172 research outputs found

    Average sedimentary rock rare Earth element patterns and crustal evolution: Some observations and implications from the 3800 Ma ISUA supracrustal belt, West Greenland

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    Rare earth element (REE) data is given on a set of clastic metasediments from the 3800 Ma Isua Supracrustal belt, West Greenland. Each of two units from the same sedimentary sequence has a distinctive REE pattern, but the average of these rocks bears a very strong resemblance to the REE pattern for the North American Shale Composite (NASC), and departs considerably from previous estimates of REE patterns in Archaean sediments. The possibility that the source area for the Isua sediments resembled that of the NASC is regarded as highly unlikely. However, REE patterns like that in the NASC may be produced by sedimentary recycling of material yielding patterns such as are found at Isua. The results lead to the following tentative conclusions: (1) The REE patterns for Isua Seq. B MBG indicate the existence of crustal materials with fractionated REE and negative Eu anomalies at 3800 Ma, (2) The average Seq. B REE pattern resembles that of the North American Shale Composite (NASC), (3) If the Seq. B average is truly representative of its crustal sources, then this early crust could have been extensively differentiated. In this regard, a proper understanding of the NASC pattern, and its relationship to post-Archaean crustal REE reservoirs, is essential, (4) The Isua results may represent a local effect

    Changes in the Prevalence of Child and Youth Mental Disorders and Perceived Need for Professional Help between 1983 and 2014: Evidence from the Ontario Child Health Study

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    © The Author(s) 2019. Objectives: To examine: 1) changes in the prevalence of mental disorders and perceived need for professional help among children (ages 4 to 11) and youth (ages 12 to 16) between 1983 and 2014 in Ontario and 2) whether these changes vary by age and sex, urban-rural residency, poverty, lone-parent status, and immigrant background. Methods: The 1983 (n = 2836) and 2014 (n = 5785) Ontario Child Health Studies are provincially representative cross-sectional surveys with identical self-report checklist measures of conduct disorder, hyperactivity, and emotional disorder, as well as perceived need for professional help, assessed by integrating parent and teacher responses (ages 4 to 11) and parent and youth responses (ages 12 to 16). Results: The overall prevalence of perceived need for professional help increased from 6.8% to 18.9% among 4- to 16-year-olds. An increase in any disorder among children (15.4% to 19.6%) was attributable to increases in hyperactivity among males (8.9% to 15.7%). Although the prevalence of any disorder did not change among youth, conduct disorder decreased (7.2% to 2.5%) while emotional disorder increased (9.2% to 13.2%). The prevalence of any disorder increased more in rural and small to medium urban areas versus large urban areas. The prevalence of any disorder decreased for children and youth in immigrant but not nonimmigrant families. Conclusions: Although there have been decreases in the prevalence of conduct disorder, increases in other mental disorders and perceived need for professional help underscore the continued need for effective prevention and intervention programs

    Clinical population pharmacokinetics and toxicodynamics of linezolid

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    Thrombocytopenia is a common side effect of linezolid, an oxazolidinone antibiotic often used to treat multidrug-resistant Gram-positive bacterial infections. Various risk factors have been suggested, including linezolid dose and duration of therapy, baseline platelet counts, and renal dysfunction; still, the mechanisms behind this potentially treatment-limiting toxicity are largely unknown. A clinical study was conducted to investigate the relationship between linezolid pharmacokinetics and toxico-dynamics and inform strategies to prevent and manage linezolid-associated toxicity. Forty-one patients received 42 separate treatment courses of linezolid (600 mg every 12 h). A new mechanism-based, population pharmacokinetic/toxicodynamic model was developed to describe the time course of plasma linezolid concentrations and platelets. A linezolid concentration of 8.06 mg/ liter (101% between-patient variability) inhibited the synthesis of platelet precursor cells by 50%. Simulations predicted treatment durations of 5 and 7 days to carry a substantially lower risk than 10- to 28-day therapy for platelet nadirs o

    Cerebral blood flow predicts differential neurotransmitter activity

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    Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific neurotransmitter systems remains unclear. We address this question by probing cerebral blood flow in healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms of action. We use a novel framework aimed at disentangling the observed effects to contribution from underlying neurotransmitter systems. We find for all evaluated compounds a reliable spatial link of respective cerebral blood flow changes with underlying neurotransmitter receptor densities corresponding to their primary mechanisms of action. The strength of these associations with receptor density is mediated by respective drug affinities. These findings suggest that cerebral blood flow is a sensitive brain-wide in-vivo assay of metabolic demands across a variety of neurotransmitter systems in humans
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