A global method for deterministic and stochastic homogenisation in BV

In this paper we study the deterministic and stochastic homogenisation of free-discontinuity functionals under linear growth and coercivity conditions. The main novelty of our deterministic result is that we work under very general assumptions on the integrands which, in particular, are not required to be periodic in the space variable. Combining this result with the pointwise Subadditive Ergodic Theorem by Akcoglu and Krengel, we prove a stochastic homogenisation result, in the case of stationary random integrands. In particular, we characterise the limit integrands in terms of asymptotic cell formulas, as in the classical case of periodic homogenisation

Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis

Background: Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels, neurotransmitter transporters, and multiple 7-transmembrane receptors. In contrast to tetra-hydrocannabinol, CBD lacks psychoactive properties, does not produce euphoric or intrusive side effects, and is largely devoid of abuse liability. Objective: The aim of the study was to estimate the efficacy and safety of CBD as adjunctive treatment in patients with epilepsy using meta-analytical techniques. Methods: Randomized, placebo-controlled, single- or double-blinded add-on trials of oral CBD in patients with uncontrolled epilepsy were identified. Main outcomes included the percentage change and the proportion of patients with ≥ 50% reduction in monthly seizure frequency during the treatment period and the incidence of treatment withdrawal and adverse events (AEs). Results: Four trials involving 550 patients with Lennox–Gastaut syndrome (LGS) and Dravet syndrome (DS) were included. The pooled average difference in change in seizure frequency during the treatment period resulted 19.5 [95% confidence interval (CI) 8.1–31.0; p = 0.001] percentage points between the CBD 10 mg and placebo groups and 19.9 (95% CI 11.8–28.1; p < 0.001) percentage points between the CBD 20 mg and placebo arms, in favor of CBD. The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07–2.88; p = 0.025]. Across the trials, drug withdrawal for any reason occurred in 11.1% and 2.6% of participants receiving CBD and placebo, respectively (RR 3.54, 95% CI 1.55–8.12; p = 0.003) [Chi squared = 2.53, degrees of freedom (df) = 3, p = 0.506; I2 = 0.0%]. The RRs to discontinue treatment were 1.45 (95% CI 0.28–7.41; p = 0.657) and 4.20 (95% CI 1.82–9.68; p = 0.001) for CBD at the doses of 10 and 20 mg/kg/day, respectively, in comparison to placebo. Treatment was discontinued due to AEs in 8.9% and 1.8% of patients in the active and control arms, respectively (RR 5.59, 95% CI 1.87–16.73; p = 0.002). The corresponding RRs for CBD at the doses of 10 and 20 mg/kg/day were 1.66 (95% CI 0.22–12.86; p = 0.626) and 6.89 (95% CI 2.28–20.80; p = 0.001). AEs occurred in 87.9% and 72.2% of patients treated with CBD and placebo (RR 1.22, 95% CI 1.11–1.33; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases. Conclusions: Adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo

Individualized Prediction of Drug Resistance in People with Post-Stroke Epilepsy: A Retrospective Study

Background: The study aimed to develop a model and build a nomogram to predict the probability of drug resistance in people with post-stroke epilepsy (PSE). Methods: Subjects with epilepsy secondary to ischemic stroke or spontaneous intracerebral hemorrhage were included. The study outcome was the occurrence of drug-resistant epilepsy defined according to International League Against Epilepsy criteria. Results: One hundred and sixty-four subjects with PSE were included and 32 (19.5%) were found to be drug-resistant. Five variables were identified as independent predictors of drug resistance and were included in the nomogram: age at stroke onset (odds ratio (OR): 0.941, 95% confidence interval (CI) 0.907–0.977), intracerebral hemorrhage (OR: 6.292, 95% CI 1.957–20.233), severe stroke (OR: 4.727, 95% CI 1.573–14.203), latency of PSE (>12 months, reference; 7–12 months, OR: 4.509, 95% CI 1.335–15.228; 0–6 months, OR: 99.099, 95% CI 14.873–660.272), and status epilepticus at epilepsy onset (OR: 14.127, 95% CI 2.540–78.564). The area under the receiver operating characteristic curve of the nomogram was 0.893 (95% CI: 0.832–0.956). Conclusions: Great variability exists in the risk of drug resistance in people with PSE. A nomogram based on a set of readily available clinical variables may represent a practical tool for an individualized prediction of drug-resistant PSE

Inflammatory myofibroblastic tumor after lung transplant-A rare and aggressive complication. A case report.

Introduction Malignant diseases are well-known complications after lung transplantation (LT). Among these, inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with a not well-known and often aggressive biological behavior. Material and Methods We hereby describe 2 cases of cystic fibrosis patients who underwent bilateral sequential LT (BSLT) complicated by IMT. Results A 26-year-old man presented a right endobronchial lesion 6 months after BSLT. Two consecutive fiber bronchoscopic biopsies showed granulation tissue. For the persistent lesion growth, the patient underwent a transthoracic biopsy showing histologic diagnosis of IMT. Therefore, he underwent to right pneumonectomy that was unfortunately complicated after 6 months with a late bronchopleural fistula and empyema with exitus 6 months later. A 31-year-old woman 1 year after BSLT presented with a left voluminous pleural-parenchymal lesion; the histologic examination after biopsy revealed an IMT. She underwent a removal of the lesion with a macroscopic R0 resection. Histologic, immunophenotypic, and cytogenetic examinations showed a strong overexpression of anaplastic lymphoma kinase requiring biological adjuvant therapies; however, the patient refused it. Four years later, she presented a recurrence treated with debulking procedure and adjuvant radiotherapy. At last follow-up, the patient was alive with stable disease and optimal graft function. Conclusions Although IMT is a rare complication after lung transplant, to obtain a careful diagnosis, an early and aggressive treatment is mandatory

A comparison of delamination models: Modeling, properties, and applications

This contribution presents recent results in the modeling and the analysis of delamination problems. It addresses adhesive contact, brittle, and cohesive zone models both in a quasistatic and a viscous, dynamic setting for the bulk part. Also different evolution laws for the delaminating surface are discussed

Radical remodeling of the Y chromosome in a recent radiation of malaria mosquitoes

open28openHall A.B.; Papathanos P.-A.; Sharma A.; Cheng C.; Akbari O.S.; Assour L.; Bergman N.H.; Cagnetti A.; Crisanti A.; Dottorini T.; Fiorentini E.; Galizi R.; Hnath J.; Jiang X.; Koren S.; Nolan T.; Radune D.; Sharakhova M.V.; Steele A.; Timoshevskiy V.A.; Windbichler N.; Zhang S.; Hahn M.W.; Phillippy A.M.; Emrich S.J.; Sharakhov I.V.; Tu Z.J.; Besansky N.J.Hall, A. B.; Papathanos, P. -A.; SHARMA DHAKAL, Apsara; Cheng, C.; Akbari, O. S.; Assour, L.; Bergman, N. H.; Cagnetti, A.; Crisanti, A.; Dottorini, T.; Fiorentini, E.; Galizi, R.; Hnath, J.; Jiang, X.; Koren, S.; Nolan, T.; Radune, D.; Sharakhova, M. V.; Steele, A.; Timoshevskiy, V. A.; Windbichler, N.; Zhang, Shangu; Hahn, M. W.; Phillippy, A. M.; Emrich, S. J.; Sharakhov, I. V.; Tu, Z. J.; Besansky, N. J

Usefulness of bronchoalveolar lavage in suspect COVID-19 repeatedly negative swab test and interstitial lung disease

The diagnosis of coronavirus disease 2019 (COVID-19) relies on nasopharyngeal swab, which shows a 20–30% risk of false negativity [1]. Bronchoalveolar lavage (BAL) is reported to be useful in patients with pulmonary interstitial infiltrates on high-resolution computed tomography (HRCT). We investigated the usefulness of BAL in symptomatic patients with positive HRCT and a repeatedly negative swab test (‘grey zone’)

Quasistatic delamination of sandwich-like Kirchhoff-Love plates

A quasistatic rate-independent adhesive delamination problem of laminated plates with a finite thickness is considered. By letting the thickness of the plates go to zero, a rate-independent delamination model for a laminated Kirchhoff-Love plate is obtained as limit of these quasistatic processes. The same dimension reduction procedure is eventually applied to processes which are sensitive to delamination modes, namely opening vs. shearing is distinguishe

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32–56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy

Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure‐freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45 years (33–56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p < 0.001); the corresponding values for ≥ 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%; p = 0.341) and seizure response (39.7% vs. 26.9%; p = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p = 0.017). Conclusion: The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations