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Edely, O. H., and M. Mursaleen. "On $A$-statistical convergence and $A$-statistical Cauchy via idea." Carpathian Mathematical Publications 14, no. 2 (December 30, 2022): 442–52. http://dx.doi.org/10.15330/cmp.14.2.442-452.
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In [Analysis 1985, 5 (4), 301-313], J.A. Fridy proved an equivalence relation between statistical convergence and statistical Cauchy sequence. In this paper, we define $A^{I^{\ast }}$-statistical convergence and find under certain conditions, that it is equivalent to $A^{I}$-statistical convergence defined in [Appl. Math. Lett. 2012, 25 (4), 733-738]. Moreover, we define $A^{I}$- and $A^{I^{\ast }}$-statistical Cauchy sequences and find some equivalent relation with $A^{I}$- and $A^{I^{\ast }}$-statistical convergence.
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Choi, Eun-Ji, Young-Uk Cho, Han-Seung Park, Jung-Hee Lee, Kyoo Hyung Lee, Sang-Hyun Hwang, Seongsoo Jang, Chan-jeoung Park, and Je-Hwan Lee. "Similar Survival and Genetic Features between Clonal Cytopenia of Undetermined Significance and Lower-Risk Myelodysplastic Syndrome." Blood 138, Supplement 1 (November 5, 2021): 3683. http://dx.doi.org/10.1182/blood-2021-150368.
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Abstract Background Idiopathic cytopenia of undetermined significance (ICUS) is characterized by a persistent and clinically significant cytopenias which does not meet the diagnostic criteria for myelodysplastic syndrome (MDS). In some patients with ICUS, disease evolution to MDS or acute myeloid leukemia after variable periods of time was observed in several studies. However, the incidence and predictive factors of progression as well as management guidelines for ICUS patients are not well established. We aimed to identify the clinical and genetic characteristics of ICUS in comparison with lower-risk MDS for understanding the pathophysiologic features and providing guidance for treating physicians. Methods We performed targeted deep sequencing including 61 myeloid neoplasm-related genes with a MiSeqDx sequencer (Illumina) using bone marrow (BM) samples obtained from the patients with ICUS (n=139) and MDS (n=226) between May 2009 and December 2019. The cut-off level of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. Cloncal cytopenia of undetermined significance (CCUS) was defined as ICUS with ≥ 2% VAF of mutations and lower-risk MDS was defined as MDS with revised international prognostic scoring system ≤3.5. Results When we compared the overall survival (OS) of the patients according to the disease subtypes, OS of CCUS (77.0% at 5-year) was significantly better than that of higher-risk MDS (41.0%, P<.001) and worse than non-clonal ICUS (94.1%, P=.050), but it was similar to the OS of lower-risk MDS (67.9%, P=.363). Next, we compared the clinical and mutational features between CCUS (n=78) and lower-risk MDS (n=99). As shown in Table, there was no significant difference of patient characteristics between two groups except for higher hemoglobin level (10.5 vs. 9.0 g/dL, P=.008) in CCUS than lower-risk MDS, and the rate of red blood cell transfusion dependency was not different (P=.738). The median number of mutated genes of CCUS and lower-risk MDS were 1 (range, 0-4) and 1 (range, 0-6) (P=.651), and the median mutation numbers were 1 (range, 0-5) in CCUS and 2 (range, 0-7) in lower-risk MDS, respectively (P=.711). The mutational profiles of 61 genes were also similar between CCUS and lower-risk MDS except for SF3B1 (2.6% in CCUS and 18.2% in lower-risk MDS; P=.001) and STAT3 (5.1% in CCUS and 0% in lower-risk MDS; P=.023). Overall, 11 of 78 CCUS and 24 of 99 MDS died, and the causes of death were not different between two groups (P=.861). Conclusion In our study, CCUS and lower-risk MDS showed similar OS which was significantly better than higher-risk MDS and worse than non-clonal ICUS. The clinical and mutational characteristics were also similar except for the degree of anemia and the SF3B1 and STAT3 mutation. Our findings suggest that the patients with CCUS may be regarded and treated as the lower-risk MDS despite a lack of significant dysplasia or MDS-associated definitive chromosomal abnormality. Disclosures Choi: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Korean Society of Hematology: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Other: Advisory board; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board.
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Dunn, Geoffrey D. "The ecclesiastical reorganisation of space and authority in late antique gaul: Zosimus' letter Multa contra (JK 334 = J3 740)." Journal of the Australian Early Medieval Association 12 (2016): 1–33. http://dx.doi.org/10.35253/jaema.2016.1.1.
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On 29 September 417 'Zosimus', bishop of Rome, wrote 'Epistula' 5 ('Multa contra' - JK 334 = J3 740) to the bishops of the Gallic provinces of Viennensis and Narbonensis Secunda. It followed a synod that had been held in Rome on 22 September to consider alleged violations by Proculus of Marseille of the hierarchical relationship between the churches of southern Gaul and the authority of metropolitan bishops over the other churches of their provinces. Episcopal authority was geographically defined and circumscribed by Roman provincial boundaries, with the bishop of a provincial capital having some authority over the other bishops of the province. What was to happen, though, when those boundaries changed or a new city within a province became capital? In a series of four letters (the others being 'Epistulae' 4 ['Cum aduersus' - JK 331 = J3 737], 6 ['Mirati admodum' - JK 332 = J3 738], and 7 [Quid de 'Proculi' - JK 333 = J3 739) written immediately after the synod, of which this letter is the last, Zosimus supported the claims of Patroclus, bishop of Arles, to be not only the metropolitan of Viennensis but, surprisingly, the sole metropolitan over several Roman provinces. This paper examines how authority within the late antique church was dependent upon spatial organisational arrangements and how temporal arguments could be advanced when such spatial arrangements did not suit the personal plans of some ambitious bishops. It further considers the religious conflict that arose over disputed areas of authority and the mechanism by which attempts were made at its resolution and how Zosimus' action contributed ultimately to a developing concept of papal primacy.
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Matsuyama, Kiyoshi, Kenji Mishima, Ryugen Ohdate, Masuhiro Chidori, and Huai Yang. "Solubilities of 7,8-Dihydroxyflavone and 3,3‘,4‘,5,7-Pentahydroxyflavone in Supercritical Carbon Dioxide." Journal of Chemical & Engineering Data 48, no. 4 (July 2003): 1040–43. http://dx.doi.org/10.1021/je030129z.
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Xu, Shan, Cheng Yu Sun, Fei Lei, Yuan Biao Tu, Wei Peng Zeng, Hui Xia, Peng Wu Zheng, and Wu Fu Zhu. "Synthesis of 4-(2-(Piperazin-1-Yl)-7,8-Dihydro-5H-Thiopyrano[4,3-d]Pyrimidin-4-yl)Morpholine and 4-Morpholino-2-(Piperazin-1-Yl)- 7,8-Dihydro-5H-Thiopyrano[4,3-d]Pyrimidine 6,6-Dioxide." Applied Mechanics and Materials 651-653 (September 2014): 111–14. http://dx.doi.org/10.4028/www.scientific.net/amm.651-653.111.
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Two novel thiopyrano [4,3-d] pyrimidine derivatives 7 and 8 were synthesized from dimethyl 3,3'-thiodipropanoate through six steps including two times of cyclization, chlorination, oxidation, substitution with morpholine and piperazine and their structures were confirmed by1H NMR and MS spectrum. The total yield of the six steps was 18.6% (calculated from methyl dimethyl 3,3'-thiodipropanoate). The synthetic routes of them can be used to synthesize PI3K/mTOR inhibitors bearing a thiopyrano [4,3-d] pyrimidine nucleus.
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Рукавицын, А. А., А. М. Ковригина, А. А. Самойлова, В. В. Богатырёв, Е. Г. Смирнова, Н. Е. Мочкин, А. А. Мамедова, С. А. Алексеев, В. О. Саржевский, and В. Я. Мельниченко. "Implant-Associated Anaplastic T-Cell Lymphoma. The Current State of the Problem, Own Experience." Гематология. Трансфузиология. Восточная Европа, no. 1 (March 24, 2023): 82–93. http://dx.doi.org/10.34883/pi.2023.9.1.010.
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Анапластическая Т-клеточная лимфома, ассоциированная с имплантами молочных желез, или имплант-ассоциированная Т-клеточная лимфома (ИА-ТКЛ), является редкой формой неходжкинскихT-клеточных лимфом (CD30+/ALK-), развивающейся в фиброзной капсуле (или за ее пределами), возникающей вследствие длительного контакта импланта с тканями реципиента. Заболеваемость данным видом лимфом неуклонно увеличивается – по данным на конец 2021 г. в мире зарегистрировано 733 случая ИА-ТКЛ и 36 летальных исходов, связанных с ИА-ТКЛ, большая часть в США – 363, Австралии – 112, Франции – 86. В России зарегистрировано только 4 случая без летальных исходов. В статье описаны современный подход к диагностике и лечению ИА-ТКЛ и собственный клинический опыт. Breast implant-associated anaplastic T-cell lymphoma or implant-associated T-cell lymphoma (BIA-TCL) is a rare type of non-Hodgkin T-cell lymphoma (CD30+/ALK-) which evolves from fibrous cap or outside due to long-term contact between the implant and the recipient tissue. The incidence of this type lymphoma is increasing – 733 cases of BIA- TCL and 36 deaths in the end of 2021 worldwide. Most cases in the United States – 363, Australia – 112, France – 86, in Russia only 4 cases are registered without fatalities. The article describes the current approach to the diagnosis and treatment of BIA-TCL and own clinical experience.
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Patel, Rahul V., Premlata Kumari, and Kishor H. Chikhalia. "Fluorinated s-Triazinyl Piperazines as Antimicrobial Agents." Zeitschrift für Naturforschung C 66, no. 7-8 (August 1, 2011): 345–52. http://dx.doi.org/10.1515/znc-2011-7-805.
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A series of 1,3,5-triazine derivatives that contain 4-amino-2-trifl uoromethyl-benzonitrile, 8-hydroxyquinoline, and different piperazines as substituents at the carbon atoms of the triazine ring have been synthesized by a simple and efficient synthetic protocol. The chemical structures of the compounds were elucidated with the aid of IR, 1H NMR and 13C NMR spectroscopy, and elemental analysis. The antimicrobial activity of the compounds was tested against seven bacteria (Staphylococcus aureus MTCC 96, Bacillus cereus MTCC 619, Escherichia coli MTCC 739, Pseudomonas aeruginosa MTCC 741, Klebsiella pneumoniae MTCC 109, Salmonella typhi MTCC 733, Proteus vulgaris MTCC 1771) and four fungi (Aspergillus niger MTCC 282, Aspergillus fumigatus MTCC 343, Aspergillus clavatus MTCC 1323, Candida albicans MTCC 183). The results indicate that some of the novel s-triazines have noteworthy activity in minimum inhibitory concentration as well as agar diffusion tests.
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Prynne, CJ, AA Paul, GM Price, KC Day, WS Hilder, and MEJ Wadsworth. "Food and nutrient intake of a national sample of 4-year-old children in 1950: comparison with the 1990s." Public Health Nutrition 2, no. 4 (April 1999): 537–47. http://dx.doi.org/10.1017/s1368980099000725.
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AbstractObjective:To evaluate the food and nutrient intake of members of a birth cohort study when young children in 1950 and investigate differences from present-day children's diets.Design:One-day recall diet records from the MRC National Survey of Health and Development (NSHD) (1946 Birth Cohort) at age 4 years were analysed for energy and selected nutrients and compared to the published results for 4-year-olds in the 1992/93 National Diet and Nutrition Survey (NDNS).Setting:England, Scotland and Wales in 1950 and 1992/93.Subjects:4599 children in 1950 and 493 children in 1992/93.Results:Mean (SD) daily intakes in 1950 were energy 1445 (343) kcal, or 6.1 (1.4) MJ, protein 46 (11)g, fat 64 (20)g, starch 117 (33)g, sugar 62 (24)g, unavailable carbohydrate 13 (4)g, calcium 736 (230)mg, iron 7.7 (2.1)mg, retinol 738 (1273) μg, carotene 1049 (1130) μg and vitamin C 40 (26) mg. Compared to 1992/93, the 1950 diet contained substantially more bread and vegetables and less sugar and soft drinks, giving it a higher starch and fibre content and making it more in line with current recommendations on healthy eating. However, fat provided 40% of energy in 1950, compared to 35% in 1992/93. In 1950, red meat was an important source of iron, but by 1992 most iron came from fortified breakfast cereals. Vitamin C came mainly from vegetables in 1950, but from soft drinks in 1992.Conclusions:The relative austerity of post-war food supplies resulted in food and nutrient intakes in 1950 which in many respects may well have been beneficial to the health of young children, despite fat intake being higher than present-day recommendations.
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Singh, Girija S., and Patrick M. Luntha. "Unanticipated products from reductive and oxidative cleavages of 1-substituted 3,3-diphenyl-1′-methylspiro[azetidine-2,3′-indoline]-2′,4-diones." Journal of Heterocyclic Chemistry 48, no. 6 (August 18, 2011): 1312–16. http://dx.doi.org/10.1002/jhet.731.
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Narkevich, Artem Nikolaevich, Konstantin Anatol’evich Vinogradov, Mikhaylovna Nataliya Koretskaya, Alina Vladimirovna Kataeva, and Ekaterina Olegovna Zhurbenko. "ОЦЕНКА ИНФОРМАТИВНОСТИ И ОТБОР ПРИЗНАКОВ ПРИ ИДЕНТИФИКАЦИИ ОБЪЕКТОВ НА ЦИФРОВЫХ ИЗОБРАЖЕНИЯХ МИКРОСКОПИЧЕСКИХ ПРЕПАРАТОВ, ОКРАШЕННЫХ ПО МЕТОДУ ЦИЛЯ-НИЛЬСЕНА." V Mire Nauchnykh Otkrytii 9, no. 4 (October 28, 2017): 106. http://dx.doi.org/10.12731/wsd-2017-4-106-121.
