Summary Background Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial ...resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10−1 to 10−3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa . In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China.
To compare the efficacy of topical non-steroidal anti-inflammatory drugs (NSAIDs) with topical capsaicin for pain relief in osteoarthritis (OA).
A systematic literature search was conducted for ...randomised controlled trials (RCTs) examining any topical NSAID or capsaicin in OA. Pain relief at or nearest to 4 weeks was pooled using a random-effects network meta-analysis (NMA) in a Frequentist and Bayesian setting. Analysis was conducted for all trials and for trials using drugs listed as licensed for OA in the British National Formulary (BNF).
The trial network comprised 28 RCTs (7372 participants), of which 17 RCTs (3174 participants) were included in the as licensed analyses. No RCTs directly compared topical NSAIDs with capsaicin. Placebo was the only common comparator for topical NSAIDs and capsaicin. Frequentist and Bayesian effect size (ES) estimates were in agreement. Topical NSAIDs were statistically superior to placebo overall (ES 0.30, 95% confidence interval CI 0.19 to 0.41) and as licensed (ES 0.32, 95% CI 0.24 to 0.39). However, capsaicin was only statistically superior to placebo when used at licensed doses (ES 0.41, 95% CI 0.17 to 0.64). No significant differences were observed in pain relief between topical NSAIDs and capsaicin (overall: ES 0.04, 95% CI −0.26 to 0.33; as licensed: ES-0.09, 95% CI −0.34 to 0.16).
Current evidence indicates that topical NSAIDs and capsaicin in licensed doses may be equally effective for pain relief in OA. Whether the equivalence varies between individuals remains unknown.
A specialized data-mining algorithm has been developed using wide-field photometry catalogs, enabling systematic and efficient searches for resolved, extremely low surface brightness satellite ...galaxies in the halo of the Milky Way (MW). Tested and calibrated with the Sloan Digital Sky Survey Data Release 6 (SDSS-DR6) we recover all 15 MW satellites recently detected in SDSS, six known MW/Local Group dSphs in the SDSS footprint, and 19 previously known globular and open clusters. In addition, 30 point-source overdensities have been found that correspond to no cataloged objects. The detection efficiencies of the algorithm have been carefully quantified by simulating more than three million model satellites embedded in star fields typical of those observed in SDSS, covering a wide range of parameters including galaxy distance, scale length, luminosity, and Galactic latitude. We present several parameterizations of these detection limits to facilitate comparison between the observed MW satellite population and predictions. We find that all known satellites would be detected with >90% efficiency over all latitudes spanned by DR6 and that the MW satellite census within DR6 is complete to a magnitude limit of MV -6.5 and a distance of 300 kpc. Assuming all existing MW satellites contain an appreciable old stellar population and have sizes and luminosities comparable with currently known companions, we predict lower and upper limit totals of 52 and 340 MW dwarf satellites within ~260 kpc if they are uniformly distributed across the sky. This result implies that many MW satellites still remain undetected. Identifying and studying these elusive satellites in future survey data will be fundamental to test the dark matter distribution on kpc scales.
Fuzzy logic is used to define a new quantity called the battery working state (BWS), which is based on both battery terminal voltage and state of charge (SOC), to overcome the problem of battery ...over-discharge and associated damage resulting from inaccurate estimates of the SOC. The BWS is used by a fuzzy logic energy-management system of a plug-in series hybrid electric vehicle (HEV) to make a decision on the power split between the battery and the engine, based on the BWS and vehicle power demand, while controlling the engine to work in its fuel economic region. The fuzzy logic management system was tested in real time using an HEV simulation test bench with a real battery in the loop. Simulation results are presented to demonstrate the performance of the proposed fuzzy logic energy-management system under different driving conditions and battery SOCs. The results indicate that the fuzzy logic energy-management system using the BWS was effective in ensuring that the engine operates in the vicinity of its maximum fuel efficiency region while preventing the battery from over-discharging.
Micronutrient deficiencies (MNDs) remain widespread among people in sub-Saharan Africa
, where access to sufficient food from plant and animal sources that is rich in micronutrients (vitamins and ...minerals) is limited due to socioeconomic and geographical reasons
. Here we report the micronutrient composition (calcium, iron, selenium and zinc) of staple cereal grains for most of the cereal production areas in Ethiopia and Malawi. We show that there is geospatial variation in the composition of micronutrients that is nutritionally important at subnational scales. Soil and environmental covariates of grain micronutrient concentrations included soil pH, soil organic matter, temperature, rainfall and topography, which were specific to micronutrient and crop type. For rural households consuming locally sourced food-including many smallholder farming communities-the location of residence can be the largest influencing factor in determining the dietary intake of micronutrients from cereals. Positive relationships between the concentration of selenium in grain and biomarkers of selenium dietary status occur in both countries. Surveillance of MNDs on the basis of biomarkers of status and dietary intakes from national- and regional-scale food-composition data
could be improved using subnational data on the composition of grain micronutrients. Beyond dietary diversification, interventions to alleviate MNDs, such as food fortification
and biofortification to increase the micronutrient concentrations in crops
, should account for geographical effects that can be larger in magnitude than intervention outcomes.
Objective There is widespread evidence that cancer confers an increased risk of deep venous thrombosis (DVT). This risk is thought to vary among different cancer types. The purpose of this study is ...to better define the incidence of thrombotic complications among patients undergoing surgical treatment for a spectrum of prevalent cancer diagnoses in contemporary practice. Methods All patients undergoing one of 11 cancer surgical operations (breast resection, hysterectomy, prostatectomy, colectomy, gastrectomy, lung resection, hepatectomy, pancreatectomy, cystectomy, esophagectomy, and nephrectomy) were identified by Current Procedural Terminology and International Classification of Diseases, Ninth Revision codes using the American College of Surgeons National Surgical Quality Improvement Program database (2007-2009). The study endpoints were DVT, pulmonary embolism (PE), and overall postoperative venous thromboembolic events (VTE) within 1 month of the index procedure. Multivariate logistic regression was utilized to calculate adjusted odds ratios for each endpoint. Results Over the study interval, 43,808 of the selected cancer operations were performed. The incidence of DVT, PE, and total VTE within 1 month following surgery varied widely across a spectrum of cancer diagnoses, ranging from 0.19%, 0.12%, and 0.28% for breast resection to 6.1%, 2.4%, and 7.3%, respectively, for esophagectomy. Compared with breast cancer, the incidence of VTE ranged from a 1.31-fold increase in VTE associated with gastrectomy (95% confidence interval, 0.73-2.37; P = .4) to a 2.68-fold increase associated with hysterectomy (95% confidence interval, 1.43-5.01; P = .002). Multivariate logistic regression revealed that inpatient status, steroid use, advanced age (≥60 years), morbid obesity (body mass index ≥35), blood transfusion, reintubation, cardiac arrest, postoperative infectious complications, and prolonged hospitalization were independently associated with increased risk of VTE. Conclusions The incidence of VTE and thromboembolic complications associated with cancer surgery varies substantially. These findings suggest that both tumor type and resection magnitude may impact VTE risk. Accordingly, such data support diagnosis and procedural-specific guidelines for perioperative VTE prophylaxis and can be used to anticipate the risk of potentially preventable morbidity.
Abstract The American College of Cardiology third decennial Professional Life Survey was completed by 2,313 cardiologists: 964 women (42%) and 1,349 men (58%). Compared with 10 and 20 years ago, ...current results reflect a substantially lower response rate (21% vs. 31% and 49%, respectively) and an aging workforce that is less likely to be in private practice. Women continue to be more likely to practice in academic centers, be pediatric cardiologists, and have a noninvasive subspecialty. Men were more likely to indicate that family responsibilities negatively influenced their careers than previously, whereas women remained less likely to marry or have children. Men and women reported similar, high levels of career satisfaction, with women reporting higher satisfaction currently. However, two-thirds of women continue to experience discrimination, nearly 3 times the rate in men. Personal life choices continue to differ substantially for men and women in cardiology, although differences have diminished.
Bone marrow lesions (BMLs) are associated with pain in osteoarthritis (OA), but histological scores for OA focus on cartilage pathology. We developed a new scoring system, the Osteoarthritis Bone ...Score (OABS), to characterise OA-related BMLs.
BML/non-BML tissues identified by Magnetic Resonance Imaging (MRI) in 10 knee OA subjects were harvested at total knee replacement (TKR). Osteochondral tissue from a further 140 TKR and 23 post-mortem (PM) cases was assessed. Histological features distinguishing MRI-defined BML/non-BML tissues on qualitative analysis were classified as present (0) or absent (1), summated for the OABS, validated by Rasch analysis and sensitivity to distinguish between sample groups. Immunohistochemistry for PGP9.5 assessed innervation.
Subchondral characteristics associated with BML tissues were cysts, fibrosis, hypervascularity, cartilage islands, trabecular thickening, loss of tidemark integrity and inflammatory cell infiltration. PGP9.5 immunoreactive perivascular nerves were associated with BMLs. OABS performed well as a measurement tool, displayed good reliability (Cronbach alpha = 0.68), had a 2-factor structure (trabecular/non-trabecular), with moderate correlation between the two factors (r = 0.56, 95% CI 0.46, 0.65). OABS scores were higher in TKR than PM cases with chondropathy, median difference 1.5 (95% CI -2, 0). OABS and Mankin scores similarly distinguished TKR from non-OA controls, but only OABS was higher in BML than non-BML tissues, median difference −4 (95% CI -5 to −2).
OABS identifies and validly quantifies histopathological changes associated with OA BMLs. Histopathology underlying BMLs may represent 2 inter-related pathological processes affecting trabecular/non-trabecular structures. Increased vascularity/perivascular innervation in BMLs might contribute to pain.
Highlights • This review is an up-date document on basic aspects of non-invasive stimulation of brain, spinal cord and nerve roots. • The main physiological, theoretical and methodological features ...of transcranial magnetic stimulation (TMS) are described. • Instructions for practical use of non-invasive stimulation in clinical applications and research are provided.
Recent experimental studies performed on human carotid plaques have focused on mechanical characterization for the purpose of developing material models for finite-element analysis without ...quantifying the tissue composition or relating mechanical behaviour to preoperative classification. This study characterizes the mechanical and biological properties of 25 human carotid plaques and also investigates the common features that lead to plaque rupture during mechanical testing by performing circumferential uniaxial tests, Fourier transform infrared (FTIR) and scanning electron microscopy (SEM) on each specimen to relate plaque composition to mechanical behaviour. Mechanical results revealed large variations between plaque specimen behaviour with no correlation to preoperative ultrasound prediction. However, FTIR classification demonstrated a statistically significant relationship between stress and stretch values at rupture and the level of calcification (P=0.002 and P=0.009). Energy-dispersive X-ray spectroscopy was carried out to confirm that the calcium levels observed using FTIR analysis were accurate. This work demonstrates the potential of FTIR as an alternative method to ultrasound forpredicting plaque mechanical behaviour. SEM imaging at the rupture sites of each specimen highlighted voids created by the nodes of calcifications in the tissue structure which could lead to increased vulnerability of the plaque.
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