Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Nocturnal sleep, daytime sleepiness, and quality of life in stable patients on hemodialysis

BACKGROUND: Although considerable progress has been made in the treatment of chronic kidney disease, compromised quality of life continues to be a significant problem for patients receiving hemodialysis (HD). However, in spite of the high prevalence of sleep complaints and disorders in this population, the relationship between these problems and quality of life remains to be well characterized. Thus, we studied a sample of stable HD patients to explore relationships between quality of life and both subjective and objective measures of nocturnal sleep and daytime sleepiness METHODS: The sample included forty-six HD patients, 24 men and 22 women, with a mean age of 51.6 (10.8) years. Subjects underwent one night of polysomnography followed the next morning by a Multiple Sleep Latency Test (MSLT), an objective measure of daytime sleepiness. Subjects also completed: 1) a brief nocturnal sleep questionnaire; 2) the Epworth Sleepiness Scale; and, 3) the Quality of Life Index (QLI, Dialysis Version) which provides an overall QLI score and four subscale scores for Health & Functioning (H&F), Social & Economic (S&E), Psychological & Spiritual (P&S), and Family (F). (The range of scores is 0 to 30 with higher scores indicating better quality of life.) RESULTS: The mean (standard deviation; SD) of the overall QLI was 22.8 (4.0). The mean (SD) of the four subscales were as follows: H&F – 21.1 (4.7); S&E – 22.0 (4.8); P&S – 24.5 (4.4); and, F – 26.8 (3.5). H&F (r(s )= -0.326, p = 0.013) and F (r(s )= -0.248, p = 0.048) subscale scores were negatively correlated with periodic limb movement index but not other polysomnographic measures. The H&F subscale score were positively correlated with nocturnal sleep latency (r(s )= 0.248, p = 0.048) while the H&F (r(s )= 0.278, p = 0.030) and total QLI (r(s )= 0.263, p = 0.038) scores were positively associated with MSLT scores. Both of these latter findings indicate that higher life quality is associated with lower sleepiness levels. ESS scores were unrelated to overall QLI scores or the subscale scores. Subjective reports of difficulty falling asleep and waking up too early were significantly correlated with all four subscale scores and overall QLI. Feeling rested in the morning was positively associated with S&E, P&S, and Total QLI scores. CONCLUSION: Selected measures of both poor nocturnal sleep and increased daytime sleepiness are associated with decreased quality of life in HD patients, underscoring the importance of recognizing and treating these patients' sleep problems

A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Studies in Humans showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF

Paradoxical Sleep Suppresses Immediate Early Gene Expression in the Rodent Suprachiasmatic Nuclei

Light stimulates neuronal activity with subsequent expression of the protein product of the immediate early gene, c-fos, in the Suprachiasmatic Nuclei (SCN). Non-photic stimuli is also thought to modulate activity within the SCN. Here, we sought to determine the effects intrinsic stimuli, specifically, the states of sleep upon c-fos protein expression in the SCN. In 16 rats, c-fos protein expression was evaluated at a fixed time of 1600 h (subjective night), following 1 h of electroencephalographically defined sleep. During sleep, as the state of paradoxical sleep (PS) increased, c-fos protein expression decreased (r = −0.41, p < 0.033). The PS-associated reduction of c-fos positive cells occurred equally between animals asleep in the light and those asleep in the dark. We propose a model whereby PS duration might function as a homeostatic-entraining mechanism to reduce neuronal activity within the SCN, and thereby modulate circadian rhythms during sleep

Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction

Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82–0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction

GWAS meta-analysis reveals key risk loci in essential tremor pathogenesis

Essential tremor (ET) is a prevalent neurological disorder with a largely unknown underlying biology. In this genome-wide association study meta-analysis, comprising 16,480 ET cases and 1,936,173 controls from seven datasets, we identify 12 sequence variants at 11 loci. Evaluating mRNA expression, splicing, plasma protein levels, and coding effects, we highlight seven putative causal genes at these loci, including CA3 and CPLX1. CA3 encodes Carbonic Anhydrase III and carbonic anhydrase inhibitors have been shown to decrease tremors. CPLX1, encoding Complexin-1, regulates neurotransmitter release. Through gene-set enrichment analysis, we identify a significant association with specific cell types, including dopaminergic and GABAergic neurons, as well as biological processes like Rho GTPase signaling. Genetic correlation analyses reveals a positive association between ET and Parkinson’s disease, depression, and anxiety-related phenotypes. This research uncovers risk loci, enhancing our knowledge of the complex genetics of this common but poorly understood disorder, and highlights CA3 and CPLX1 as potential therapeutic targets

Sleep characteristics of persons with chronic fatigue syndrome and non-fatigued controls: results from a population-based study

BACKGROUND: The etiology and pathophysiology of chronic fatigue syndrome (CFS) remain inchoate. Attempts to elucidate the pathophysiology must consider sleep physiology, as unrefreshing sleep is the most commonly reported of the 8 case-defining symptoms of CFS. Although published studies have consistently reported inefficient sleep and documented a variable occurrence of previously undiagnosed primary sleep disorders, they have not identified characteristic disturbances in sleep architecture or a distinctive pattern of polysomnographic abnormalities associated with CFS. METHODS: This study recruited CFS cases and non-fatigued controls from a population based study of CFS in Wichita, Kansas. Participants spent two nights in the research unit of a local hospital and underwent overnight polysomnographic and daytime multiple sleep latency testing in order to characterize sleep architecture. RESULTS: Approximately 18% of persons with CFS and 7% of asymptomatic controls were diagnosed with severe primary sleep disorders and were excluded from further analysis. These rates were not significantly different. Persons with CFS had a significantly higher mean frequency of obstructive apnea per hour (p = .003); however, the difference was not clinically meaningful. Other characteristics of sleep architecture did not differ between persons with CFS and controls. CONCLUSION: Although disordered breathing during sleep may be associated with CFS, this study generally did not provide evidence that altered sleep architecture is a critical factor in CFS. Future studies should further scrutinize the relationship between subjective sleep quality relative to objective polysomnographic measures

A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis

Bell et al. report 46 new loci associated with biomarkers of iron homeostasis, including ferritin levels, iron binding capacity, and iron saturation, in the Icelandic, Danish and UK populations. The associated loci point to new iron-regulating proteins and important genetic differences between men and women