Devil's staircase phase diagram of the fractional quantum Hall effect in the thin-torus limit

After more than three decades the fractional quantum Hall effect still poses challenges to contemporary physics. Recent experiments point toward a fractal scenario for the Hall resistivity as a function of the magnetic field. Here, we consider the so-called thin-torus limit of the Hamiltonian describing interacting electrons in a strong magnetic field, restricted to the lowest Landau level, and we show that it can be mapped onto a one-dimensional lattice gas with repulsive interactions, with the magnetic field playing the role of a chemical potential. The statistical mechanics of such models leads to interpret the sequence of Hall plateaux as a fractal phase diagram, whose landscape shows a qualitative agreement with experiments.Comment: 5 pages main text, 11 pages supplementary, 2 figure

Troubles du sommeil dans la maladie de Parkinson et les autres synucléinopathies

Notre premier objectif était d'explorer des troubles du sommeil peu étudiés chez des patients avec synucléinopathies (maladie de Parkinson (MP), démence en corps de Lewy (DCL), démence associée à la maladie de Parkinson (DMP) et atrophie multisystématisée (AMS)): l'insomnie d'une part et les comportements parasomniaques d'autre part. Parmi ces derniers, nous nous sommes surtout intéressés aux comportements moteurs anormaux survenant lors du sommeil non-paradoxal (sommeil NREM) chez ces patients. Insomnie : Nos données ont montré que les symptômes d'insomnie sont plus fréquents chez des patients avec une MP par rapport à des malades atteints d'autres pathologies chroniques. Les symptômes d'insomnie sont corrélés avec la durée de la MP, mais pas avec les symptômes et signes moteurs ou non-moteurs de la maladie (article 1). Comportements moteurs à partir d'éveils : Les patients avec MP, DCL/DMP et AMS rapportent souvent des comportements à expression motrice, simples et complexes, liés au sommeil, que nous proposons de regrouper sous le terme " comportements parasomniaques " (" parasomnia behaviors "). Dans tous ces épisodes, les patients semblent se comporter comme s'ils étaient en train de vivre leurs rêves ou une mise en scène onirique. A la vidéo-polysomnographie, ces épisodes surviennent soit dans une période de sommeil paradoxal stable où les mécanismes physiologiques d'abolition du tonus musculaire sont déficients, soit lors d'états intermédiaires de conscience entre le sommeil et un réveil qui se produit. Dans ce travail, nous décrivons systématiquement pour la première fois les aspects vidéo-polysomnographiques des comportement parasomniaques NREM (" NREM Parasomnia Behaviors, NPBs " dans une population sélectionnée de patients avec une MP, DCL/DMP et AMS. Par une analyse quantitative du spectre des fréquences EEG, nous avons montré que ces phénomènes sont probablement expliqués par des mécanismes physiopathologiques différents par rapport aux troubles d'éveil (autrement dits parasomnies NREM) de l'enfance. Les NPBs sembleraient être des phénomènes plutôt rares, d'apparition tardive dans les synucléinopathies (article 3). Nous avons démontré que les comportements moteurs à partir d'éveils NREM étaient plus fréquents chez les patients atteints de DCL/DMP que chez ceux atteints de la MP et nous faisons l'hypothèse que leur présence soit un indicateur d'évolutivité vers un stade avancé de la maladie plutôt qu'un marqueur spécifique de démence (article 2). D'un point de vue physiopathologique, les comportements observés lors des parasomnies du sommeil paradoxal et non-paradoxal pourraient être vus comme des " fenêtres " permissives pour l'exploration de l'activité mentale pendant le sommeil. Dans les NPBs cette fenêtre serait représentée par une défaillance des circuits de l'éveil (" arousal "), de l'attention et de la cognition lors des transitions du sommeil à la veille, tandis que dans le trouble du comportement en sommeil paradoxal (TCSP), par une défaillance des circuits du contrôle de l'atonie musculaire. En synthèse, les résultats de nos travaux suggèrent que l'insomnie et les comportements parasomniaques pourraient représenter l'expression clinique d'une altération fonctionnelle des circuits régulateurs du sommeil et de la veille et du déclin cognitif lié à la neurodégénérescence de la MP, la DCL/DMP et l'AMS, leur présence étant un indicateur d'un stade évolutif avancé de la maladie. Le TCSP comme modèle physiopathologique pour étudier l'akinésie et la bradykinésie : Notre deuxième objectif a été la mise en place d'un protocole visant à enregistrer de façon couplée à une vidéopolysomnographie, les potentiels de champ local des neurones des noyaux sous-thalamiques (NSTs) pendant le sommeil et la veille chez des patients avec un TCSP secondaire à une MP au moyen d'électrodes implantées dans le but d'une stimulation à haute fréquence des NSTs. Cette étude est basée sur l'observation que, dans la MP, les mouvements produits en sommeil paradoxal ne sont akinétiques mais proches de la normale. A ce jour, 3 patients ont pu être recrutés et participer à cette étude (étude Rêves Park NST).Our first aim was to evaluate some sleep disorders which are still poorly investigated in patients with synucleinopathies (Parkinson's disease (PD), dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) and multiple system atrophy (MSA)): insomnia, motor and behavioral phenomena emerging upon arousals from REM, and, particularly, non-REM sleep. Insomnia : Our data show that insomnia symptoms are more common in patients with PD compared to patients with other chronic medical conditions. Insomnia symptoms proved to be related to the duration of PD, but not to motor or non-motor symptoms or signs of PD (Article 1). Motor and behavioral phenomena emerging upon arousals : Patients with MP, DLB/PDD and AMS often seek medical attention for sleep-related movements and behaviors, which we proposed to label with the umbrella definition of "Parasomnia Behaviors". During these events, the patients seem to behave as if they were being enacting a dream or a fantastic setting. At video-polysomnography, these episodes prove to occur either during stable REM sleep in which physiological motor control mechanisms fail (so called REM without atonia) or during states of consciousness intermediate between sleep and wakefulness upon nocturnal arousals. In this work, we systematically studied and described for the first time the video-polysomnographic features of NREM Parasomnia Behaviors (NPBs) in a selected population of patients with MP, DLB/PDD and MSA. At quantitative analysis of the EEG frequency spectrum, we found patterns that are in favour of the hypothesis that the NPBs are likely to be underpinned by pathophysiologic mechanisms different from those underlying disorders of arousals in childhood (DOA, otherwise called NREM parasomnias). NPBs probably represent a rare, late-onset phenomenon observed in synucleinopathies (Article 3). We demonstrated that parasomnia behaviors were more common in patients with DLB/PDD than in those with PD and hypothesized that they may represent a sign of advanced disease rather than a specific hallmark of dementia (Article 2). From a pathophysiologic perspective, REM and NREM sleep parasomnias may be viewed as permissive "windows" for the exploration of sleep mental activity. In NPBs, this window would traduce a failure of the mechanisms of vigilance ("arousal"), attentional and cognitive processing during transitions from sleep to wakefulness, while in the REM sleep behavior disorder (RBD) by a failure of motor control. Overall, the findings of these studies indicate that insomnia and parasomnia behaviors could be the clinical endpoint of a functional alteration of regulators of sleep-wake activity and cognition due to the neurodegeneration associated with PD, DLB/DMP and AMS, and could reflect a more advanced stage of disease. RBD as a pathophysiological model to study the akinesia and bradykinesia : Our second aim was to set up a protocol to simultaneously record local field potentials from subthalamic nuclei neurons and video-polysomnography recordings during sleep and wakefulness in PD patients with RBD undergoing surgery for implantation of intracerebral electrodes for deep brain stimulation. This study is based on the previous observation that, during RBD, patients show, while asleep, movements and behaviors which are closer to normal movements in healthy subjects than to the movements of as PD. Three patients have been recruited and participated in this study so far (Rêves Park NST study)

