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https://www.readbyqxmd.com/read/29667066/population-exposure-response-analysis-of-cabozantinib-efficacy-and-safety-endpoints-in-patients-with-renal-cell-carcinoma
#1
Steven Lacy, Jace Nielsen, Bei Yang, Dale Miles, Linh Nguyen, Matt Hutmacher
BACKGROUND: In the phase III METEOR trial, tyrosine kinase inhibitor cabozantinib significantly improved progression-free survival (PFS), objective response rate (ORR), and overall survival compared to everolimus in patients with advanced renal cell carcinoma (RCC) who had received prior VEGFR inhibitor therapy. In METEOR, RCC patients started at a daily 60-mg cabozantinib tablet (Cabometyx™) dose but could reduce to 40- or 20-mg to achieve a tolerated exposure. OBJECTIVES AND METHODS: Exposure-response (ER) models were developed to characterize the relationship between cabozantinib at clinically relevant exposures in RCC patients enrolled in METEOR and efficacy (PFS and tumor response) and safety endpoints...
April 17, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29662880/common-evaluations-of-disease-activity-in-rheumatoid-arthritis-reach-discordant-classifications-across-different-populations
#2
Helena Canhão, Ana Maria Rodrigues, Maria João Gregório, Sara S Dias, José António Melo Gomes, Maria José Santos, Augusto Faustino, José António Costa, Cornelia Allaart, Emilia Gvozdenović, Desirée van der Heijde, Pedro Machado, Jaime C Branco, João Eurico Fonseca, José António Silva
Objectives: The classification of disease activity states in rheumatoid arthritis (RA) can be achieved through disease activity indices, such as the Disease Activity Score in 28 joints erythrocyte sedimentation rate (DAS28-ESR), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Subjective measurements, such as patient reported outcomes have been incorporated into several of these indices alongside more objective assessments, such as increases in the ESR and C-reactive protein...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29576624/long-term-follow-up-of-overall-survival-for-cabozantinib-versus-everolimus-in-advanced-renal-cell-carcinoma
#3
Robert J Motzer, Bernard Escudier, Thomas Powles, Christian Scheffold, Toni K Choueiri
BACKGROUND: In the phase 3 METEOR trial (NCT01865747), cabozantinib significantly improved progression-free survival, overall survival, and objective response rate compared with everolimus in patients with advanced renal cell carcinoma (RCC) after prior antiangiogenic therapy. A statistically significant improvement in overall survival was observed at a second interim analysis with 320 recorded deaths. METHODS: 658 patients with advanced RCC who had received at least one prior VEGFR tyrosine kinase inhibitor were randomised 1:1 to cabozantinib (60 mg daily) or everolimus (10 mg daily)...
March 26, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29567323/circular-rna-circrna-was-an-important-bridge-in-the-switch-from-the-rna-world-to-the-dna-world
#4
Gerald Soslau
The concept that life on Earth began as an RNA world has been built upon extensive experimentation demonstrating that many of the building blocks required for living cells could be synthesized in the laboratory under conditions approximating our primordial world. Many of the building blocks for life have also been found in meteorites indicating that meteors may have been a source for these molecules, or more likely, that they represent the chemical library present in most/all bodies in the universe after the big bang...
March 19, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29549742/metabolism-of-the-synthetic-cannabinoids-amb-chmica-and-5c-akb48-in-pooled-human-hepatocytes-and-rat-hepatocytes-analyzed-by-uhplc-ims-hr-ms-e
#5
Marie Mardal, Petur Weihe Dalsgaard, Bing Qi, Christian Brinch Mollerup, Pieter Annaert, Kristian Linnet
The main analytical targets of synthetic cannabinoids are often metabolites. With the high number of new psychoactive substances entering the market, suitable workflows are needed for analytical target identification in biological samples. The aims of this study were to identify the main metabolites of the synthetic cannabinoids, AMB-CHMICA and 5C-AKB48, using an in silico-assisted workflow with analytical data acquired using ultra-high-performance liquid chromatography-(ion mobility spectroscopy)-high resolution-mass spectrometry in data-independent acquisition mode (UHPLC-(IMS)-HR-MSE )...
March 10, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29545651/activity-of-the-2013-geminid-meteoroid-stream-at-the-moon
#6
Jamey R Szalay, Petr Pokorný, Peter Jenniskens, Mihály Horányi
The Lunar Dust Experiment (LDEX) onboard the Lunar Atmosphere and Dust Environment Explorer mission orbited the Moon from 2013 October to 2014 April and detected impact ejecta generated by the continual bombardment of meteoroids to the lunar surface. While the Moon transited the Geminid meteoroid stream, LDEX observed a large enhancement in the lunar impact ejecta cloud, particularly above the portion of lunar surface normal to the Geminids radiant. Here, we present the LDEX measurements during the Geminids, using the surface density of impact ejecta at the Moon as a proxy for meteoroid activity...
March 2018: Monthly Notices of the Royal Astronomical Society
https://www.readbyqxmd.com/read/29512045/what-to-consider-when-designing-a-laparoscopic-colorectal-training-curriculum-a-review-of-the-literature
#7
REVIEW
A Gaitanidis, C Simopoulos, M Pitiakoudis
Multiple studies have demonstrated the benefits of laparoscopic colorectal surgery (LCS), but in several countries it has still not been widely adopted. LCS training is associated with several challenges, such as patient safety concerns and a steep learning curve. Current evidence may facilitate designing of efficient training curricula to overcome these challenges. Basic training with virtual reality simulators has witnessed meteoric advances and may be essential during the early parts of the learning curve...
March 6, 2018: Techniques in Coloproctology
https://www.readbyqxmd.com/read/29511898/relationship-between-abdominal-symptoms-and-fructose-ingestion-in-children-with-chronic-abdominal-pain
#8
Veronika Hammer, Katharina Hammer, Nima Memaran, Wolf-Dietrich Huber, Karin Hammer, Johann Hammer
BACKGROUND: Limited valid data are available regarding the association of fructose-induced symptoms, fructose malabsorption, and clinical symptoms. AIM: To develop a questionnaire for valid symptom assessment before and during a carbohydrate breath test and to correlate symptoms with fructose breath test results in children/adolescents with functional abdominal pain. METHODS: A Likert-type questionnaire assessing symptoms considered relevant for hydrogen breath test in children was developed and underwent initial validation...
March 7, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29505930/hydrogeochemical-and-isotopic-evaluation-of-groundwater-with-elevated-arsenic-in-alkaline-aquifers-in-eastern-punjab-pakistan
#9
Nisbah Mushtaq, Ayesha Younas, Azhar Mashiatullah, Tariq Javed, Arslan Ahmad, Abida Farooqi
Geochemical investigation was carried out for delineating factors responsible for the mobilization of arsenic (As) from aquifer material into the groundwater. Four sites along Ravi River, (Samada, Sarai Chimba, Kot Maiga and Chah Fatehwala), were selected based on the blanket survey. Groundwater-rock interaction and evaporation were the key phenomena controlling groundwater chemistry, as shown by the hydrogeochemical data. Groundwater was predominantly Na-Cl type, with other principle facies being Na-HCO3 , Na-Ca-HCO3 and Ca-Mg-Cl...
February 26, 2018: Chemosphere
https://www.readbyqxmd.com/read/29499620/influence-of-the-balance-of-the-intertropical-front-on-seasonal-variations-of-the-isotopic-composition-in-rainfall-at-kisiba-masoko-rungwe-volcanic-province-sw-tanzania
#10
Fantine Nivet, Laurent Bergonzini, Pierre-Etienne Mathé, Aurélie Noret, Gaël Monvoisin, Amos Majule, David Williamson
Tropical rainfall isotopic composition results from complex processes. The climatological and environmental variability in East Africa increases this complexity. Long rainfall isotope datasets are needed to fill the lack of observations in this region. At Kisiba Masoko, Tanzania, rainfall and rain isotopic composition have been monitored during 6 years. Mean year profiles allow to analyse the seasonal variations. The mean annual rainfall is 2099 mm with a rain-weighted mean composition of -3.2 ‰ for δ18 O and -11...
March 2, 2018: Isotopes in Environmental and Health Studies
https://www.readbyqxmd.com/read/29381808/pre-drill-groundwater-geochemistry-in-the-karoo-basin-south-africa
#11
Jennifer S Harkness, Kelley Swana, William K Eymold, Jodie Miller, Ricky Murray, Siep Talma, Colin J Whyte, Myles T Moore, Erica L Maletic, Avner Vengosh, Thomas H Darrah
Enhanced production of unconventional hydrocarbons in the United States has driven interest in natural gas development globally, but simultaneously raised concerns regarding water quantity and quality impacts associated with hydrocarbon extraction. We conducted a pre-development assessment of groundwater geochemistry in the critically water-restricted Karoo Basin, South Africa. Twenty-two springs and groundwater samples were analyzed for major dissolved ions, trace elements, water stable isotopes, strontium and boron isotopes, hydrocarbons and helium composition...
January 30, 2018: Ground Water
https://www.readbyqxmd.com/read/29377755/quality-of-life-outcomes-for-cabozantinib-versus-everolimus-in-patients-with-metastatic-renal-cell-carcinoma-meteor-phase-iii-randomized-trial
#12
David Cella, Bernard Escudier, Nizar M Tannir, Thomas Powles, Frede Donskov, Katriina Peltola, Manuela Schmidinger, Daniel Y C Heng, Paul N Mainwaring, Hans J Hammers, Jae Lyun Lee, Bruce J Roth, Florence Marteau, Paul Williams, John Baer, Milan Mangeshkar, Christian Scheffold, Thomas E Hutson, Sumanta Pal, Robert J Motzer, Toni K Choueiri
Purpose In the phase III METEOR trial ( ClinicalTrials.gov identifier: NCT01865747), 658 previously treated patients with advanced renal cell carcinoma were randomly assigned 1:1 to receive cabozantinib or everolimus. The cabozantinib arm had improved progression-free survival, overall survival, and objective response rate compared with everolimus. Changes in quality of life (QoL), an exploratory end point, are reported here. Patients and Methods Patients completed the 19-item Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19) and the five-level EuroQol (EQ-5D-5L) questionnaires at baseline and throughout the study...
January 29, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29340852/a-geochemical-view-into-continental-palaeotemperatures-of-the-end-permian-using-oxygen-and-hydrogen-isotope-composition-of-secondary-silica-in-chert-rubble-breccia-kaibab-formation-grand-canyon-usa
#13
Ray Kenny
The upper carbonate member of the Kaibab Formation in northern Arizona (USA) was subaerially exposed during the end Permian and contains fractured and zoned chert rubble lag deposits typical of karst topography. The karst chert rubble has secondary (authigenic) silica precipitates suitable for estimating continental weathering temperatures during the end Permian karst event. New oxygen and hydrogen isotope ratios of secondary silica precipitates in the residual rubble breccia: (1) yield continental palaeotemperature estimates between 17 and 22 °C; and, (2) indicate that meteoric water played a role in the crystallization history of the secondary silica...
January 16, 2018: Geochemical Transactions
https://www.readbyqxmd.com/read/29304500/dual-oxygen-and-nitrogen-isotopic-characterization-of-the-museum-archived-nitrates-from-the-united-states-of-america-south-africa-and-australia
#14
Chitoshi Mizota, Takahiro Hosono, Midori Matsunaga, Azusa Okumura
Dual (oxygen and nitrogen) isotopic composition of the museum archived nitrates from the United States of America, South Africa and Australia was studied. The analyzed specimens were collected in middle 19th to early 20th centuries, and represent world-wide acquisition of the Smithsonian Institution Natural Museum of Natural History (Washington, D. C., USA) and the Natural History Museum (London, UK). The samples consist of transparent to semi-transparent aggregates of minute nitrate, euhedral crystallites which imply precipitation from percolating fluids under ample space and dry regimes...
June 1, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29289785/stable-isotopic-composition-reveals-the-spatial-and-temporal-dynamics-of-discharge-in-the-large-river-of-yarlungzangbo-in-the-tibetan-plateau
#15
Wei Ren, Tandong Yao, Shiyou Xie
Spatial and temporal variability in stable isotopic compositions (δ18 O and δD) in river water of the Yarlungzangbo was investigated to identify major hydrological processes along the river channel and evaluate the isotopic response to discharge variation. The results show geographic, distinct isotopic evolutions in the Yarlungzangbo system. Along the main stem, river δ18 O exhibits a decreasing trend from the headwaters to the middle reach but an increasing one from the middle to the lower reaches, and main flows demonstrate much greater δ18 O-δD slope and intercept compared to the global meteoric water line (GMWL) and reported local meteoric water lines (LMWLs) for sites within the basin...
June 1, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29286294/real-time-detection-of-sporadic-meteors-in-the-intensified-tv-imaging-systems
#16
Stanislav Vítek, Maria Nasyrova
The automatic observation of the night sky through wide-angle video systems with the aim of detecting meteor and fireballs is currently among routine astronomical observations. The observation is usually done in multi-station or network mode, so it is possible to estimate the direction and the speed of the body flight. The high velocity of the meteorite flying through the atmosphere determines the important features of the camera systems, namely the high frame rate. Thanks to high frame rates, such imaging systems produce a large amount of data, of which only a small fragment has scientific potential...
December 29, 2017: Sensors
https://www.readbyqxmd.com/read/29260479/the-hydrogen-and-oxygen-isotopic-compositions-of-precipitation-in-a-forested-watershed-of-the-south-qinling-mts-china
#17
Hongmei Bu, Xianfang Song, Jun Xia
The stable isotopic compositions (δD and δ18 O) of precipitation were firstly investigated from May 2012 to November 2013 in the Jinshui River basin of the South Qinling Mts., China. The local meteoric water lines (LMWLs) based on all daily and monthly precipitation-weighted data were defined as δD = 8.32 δ18 O + 12.57 (r2  = 0.957, n = 47, p < 0.001) and δD = 8.11 δ18 O + 11.59 (r2  = 0.946, n = 15, p < 0.001), respectively. The fluctuations of daily deuterium excess (d-excess) values indicated the mixing moisture sources from the monsoon circulation during the rainy season and the local moisture recycling during the dry season in the river basin...
March 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29245376/the-genus-i-diphasia-i-l-agassiz-1862-cnidaria-hydrozoa-in-northwest-africa
#18
Marta Gil, Fran Ramil
This paper is the result of the study of large collections of Sertulariidae Lamouroux, 1812 (Cnidaria, Hydrozoa, Hydroidolina) obtained from continental margins of Northwest Africa by several Spanish and Norwegian surveys between 2004 and 2012. Material collected from Lusitanian seamounts by the French Seamount 1 expedition and from the Great Meteor Bank by the German survey Meteor 42/3 were also examined. A total of 12 species belonging to the genus Diphasia were studied and illustrated, and four new species were described: Diphasia leonisae n...
December 12, 2017: Zootaxa
https://www.readbyqxmd.com/read/29220761/climate-change-potential-effects-on-the-hydrological-regime-of-freshwater-springs-in-the-italian-northern-apennines
#19
Federico Cervi, Francesca Petronici, Attilio Castellarin, Marco Marcaccio, Andrea Bertolini, Lisa Borgatti
In large areas of the Italian Northern Apennines, hundreds of low-yield springs provide water for drinking and industrial purposes, with short groundwater flow paths being formed within fractured sedimentary rock units. This hydrogeological setting results in spring water discharges that closely follow meteoric water recharge patterns, leading to low-flow periods concentrated in the summer/early autumn. Therefore, the springs' outflow can be very sensitive to a shortage in water recharge, as it was the case in 2003 and 2017, when a prolonged period of drought caused severe water management issues...
May 1, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29209551/synchronous-occurrence-of-primary-breast-carcinoma-and-primary-colon-adenocarcinoma
#20
Gurkan Yetkin, Fevzi Celayir, Ismail Ethem Akgun, Ramazan Ucak
A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast...
2017: Case Reports in Surgery
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