Antibiotic resistance among Ureaplasma spp isolates: cause for concern?

There is growing global concern regarding the rise of antibiotic-resistant organisms. Many of these reports have focused on various Gram-positive and Gram-negative pathogens, with little attention to the genus Ureaplasma. Ureaplasma spp. are associated with numerous infectious diseases affecting pregnant women, neonates and the immunocompromised. Treatment options are extremely limited due to high levels of intrinsic resistance resulting from the unique physiology of these organisms and further restricted in cases of the developing fetus or neonate, often limiting therapeutic options to predominantly macrolides or rarely fluoroquinolones. The increasing presence of macrolide- and fluoroquinolone-resistant strains among neonatal infections may result in pan-drug resistance and potentially untreatable conditions. Here, we review the requirements for accurate measurement of antimicrobial susceptibility, provide a comprehensive review of the antimicrobial resistance (AMR) for Ureaplasma species in the literature and contextualize these results relative to some investigators' reliance on commercial kits that are not CLSI compliant when determining AMR. The dramatic variation in the resistance patterns and impact of high levels of AMR amongst neonatal populations suggests the need for continued surveillance. Commercial kits represent an excellent tool for initial antibiotic susceptibility determination and screening. However, AMR reporting must utilize internationally standardized methods, as high-titre samples, or Mycoplasma hominis-contaminated samples routinely give false AMR results. Furthermore, there is a requirement for future reports to determine the underlying AMR mechanisms and determine whether expanding AMR is due to spontaneous mutation, transmission of resistance genes on mobile elements or selection and expansion of resistant clones

Object localization using deformable templates

Object localization refers to the detection, matching and segmentation of objects in images. The localization model presented in this paper relies on deformable templates to match objects based on shape alone. The shape structure is captured by a prototype template consisting of hand-drawn edges and contours representing the object to be localized. A multistage, multiresolution algorithm is utilized to reduce the computational intensity of the search. The first stage reduces the physical search space dimensions using correlation to determine the regions of interest where a match it likely to occur. The second stage finds approximate matches between the template and target image at progressively finer resolutions, by attracting the template to salient image features using Edge Potential Fields. The third stage entails the use of evolutionary optimization to determine control point placement for a Local Weighted Mean warp, which deforms the template to fit the object boundaries. Results are presented for a number of applications, showing the successful localization of various objects. The algorithm’s invariance to rotation, scale, translation and moderate shape variation of the target objects is clearly illustrated

Estimation of Decay Losses and Dynamic Vacuum for the Beta-beam Accelerator Chain

The beta-beam is based on the acceleration and storage of radioactive ions. Due to the large number of ions required and their relatively short lifetime, beam losses are a major concern. This paper estimates the decay losses for the part of the accelerator chain comprising the CERN PS and SPS machines. For illustration purposes, the power deposition in these accelerators is compared to that expected for nominal CNGS proton operation. The beam losses induced vacuum dynamics is simulated and the consequences for machine operation are discussed

Calcium-dependent regulation of the cell cycle via a novel MAPK–NF-κB pathway in Swiss 3T3 cells

Nuclear factor kappa B (NF-κB) has been implicated in the regulation of cell proliferation and transformation. We investigated the role of the serum-induced intracellular calcium increase in the NF-κB–dependent cell cycle progression in Swiss 3T3 fibroblasts. Noninvasive photoactivation of a calcium chelator (Diazo-2) was used to specifically disrupt the transient rise in calcium induced by serum stimulation of starved Swiss 3T3 cells. The serum-induced intracellular calcium peak was essential for subsequent NF-κB activation (measured by real-time imaging of the dynamic p65 and IκBα fluorescent fusion proteins), cyclin D1 (CD1) promoter-directed transcription (measured by real-time luminescence imaging of CD1 promoter-directed firefly luciferase activity), and progression to cell division. We further showed that the serum-induced mitogen-activated protein kinase (MAPK) phosphorylation is calcium dependent. Inhibition of the MAPK- but not the PtdIns3K-dependent pathway inhibited NF-κB signaling, and further, CD1 transcription and cell cycle progression. These data suggest that a serum-dependent calcium signal regulates the cell cycle via a MAPK–NF-κB pathway in Swiss 3T3 cells

Organic Farming in Wales 2003 - 2004

Organic Centre Wales (OCW) was originally formed to act as an information source for producers enquiring into organic farming; in our second phase, in response to changes in the sector, we have an increased remit on policy issues. It has been a busy time, seeing the production of a second Organic Action Plan, the implementation of the CAP reform and development work on agri-environment reforms. The year also saw the start of organic maintenance payments for farmers. This Annual Report contains accounts of the progress that has been made on many fronts during the last 12 months, particularly in market knowledge due to the research for the recently published report, 'Organic Food: understanding the consumer and increasing sales'. This information, together with continuing product development work, will enable Welsh organic producers to be proactive in building a solid consumer base

Antibiotic resistance among clinical Ureaplasma Isolates Recovered from Neonates in England and Wales between 2007 and 2013

Ureaplasma spp. are associated with numerous clinical sequelae with treatment options being limited due to patient and pathogen factors. This report examines the prevalence and mechanisms of antibiotic resistance among clinical strains isolated from 95 neonates, 32 women attending a sexual health clinic, and 3 patients under investigation for immunological disorders, between 2007 and 2013 in England and Wales. MICs were determined by using broth microdilution assays, and a subset of isolates were compared using the broth microdilution method and the Mycoplasma IST2 assay. The underlying molecular mechanisms for resistance were determined for all resistant isolates. Three isolates carried the tet(M) tetracycline resistance gene (2.3%; confidence interval [CI], 0.49 to 6.86%); two isolates were ciprofloxacin resistant (1.5%; CI, 0.07 to 5.79%) but sensitive to levofloxacin and moxifloxacin, while no resistance was seen to any macrolides tested. The MIC values for chloramphenicol were universally low (2 μg/ml), while inherently high-level MIC values for gentamicin were seen (44 to 66 μg/ml). The Mycoplasma IST2 assay identified a number of false positives for ciprofloxacin resistance, as the method does not conform to international testing guidelines. While antibiotic resistance among Ureaplasma isolates remains low, continued surveillance is essential to monitor trends and threats from importation of resistant clones

Visual experience facilitates allocentric spatial representation

Representing the position of the objects independently from our own position is a fundamental cognitive ability. Here we investigated whether this ability depends on visual experience. Congenitally blind, late blind and blindfolded sighted participants haptically learnt a room-sized regularly shaped array of objects, and their spatial memory was tested to determine which spatial reference frame was used. Crucially, the use of an object-based reference frame requires representing the regular structure of the array. We found that blindfolded sighted and late blind participants, that is those with visual experience, showed a preferential use of the object-based or ‘allocentric’ reference frame. On the contrary, congenitally blind participants preferred a self-based, or egocentric, reference frame. This suggests that, due to its developmental effect on the multisensory brain areas involved in spatial cognition, visual experience is necessary to develop a preference for an object-based, allocentric reference frame

Software Application Profile:mrrobust - A Tool For Performing Two-Sample Summary Mendelian Randomization Analyses

AbstractMotivationIn recent years Mendelian randomization analysis using summary data from genome-wide association studies has become a popular approach for investigating causal relationships in epidemiology. The mrrobust Stata package implements several of the recently developed methods.Implementationmrrobust is freely available as a Stata package.General FeaturesThe package includes inverse variance weighted estimation, as well as a range of median and MR-Egger estimation methods. Using mrrobust, plots can be constructed visualising each estimate either individually or simultaneously. The package also provides statistics such as which are useful in assessing attenuation bias in causal estimates.AvailabilityThe software is freely available from GitHub [https://raw.github.com/remlapmot/mrrobust/master/].</jats:sec

Relationship of Proteinases and Proteinase Inhibitors with Microbial Presence in Chronic Lung Disease of Prematurity

Background: A proteolytic imbalance has been implicated in the development of “classical” chronic lung disease of prematurity (CLD). However, in “new” CLD this pattern has changed. This study examines the longitudinal relationship between neutrophil proteinases and their inhibitors in ventilated preterm infants and their relationship to microbial colonisation. Methods: Serial bronchoalveolar lavage fluid was obtained from ventilated newborn preterm infants. Neutrophil elastase (NE) activity, cell counts, metalloproteinase (MMP)-9, MMP-9/TIMP-1 complex, SerpinB1 concentration and percentage of SerpinB1 and α1-antitrypsin (AAT) in complex with elastase were measured. The presence of microbial genes was examined using PCR for 16S rRNA genes. Results: Statistically more infants who developed CLD had NE activity in at least one sample (10/20) compared with infants with resolved respiratory distress syndrome (RDS) (2/17). However, NE activity was present in a minority of samples, occurring as episodic peaks. Peak levels of MMP-9, MMP-9/TIMP-1 complex, percentage of AAT and SerpinB1 in complex and cell counts were all statistically greater in infants developing CLD than in infants with resolved RDS. Peak values frequently occurred as episodic spikes and strong temporal relationships were noted between all markers. The peak values for all variables were significantly correlated to each other. The presence of bacterial 16S rRNA genes was associated with the development of CLD and with elevated elastase and MMP-9. Conclusion: NE activity and MMP-9 appear to be important in the development of “new” CLD with both proteinase and inhibitor concentrations increasing episodically, possibly in response to postnatal infection