Association of NEDA-4 With No Long-term Disability Progression in Multiple Sclerosis and Comparison With NEDA-3

No evidence of disease activity (NEDA)-4 has been suggested as a treatment target for disease-modifying therapy (DMT) in relapsing-remitting multiple sclerosis (RRMS). However, the ability of NEDA-4 to discriminate long-term outcomes in MS and how its performance compares with NEDA-3 remain uncertain. We conducted a systematic review and meta-analysis to evaluate (1) the association between NEDA-4 and no long-term disability progression in MS and (2) the comparative performance of NEDA-3 and NEDA-4 in predicting no long-term disability progression. English-language abstracts and manuscripts were systematically searched in MEDLINE, Embase, and the Cochrane databases from January 2006 to November 2021 and reviewed independently by 2 investigators. We selected studies that assessed NEDA-4 at 1 or 2 years after DMT start and had at least 4 years of follow-up for determination of no confirmed disability progression. We conducted a meta-analysis using random-effects model to determine the pooled odds ratio (OR) for no disability progression with NEDA-4 vs EDA-4. For the comparative analysis, we selected studies that evaluated both NEDA-3 and NEDA-4 with at least 4 years of follow-up and examined the difference in the association of NEDA-3 and NEDA-4 with no disability progression. Five studies of 1,000 patients (3 interferon beta and 2 fingolimod) met inclusion criteria for both objectives. The median duration of follow-up was 6 years (interquartile range: 4-6 years). The prevalence of NEDA-4 ranged from 4.2% to 13.9% on interferon beta therapy and 24.9% to 25.1% on fingolimod therapy. The pooled OR for no long-term confirmed disability progression with NEDA-4 vs EDA-4 was 2.14 (95% confidence interval: 1.36-3.37; I 2 = 0). We did not observe any significant difference between NEDA-4 and NEDA-3 in the comparative analyses. In patients with RRMS, NEDA-4 at 1-2 years was associated with 2 times higher odds of no long-term disability progression, at 6 years compared with EDA-4, but offered no advantage over NEDA-3

Random graph states, maximal flow and Fuss-Catalan distributions

For any graph consisting of $k$ vertices and $m$ edges we construct an ensemble of random pure quantum states which describe a system composed of $2m$ subsystems. Each edge of the graph represents a bi-partite, maximally entangled state. Each vertex represents a random unitary matrix generated according to the Haar measure, which describes the coupling between subsystems. Dividing all subsystems into two parts, one may study entanglement with respect to this partition. A general technique to derive an expression for the average entanglement entropy of random pure states associated to a given graph is presented. Our technique relies on Weingarten calculus and flow problems. We analyze statistical properties of spectra of such random density matrices and show for which cases they are described by the free Poissonian (Marchenko-Pastur) distribution. We derive a discrete family of generalized, Fuss-Catalan distributions and explicitly construct graphs which lead to ensembles of random states characterized by these novel distributions of eigenvalues.Comment: 37 pages, 24 figure

DIFFUSION IN ONE DIMENSIONAL RANDOM MEDIUM AND HYPERBOLIC BROWNIAN MOTION

Classical diffusion in a random medium involves an exponential functional of Brownian motion. This functional also appears in the study of Brownian diffusion on a Riemann surface of constant negative curvature. We analyse in detail this relationship and study various distributions using stochastic calculus and functional integration.Comment: 18 page

miRNATissueAtlas2: an update to the human miRNA tissue atlas

Small non-coding RNAs (sncRNAs) are pervasive regulators of physiological and pathological processes. We previously developed the human miRNA Tissue Atlas, detailing the expression of miRNAs across organs in the human body. Here, we present an updated resource containing sequencing data of 188 tissue samples comprising 21 organ types retrieved from six humans. Sampling the organs from the same bodies minimizes intra-individual variability and facilitates the making of a precise highresolution body map of the non-coding transcriptome. The data allow shedding light on the organ- and organ system-specificity of piwi-interacting RNAs (piRNAs), transfer RNAs (tRNAs), microRNAs (miRNAs) and other non-coding RNAs. As use case of our resource, we describe the identification of highly specific ncRNAs in different organs. The update also contains 58 samples from six tissues of the Tabula Muris collection, allowing to check if the tissue specificity is evolutionary conserved between Homo sapiens and Mus musculus. The updated resource of 87 252 non-coding RNAs from nine noncoding RNA classes for all organs and organ systems is available online without any restrictions (https: //www.ccb.uni-saarland.de/tissueatlas2)

Diagnostic and treatment characteristics of polycystic ovary syndrome: descriptive measurements of patient perception and awareness from 657 confidential self-reports

BACKGROUND: This investigation was undertaken to describe patient perception and awareness of the polycystic ovary syndrome (PCOS), the most common cause of anovulation/oligoovulation among women of reproductive age. METHODS: Fifteen parameters were evaluated by a computer-based research instrument accessed by a large, unscreened population. Incomplete questionnaires were not entered, and responses were electronically tabulated to block duplicate submissions. RESULTS: From 657 participants, the majority (63%) were between 26–34 years old; mean BMI was 30.4 kg/m(2). 343 of 657 had at least one pregnancy and 61% of the study group had taken fertility medicine (any type) at least once. Physicians were the most common provider of PCOS information for all study participants, irrespective of age. Patient emotions associated with the diagnosis of PCOS included "frustration" (67%), "anxiety" (16%), "sadness" (10%), and "indifference" (2%). Self-reported patient aptitude regarding PCOS was scored as high or "very aware" in >60% of women. Respondents were also asked: "If your PCOS could be safely and effectively helped by something else besides fertility drugs or birth control pills, would that interest you?" Interest in alternative PCOS treatments was expressed by 99% of the sample (n = 648). CONCLUSIONS: In our study population, most women associated negative emotions with PCOS although the self-reported knowledge level for the disorder was high. While these women regarded their obstetrician-gynecologist as integral to their PCOS education, traditional PCOS therapies based on oral contraceptives or ovulation induction agents were regarded as unsatisfactory by most women

Performance/mathematics: a dramatisation of mathematical methods

This essay conceptualises the notion of performance mathematics in terms of a paradoxical relationship with the constructed notion of truth, which is shared by theatrical and mathematical performance. Specifically, I argue that these two disciplines can and cannot be reconciled with truthfulness. Grounding my comparison on the notion of an axiomatic method common to both disciplines, I argue that theatrical and mathematical performance can speak of truths only when these truths are properly staged or methodologically grounded according to the internal rules and conditions laid out by each discipline. But in the same way that these truths can be constructed, or they can be done, so they can be undone. Arguing that mathematics can be described as a performance of specific outcomes involving abstract objects and functions, I trace a cross-disciplinary comparative analysis of performance elements (especially axioms and functions), drawing on a number of theatre and mathematical theories. Some suggestions are also put forward in terms of the connection between the performance of mathematised texts and computational mathematics, particularly in terms of an inherent poetics and theatricality inside the performance-oriented, mathematised languages of digital computing

Validation, Deployment, and Real-World Implementation of a Modular Toolbox for Alzheimer’s Disease Detection and Dementia Risk Reduction: The AD-RIDDLE Project

The Real-World Implementation, Deployment, and Validation of Early Detection Tools and Lifestyle Enhancement (AD-RIDDLE) project, recently launched with the support of the EU Innovative Health Initiative (IHI) public-private partnership and UK Research and Innovation (UKRI), aims to develop, test, and deploy a modular toolbox platform that can reduce existing barriers to the timely detection, and therapeutic approaches in Alzheimer’s disease (AD), thus accelerating AD innovation. By focusing on health system and health worker practices, AD-RIDDLE seeks to improve and smooth AD management at and between each key step of the clinical pathway and across the disease continuum, from at-risk asymptomatic stages to early symptomatic ones. This includes innovation and improvement in AD awareness, risk reduction and prevention, detection, diagnosis, and intervention. The 24 partners in the AD-RIDDLE interdisciplinary consortium will develop and test the AD-RIDDLE toolbox platform and its components individually and in combination in six European countries. Expected results from this cross-sectoral research collaboration include tools for earlier detection and accurate diagnosis; validated, novel digital cognitive and blood-based biomarkers; and improved access to individualized preventative interventions (including multimodal interventions and symptomatic/disease-modifying therapies) across diverse populations, within the framework of precision medicine. Overall, AD-RIDDLE toolbox platform will advance management of AD, improving outcomes for patients and their families, and reducing costs

Brain Health Services: organization, structure, and challenges for implementation. A user manual for Brain Health Services—part 1 of 6

Dementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence suggests that, in higher-income countries, dementia incidence is decreasing as a result of healthier lifestyles. This observation supports the notion that preventing dementia is possible and that a certain degree of prevention is already in action. Further reduction of dementia incidence through deliberate prevention plans is needed to counteract its growing prevalence due to increasing life expectancy. An increasing number of individuals with normal cognitive performance seek help in the current memory clinics asking an evaluation of their dementia risk, preventive interventions, or interventions to ameliorate their cognitive performance. Consistent evidence suggests that some of these individuals are indeed at increased risk of dementia. This new health demand asks for a shift of target population, from patients with cognitive impairment to worried but cognitively unimpaired individuals. However, current memory clinics do not have the programs and protocols in place to deal with this new population. We envision the development of new services, henceforth called Brain Health Services, devoted to respond to demands from cognitively unimpaired individuals concerned about their risk of dementia. The missions of Brain Health Services will be (i) dementia risk profiling, (ii) dementia risk communication, (iii) dementia risk reduction, and (iv) cognitive enhancement. In this paper, we present the organizational and structural challenges associated with the set-up of Brain Health Services

Between Antagonism and Eros: The Feud as Couple Form and Netflix’s GLOW

A feud is an antagonism that is continuous and extended; “a state of prolonged mutual hostility” (OED). Historically, feuds take place between families or communities, or result from failed couples. Considered as a couple form in its own right, however, the feud is associated with aesthetic forms often coded as camp, queer, or feminized. In such popular, serialized forms, the feud must be open ended and of unforeseen futurity, for resolution brings an end to the feud as such and dissolves the couple. Thus, feuds reject normative modes of coupling (such as the nuclear family) that center harmonious or happy feelings. The article begins with the political economy of the feud through an examination of the pre-modern form of the blood feud and continues with its late-modern presence in popular culture. We rehearse the idea of the feud as it emerges from anthropology and philosophy, especially as it impacts notions of debt and alternative economies, before thinking through the contemporary “coupling” of the feud in popular culture, fandom, and, via the performance form of professional wrestling and Netflix’s GLOW