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The Giant Radio Array for Neutrino Detection (GRAND) is a planned array of ~ 2·105 radio antennas deployed over ~ 200 000 km2 in a mountainous site. It aims primarly at detecting high-energy neutrinos via the observation of extensive air showers induced by the decay in the atmosphere of taus produced by the interaction of cosmic neutrinos under the Earth surface. GRAND aims at reaching a neutrino sensitivity of 5 · 10−11 E−2 GeV−1 cm−2 s−1 sr−1 above 3 · 1016 eV. This ensures the detection of cosmogenic neutrinos in the most pessimistic source models, and ~50 events per year are expected for the standard models. The instrument will also detect UHECRs and possibly FRBs. Here we show how our preliminary design should enable us to reach our sensitivity goals, and discuss the steps to be taken to achieve GRAND, while the compelling science case for GRAND is discussed in more details in [1].

Objectives The aim of our study was to identify the potential distinct phenotypes within a broad SpA population. Methods We conducted a cross-sectional study using the REGISPONSER registry, which has data from 31 specialist centres in Spain, including patients with SpA who have fulfilled the ESSG criteria. A latent class analysis (LCA) was performed to identify the latent classes underlying SpA according to a set of predefined clinical and radiographic features, independently of expert opinion. Results In a population of 2319 SpA patients, a five-classes LCA model yielded the best fit. Classes named 'Axial with spine involvement' and 'Axial with isolated SI joint involvement' showed a primarily axial SpA phenotype defined by inflammatory back pain and high HLA-B27 prevalence. Patients in class 'Axial + peripheral' showed a similar distribution of manifest variables to previous classes but also had a higher likelihood of peripheral involvement (peripheral arthritis/dactylitis) and enthesitis, therefore representing a mixed (axial and peripheral) subtype. Classes 'Peripheral + psoriasis' and 'Axial + peripheral + psoriasis' were indicative of peripheral SpA (and/or PsA) with high likelihood of psoriasis, peripheral involvement, dactylitis, nail disease, and low HLA-B27 prevalence, while class 'Axial + peripheral + psoriasis' also exhibited increased probability of axial involvement both clinically and radiologically. Conclusion The identification of five latent classes in the REGISPONSER registry with significant overlap between axial and peripheral phenotypes is concordant with a unifying concept of SpA. Psoriasis and related features (nail disease and dactylitis) influenced the phenotype of both axial and peripheral manifestations. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the impact of protocol violations in the treat‐to‐target group in the Tight Control in Spondyloarthritis (TICOSPA) trial and to compare the proportion of patients optimally treated according to the Assessment of Spondyloarthritis International Society (ASAS)/EULAR 2016 recommendations for patients with axial spondyloarthritis (axSpA) between the treat‐to‐target versus usual care (UC) arms. Methods: This study was a cluster‐randomized, controlled 48‐week trial including patients with axSpA who fulfilled the ASAS criteria, had an Axial Spondyloarthritis Disease Activity Score >2.1, and were biologic disease‐modifying antirheumatic drug naive. Eighteen axSpA expert centers were randomly allocated to one treatment arm: (a) treat‐to‐target prespecified management strategy (four‐week visits), and (b) UC treatment decisions at the rheumatologist's discretion (12‐week visits). Protocol violations in the treat‐to‐target arm and the fulfillment of the 2016 ASAS/EULAR recommendations in both arms were evaluated at every visit. ASAS Health Index (ASAS‐HI) and disease activity outcomes at 48 weeks were compared between treat‐to‐target violators versus nonviolators. Patients treated according to the ASAS/EULAR recommendations were compared between both arms. Results: A total of 160 patients initiated the trial (80 patients with treat to target; 80 patients with UC). In the treat‐to‐target arm, 51.2% patients violated the protocol at least once (62.2% of violations resulting in maintenance/reduction of treatment against protocol). After 48 weeks, treat‐to‐target violators versus nonviolators showed similar ratios of ASAS‐HI improvement. The proportion of patients managed according to the ASAS/EULAR recommendations after the first 12 weeks were 63.9% versus 61.8% for the treat‐to‐target and UC arms, respectively. Conclusion: Protocol violations in the treat‐to‐target arm in the TICOSPA trial were frequent, although they did not have an impact on the rate of the primary outcome. The groups with UC was optimally treated, partly explaining the nonachievement of the primary objective in the TICOSPA trial. [ABSTRACT FROM AUTHOR]

