24 research outputs found
Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies.
OBJECTIVE: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy.
METHODS: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical control threshold (65.3%).
RESULTS: Pooled exit rates were as follows: ESL 1,600 mg = 20.6% (95% confidence interval: 15.6%-26.8%); ESL 1,200 mg = 30.8% (23.0%-40.5%). Use of 2 baseline AEDs or rescue medication, US location, epilepsy duration ≥20 years, and higher maximum baseline seizure frequency were associated with higher exit risks. Median percent reductions in standardized seizure frequency between baseline and the 18-week double-blind period were as follows: ESL 1,600 mg = 43.2%; ESL 1,200 mg = 35.7%; baseline carbamazepine use was associated with smaller reductions. Safety profiles were similar between ESL doses.
CONCLUSIONS: Exit rates for ESL monotherapy (1,600 mg and 1,200 mg once daily) were lower than the historical control threshold, irrespective of baseline AED use and region, with no additional safety concerns identified. Clinical factors and location clearly influence treatment responses in conversion-to-monotherapy trials.
CLASSIFICATION OF EVIDENCE: This pooled analysis provides Class IV evidence that for adults with medically uncontrolled partial-onset seizures, ESL monotherapy is well tolerated and effective
Age-related changes in EEG coherence
Background and purpose
Coherence changes can reflect the pathophysiological processes involved in human ageing. We conducted a retrospective population study that sought to analyze the age-related changes in EEG coherence in a group of 17,722 healthy professional drivers.
Materials and methods
The EEGs were obtained using a standard 10–20 electrode configuration on the scalp. The recordings from 19 scalp electrodes were taken while the participants’ eyes were closed. The linear correlations between the age and coherence were estimated by linear regression analysis.
Results
Our results showed a significant decrease in coherence with age in the theta and alpha bands, and there was an increasing coherence with the beta bands. The most prominent changes occurred in the alpha bands. The delta bands contained movement artefacts, which most likely do not change with age.
Conclusions
The age-related EEG desynchrony can be partly explained by the age-related reduction of cortical connectivity. Higher frequencies of oscillations require less cortical area of high coherence. These findings explain why the lowest average coherence values were observed in the beta and sigma bands, as well as why the beta bands show borderline statistical significance and the sigma bands show non-significance. The age-dependent decrease in coherence may influence the estimation of age-related changes in EEG energy due to phase cancellation
Sea ice working group (SIP)
The sea ice is a crucial component of
the polar climate system, and has
an impact on albedo, heat and gas ex-
change, primary productivity and car-
bon export, atmospheric and ocean
circulation, freshwater budget, ocean
stratification, and deep water mass for-
mation. It is therefore critical that it is
correctly specified as a forcing or pre-
dicted as a feedback in modeling stud-
ies
A Phase 2 Randomized Controlled Trial of the Efficacy and Safety of Cannabidivarin as Add-on Therapy in Participants with Inadequately Controlled Focal Seizures
Antiepileptic drug; Cannabinoid; EpilepsyFármaco antiepiléptico; Cannabinoide; EpilepsiaFàrmac antiepilèptic; Cannabinoide; EpilèpsiaObjective: We assessed the efficacy, safety, and tolerability of cannabidivarin (CBDV) as add-on therapy in adults with inadequately controlled focal seizures.
Materials and Methods: One hundred and sixty-two participants (CBDV n=81; placebo n=81) were enrolled. After a 4-week baseline, participants titrated from 400 to 800 mg CBDV twice daily (b.i.d.) (or placebo) over 2 weeks, followed by 6 weeks stable dosing (at 800 mg b.i.d.) and a 12-day taper period. The primary endpoint was the change from baseline in focal seizure frequency during the 8-week treatment period. Secondary endpoints included additional efficacy measures relating to seizures, physician- and participant-reported outcomes, change in the use of rescue medication, cognitive assessments, and safety.
