Challenges of Antibiotic Prescribing for Assisted Living Residents: Perspectives of Providers, Staff, Residents, and Family Members

To better understand the antibiotic prescribing process in assisted living (AL) communities given the growing rates of antibiotic resistance

Virtual Machine Support for Many-Core Architectures: Decoupling Abstract from Concrete Concurrency Models

The upcoming many-core architectures require software developers to exploit concurrency to utilize available computational power. Today's high-level language virtual machines (VMs), which are a cornerstone of software development, do not provide sufficient abstraction for concurrency concepts. We analyze concrete and abstract concurrency models and identify the challenges they impose for VMs. To provide sufficient concurrency support in VMs, we propose to integrate concurrency operations into VM instruction sets. Since there will always be VMs optimized for special purposes, our goal is to develop a methodology to design instruction sets with concurrency support. Therefore, we also propose a list of trade-offs that have to be investigated to advise the design of such instruction sets. As a first experiment, we implemented one instruction set extension for shared memory and one for non-shared memory concurrency. From our experimental results, we derived a list of requirements for a full-grown experimental environment for further research

The Plasma and Suprathermal Ion Composition (PLASTIC) investigation on the STEREO observatories

The Plasma and Suprathermal Ion Composition (PLASTIC) investigation provides the in situ solar wind and low energy heliospheric ion measurements for the NASA Solar Terrestrial Relations Observatory Mission, which consists of two spacecraft (STEREO-A, STEREO-B). PLASTIC-A and PLASTIC-B are identical. Each PLASTIC is a time-of-flight/energy mass spectrometer designed to determine the elemental composition, ionic charge states, and bulk flow parameters of major solar wind ions in the mass range from hydrogen to iron. PLASTIC has nearly complete angular coverage in the ecliptic plane and an energy range from ∼0.3 to 80 keV/e, from which the distribution functions of suprathermal ions, including those ions created in pick-up and local shock acceleration processes, are also provided

A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy

Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naive female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2% sensitivity and 97.8% specificity when tested in an independent validation cohort consisting of 17 treatment-naive Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy

Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract Infections

Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5′UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers

A Cognitive Architecture Based on a Learning Classifier System with Spiking Classifiers

© 2015, Springer Science+Business Media New York. Learning classifier systems (LCS) are population-based reinforcement learners that were originally designed to model various cognitive phenomena. This paper presents an explicitly cognitive LCS by using spiking neural networks as classifiers, providing each classifier with a measure of temporal dynamism. We employ a constructivist model of growth of both neurons and synaptic connections, which permits a genetic algorithm to automatically evolve sufficiently-complex neural structures. The spiking classifiers are coupled with a temporally-sensitive reinforcement learning algorithm, which allows the system to perform temporal state decomposition by appropriately rewarding “macro-actions”, created by chaining together multiple atomic actions. The combination of temporal reinforcement learning and neural information processing is shown to outperform benchmark neural classifier systems, and successfully solve a robotic navigation task

In Vitro Effect of Porphyromonas gingivalis Methionine Gamma Lyase on Biofilm Composition and Oral Inflammatory Response

Methanethiol (methyl mercaptan) is an important contributor to oral malodour and periodontal tissue destruction. Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum are key oral microbial species that produce methanethiol via methionine gamma lyase (mgl) activity. The aim of this study was to compare an mgl knockout strain of P. gingivalis with its wild type using a 10-species biofilm co-culture model with oral keratinocytes and its effect on biofilm composition and inflammatory cytokine production. A P. gingivalis mgl knockout strain was constructed using insertion mutagenesis from wild type W50 with gas chromatographic head space analysis confirming lack of methanethiol production. 10-species biofilms consisting of Streptococcus mitis, Streptococcus oralis, Streptococcus intermedius, Fusobacterium nucleatum ssp polymorphum, Fusobacterium nucleatum ssp vincentii, Veillonella dispar, Actinomyces naeslundii, Prevotella intermedia and Aggregatibacter actinomycetemcomitans with either the wild type or mutant P. gingivalis were grown on Thermanox cover slips and used to stimulate oral keratinocytes (OKF6-TERT2), under anaerobic conditions for 4 and 24 hours. Biofilms were analysed by quantitative PCR with SYBR Green for changes in microbial ecology. Keratinocyte culture supernatants were analysed using a multiplex bead immunoassay for cytokines. Significant population differences were observed between mutant and wild type biofilms; V. dispar proportions increased (p<0.001), whilst A. naeslundii (p<0.01) and Streptococcus spp. (p<0.05) decreased in mutant biofilms. Keratinocytes produced less IL-8, IL-6 and IL-1α when stimulated with the mutant biofilms compared to wild type. Lack of mgl in P. gingivalis has been shown to affect microbial ecology in vitro, giving rise to a markedly different biofilm composition, with a more pro-inflammatory cytokine response from the keratinocytes observed. A possible role for methanethiol in biofilm formation and cytokine response with subsequent effects on oral malodor and periodontitis is suggested