Traveling waves for nonlinear Schr\"odinger equations with nonzero conditions at infinity, II

We prove the existence of nontrivial finite energy traveling waves for a large class of nonlinear Schr\"odinger equations with nonzero conditions at infinity (includindg the Gross-Pitaevskii and the so-called "cubic-quintic" equations) in space dimension $N \geq 2$. We show that minimization of the energy at fixed momentum can be used whenever the associated nonlinear potential is nonnegative and it gives a set of orbitally stable traveling waves, while minimization of the action at constant kinetic energy can be used in all cases. We also explore the relationship between the families of traveling waves obtained by different methods and we prove a sharp nonexistence result for traveling waves with small energy.Comment: Final version, accepted for publication in the {\it Archive for Rational Mechanics and Analysis.} The final publication is available at Springer via http://dx.doi.org/10.1007/s00205-017-1131-

Glucose enhancement of memory is modulated by trait anxiety in healthy adolescent males

Glucose administration is associated with memory enhancement in healthy young individuals under conditions of divided attention at encoding. While the specific neurocognitive mechanisms underlying this ‘glucose memory facilitation effect’ are currently uncertain, it is thought that individual differences in glucoregulatory efficiency may alter an individual’s sensitivity to the glucose memory facilitation effect. In the present study, we sought to investigate whether basal hypothalamic–pituitary–adrenal axis function (itself a modulator of glucoregulatory efficiency), baseline self-reported stress and trait anxiety influence the glucose memory facilitation effect. Adolescent males (age range = 14–17 years) were administered glucose and placebo prior to completing a verbal episodic memory task on two separate testing days in a counter-balanced, within-subjects design. Glucose ingestion improved verbal episodic memory performance when memory recall was tested (i) within an hour of glucose ingestion and encoding, and (ii) one week subsequent to glucose ingestion and encoding. Basal hypothalamic–pituitary–adrenal axis function did not appear to influence the glucose memory facilitation effect; however, glucose ingestion only improved memory in participants reporting relatively higher trait anxiety. These findings suggest that the glucose memory facilitation effect may be mediated by biological mechanisms associated with trait anxiety

Drug Development for Rare Paediatric Epilepsies: Current State and Future Directions

Rare diseases provide a challenge in the evaluation of new therapies. However, orphan drug development is of increasing interest because of the legislation enabling facilitated support by regulatory agencies through scientific advice, and the protection of the molecules with orphan designation. In the landscape of the rare epilepsies, very few syndromes, namely Dravet syndrome, Lennox-Gastaut syndrome and West syndrome, have been subject to orphan drug development. Despite orphan designations for rare epilepsies having dramatically increased in the past 10 years, the number of approved drugs remains limited and restricted to a handful of epilepsy syndromes. In this paper, we describe the current state of orphan drug development for rare epilepsies. We identified a large number of compounds currently under investigation, but mostly in the same rare epilepsy syndromes as in the past. A rationale for further development in rare epilepsies could be based on the match between the drug mechanisms of action and the knowledge of the causative gene mutation or by evidence from animal models. In case of the absence of strong pathophysiological hypotheses, exploratory/basket clinical studies could be helpful to identify a subpopulation that may benefit from the new drug. We provide some suggestions for future improvements in orphan drug development such as promoting paediatric drug investigations, better evaluation of the incidence and the prevalence, together with the natural history data, and the development of new primary outcomes

Relevance of a photo-Fenton like technology based on peroxymonosulphate for 17b-estradiol removal from wastewater

The objective of this work was to evaluate the effectiveness of sulphate radical based homogeneous advanced oxidation technologies (SR-AOTs) involving peroxymonosulphate (PMS) as an oxidant and ferrous iron (Fe(II)) as a catalyst, for the removal of 17b-estradiol (E2) from wastewater effluents collected downstream of a biological WWTP in Perpignan (France). This molecule is used as a surrogate for endocrine disrupting compounds (EDCs) due to its high biological activity at very low concentration levels (ng/ L). For this purpose, two different laboratory-scale devices have been employed, one for indoor experiments working with controlled and artificial UV light centered on k = 365 nm emission, and the other at a larger scale for outdoor experiments using direct solar irradiation. Comparison of kinetic studies with those obtained with commonly used hydroxyl radical based advanced oxidation technologies (HR-AOTs), i.e., UV–Vis/H2O2/Fe(II) and UV/TiO2 revealed the higher efficiency of the former over the latter ones. Estrogenicity measurement through bioassays confirmed the complete removal of 17b-estradiol after only a few minutes treatment. Determination of E2 transformation pathways upon sulphate radical reactivity through intermediates identification by mass spectrometry revealed that the oxidation of phenol moiety into quinone might be the main step responsible for the decrease in estrogenicity. UV–Vis/PMS/Fe(II) system appears to be the most suitable method for the treatment of aqueous solutions containing E2

Convergence of Ginzburg-Landau functionals in 3-d superconductivity

In this paper we consider the asymptotic behavior of the Ginzburg- Landau model for superconductivity in 3-d, in various energy regimes. We rigorously derive, through an analysis via {\Gamma}-convergence, a reduced model for the vortex density, and we deduce a curvature equation for the vortex lines. In a companion paper, we describe further applications to superconductivity and superfluidity, such as general expressions for the first critical magnetic field H_{c1}, and the critical angular velocity of rotating Bose-Einstein condensates.Comment: 45 page