Results: Median baseline focal seizure frequencies were 17–18 per 28 days in both groups, and similar reductions in frequency were observed in the CBDV (40.5%) and placebo (37.7%) groups during the treatment period (treatment ratio [% reduction] CBDV/placebo: 0.95 [4.6]; confidence interval: 0.78–1.17 [−16.7 to 21.9]; p=0.648). There were no differences between the CBDV and placebo groups for any seizure subtype. There were no significant treatment differences between CBDV and placebo groups for any of the secondary efficacy outcome measures. Overall, 59 (72.8%) of participants in the CBDV group and 39 (48.1%) in the placebo group had ≥1 treatment-emergent adverse event (AE); the 3 most common were diarrhea, nausea, and somnolence. The incidence of serious AEs was low (3.7% in the CBDV group vs. 1.2% in the placebo group). There was little or no effect of CBDV on vital signs, physical examination, or electrocardiogram findings. Elevations in serum transaminases (alanine aminotransferase or aspartate aminotransferase) to levels >3×upper limit of normal occurred in three participants taking CBDV (two discontinued as a result) and one taking placebo; however, none met the criteria for potential Hy's Law cases.
Conclusion: It is likely the 40.5% seizure reduction with CBDV represents an appropriate pharmacological response in this population with focal seizures. The placebo response was, however, high, which may reflect the participants' expectations of CBDV, and a treatment difference from placebo was not observed. CBDV was generally well tolerated.The trial was sponsored by GW Research Ltd
Adsorption and time dependent fixation of uranium (VI) in synthetic and natural matrices
Disposal of low level radioactive liquid waste to soil is commonly practiced. Therefore, sorption of uranium from aqueous solution and fixation of uranium into soil are processes which are crucial to the attenuation of uranium and protection of groundwater. Exposure of human populations is either by direct water consumption or through crop irrigation and transfer into the food chain. In this study a range of materials, including natural materials (e.g. biochar and the natural zeolites ‘Chabazite and Mordenite’) and the synthetic zeolite ‘Faujasite-X’, were investigated as potential adsorbents for UVI from aqueous solution. A range of experiments were carried out to investigate the efficacy of using these adsorbents to successfully adsorb and fix UVI from aqueous solutions. These included sorption and desorption experiments, quantifying time-dependent fixation of UVI and applying kinetic models of this process and measuring isotopically exchangeable UVI within adsorbent materials when possible. The factors affecting adsorption processes, such as solution pH, initially added UVI concentrations and adsorption contact time, were also investigated. Speciation of U in the solution phase was investigated using the Windermere Humic Aqueous Model (WHAM-VII). Saturation indices of potential solid phases were also configured using known solubility products and the free ion activities predicted from the speciation model, WHAM-VII.
Mordenite zeolite showed a poor adsorption affinity for UVI as the solution pH was continuously buffered towards high pH values > 6.5 which favours UVI ion solubilisation as a result of uranyl carbonate complex formation. Uranium (VI) ion adsorption on chabazite at pH 4.7 at 20 oC was found to fit the Freundlich adsorption isotherm but the optimised equation parameters were unique for each contact time of 1, 5, 10, 20 and 30 days. The time-dependent fixation of UVI on chabazite was found to follow an irreversible first-order kinetic equation and an intraparticle diffusion model suggesting slow penetration of chabazite porous structure following initial surface adsorption. Isotopically exchangeable 238UVI (the E-value, UE) adsorbed on chabazite showed that > 65% of initially added UVI remained isotopically exchangeable.
Faujasite-X also showed time-dependent fixation of UVI over 35 days of adsorption contact time at pH values 4, 5 and 6. The adsorption kinetics were best described by an irreversible first-order equation and a spherical diffusion model. Desorption trends showed that UVI adsorption into faujasite- X was almost wholly irreversible. Saturation indices calculated from the solubility products and free ion activities of constituent ions showed that the fixation of UVI was not controlled by the precipitation of any solid phase investigated at the studied range of pH values.
Bone biochar, a by-product from the production of biofuel and syngas by gasification, was tested as a material for adsorption and fixation of UVI from aqueous solutions. A batch experiment was conducted to study the factors that influence the adsorption and time-dependent fixation on biochar at 20◦C, including pH, initial concentration of UVI and contact time. Uranium (UVI) adsorption was highly dependent on pH. However, it was found that UVI adsorption on biochar was high over a wide range of pH values, from 4.5 to 9.0, and adsorption strength was time-dependent over several days. The experimental data for pH> 7 were most effectively modelled using a Freundlich adsorption isotherm coupled to a reversible first order kinetic equation to describe the time-dependent fixation of UVI within the biochar structure. Desorption experiments showed that UVI was only sparingly desorbable from the biochar with time and isotopic dilution with 233UVI confirmed the low, and time-dependent, lability of adsorbed 238UVI. Below pH 7 the adsorption isotherm trend suggested that precipitation, rather than true adsorption, may occur. Across all pH values (4.5–9) measured saturation indices suggested precipitation was possible: autunite below pH 6.5 and swartzite, liebigite or bayleyite above pH 6.5
Another source of bone biochar with a fraction size of (20x 60 mesh) was investigated as candidate materials for soil remediation. Its ability both to adsorb uranium and to render it non-labile (i.e. chemically inactive) was tested by addition to a wide range of soils recently spiked with 238UVI and incubated under moist conditions. The overall aim was to recommend improved strategies for immobilisation of uranium in soils subject to application of low level radioactive waste solutions. Several measurements were made to assess possible reductions in U availability from biochar addition, including U solubility in 0.01 M Ca(NO3)2, exchangeability in 1 M Mg(NO3)2 solution and isotopic dilution with 233U and 236U. Results showed that 41.3 %, 27.6%, 28.9% and 31.7% were isotopically exchangeable on average for soil amended with 0%, 3%, 5% and 10% loading of biochar, but overall there appeared to be only marginal advantages in adding even large concentrations of biochar to soil. The major factor controlling U solubility, exchangeability and lability was soil pH and the pH value resulting from biochar, rather than the biochar itself. Therefore, while the use of biochar to effectively remove U from water is clear, its role in adsorbing U in the highly buffered soil environment is probably minimal
Opicapone as adjunct to levodopa in treated Parkinson's disease without motor complications: A randomized clinical trial
BACKGROUND: Catechol-O-methyl transferase (COMT) inhibitors are routinely used to manage motor fluctuations in Parkinson's disease (PD). We assessed the effect of opicapone on motor symptom severity in levodopa-treated patients without motor complications. METHODS: This was a randomized, double-blind, 24-week, placebo-controlled study of opicapone 50 mg as adjunct to levodopa (NCT04978597). Levodopa-treated patients without motor complications were randomized to 24 weeks of double-blind treatment with adjunct opicapone 50 mg or matching placebo. The primary efficacy endpoint was the mean change from baseline to week 24 in Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) total score. RESULTS: A total of 355 patients were randomized (opicapone 50 mg n = 177, placebo n = 178) and 322 (91%) completed the double-blind period. The adjusted mean [95% CI] change from baseline to week 24 in MDS-UPDRS-III subscore was -6.5 [-7.9, -5.2] in the opicapone group versus -4.3 [-5.7, 3.0] in the placebo group resulting in a significant difference of -2.2 [-3.9, -0.5] favoring opicapone (p = 0.010). There was no difference in the incidence of patients who developed motor complications (5.5% with opicapone vs. 9.8% with placebo) and the incidence of adverse events considered related to study medication was similar between groups (opicapone 10.2% vs. placebo 13.5%). CONCLUSIONS: Treatment with once-daily adjunct opicapone was well tolerated, improved motor severity, and did not induce the development of motor complications. These results support the clinical usefulness of opicapone in the management of PD patients without motor complications
Online ordering system for restaurants using QR codes
Tato bakalářská práce se zabývá návrhem a implementací online objednávkového systému pro restaurace, který využívá QR kódy k propojení zákazníka s digitálním menu, objednávkami a platbami. Cílem systému je zrychlení obsluhy, snížení provozní zátěže personálu a zvýšení komfortu zákazníků. Aplikace je realizována jako webový systém v architektuře klient-server s frontendem v Reactu a backendem ve Spring Boot. Funkcionalita pokrývá celý provozní cyklus od vytvoření objednávky po online platbu. Systém podporuje více uživatelských rolí, správu nabídky, přehled účtů a evidenci účtenek. V závěru práce jsou prezentovány výsledky testování a návrhy dalšího rozvoje.This bachelor thesis presents the design and implementation of an online ordering system for restaurants using QR codes to connect the customer with a digital menu, orders and payments directly from mobile devices. The system aims to streamline service, reduce staff workload, and improve the customer experience. The application is developed as a web-based client-server system using React for the frontend and Spring Boot for the backend. It supports multiple user roles, menu and table management, order tracking, and online payments. The final part of the thesis includes usability testing results and suggestions for further system improvements
Příspěvek k řešení konstrukce třídičů s uplatněním systému dynamického tlumení
Samostatný svazek příloh zpracovaný pod signaturou 33101/5528PrezenčníNeuvedenoNeuveden
Rekonstrukce přehříváku kotle IGNIFLUID
Import 20/04/2006Prezenční výpůjčkaVŠB - Technická univerzita Ostrava. Fakulta strojní. Katedra (361) energetik