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Цель. Оценка информативности и осуществление отбора признаков для классификации объектов, на цифровых изображениях микроскопических препаратов, окрашенных по методу Циля-Нильсена с помощью методов Шеннона и Кульбака, а также сравнение результатов их применения.Материалы и методы. Использовались данные о 343 687 объектах, выделенных на цифровых изображениях микроскопических препаратов: 6 708 объектов – кислотоустойчивые микобактерии, 336 979 – иные объекты. Анализ объектов производился по 240 цветовым и морфометрическим признакам, оценка информативности которых осуществлялась с помощью методов Шеннона и Кульбака. Оценка качества отбора признаков осуществлялась с применением наивного Байесовского классификатора.Результаты. Наибольшую информативность по методу Шеннона имели цветовые признаки объектов и соотношения их размеров, а наибольшая доля верно классифицированных объектов (84,6%) была достигнута при включении в классификационную модель 6 признаков с наибольшей информативностью по методу Шеннона. Наибольшую информативность по методу Кульбака имели радиальные размеры объектов и их соотношения, а наибольшая доля верно классифицированных объектов (78,0%) была достигнута при включении в классификационную модель 14 признаков с наибольшей информативностью по методу Кульбака.Заключение. Методы Шеннона и Кульбака могут применяться для снижения признакового пространства при классификации объектов. Метод Шеннона позволяет в большей мере сократить количество признаков, обеспечивая при этом наибольшую долю верной классификации объектов.
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Demetrio, D., A. Magalhaes, M. Oliveira, R. Santos, and R. Chebel. "11 Invivo-derived embryo pregnancy rates at Maddox Dairy from 2008 to 2018." Reproduction, Fertility and Development 32, no. 2 (2020): 130. http://dx.doi.org/10.1071/rdv32n2ab11.
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Maddox Dairy, located in Riverdale, CA, USA, is a Holstein herd that milks 3500 cows with a 305-day mature-equivalent milk production of 12 800 kg, and they have been producing high genetic animals by embryo transfer (ET) since the early 1980s. Invivo-derived embryos from Holstein donors were transferred fresh (grade 1 or 2) or frozen (grade 1), at morula (4), early blastocyst (5), or blastocyst (6) stage, to virgin heifers (VH, natural oestrus, 13-15 months old) or lactating cows (LC, Presynch-Ovsynch, 86 days in milk, first or second lactation) 6 to 9 days after oestrus. Pregnancy diagnosis was done by transrectal ultrasonography at 32-46 days in VH and by the IDEXX PAG test at 30 days in LC. June, July, August, September, and October were called critical months (first service AI conception rate drops below 44%) and compared with the other months. The data from 32 503 ETs between January 2008 and December 2018 are summarised on Table 1. Pregnancy rates (PR) are lower for LC recipients than for VH. Embryo transfers performed 7 or 8 days after oestrus had higher PR in both types of recipients and embryos, but Day 6 and 9 oestrus are also used with fair results. The season does not seem to affect PR. There is not enough difference in the combination of stage and days from oestrus for invivo-derived embryos. These numbers do not belong to a planned experiment. Several management changes during the years were made, which make it very difficult to apply statistical methods to analyse the data correctly. They are used as a tool to make decisions in an attempt to improve future results. Table 1.Pregnancy rate (PR) of virgin heifers (top) and lactating cows (bottom)-fresh (SH) and frozen (OZ) invivo-derived embryo transfer1 Heat-months SH-ST4 SH-ST5 SH-ST6 SH-All OZ-ST4 OZ-ST5 OZ-ST6 OZ-All PR% n PR% n PR% n PR% n PR% n PR% n PR% n PR% n Heifers 6 d-CM 62 934 66 243 68 69 63 1246 56 473 58 219 62 42 57 734 6 d-OM 62 1623 67 489 69 211 64 2323 56 600 55 296 48 137 55 1033 6 d-T 62 2557 67 732 69 280 63 3569 56 1073 57 515 51 179 56 1767 7 d-CM 64 1506 68 495 67 221 65 2222 60 822 62 340 63 156 61 1318 7 d-OM 66 2723 68 1021 69 510 67 4254 57 1120 59 581 57 231 58 1932 7 d-T 66 4229 68 1516 69 731 67 6476 58 1942 60 921 60 387 59 3250 8 d-CM 65 1348 64 518 67 322 65 2188 59 595 64 258 63 108 61 961 8 d-OM 66 2166 68 886 70 510 67 3562 61 770 60 364 51 130 60 1264 8 d-T 66 3514 67 1404 69 832 66 5750 60 1365 62 622 56 238 60 2225 9 d-CM 60 109 56 43 70 20 60 172 60 5 33 6 50 4 47 15 9 d-OM 58 129 63 57 60 40 60 226 63 16 50 18 75 4 58 38 9 d-T 59 238 60 100 63 60 60 398 62 21 46 24 63 8 55 53 All-CM 64 3897 66 1299 67 632 65 5828 58 1895 61 823 63 310 60 3028 All-OM 65 6641 67 2453 69 1271 66 10 365 58 2506 58 1259 53 502 58 4267 All-T 65 10 538 67 3752 69 1903 66 16 193 58 4401 60 2082 57 812 59 7295 Lactating cows 6 d-CM 54 265 48 86 50 12 53 363 38 141 31 77 50 10 36 228 6 d-OM 49 463 52 203 45 56 50 723 46 101 48 54 59 27 48 182 6 d-T 51 728 51 289 46 68 51 1086 41 242 38 131 57 37 42 410 7 d-CM 54 755 59 274 56 103 55 1137 43 928 48 450 43 192 45 1570 7 d-OM 55 914 66 367 54 109 58 1393 46 1052 45 564 47 353 46 1969 7 d-T 55 1669 63 641 55 212 57 2530 45 1980 46 1014 46 545 45 3539 8 d-CM 63 252 68 82 76 33 65 368 48 219 56 80 42 33 50 332 8 d-OM 61 257 64 161 53 47 61 466 50 191 53 77 56 16 51 284 8 d-T 62 509 65 243 63 80 63 834 49 410 55 157 47 49 50 616 All-CM 56 1272 58 442 60 148 57 1868 44 1288 47 607 43 235 45 2130 All-OM 55 1634 62 731 51 212 56 2582 47 1344 46 695 48 396 47 2435 All-T 55 2906 60 1173 55 360 57 4450 45 2632 47 1302 46 631 46 4565 1ST=stage; CM=critical months (June, July, August, September, and October); OM=other months.
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Djemal, Serpil, Mohammadreza Aryafar, Aviva Petrie, Nectaria Polycarpou, Edward Brady, and Sadia Niazi. "Traumatic dental injuries in adults attending a London-based trauma clinic in the UK: a seven-year survey." British Dental Journal 233, no. 12 (December 16, 2022): 1022–28. http://dx.doi.org/10.1038/s41415-022-5313-4.
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AbstractIntroduction This survey reports the incidence of traumatic dental injuries in an adult population attending an adult dental trauma clinic in a London teaching hospital.Materials and methods Retrospective data were collected from patients attending an adult dental trauma clinic between 2012 and 2018.Results In total, 1,769 patients attended, with more men seen (1,030; 58.2%) compared to women (739; 41.8%) and this was statistically significant (p <0.05). The most common aetiological factor was an accidental fall (728; 41.15%), followed by assaults (413; 23.35%), bicycle accidents (253; 14.3%), sports injuries (132; 7.46%) and road traffic accidents (84; 4.75%). Lateral luxation (833) was the most common traumatic injury and this was followed by avulsions (362; 17%). Enamel-dentine fractures were the most common type of fracture injury (1,273; 64%).Discussion This retrospective survey attempts to report on the incidence of traumatic dental injuries in a London-based cohort of patients attending a specialised dental trauma clinic. In line with other reports, there were more men than women affected, which is probably attributed to behavioural activities.Conclusion(s) Accidental falls are the most common cause of a traumatic dental injury, lateral luxation was the most common type of displacement injury and enamel-dentine fractures were the most common type of fracture injury.
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Sun, Xiaowei, Huijiao Yan, Yujie Zhang, Xiao Wang, Dawei Qin, and Jinqian Yu. "Preparative Separation of Diterpene Lactones and Flavones from Andrographis paniculate Using Off-Line Two-Dimensional High-Speed Counter-Current Chromatography." Molecules 24, no. 3 (February 11, 2019): 620. http://dx.doi.org/10.3390/molecules24030620.
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Seven diterpene lactones, andrographolide (1), isoandrographolide (2), neo-andrographolide (3), 14-deoxy-11,12-didehydroandrographolide (4), 14-deoxyandrographiside (5), 14-deoxy-11,12-didehydroandrographiside (6), 3,14-dideoxyandrographolide (10), and three flavones, andrographidine C (7), andrographidine A (8), 5-hydroxy-7,8-dimethoxyflavanone (9) have been successfully and efficiently isolated from A. paniculata using an off-line two dimensional (2D) high-speed counter-current chromatography (HSCCC) method for the first time. For the first dimension HSCCC separation, petroleum ether-ethyl acetate-methanol-water 3:7:5:5 (v/v) was employed to isolate 14.4 mg of compound 1, 3.1 mg of compound 2, 7.8 mg of compound 3, and 18.0 mg of compound 4 from 200 mg of the A. paniculata extract. For the second dimension HSCCC separation, petroleum ether-ethyl acetate-methanol-water 2:8:1:9 (v/v) and 5:5:6:4 (v/v) were employed to isolate the collected fractions ranged from 55 to 79 min and the flow out fraction, respectively, which led to 5.1 mg of compound 5, 4.4 mg of compound 6, 2.4 mg of compound 7, 3.3 mg of compound 8, 4.0 mg of compound 9, 7.0 mg of compound 10. The structures of these diterpene lactones and flavones were elucidated by extensive spectroscopic methods.
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Demurin, Ya N., V. D. Savchenko, O. M. Borisenko, A. N. Levutskaya, N. N. Tolmachyova, Yu V. Chebanova, O. A. Rubanova, E. N. Ryzhenko, T. S. Antonova, and N. M. Araslanova. "Broomrape-resistant sunflower hybrid Taizar." Oil Crops 184, no. 4 (December 25, 2020): 87–90. http://dx.doi.org/10.25230/2412-608x-2020-4-184-87-90.
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A simple sunflower hybrid Taizar was developed at V.S. Pustovoit All-Russian Research Institute of Oil Crops as part of a breeding and genetic program for developing highly productive hybrids resistant to the new virulent races of broomrape by using the method of backcrossing in combination with an evaluation of resistance in each generation for the target gene Or7. The hybrid Taizar is of mid-early group of ripeness, it has a high yield, it is resistant to Orobanche cumana Wallr. (races A-G) and downy mildew (races 330, 710, 730, 334, 734). The line-restorer of pollen fertility VK 305 is the paternal form of the hybrid Taizar. The line was developed as a result of the introduction of the Or7 gene from the RG line by two backcrosses into the line VK 303, subsequent inbreeding and selection of broomrape-resistant genotypes. The line VK 305 has narrow widely spaced ray flowers strongly curved towards the back of the head, which can serve as a morphological marker of genetic purity.
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Ari-Gur, Pnina, V. Ovidiu Garlea, Ashley Coke, Yan Ling Ge, Ilkka Aaltio, Simo Pekka Hannula, Hui Bo Cao, Amila S. B. Madiligama, and Victor V. Koledov. "Neutron Diffraction Study of a Non-Stoichiometric Ni-Mn-Ga MSM Alloy." Materials Science Forum 738-739 (January 2013): 103–7. http://dx.doi.org/10.4028/www.scientific.net/msf.738-739.103.
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Abstract. The structure and chemical order of a Heusler alloy of non-stoichiometric composition Ni-Mn-Ga were studied using constant-wavelength (1.538 Å) neutron diffraction at 363K and the diffraction pattern was refined using the FullProf software. At this temperature the structure is austenite (cubic) with Fm space group and lattice constant of a = 5.83913(4) [Å]. The chemical order is of critical importance in these alloys, as Mn becomes antiferromagnetic when the atoms are closer than the radius of the 3d shell. In the studied alloy the refinement of the site occupancy showed that the 4b (Ga site) contained as much as 22% Mn; that significantly alters the distances between the Mn atoms in the crystal and, as a result, also the exchange energy between some of the Mn atoms. Based on the refinement, the composition was determined to be Ni1.91Mn1.29Ga0.8
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Di Paola, Jorge. "Novel Congenital Platelet Disorders." Blood 128, no. 22 (December 2, 2016): SCI—39—SCI—39. http://dx.doi.org/10.1182/blood.v128.22.sci-39.sci-39.
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The processes of megakaryocyte differentiation, proplatelet formation, and the daily release of 1011 platelets into the bloodstream are tightly regulated. Genetic disturbances can lead to a cascade of downstream molecular alterations that markedly affect the function of megakaryocytes and platelets. Therefore, identifying new genes and their function in megakaryocytes and platelets is critical for understanding how these unique cells contribute to health and disease. Over the last decade advances in genomics, specifically next generation sequencing, have allowed for the discovery of several mutations and genetic variants that cause disease or influence associated hematological traits. By performing platelet RNA-Seq we were among the first to identify NBEAL2 as the causative gene for gray platelet syndrome (GPS) and showed that NBEAL2 regulates megakaryocyte development and platelet function.1-3 Mice carrying targeted Nbeal2 null alleles not only replicated the thrombocytopenia and lack of alpha granules observed in humans, but also provided new information about the role of platelets in thromboinflammation, wound healing, myelofibrosis and metastasis dissemination.4-7 More recently, we and others found that germline mutations in ETV6 lead to thrombocytopenia, red cell macrocytosis, and predisposition to lymphoblastic leukemia.8,9ETV6 encodes an ETS family transcriptional repressor, which exerts its activity by binding a consensus sequence in the promoter regions of DNA. Mice with conditional Etv6 knockout in megakaryocytic-erythroid cells are thrombocytopenic indicating the involvement of Etv6 in thrombopoiesis.10 Several of the families recently described have a missense mutation in the central domain of ETV6 (p.P214L). This mutation results in aberrant cellular localization of ETV6, decreased transcriptional repression, and impaired megakaryocyte maturation. The bone marrow of individuals affected by this mutation show hyperplasia of immature megakaryocytes suggesting a differentiation arrest. Deep sequencing of the platelet transcriptome also revealed significant differences in mRNA expression levels between patients with the ETV6 p.P214L mutation and non-affected family members, indicating that ETV6 is critically involved in defining the molecular phenotype and function of platelets. Consistent with this notion, individuals with the ETV6 p.P214L mutation experience bleeding that is disproportionate to their mild thrombocytopenia. We have also used CRISPR/Cas9 technology to generate a mouse colony where the human p.P214L ETV6 mutation was inserted into the conserved site of Etv6. Mice with this mutation (Etv6H.P214L) have reduced platelet counts. In summary, advances in human genetics that led to the discovery of novel congenital platelet disorders coupled with relevant animal models will likely contribute to our understanding of megakaryopoiesis and platelet function. References 1. Kahr WH, Hinckley J, Li L, et al. Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. Nature genetics. 2011;43(8):738-740. 2. Gunay-Aygun M, Falik-Zaccai TC, Vilboux T, et al. NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet alpha-granules. Nature genetics. 2011;43(8):732-734. 3. Albers CA, Cvejic A, Favier R, et al. Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndrome. Nature genetics. 2011;43(8):735-737. 4. Deppermann C, Cherpokova D, Nurden P, et al. Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice. The Journal of clinical investigation. 2013. 5. Kahr WH, Lo RW, Li L, et al. Abnormal megakaryocyte development and platelet function in Nbeal2(-/-) mice. Blood. 2013;122(19):3349-3358. 6. Guerrero JA, Bennett C, van der Weyden L, et al. Gray platelet syndrome: proinflammatory megakaryocytes and alpha-granule loss cause myelofibrosis and confer metastasis resistance in mice. Blood.2014;124(24):3624-3635. 7. Tomberg K, Khoriaty R, Westrick RJ, et al. Spontaneous 8bp Deletion in Nbeal2 Recapitulates the Gray Platelet Syndrome in Mice. PLoS One. 2016;11(3):e0150852. 8. Noetzli L, Lo RW, Lee-Sherick AB, et al. Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. Nature Genetics. 2015;47(5):535-538. 9. Zhang MY, Churpek JE, Keel SB, et al. Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. Nature genetics. 2015;47(2):180-185. 10. Wang LC, Swat W, Fujiwara Y, et al. The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow. Genes & development. 1998;12(15):2392-2402. Disclosures Di Paola: CSL BEhring: Consultancy; Biogen: Consultancy.
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Kahn, Justine, Sergio Barrera, Randy Davila, Emily Roberts, ZheZhen Jin, Kristen Stevenson, Traci M. Blonquist, et al. "Higher Incidence of Treatment-Related Toxicities in Non-Hispanic Patients Undergoing Therapy for Newly Diagnosed Pediatric Acute Lymphoblastic Leukemia on Dana-Farber Cancer Institute ALL Consortium Protocol 05-001." Blood 126, no. 23 (December 3, 2015): 248. http://dx.doi.org/10.1182/blood.v126.23.248.248.
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Abstract Background: Risk-adapted treatment strategies have contributed to excellent outcomes in pediatric acute lymphoblastic leukemia (ALL); however, treatment-associated acute and long-term toxicities persist. Therapy-associated toxicities of note in pediatric ALL are related to a treatment backbone that relies heavily on corticosteroids (prednisone and dexamethasone) and asparaginase (ASP). The most frequently observed toxicities include, but are not limited to, serious infection, pancreatitis, thrombosis and bony morbidities including osteonecrosis (ON) and fracture. Previous studies suggest that children of racial and ethnic minorities are at higher risk for treatment-associated toxicities. We assessed the incidence of treatment-related toxicities in Hispanic and non-Hispanic patients undergoing treatment for pediatric ALL. Patients and Methods: Retrospective cohort study investigating the incidence of treatment-related toxicities including infection, allergy to ASP, pancreatitis, thrombosis and bony morbidities in Hispanic and non-Hispanic children and adolescents with newly diagnosed ALL undergoing therapy on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 05-001. The ethnicity of each patient was designated at the time of study enrollment by research coordinators. Descriptive statistics were calculated, mean +/- SD for continuous variables and frequency and percentages for categorical variables. Toxicity rates were based on number of patients. Comparison between groups was done by Chi-square test or FisherÕs exact test and p -value < 0.05 was considered significant. Results: Between 2005 and 2011, 794 children and adolescents (ages 1 - 18 years) were enrolled on Protocol 05-001, 730 of whom were evaluable for this investigation: 150 Hispanic (18%), 580 non-Hispanic (73%). Sixty-four patients did not have ethnicity documented. There was no significant difference in disease-risk group, age or gender between the two groups. Weight was significantly higher in Hispanic patients (31.9 ± 24.4 kg in Hispanic and 26.9 ± 18.7 kg in non-Hispanic, p = 0.021). There was no significant difference in the incidence of ASP-related toxicities (allergy, pancreatitis, thrombosis) between Hispanic and non-Hispanic patients. There was no significant difference in the overall incidence of infection between the two groups (42% in Hispanic and 50% in non-Hispanic, p = 0.081). Non-Hispanic patients had significantly higher rates of opportunistic infection (Pneumocystis pneumonia) than Hispanic patients (0.7% in Hispanic and 4% in non-Hispanic, p = 0.041). A similar difference in the incidence of bacteremia between the two groups approached, but did not reach statistical significance (p = 0.052). The overall incidence of fracture in all patients was 14.5% and was significantly higher in non-Hispanic patients (6% in Hispanic and 16.7% in non-Hispanic, p < 0.001). The overall incidence of ON was 8.9% and was significantly higher in non-Hispanic patients (3.3% in Hispanic and 10.3% in non-Hispanic, p = 0.007). (Table 1) Conclusion: The incidence of opportunistic infections and bony morbidities was significantly higher in non-Hispanic patients undergoing treatment for pediatric ALL on the DFCI ALL Consortium Protocol 05-001. The risk for, and impact of therapy-related toxicities varies by a patientÕs treatment tolerance, perhaps as a function of age and gender or as a result of disease biology or genetic polymorphisms affecting drug metabolism. Additionally, non-biologic factors such as medication adherence and nutritional status may also contribute to toxicity incidence in patients undergoing treatment for pediatric ALL. Prospective studies to further investigate our findings are warranted. Table. All Patients, (N = 730) Non-Hispanic, (N = 580) Hispanic, (N = 150) p -value Overall Infection 353/730 (48.4%) 290/580 (50%) 63/150 (42%) 0.081 Bacteremia 289/730 (39.6%) 240/580 (41.4%) 49/150 (9.3%) 0.052 Opportunistic Infection 24/730 (3.3%) 23/580 (4%) 1/150 (0.7%) 0.041 Fracture 106/730 (14.5%) 97/580 (16.7%) 9/150 (6%) <0.001 Osteonecrosis 65/730 (8.9%) 60/580 (10.3%) 5/150 (3.3%) 0.007 Thrombosis* 36/730 (4.9%) 26/580 (4.5%) 10/150 (6.7%) 0.271 Pancreatitis* 78/730 (10.7%) 60/580 (10.3%) 18/150 (12%) 0.559 ASP Allergy* 76/730 (10.4%) 57/580 (9.8%) 19/150 (12.7%) 0.310 *ASP-related toxicity Disclosures No relevant conflicts of interest to declare.
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Barata, Pedro C., Umang Swami, Adam Kessel, Ellen Jaeger, Sergiusz Wesolowski, Jonathan Chipman, Mehmet Asim Bilen, et al. "Landscape of circulating tumor DNA (ctDNA) abnormalities in advanced prostate cancer (aPCa): Distinctions in African American (AA) versus Caucasian (Ca) patients." Journal of Clinical Oncology 39, no. 6_suppl (February 20, 2021): 156. http://dx.doi.org/10.1200/jco.2021.39.6_suppl.156.
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156 Background: AA have substantially higher prostate cancer incidence rates, are diagnosed at a younger age and with a more advanced stage as compared to Ca. However, after adjusting for known prognostic factors, AA have an increased overall survival. We hypothesized that these differences might be due to the underlying changes in the genomic landscape which can be revealed by liquid biopsy. Methods: Real world comprehensive genomic profiling of ctDNA from aPCa patients from two institutions. The first ctDNA results as reported by Guardant 360 panel (Redwood City, CA) were included. Association between genetic mutation and gene were tested using Barnard’s test. To account for multiple testing, we used Benjamini-Hochberg’s False Discovery Rate adjustment across all tests to determine thresholds for false discovery rates. Same analysis was performed using a Bayesian Network Machine learning approach. Results: Overall, 361 patients with aPCa (81 AA and 280 Ca) were included in the analysis. Pathogenic genomic alterations were found in 87.0% of the cases, more frequently TP53 (42.4%), AR (34.1%), PIK3CA (13.9%), BRAF (12.7%), NF1 (10.8%) and MYC (10.0%). Targetable alterations of interest included DNA repair genes [BRCA 2 (7.8%), BRCA 1 (4.4%), ATM (6.4%), CDK12 (2.2%)], PIK3CA/mTOR/AKT (19.1%), PTEN (3.3%) and NTRK (1.9%). MSI-high was found in 4 patients. AA as compared to Ca had a significantly higher prevalence of CDK12 (20.7% vs. 3.8%, p=0.016) and GNA11 mutations (3.7% vs. 0.4%, p=0.0225). BayesNet analysis also supported these results (table). Conclusions: In this dataset, liquid biopsy of ctDNA was useful for genetic characterization of aPCa and reveal differences in the molecular phenotype of AA and Ca in aPCa with potential clinical implications. These findings support ongoing research on the clinical utility of non-invasive genotyping and therapeutic response monitoring with a focus on AA population. [Table: see text]
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Ahmed, Sayed A., and Emadeldin M. Kamel. "Cytotoxic Activities of Flavonoids fromCentaurea scoparia." Scientific World Journal 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/274207.
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Phytochemical studies on the ethanolic extract of the aerial parts ofCentaurea scoparialed to the isolation of two new flavonoids, 3′,4′-dihydroxy-(3′′,4′′-dihydro-3′′-hydroxy-4′′-acetoxy)-2′′,2′′-dimethylpyrano-(5′′,6′′:7,8)-flavone-3-O-β-D-glucopyranoside (1) and 3,3′,4′-trihydroxy-(3′′,4′′-dihydro-3′′,4′′-dihydroxy)-2′′,2′′-dimethylpyrano-(5′′,6′′:7,8)-flavone (2), along with eight known flavonoids isolated for the first time from this plant, cynaroside (3), Apigetrin (4), centaureidin (5), oroxylin A (6), 5,7-dihydroxy-3′,4′,5′-trimethoxyflavone (7), atalantoflavone (8), 5-hydroxy-3′,4′,8-trimethoxy-2′′,2′′-dimethylpyrano (5′′,6′′:6,7)-flavone (9), and 3′,4′,5,8-tetramethoxy-2′′,2′′-dimethylpyrano (5′′,6′′:6,7)-flavone (10). The structures of the isolated compounds were elucidated by means of spectroscopic tools including 1D and 2D NMR, UV, IR, and mass spectroscopy. Cytotoxic activities of the isolated compounds were evaluated against human cervical carcinoma HeLa, human hepatocellular carcinoma HepG2, and human breast carcinoma MCF-7. Compound2was the most potent cytotoxic agent against HeLa cells with an IC500.079 μM.
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Yonce, Carroll E. "Nectarine, Carzol for Thrips Control, 1987." Insecticide and Acaricide Tests 13, no. 1 (January 1, 1988): 57. http://dx.doi.org/10.1093/iat/13.1.57.
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Abstract The test was conducted in a small block of nectarines (selection 7-738) at Byron, Ga. Control was directed at critical times of flower and fruit development to determine which treatment times were best for effective control. Carzol 90SP at 0.5 lb (AI)/acre was applied at 4 different timing regimens based on previous population distribution patterns in the same orchard location. A randomized complete experimental block design was used. Emphasis was directed at early season and population build-up of flower thrips populations. Thrips sampling began at pink bud and continued each 2 wk until harvest. Fruit samples were taken just following shuck split, and sampling continued each 2 wk until harvest. A total of 360 fruit were examined for thrips damage from each treatment during the entire sampling period.
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Qin, Jian-Jun, Ying Li, Leng-Siang Lee, and Hsiaowan Lee. "Cellulose acetate hollow fiber ultrafiltration membranes made from CA/PVP 360 K/NMP/water." Journal of Membrane Science 218, no. 1-2 (July 1, 2003): 173–83. http://dx.doi.org/10.1016/s0376-7388(03)00170-4.
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Zatsepina, I. V. "THE EFFECT OF THE PLANT GROWTH REGULATOR KORNEVIN ON THE ROOTABILITY OF PEAR VARIETIES AND FORMS IN CONDITIONS OF ARTIFICIAL FOG." Izvestia Ufimskogo Nauchnogo Tsentra RAN, no. 1 (March 12, 2024): 96–101. http://dx.doi.org/10.31040/2222-8349-2024-0-1-96-101.
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Pear is a seed crop that grows and is consumed all over the world, grows on trees and is harvested in the Northern Hemisphere from late summer to October. Plant growth regulators are such chemicals that are capable of various green and lignified cuttings to increase the root system, they are also able to increase yields. Kornevin is an effective plant growth regulator (phytohormone). It is a biological product that stimulates root formation. The drug has a mild effect, is not phytotoxic, eliminates overdoses. It has a long-lasting prolonged effect. Green pear cuttings K-1, K-2, OHF 333, Piro II had the greatest rootability when using the plant growth regulator kornevin (30.0 mg/l) (from 85.0 to 87.7%). Without the use of plant growth regulators, the forms K-1, K-2, OHF 333, Piro II had high rooting rates of green pear cuttings (from 70.5 to 75.9%). The highest growth height when using the plant growth regulator kornevin (30.0 mg/l) was possessed by the rootstock forms of the Caucasian pear, 4-26, 4-39, K-1, K-2, OHF 333, Piro II, this indicator varied from 12.5 to 14.0 cm. The largest diameter of the conditional root neck (from 1.3 to 1.6 cm) had the forms of pears Caucasian, 4-26, 4-39, K-1, K-2, OHF 333, Piro II and varieties ‘Pervomayskaya’, ‘Yakovlevskaya’, ‘Avgustovskaya Rosa’, ‘Irista’, ‘Chudesnitsa’, ‘Fevral'skiy Suvenir’. The largest number of roots (from 7.5 to 8.5 pcs.) were demonstrated by the forms of the Caucasian pear, 4-26, 4-39, K-1, K-2, OHF 333, Piro II. The largest root length (from 9.0 to 9.8 cm) was possessed by the rootstocks of the Caucasian pear, 4-26, 4-39, K-1, K-2, OHF 333, Piro II and varieties ‘Nika’, ‘Avgustovskaya Rosa’, ‘Irista’, ‘Fevral'skiy Suvenir’. Without the use of plant growth regulators, the largest plant height (from 10.0 to 12.0 cm) was possessed by the forms of Caucasian pear, 4-26, 4-39, K-1, K-2, OHF 333, Piro II. The largest number of roots (from 5.0 to 6.6 pcs.) had pear shapes 4-39, K-2, OHF 333, Piro II and varieties ‘Svetlyanka (k)’, ‘Nika’, ‘Pervomayskaya’. The largest root length without the use of plant growth regulators was characterized by the forms of the Caucasian pear, 4-26, 4-39, K-1, K-2, OHF 333, Piro II and varieties ‘Nika’, ‘Fevral'skiy Suvenir’, this indicator varied from 7.0 to 7.8 cm.
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Ullah, Rehmat, Kapeel Raja, Sohail Hussain, Zille Huma, Farhana Mukhtar, and Khalil Ur Rehman. "Analyze the Efficacy of the AST to Platelet Ratio (APRI) and the Fibronectin Fibrinolysis-4 (FIB-4) using Transient Elastography (FIB-SCAN) in Patients with Chronic Hepatitis C." Pakistan Journal of Medical and Health Sciences 16, no. 8 (August 31, 2022): 400–402. http://dx.doi.org/10.53350/pjmhs22168400.
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Objective: The purpose of this study was to compare the effectiveness of AST to platelet index (APRI) and FIB-4 with transient elastography, also known as fibro scan, in patients who suffered from chronic Hepatitis C. Study Design: Retro-prospective/ Cross-sectional Place & Duration: Khalifa Gulnawaz Teaching Hospital Bannu Pakistan, From August, 2021 to May, 2022. Material and Methods: This research included 360 men and women. After obtaining written consent, detailed demographics of all cases were recorded. In 360 HCV infected individuals, the diagnosis comprised CBC, LFTs, ELISA, PCR, and fibro. We compared AST, apric, FIB-4, and fibro scans for detecting HCV fibrosis progression. SPSS 22.0 was used to analyze all data. Results: There were majority males 220 (61.1%) and 140 (38.9%) females. 85 (23.6%) had age 20-30 years 180 (50%) cases had age 31-40 years and 95 (26.4%) patients had age >40 years. We found that 210 (58.3%) patients had fibrosis stage F0-F1, F2 stage was in 28 (7.8%) cases, F3 stage was in 52 (14.4%) patients and F4 stage in 70 (19.4%) cases. Among 360cases, genotype 3a was found in 260 (72.2%) patients, genotype 1b in 70 (20.8%) cases and genotyped 1a in 30 (8.3%) cases. Conclusion: In this study, we found that the AST to Platelet Index (APRI) and FIB 4 were able to successfully identify among cirrhotic and non-cirrhotic phases among HCV-infected patients. Keywords: Liver, Hepatitis C, Fibrosis
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Kim, Y. E., S. M. Ahn, J. S. Oh, Y. G. Kim, C. K. Lee, B. Yoo, and S. Hong. "AB1253 FEBUXOSTAT DOSE ADJUSTMENT ACCORDING TO RENAL FUNCTION TO ATTAIN TARGET SERUM URATE LEVEL: A RETROSPECTIVE COHORT STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1852.3–1853. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2473.
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BackgroundCurrent guideline for gout recommends the use of allopurinol or febuxostat in moderate-to-severe chronic kidney disease (CKD). However, the appropriate febuxostat dosage required to attain the target serum urate (SU) level remains unclear, especially in patients with renal impairment.ObjectivesWe aim to investigate the different febuxostat dosages stratified by renal function to achieve the target SU level.MethodsWe collected the clinical and laboratory information of patients using the Clinical Research Data Warehouse system of Asan Medical Center, Seoul, South Korea. Of the 3153 patients with gout and a prescription for febuxostat at a tertiary-care referral center, 731 with initial SU levels >6 mg/dL were collected and categorized, according to their eGFR levels at febuxostat therapy initiation, into three groups based on CKD stage: 1, 2–3, and 4–5. We defined the cumulative febuxostat as the total dose of febuxostat used from the initiation of febuxostat to the moment patient reached the SU target (SU<6 mg/dL).ResultsThis cohort of 731 gout patients, with a median age of 52 (IQR, 41-63) years, included 64 (8.8%) women. Compared with the other groups, in the CKD 4–5 group, the mean SU value at febuxostat initiation was significantly higher (9.6 [SD, 3.1] mg/dL; CKD 2–3, 8.6 [SD, 1.6] mg/dL; CKD 1, 8.8 [SD, 1.8] mg/dL; p<0.001) and significantly fewer patients achieved the SU target during the follow-up period, median 31 (IQR, 13-55) months. In the subgroup analysis of patients who achieved target SU levels, the cumulative dose of febuxostat was significantly lower in CKD 4-5 patients compared to those with other groups (CKD 4–5, 5.9 (IQR, 2.5–12.0) g; CKD 2–3, 7.1 (IQR, 3.5–15.7) g; CKD 1, 7.0 (IQR, 2.7–20.1) g; p=0.010 for CKD 4–5 and CKD 1, p=0.006 for CKD 4–5 and CKD 2–3). The average febuxostat dose used during 4 months to reach the SU target was 50.0 (IQR, 21.0–101.0) mg in the CKD 4-5 group, which was significantly lower than in other groups (CKD 2–3, 59.3 (IQR, 29.4–130.7) mg; CKD 1, 58.5 (IQR, 22.7–167.8) mg; p=0.006 for CKD 4–5 and CKD 1, p=0.003 for CKD 4–5 and CKD 2–3). In addition, when we examined the clinical factors associated with the required dose of febuxostat to achieve SU target, CKD 4-5 group showed a significant negative correlation with cumulative febuxostat dosage to reach target SU compared with CKD 1 (rho -2.334, p=0.02).ConclusionThe febuxostat dose required to reach the target SU level was significantly lower in patients with markedly decreased renal function (CKD stage 4–5).References[1]Tan VS et al. The 3-Year Incidence of Gout in Elderly Patients with CKD. Clinical Journal of the American Society of Nephrology. 