Interaction of Ketotifen Fumarate with Anhydrous Theophylline in Simulated Gastric and Intestinal Media and Effect on Protein Binding

Purpose: The purpose of the present study was to investigate interaction between ketotifen fumarate and anhydrous theophylline in aqueous media of various pH.Methods: By using Job’s continuous-variation analysis and Ardon’s spectrophotomeric methods, the values of stability constants of theophylline with ketotifen were determined at a fixed temperature (37 0C) at each of the medium pH. In vitro study of protein (bovine albumin, fraction v) binding was carried out by equilibrium dialysis method at pH 7.4 to ascertain the influence of ketotifen on the protein binding of theophylline.Results: Stability constant, ranging between 5.07 and 6.35, were derived from Ardon’s plot, indicating that complexes formed, as a result of interaction between the drugs, were comparatively stable. However, following theophylline interaction with ketotifen, stability constant was < 1 at gastric pH (0.4 and 2.0) and 4.12 at intestinal pH. (6.0)The highest degree of protein binding by ketotifen was 98 % and the lowest 90 %. For theophylline, the highest and lowest degrees of protein binding were 90 and 85 %, respectively.Conclusion: Concurrent administration of ketotifen and theophylline would result in the formation of a stable complex and this is likely to reduce the therapeutic activities of both drugs. With regard to protein binding, the concentration of theophylline increased with decrease in ketotifen concentration.Keywords: Stability constant, Job’s method, Ardon’s method, Ketotifen fumarate, Complex formation, Protein binding, Theophyllin

(Un)informed Consent: Studying GDPR Consent Notices in the Field

Since the adoption of the General Data Protection Regulation (GDPR) in May 2018 more than 60 % of popular websites in Europe display cookie consent notices to their visitors. This has quickly led to users becoming fatigued with privacy notifications and contributed to the rise of both browser extensions that block these banners and demands for a solution that bundles consent across multiple websites or in the browser. In this work, we identify common properties of the graphical user interface of consent notices and conduct three experiments with more than 80,000 unique users on a German website to investigate the influence of notice position, type of choice, and content framing on consent. We find that users are more likely to interact with a notice shown in the lower (left) part of the screen. Given a binary choice, more users are willing to accept tracking compared to mechanisms that require them to allow cookie use for each category or company individually. We also show that the wide-spread practice of nudging has a large effect on the choices users make. Our experiments show that seemingly small implementation decisions can substantially impact whether and how people interact with consent notices. Our findings demonstrate the importance for regulation to not just require consent, but also provide clear requirements or guidance for how this consent has to be obtained in order to ensure that users can make free and informed choices.Comment: 18 pages, 6 figures, 2019 ACM SIGSAC Conference on Computer and Communications Security (CCS '19), November 11-15, 2019, London, United Kingdo

A Randomised Controlled Trial of Two Infusion Rates to Decrease Reactions to Antivenom

Background: Snake envenoming is a major clinical problem in Sri Lanka, with an estimated 40,000 bites annually. Antivenom is only available from India and there is a high rate of systemic hypersensitivity reactions. This study aimed to investigate whether the rate of infusion of antivenom reduced the frequency of severe systemic hypersensitivity reactions. Methods and findings: This was a randomized comparison trial of two infusion rates of antivenom for treatment of non-pregnant adult patients (>14 y) with snake envenoming in Sri Lanka. Snake identification was by patient or hospital examination of dead snakes when available and confirmed by enzyme-immunoassay for Russell’s viper envenoming. Patients were blindly allocated in a 11 randomisation schedule to receive antivenom either as a 20 minute infusion (rapid) or a two hour infusion (slow). The primary outcome was the proportion with severe systemic hypersensitivity reactions (grade 3 by Brown grading system) within 4 hours of commencement of antivenom. Secondary outcomes included the proportion with mild/moderate hypersensitivity reactions and repeat antivenom doses. Of 1004 patients with suspected snakebites, 247 patients received antivenom. 49 patients were excluded or not recruited leaving 104 patients allocated to the rapid antivenom infusion and 94 to the slow antivenom infusion. The median actual duration of antivenom infusion in the rapid group was 20 min (Interquartile range[IQR]:20–25 min) versus 120 min (IQR:75–120 min) in the slow group. There was no difference in severe systemic hypersensitivity reactions between those given rapid and slow infusions (32% vs. 35%; difference 3%; 95%CI:−10% to +17%;p = 0.65). The frequency of mild/moderate reactions was also similar. Similar numbers of patients in each arm received further doses of antivenom (30/104 vs. 23/94). Conclusions: A slower infusion rate would not reduce the rate of severe systemic hypersensitivity reactions from current high rates. More effort should be put into developing better quality antivenoms

Measurement of psychological entitlement in 28 countries

This article presents the cross-cultural validation of the Entitlement Attitudes Questionnaire, a tool designed to measure three facets of psychological entitlement: active, passive, and revenge entitlement. Active entitlement was defined as the tendency to protect individual rights based on self-worthiness. Passive entitlement was defined as the belief in obligations to and expectations toward other people and institutions for the fulfillment of the individual’s needs. Revenge entitlement was defined as the tendency to protect one’s individual rights when violated by others and the tendency to reciprocate insults. The 15-item EAQ was validated in a series of three studies: the first one on a general Polish sample (N = 1,900), the second one on a sample of Polish students (N = 199), and the third one on student samples from 28 countries (N = 5,979). A three-factor solution was confirmed across all samples. Examination of measurement equivalence indicated partial metric invariance of EAQ for all national samples. Discriminant and convergent validity of the EAQ was also confirmed

Symptomatic and Asymptomatic Neurological Complications of Infective Endocarditis: Impact on Surgical Management and Prognosis

International audienceObjectives:Symptomatic neurological complications (NC) are a major cause of mortality in infective endocarditis (IE) but the impact of asymptomatic complications is unknown. We aimed to assess the impact of asymptomatic NC (AsNC) on the management and prognosis of IE.Methods: From the database of cases collected for a population-based study on IE, we selected 283 patients with definite left-sided IE who had undergone at least one neuroimaging procedure (cerebral CT scan and/or MRI) performed as part of initial evaluation.Results Among those 283 patients, 100 had symptomatic neurological complications (SNC) prior to the investigation, 35 had an asymptomatic neurological complications (AsNC), and 148 had a normal cerebral imaging (NoNC). The rate of valve surgery was 43% in the 100 patients with SNC, 77% in the 35 with AsNC, and 54% in the 148 with NoNC (p<0.001). In-hospital mortality was 42% in patients with SNC, 8.6% in patients with AsNC, and 16.9% in patients with NoNC (p<0.001). Among the 135 patients with NC, 95 had an indication for valve surgery (71%), which was performed in 70 of them (mortality 20%) and not performed in 25 (mortality 68%). In a multivariate adjusted analysis of the 135 patients with NC, age, renal failure, septic shock, and IE caused by S. aureus were independently associated with in-hospital and 1-year mortality. In addition SNC was an independent predictor of 1-year mortality.Conclusions The presence of NC was associated with a poorer prognosis when symptomatic. Patients with AsNC had the highest rate of valve surgery and the lowest mortality rate, which suggests a protective role of surgery guided by systematic neuroimaging results

Annual Incidence of Snake Bite in Rural Bangladesh

Snake bite is one of the major causes of morbidity and mortality in many rural tropical areas. As a neglected public health problem, estimate of the risk is largely unknown. However, the associated personal and economic impact of snake bite is substantial across developing countries. This national survey investigated the risk and consequences of snake bite among the rural Bangladeshi population. We surveyed 18857 individuals from 24 out of 64 districts in Bangladesh where 98 snake bites including one death were reported. The estimated incidence density of snake bite is 623.4/ 100,000 person years (95% CI: 513.4–789.2/100,000 person years). Biting occurs mostly when individuals are at work. The majority of the victims (71%) received snake bites to their lower extremities. Eighty-six percent of the victims received some form of management within two hours of snake bite, although only three percent of them went directly to either a medical doctor or a hospital. The observed rate of snake bite in rural Bangladesh is substantially higher than anticipated. This coupled with poor access to health services led to an increase in related morbidity and mortality. An improvement in public health actions is therefore warranted

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO