37 research outputs found

    V*-algebras, independence algebras and logic

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    Independence algebras were introduced in the early 1990s by specialists in semigroup theory, as a tool to explain similarities between the transformation monoid on a set and the endomorphism monoid of a vector space. It turned out that these algebras had already been defined and studied in the 1960s, under the name of v*-algebras, by specialists in universal algebra (and statistics). Our goal is to complete this picture by discussing how, during the middle period, independence algebras began to play a very important role in logic

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    Add-on cannabidiol treatment for drug-resistant seizures in tuberous sclerosis complex

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    Importance Efficacy of cannabidiol has been demonstrated in seizures associated with Lennox-Gastaut and Dravet syndromes but appears not yet to have been established in conditions with primarily focal seizures, such as tuberous sclerosis complex (TSC).Objective To evaluate efficacy and safety of 25-mg/kg/day and 50-mg/kg/day cannabidiol dosages vs placebo against seizures associated with TSC.Design, Setting, and Participants This double-blind, placebo-controlled randomized clinical trial (GWPCARE6) enrolled patients between April 6, 2016, and October 4, 2018; follow-up was completed on February 15, 2019. The trial was conducted at 46 sites in Australia, Poland, Spain, the Netherlands, United Kingdom, and United States. Eligible patients (aged 1-65 years) were those with a clinical diagnosis of TSC and medication-resistant epilepsy who had had at least 8 TSC-associated seizures during the 4-week baseline period, with at least 1 seizure occurring in at least 3 of the 4 weeks, and were currently taking at least 1 antiepileptic medication.Interventions Patients received oral cannabidiol at 25 mg/kg/day (CBD25) or 50 mg/kg/day (CBD50) or a matched placebo for 16 weeks.Main Outcomes and Measures The prespecified primary outcome was the change from baseline in number of TSC-associated seizures for cannabidiol vs placebo during the treatment period.Results Of 255 patients screened for eligibility, 31 were excluded and 224 were randomized. Of the 224 included patients (median [range] age, 11.4 [1.1-56.8] years; 93 female patients [41.5%]), 75 were randomized to CBD25, 73 to CBD50, and 76 to placebo, with 201 completing treatment. The percentage reduction from baseline in the type of seizures considered the primary end point was 48.6% (95% CI, 40.4%-55.8%) for the CBD25 group, 47.5% (95% CI, 39.0%-54.8%) for the CBD50 group, and 26.5% (95% CI, 14.9%-36.5%) for the placebo group; the percentage reduction from placebo was 30.1% (95% CI, 13.9%-43.3%; P < .001) for the CBD25 group and 28.5% (95% CI, 11.9%-42.0%; nominal P = .002) for the CBD50 group. The most common adverse events were diarrhea (placebo group, 19 [25%]; CBD25 group, 23 [31%]; CBD50 group, 41 [56%]) and somnolence (placebo group, 7 [9%]; CBD25 group, 10 [13%]; CBD50 group, 19 [26%]), which occurred more frequently with cannabidiol than placebo. Eight patients in CBD25 group, 10 in CBD50 group, and 2 in the placebo group discontinued treatment because of adverse events. Twenty-eight patients taking cannabidiol (18.9%) had elevated liver transaminase levels vs none taking placebo.Conclusions and Relevance Cannabidiol significantly reduced TSC-associated seizures compared with placebo. The 25-mg/kg/day dosage had a better safety profile than the 50-mg/kg/day dosage

    Ultra-rare genetic variation in common epilepsies: a case-control sequencing study

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    BACKGROUND:Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies. METHODS:We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. FINDINGS:We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7-3·2, p=9·1 × 10-8; familial non-acquired focal epilepsy 3·6, 2·7-4·9, p=1·1 × 10-17). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10-8) that were lower than expected from a random sampling of genes. INTERPRETATION:We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. FUNDING:National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK

    Effects of a 15-day low carbohydrate, highfat diet in resistance-Trained men

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    © 2017 National Strength and Conditioning Association. Waldman, HS, Krings, BM, Basham, SA, Smith, JW, Fountain, BJ, and McAllister, MJ. Effects of a 15-day low carbohydrate, high-fat diet in resistance-Trained men. J Strength Cond Res 32(11): 3103-3111, 2018-This study examined the effects of a 15-day isocaloric low carbohydrate (,25% E), high-fat (.50% E) (LCHF) diet on physiological and metabolic alterations in resistance-Trained (RT) men. College-Aged RT men (n = 11) completed 4 V- O2max tests using treadmill every 5 days during the 15-day trial. Blood was drawn intravenously pre-exercise across each experimental trial for insulin, cortisol, and glucose. Pulmonary data were collected and substrate oxidation (OXI) was calculated during exercise. Body mass decreased (p , 0.04) with no further changes in anthropometric measures. Time to exhaustion was not affected across each day. Insulin dropped below baseline values (p , 0.0005). Cortisol increased from baseline to day 5 (p , 0.004) but returned back to near baseline at day 10, whereas glucose remained within normal range throughout the duration of the study. Carbohydrate (CHO) OXI dropped (p , 0.001) from baseline to day 5, and fat OXI increased from baseline to day 5 (p , 0.0001). Heart rate decreased from baseline to day 5 (p , 0.001) and again from day 10 to 15 (p , 0.02). Oxygen uptake (V- O2) decreased from day 5 to 10 (p , 0.0001). A nonketo LCHF diet appears to favor RT men by altering metabolic markers without decrements in aerobic performance and be a potential diet intervention used by coaches. However, the reported cardiorespiratory responses should be interpreted reasonably because of the possibility the subjects running economy improved over experimental trials

    Health-Related Quality of Life and Functional Status Are Associated with Cardiac Status and Clinical Outcome in Children with Cardiomyopathy

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    To measure the health-related quality of life (HRQOL) and functional status of children with cardiomyopathy and to determine whether they are correlated with sociodemographics, cardiac status, and clinical outcomes. Parents of children in the Pediatric Cardiomyopathy Registry completed the Child Health Questionnaire (CHQ; age ≥ 5 years) and Functional Status II (Revised) (age ≤ 18 years) instruments. Linear and Cox regressions were used to examine hypothesized associations with HRQOL. The 355 children evaluated at ≥ 5 years (median 8.6 years) had lower functioning (CHQ Physical and Psychosocial Summary Scores 41.7 ± 14.4 and 47.8 ± 10.7) than that of healthy historical controls. The most extreme CHQ domain score, Parental Impact-Emotional, was one SD below normal. Younger age at diagnosis and smaller left ventricular end-diastolic dimension z score were associated independently with better physical functioning in children with dilated cardiomyopathy. Greater income/education correlated with better psychosocial functioning in children with hypertrophic and mixed/other types of cardiomyopathy. In the age ≥ 5 year cohort, lower scores on both instruments predicted earlier death/transplant and listing for transplant in children with dilated and mixed/other types of cardiomyopathy (P < .001). Across all ages (n = 565), the Functional Status II (Revised) total score was 87.1 ± 16.4, and a lower score was associated with earlier death/transplant for all cardiomyopathies. HRQOL and functional status in children with cardiomyopathy is on average impaired relative to healthy children. These impairments are associated with older age at diagnosis, lower socioeconomic status, left ventricular size, and increased risk for death and transplant. Identification of families at risk for functional impairment allows for provision of specialized services early in the course of disease. ClinicalTrials.gov: NCT00005391

    Wet adhesion of buckypaper produced from oxidized multi-wall carbon nanotubes on soft animal tissue

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    Buckypaper (BP) is the general definition of a macroscopic assembly of entangled carbon nanotubes. In this paper a new property of a BP film produced from oxidized multi-wall carbon nanotubes was investigated. In particular, BP shows to be able to promptly and strongly adhere to animal internal soft and wet tissues, as evaluated by peeling and shear tests. BP adhesion strength is higher than that recorded for a commercial prosthetic fabric (sealed to the tissue by fibrin glue) and comparable with that of other reported optimized nano-patterned surfaces. In order to give an interpretation of the observed behavior, the BP composition, morphology, porosity, water wettability and mechanical properties were analyzed by AFM, Xray photoelectron spectroscopy, wicking tests, contact angle and stress-strain measurements. Although further investigations are needed to assess the biocompatibility and safety of the BP film used in this work, the obtained results pave the way for a possible future use of buckypaper as adhesive tape in abdominal prosthetic surgery. This would allow the substitution of conventional sealants or the reduction in the use of perforating fixation
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