1,097 research outputs found
An optimized Belief-Rule-Based (BRB) approach to ensure the trustworthiness of interpreted time-series decisions
The accuracy and reliability of XAI methods are important to establish their credibility and use in complex decision-making tasks. Existing XAI methods provide little information about the correctness and reliability of their outputs. Furthermore, post-hoc explanation approaches explain the outcomes after producing them, not in a step-by-step glass-box manner to explain how an output is reached. Our proposed approach addresses these drawbacks by designing a Belief-Rule-Based (BRB) framework that interprets in a glass-box manner why a particular decision has been reached. It does that by determining the chance of different output classes occurring for a specific time period by considering the different possible permutations of the inputs along with their influence. This also assists the user to determine if the given input dataset is incomplete, vague, imprecise or inconsistent before trusting the analysis emanating from it. We compare the performance of the proposed BRB approach against the different eXplainable artificial intelligence (XAI) methods, such as SHAP, LIME and LINDA-BN to ensure the users of the trustworthiness of its analysis. This also enables users to determine the extent to which each of the XAI techniques meets the requirements of XAI and the gaps that need to be addressed
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Extensive Copy-Number Variation of Young Genes across Stickleback Populations
MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
LLL-3 inhibits STAT3 activity, suppresses glioblastoma cell growth and prolongs survival in a mouse glioblastoma model
Persistent activation of the signal transducer and activator of transcription 3 (STAT3) signalling has been linked to oncogenesis and the development of chemotherapy resistance in glioblastoma and other cancers. Inhibition of the STAT3 pathway thus represents an attractive therapeutic approach for cancer. In this study, we investigated the inhibitory effects of a small molecule compound known as LLL-3, which is a structural analogue of the earlier reported STAT3 inhibitor, STA-21, on the cell viability of human glioblastoma cells, U87, U373, and U251 expressing constitutively activated STAT3. We also investigated the inhibitory effects of LLL-3 on U87 glioblastoma cell growth in a mouse tumour model as well as the impact it had on the survival time of the treated mice. We observed that LLL-3 inhibited STAT3-dependent transcriptional and DNA binding activities. LLL-3 also inhibited viability of U87, U373, and U251 glioblastoma cells as well as induced apoptosis of these glioblastoma cell lines as evidenced by increased poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavages. Furthermore, the U87 glioblastoma tumour-bearing mice treated with LLL-3 exhibited prolonged survival relative to vehicle-treated mice (28.5 vs 16 days) and had smaller intracranial tumours and no evidence of contralateral invasion. These results suggest that LLL-3 may be a potential therapeutic agent in the treatment of glioblastoma with constitutive STAT3 activation. Originally published in British Journal of Cancer 2009 Vol. 110, No.
Genetic Organisation, Mobility and Predicted Functions of Genes on Integrated, Mobile Genetic Elements in Sequenced Strains of Clostridium difficile
Background: Clostridium difficile is the leading cause of hospital-associated diarrhoea in the US and Europe. Recently the incidence of C. difficile-associated disease has risen dramatically and concomitantly with the emergence of 'hypervirulent' strains associated with more severe disease and increased mortality. C. difficile contains numerous mobile genetic elements, resulting in the potential for a highly plastic genome. In the first sequenced strain, 630, there is one proven conjugative transposon (CTn), Tn5397, and six putative CTns (CTn1, CTn2 and CTn4-7), of which, CTn4 and CTn5 were capable of excision. In the second sequenced strain, R20291, two further CTns were described.Results: CTn1, CTn2 CTn4, CTn5 and CTn7 were shown to excise from the genome of strain 630 and transfer to strain CD37. A putative CTn from R20291, misleadingly termed a phage island previously, was shown to excise and to contain three putative mobilisable transposons, one of which was capable of excision. In silico probing of C. difficile genome sequences with recombinase gene fragments identified new putative conjugative and mobilisable transposons related to the elements in strains 630 and R20291. CTn5-like elements were described occupying different insertion sites in different strains, CTn1-like elements that have lost the ability to excise in some ribotype 027 strains were described and one strain was shown to contain CTn5-like and CTn7-like elements arranged in tandem. Additionally, using bioinformatics, we updated previous gene annotations and predicted novel functions for the accessory gene products on these new elements.Conclusions: The genomes of the C. difficile strains examined contain highly related CTns suggesting recent horizontal gene transfer. Several elements were capable of excision and conjugative transfer. The presence of antibiotic resistance genes and genes predicted to promote adaptation to the intestinal environment suggests that CTns play a role in the interaction of C. difficile with its human host
