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Takay, Bahar, and Güler Aydın. "What if Marx and Veblen met…" Ekonomski anali 59, no. 202 (2014): 131–56. http://dx.doi.org/10.2298/eka1402131t.
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The aim of this study is to analyse both the differences and the similarities between Marx and Veblen regarding historical specificity, evolution, and alienation. Starting with their discussions on these subjects, this article builds on the analyses of capitalism. The goal of this study is not to collapse Marx and Veblen into one another but rather to understand capitalism by presenting the complementary relationship of the two economists? analyses and to introduce an appropriate analytical framework for understanding capitalism. This study consists of three parts. The first part examines how Veblen regarded Marx?s analysis, and how Marx especially viewed Darwin?s theory of evolution. Marx?s approach to evolution and Veblen?s criticism of Marx on this topic will constitute the general framework of this part. The second part of the study evaluates the level of agreement or disagreement between Veblen and Marx on the idea of historicism from the perspective of dialectical materialism. The last part analyses Marx and Veblen?s different ideas of the concept of alienation. The two economists? views on the capitalist system will be determined based on these three concepts, introducing the similarities between them as well as the differences.
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van Heest, Cocky. "Met Het Oog op Vertalingen." Toegepaste Taalwetenschap in Artikelen 59 (January 1, 1998): 117–28. http://dx.doi.org/10.1075/ttwia.59.11hee.
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After studying the functional model for translation quality assessment created by Hulst (1995) and primarily aimed at revealing textual relations, we addressed the question whether this model would enable us to define 'functional' errors, i.e. errors that obscure the textual relations in such a way that the text function cannot be understood properly. To find an answer to this question, two Spanish texts were analysed according to the method of text analysis of Hulst's model, and subsequently, 26 Dutch translations were broadly analysed. A systematic comparison of the translation errors with the analyses of the source texts demonstrated that errors causing changes in textual relations nearly always reduce the comprehensibility of the text, while other mistakes do not cause misunder-standing. Hence, the research has demonstrated that in fact a distinction can be made between 'functional' and 'non-functional' errors, and the criterion for such a classification is not the type of error, but its effect on the textual relations. An investigation among Dutch readers of the translations has convincingly confirmed this conclusion.
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Minzhong, Wang, Wei Wenshou, He Qing, Yang Lianmei, Qin He, and Zhang Yunhui. "Application of wind profiler data to rainstorm analyses in Aksu, Xinjiang." Meteorological Applications 20, no. 4 (June 1, 2012): 504–12. http://dx.doi.org/10.1002/met.1326.
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Long, D. J., D. R. Jackson, J. Thuburn, and C. Mathison. "Validation of Met Office upper stratospheric and mesospheric analyses." Quarterly Journal of the Royal Meteorological Society 139, no. 674 (October 30, 2012): 1214–28. http://dx.doi.org/10.1002/qj.2031.
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Pinson, Pierre, and Renate Hagedorn. "Verification of the ECMWF ensemble forecasts of wind speed against analyses and observations." Meteorological Applications 19, no. 4 (August 8, 2011): 484–500. http://dx.doi.org/10.1002/met.283.
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Alfthan, Georg, Jouko Sundvall, Laura Råman, Kari Kuulasmaa, and Hanna Tolonen. "Standardisation of laboratories engaged in lipid analyses of population health examination surveys." Journal of Epidemiology and Community Health 72, no. 7 (April 10, 2018): 653–57. http://dx.doi.org/10.1136/jech-2018-210763.
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BackgroundReliable data on clinical biomarkers are necessary in order to assess the health risks of populations and especially in assessing long-term trends related to disease incidence.MethodsTen European laboratories participated in a two-phase quality control exercise of total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) analysis. The European Health Examination Survey Reference Laboratory prepared plasma batches for analysis, and provided target values for them. Two criteria were set for the precision and the systematic error (bias). Three plasma samples were analysed in duplicate on separate days (n=12).ResultsIn Round 1, all laboratories met the acceptable criterion (3%) for precision of TC. The mean bias of all laboratories was 0.99% (95% CI 0.03% to 1.95%). Six laboratories measured samples from Round 2. Five laboratories met the goal criterion of 3%; one failed to meet the acceptable criterion of 5%. The mean bias for HDL-C of the three batches of six laboratories was within goal limits (±5% from target) and that of all 10 within acceptable (±10%). The mean bias of all laboratories was 1.1% (95% CI −0.18 to 2.32). In Round 2 four laboratories met the goal criterion and one the acceptable criterion.ConclusionThe quality control exercise demonstrated that although the majority of the laboratories met the strict criteria for systematic error for TC and HDL-C, standardisation of methods is still needed to improve the accuracy of biomarker measurements of laboratories engaged in population health surveys. A protocol is recommended for obtaining reliable and comparable biomarker data between countries.
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Hand, Will H., and Gennaro Cappelluti. "A global hail climatology using the UK Met Office convection diagnosis procedure (CDP) and model analyses." Meteorological Applications 18, no. 4 (January 4, 2011): 446–58. http://dx.doi.org/10.1002/met.236.
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Sanders, Mathijs. "EEN UURTJE MET DIRK COSTER." De Moderne Tijd 1, no. 2 (January 1, 2017): 118–33. http://dx.doi.org/10.5117/dmt2017.2.002.sand.
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AN HOUR WITH DIRK COSTER The self-fashioning of a literary informant In 1927, the French literary magazine La Nouvelle Littéraire published an interview with the Dutch writer Dirk Coster by the renowned critic Frédéric Lefèvre in the series ‘Une heure avec ...’. Coster used the opportunity to present himself as an international cultural mediator and as a spokesman of a humanistic conception of literature. This article analyses the interview by focussing on the way Coster was portrayed in front of a French audience and by interpreting his statements concerning both Dutch and French literature.
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Deshpande, R. D., Medha Dave, Virendra Padhya, Hrishikesh Kumar, and S. K. Gupta. "Water vapour source identification for daily rain events at Ahmedabad in semi-arid western India: wind trajectory analyses." Meteorological Applications 22, no. 4 (October 2015): 754–62. http://dx.doi.org/10.1002/met.1515.
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Han, Jing, Zhigang Chu, Zhenhui Wang, Dan Xu, Nan Li, Leilei Kou, Fen Xu, and Yiqing Zhu. "The establishment of optimal ground-based radar datasets by comparison and correlation analyses with space-borne radar data." Meteorological Applications 25, no. 1 (December 5, 2017): 161–70. http://dx.doi.org/10.1002/met.1682.
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Assië, Chantal, and Merit Hondelink. "Appels met (kwee)peren vergelijken." Paleo-aktueel, no. 30 (December 14, 2019): 93–99. http://dx.doi.org/10.21827/pa.30.93-99.
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Comparing apples, quinces and pears. While establishing the identification possibilities of subfossil plant tissues derived from cesspits, the following question arose: is variation within species a limiting factor for establishing diagnostic characteristics? In order to answer this question core fragments of modern fruits of Apples, Quinces and Pears were examined. These fragments are frequently encountered during archaeobotanical analyses of cesspits. However, they are rarely identified to a species level, due to a lack of criteria for identification. This study also aims to provide criteria for identification in addition to visual reference material. A comparison of modern and subfossil remains revealed that the characteristics of Apple and Quince show similarities, which complicates the identification possibilities of these two species. However, it is possible to distinguish between the core fragments of Apple and Pear.
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LEAR, T. L., and E. BAILEY. "Southern blot analyses of the MET locus in horses and cattle." Animal Genetics 22, no. 3 (April 24, 2009): 307. http://dx.doi.org/10.1111/j.1365-2052.1991.tb00682.x.
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Nugent, William R. "Variability in the Results of Meta-Analysis as a Function of Comparing Effect Sizes Based on Scores From Noncomparable Measures: A Simulation Study." Educational and Psychological Measurement 77, no. 3 (June 16, 2016): 449–70. http://dx.doi.org/10.1177/0013164416654517.
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Meta-analysis is a significant methodological advance that is increasingly important in research synthesis. Fundamental to meta-analysis is the presumption that effect sizes, such as the standardized mean difference (SMD), based on scores from different measures are comparable. It has been argued that population observed score SMDs based on scores from different measures A and B will be equal only if the conjunction of three conditions are met: construct equivalence (CE), equal reliabilities (ER), and the absence of differential test functioning (DTF) in all subpopulations of the combined populations of interest. It has also been speculated the results of a meta-analysis of SMDs might differ between circumstances in which the SMDs included in a meta-analysis are based on measures which all met the conjunction of these conditions and that in which the conjunction of these conditions is violated. No previous studies have tested this conjecture. This Monte Carlo study investigated this hypothesis. A population of studies comparing one of five hypothetical treatments with a placebo condition was simulated. The SMDs in these simulated studies were based on true scores from six hypothetical measures. The scores from some of these measures met the conjunction of CE, ER, and, the absence of DTF, while others failed to meet CE. Three meta-analyses were conducted using both fixed effects and random effects methods. The results suggested that the results of meta-analyses can vary to a practically significant degree when the SMDs were based on scores from measures failing to meet the CE condition. Implications for future research are considered.
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Kang, Ji-hun, and Yun-Mi Song. "Association Between Cotinine-Verified Smoking Status and Metabolic Syndrome: Analyses of Korean National Health and Nutrition Examination Surveys 2008–2010." Metabolic Syndrome and Related Disorders 13, no. 3 (April 2015): 140–48. http://dx.doi.org/10.1089/met.2014.0124.
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Bertolotto, Paolo A., and Guido Roggero. "Comparison of instability indices from COSMO-I7 and ECMWF-IFS analyses over the Piedmont Region, Italy, and new modifications to theKIndex." Meteorological Applications 23, no. 4 (October 2016): 605–13. http://dx.doi.org/10.1002/met.1582.
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Raghav, Kanwal Pratap Singh, Chad Tang, M. Pia Morelli, Hesham M. Amin, Ken Chen, Ganiraju C. Manyam, Bradley McIntosh Broom, et al. "Multiple independent methods fail to confirm MET amplification rate reported in literature for metastatic colorectal cancer (mCRC)." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 572. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.572.
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572 Background: MET inhibition is emerging as a potent therapeutic strategy and MET gene amplification has shown predictive significance. MET amplification rate in mCRC, as previously reported in literature, varies from 9% in primary to 18% in metastases but intermixes increased copy number from chromosomal level aberrations with focal gene amplification. Validation of MET amplification rate in mCRC is needed. Methods: We performed analyses of MET amplification in mCRC patients (pts) (n = 636) across multiple cohorts. Cohort 1 (n = 103) included tissue microarray from liver metastases analysed using fluorescence in situ hybridization (FISH) [cMET and CEP7 probes, MET/CEP7 ratio > 2]. Cohort 2 (n = 205) included pts referred for phase I trials who had MET amplification testing using FISH. Cohort 3 (n = 279) included cases sequenced with HiSeq (Illumina) with full exome coverage for 202 genes including MET (average depth 800) with focal gene amplification (≥ 4 copies) identified by an in-house algorithm. Cohort 4 (n = 49) included pts refractory to EGFR monoclonal antibodies enrolled in the ATTACC (a prospective molecular screening) program for mCRC, in whom plasma circulating-free DNA (cfDNA) was analyzed by Guardant sequencing technology. Results: In tissue based analyses, focal MET amplification rate was 1.7% and was higher in primary tumors compared to metastases [3.1% (9/291) vs. 0.4% (1/288), p = 0.02] [Table]. In cohorts 2 & 3 MET amplification was found in 4 [MET/CEP7: 2.1 – 7.7; primary (4/130), metastases (0/75)] and 6 [copy number: 4.0 – 6.7; primary (5/161), metastases (1/110)] cases, respectively. MET amplification rate in pts who had progressed on anti-EGFR therapy was 14.3% (Table). Conclusions: Contrary to prior reports, in this large cohort, MET amplification was a rare event in mCRC pts and the rate was not higher in metastatic sites. However, MET amplification occurred in a sizable subset of pts refractory to anti-EGFR therapy as identified by cfDNA analysis. MET amplification appears to play a minor role in de novo colorectal carcinogenesis but may play an important role in acquired resistance to anti-EGFR therapy. [Table: see text]
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Gómez, Breogán, Cristina L. Charlton-Pérez, Huw Lewis, and Brett Candy. "The Met Office Operational Soil Moisture Analysis System." Remote Sensing 12, no. 22 (November 11, 2020): 3691. http://dx.doi.org/10.3390/rs12223691.
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In this study, the current Met Office operational land surface data assimilation system used to produce soil moisture analyses is presented. The main aim of including Land Surface Data Assimilation (LSDA) in both the global and regional systems is to improve forecasts of surface air temperature and humidity. Results from trials assimilating pseudo-observations of 1.5 m air temperature and specific humidity and satellite-derived soil wetness (ASCAT) observations are analysed. The pre-processing of all the observations is described, including the definition and construction of the pseudo-observations. The benefits of using both observations together to produce improved forecasts of surface air temperature and humidity are outlined both in the winter and summer seasons. The benefits of using active LSDA are quantified by the root mean squared error, which is computed using both surface observations and European Centre for Medium-Range Weather Forecasts (ECMWF) analyses as truth. For the global model trials, results are presented separately for the Northern (NH) and Southern (SH) hemispheres. When compared against ground-truth, LSDA in winter NH appears neutral, but in the SH it is the assimilation of ASCAT that contributes to approximately a 2% improvement in temperatures at lead times beyond 48 h. In NH summer, the ASCAT soil wetness observations degrade the forecasts against observations by about 1%, but including the screen level pseudo-observations provides a compensating benefit. In contrast, in the SH, the positive effect comes from including the ASCAT soil wetness observations, and when both observations types are assimilated there is a compensating effect. Finally, we demonstrate substantial improvements to hydrological prediction when using land surface data assimilation in the regional model. Using the Nash-Sutcliffe Efficiency (NSE) metric as an aggregated measure of river flow simulation skill relative to observations, we find that NSE was improved at 106 of 143 UK river gauge locations considered after LSDA was introduced. The number of gauge comparisons where NSE exceeded 0.5 is also increased from 17 to 28 with LSDA.
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Koltai, Zsófia, Bernadett Szabó, Judit Jakus, and Péter Vajdovich. "Tyrosine kinase expression analyses in canine mammary gland tumours – A pilot study." Acta Veterinaria Hungarica 66, no. 2 (June 2018): 294–308. http://dx.doi.org/10.1556/004.2018.027.
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Messenger RNA levels of oncogenic tyrosine kinases were determined in canine mammary tumours using real-time RT-PCR. The following tyrosine kinases and vascular endothelial growth factors (VEGF) were examined in malignant and healthy mammary tissues of 13 dogs: VEGFR1, VEGFR2, EGFR, ErbB2, PDGFR1, c-KIT and c-MET. Expression levels of all these factors were significantly higher in tumour samples than in normal mammary tissues taken from the same animal. Higher grading was associated with higher VEGFR1 levels. Grade III tumours showed significantly higher VEGF, c-MET and c-KIT mRNA expression, while Grade I tumours with lower malignancy showed significantly higher PDGFR1 and EGFR expression than tumours classified as Grade II or III. The increased presence of VEGF, VEGFR1, c-KIT and c-MET is a negative prognostic factor as these signal transduction molecules contribute to increased tumour malignancy. The presented data provide evidence, for the first time, for the existence of a complex overexpression and dysregulation of VEGF and several oncogenic tyrosine kinases such as VEGR1, PDGFR1, c-KIT and c-MET in canine mammary tumours. Therefore, canine mammary tumours may be potential targets for tyrosine kinase inhibitor therapy.
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Dubbink, Hendrikus J., Willemina Geurts-Giele, Isabelle Meijssen, Cor van der Leest, Robert Peric, Jan Von Der Thusen, Joachim Aerts, and Winand N. M. Dinjens. "One year experience of MET gene exon 14 skipping analysis in lung cancer: Identification of 18 cases by NGS." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e20055-e20055. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e20055.
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e20055 Background: Lung adenocarcinoma (LAC) is the most common histological type of non-small-cell lung cancer and is one of the malignancies with the most evolved personalized treatments based on molecular characteristics of the tumor. Mutations in EGFR, HER2 and BRAF, specific translocations of ALK, ROS1, RET and amplification of MET all have standard diagnostic importance and lead to specific treatment options for the individual LAC patients. Recently, in 2-4% of LAC MET gene mutations leading to skipping of exon 14 were found. These mutations were described to occur more frequently in tumors with sarcomatoid histology. LAC with MET exon 14 skipping mutations showed impressive, although temporary, responses to MET tyrosine kinase inhibitors (TKI) crizotinib, cabozantinib and capmatinib. We will present our experience with routine molecular diagnostic detection of the most common MET exon 14 skipping mutations. Methods: In January 2016 we included in our standard, DNA based, molecular diagnostics custom-made NGS analyses 4 amplicons for detection of MET skipping mutations. The analyses were performed on microdissected FFPE tissue sections or routine histology or cytology stained preparations. Nine different mutations were validated for their effect on splicing by RT-PCR on RNA isolated from the same tissue samples. Results: Between January 2016 and January 2017 676 routine molecular diagnostic analyses on LAC were performed. In 18 (2.7%) cases MET mutations were detected possibly resulting in exon 14 skipping. Nine out of 16 different mutations were tested by RT-PCR and all 9 were demonstrated to result in MET exon 14 skipping. Conclusions: MET exon 14 skipping mutations can reliably be detected in routine pathology tissue samples. These analyses can easily be included in routine molecular diagnostic NGS. When necessary, confirmation of the mutational effect on RNA splicing can be implemented as well. Routine identification of MET skipping mutations (2.7% of cases) adds substantially to the personalized targeted treatment strategies for LAC patients.
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Borelli, Noah, Bouzid Choubane, James Greene, Charles Holzschuher, and James Fletcher. "Cross-Correlation Analysis of Line Laser High-speed Inertial Profilers." Transportation Research Record: Journal of the Transportation Research Board 2674, no. 5 (May 2020): 626–36. http://dx.doi.org/10.1177/0361198120917371.
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Thirteen different line-laser high-speed inertial profilers from four different manufacturers were recently tested at the Florida Department of Transportation (FDOT) Inertial Profiler Test Track. The hot-mix asphalt (HMA) track incorporates both dense and open-graded sections with international roughness index (IRI) values ranging from 34 to 104 in./mi. A cross-correlation analysis was performed on the resulting ride data. The accuracy comparison was performed using a SurPro reference profiler. The profilers as a group met the AASHTO R 56 cross-correlation criteria on each section except on a smooth, open-graded section. The profilers as a group met the repeatability cross-correlation on this section, but did not meet the accuracy cross-correlation requirement. This paper presents a description of the testing program, data collection efforts and subsequent analyses and findings.
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Stortelder, M., C. de Graauw, and T. J. M. van Els. "Nederlands Leren Met De Edittraining." Computer-ondersteund talenonderwijs 33 (January 1, 1989): 82–88. http://dx.doi.org/10.1075/ttwia.33.11sto.
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At the Institute of Applied Social Sciences in Nijmegen a computer based language training programme is being developed and experimentally evaluated in secondary schools. The programme called Edittraining, is based on the principle of the editing-test. This editing-test is a test of general language competence and consists of a reading text in which randomly chosen words have been randomly inserted; the number of the 'intruders1 is about 12 per cent of the original number of words. The main task is to delete these intruders. To execute the task not only lexical but also grammatical competence is needed. The four main components of the programme are: a set of 12 reading texts processed as editing tasks, grammatical feedback supplied with various text elements, a students' grammar, and a lexicon. In experiments executed in secondary schools empirical data have been obtained on the effectiveness of the programme. The main hypothesis is that learning by Edittraining leads to improvement of language proficiency. The specific hypotheses pertain to the improvement of general language competence, reading competence, grammatical compe-tence and knowledge of grammatical concepts. The design chosen was a pre- and post-test design, with experimental and control groups. The pre-tests used were a cloze-test and a grammatical knowledge test; the post-tests were the same cloze-test, a parallel version of the grammatical knowledge test, a multiple choice test for reading comprehension, and a grammatical skill test. The results of a covariance-analysis showed a positive significant effect for the experimental group on the cloze-test, on a subtest of the grammatical knowlegde test called 'concepts' and on a subtest of the grammatical skill test called 'composition of noun and preposition groups'. Most of the grammar subtests turned out to be rather easy for these pupils. Analyses for subgroups, with less than or equal to 60 or 80% correct on the pre-test, did not greatly alter the results except for the cloze-test. For the group with less than or equal to 50% correct on the pre-test of the cloze-test, the effect of the Edittraining was a little stronger than for the group as a whole. We can conclude that learning by Edittraining leads to a significant improvement of general language proficiency and of some grammar subskills but not of reading comprehension and the other grammar subskills that were tested. Other specific hypotheses concerning special versions of the programme such as working in groups or individually, positive versus neutral feedback, and feedback following each separate part or the whole of the text, showed no clear results.
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Bos, Kelly, Dave A. Dongelmans, Jop Groeneweg, Dink A. Legemate, Ian P. Leistikow, and Maarten J. van der Laan. "Criteria for recommendations after perioperative sentinel events." BMJ Open Quality 10, no. 3 (September 2021): e001493. http://dx.doi.org/10.1136/bmjoq-2021-001493.
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BackgroundThe recurrence of sentinel events (SEs) is a persistent problem worldwide, despite repeated analyses and recommendations formulated to prevent recurrence. Research suggests this is partly attributable to the quality of the recommendations, and determining if a recommendation will be effective is not yet covered by an adequate guideline. Our objectives were to (1) develop and validate criteria for high-quality recommendations, and (2) evaluate recommendations using the criteria developed.Methods(1) Criteria were developed by experts using the bowtie method. Medical doctors then determined if the recommendations of Dutch in-hospital SE analysis reports met the criteria, after which interobserver variability was tested. (2) Researchers determined which recommendations of Dutch perioperative SE analysis reports produced from 2017 to 2018 met the criteria.ResultsThe criteria were: (1) a recommendation needs to be well defined and clear, (2) it needs to specifically describe the intended changes, and (3) it needs to describe how it will reduce the risk or limit the consequences of a similar SE. Validation of criteria showed substantial interobserver agreement. The SE analysis reports (n=115) contained 442 recommendations, of which 64% failed to meet all criteria, and 28% of reports did not contain a single recommendation that met the criteria.ConclusionWe developed and validated criteria for high-quality recommendations. The majority of recommendations did not meet our criteria. It was disconcerting to find that over a quarter of the investigations did not produce a single recommendation that met the criteria, not even in SEs with a fatal outcome. Healthcare providers have an obligation to prevent SEs, and certainly their recurrence. We anticipate that using these criteria to determine the potential of recommendations will aid in this endeavour.
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Steiner, A. K., G. Kirchengast, and H. P. Ladreiter. "Inversion, error analysis, and validation of GPS/MET occultation data." Annales Geophysicae 17, no. 1 (January 31, 1999): 122–38. http://dx.doi.org/10.1007/s00585-999-0122-5.
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Abstract. The global positioning system meteorology (GPS/MET) experiment was the first practical demonstration of global navigation satellite system (GNSS)-based active limb sounding employing the radio occultation technique. This method measures, as principal observable and with millimetric accuracy, the excess phase path (relative to propagation in vacuum) of GNSS-transmitted radio waves caused by refraction during passage through the Earth's neutral atmosphere and ionosphere in limb geometry. It shows great potential utility for weather and climate system studies in providing an unique combination of global coverage, high vertical resolution and accuracy, long-term stability, and all-weather capability. We first describe our GPS/MET data processing scheme from excess phases via bending angles to the neutral atmospheric parameters refractivity, density, pressure and temperature. Special emphasis is given to ionospheric correction methodology and the inversion of bending angles to refractivities, where we introduce a matrix inversion technique (instead of the usual integral inversion). The matrix technique is shown to lead to identical results as integral inversion but is more directly extendable to inversion by optimal estimation. The quality of GPS/MET-derived profiles is analyzed with an error estimation analysis employing a Monte Carlo technique. We consider statistical errors together with systematic errors due to upper-boundary initialization of the retrieval by a priori bending angles. Perfect initialization and properly smoothed statistical errors allow for better than 1 K temperature retrieval accuracy up to the stratopause. No initialization and statistical errors yield better than 1 K accuracy up to 30 km but less than 3 K accuracy above 40 km. Given imperfect initialization, biases >2 K propagate down to below 30 km height in unfavorable realistic cases. Furthermore, results of a statistical validation of GPS/MET profiles through comparison with atmospheric analyses of the European Centre for Medium-range Weather Forecasts (ECMWF) are presented. The comparisons indicate the high utility of the occultation data in that very good agreement of upper troposphere/lower stratosphere temperature (better than 1.5 K rms, <0.5 K bias) is found for a region (Europe+USA) where the ECMWF analyses are known to be good, but poorer agreement for a region (Southern Pacific) where the analyses are known to be degraded.Key words. Atmospheric composition and structure (pressure; density and temperature), Meteorology and atmospheric dynamics (instruments and techniques), Radio science (remote sensing)
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Olson, C. T., R. G. Menton, J. A. Blank, and D. W. Hobson. "An Automated Method for the Analysis of Methemoglobin." International Journal of Toxicology 16, no. 2 (March 1997): 165–73. http://dx.doi.org/10.1080/109158197227251.
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Production of methemoglobin (met Hb) is effective in treating or preventing cyanide intoxication due to the affinity of cyanide for met Hb. This paper describes an automated method for measuring met Hb in mouse blood utilizing the Roche COB AS FARA centrifugal analyzer and a modified Evelyn–Malloy procedure. Blood samples were spiked with various quantities of potassium ferricyanide to produce met Hb, and automated and manual analyses of these samples were compared. Following validation of the COB AS method, two known met Hb inducers, sodium nitrite and p-aminopropiophenone (PAPP), and two sulfur donor compounds, sodium thiosulfate and ICD #1021, not known to produce met Hb were tested in vivo. Five mice per compound were injected IP and blood samples were analyzed periodically over a time period of approximately 2 h. The automated technique requires only a drop of blood, which allows repeated sampling from the same animal, and can be adapted for blood from different species. A nalyses are rapid and sensitive, and results are reproducible.
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Yang, Zhongyue, Md Shamimul Hasan, John K. Htoo, Derris D. Burnett, Jean M. Feugang, Mark A. Crenshaw, and Shengfa F. Liao. "Effects of dietary supplementation of l-methionine vs. dl-methionine on performance, plasma concentrations of free amino acids and other metabolites, and myogenesis gene expression in young growing pigs." Translational Animal Science 3, no. 1 (September 27, 2018): 329–39. http://dx.doi.org/10.1093/tas/txy109.
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Abstract Methionine (Met), the second or third limiting amino acid (AA) in typical swine diets, plays important roles in promoting swine health and growth, especially, muscle growth. Whereas dl-Met products have been used in swine industry for many years, l-Met products have been developed recently. This research was conducted to study the effects of supplemental l-Met or dl-Met on nutrient metabolism, muscle gene expression, and growth performance of pigs. Twenty crossbred young barrows (initial body weight [BW] 21.2 ± 2.7 kg) were randomly assigned to 20 individual pens and two dietary treatments according to a completely randomized design with pigs serving as the experiment unit (n = 10). Two corn and soybean meal-based diets (diets 1 and 2) were formulated to meet or exceed the recommended requirements for energy, AA, and other nutrients (NRC. 2012. Nutrient requirements of swine, 11th ed. Washington, DC: The National Academies Press; AMINODat 5.0). Crystalline l-Met and dl-Met were supplemented to diets 1 and 2 (both at 0.13%, as-fed basis), respectively. After 4 wk of an ad libitum feeding trial, BW and feed intake were measured to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F). Blood samples were collected from the jugular vein for analyses of plasma AA and metabolite concentrations. The longissimus dorsi muscle samples were collected for analysis of myogenesis gene expression. Data were analyzed using Student’s t-test. There were no differences (P = 0.56 to 0.94) in ADG, ADFI, or G:F between pigs fed the two experimental diets and no differences between diets were observed in plasma free AA concentrations. No differences were observed between pigs fed the two diets in expression of mRNA for eight myogenesis-related genes, which were myogenic differentiation 1, myogenin, myogenic factors 5, muscle regulatory factor 4 (a.k.a. myogenic factors 6), and myocyte enhancer factors 2A, 2B, 2C, and 2D. In conclusion, results of this experiment indicate that the bioefficacy of l-Met is not different from that of dl-Met, which is likely because of an efficient conversion of d-Met to l-Met by pigs.
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Long, D. J., D. R. Jackson, and J. Thuburn. "Offline estimates and tuning of mesospheric gravity-wave forcing using Met Office analyses." Quarterly Journal of the Royal Meteorological Society 140, no. 680 (June 19, 2013): 1025–38. http://dx.doi.org/10.1002/qj.2168.
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John, Tom, Carmel Murone, Khashayar Asadi, Adrienne Morey, Simon Knight, and Paul Mitchell. "Prognostic role of MET expression in early stage NSCLC." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 7567. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.7567.
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7567 Background: The MET receptor tyrosine kinase and its ligand are associated with the malignant phenotype. In non-small cell lung cancer (NSCLC) MET expression increases with disease stage and is involved in de novo and acquired resistance to tyrosine kinase inhibitors. Despite this, in early stage NSCLC small data series have failed to demonstrate MET expression to be prognostic. We investigated a large cohort of patients who underwent curative surgical resection at our institution to determine whether MET receptor or gene amplification was prognostic. Methods: Tissue Microarrays (TMAs) were constructed using 1mm cores of FFPE primary NSCLC tissues in triplicate. TMAs were stained with the SP44 clone (Novus Biologicals) and a H-score calculated based on % cells stained and intensity; (%cellsx1)+(%cellsx2)+(%cellsx3) with a minimum of 0 and maximum of 300. The mean of triplicate values was calculated. MET gene amplification was detected using Ventana’s MET DNP probe with ultraView SISH DNP silver detection, performed on Ventana’s XT autostainer. DNA was isolated and subjected to mutational profiling using Sequenom’s LungCarta panel. Results: Data for 508 patients, 352 (69%) male, were available for analysis including 329 pathological node negative (pN0), 67 pN1, 104 pN2 and 8 patients with resected primaries and solitary brain metastases (M1). Most patients were smokers with only 33 (6%) non-smokers. The median MET H-score was 100 and consistent across N0, N1 and N2 patients, although was higher in M1 patients. Median H-scores were significantly higher in adenocarcinoma compared to squamous cell carcinoma (140 vs 91.5, p<0.0001). Increased MET expression (H-score>100) was seen in 227 (45%) patients and associated with significantly improved overall survival (HR 1.28 95% CI 1.04-1.59; p=0.023). In univariate analyses improved survival occurred in all stages and histologies. DNA and multivariate analyses are pending. MET gene copy number amplification was detected in 11 cases. Conclusions: In contradistinction to advanced NSCLC, increased MET receptor expression is associated with improved survival in a large cohort of early stage lung cancer. Further correlation with mutation status and gene rearrangements will be reported.
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Oh, Jeong-Woo, Yun Jeong Oh, Suji Han, Nam-Gu Her, and Do-Hyun Nam. "High-Content Analysis-Based Sensitivity Prediction and Novel Therapeutics Screening for c-Met-Addicted Glioblastoma." Cancers 13, no. 3 (January 20, 2021): 372. http://dx.doi.org/10.3390/cancers13030372.
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(1) Background: Recent advances in precision oncology research rely on indicating specific genetic alterations associated with treatment sensitivity. Developing ex vivo systems to identify cancer patients who will respond to a specific drug remains important. (2) Methods: cells from 12 patients with glioblastoma were isolated, cultured, and subjected to high-content screening. Multi-parameter analyses assessed the c-Met level, cell viability, apoptosis, cell motility, and migration. A drug repurposing screen and large-scale drug sensitivity screening data across 59 cancer cell lines and patient-derived cells were obtained from 125 glioblastoma samples. (3) Results: High-content analysis of patient-derived cells provided robust and accurate drug responses to c-Met-targeted agents. Only the cells of one glioblastoma patient (PDC6) showed elevated c-Met level and high susceptibility to the c-Met inhibitors. Multi-parameter image analysis also reflected a decreased c-Met expression and reduced cell growth and motility by a c-Met-targeting antibody. In addition, a drug repurposing screen identified Abemaciclib as a distinct CDK4/6 inhibitor with a potent c-Met-inhibitory function. Consistent with this, we present large-scale drug sensitivity screening data showing that the Abemaciclib response correlates with the response to c-Met inhibitors. (4) Conclusions: Our study provides a new insight into high-content screening platforms supporting drug sensitivity prediction and novel therapeutics screening.
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Wang, Jun, Fuquan Zhang, Wenxian Zhu, Yansong Liu, and Zhenhe Zhou. "Meta-analysis of the association of brain-derived neurotrophic factor Val66Met polymorphism with obsessive–compulsive disorder." Acta Neuropsychiatrica 27, no. 6 (June 4, 2015): 327–35. http://dx.doi.org/10.1017/neu.2015.38.
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ObjectiveBrain-derived neurotrophic factor (BDNF) plays an important role in neural survival and was proposed to be related to psychiatric disorders. Val66Met (also known as rs6265 or G196A), the only known functional polymorphism of the BDNF gene, has been widely studied and considered to be associated with risk of some psychiatric disorders such as bipolar disorder and schizophrenia. However, studies evaluating its association with obsessive–compulsive disorder (OCD) obtained inconsistent results. The purpose of this study was to derive a more precise estimation of the association between BDNF Val66Met polymorphism and OCD susceptibility by a meta-analysis.MethodWe carried a structured literature search in PubMed, Embase, PsycINFO and Chinese Biomedical Database up to December 2014; and retrieved all eligible case–control studies according to the including criteria. Meta-analysis was performed for four genetic models: allelic model: Met versus Val; additive model: Met/Met versus Val/Val; recessive model: Met/Met versus Val/Val+Val/Met; and dominant model: Val/Met+Met/Met versus Val/Val. Stratified analyses were performed by ethnicity and gender where appropriate.ResultsA total of eight articles with nine studies including 1632 OCD cases and 2417 controls were identified. No significant association was detected in any comparison when the whole data were pooled together or stratified by ethnicity or gender in all four genetic models (p>0.05 for each comparison).ConclusionDespite some limitations, our meta-analysis suggests that no significant association exists between the BDNF Val66Met polymorphism and OCD susceptibility.
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Mondelo-Macía, Patricia, Carmela Rodríguez-López, Laura Valiña, Santiago Aguín, Luis León-Mateos, Jorge García-González, Alicia Abalo, et al. "Detection of MET Alterations Using Cell Free DNA and Circulating Tumor Cells from Cancer Patients." Cells 9, no. 2 (February 24, 2020): 522. http://dx.doi.org/10.3390/cells9020522.
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MET alterations may provide a potential biomarker to evaluate patients who will benefit from treatment with MET inhibitors. Therefore, the purpose of the present study is to investigate the utility of a liquid biopsy-based strategy to assess MET alterations in cancer patients. We analyzed MET amplification in circulating free DNA (cfDNA) from 174 patients with cancer and 49 healthy controls and demonstrated the accuracy of the analysis to detect its alteration in patients. Importantly, a significant correlation between cfDNA concentration and MET copy number (CN) in cancer patients (r = 0.57, p <10−10) was determined. Furthermore, we evaluated two approaches to detect the presence of MET on circulating tumor cells (CTCs), using the CellSearch® and Parsortix systems and monitored patients under anti-EGFR treatment (n = 30) combining both cfDNA and CTCs analyses. This follow-up provides evidence for the potential of MET CN assessment when patients develop resistance to anti-EGFR therapy and a significant association between the presence of CTCs MET+ and the Overall Survival (OS) in head and neck cancer patients (P = 0.05; HR = 6.66). In conclusion, we develop specific and noninvasive assays to monitor MET status in cfDNA/CTCs and demonstrate the utility of plasma MET CN determination as a biomarker for monitoring the appearance of resistance to anti-EGFR therapy.
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Cañadas, I., M. Arumi, L. Lema, A. Martinez, E. Grande, B. Bellosillo, F. Rojo, A. Rovira, J. Albanell, and E. Arriola. "MET in small cell lung carcinoma (SCLC): Effects of a MET inhibitor in SCLC cell lines and prognostic role of MET status in patients." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e14617-e14617. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e14617.
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e14617 Purpose: HGF/MET pathway is aberrantly activated by receptor overexpression and mutations in SCLC preclinical models, enhancing their oncogenicity. The significance of MET expression in SCLC remains unclear. Our aim was to analyze the effects of MET inhibition in chemosensitive/refractory SCLC models and to study the expression pattern and prognostic impact of total and phosphorylated (p) MET in SCLC patients. Methods: Total and p-MET expression (Western Blot), gene copy number (FISH), and exon 14 activating mutations (sequencing) were evaluated in H69 and H69AR SCLC cell lines. PHA-665752 (PHA), alone or combined with doxorubicin, was used to study the effects of pathway inhibition on viability, colony formation and invasion assays in basal/stimulated conditions (HGF). Fifty-eight SCLC cases were evaluated for MET and p-MET expression by immunohistochemistry. Survival analyses were performed. Results: H69 and H69AR (both R988C mutated) expressed MET at basal conditions, but not p-MET. HGF induced MET phosphorylation, increased proliferation (20%) and protected cells from doxorubicin cytotoxicity. PHA 0.5μM blocked MET phosphorylation, decreased colony formation by 50% in H69, counteracted the cytoprotective effect of HGF and inhibited invasion in H69AR. MET expression was found in 98% normal bronchial epithelia, and 78% tumor samples (overexpression 38%). Activated MET was focally detected in normal and metaplastic mucosa and expressed in 22% tumors. MET expression was associated with improved overall and disease free survival (p: 0.06 and 0.051, respectively). All p-MET positive cases within MET expressing tumors, showed relapsed disease (83% in negative p-MET samples, p=0.065), suggesting MET activation may revert the good prognosis linked to total MET expression. Conclusions: MET activation, results in a more aggressive phenotype in SCLC cells. PHA at MET inhibiting concentrations reverses this phenotype. In SCLC specimens, MET expression was more prevalent than p-MET and associated with raised prognosis. All these data suggest that studies with MET inhibitors should focus on p-MET positive SCLC. [Table: see text]
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Henechowicz, Tara L., Joyce L. Chen, Leonardo G. Cohen, and Michael H. Thaut. "The prevalence of the Val66Met polymorphism in musicians: Possible evidence for compensatory neuroplasticity from a pilot study." PLOS ONE 16, no. 6 (June 9, 2021): e0245107. http://dx.doi.org/10.1371/journal.pone.0245107.
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The study compared the prevalence of the Val66Met Brain-derived Neurotrophic Factor single nucleotide polymorphism (rs6265) in a sample of musicians (N = 50) to an ethnically matched general population sample from the 1000 Human Genome Project (N = 424). Met-carriers of the polymorphism (Val/Met and Met/Met genotypes) are typically present in 25–30% of the general population and have associated deficits in motor learning and plasticity. Many studies have assessed the benefits of long-term music training for neuroplasticity and motor learning. This study takes a unique genetic approach investigating if the prevalence of the Val66Met BDNF polymorphism, which negatively affects motor learning, is significantly different in musicians from the general population. Our genotype and allele frequency analyses revealed that the distribution of the Val66Met polymorphism was not significantly different in musicians versus the general population (p = 0.6447 for genotype analysis and p = 0.8513 allele analysis). In the Musician sample (N = 50), the prevalence of the Val/Met genotype was 40% and the prevalence of the Met/Met genotype was 2%. In the 1000 Human Genome Project subset (N = 424), the prevalence of Val/Met was 33.25% and the Met/Met genotype prevalence was 4%. Therefore, musicians do exist with the Val66Met polymorphism and the characteristics of long-term music training may compensate for genetic predisposition to motor learning deficits. Since the polymorphism has significant implications for stroke rehabilitation, future studies may consider the implications of the polymorphism in music-based interventions such as Neurologic Music Therapy.
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Cho, Jeong Ho, Kilwon Cho, and Hwa Sung Shin. "Kinetic and thermodynamic analyses of adhesion of a peptide, Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), and human formyl peptide receptor (hFPR)." Biotechnology Letters 32, no. 6 (March 11, 2010): 773–79. http://dx.doi.org/10.1007/s10529-010-0226-8.
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Cao, Tong, Jing Pan, Xiulian Li, Yanli He, Yifei Jiang, Yajing Chang, Qi Zhang, et al. "Isolation and Characterization of a Chinese Hamster Ovary Heparan Sulfate Cell Mutant Defective in Both Met Receptor Binding and Hepatocyte Growth Factor NK1/Met Signaling." Cellular Physiology and Biochemistry 48, no. 4 (2018): 1480–91. http://dx.doi.org/10.1159/000492258.
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Background/Aims: The up-regulation of hepatocyte growth factor/receptor, HGF/Met, signal transduction is observed in most of human cancers. Specific heparan sulfate structures enhance the HGF/Met signaling at both cell and animal-based model systems. Biochemical studies indicate that heparan sulfate interacts with HGF and a natural occurring splicing variant NK1 of HGF with similar affinity. However, it is currently unknown if cell surface heparan sulfate binds to Met at physiological conditions and if specific cell surface heparan sulfate structures are required for effective HGF/Met or NK1/Met signaling. Methods: An established flow sorting strategy was used to isolate a soluble Met recombinant protein-binding positive or negative CHO cell clones different only in specific heparan sulfate structures. The cell surface bindings were imaged by confocal microscopy and flow cytometry analysis. Glucosamine vs. galactosamine contents from media-, cell surface-, and cell association glycosaminoglycans were quantified by HPLC. 35S-sulfate labeled glycosaminoglycans were characterized by anion exchange and size-exclusion HPLC. Heparan sulfate disaccharide compositions were determined by HPLC-MS analysis. Western blot analyses of MAPK-p42/44 were used to monitor HGF- and NK1-facillated Met signaling. Results: CHO-Positive but not CHO-Negative cell surface heparan sulfate bound to Met recombinant protein and HGF/NK1 further promoted the binding. Overall glycosaminoglycan analysis results indicated that the CHO-Negative cells had reduced amount of heparan sulfate, shorter chain length, and less 6-O-sulfated disaccharides compared to that of CHO-Positive cells. Moreover, CHO-Negative cells were defective in NK1/Met but not HGF/Met signaling. Conclusions: This study demonstrated that soluble Met recombinant protein bound to cell surface HS at physiological conditions and a Met /HGF or NK1/HS ternary signaling complex might be involved in Met signaling. Shorter HS chains and reduced 6-O-sulfation might be responsible for reduced Met binding and the diminished NK1-initiated signaling in the CHO-Negative cells. The unique CHO-Positive and CHO-Negative cell clones established in current study should be effective tools for studying the role of specific glycosaminoglycan structures in regulating Met signaling. Such knowledge should be useful in developing glycosaminoglycan-based compounds that target HGF/Met signaling.
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Zhang, Xianghong, Junwei Yang, Yingjian Li, and Youhua Liu. "Both Sp1 and Smad participate in mediating TGF-β1-induced HGF receptor expression in renal epithelial cells." American Journal of Physiology-Renal Physiology 288, no. 1 (January 2005): F16—F26. http://dx.doi.org/10.1152/ajprenal.00318.2003.
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Hepatocyte growth factor (HGF) receptor is a transmembrane receptor tyrosine kinase encoded by the c-met protooncogene. In this study, we demonstrated that c-met expression was upregulated in the kidney after obstructive injury in mice. Because the pattern of c-met induction was closely correlated with transforming growth factor-β1 (TGF-β1) expression in vivo, we further investigated the regulation of c-met expression in renal tubular epithelial (HKC) cells by TGF-β1 in vitro. Real-time RT-PCR and Northern and Western blot analyses revealed that TGF-β1 significantly induced c-met expression in HKC cells, which primarily took place at the gene transcriptional level. Overexpression of inhibitory Smad7 completely abolished c-met induction, indicating its dependence on Smad signaling. Interestingly, TGF-β1-induced c-met expression was also contingent on a functional Sp1, as ablation of Sp1 binding with mithramycin A abrogated c-met induction in HKC cells. Transfection and sequence analysis identified a cis-acting TGF-β1-responsive region in the c-met promoter, in which resided a putative Smad-binding element (SBE) and an adjacent Sp1 site. TGF-β1 not only induced Smad binding to the SBE/Sp1 sites in the c-met promoter, but also enhanced the binding of Sp proteins. Furthermore, Sp1 could form a complex with Smads in a TGF-β1-dependent fashion. These results suggest a novel regulatory mechanism controlling c-met expression by TGF-β1 in renal epithelial cells, in which both Smad and Sp proteins participate and cooperate in activating c-met gene transcription.
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Ferrera, David, Francisco Mercado, Irene Peláez, David Martínez-Iñigo, Roberto Fernandes-Magalhaes, Paloma Barjola, Carmen Écija, Gema Díaz-Gil, and Francisco Gómez-Esquer. "Fear of pain moderates the relationship between self-reported fatigue and methionine allele of catechol-O-methyltransferase gene in patients with fibromyalgia." PLOS ONE 16, no. 4 (April 28, 2021): e0250547. http://dx.doi.org/10.1371/journal.pone.0250547.
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Previous research has shown a consistent association among genetic factors, psychological symptoms and pain associated with fibromyalgia. However, how these symptoms interact to moderate genetic factors in fibromyalgia has rarely been studied to date. The present research investigates whether psychological symptoms can moderate the effects of catechol-O-methyltransferase on pain and fatigue. A total of 108 women diagnosed with fibromyalgia and 77 healthy control participants took part in the study. Pain, fatigue, and psychological symptoms (anxiety, depression, pain catastrophizing, fear of pain and fear of movement) were measured by self-report questionnaires. Two types of statistical analyses were performed; the first was undertaken to explore the influences of COMT genotypes on clinical symptoms by comparing patients with fibromyalgia and healthy controls. In the second analysis, moderation analyses to explore the role of psychological symptoms as potential factors that moderate the relationship between pain/fatigue and COMT genotypes were performed. The main results indicated that patients carrying the Met/Met genotype reported significantly higher levels of fatigue than heterozygote carriers (i.e., Met/Val genotype) and higher levels of fatigue, but not significantly different, than Val homozygote carriers. Among patients with fibromyalgia carrying methionine alleles (i.e., Met/Met + Met/Val carriers), only those who scored high on medical fear of pain, experienced an intensified feeling of fatigue. Thus, the present research suggests that fear of pain, as a psychological symptom frequently described in fibromyalgia may act as a moderating factor in the relationship between the Met allele of the COMT gene and the increase or decrease in self-reported fatigue. Although further research with wider patient samples is needed to confirm the present findings, these results point out that the use of psychological interventions focused on affective symptomatology might be a useful tool to reduce the severity of fibromyalgia.
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Kim, Jooseok, Kyung Eui Park, Yoo-Seong Jeong, YeongMun Kim, Hayeon Park, Ji-Hye Nam, Kyungsoo Jung, et al. "Therapeutic Efficacy of ABN401, a Highly Potent and Selective MET Inhibitor, Based on Diagnostic Biomarker Test in MET-Addicted Cancer." Cancers 12, no. 6 (June 15, 2020): 1575. http://dx.doi.org/10.3390/cancers12061575.
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The receptor tyrosine kinase c-MET regulates processes essential for tissue remodeling and mammalian development. The dysregulation of c-MET signaling plays a role in tumorigenesis. The aberrant activation of c-MET, such as that caused by gene amplification or mutations, is associated with many cancers. c-MET is therefore an attractive therapeutic target, and inhibitors are being tested in clinical trials. However, inappropriate patient selection criteria, such as low amplification or expression level cut-off values, have led to the failure of clinical trials. To include patients who respond to MET inhibitors, the selection criteria must include MET oncogenic addiction. Here, the efficacy of ABN401, a MET inhibitor, was investigated using histopathologic and genetic analyses in MET-addicted cancer cell lines and xenograft models. ABN401 was highly selective for 571 kinases, and it inhibited c-MET activity and its downstream signaling pathway. We performed pharmacokinetic profiling of ABN401 and defined the dose and treatment duration of ABN401 required to inhibit c-MET phosphorylation in xenograft models. The results show that the efficacy of ABN401 is associated with MET status and they highlight the importance of determining the cut-off values. The results suggest that clinical trials need to establish the characteristics of each sample and their correlations with the efficacy of MET inhibitors.
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de Souza, Michel Henriques, José Domingos Pereira Júnior, Skarlet De Marco Steckling, Jussara Mencalha, Fabíola dos Santos Dias, João Romero do Amaral Santos de Carvalho Rocha, Pedro Crescêncio Souza Carneiro, and José Eustáquio de Souza Carneiro. "Adaptability and stability analyses of plants using random regression models." PLOS ONE 15, no. 12 (December 2, 2020): e0233200. http://dx.doi.org/10.1371/journal.pone.0233200.
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The evaluation of cultivars using multi-environment trials (MET) is an important step in plant breeding programs. One of the objectives of these evaluations is to understand the genotype by environment interaction (GEI). A method of determining the effect of GEI on the performance of cultivars is based on studies of adaptability and stability. Initial studies were based on linear regression; however, these methodologies have limitations, mainly in trials with genetic or statistical unbalanced, heterogeneity of residual variances, and genetic covariance. An alternative would be the use of random regression models (RRM), in which the behavior of the genotypes is characterized as a reaction norm using longitudinal data or repeated measurements and information regarding a covariance function. The objective of this work was the application of RRM in the study of the behavior of common bean cultivars using a MET, based on Legendre polynomials and genotype-ideotype distances. We used a set of 13 trials, which were classified as unfavorable or favorable environments. The results revealed that RRM enables the prediction of the genotypic values of cultivars in environments where they were not evaluated with high accuracy values, thereby circumventing the unbalanced of the experiments. From these values, it was possible to measure the genotypic adaptability according to ideotypes, according to their reaction norms. In addition, the stability of the cultivars can be interpreted as variation in the behavior of the ideotype. The use of ideotypes based on real data allowed a better comparison of the performance of cultivars across environments. The use of RRM in plant breeding is a good alternative to understand the behavior of cultivars in a MET, especially when we want to quantify the adaptability and stability of genotypes.
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Rosso, Andrea L., Nicolaas I. Bohnen, Lenore J. Launer, Howard J. Aizenstein, Kristine Yaffe, and Caterina Rosano. "Vascular and dopaminergic contributors to mild parkinsonian signs in older adults." Neurology 90, no. 3 (December 15, 2017): e223-e229. http://dx.doi.org/10.1212/wnl.0000000000004842.
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ObjectiveMild parkinsonian signs (MPS) are an underappreciated neurologic condition in older adults; we assessed associations of MPS with measures of dopaminergic (catechol-O-methyltransferase [COMT] genotype, an indicator of synaptic dopamine levels) and vascular (white matter hyperintensities [WMH], an indicator of cerebral small vessel disease) factors.MethodsIn a cohort of older adults (mean age 82.6 years [SD 2.6]; 58.0% female; 38.8% black), we assessed cross-sectional associations of WMH volume and COMT Val158Met (rs4680) genotype (n = 35 Met/Met, n = 180 Val carriers) with MPS by regression models adjusted for demographic and health characteristics. Interactions between WMH and COMT were assessed and analyses were repeated stratified by COMT genotype (Met/Met related to higher synaptic dopamine vs Val carriers related to lower synaptic dopamine).ResultsMPS was present in 42.3% of our sample. WMH (odds ratio [OR] 1.16, confidence interval [CI] 1.05–1.27) but not COMT (Met/Met compared to Val carrier: OR 0.62, CI 0.27–1.42) was related to MPS. There was a significant interaction between WMH and COMT (p = 0.03). Stratified analyses reveled a strong association between WMH and MPS among COMT Val carriers (OR 1.23, CI 1.09–1.38), but not for Met/Met (OR 0.68, CI 0.45–1.02), independent of covariates.ConclusionsWMH had a direct relation with MPS. In contrast, COMT was not associated with MPS, but it did modify the effect of WMH on MPS. The dopaminergic system may provide compensation for the effects of WMH on MPS. These findings suggest that MPS has a vascular rather than dopaminergic origin in older adults, but both factors are important in MPS manifestation.
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Yang, Ya’nan, Chenchen Wang, Congqi Dai, Xinyang Liu, Wenhua Li, Mingzhu Huang, Xiaoying Zhao, Dongmei Ji, Jin Li, and Weijian Guo. "Amplification and expression of c-MET correlate with poor prognosis of patients with gastric cancer and upregulate the expression of PDL1." Acta Biochimica et Biophysica Sinica 53, no. 5 (March 8, 2021): 547–57. http://dx.doi.org/10.1093/abbs/gmab026.
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Abstract The prognostic significance of c-MET in gastric cancer (GC) remains uncertain. In the present study, we examined the amplification, expression, and the prognostic value of c-MET, human epidermal growth factor receptor 2 (HER2), and programmed cell death 1 ligand 1 (PDL1), together with the correlations among them in a large cohort of Chinese samples. A total of 444 patients were included. The immunohistochemistry (IHC) and the dual-color silver in situ hybridization (SISH) were performed to examine their expression and amplification. Univariate and multivariate analyses were performed by the Cox proportional hazard regression model, and survival curves were estimated by the Kaplan–Meier method. The positivity determined by IHC of c-MET was 24.8%, and the MET amplification rate was 2.3%. The positivity rates of HER2 and PDL1 were 8% and 34.7%, respectively. PDL1 expression had a significantly positive association with c-MET expression. c-MET positivity played a significant prognostic role in disease-free survival (DFS) (P = 0.032). Patients with mesenchymal-epithelial transition (MET) amplification had significantly poorer prognosis on both DFS and overall survival (OS). Subgroup analysis showed that in HER2-negative patients, but not in HER2-positive patients, MET-positive patients had significantly worse DFS (P = 0.000) and OS (P = 0.006). c-MET regulated the expression of PDL1 through an AKT-dependent pathway. c-MET inhibitor enhanced the T-cell killing ability and increased the efficacy of PD1 antibody. c-MET was found to be an independent prognostic factor for DFS of GC patients. A combination of c-MET inhibitors and PD1 antibodies could enhance the killing capacity of T cells, providing a preliminary basis for the clinical research on the same combination in GC treatment.
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Zhao, Hailong, Shuicai Xiong, Zhiwei Li, Xuebiao Wu, and Lijuan Li. "Meta-analytic method reveal a significant association of theBDNF Val66Met variant with smoking persistence based on a large samples." Pharmacogenomics Journal 20, no. 3 (December 2, 2019): 398–407. http://dx.doi.org/10.1038/s41397-019-0124-y.
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AbstractAlthough numerous genetic studies have reported the link between Val66Met in BDNF gene with smoking, the findings remain controversial, mainly due to small-to-moderate sample sizes. The main aim of current investigation is to explore whether the variant of Val66Met has any genetic functions in the progress of smoking persistence. The Val-based dominant genetic model considering Val/* (namely, Val/Val + Val/Met) and Met/Met as two genotypes with comparison of the frequency of each genotype in current smokers and never smokers. There were seven genetic association articles including eight independent datasets with 10,160 participants were chosen in current meta-analytic investigation. In light of the potent effects of ethnicity on homogeneity across studies, we carried out separated meta-analyses according to the ancestry origin by using the wide-used tool of Comprehensive Meta-analysis software (V 2.0). Our meta-analyses results indicated that the Val66Met polymorphism was significantly linked with smoking persistence based on either all the chosen samples (N = 10,160; Random and fixed models: pooled OR = 1.23; 95% CI = 1.03–1.46; P value = 0.012) or Asian samples (N = 2,095; Fixed model: pooled OR = 1.25; 95% CI = 1.01–1.54; P value = 0.044; Random model: pooled OR = 1.25; 95% CI = 1.001–1.56; P value = 0.049). No significant clue of bias in publications or heterogeneity across studies was detected. Thus, we conclude that the Val66Met (rs6265) variant conveys genetic susceptibility to maintaining smoking, and smokers who carry Val/* genotypes have a higher possibility of maintaining smoking than those having Met/Met genotype.
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Jones, Lee W., Qi Liu, Gregory T. Armstrong, Kirsten K. Ness, Yutaka Yasui, Katie Devine, Emily Tonorezos, et al. "Exercise and Risk of Major Cardiovascular Events in Adult Survivors of Childhood Hodgkin Lymphoma: A Report From the Childhood Cancer Survivor Study." Journal of Clinical Oncology 32, no. 32 (November 10, 2014): 3643–50. http://dx.doi.org/10.1200/jco.2014.56.7511.
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Purpose Survivors of Hodgkin lymphoma (HL) are at increased risk of treatment-related cardiovascular (CV) events; whether exercise modifies this risk is unknown. Methods Survivors of HL (n = 1,187; median age, 31.2 years) completed a questionnaire evaluating vigorous-intensity exercise behavior. CV events were collected in follow-up questionnaires and graded according to Common Terminology Criteria for Adverse Events (version 4.03). The primary end point was incidence of any major (grade 3 to 5) CV event. Poisson regression analyses were used to estimate the association between exercise exposure (metabolic equivalent [MET] hours/week−1) and risk of major CV events after adjustment for clinical covariates and cancer treatment. Results Median follow-up was 11.9 years (range, 1.7 to 14.3 years). Cumulative incidence of any CV event was 12.2% at 10 years for survivors reporting 0 MET hours/week−1 compared with 5.2% for those reporting ≥ 9 MET hours/week−1. In multivariable analyses, the incidence of any CV event decreased across increasing MET categories (Ptrend = .002). Compared with survivors reporting 0 MET hours/week−1, the adjusted rate ratio for any CV event was 0.87 (95% CI, 0.56 to 1.34) for 3 to 6 MET hours/week−1, 0.45 (95% CI, 0.26 to 0.80) for 9 to 12 MET hours/week−1, and 0.47 (95% CI, 0.23 to 0.95) for 15 to 21 MET hours/week−1. Adherence to national vigorous intensity exercise guidelines (ie, ≥ 9 MET hours/week−1) was associated with a 51% reduction in the risk of any CV event in comparison with not meeting the guidelines (P = .002). Conclusion Vigorous exercise was associated with a lower risk of CV events in a dose-dependent manner independent of CV risk profile and treatment in survivors of HL.
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Stanišić, Nikola, Nenad Parunović, Slaviša Stajić, Milica Petrović, Čedomir Radović, Dušan Živković, and Maja Petričević. "Differences in meat colour between free-range Swallow Belly Mangalitsa and commercially reared Swedish Landrace pigs during 6 days of vacuum storage." Archives Animal Breeding 59, no. 1 (April 1, 2016): 159–66. http://dx.doi.org/10.5194/aab-59-159-2016.
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Abstract. The influence of storage on meat colour differences between free-range Swallow Belly Mangalitsa (MA, n = 19) and commercially reared Swedish Landrace (SL, n = 17) pigs, are investigated in the present study. Proximate composition analyses were done on fresh samples of M. longissimus thoracis (LT) and M. gluteus medius (GM), while pH values and colour quality attributes were determined on fresh cuts of the muscles (day 1) and after 3 and 6 days of vacuum storage at 4 ± 1 °C. MA pork had a significantly higher share of intramuscular fat, a darker colour, a higher deoxymyoglobin (Mb) content and oxy ∕ met (oxymyoglobin ∕ metmyoglobin) ratio, higher pH24 h values and a slower pH decline compared to the control SL group (P < 0.05). Greater changes in myoglobin forms during storage were observed in MA pork, which were reflected in a significant decrease in the content of Mb and an increase in the oxy ∕ met ratio (P < 0.05).After 6 days of vacuum storage, higher pH6d values, a lower metmyoglobin (MetMb) content and a higher oxy ∕ met ratio of MA pork lead to the conclusion that aged meat from free-range Swallow Belly Mangalitsa pigs had better colour quality compared to Swedish Landrace pigs.
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Montag, C., B. Weber, K. Fliessbach, C. Elger, and M. Reuter. "The BDNF Val66Met polymorphism impacts parahippocampal and amygdala volume in healthy humans: incremental support for a genetic risk factor for depression." Psychological Medicine 39, no. 11 (April 1, 2009): 1831–39. http://dx.doi.org/10.1017/s0033291709005509.
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BackgroundThe role of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of affective disorders such as depression has been controversial. Mounting evidence comes from structural imaging, that the functional BDNF Val66Met polymorphism influences the hippocampal volume with carriers of the 66Met allele (Val/Met and Met/Met group) having smaller hippocampi. Given that stress-induced atrophy of the hippocampus is associated with the pathogenesis of affective disorders, the functional BDNF Val66Met polymorphism could be an incremental risk factor.MethodEighty-seven healthy Caucasian participants underwent structural imaging and were genotyped for the BDNF Val66Met polymorphism. Data were analysed by means of voxel-based morphometry (VBM).ResultsRegion of interest (ROI) analyses revealed an association between the 66Met allele and smaller parahippocampal volumes and a smaller right amygdala. In addition, the whole-brain analysis showed that the thalamus, fusiformus gyrus and several parts of the frontal gyrus were smaller in 66Met allele carriers.ConclusionsThis study demonstrates that the impact of the BDNF Val66Met polymorphism is not confined to the hippocampus but also extends to the parahippocampal gyrus and the amygdala.
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Folprecht, Gunnar, Eric Van Cutsem, Carsten Bokemeyer, Michael Schlichting, Steffen Heeger, and Claus-Henning Kohne. "First-line chemotherapy plus cetuximab in patients grouped according to prognostic risk factors: Analysis of the CRYSTAL and OPUS studies." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 3591. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.3591.
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3591 Background: Analysis of randomized trials has shown that mCRC patients (pts) can be divided into prognostic risk groups according to baseline clinical parameters including ECOG performance status, white blood cell count (WBC), alkaline phosphatase (ALP) and number of metastatic (met) sites (Köhne C, et al. Ann Oncol 2002;13:308-17). The effect of adding cetuximab to first-line chemotherapy (CT) on overall survival (OS) in these groups of KRAS wild-type mCRC pts was investigated in the CRYSTAL and OPUS studies. Methods: Pt risk groups were: low-risk (LRG= ECOG 0/1, 1 met site) intermediate-risk (IRG= ECOG <1, >1 met site, ALP <300 U/L or, ECOG>1, low WBC, 1 met site) and high-risk (HRG= ECOG<1, >1 met site, ALP>300 U/L or ECOG>1, high WBC, or ECOG>1, low WBC and >2 met sites). Exploratory analyses comprised estimates of effects using Cox‘s proportional hazards model for OS on individual pt data and comparison of treatment arms by log-rank test. Results: Data are shown in the table. In the pooled analyses, in both treatment arms OS was longest in LRG pts and shortest in HRG pts. Adding cetuximab to CT led to marked improvements in OS in the HRG (Hazard ratio [HR] 0.765, 95% CI 0.506–1.157, p=0.203) and IRG (HR 0.781, 95% CI 0.622–0.981, p=0.033), while improvements in LRG pts (HR 0.869, 95% CI 0.672–1.124, p=0.287) were observed only after prolonged follow up. Data were similar in the separate CRYSTAL and OPUS studies. Conclusions: The analysis confirms the concept of prognostic risk groups for OS according to baseline clinical parameters in pts with KRAS wt mCRC. Benefit from the addition of cetuximab to first-line CT in terms of OS appears to be more pronounced in the IRG and HRG. [Table: see text]
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Huang, Boyin, William Angel, Tim Boyer, Lijing Cheng, Gennady Chepurin, Eric Freeman, Chunying Liu, and Huai-Min Zhang. "Evaluating SST Analyses with Independent Ocean Profile Observations." Journal of Climate 31, no. 13 (July 2018): 5015–30. http://dx.doi.org/10.1175/jcli-d-17-0824.1.
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The difficulty in effectively evaluating sea surface temperature (SST) analyses is finding independent observations, since most available observations have been used in the SST analyses. In this study, the ocean profile measurements [from reverse thermometer, CTD, mechanical bathythermograph (MBT), and XBT] above 5-m depth over 1950–2016 from the World Ocean Database (WOD) are used (data labeled pSSTW). The biases of MBT and XBT are corrected based on currently available algorithms. The bias-corrected pSSTW over 1950–2016 and satellite-based SST from the European Space Agency (ESA) Climate Change Initiative (CCI) over 1992–2010 are used to evaluate commonly available SST analyses. These SST analyses are the Extended Reconstructed SST (ERSST), versions 5, 4, and 3b, the Met Office Hadley Centre Sea Ice and SST dataset (HadISST), and the Japan Meteorological Administration (JMA) Centennial In Situ Observation-Based Estimates of SST version 2.9.2 (COBE-SST2). Our comparisons show that the SST from COBE-SST2 is the closest to pSSTW and CCI in most of the Pacific, Atlantic, and Southern Oceans, which may result from its unique bias correction to ship observations. The SST from ERSST version 5 is more consistent with pSSTW than its previous versions over 1950–2016, and is more consistent with CCI than its previous versions over 1992–2010. The better performance of ERSST version 5 over its previous versions is attributed to its improved bias correction applied to ship observations with a baseline of buoy observations, and is seen in most of the Pacific and Atlantic.
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Efentakis, Panagiotis, Hendrik Doerschmann, Claudius Witzler, Svenja Siemer, Panagiota-Efstathia Nikolaou, Efstathios Kastritis, Roland Stauber, et al. "Investigating the Vascular Toxicity Outcomes of the Irreversible Proteasome Inhibitor Carfilzomib." International Journal of Molecular Sciences 21, no. 15 (July 22, 2020): 5185. http://dx.doi.org/10.3390/ijms21155185.
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Background: Carfilzomib’s (Cfz) adverse events in myeloma patients include cardiovascular toxicity. Since carfilzomib’s vascular effects are elusive, we investigated the vascular outcomes of carfilzomib and metformin (Met) coadministration. Methods: Mice received: (i) saline; (ii) Cfz; (iii) Met; (iv) Cfz+Met for two consecutive (acute) or six alternate days (subacute protocol). Leucocyte-derived reactive oxygen species (ROS) and serum NOx levels were determined and aortas underwent vascular and molecular analyses. Mechanistic experiments were recapitulated in aged mice who received similar treatment to young animals. Primary murine (prmVSMCs) and aged human aortic smooth muscle cells (HAoSMCs) underwent Cfz, Met and Cfz+Met treatment and viability, metabolic flux and p53-LC3-B expression were measured. Experiments were recapitulated in AngII, CoCl2 and high-glucose stimulated HAoSMCs. Results: Acutely, carfilzomib alone led to vascular hypo-contraction and increased ROS release. Subacutely, carfilzomib increased ROS release without vascular manifestations. Cfz+Met increased PGF2α-vasoconstriction and LC3-B-dependent autophagy in both young and aged mice. In vitro, Cfz+Met led to cytotoxicity and autophagy, while Met and Cfz+Met shifted cellular metabolism. Conclusion: Carfilzomib induces a transient vascular impairment and oxidative burst. Cfz+Met increased vascular contractility and synergistically induced autophagy in all settings. Therefore, carfilzomib cannot be accredited for a permanent vascular dysfunction, while Cfz+Met exert vasoprotective potency.
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Usmani, Saad, Tahamtan Ahmadi, Yvette Ng, Annette Lam, Ravi Potluri, and Maneesha Mehra. "Analyses of Real World Data on Overall Survival in Multiple Myeloma Patients with at Least 3 Prior Lines of Therapy Including a PI and an IMiD, or Double Refractory to a PI and an IMiD." Blood 126, no. 23 (December 3, 2015): 4498. http://dx.doi.org/10.1182/blood.v126.23.4498.4498.
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Abstract Background: To fully evaluate the potential benefit of novel agents for the treatment of patients with multiple myeloma (MM) who are heavily pretreated and refractory, it is important to understand the outcomes of this patient population based on current real-world experience. An International Myeloma Working Group study determined that the median overall survival (OS) of patients refractory to bortezomib (proteasome inhibitor, PI) and at least 1 immunomodulatory drug (IMiD) was 9 months (Kumar S et al. Leukemia 2012; 26: 149). Since then, other therapies have been approved for relapsed and refractory MM in the United States (US), including pomalidomide (IMiD) and carfilzomib (PI). In this analysis, real-world data were used to define the treatment landscape and outcomes of patients with MM refractory to PIs and IMiDs or who had received ³3 prior lines of therapy (LOT; including a PI and an IMiD) and provide context to results from the single-agent daratumumab phase 2 study MMY2002 (Sirius) recently presented at ASCO 2015 (Lonial S. J Clin Oncol 33, 2015 suppl; abstr LBA8512). Methods: Two independent databases were analyzed.TheIMS LifeLink: IMS Oncology Electronic Medical Records (EMR) Database (IMS Health Incorporated, Danbury, CT) and the OPTUM Database (OPTUM, Inc., Eden Prairie, MN) both comprised US patients only. For the IMS LifeLink database, patient records from the index period of 2000-2011 were screened. For the OPTUM database, the indexing period was 2007-2014. Median OS was assessed for cohorts that met the criteria of disease that was double refractory to a PI and IMiD (Criteria 1) or had been treated with ³3 LOT including a PI and IMiD and showed disease progression within 60 days on completion of last regimen (Criteria 2). Patients who met Criteria 1 could have received ³3 prior LOT, however those who met Criteria 2 only did not meet the double refractory criteria. Subgroup analyses of the eligible population were conducted on those who were only double refractory and triple/quadruple refractory. Results: For the IMS LifeLink database, 4,030 patients with MM were screened, approximately 90% of patients were diagnosed with MM in 2006 or later, and 500 met the criteria for the target population. Of the 500 patients, 323 patients met Criteria 1 and 177 patients only met Criteria 2. For the OPTUM database, 3,837 patients with MM were screened, approximately 90% of patients were diagnosed after 2009, and 162 met the criteria for the target population, 120 of whom met Criteria 1 and 42 of whom only met Criteria 2. In the total eligible populations, median OS was 239 days in the IMS LifeLink dataset compared with 240 days in the OPTUM dataset (P = 0.5358). Among patients that were only double refractory (triple/quadruple refractory patients excluded), median OS was 228 days (n = 253) in the IMS LifeLink dataset compared with 259 days (n = 97) in the OPTUM dataset (P = 0.8052). In triple/quadruple refractory patients, median OS was 154 days (n = 70) in the IMS LifeLink dataset and 95 days (n = 23) in the OPTUM dataset (P = 0.6675). The results from both databases were consistent, hence the data were pooled for further analyses; the pooled analyses indicated that the median OS was 240 days for the eligible population (n = 662), 237 days for patients who were only double refractory (n = 350), and 154 days for patients who were triple/quadruple refractory (n = 93). A naïve comparison of the OS curves from the MMY2002 study and the pooled analysis suggests a survival benefit with daratumumab versus the real-world historical control (Figure). Conclusions: Analyses of real-world data from two independent US patient databases indicated that outcomes remain poor among patients with MM who are heavily pretreated and/or highly refractory despite the availability and use of newer PIs and IMiDs, such as carfilzomib and pomalidomide. Median OS of approximately 8 months was observed in patients with ≥3 LOT (including a PI and IMiD) or refractory to a PI and IMiD. These data not only highlight the critical need for new MM treatments for patients with advanced MM, but also provide a point of reference against which novel agents such as daratumumab could be evaluated. Disclosures Usmani: Onyx: Consultancy, Honoraria, Research Funding; Janssen: Research Funding; Celgene Corporation: Consultancy, Honoraria. Ahmadi:Janssen: Employment. Ng:Janssen: Employment. Lam:Janssen: Employment. Potluri:Smart Analyst: Employment. Mehra:Janssen: Employment.
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Williams, K. D., and M. E. Brooks. "Initial Tendencies of Cloud Regimes in the Met Office Unified Model." Journal of Climate 21, no. 4 (February 15, 2008): 833–40. http://dx.doi.org/10.1175/2007jcli1900.1.
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Abstract The Met Office unified forecast–climate model is used to compare the properties of simulated climatological cloud regimes with those produced in short-range forecasts initialized from operational analyses. The regimes are defined as principal clusters of joint cloud-top pressure–optical depth histograms. In general, the cloud regime properties are found to be similar at all forecast times, including the climatological mean. This suggests that weaknesses in the representation of fast local processes are responsible for errors in the simulation of the cloud regimes. The increased horizontal resolution of the model used for numerical weather prediction generally has little impact on the cloud regimes, although the simulation of tropical shallow cumulus is improved, while the relative frequency of tropical deep convection and cirrus compare less favorably with observations. Analysis of the initial temperature tendency profiles for each cloud regime indicates that some of the initial temperature tendency, which leads to a systematic bias in the model climatology, is associated with a particular cloud regime.
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Feng, Xiaojie, Wentao Wu, Fanfan Zhao, Fengshuo Xu, Didi Han, Xiaojuan Guo, and Jun Lyu. "Association between physical activity and kidney stones based on dose–response analyses using restricted cubic splines." European Journal of Public Health 30, no. 6 (September 3, 2020): 1206–11. http://dx.doi.org/10.1093/eurpub/ckaa162.
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Abstract Background This study aimed to determine whether there is a dose–response relationship between physical activity and the self-reported prevalence of kidney stone, based on a restricted cubic splines (RCS) method. Methods This study analyzed 8931 adults aged ≥20 years who had participated in the National Health and Nutrition Examination Survey (NHANES) during 2013–16. Kidney stones and physical activity were defined using a standard questionnaire, and metabolic equivalents (MET) were used to quantify the physical activity level. Logistic regression was used to assess the association between physical activity and the risk of kidney stones, and the dose–response relationship was explored using RCS. Results Kidney stones were present in 10.3% of the analyzed individuals: 11.5% of males and 9.2% of females. After adjusting for potential confounders, compared with the first quartile (Q1) of MET, the odds ratios (ORs) of kidney stones for those with Q2, Q3 and Q4 of MET were 0.72 [95% confidence interval (CI)=0.59–0.87], 0.77 (95% CI = 0.63–0.93) and 0.63 (95% CI = 0.51–0.78), respectively (all P < 0.01). The RCS regression showed that physical activity was related to kidney stones in a non-linear manner (P for non-linearity = 0.0100). The prevalence of kidney stones decreasing as physical activity increased, reaching a plateau for physical activity at approximately 2480 MET-min week−1 (OR = 0.75, 95% CI = 0.63–0.91). Conclusions Physical activity is inversely associated with the prevalence of kidney stones, and the dose–response relationship has a plateau, after which the prevalence of kidney stones does not change with the increase of physical activity.