Molecular dynamics simulations of oxide memristors: crystal field effects

We present molecular-dynamic simulations of memory resistors (memristors) including the crystal field effects on mobile ionic species such as oxygen vacancies appearing during operation of the device. Vacancy distributions show different patterns depending on the ratio of a spatial period of the crystal field to a characteristic radius of the vacancy-vacancy interaction. There are signatures of the orientational order and of spatial voids in the vacancy distributions for some crystal field potentials. The crystal field stabilizes the patterns after they are formed, resulting in a non-volatile switching of the simulated devices.Comment: 9 pages, 3 figure

First hospital outbreak of the globally emerging Candida auris in a European hospital

Background: Candida auris is a globally emerging multidrug resistant fungal pathogen causing nosocomial transmission. We report an ongoing outbreak of C. auris in a London cardio-thoracic center between April 2015 and July 2016. This is the first report of C. auris in Europe and the largest outbreak so far. We describe the identification, investigation and implementation of control measures. Methods: Data on C. auris case demographics, environmental screening, implementation of infection prevention/control measures, and antifungal susceptibility of patient isolates were prospectively recorded then analysed retrospectively. Speciation of C. auris was performed by MALDI-TOF and typing of outbreak isolates performed by amplified fragment length polymorphism (AFLP). Results: This report describes an ongoing outbreak of 50 C. auris cases over the first 16 month (April 2015 to July 2016) within a single Hospital Trust in London. A total of 44 % (n = 22/50) patients developed possible or proven C. auris infection with a candidaemia rate of 18 % (n = 9/50). Environmental sampling showed persistent presence of the yeast around bed space areas. Implementation of strict infection and prevention control measures included: isolation of cases and their contacts, wearing of personal protective clothing by health care workers, screening of patients on affected wards, skin decontamination with chlorhexidine, environmental cleaning with chorine based reagents and hydrogen peroxide vapour. Genotyping with AFLP demonstrated that C. auris isolates from the same geographic region clustered. Conclusion: This ongoing outbreak with genotypically closely related C. auris highlights the importance of appropriate species identification and rapid detection of cases in order to contain hospital acquired transmission

Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis

Acknowledgements: The authors would like to acknowledge Fraser P. Coxon and Ian Ganley for providing LC3-GFP-mCherry BMDMs. M.S.G. was supported by an FEMS research grant and F.L.v.d.V. was supported by ZonMW under the name EURO-CMC frame of E-Rare-2, the ERA-Net for Research on Rare Diseases.Peer reviewe

Different colonization patterns of Aspergillus terreus in patients with cystic fibrosis

Due to the abnormal viscosity of airway secretions, patients with cystic fibrosis (CF) are athigh risk of fungal colonization of the respiratory tract. Aspergillus fumigatus is by far the most common fungal specie encountered in the CF context, but other species are increasingly reported such as Scedosporium spp. or Geosmithia argillacea, as well as other aspergilli including Aspergillus terreus. In our experience, this saprophytic fungus ranks the third among the filamentous fungi colonizing the respiratory tract of CF patients. Additionally, although relatively uncommon, infections caused by A. terreus present a high mortality rate due to its usually low susceptibility to systemic antifungals. Nevertheless, little is known about the epidemiology of A. terreus colonization/infections. In the present study, nine short tandem repeats of A. terreus were used to genotype 122 clinical isolates recovered from sputum samples from five patients with CF followed-up in two distinct hospitals in France (Angers and Giens hospitals). Sputum samples were collected over a two-month to seven-year period depending on the patients, and for each sample, all the obtained isolates were studied, with a maximum of five per sample. Three colonization patterns were observed. The first colonization pattern consisted of a chronic colonization (defined as the presence of the same genotype in at least two successive samples collected over a minimum period of two months) by a largely dominant genotype associated with two or three other genotypes found occasionally (patient 4) or over a short period (patient 3). The second colonization pattern consisted of a chronic colonization by two distinct genotypes simultaneously detected (patients 1 and 2). For the last patient (patient 5), who was followed during four years, 16 isolates recovered from 6 sputum samples were analyzed, corresponding to 8 genetically distinct genotypes which succeeded to each other. Numerous questions therefore raise from these different colonization patterns, regarding (i) the origin of the contamination of the patients by this relatively uncommon environmental fungus, (ii) the differences between genotypes in their ability to chronically colonize the airways of the CF patients, or (iii) the differences between CF patients in their individual susceptibility to same genotypes

Molecular dynamics simulations of oxide memory resistors (memristors)

Reversible bipolar nano-switches that can be set and read electronically in a solid-state two-terminal device are very promising for applications. We have performed molecular-dynamics simulations that mimic systems with oxygen vacancies interacting via realistic potentials and driven by an external bias voltage. The competing short- and long-range interactions among charged mobile vacancies lead to density fluctuations and short-range ordering, while illustrating some aspects of observed experimental behavior, such as memristor polarity inversion.Comment: 15 pages, 5 figure

Different colonization patterns of Aspergillus terreus in patients with cystic fibrosis