Subjective sleep dysfunction and insomnia symptoms in Parkinson's disease: Insights from a cross-sectional evaluation of the French CoPark cohort

Introduction: Twenty-seven to 80% of patients with Parkinson's Disease (PD) complain of subjective sleep dysfunction and insomnia symptoms. Our aim is to describe the prevalence and features of subjective sleep dysfunction and insomnia symptoms in patients with PD compared to other patients. Methods: Cross-sectional analysis of 636 adult PD patients compared to 143 age and sex-matched non-PD control patients consulting their general practitioners. Insomnia symptoms and other sleep features were assessed by the Pittsburgh Sleep Quality Index (PSQI), a global score > 5 defining impaired sleep. The Chi-square test or the Student's t-test were used to assess the potential clinical and demographic differences between groups and between PD patients with vs. without sleep dysfunction. Logistic regression analysis was employed to test multivariate effects. Results: Sleep dysfunction and insomnia symptoms were more frequent in PD patients compared to control patients (63 vs. 45%, p = 0.001). Female gender, PD duration, presence of depression and anxiety were associated with the presence of insomnia in PD. Subjective sleep efficiency, habitual sleep quality, sleep disturbance and daytime dysfunction, but not sleep latency, were reduced in PD patients compared to controls. Conclusions: The prevalence of sleep dysfunction is higher in PD than in other general medical conditions. Insomnia in PD seems to affect sleep maintenance and consolidation, but not sleep onset.Fil: Ratti, Pietro Luca. Université Paul Sabatier; Francia. Inserm; Francia. Sleep and Epilepsy Center; Suiza. Toulouse University Hospital; FranciaFil: Negre Pages, Laurence. Toulouse University Hospital; Francia. Université Paul Sabatier; FranciaFil: Pérez Lloret, Santiago. Toulouse University Hospital; Francia. Université Paul Sabatier; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Manni, Raffaele. Istituto di Ricovero e Cura a Carattere Scientifico. Istituto Neurologico Nazionale a Carattere Scientifico; ItaliaFil: Damier, Philippe. Universite de Nantes; FranciaFil: Tison, Francois. Universite de Bordeaux; FranciaFil: Destée, Alain. Centre Hospitalier Universitaire de Lille. Pôle de Neurologie. Service de Neurologie et pathologie du mouvement; FranciaFil: Rascol, Olivier. Toulouse University Hospital; Francia. Inserm; Francia. Toulouse University Hospital; Francia. Université Paul Sabatier; Franci

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons