71 research outputs found

    Galois theory and commutators

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    We prove that the relative commutator with respect to a subvariety of a variety of Omega-groups introduced by the first author can be described in terms of categorical Galois theory. This extends the known correspondence between the Froehlich-Lue and the Janelidze-Kelly notions of central extension. As an example outside the context of Omega-groups we study the reflection of the category of loops to the category of groups where we obtain an interpretation of the associator as a relative commutator.Comment: 14 page

    Prognostic value of test(s) for O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation for predicting overall survival in people with glioblastoma treated with temozolomide

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    BACKGROUND: Glioblastoma is an aggressive form of brain cancer. Approximately five in 100 people with glioblastoma survive for five years past diagnosis. Glioblastomas that have a particular modification to their DNA (called methylation) in a particular region (the O(6)‐methylguanine–DNA methyltransferase (MGMT) promoter) respond better to treatment with chemotherapy using a drug called temozolomide. OBJECTIVES: To determine which method for assessing MGMT methylation status best predicts overall survival in people diagnosed with glioblastoma who are treated with temozolomide. SEARCH METHODS: We searched MEDLINE, Embase, BIOSIS, Web of Science Conference Proceedings Citation Index to December 2018, and examined reference lists. For economic evaluation studies, we additionally searched NHS Economic Evaluation Database (EED) up to December 2014. SELECTION CRITERIA: Eligible studies were longitudinal (cohort) studies of adults with diagnosed glioblastoma treated with temozolomide with/without radiotherapy/surgery. Studies had to have related MGMT status in tumour tissue (assessed by one or more method) with overall survival and presented results as hazard ratios or with sufficient information (e.g. Kaplan‐Meier curves) for us to estimate hazard ratios. We focused mainly on studies comparing two or more methods, and listed brief details of articles that examined a single method of measuring MGMT promoter methylation. We also sought economic evaluations conducted alongside trials, modelling studies and cost analysis. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook all steps of the identification and data extraction process for multiple‐method studies. We assessed risk of bias and applicability using our own modified and extended version of the QUality In Prognosis Studies (QUIPS) tool. We compared different techniques, exact promoter regions (5'‐cytosine‐phosphate‐guanine‐3' (CpG) sites) and thresholds for interpretation within studies by examining hazard ratios. We performed meta‐analyses for comparisons of the three most commonly examined methods (immunohistochemistry (IHC), methylation‐specific polymerase chain reaction (MSP) and pyrosequencing (PSQ)), with ratios of hazard ratios (RHR), using an imputed value of the correlation between results based on the same individuals. MAIN RESULTS: We included 32 independent cohorts involving 3474 people that compared two or more methods. We found evidence that MSP (CpG sites 76 to 80 and 84 to 87) is more prognostic than IHC for MGMT protein at varying thresholds (RHR 1.31, 95% confidence interval (CI) 1.01 to 1.71). We also found evidence that PSQ is more prognostic than IHC for MGMT protein at various thresholds (RHR 1.36, 95% CI 1.01 to 1.84). The data suggest that PSQ (mainly at CpG sites 74 to 78, using various thresholds) is slightly more prognostic than MSP at sites 76 to 80 and 84 to 87 (RHR 1.14, 95% CI 0.87 to 1.48). Many variants of PSQ have been compared, although we did not see any strong and consistent messages from the results. Targeting multiple CpG sites is likely to be more prognostic than targeting just one. In addition, we identified and summarised 190 articles describing a single method for measuring MGMT promoter methylation status. AUTHORS' CONCLUSIONS: PSQ and MSP appear more prognostic for overall survival than IHC. Strong evidence is not available to draw conclusions with confidence about the best CpG sites or thresholds for quantitative methods. MSP has been studied mainly for CpG sites 76 to 80 and 84 to 87 and PSQ at CpG sites ranging from 72 to 95. A threshold of 9% for CpG sites 74 to 78 performed better than higher thresholds of 28% or 29% in two of three good‐quality studies making such comparisons

    Groundwater discharge impacts marine isotope budgets of Li, Mg, Ca, Sr, and Ba

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    © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Mayfield, K. K., Eisenhauer, A., Santiago Ramos, D. P., Higgins, J. A., Horner, T. J., Auro, M., Magna, T., Moosdorf, N., Charette, M. A., Gonneea, M. E., Brady, C. E., Komar, N., Peucker-Ehrenbrink, B., & Paytan, A. Groundwater discharge impacts marine isotope budgets of Li, Mg, Ca, Sr, and Ba. Nature Communications, 12(1), (2021): 148-020-20248-3, doi:10.1038/s41467-020-20248-3.Groundwater-derived solute fluxes to the ocean have long been assumed static and subordinate to riverine fluxes, if not neglected entirely, in marine isotope budgets. Here we present concentration and isotope data for Li, Mg, Ca, Sr, and Ba in coastal groundwaters to constrain the importance of groundwater discharge in mediating the magnitude and isotopic composition of terrestrially derived solute fluxes to the ocean. Data were extrapolated globally using three independent volumetric estimates of groundwater discharge to coastal waters, from which we estimate that groundwater-derived solute fluxes represent, at a minimum, 5% of riverine fluxes for Li, Mg, Ca, Sr, and Ba. The isotopic compositions of the groundwater-derived Mg, Ca, and Sr fluxes are distinct from global riverine averages, while Li and Ba fluxes are isotopically indistinguishable from rivers. These differences reflect a strong dependence on coastal lithology that should be considered a priority for parameterization in Earth-system models.We thank A. Beck, H. Dulai, I. Santos, C. Benitez-Nelson, W. Moore, A. Martin, and H. Windom for sample access. We also thank A. Kolevica, A. Heuser, H. Pryer, J. Middleton, R. Franks, F. Lon, N. Slater, and O. Šebek for their laboratory and analytical assistance. This material is based upon research supported by the National Science Foundation Graduate Research Fellowship Program and an internship provided through the U.S. Geological Survey Graduate Research Internship Program (GRIP). This research was also supported by grants from: the German Academic Exchange Service (DAAD), Northern California chapter of the Achievement Rewards for College Scientists Foundation, International Association of GeoChemistry, Geological Society of America, Northern California Geological Society, Myers Trust, Friends of Long Marine Lab, and UC MEXUS (to K.K.M.). We acknowledge funding from EU-ITN Horizon project 643084 (to A.E. and T.M.) and NSF grant Award Number 1259440 (to A.P.). We also acknowledge funding from NSF grant award number OCE-1736949 (to T.J.H.). Any use of trade, firm or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government

    Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis

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    <p><b>Background:</b> Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.</p> <p><b>Methods and Findings:</b> Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.</p> <p><b>Conclusions:</b> Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.</p&gt

    Three major haplotypes of the β2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder

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    Adrenergic receptor β2 (ADRB2) is a primary target for epinephrine. It plays a critical role in mediating physiological and psychological responses to environmental stressors. Thus, functional genetic variants of ADRB2 will be associated with a complex array of psychological and physiological phenotypes. These genetic variants should also interact with environmental factors such as physical or emotional stress to produce a phenotype vulnerable to pathological states. In this study, we determined whether common genetic variants of ADRB2 contribute to the development of a common chronic pain condition that is associated with increased levels of psychological distress and low blood pressure, factors which are strongly influenced by the adrenergic system. We genotyped 202 female subjects and examined the relationships between three major ADRB2 haplotypes and psychological factors, resting blood pressure, and the risk of developing a chronic musculoskeletal pain condition - Temporomandibular Joint Disorder (TMD). We propose that the first haplotype codes for lower levels of ADRB2 expression, the second haplotype codes for higher ADRB2 expression, and the third haplotype codes for higher receptor expression and rapid agonist-induced internalization. Individuals who carried one haplotype coding for high and one coding for low ADRB2 expression displayed the highest positive psychological traits, had higher levels of resting arterial pressure, and were about 10 times less likely to develop TMD. Thus, our data suggest that either positive or negative imbalances in ADRB2 function increase the vulnerability to chronic pain conditions such as TMD through different etiological pathways that imply the need for tailored treatment options

    Exercise and global well-being in community-dwelling adults with fibromyalgia: a systematic review with meta-analysis

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    <p>Abstract</p> <p>Background</p> <p>Exercise has been recommended for improving global-well being in adults with fibromyalgia. However, no meta-analysis has determined the effects of exercise on global well-being using a single instrument and when analyzed separately according to intention-to-treat and per-protocol analyses. The purpose of this study was to fill that gap.</p> <p>Methods</p> <p>Studies were derived from six electronic sources, cross-referencing from retrieved studies and expert review. Dual selection of randomized controlled exercise training studies published between January 1, 1980 and January 1, 2008 and in which global well-being was assessed using the Fibromyalgia Impact Questionnaire (FIQ) were included. Dual abstraction of data for study, subject and exercise program characteristics as well as assessment of changes in global well-being using the total score from the FIQ was conducted. Risk of bias was assessed using the Cochrane bias assessment tool. Random-effects models and Hedge's standardized effect size (<it>g</it>) were used to pool results according to per-protocol and intention-to-treat analyses.</p> <p>Results</p> <p>Of 1,025 studies screened, 7 representing 5 per-protocol and 5 intention-to-treat outcomes in 473 (280 exercise, 193 control) primarily female (99%) participants 18-73 years of age were included. Small, statistically significant improvements in global well-being were observed for per-protocol (<it>g </it>and 95% confidence interval, -0.39, -0.69 to -0.08) and intention-to-treat (-0.34, -0.53 to -0.14) analyses. No statistically significant within-group heterogeneity was found (per-protocol, Q<sub>w </sub>= 6.04, <it>p </it>= 0.20, <it>I</it><sup>2 </sup>= 33.8%; intention-to-treat, Q<sub>w </sub>= 3.19, <it>p </it>= 0.53, <it>I</it><sup>2 </sup>= 0%) and no between-group differences for per-protocol and intention-to-treat outcomes were observed (Q<sub>b </sub>= 0.07, <it>p </it>= 0.80). Changes were equivalent to improvements of 8.2% for per-protocol analyses and 7.3% for intention-to-treat analyses.</p> <p>Conclusions</p> <p>The results of this study suggest that exercise improves global well-being in community-dwelling women with fibromyalgia. However, additional research on this topic is needed, including research in men as well as optimal exercise programs for improving global well-being in adults.</p
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