Patients with cystic fibrosis (CF) are at high risk of colonization of the respiratory tract by filamentous fungi, mainly Aspergillus fumigatus, but also other Aspergillus species including A. terreus. In our experience, this last fungus ranks the third among the filamentous fungi colonizing the respiratory tract of CF patients. Additionally, although uncommon, infections caused by A. terreus present a high mortality rate due to its usually low susceptibility to systemic antifungals. The recent development of a microsatellite typing system allowed us to investigate the molecular epidemiology of the airway colonization by this fungus in CF. Nine short tandem repeats of A. terreus were used to genotype multiple and sequential isolates from sputum samples from CF patients followed-up in Angers and Giens hospitals (France). Sputum samples were collected over a 2 month to 7 year period, and for each sample, all the obtained isolates were studied, with a maximum of five per sample. Thus a total of 122 isolates was studied, corresponding to 47 samples collected from 5 distinct patients. Three colonization patterns were observed. The first one consisted of a chronic colonization (presence of the same genotype in at least two successive samples collected over a minimum period of two months) by a largely dominant genotype associated with two or three other genotypes found occasionally (patient 1) or over a short period (patient 2). The second pattern consisted of a chronic colonization by two distinct genotypes simultaneously detected (patients 3 and 4). For the last patient (patient 5), 16 isolates recovered from 6 sputum samples collected during four years were analyzed, corresponding to 8 distinct genotypes which succeeded to each other. Numerous questions rise from these different colonization patterns, relatively uncommon environmental fungus; and (ii) differences between genotypes in their ability to chronically colonize the airways of the CF patients or differences between CF patients in their individual susceptibility to same genotypes. Strikingly, some genotypes shared by some patients were responsible for a chronic colonization in some patients while they rapidly disappear in other patients. A multicenter study should be conducted combining genetic study of the host and genotyping of fungal isolates, searching for predisposing factors to the airway colonization by A. terreus

Epidemiology of airway colonization by Scedosporium apiospermum during cystic fibrosis

With a frequency of about 10%, species of the Scedosporium apiospermum complex (which comprises at least five distinct species with different antifungal susceptibility patterns) rank the second among the filamentous fungi colonizing the airways in cystic fibrosis (CF). Additionally, it is clearly established that these fungi may disseminate in case of immunodeficiency and that a chronic colonization of the airways by these pathogens may hinder the success of lung transplantation. In this study, we develop a new genotyping method to investigate the epidemiology of the airway colonization by these fungi. 63 multiple and sequential isolates of S. apiospermum collected from 9 CF patients, and selected among those previously studied by random amplification of polymorphic DNA (RAPD), were analyzed using the automated typing system DiversiLab (bioMérieux) based on PCR amplification of repetitive sequences. The DiversiLab Aspergillus rep-PCR kit which uses specific primers designed for Aspergillus fumigatus, was compared with the pan-fungus DiversiLab Fungal kit. Amplification products were separated by capillary electrophoresis on Agilent B2100 bioanalyzer, leading to single profiles for each isolate which were then compared using the DiversiLab software. In addition, species identification of these isolates was clarified by sequencing the betatubulin gene. Results obtained with both kits were comparable. Nevertheless, differentiation was easier using the DiversiLab Fungal kit. Additionally, rep-PCR usually confirmed the colonization patterns described by RAPD. Only two patients showed distinct genotypes. For Patient 2, two isolates were analyzed which were undistinguishable by RAPD, but rep-PCR revealed that they belonged to distinct genotypes, suggesting a transient colonization. For Patient 8 which showed by RAPD two distinct genotypes, 5 genotypes were found by rep-PCR with a dominant one represented by 5 isolates and two very close genotypes (corresponding to 3 isolates), while 4 other isolates belonged to two distant genotypes. In conclusion, the automated typing system DiversiLab proved to be an easy and efficient method to investigate the molecular epidemiology of the airway colonization by S. apiospermum in CF. Our results also confirm the capacity of the different species from the S. apiospermum complex to chronically colonize the airways of CF patients

Molecular dynamics simulations of oxide memristors: thermal effects

We have extended our recent molecular-dynamic simulations of memristors to include the effect of thermal inhomogeneities on mobile ionic species appearing during operation of the device. Simulations show a competition between an attractive short-ranged interaction between oxygen vacancies and an enhanced local temperature in creating/destroying the conducting oxygen channels. Such a competition would strongly affect the performance of the memristive devices.Comment: submit/0169777; 6 pages, 4 figure

Trial protocol OPPTIMUM : does progesterone prophylaxis for the prevention of preterm labour improve outcome?

Background Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth). Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth. Methods/Design The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks), improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites. Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome

The <i>Plasmodium</i> eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands

Sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in the insect salivary glands. Sporozoites only differentiate inside of the hepatocytes of the mammalian host. We show that sporozoite latency is an active process controlled by a eukaryotic initiation factor-2α (eIF2α) kinase (IK2) and a phosphatase. IK2 activity is dominant in salivary gland sporozoites, leading to an inhibition of translation and accumulation of stalled mRNAs into granules. When sporozoites are injected into the mammalian host, an eIF2α phosphatase removes the PO4 from eIF2α-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2α is not phosphorylated and the parasites transform prematurely into liver stages and lose their infectivity. Thus, to complete their life cycle, Plasmodium sporozoites exploit the mechanism that regulates stress responses in eukaryotic cells