Transcutaneous tibial nerve stimulation: 2 years follow-up outcomes in the management of anticholinergic refractory overactive bladder

PURPOSE: To evaluate long-term use, efficacy and tolerability of transcutaneous tibial nerve stimulation (TTNS) in the treatment of refractory overactive bladder (OAB). METHODS: We performed a prospective observational study and included all patients treated in a single center for OAB persisting after first-line anticholinergic treatment, with ≥ 24 months follow-up. The protocol consisted of daily stimulation at home. The primary outcome was treatment persistence. Amelioration was defined as an improvement in urinary symptom profile (USP) score. RESULTS: We assessed 84 consecutive patients. After a mean follow-up of 39.3 months and a mean treatment use of 8.3 months, almost two-thirds of patients (71.8%) had discontinued TTNS. Treatment continuation was > 12 months for 28 patients (33.3%) and > 18 months for 16 patients (19%). TTNS was successful following 3 months of treatment in 60 (71%) patients. Mean USP score stayed significantly lower than baseline until 12 months of treatment, but was not significant anymore after 18 months. Discontinuation therapy reasons were a lack of sufficient symptom relief for 59 (70%) patients, compliance difficulty for 5 (6%) patients and becoming asymptomatic for 6 (8%) patients. No serious adverse events occurred. CONCLUSIONS: The present study confirms the utility of TTNS as a treatment option for patients with resistant OAB. In the long-term use, few patients continued with therapy, mostly because of a decreased effectiveness with time

Forward Analysis and Model Checking for Trace Bounded WSTS

We investigate a subclass of well-structured transition systems (WSTS), the bounded---in the sense of Ginsburg and Spanier (Trans. AMS 1964)---complete deterministic ones, which we claim provide an adequate basis for the study of forward analyses as developed by Finkel and Goubault-Larrecq (Logic. Meth. Comput. Sci. 2012). Indeed, we prove that, unlike other conditions considered previously for the termination of forward analysis, boundedness is decidable. Boundedness turns out to be a valuable restriction for WSTS verification, as we show that it further allows to decide all $\omega$-regular properties on the set of infinite traces of the system

How to Tackle Integer Weighted Automata Positivity

International audienceThis paper is dedicated to candidate abstractions to capture relevant aspects of the integer weighted automata. The expected effect of applying these abstractions is studied to build the deterministic reachability graphs allowing us to semi-decide the positivity problem on these automata. Moreover, the papers reports on the implementations and experimental results, and discusses other encodings

Atom lasers: production, properties and prospects for precision inertial measurement

We review experimental progress on atom lasers out-coupled from Bose-Einstein condensates, and consider the properties of such beams in the context of precision inertial sensing. The atom laser is the matter-wave analog of the optical laser. Both devices rely on Bose-enhanced scattering to produce a macroscopically populated trapped mode that is output-coupled to produce an intense beam. In both cases, the beams often display highly desirable properties such as low divergence, high spectral flux and a simple spatial mode that make them useful in practical applications, as well as the potential to perform measurements at or below the quantum projection noise limit. Both devices display similar second-order correlations that differ from thermal sources. Because of these properties, atom lasers are a promising source for application to precision inertial measurements.Comment: This is a review paper. It contains 40 pages, including references and figure

Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins

The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection. We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957–1982) with mumps virus genotype G strains (from 2004 onwards). Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan. Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein. There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein. These differences may account for the reported antigenic differences between Jeryl Lynn and genotype G strains. We also found amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis. These differences may contribute to the occurrence of genotype G outbreaks in vaccinated communities

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Item does not contain fulltextBACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m(2) increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat