Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity

<p>Abstract</p> <p>Background</p> <p>The relationship between relative metabolic disturbances and developmental disorders is an emerging research focus. This study compares the nutritional and metabolic status of children with autism with that of neurotypical children and investigates the possible association of autism severity with biomarkers.</p> <p>Method</p> <p>Participants were children ages 5-16 years in Arizona with Autistic Spectrum Disorder (n = 55) compared with non-sibling, neurotypical controls (n = 44) of similar age, gender and geographical distribution. Neither group had taken any vitamin/mineral supplements in the two months prior to sample collection. Autism severity was assessed using the Pervasive Development Disorder Behavior Inventory (PDD-BI), Autism Treatment Evaluation Checklist (ATEC), and Severity of Autism Scale (SAS). Study measurements included: vitamins, biomarkers of vitamin status, minerals, plasma amino acids, plasma glutathione, and biomarkers of oxidative stress, methylation, sulfation and energy production.</p> <p>Results</p> <p>Biomarkers of children with autism compared to those of controls using a t-test or Wilcoxon test found the following statistically significant differences (p < 0.001): Low levels of biotin, plasma glutathione, RBC SAM, plasma uridine, plasma ATP, RBC NADH, RBC NADPH, plasma sulfate (free and total), and plasma tryptophan; also high levels of oxidative stress markers and plasma glutamate. Levels of biomarkers for the neurotypical controls were in good agreement with accessed published reference ranges. In the Autism group, mean levels of vitamins, minerals, and most amino acids commonly measured in clinical care were within published reference ranges.</p> <p>A stepwise, multiple linear regression analysis demonstrated significant associations between several groups of biomarkers with all three autism severity scales, including vitamins (adjusted R²of 0.25-0.57), minerals (adj. R²of 0.22-0.38), and plasma amino acids (adj. R²of 0.22-0.39).</p> <p>Conclusion</p> <p>The autism group had many statistically significant differences in their nutritional and metabolic status, including biomarkers indicative of vitamin insufficiency, increased oxidative stress, reduced capacity for energy transport, sulfation and detoxification. Several of the biomarker groups were significantly associated with variations in the severity of autism. These nutritional and metabolic differences are generally in agreement with other published results and are likely amenable to nutritional supplementation. Research investigating treatment and its relationship to the co-morbidities and etiology of autism is warranted.</p

The hibernating mobile phone: Dead storage as a barrier to efficient electronic waste recovery

© 2016 The Authors Hibernation, the dead storage period when a mobile phone is still retained by the user at its end-of-life, is both a common and a significant barrier to the effective flow of time-sensitive stock value within a circular economic model. In this paper we present the findings of a survey of 181 mobile phone owners, aged between 18–25years old, living and studying in the UK, which explored mobile phone ownership, reasons for hibernation, and replacement motives. This paper also outlines and implements a novel mechanism for quantifying the mean hibernation period based on the survey findings. The results show that only 33.70% of previously owned mobile phones were returned back into the system. The average duration of ownership of mobile phones kept and still in hibernation was 4years 11months, with average use and hibernation durations of 1year 11months, and 3years respectively; on average, mobile phones that are kept by the user are hibernated for longer than they are ever actually used as primary devices. The results also indicate that mobile phone replacement is driven primarily by physical (technological, functional and absolute) obsolescence, with economic obsolescence, partly in response to the notion of being ‘due an upgrade’, also featuring significantly. We also identify in this paper the concept of a secondary phone, a recently replaced phone that holds a different function for the user than their primary phone but is still valued and intentionally retained by the user, and which, we conclude, should be accounted for in any reverse logistics strategy

Effect of a vitamin/mineral supplement on children and adults with autism

<p>Abstract</p> <p>Background</p> <p>Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited.</p> <p>Method</p> <p>This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism were assessed. None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study. For a subset of the participants (53 children ages 5-16) pre and post measurements of nutritional and metabolic status were also conducted.</p> <p>Results</p> <p>The vitamin/mineral supplement was generally well-tolerated, and individually titrated to optimum benefit. Levels of many vitamins, minerals, and biomarkers improved/increased showing good compliance and absorption. Statistically significant improvements in metabolic status were many including: total sulfate (+17%, p = 0.001), S-adenosylmethionine (SAM; +6%, p = 0.003), reduced glutathione (+17%, p = 0.0008), ratio of oxidized glutathione to reduced glutathione (GSSG:GSH; -27%, p = 0.002), nitrotyrosine (-29%, p = 0.004), ATP (+25%, p = 0.000001), NADH (+28%, p = 0.0002), and NADPH (+30%, p = 0.001). Most of these metabolic biomarkers improved to normal or near-normal levels.</p> <p>The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised (PGI-R, Average Change, p = 0.008), and on the subscores for Hyperactivity (p = 0.003), Tantrumming (p = 0.009), Overall (p = 0.02), and Receptive Language (p = 0.03). For the other three assessment tools the difference between treatment group and placebo group was not statistically significant.</p> <p>Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers (adj. R²= 0.61, p < 0.0005) with the initial levels of biotin and vitamin K being the most significant (p < 0.05); both biotin and vitamin K are made by beneficial intestinal flora.</p> <p>Conclusions</p> <p>Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism.</p> <p>Trial Registration</p> <p><b>Clinical Trial Registration Number: </b><a href="http://www.clinicaltrials.gov/ct2/show/NCT01225198">NCT01225198</a></p

CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention in Diverse Clinical Settings.

Background Studies have demonstrated increased risk of major atherothrombotic events in CYP2C19 loss-of-function (LOF) variant carriers versus non-carriers treated with clopidogrel after percutaneous coronary intervention (PCI). We sought to evaluate real-world outcomes with the clinical implementation of CYP2C19-guided antiplatelet therapy after PCI. Methods and Results Data from 9 medical centers where genotyping was performed in the setting of PCI were included. Alternative therapy with prasugrel or ticagrelor was recommended for patients with a CYP2C19 LOF variant. The primary outcome was the composite of major atherothrombotic events (all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or hospitalization for unstable angina) within 12 months following PCI. Moderate or severe/life-threatening bleeding within 12 months was a secondary outcome. Among 3342 patients, 1032 (31%) were LOF carriers, of whom 571/1032 (55%) were treated with alternative therapy. In LOF carriers, the rate of major atherothrombotic events was lower in patients treated with alternative therapy versus clopidogrel (adjusted HR, 0.56; 95% CI 0.39-0.82). In those without a LOF allele, no difference was observed (adjusted HR, 1.07; 95% CI 0.71-1.60). There was no difference in bleeding with alternative therapy versus clopidogrel in either LOF carriers or those without a LOF allele. Conclusions Real-world data demonstrate lower atherothrombotic risk in CYP2C19 LOF carriers treated with alternative therapy versus clopidogrel and similar risk in those without a LOF allele treated with clopidogrel or alternative therapy. These data suggest that PCI patients treated with clopidogrel should undergo genotyping so that CYP2C19 LOF carriers can be identified and treated with alternative therapy

Impact of the CYP2C19*17 Allele on Outcomes in Patients Receiving Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results for the increased function CYP2C19*17 allele are also reported, its clinical relevance in this setting remains unclear. A collaboration across nine sites examined antiplatelet therapy prescribing and clinical outcomes in 3,342 patients after implementation of CYP2C19-guided antiplatelet therapy. Risk of major atherothrombotic and bleeding events over 12 months after PCI were compared across cytochrome P450 2C19 isozyme (CYP2C19) metabolizer phenotype and antiplatelet therapy groups by proportional hazards regression. Clopidogrel was prescribed to a similar proportion of CYP2C19 normal (84.5%), rapid (82.9%), and ultrarapid metabolizers (80.6%) (P = 0.360). Clopidogrel-treated normal metabolizers (20.4 events/100 patient-years; adjusted hazard ratio (HR) 1.00, 95% confidence interval (CI), 0.75-1.33, P = 0.993) and clopidogrel-treated rapid or ultrarapid metabolizers (19.1 events/100 patient-years; adjusted HR 0.95, 95% CI, 0.69-1.30, P = 0.734) exhibited no difference in major atherothrombotic events compared with patients treated with prasugrel or ticagrelor (17.6 events/100 patient-years). In contrast, clopidogrel-treated intermediate and poor metabolizers exhibited significantly higher atherothrombotic event risk compared with prasugrel/ticagrelor-treated patients (adjusted HR 1.56, 95% CI, 1.12-2.16, P = 0.008). When comparing clopidogrel-treated rapid or ultrarapid metabolizers to normal metabolizers, no difference in atherothrombotic (adjusted HR 0.97, 95% CI, 0.73-1.29, P = 0.808) or bleeding events (adjusted HR 1.34, 95% CI, 0.83-2.17, P = 0.224) were observed. In a real-world setting of genotype-guided antiplatelet therapy, the CYP2C19*17 allele did not significantly impact post-PCI prescribing decisions or clinical outcomes. These results suggest the CYP2C19 *1/*17 and *17/*17 genotypes have limited clinical utility to guide antiplatelet therapy after PCI

Variations of Li and Mg isotope ratios in bulk chondrites and mantle xenoliths

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 75 (2011): 5247-5268, doi:10.1016/j.gca.2011.06.026.We present whole rock Li and Mg isotope analyses of 33 ultramafic xenoliths from the terrestrial mantle, which we compare with analyses of 30 (mostly chondritic) meteorites. The accuracy of our new Mg isotope ratio measurement protocol is substantiated by a combination of standard addition experiments, the absence of mass independent effects in terrestrial samples and our obtaining identical values for rock standards using 2 different separation chemistries and 3 different mass-spectrometric introduction systems. Carbonaceous, ordinary and enstatite chondrites have irresolvable mean stable Mg isotopic compositions (δ25Mg = -0.14 ± 0.06; δ26Mg = - 0.27 ± 0.12‰, 2sd), but our enstatite chondrite samples have lighter δ7Li (by up to ~3‰) than our mean carbonaceous and ordinary chondrites (3.0 ± 1.5‰, 2sd), possibly as a result of spallation in the early solar system. Measurements of equilibrated, fertile peridotites give mean values of δ7Li = 3.5 ± 0.5‰, δ25Mg = -0.10 ± 0.03‰ and δ26Mg = -0.21 ± 0.07‰. We believe these values provide a useful estimate of the primitive mantle and they are within error of our average of bulk carbonaceous and ordinary chondrites. A fuller range of fresh, terrestrial, ultramafic samples, covering a variety of geological histories, show a broad positive correlation between bulk δ7Li and δ26Mg, which vary from -3.7 to +14.5‰, and -0.36 to +0.06‰, respectively. Values of δ7Li and δ26Mg lower than our estimate of primitive mantle are strongly linked to kinetic isotope fractionation, occurring during transport of the mantle xenoliths. We suggest Mg and Li diffusion into the xenoliths is coupled to H loss from nominally anhydrous minerals following degassing. Diffusion models suggest that the co-variation of Mg and Li isotopes requires comparable diffusivities of Li and Mg in olivine. The isotopically lightest samples require ~5-10 years of diffusive ingress, which we interpret as a time since volatile loss in the host magma. Xenoliths erupted in pyroclastic flows appear to have retained their mantle isotope ratios, likely as a result of little prior degassing in these explosive events. High δ7Li, coupled with high [Li], in rapidly cooled arc peridotites may indicate that these samples represent fragments of mantle wedge that has been metasomatised by heavy, slab-derived fluids. If such material is typically stirred back into the convecting mantle, it may account for the heavy δ7Li seen in some oceanic basalts.PPvS was supported by NERC grant NER/C510983/

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention

OBJECTIVES: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value

The influence of body weight on the pulmonary oxygen uptake kinetics in pre-pubertal children during moderate- and heavy intensity treadmill exercise

To assess the influence of obesity on the oxygen uptake (V˙O2) kinetics of pre-pubertal children during moderate- and heavy intensity treadmill exercise. We hypothesised that obese (OB) children would demonstrate significantly slower V˙O2 kinetics than their normal weight (NW) counterparts during moderate- and heavy intensity exercise. 18 OB (9.8 ± 0.5 years; 24.1 ± 2.0 kg m2) and 19 NW (9.7 ± 0.5 years; 17.6 ± 1.0 kg m2) children completed a graded-exercise test to volitional exhaustion and two submaximal constant work rate treadmill tests at moderate (90 % gas exchange threshold) and heavy (∆40 %) exercise intensities. Bodyweight significantly influenced the V˙O2 kinetics during both moderate- and heavy exercise intensities (P < 0.05). During moderate intensity exercise, the phase II τ (OB: 30 ± 13 cf. NW: 22 ± 7 s), mean response time (MRT; OB: 35 ± 16 cf. NW: 25 ± 10 s), phase II gain (OB: 156 ± 21 cf. NW: 111 ± 18 mLO2 kg−1 km−1) and oxygen deficit (OB: 0.36 ± 0.11 cf. NW: 0.20 ± 0.06 L) were significantly higher in the OB children (all P < 0.05). During heavy intensity exercise, the τ (OB: 33 ± 9 cf. NW: 27 ± 6 s; P < 0.05) and phase II gain (OB: 212 ± 61 cf. NW: 163 ± 23 mLO2 kg−1 km−1; P < 0.05) were similarly higher in the OB children. A slow component was observed in all participants during heavy intensity exercise, but was not influenced by weight status. In conclusion, this study demonstrates that weight status significantly influences the dynamic V˙O2 response at the onset of treadmill exercise in children and highlights that the deleterious effects of being obese are already manifest pre-puberty

Motivation of UK school pupils towards foreign languages: a large-scale survey at Key Stage 3

Motivation is one of the most significant predictors of success in foreign language learning. While individual and governmental commitment to the learning of foreign languages is growing throughout most of Europe and across the globe, it is stuttering in the United Kingdom. An entitlement to language learning in primary school is not yet fully in place, whilst the removal of language from the core curriculum at Key Stage 4 (ages 14 to 16) has led to a dramatic fall in numbers of language learners. Among national initiatives seeking to enhance learners’ interest in languages among school pupils are Specialist Language Colleges and the Languages Ladder. The latter, by certifying achievement through its associated accreditation scheme Asset Languages, seeks to engender a sense of success and motivate continuation of language study. This article reports on a study conducted in 2005-06 of the language learning motivation of over ten thousand school pupils at Key Stage 3 – the only group currently obliged to study a foreign language. The study analyses the nature of learner motivation and its relationship with gender, level of study (Years 7, 8 and 9) and type of school, and thus provides evidence for possible measures to increase numbers of teenagers studying a foreign language, and a baseline against which the success of policy initiatives can be measured in the future

Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke

Background and Objectives Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.Peer reviewe