sriram, 1983, et al. (författare)
  • Optical dna mapping of plasmids reveals clonal spread of carbapenem-resistant klebsiella pneumoniae in a large thai hospital
  • 2021
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 10:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbapenem-resistant Klebsiella pneumoniae (CR-KP) in patients admitted to hospitals pose a great challenge to treatment. The genes causing resistance to carbapenems are mostly found in plasmids, mobile genetic elements that can spread easily to other bacterial strains, thus exacerbating the problem. Here, we studied 27 CR-KP isolates collected from different types of samples from 16 patients admitted to the medical ward at Siriraj Hospital in Bangkok, Thailand, using next generation sequencing (NGS) and optical DNA mapping (ODM). The majority of the isolates belonged to sequence type (ST) 16 and are described in detail herein. Using ODM, we identified the plasmid carrying the blaNDM-1 gene in the ST16 isolates and the plasmids were very similar, highlighting the possibility of using ODM of plasmids as a surrogate marker of nosocomial spread of bacteria. We also demonstrated that ODM could identify that the blaCTX-M-15 and blaOXA-232 genes in the ST16 isolates were encoded on separate plasmids from the blaNDM-1 gene and from each other. The other three isolates belonged to ST147 and each of them had distinct plasmids encoding blaNDM-1 .
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  • Lagerstedt, Jens, et al. (författare)
  • EPR assessment of protein sites for incorporation of Gd(III) MRI contrast labels.
  • 2013
  • Ingår i: Contrast Media & Molecular Imaging. - : Wiley. - 1555-4317 .- 1555-4309. ; 8:3, s. 252-264
  • Tidskriftsartikel (refereegranskat)abstract
    • We have engineered apolipoprotein A-I (apoA-I), a major protein constituent of high-density lipoprotein (HDL), to contain DOTA-chelated Gd(III) as an MRI contrast agent for the purpose of imaging reconstituted HDL (rHDL) biodistribution, metabolism and regulation in vivo. This protein contrast agent was obtained by attaching the thiol-reactive Gd[MTS-ADO3A] label at Cys residues replaced at four distinct positions (52, 55, 76 and 80) in apoA-I. MRI of infused mice previously showed that the Gd-labeled apoA-I migrates to both the liver and the kidney, the organs responsible for HDL catabolism; however, the contrast properties of apoA-I are superior when the ADO3A moiety is located at position 55, compared with the protein labeled at positions 52, 76 or 80. It is shown here that continuous wave X-band (9 GHz) electron paramagnetic resonance (EPR) spectroscopy is capable of detecting differences in the Gd(III) signal when comparing the labeled protein in the lipid-free with the rHDL state. Furthermore, the values of NMR relaxivity obtained for labeled variants in both the lipid-free and rHDL states correlate to the product of the X-band Gd(III) spectral width and the collision frequency between a nitroxide spin label and a polar relaxation agent. Consistent with its superior relaxivity measured by NMR, the rHDL-associated apoA-I containing the Gd[MTS-ADO3A] probe attached to position 55 displays favorable dynamic and water accessibility properties as determined by X-band EPR. While room temperature EPR requires >1 m m Gd(III)-labeled and only >10 µ m nitroxide-labeled protein to resolve the spectrum, the volume requirement is exceptionally low (~5 µl). Thus, X-band EPR provides a practical assessment for the suitability of imaging candidates containing the site-directed ADO3A contrast probe. Copyright © 2013 John Wiley & Sons, Ltd.
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21.
  • Lee, Seunghyun, et al. (författare)
  • Plasmonic polymer nanoantenna arrays for electrically tunable and electrode-free metasurfaces
  • 2023
  • Ingår i: Journal of Materials Chemistry A. - : ROYAL SOC CHEMISTRY. - 2050-7488 .- 2050-7496. ; 11:40, s. 21569-21576
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrically tunable metasurfaces and interrelated nanofabrication techniques are essential for metasurface-based optoelectronic applications. We present a nanofabrication method suitable for various types of plasmonic polymer metasurfaces including inverted arrays of nanoantennas. Inverted metasurfaces are of particular interest since the metasurface itself can work as an electrode due to its interconnected nature, which enables electrical control without adopting an additional electrode. In comparison with inverted nanodisk arrays that support relatively weak resonance features, we show that inverted nanorod arrays can possess stronger resonances, even comparable with those of nanorod arrays. The origin of plasmon resonances in inverted arrays is systematically investigated using finite-difference time-domain (FDTD) simulations. Further, we demonstrate electrically tunable electrode-free metasurface devices using polymer inverted nanorod arrays, which can operate in the full spectral range of the material including the mid-infrared region. Electrically tunable and electrode-free metasurfaces using plasmonic polymer inverted nanoantenna arrays can operate across the entire spectral range of the material, including the mid-infrared region.
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22.
  • Min, Hong, et al. (författare)
  • Pattern Matching Based Sensor Identification Layer for an Android Platform
  • 2018
  • Ingår i: Wireless Communications & Mobile Computing. - : John Wiley & Sons. - 1530-8669 .- 1530-8677.
  • Tidskriftsartikel (refereegranskat)abstract
    • As sensor-related technologies have been developed, smartphones obtain more information from internal and external sensors. This interaction accelerates the development of applications in the Internet of Things environment. Due to many attributes that may vary the quality of the IoT system, sensor manufacturers provide their own data format and application even if there is a well-defined standard, such as ISO/IEEE 11073 for personal health devices. In this paper, we propose a client-server-based sensor adaptation layer for an Android platform to improve interoperability among nonstandard sensors. Interoperability is an important quality aspect for the IoT that may have a strong impact on the system especially when the sensors are coming from different sources. Here, the server compares profiles that have clues to identify the sensor device with a data packet stream based on a modified Boyer-Moore-Horspool algorithm. Our matching model considers features of the sensor data packet. To verify the operability, we have implemented a prototype of this proposed system. The evaluation results show that the start and end pattern of the data packet are more efficient when the length of the data packet is longer.
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23.
  • Nyblom, My, 1995, et al. (författare)
  • Strain-level bacterial typing directly from patient samples using optical DNA mapping
  • 2023
  • Ingår i: COMMUNICATIONS MEDICINE. - : Springer Science and Business Media LLC. - 2730-664X. ; 3:31
  • Tidskriftsartikel (refereegranskat)abstract
    • For bacterial infections, it is important to rapidly and accurately identify and characterize the type of bacteria involved so that optimal antibiotic treatment can be given quickly to the patient. However, current diagnostic methods are sometimes slow and cannot be used for mixtures of bacteria. We have, therefore, developed a method to identify bacteria directly from patient samples. The method was tested on two common species of disease-causing bacteria - Escherichia coli and Klebsiella pneumoniae - and it could correctly identify the bacterial strain or subtype in both urine samples and mixtures. Hence, the method has the potential to provide fast diagnostic information for choosing the most suited antibiotic, thereby reducing the risk of death and suffering. Nyblom, Johnning et al. develop an optical DNA mapping approach for bacterial strain typing of patient samples. They demonstrate rapid identification of clinically relevant E. coli and K. pneumoniae strains, without the need for cultivation. BackgroundIdentification of pathogens is crucial to efficiently treat and prevent bacterial infections. However, existing diagnostic techniques are slow or have a too low resolution for well-informed clinical decisions.MethodsIn this study, we have developed an optical DNA mapping-based method for strain-level bacterial typing and simultaneous plasmid characterisation. For the typing, different taxonomical resolutions were examined and cultivated pure Escherichia coli and Klebsiella pneumoniae samples were used for parameter optimization. Finally, the method was applied to mixed bacterial samples and uncultured urine samples from patients with urinary tract infections. Results We demonstrate that optical DNA mapping of single DNA molecules can identify Escherichia coli and Klebsiella pneumoniae at the strain level directly from patient samples. At a taxonomic resolution corresponding to E. coli sequence type 131 and K. pneumoniae clonal complex 258 forming distinct groups, the average true positive prediction rates are 94% and 89%, respectively. The single-molecule aspect of the method enables us to identify multiple E. coli strains in polymicrobial samples. Furthermore, by targeting plasmid-borne antibiotic resistance genes with Cas9 restriction, we simultaneously identify the strain or subtype and characterize the corresponding plasmids. Conclusion The optical DNA mapping method is accurate and directly applicable to polymicrobial and clinical samples without cultivation. Hence, it has the potential to rapidly provide comprehensive diagnostics information, thereby optimizing early antibiotic treatment and opening up for future precision medicine management.
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  • Roy, Sharon L, et al. (författare)
  • Assessment of blood-brain barrier penetration of miltefosine used to treat a fatal case of granulomatous amebic encephalitis possibly caused by an unusual Balamuthia mandrillaris strain.
  • 2015
  • Ingår i: Parasitology Research. - : Springer Science and Business Media LLC. - 0932-0113 .- 1432-1955. ; 114:12, s. 4431-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Balamuthia mandrillaris, a free-living ameba, causes rare but frequently fatal granulomatous amebic encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 μg/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 μg/mL. These are the first results confirming some blood-brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug's toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities.
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27.
  • Shankar, K. V., et al. (författare)
  • Investigation of SiC particle size variation on the tribological properties of Cu-6Sn-SiC composite
  • 2020
  • Ingår i: Archives of Foundry Engineering. - 1897-3310 .- 2299-2944. ; 20:4, s. 133-138
  • Tidskriftsartikel (refereegranskat)abstract
    • Copper have always been an important material and incorporation of elements into copper for property enhancement. Bronze is a relevant cuprous alloy which is important for many industrial and automotive applications like bearings and machineries. The present research is directed towards the fabrication and tribological analysis of regular bronze (Cu-6Sn) and metal matrix composites reinforced with varying particle sized SiC ceramic reinforcement (30, 35 and 40 µm). The developed specimens were subjected to wear analysis according to ASTM standards, to identify the tribological properties utilizing a pin on disk tribometer. It was noted that the wear rates of developed MMC's phenomenally decremented with an increase in size of SiC particle reinforcement. Also, the test parameters were influential in altering the wear rates to notable margins. The standard scanning electron microscopy techniques aided in identifying the influence of adhesive wear on the specimen surface.
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