Results of a Phase 2b Trial With GB001, a Prostaglandin D2 Receptor 2 Antagonist, in Moderate to Severe Eosinophilic Asthma

Asthma; Asthma worsening; Eosinophilic asthmaAsma; Empitjorament de l'asma; Asma eosinofílicaAsma; Empeoramiento del asma; Asma eosinofílicaBackground Prostaglandin D2 receptor 2 (DP2) antagonists inhibit prostaglandin D2-induced effects, including recruitment and activation of cells driving asthma pathogenesis. However, challenges identifying target population and end points persist. Research Question What is the effect of the DP2 antagonist GB001 on asthma worsening in patients with moderate to severe eosinophilic asthma? Study Design and Methods In this phase IIb, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group, multicenter study, GB001 or placebo was added to standard-of-care treatment in patients with moderate to severe asthma with a blood eosinophil count ≥ 250 cells/μL. Patients aged ≥ 18 years to < 75 years received one of four once-daily treatments (GB001 20 mg, 40 mg, or 60 mg or placebo). The primary end point was the proportion of patients who experienced asthma worsening by 24 weeks. Efficacy analyses were performed for the intention-to-treat population and safety analyses for patients who received at least one dose of study treatment. Results A total of 480 patients were treated. The ORs for asthma worsening for GB001 20 mg, 40 mg, and 60 mg vs placebo were 0.674 (95% CI, 0.398-1.142), 0.677 (95% CI, 0.399-1.149), and 0.651 (95% CI, 0.385-1.100), respectively. Analysis according to baseline blood eosinophil levels and/or fractional exhaled nitric oxide did not show greater treatment effects with higher values. Elevated liver aminotransferase levels and adverse events leading to discontinuation were more frequent for GB001 60 mg than with placebo, GB001 20 mg, and GB001 40 mg. Interpretation Although GB001 did not significantly reduce the odds of asthma worsening, reductions favoring GB001 were observed. Treatment effects were consistent regardless of high/low type 2 phenotype. The overall safety profile was acceptable, although GB001 60 mg was associated with risk of liver injury.This work was supported by GB001, Inc., a wholly owned subsidiary of Gossamer Bio, Inc

Mental health problems in children of somatically ill parents, e.g. multiple sclerosis

Objectives: Based on the investigation of 144 families (144 patients affected by Multiple Sclerosis (MS), 109 partners, and 192 children) examined in three different European child and adolescent psychiatric University centres by means of questionnaires, we evaluated the prevalence of psychological symptoms in the offspring and associated risk factors such as duration and severity of the disease as well as depression of the ill and the healthy parent. Results: Indicate that the severe disease of MS is associated with depression of the ill and healthy parent. Ill parents, especially ill mothers, as well as depressed ill, or depressed healthy parents evaluate their children's mental health problems with a higher prevalence within the internalizing spectrum. Healthy parents report normal psychological adjustment of their children. If two parents present a depressive state, the prevalence of relevant psychological internalizing symptoms is twice or three times as high as the age norms. Conclusion: Children in families with a parent affected by MS and associated depression of the parental couple are at high risk of mental health problems, especially internalizing disorders. In focusing on the mental health of children one must also be aware of the potential opportunities to address the parents' own psychological need

Landau-Ginzburg Description of Boundary Critical Phenomena in Two Dimensions

The Virasoro minimal models with boundary are described in the Landau-Ginzburg theory by introducing a boundary potential, function of the boundary field value. The ground state field configurations become non-trivial and are found to obey the soliton equations. The conformal invariant boundary conditions are characterized by the reparametrization-invariant data of the boundary potential, that are the number and degeneracies of the stationary points. The boundary renormalization group flows are obtained by varying the boundary potential while keeping the bulk critical: they satisfy new selection rules and correspond to real deformations of the Arnold simple singularities of A_k type. The description of conformal boundary conditions in terms of boundary potential and associated ground state solitons is extended to the N=2 supersymmetric case, finding agreement with the analysis of A-type boundaries by Hori, Iqbal and Vafa.Comment: 42 pages, 13 figure

Managing Polyploidy in Ex Situ Conservation Genetics: The Case of the Critically Endangered Adriatic Sturgeon (Acipenser naccarii)

While the current expansion of conservation genetics enables to address more efficiently the management of threatened species, alternative methods for genetic relatedness data analysis in polyploid species are necessary. Within this framework, we present a standardized and simple protocol specifically designed for polyploid species that can facilitate management of genetic diversity, as exemplified by the ex situ conservation program for the tetraploid Adriatic sturgeon Acipenser naccarii. A critically endangered endemic species of the Adriatic Sea tributaries, its persistence is strictly linked to the ex situ conservation of a single captive broodstock currently decimated to about 25 individuals, which represents the last remaining population of Adriatic sturgeon of certain wild origin. The genetic variability of three F1 broodstocks available as future breeders was estimated based on mitochondrial and microsatellite information and compared with the variability of the parental generation. Genetic data showed that the F1 stocks have only retained part of the genetic variation present in the original stock due to the few parent pairs used as founders. This prompts for the urgent improvement of the current F1 stocks by incorporating new founders that better represent the genetic diversity available. Following parental allocation based on band sharing values, we set up a user-friendly tool for selection of candidate breeders according to relatedness between all possible parent-pairs that secures the use of non-related individuals. The approach developed here could also be applied to other endangered tetraploid sturgeon species overexploited for caviar production, particularly in regions lacking proper infrastructure and/or expertise

Intervalley coherence and intrinsic spin-orbit coupling in rhombohedral trilayer graphene

Rhombohedral graphene multilayers provide a clean and highly reproducible platform to explore the emergence of superconductivity and magnetism in a strongly interacting electron system. Here, we use electronic compressibility and local magnetometry to explore the phase diagram of this material class in unprecedented detail. We focus on rhombohedral trilayer in the quarter metal regime, where the electronic ground state is characterized by the occupation of a single spin and valley isospin flavor. Our measurements reveal a subtle competition between valley imbalanced (VI) orbital ferromagnets and intervalley coherent (IVC) states in which electron wave functions in the two momentum space valleys develop a macroscopically coherent relative phase. Contrasting the in-plane spin susceptibility of the IVC and VI phases reveals the influence of graphene's intrinsic spin-orbit coupling, which drives the emergence of a distinct correlated phase with hybrid VI and IVC character. Spin-orbit also suppresses the in-plane magnetic susceptibility of the VI phase, which allows us to extract the spin-orbit coupling strength of $\lambda \approx 50\mu$eV for our hexagonal boron nitride-encapsulated graphene system. We discuss the implications of finite spin-orbit coupling on the spin-triplet superconductors observed in both rhombohedral and twisted graphene multilayers

Comparison of Technetium-99m-MIBI imaging with MRI for detection of spine involvement in patients with multiple myeloma

BACKGROUND: Recently, radiopharmaceutical scanning with Tc-99m-MIBI was reported to depict areas with active bone disease in multiple myeloma (MM) with both high sensitivity and specificity. This observation was explained by the uptake of Tc-99m-MIBI by neoplastic cells. The present investigation evaluates whether Tc-99m-MIBI imaging and magnetic resonance imaging (MRI) perform equally well in detecting myelomatous bone marrow lesions. METHODS: In 21 patients with MM, MRIs of the vertebral region TH12 to S1 and whole body scans with Tc-99m-MIBI were done. RESULTS: Tc-99m-MIBI scanning missed bone marrow infiltration in 43 of 87 vertebrae (50.5%) in which MRI showed neoplastic bone marrow involvement. In patients with disease stage I+II, Tc-99m-MIBI scanning was negative in all of 24 vertebrae infiltrated according to MRI. In patients with disease stage III, Tc-99m-MIBI scanning detected 44 of 63 (70%) vertebrae involved by neoplastic disease. CONCLUSION: Tc-99m-MIBI scanning underestimated the extent of myelomatous bone marrow infiltration in the spine, especially in patients with low disease stage

Consumption patterns of sweet drinks in a population of Australian children and adolescents (2003–2008)

<p>Abstract</p> <p>Background</p> <p>Intake of sweet drinks has previously been associated with the development of overweight and obesity among children and adolescents. The present study aimed to assess the consumption pattern of sweet drinks in a population of children and adolescents in Victoria, Australia.</p> <p>Methods</p> <p>Data on 1,604 children and adolescents (4–18 years) from the comparison groups of two quasi-experimental intervention studies from Victoria, Australia were analysed<it>.</it> Sweet drink consumption (soft drink and fruit juice/cordial) was assessed as one day’s intake and typical intake over the last week or month at two time points between 2003 and 2008 (mean time between measurement: 2.2 years).</p> <p>Results</p> <p>Assessed using dietary recalls, more than 70% of the children and adolescents consumed sweet drinks, with no difference between age groups (p = 0.28). The median intake among consumers was 500 ml and almost a third consumed more than 750 ml per day. More children and adolescents consumed fruit juice/cordial (69%) than soft drink (33%) (p < 0.0001) and in larger volumes (median intake fruit juice/cordial: 500 ml and soft drink: 375 ml). Secular changes in sweet drink consumption were observed with a lower proportion of children and adolescents consuming sweet drinks at time 2 compared to time 1 (significant for age group 8 to <10 years, p = 0.001).</p> <p>Conclusion</p> <p>The proportion of Australian children and adolescents from the state of Victoria consuming sweet drinks has been stable or decreasing, although a high proportion of this sample consumed sweet drinks, especially fruit juice/cordial at both time points.</p

Antibody Response to Shiga Toxins in Argentinean Children with Enteropathic Hemolytic Uremic Syndrome at Acute and Long-Term Follow-Up Periods

Shiga toxin (Stx)-producing Escherichia coli (STEC) infection is associated with a broad spectrum of clinical manifestations that include diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Systemic Stx toxemia is considered to be central to the genesis of HUS. Distinct methods have been used to evaluate anti-Stx response for immunodiagnostic or epidemiological analysis of HUS cases. The development of enzyme-linked immunosorbent assay (ELISA) and western blot (WB) assay to detect the presence of specific antibodies to Stx has introduced important advantages for serodiagnosis of HUS. However, application of these methods for seroepidemiological studies in Argentina has been limited. The aim of this work was to develop an ELISA to detect antibodies against the B subunit of Stx2, and a WB to evaluate antibodies against both subunits of Stx2 and Stx1, in order to analyze the pertinence and effectiveness of these techniques in the Argentinean population. We studied 72 normal healthy children (NHC) and 105 HUS patients of the urban pediatric population from the surrounding area of Buenos Aires city. Using the WB method we detected 67% of plasma from NHC reactive for Stx2, but only 8% for Stx1. These results are in agreement with the broad circulation of Stx2-expressing STEC in Argentina and the endemic behavior of HUS in this country. Moreover, the simultaneous evaluation by the two methods allowed us to differentiate acute HUS patients from NHC with a great specificity and accuracy, in order to confirm the HUS etiology when pathogenic bacteria were not isolated from stools