Crystal structure of Enterobacter cloacae 908R class C beta-lactamase bound to iodo-acetamido-phenyl boronic acid, a transition-state analogue

peer reviewedThe structures of the, class C beta-lactamase from Enterobacter cloacae 908R alone and in complex with a baronic acid transition-state analogue were determined by X-ray crystallography at 2.1 and 2.3 Angstrom, respectively. The structure of the enzyme resembles those of other class C beta-lactamases. The structure of the. complex with the transition-state analogue, iodo-acetamido-phenyl boronic acid, shows that the inhibitor is covalently, bound to the active-site serine (Ser64). Binding of the inhibitor within the active site is compared with previously determined structures of complexes with other class C enzymes. The structure of the boronic acid adduct indicates ways to improve the affinity of this class of inhibitors. This structure of 908R class C beta-lactamase in complex with a transitionstate analogue provides further insights into the mechanism of action of these hydrolases

Temporal Stabilisation of Flux Reconstruction on Linear Problems

Filtering is often used in Large Eddy Simulation with a global filter width, instead here a filter width in the reference domain of high order Flux Reconstruction is considered. It is shown via Von Neumann analysis how filtering effects the dispersion and dissipation of the scheme when spatially and temporally discretised. With it being shown that filtering stabilises the scheme temporally by upto $25\%$ for forth order FR. The impact of filtering on error production is calculated, highlighting the reduction in convective velocity caused and showing numerically the impact on order of accuracy. Finally, the turbulent Taylor-Green case is used to understand the effect of reference domain filtering on the transition to turbulence, and a filter Reynolds number is defined that is shown to be useful in understanding the effect of filtering on simulations.Comment: AIAA Aviation Forum June 201

Increased prevalence of sleep disturbances and daytime sleepiness in subjects with bronchial asthma: a population study of young adults in three European countries

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe aim of this study was to investigate whether asthma is associated with decreased quality of sleep and increased daytime sleepiness. The study involved a random population of 2,202 subjects supplemented by 459 subjects with suspected asthma, aged 20-45 yrs. The subjects were from Reykjavik (Iceland), Uppsala and Göteborg (Sweden) and Antwerp (Belgium), and participated in the European Community Respiratory Health Survey. The investigation included a structured interview, methacholine challenge, skinprick tests and a questionnaire on sleep disturbances. Participants in Iceland and Sweden also estimated their sleep times and made peak expiratory flow (PEF) recordings during a period of 1 week. Asthma was defined as self-reported physician-diagnosed asthma with current asthma-related symptoms (n = 267). Difficulties inducing sleep (DIS) and early morning awakenings (EMA) were about twice as common, and daytime sleepiness 50% more common, in asthmatics compared with subjects without asthma. After adjusting for possible confounders, a positive association was found between asthma and: DIS (odds ratio (OR) = 1.8); EMA (OR = 2.0); daytime sleepiness (OR = 1.6); snoring (OR = 1.7); and self reported apnoeas (OR = 3.7). Allergic rhinitis, which was reported by 71% of subjects with asthma, was independently related to DIS (OR = 2.0) and daytime sleepiness (OR = 1.3). A significant correlation was found between the number of asthma-related symptoms and sleep disturbances (p < 0.001). Asthma is associated with decreased subjective quality of sleep and increased daytime sleepiness. Concurrent allergic rhinitis may be an important underlying cause of sleep impairment in asthmatic patients

Relationship between emergency presentation, systemic inflammatory response, and cancer-specific survival in patients undergoing potentially curative surgery for colon cancer

Background Emergency presentation is recognized to be associated with poorer cancer-specific survival following curative resection for colorectal cancer. The present study examined the hypothesis that an enhanced systemic inflammatory response, prior to surgery, might explain the impact of emergency presentation on survival. Methods In all, 188 patients undergoing potentially curative resection for colorectal cancer were studied. Of these, 55 (29&#37;) presented as emergencies. The systemic inflammatory response was assessed using the Glasgow Prognostic Score (mGPS), which is the combination of an elevated C-reactive protein (&gt;10 mg/L) and hypoalbuminemia (&lt;35 g/L). Results In the emergency group, tumor stage was greater (P &lt; 0.01), more patients received adjuvant therapy (P &lt; 0.01) more patients had an elevated mGPS (P &lt; 0.01), and more patients died of their disease (P &lt; 0.05). The minimum follow-up was 12 months; the median follow-up of the survivors was 48 months. Emergency presentation was associated with poorer 3-year cancer-specific survival in those patients aged 65 to 74 years (P &lt; 0.01), in both males and females (P &lt; 0.05), in the deprived (P &lt; 0.01), in patients with tumor-node-metastasis (TNM) stage II disease (P &lt; 0.01), in those who received no adjuvant therapy (P &lt; 0.01), and in the mGPS 0 and 1 groups (P &lt; 0.05) groups. On multivariate survival analysis of patients undergoing potentially curative surgery for TNM stage II colon cancer, emergency presentation (P &lt; 0.05) and mGPS (P &lt; 0.05) were independently associated with cancer-specific survival. Conclusions These results suggest that emergency presentation and the presence of systemic inflammatory response prior to surgery are linked and account for poorer cancer-specific survival in patients undergoing potentially curative surgery for colon cancer. Both emergency presentation and an elevated mGPS should be taken into account when assessing the likely outcome of these patients

A class of Poisson-Nijenhuis structures on a tangent bundle

Equipping the tangent bundle TQ of a manifold with a symplectic form coming from a regular Lagrangian L, we explore how to obtain a Poisson-Nijenhuis structure from a given type (1,1) tensor field J on Q. It is argued that the complete lift of J is not the natural candidate for a Nijenhuis tensor on TQ, but plays a crucial role in the construction of a different tensor R, which appears to be the pullback under the Legendre transform of the lift of J to co-tangent manifold of Q. We show how this tangent bundle view brings new insights and is capable also of producing all important results which are known from previous studies on the cotangent bundle, in the case that Q is equipped with a Riemannian metric. The present approach further paves the way for future generalizations.Comment: 22 page

Wake up, wake up! It's me! It's my life! patient narratives on person-centeredness in the integrated care context: a qualitative study

Person-centered care emphasizes a holistic, humanistic approach that puts patients first, at the center of medical care. Person-centeredness is also considered a core element of integrated care. Yet typologies of integrated care mainly describe how patients fit within integrated services, rather than how services fit into the patient's world. Patient-centeredness has been commonly defined through physician's behaviors aimed at delivering patient-centered care. Yet, it is unclear how 'person-centeredness' is realized in integrated care through the patient voice. We aimed to explore patient narratives of person-centeredness in the integrated care context

Twin-screw granulation – a systematic analysis of process parameters

Twin-screw granulation has a significant advantage over traditional granulation methods leading to the possibility of continuous manufacturing. Although this technology has drawn attention in recent years, the general understanding of the process is limited. This study gives a brief overview of the most important process parameters and their influence on product quality. Experimental results from a benchtop granulator and an in-line particle size measurement have been analysed. From this basic study conclusions can be drawn how to tailor the particle size distribution in twin-screw granulation. The most crucial parameters are the liquid-to-solid ratio and the filling level of the screws

Changes in the use of anti-asthmatic medication in an international cohort

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe aim of this study was to describe changes in pharmacotherapy for asthma since the early 1990s in an international cohort of young and middle-aged adults. A total of 28 centres from 14 countries participated in a longitudinal study. The study included 8,829 subjects with a mean follow-up time of 8.7 yrs. Change in the prevalence of use for medication was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. The use of anti-asthmatics was found to have increased by 3.1% (2.4-3.7%) and the prevalence of symptomatic asthma by 4.0% (3.5-4.5%). In the sample with asthma in both surveys (n=423), the use of inhaled corticosteroids increased by 12.2% (6.6-17.8%). Despite this, only 17.2% were using inhaled corticosteroids on a daily basis at follow-up. Females with continuous asthma were more likely, compared with males, and smokers with asthma, to have started using inhaled corticosteroids since the first survey. The use of anti-asthmatics has increased in a pattern consistent with current consensus on treatment. However, despite increased use of inhaled corticosteroids, a large majority of subjects with symptomatic asthma do not use this treatment on a daily basis, particularly males and smokers with asthma