Coping with the Dynamics of Open, Social Media on Mobile Devices with Mobile Facets

When traveling to a foreign city or wanting to know what is happening in one's home area, users today often search and explore dierent social media platforms. In order to provide dierent social media sources in an integrated manner on a mobile device, we have developed Mobile Facets. Mobile Facets allows for the faceted, interactive search and exploration of social media on a touchscreen mobile phone. The social media is queried live from dierent data sources and professional content sources like DBpedia, a Semantic Web version of Wikipedia, the event directories Eventful and Upcoming, geo-located Flickr photos, and GeoNames. Mobile Facets provides an integrated retrieval and interactive exploration of resources from these social media sources such as places, persons, organizations, and events. One does not know in advance how many facets the application will receive from such sources in a specic contextual situation and how many data items for the facets will be provided. Thus, the user interface of Mobile Facets is to be designed to cope with this dynamics of social media

Pharmacometric Characterization of Dabigatran Hemodialysis

BACKGROUND: Hemodialysis has been shown to be a useful method of decreasing dabigatran plasma levels in situations that require rapid elimination of this thrombin inhibitor. However, there is currently no clinical recommendation for the accelerated/optimized elimination of dabigatran via hemodialysis (e.g., flow rates, filter type, duration of dialysis). OBJECTIVES: The primary objective of the present work was to characterize, via pharmacometric methods, the effects of different blood flow rates in hemodialysis on the pharmacokinetics of dabigatran, using data from a dedicated phase I dialysis study of end-stage renal disease (ESRD) patients. In addition, the effects of various clinically relevant hemodialysis settings were evaluated by simulation to assess their potential use in non-ESRD situations. METHODS: Seven patients with ESRD were investigated in an open-label, fixed-sequence, two-period comparison trial. A population pharmacokinetic model was developed to fit the data and then used for various simulations. Data analyses were performed using NONMEM(®), Berkeley Madonna, or SAS. RESULTS: The pharmacokinetics of dabigatran were best described by a two-compartment model with first-order absorption and a lag time. In addition to total body clearance in ESRD subjects, a first-order dialysis clearance was implemented which was greater than zero during hemodialysis and zero during the interdialytic periods. The relationship between the dialysis clearance and the blood flow rate was best described by the Michaels function. Simulations showed that varying clinically relevant dialysis settings such as filter properties or flow rates had only minor effects. Dialysis duration had the strongest impact on dabigatran plasma concentration. The observed geometric mean redistribution effect after hemodialysis was low (<16 %). The final model was successfully evaluated through the prediction of plasma concentrations from a case report undergoing dialysis. CONCLUSIONS: This analysis allowed the influences of various hemodialysis parameters on the dabigatran plasma concentration to be predicted in detail for the first time. Dialysis duration was identified as having the strongest impact on the reduction in dabigatran plasma concentration. The model developed here can potentially serve as a tool to provide guidance when considering the use of hemodialysis in patients who have received dabigatran

Severe infections of Panton-Valentine leukocidin positive Staphylococcus aureus in children

Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures

Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interaction

IntroductionP2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and have been involved in similar physiological processes, such as pain and inflammation as well as various immune cell functions. While formation of P2X2/P2X3 heterotrimers produces a distinct pharmacological phenotype and has been well established, functional identification of a P2X4/P2X7 heteromer has been difficult and evidence for and against a physical association has been found. Most of this evidence stems, however, from in vitro model systems.MethodsHere, we used a P2X7-EGFP BAC transgenic mouse model as well as P2X4 and P2X7 knock-out mice to re-investigate a P2X4-P2X7 interaction in mouse lung by biochemical and immunohistochemical experiments as well as quantitative expression analysis.ResultsNo detectable amounts of P2X4 could be co-purified from mouse lung via P2X7-EGFP. In agreement with these findings, immuno-histochemical analysis using a P2X7-specific nanobody revealed only limited overlap in the cellular and subcellular localizations of P2X4 and P2X7 in both the native lung tissue and primary cells. Comparison of P2X4 and P2X7 transcript and protein levels in the respective gene-deficient and wild type mice showed no mutual interrelation between their expression levels in whole lungs. However, a significantly reduced P2rx7 expression was found in alveolar macrophages of P2rx4-/- mice.DiscussionIn summary, our detailed analysis of the cellular and subcellular P2X4 and P2X7 localization and expression does not support a physiologically relevant direct association of P2X4 and P2X7 subunits or receptors in vivo

Stabilisation of metastable polymorphs: the case of paracetamol form III

YesThe design of a melt synthesis of the first air-stable formulation of the metastable form III of paracetamol is derived from thermo-spectroscopic and thermo-diffraction experiments. Melt crystallisation in the presence of β-1,4-saccharides produces form III selectively and the excipients appear to act as stabilising ‘active’ templates of the metastable polymorph.This article is part of themed collection: Pharmaceutical Solids

Acetaminophen Influences Musculoskeletal Signaling but Not Adaptations to Endurance Exercise Training

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% incline for 2 min at 15 cm/s, 2 min at 20 cm/s, and 26 min at 25 cm/s. A human equivalent dose of ACE was administered (379 mg/kg body weight) in drinking water and adjusted each week based on body weight. Food, water intake, and body weight were measured daily. At the beginning of week 6, animals in the exercise group completed a maximal treadmill test. At the end of week 6, rats were euthanized, and muscle cross-sectional area (CSA), fiber type, and signaling pathways were measured. Additionally, three-point bending and microcomputer tomography were measured in the femur. Follow-up experiments in human primary muscle cells were used to explore supra-physiological effects of ACE. Data were analyzed using a two-way ANOVA for treatment (ACE or placebo) and condition (exercise or non-exercise) for all animal outcomes. Data for cell culture experiments were analyzed via ANOVA. If omnibus significance was found in either ANOVA, a post hoc analysis was completed, and a Tukey\u27s adjustment was used. ACE did not alter body weight, water intake, food intake, or treadmill performance (p \u3e .05). There was a treatment-by-condition effect for Young\u27s Modulus where placebo exercise was significantly lower than placebo control (p \u3c .05). There was no treatment by condition effects for microCT measures, muscle CSA, fiber type, or mRNA expression. Phosphorylated-AMPK was significantly increased with exercise (p \u3c .05) and this was attenuated with ACE treatment. Furthermore, phospho-4EBP1 was depressed in the exercise group compared to the control (p \u3c .05) and increased in the ACE control and ACE exercise group compared to placebo exercise (p \u3c .05). A low dose of ACE did not influence chronic musculoskeletal adaptations in exercising rodents but acutely attenuated AMPK phosphorylation and 4EBP1 dephosphorylation post-exercise

The effect of ISM absorption on stellar activity measurements and its relevance for exoplanet studies

Past ultraviolet and optical observations of stars hosting close-in Jupiter-mass planets have shown that some of these stars present an anomalously low chromospheric activity, significantly below the basal level. For the hot Jupiter planet host WASP-13, observations have shown that the apparent lack of activity is possibly caused by absorption from the intervening interstellar medium (ISM). Inspired by this result, we study the effect of ISM absorption on activity measurements (S and log R'HK indices) for main-sequence late-type stars. To this end, we employ synthetic stellar photospheric spectra combined with varying amounts of chromospheric emission and ISM absorption. We present the effect of ISM absorption on activity measurements by varying several instrumental (spectral resolution), stellar (projected rotational velocity, effective temperature, and chromospheric emission flux), and ISM parameters (relative velocity between stellar and ISM Ca II lines, broadening b-parameter, and Ca II column density). We find that for relative velocities between the stellar and ISM lines smaller than 30–40 km s−1 and for ISM Ca II column densities log NCaII ⪆ 12, the ISM absorption has a significant influence on activity measurements. Direct measurements and three dimensional maps of the Galactic ISM absorption indicate that an ISM Ca II column density of log NCaII = 12 is typically reached by a distance of about 100 pc along most sight lines. In particular, for a Sun-like star lying at a distance greater than 100 pc, we expect a depression (bias) in the log R'HK value larger than 0.05–0.1 dex, about the same size as the typical measurement and calibration uncertainties on this parameter. This work shows that the bias introduced by ISM absorption must always be considered when measuring activity for stars lying beyond 100 pc. We also consider the effect of multiple ISM absorption components. We discuss the relevance of this result for exoplanet studies and revise the latest results on stellar activity versus planet surface gravity correlation. We finally describe methods with which it would be possible to account for ISM absorption in activity measurements and provide a code to roughly estimate the magnitude of the bias. Correcting for the ISM absorption bias may allow one to identify the origin of the anomaly in the activity measured for some planet-hosting stars

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Purpose: The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation. Material and Methods: The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 mu m. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed. Results: GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders. Conclusion: In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney

Aquatic-terrestrial transitions of feeding systems in vertebrates : a mechanical perspective

Transitions to terrestrial environments confront ancestrally aquatic animals with several mechanical and physiological problems owing to the different physical properties of water and air. As aquatic feeders generally make use of flows of water relative to the head to capture, transport and swallow food, it follows that morphological and behavioral changes were inevitably needed for the aquatic animals to successfully perform these functions on land. Here, we summarize the mechanical requirements of successful aquatic-to-terrestrial transitions in food capture, transport and swallowing by vertebrates and review how different taxa managed to fulfill these requirements. Amphibious ray-finned fishes show a variety of strategies to stably lift the anterior trunk, as well as to grab ground-based food with their jaws. However, they still need to return to the water for the intra-oral transport and swallowing process. Using the same mechanical perspective, the potential capabilities of some of the earliest tetrapods to perform terrestrial feeding are evaluated. Within tetrapods, the appearance of a mobile neck and a muscular and movable tongue can safely be regarded as key factors in the colonization of land away from amphibious habitats. Comparative studies on taxa including salamanders, which change from aquatic feeders as larvae to terrestrial feeders as adults, illustrate remodeling patterns in the hyobranchial system that can be linked to its drastic change in function during feeding. Yet, the precise evolutionary history in form and function of the hyolingual system leading to the origin(s) of a muscular and adhesive tongue remains unknown