A review of wearable motion tracking systems used in rehabilitation following hip and knee replacement
Clinical teams are under increasing pressure to facilitate early hospital discharge for total hip replacement and total knee replacement patients following surgery. A wide variety of wearable devices are being marketed to assist with rehabilitation following surgery. A review of wearable devices was undertaken to assess the evidence supporting their efficacy in assisting rehabilitation following total hip replacement and total knee replacement. A search was conducted using the electronic databases including Medline, CINAHL, Cochrane, PsycARTICLES, and PubMed of studies from January 2000 to October 2017. Five studies met the eligibility criteria, and all used an accelerometer and a gyroscope for their technology. A review of the studies found very little evidence to support the efficacy of the technology, although they show that the use of the technology is feasible. Future work should establish which wearable technology is most valuable to patients, which ones improve patient outcomes, and the most economical model for deploying the technolog
Blood Eosinophils and outcomes in severe hospitalized exacerbations of COPD
Background Patients with moderate exacerbations of COPD and the eosinophilic phenotype have better outcomes with prednisolone. Whether this outcome is similar in patients hospitalized with a severe exacerbation of COPD is unclear. We investigated the rate of recovery of eosinophilic and noneosinophilic exacerbations in patients participating in a multicenter randomized controlled trial assessing health outcomes in hospitalized exacerbations. Methods Patients were recruited at presentation to the hospital with an exacerbation of COPD. They were stratified into groups according to eosinophilic exacerbations if the peripheral blood eosinophil count on admission was ≥ 200 cells/μL and/or ≥ 2% of the total leukocyte count. Admission details, serum C-reactive protein levels, length of stay, and subsequent rehospitalization data were compared between groups. Results A total of 243 patients with COPD (117 men) with a mean age of 71 years (range, 45-93 years) were recruited. The inpatient mortality rate was 3% (median time to death, 12 days; range, 9-16 days). The median absolute eosinophil count was 100 cells/μL (range, 10-1,500 cells/μL), and 25% met our criteria for an eosinophilic exacerbation; in this population, the mean length of stay (in days) was shorter than in patients with noneosinophilic exacerbations (5.0 [range, 1-19] vs 6.5 [range, 1-33]; P = .015) following treatment with oral corticosteroids and independent of treatment prior to admission. Readmission rates at 12 months were similar between groups. Conclusions The study patients presenting to the hospital with a severe eosinophilic exacerbation of COPD had a shorter length of stay. The exacerbations were usually not associated with elevated C-reactive protein levels, suggesting that better treatment stratification of exacerbations can be used
Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases
Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics
Identification and characterization of antibacterial compound(s) of cockroaches (Periplaneta americana)
Infectious diseases remain a significant threat to human health, contributing to more than 17 million deaths, annually. With the worsening trends of drug resistance, there is a need for newer and more powerful antimicrobial agents. We hypothesized that animals living in polluted environments are potential source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of microbes, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances. Here, we characterized antibacterial properties in extracts of various body organs of cockroaches (Periplaneta americana) and showed potent antibacterial activity in crude brain extract against methicillin-resistant Staphylococcus aureus and neuropathogenic E. coli K1. The size-exclusion spin columns revealed that the active compound(s) are less than 10 kDa in molecular mass. Using cytotoxicity assays, it was observed that pre-treatment of bacteria with lysates inhibited bacteria-mediated host cell cytotoxicity. Using spectra obtained with LC-MS on Agilent 1290 infinity liquid chromatograph, coupled with an Agilent 6460 triple quadruple mass spectrometer, tissues lysates were analyzed. Among hundreds of compounds, only a few homologous compounds were identified that contained isoquinoline group, chromene derivatives, thiazine groups, imidazoles, pyrrole containing analogs, sulfonamides, furanones, flavanones, and known to possess broad-spectrum antimicrobial properties, and possess anti-inflammatory, anti-tumour, and analgesic properties. Further identification, characterization and functional studies using individual compounds can act as a breakthrough in developing novel therapeutics against various pathogens including superbugs
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