Evaluation of onset of pain relief from micronized aspirin in a dental pain model

A new formulation of a micronized acetylsalicylic acid swallowable tablet with an effervescent component (FR-aspirin) was evaluated in two independent studies using the dental impaction pain model. These clinical studies were performed to confirm the results of preclinical dissolution studies and human pharmacokinetic studies, which indicated an improved onset of analgesia without compromising duration of effect or safety. Study 1 evaluated a 650-mg dose of aspirin and Study 2 evaluated a 1,000-mg dose of aspirin. Both studies were double-blinded, parallel group and compared to regular aspirin (R-aspirin) and placebo. Speed of onset was measured by the double stopwatch method for time to both first perceptible relief and meaningful relief. In both studies, the FR-aspirin was significantly faster (p < 0.038–0.001) than both R-aspirin and placebo for both onset measures. There were no significant differences between FR-aspirin and R-aspirin for peak or total effects and both treatments were significantly better than placebo. For first perceptible relief, FR-aspirin onset was 19.8 and 16.3 min for 650 mg and 1,000 mg, respectively, compared to 23.7 and 20.0 for R-aspirin. For meaningful relief, FR-aspirin onset was 48.9 and 49.4 min for 650 mg and 1,000 mg, respectively, compared to 119.2 and 99.2 for R-aspirin. These efficacy studies clearly demonstrate that the onset of analgesic efficacy is dramatically improved by adding an effervescent component and micronized active ingredient to the swallowable tablet aspirin formulation. The enhanced onset did not adversely impact either the peak effect or duration of effect or tolerability compared to regular aspirin

Gastrointestinal Safety of Aspirin for a High-Dose, Multiple-Day Treatment Regimen: A Meta-Analysis of Three Randomized Controlled Trials

Background and Aim: Aspirin is a commonly used over-the-counter (OTC) agent for the symptomatic treatment of acute pain, fever, or the common cold, but data regarding safety in this context are limited. In order to characterize the safety of aspirin beyond single-dose or long-term use data, we conducted a meta-analysis of multiple-dose, multiple-day studies of OTC aspirin at a label-approved dosage. Methods: We conducted a meta-analysis of individual patient data from three Bayer-sponsored studies. The meta-analysis was performed in 2015; the individual studies were conducted between 2008 and 2012 and were of a randomized, parallel-group, placebo-controlled design. Patients received a minimum dosage of aspirin of 2000 mg/day over at least 3 days. The endpoints were patient-reported adverse events (AEs) with an emphasis on the system organ class gastrointestinal system. Event incidences were estimated and an analysis of the odds ratios (ORs) and risk differences (RDs) of aspirin versus placebo were performed. Results: Of the 819 patients included, 433 were treated with aspirin and 386 were treated with placebo. The majority of patients (85.7 %) received a median dose of aspirin of 3000 mg/day for 3 days. The incidence of the overall AEs was low and rates were comparable between the aspirin (10.9 %) and placebo (12.4 %) groups [OR: 0.86 (95 % confidence interval [CI] 0.56, 1.34); RD: -1.49 (95 % CI -6.01, 3.03)]. Gastrointestinal AEs were more common in subjects treated with aspirin (7.4 %) than with placebo (5.4 %), and although this difference did not reach statistical significance, a trend towards increased risk was observed with aspirin use [OR: 1.41 (95 % CI 0.78, 2.54); RD: 2.00 (95 % CI -1.35, 5.35)]. Nausea, upper abdominal pain, dyspepsia, and diarrhea were the most frequently reported gastrointestinal AEs. There were no reports of serious gastrointestinal complications such as bleeding, perforation, or ulceration.: Conclusions: The multiple-dose regimen of aspirin used for several days according to the OTC label is well-tolerated by otherwise healthy non-elderly subjects for short-term and symptomatic treatment of pain, fever, and the common cold. There were no reports of serious gastrointestinal complications in either of the groups

Detecting and characterizing lateral phishing at scale

We present the first large-scale characterization of lateral phishing attacks, based on a dataset of 113 million employee-sent emails from 92 enterprise organizations. In a lateral phishing attack, adversaries leverage a compromised enterprise account to send phishing emails to other users, benefit-ting from both the implicit trust and the information in the hijacked user's account. We develop a classifier that finds hundreds of real-world lateral phishing emails, while generating under four false positives per every one-million employee-sent emails. Drawing on the attacks we detect, as well as a corpus of user-reported incidents, we quantify the scale of lateral phishing, identify several thematic content and recipient targeting strategies that attackers follow, illuminate two types of sophisticated behaviors that attackers exhibit, and estimate the success rate of these attacks. Collectively, these results expand our mental models of the 'enterprise attacker' and shed light on the current state of enterprise phishing attacks

GazeConduits: Calibration-Free Cross-Device Collaboration through Gaze and Touch

We present GazeConduits, a calibration-free ad-hoc mobile interaction concept that enables users to collaboratively interact with tablets, other users, and content in a cross-device setting using gaze and touch input. GazeConduits leverages recently introduced smartphone capabilities to detect facial features and estimate users' gaze directions. To join a collaborative setting, users place one or more tablets onto a shared table and position their phone in the center, which then tracks users present as well as their gaze direction to determine the tablets they look at. We present a series of techniques using GazeConduits for collaborative interaction across mobile devices for content selection and manipulation. Our evaluation with 20 simultaneous tablets on a table shows that GazeConduits can reliably identify which tablet or collaborator a user is looking at