Background: Few studies have been conducted to investigate the socioeconomic profiles of patients with ankylosing spondylitis (AS) and their associations with disease severity and disability. Objectives: The objectives of this study were to identify clusters of patients with AS according to their socioeconomic characteristics and to evaluate the associations between these clusters and the severity of the disease and permanent disability. Design: This was a cross-sectional and multicentre study. Methods: Patients with AS from the REGISPONSER study were included in this analysis. A cluster analysis was conducted using information on sociodemographic (age, sex, race, marital status, education) and socioeconomic (employment, profession, housing conditions and social level) characteristics. Disease burden and permanent disability were compared between the different clusters using logistic regression adjusted for disease duration and disease activity. Results: A total of 866 patients with AS were included. Two clusters were identified according to socioeconomic characteristics: Cluster 1 (n = 476), with a predominantly low socioeconomic profile, and Cluster 2 (n = 390), with a predominantly high socioeconomic profile. After adjusting for disease duration, patients in Cluster 1 had a longer diagnosis delay, greater body mass index and greater structural damage than those in Cluster 2. Access to biologic disease-modifying anti-rheumatic drugs (bDMARDs) was similar for both groups. However, patients in Cluster 1 had a greater prevalence of permanent disability than those in Cluster 2 after adjusting for disease duration and disease activity (30.8% vs 13.2%, odds ratio 2.58 (95% confidence interval 1.76–3.83)). Conclusion: This study suggests that the socioeconomic status of patients with AS may have implications for disease severity and permanent disability, despite the similar use of bDMARDs. [ABSTRACT FROM AUTHOR]

Psoriatic disease, encompassing both psoriasis (Pso) and psoriatic arthritis (PsA), is closely intertwined with a significantly elevated risk of developing cardiovascular diseases. This connection is further compounded by a higher prevalence of cardiometabolic comorbidities, including type 2 diabetes, obesity, insulin resistance, arterial hypertension, and dysregulated lipid profiles. These comorbidities exceed the rates seen in the general population and compound the potential for increased mortality among those living with this condition. Recognizing the heightened cardiometabolic risk inherent in psoriatic disease necessitates a fundamental shift in the treatment paradigm. It is no longer sufficient to focus solely on mitigating inflammation. Instead, there is an urgent need to address and effectively manage the metabolic parameters that have a substantial impact on cardiovascular health. Within this context, apremilast emerges as a pivotal treatment option for psoriatic disease. What sets apremilast apart is its dual-action potential, addressing not only inflammation but also the critical metabolic parameters. This comprehensive treatment approach opens up new opportunities to improve the well-being of people living with psoriatic disease. This review delves into the multifaceted aspects involved in the development of cardiovascular disease and its intricate association with psoriatic disease. We then provide an in-depth exploration of the pleiotropic effects of apremilast, highlighting its potential to simultaneously mitigate metabolic complications and inflammation in individuals affected by these conditions. [ABSTRACT FROM AUTHOR]

Objectives We aimed to identify determinants of health-related quality of life (HRQoL) and global functioning and health (GH) in axial SpA (axSpA), peripheral SpA (pSpA) and (PsA). Methods The ASAS-perSpA study data were analysed. Models for the three patient groups were run separately to explore factors associated with HRQoL and GH, assessed by EQ-5D and ASAS-HI, respectively. Results The analyses included 4185 patients: 2719 with axSpA, 433 with pSpA, and 1033 with PsA. In axSpA, disease activity (β = –0.061), physical function (β = –0.041), female sex (β = –0.019) and fibromyalgia (FM) (β = –0.068) were associated with worse HRQoL; age (β = 0.001) and university education (β = 0.014) were associated with better HRQoL. In pSpA, disease activity (β = –0.04) and physical function (β = –0.054) were associated with worse HRQoL. In PsA, disease activity (β = –0.045), physical function (β = –0.053), axial disease (β = –0.041) and female sex (β = –0.028) were associated with worse HRQoL. In axSpA, disease activity (β = 0.889), physical function (β = 0.887), peripheral disease (β = 0.564), female sex (β = 0.812) and FM (β = 1.639) were associated with worse GH; age (β = –0.013) and university education (β = –0.274) were associated with better GH. In pSpA, physical function (β = 1.142) and female sex (β = 1.060) were associated with worse GH; university education (β = –0.611) was associated with better GH. In PsA, disease activity (β = 0.703), physical function (β = 1.025), axial involvement (β = 0.659), female sex (β = 0.924) and FM (β = 1.387) were associated with worse GH; age (β = –0.024) and university education (β = –0.856) were associated with better GH. Conclusion Disease activity and physical function are major HRQoL and GH determinants across SpA types, and clinical characteristics and sociodemographic factors play an important role, highlighting the importance of a holistic approach for individual patients. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis is a chronic rheumatic disease that poses challenges in its diagnosis, evaluation, and management. The heterogeneity in the manifestations and the absence of definitive diagnosis biomarkers often complicates the process of accurate diagnosis. Furthermore, the involvement of multiple disease domains poses difficulties in assessing disease activity and defining the concept of remission. Despite therapeutic advancements, a subset of patients remains refractory to treatment, leading to the emergence of the concept of "difficult-to-treat" patients and the necessity for novel therapeutic approaches (e.g., drugs with novel mechanisms of action; combinations of treatments). This review addresses key unmet needs in psoriatic arthritis, in terms of diagnosis, classification, evaluation, comorbidities and treatment. [ABSTRACT FROM AUTHOR]