Travelling waves for the Gross-Pitaevskii equation II

The purpose of this paper is to provide a rigorous mathematical proof of the existence of travelling wave solutions to the Gross-Pitaevskii equation in dimensions two and three. Our arguments, based on minimization under constraints, yield a full branch of solutions, and extend earlier results, where only a part of the branch was built. In dimension three, we also show that there are no travelling wave solutions of small energy.Comment: Final version accepted for publication in Communications in Mathematical Physics with a few minor corrections and added remark

Temporal changes in ewe vaginal microbiota throughout gestation

Introduction: Numerous factors are known to influence reproductive efficiency in ewes, but few studies have investigated the potential role of vaginal microbiota in sheep reproductive success. The objective of this study was to thoroughly characterize the ewe vaginal microbiota throughout the course of pregnancy. Methods: Vaginal samples were collected from 31 pregnant Hampshire and Hampshire X Suffolk crossbred ewes on a weekly basis from pre-breeding to pregnancy testing and then biweekly until just after lambing. To characterize the vaginal microbial communities, DNA was extracted and 16S rRNA gene Illumina MiSeq amplicon sequencing was performed. Results and Discussion: Alpha diversity metrics indicated an increase in species richness, evenness, and overall diversity throughout gestation. Distinct shifts in the bacterial communities were observed during gestation and were segregated into three periods: early gestation, a transitional period and mid/late gestation. During early gestation, Actinobacillus, Histophilus, and unclassified Leptotrichiaceae were found in greater relative abundance. During the transitional period, a population shift occurred characterized by increasing relative abundance of Streptococcus and Staphylococcus. During mid/late gestation, Staphylococcus, Streptococcus, and Ureaplasma had the greatest relative abundance. These shifts in the microbial population throughout the ewe’s gestation are likely related to hormonal changes triggered by the growing conceptus, specifically increasing blood concentration of progesterone. The transitional period shift in vaginal microbial communities potentially aligns with the placental take-over of progesterone production from the corpus luteum at approximately day 50 after conception (gestational week 7). Understanding the observed variability of the vaginal microbiota throughout pregnancy will allow for future comparison of ewes that did not become pregnant or had abnormal pregnancies, which could lead to the discovery of potential bacterial biomarkers for pregnancy outcome; this understanding could also lead to development of probiotics to improve sheep reproductive success.This article is published as Cassas MS, Jonas LC, Anderson CJ, Schmitz-Esser S and Youngs CR (2024) Temporal changes in ewe vaginal microbiota throughout gestation. Front. Microbiol. 15:1359678. doi: 10.3389/fmicb.2024.1359678.© 2024 Cassas, Jonas, Anderson, Schmitz-Esser and Youngs. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol-Inclusive Regimens A Randomized Clinical Trial

IMPORTANCE Fenfluramine treatment may reduce monthly convulsive seizure frequency in patients with Dravet syndrome who have poor seizure control with their current stiripentol-containing antiepileptic drug regimens. OBJECTIVE To determine whether fenfluramine reduced monthly convulsive seizure frequency relative to placebo in patients with Dravet syndrome who were taking stiripentol-inclusive regimens. DESIGN, SETTING, AND PARTICIPANTS This double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted in multiple centers. Eligible patients were children aged 2 to 18 years with a confirmed clinical diagnosis of Dravet syndrome who were receiving stable, stiripentol-inclusive antiepileptic drug regimens. INTERVENTIONS Patients with 6 or more convulsive seizures during the 6-week baseline period were randomly assigned to receive fenfluramine, 0.4 mg/kg/d (maximum, 17 mg/d), or a placebo. After titration (3 weeks), patients’ assigned dosages were maintained for 12 additional weeks. Caregivers recorded seizures via a daily electronic diary. MAIN OUTCOMES AND MEASURES The primary efficacy end point was the change in mean monthly convulsive seizure frequency between fenfluramine and placebo during the combined titration and maintenance periods relative to baseline. RESULTS A total of 115 eligible patients were identified; of these, 87 patients (mean [SD], age 9.1 [4.8] years; 50 male patients [57%]; mean baseline frequency of seizures, approximately 25 convulsive seizures per month) were enrolled and randomized to fenfluramine, 0.4 mg/kg/d (n = 43) or placebo (n = 44). Patients treated with fenfluramine achieved a 54.0% (95% CI, 35.6%-67.2%; P < .001) greater reduction in mean monthly convulsive seizure frequency than those receiving the placebo. With fenfluramine, 54% of patients demonstrated a clinically meaningful (50%) reduction in monthly convulsive seizure frequency vs 5% with placebo (P < .001). The median (range) longest seizure-free interval was 22 (3.0-105.0) days with fenfluramine and 13 (1.0-40.0) days with placebo (P = .004). The most common adverse events were decreased appetite (19 patients taking fenfluramine [44%] vs 5 taking placebo [11%]), fatigue (11 [26%] vs 2 [5%]), diarrhea (10 [23%] vs 3 [7%]), and pyrexia (11 [26%] vs 4 [9%]). Cardiac monitoring demonstrated no clinical or echocardiographic evidence of valvular heart disease or pulmonary arterial hypertension. CONCLUSIONS AND RELEVANCE Fenfluramine demonstrated significant improvements in monthly convulsive seizure frequency in patients with Dravet syndrome whose conditions were insufficiently controlled with stiripentol-inclusive antiepileptic drug regimens. Fenfluramine was generally well tolerated. Fenfluramine may represent a new treatment option for Dravet syndrome. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT0292689