A Fistful of Bitcoins: Characterizing Payments among Men with No Names

Bitcoin is a purely online virtual currency, unbacked by either physical commodities or sovereign obligation; instead, it relies on a combination of cryptographic protection and a peer-to-peer protocol for witnessing settlements. Consequently, Bitcoin has the unintuitive property that while the ownership of money is implicitly anonymous, its flow is globally visible. In this paper we explore this unique characteristic further, using heuristic clustering to group Bitcoin wallets based on evidence of shared authority, and then using re-identification attacks (i.e., empirical purchasing of goods and services) to classify the operators of those clusters. From this analysis, we consider the challenges for those seeking to use Bitcoin for criminal or fraudulent purposes at scale

The transient IDEMIX model as a nonorographic gravity wave parameterization in an atmospheric circulation model

The Internal wave Dissipation, Energy and Mixing (IDEMIX) model presents a novel way of parameterizing internal gravity waves in the atmosphere. Using a continuous full wave spectrum in the energy balance equation and integrating over all vertical wavenumbers and frequencies results in prognostic equations for the energy density of gravity waves in multiple azimuthal compartments. It includes their non-dissipative interaction with the mean flow, allowing for an evolving and local description of momentum flux and gravity wave drag. A saturation mechanism maintains the wave field within convective stability limits, and an energetically consistent closure for critical-layer effects controls how much wave flux propagates from the troposphere into the middle atmosphere. IDEMIX can simulate zonal gravity wave drag around the mesopause, similar to a traditional gravity wave parameterization and to a state-of-the-art wave ray tracing model in an atmospheric circulation model. In addition, IDEMIX shows a reversal of the gravity wave drag around the mesopause region due to changes in the momentum flux there. When compared to empirical model data, IDEMIX captures well the summer hemisphere flow reversal, the cold summer mesospheric pole and the alternate positive and negative structures in the meridional mean flow.Comment: 21 pages, 19 figure

Photo editing: Enhancing social media images to reflect appearance ideals

Many of the images used in traditional forms of mass media have been modified to portray unrealistic and idealised beauty characteristics. Further to this, members of the general public have now begun to digitally enhance their own pictures for social media posts, in order to fulfil these often unattainable standards. Ella Guest explores the impact exposure to idealised images of peers may have on health and wellbein

Short-term acetylsalicylic acid (aspirin) use for pain, fever, or colds - Gastrointestinal adverse effects: A meta-analysis of randomized clinical trials

Background and Aim: Acetylsalicylic acid (ASA [aspirin]) is a commonly used over-the-counter drug for the treatment of pain, fever, or colds, but data on the safety of this use are very limited. The aim of this study was to provide data on the safety of this treatment pattern, which is of interest to clinicians, regulators, and the public. Methods: A meta-analysis of individual patient data from 67 studies sponsored by Bayer HealthCare was completed. The primary endpoints were patient-reported gastrointestinal (GI) adverse events (AEs); the secondary endpoints were the incidence of patient-reported non-GI AEs. Event incidence and odds ratios (ORs) based on Cochran-Mantel-Haenszel estimates are reported. In total, 6181 patients were treated with ASA, 3515 with placebo, 1145 with acetaminophen (paracetamol), and 754 with ibuprofen. Exposure to ASA was short term (82.5% of patients had a single dose). Results: GI AEs were more frequent with ASA (9.9%) than with placebo (9.0%) [OR 1.3; 95% CI 1.1, 1.5]. Dyspeptic symptoms were infrequent (4.6% in placebo subjects). The ORs for ASA were 1.3 (95% CI 1.1, 1.6) versus placebo; 1.55 (95% CI 0.7, 3.3) versus ibuprofen; and 1.04 (95% CI 0.8, 1.4) versus acetaminophen. There were very few serious GI AEs (one ASA case; three placebo cases). No differences were found for non-GI AEs and no cases of cerebral hemorrhage were reported. Conclusion: Short-term, mostly single-dose exposure to ASA for the treatment of pain, fever, or colds was associated with a small but significant increase in the risk of dyspepsia relative to placebo.No serious GI complications were reported

MS-GWaM: A 3-dimensional transient gravity wave parametrization for atmospheric models

Parametrizations for internal gravity waves in atmospheric models are traditionally subject to a number of simplifications. Most notably, they rely on both neglecting wave propagation and advection in the horizontal direction (single-column assumption) and an instantaneous balance in the vertical direction (steady-state assumption). While these simplifications are well justified to cover some essential dynamic effects and keep the computational effort small it has been shown that both mechanisms are potentially significant. In particular, the recently introduced Multiscale Gravity Wave Model (MS-GWaM) successfully applied ray-tracing methods in a novel type of transient but columnar internal gravity wave parameterization (MS-GWaM-1D). We extend this concept to a three-dimensional version of the parameterization (MS-GWaM-3D) to simulate subgrid-scale non-orographic internal gravity waves. The resulting global wave model -- implemented into the weather-forecast and climate code ICON -- contains three-dimensional transient propagation with accurate flux calculations, a latitude-dependent background source, and convectively generated waves. MS-GWaM-3D helps reproducing expected temperature and wind patterns in the mesopause region in the climatological zonal mean state and thus proves a viable IGW parameterization. Analyzing the global wave action budget, we find that horizontal wave propagation is as important as vertical wave propagation. The corresponding wave refraction includes previously missing but well-known effects such as wave refraction into the polar jet streams. On a global scale, three-dimensional wave refraction leads to a horizontal flow-dependent redistribution of waves such that the structures of the zonal mean wave drag and consequently the zonal mean winds are modified.Comment: 39 pages, 9 figures; This Work has been submitted to the Journal of Atmospheric Sciences. Copyright in this Work may be transferred without further notic