2017; 12(4):577-584.[2]Stamp LK et al. A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout. Annals of the Rheumatic Diseases. 2017; 76(9):1522-1528.[3]Ahn E et al. Comparison of Efficacy and Safety of Febuxostat in Gout Patients with Chronic Kidney Disease Stage 3 and Stage 4/5. Journal of Rheumatic Diseases. 2019; 26(2):118.Table 1.Febuxostat acquirement to reach target SUTotal(n=731)CKD 1(n=204)CKD 2-3(n=388)CKD 4-5(n=139)p-valueCKD1 vs 4-5CKD2-3 vs 4-5SU target achievement, n (%)626 (85.6)176 (86.3)336 (86.6)114 (82.0)0.250.0430.045Patients achieving SU targetMean SU at 4 months, mg/dL6.2 (5.1, 7.2)6.2 (5.1, 7.3)6.0 (5.1, 7.1)6.3 (5.1, 7.2)0.490.270.05Duration to achieve SU target, months4.0 (1.9, 9.6)3.3 (1.8, 11.7)4.1 (2.1, 9.2)3.2 (1.4, 7.4)0.220.0380.08Cumulative febuxostat dose, g7.0 (3.0, 15.7)7.0 (2.7, 20.1)7.1 (3.5, 15.7)5.9 (2.5, 12.0)0.120.0100.006Average dose of febuxostat, mg58.3 (25.7, 130.7)58.5 (22.7, 167.8)59.3 (29.4, 130.7)50.0 (21.0, 101.0)0.090.0060.003Percentage change in SU-41.4 (-51.3, -30.1)-39.4 (-49.2, -31.1)-40.2 (-50.0, -29.7)-47.2 (-58.3, -35.6)<0.001<0.001<0.001Delta SU, mg/dL-3.4 (-5.0, -2.4)-3.3 (-4.8, -2.3)-3.4 (-4.8, -2.3)-4.2 (-6.4, -3.0)<0.001<0.001<0.001ap-value was obtained using ANOVA statistical analysisAcknowledgements:NIL.Disclosure of InterestsNone Declared.
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Neoptolemos, John P., Daniel H. Palmer, Paula Ghaneh, Juan W. Valle, David Cunningham, Jonathan Wadsley, Tim Meyer, et al. "ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma: Five year follow-up." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 4516. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.4516.
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4516 Background: The ESPAC-4 trial demonstrated that adjuvant GEM/CAP for pancreatic cancer significantly improved survival compared to GEM monotherapy. The aim of this study is to evaluate the long-term outcomes in the ESPAC-4 trial. Methods: Patients with pancreatic ductal adenocarcinoma were randomized within 12 weeks of surgery (stratified for R0/R1 resection margin status and country) to have either six 4-week cycles of IV GEM alone or GEM with oral CAP. The primary endpoint was five-year survival; secondary endpoints were toxicity and relapse free survival. 722 patients (480 expected events), 361 in each arm, were needed to detect a 10% difference in 2-year survival rates with 90% power (log-rank test with 5% two-sided alpha). Results: Between Nov 10 2008 and Sep 11 2014, 732 patients were randomized with 730 included in the full analysis set (366 GEM, 364 GEM/CAP). Median age was 65 years, 57% were men. WHO performance status was 0, 1 or 2 in 42% 55% and 3% respectively. Postoperative median CA19-9 was 19 kU/L. Median maximum tumor size was 30 mm, 61% were R1 resections, 80% were node positive and 40% were poorly differentiated. The data freeze was on 24 February 2020; median follow up was 60 months with 531 overall deaths, 280 in GEM, and 251 in GEM/CAP. Median (95% CI) survival (months) for patients treated with GEM/CAP was 27.7 23.3 – 31.2) and 26.0 (22.7 – 28.4) for GEM. Five-year (95% CI) survival rates were 20 (16 – 25) % for GEM and 28 (23 – 33) % for GEM/CAP. Stratified log-rank analysis revealed an HR=0.84 [95% CI, 0.70 – 0.99]; χ2 (1) = 3.87, P=0.049. 70 out of 366 GEM patients in the safety set reported 101 grade 3/4 serious adverse events, while 65 out of 359 GEM/CAP patients reported 97 grade 3/4 serious adverse events ( P=0.724). Conclusions: Adjuvant GEM/CAP for pancreatic cancer had a statistically significant improvement in survival compared to GEM monotherapy. Clinical trial information: 96397434 .
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Dzubiel, Darinka, Heiko Ihmels, Mohamed M. A. Mahmoud, and Laura Thomas. "A comparative study of the interactions of cationic hetarenes with quadruplex-DNA forming oligonucleotide sequences of the insulin-linked polymorphic region (ILPR)." Beilstein Journal of Organic Chemistry 10 (December 11, 2014): 2963–74. http://dx.doi.org/10.3762/bjoc.10.314.
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The interactions of the ILPR sequence (ILPR = "insulin-linked polymorphic region") a2 [d(ACAG4TGTG4ACAG4TGTG4)] with [2.2.2]heptamethinecyanine derivatives 1a–e and with the already established quadruplex ligands coralyne (2), 3,3′-[2,6-pyridinediylbis(carbonylimino)]bis[1-methylquinolinium] (3), 4,4′,4′′,4′′′-(21H,23H-porphine-5,10,15,20-tetrayl)tetrakis[1-methylpyridinium] (4), naphtho[2,1-b:3,4-b′:6,5-b′′:7,8-b′′′]tetraquinolizinium (5) and thiazole orange (6) were studied. It is demonstrated with absorption, fluorescence and CD spectroscopy that all investigated ligands bind with relatively high affinity to the ILPR-quadruplex DNA a2 (0.2–5.5 × 106 M−1) and that in most cases the binding parameters of ligand-ILPR complexes are different from the ones observed with other native quadruplex-forming DNA sequences.
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Imanov, H. A., and G. M. Huseynov. "STUDY OF THE CONDITIONS FOR THE ACQUISITION OF Tl3AsS4 IN ETHYLENE GLYCOL." Chemical Problems 19, no. 3 (2021): 135–42. http://dx.doi.org/10.32737/2221-8688-2021-3-135-142.
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The article presents the results of obtaining thallium thioarsenate in ethylene glycol medium and physicochemical analysis methods (XRD, DTG, TG and SEM). It was found that when ethylene glycol is used as a solvent and TlNO3 and As2S5 as the initial component, thallium thioarsenate is obtained at 353 K temperature. Thallium thioarsenate is formed by the interaction of TlNO3 and As2S5 at a ratio of 4:15 mol. After the compound was obtained at a temperature of 353 K (pH = 7-8), thermally processed at a temperature of 523-543 K, the melting point of the thallium thioarsenate sample has been 683 K. According to the results of thermogravimetric analysis, at temperatures above 733 K thallium thioarsenate decomposes in nitrogen gas environment. The micromorphology of the Tl3AsS4 compound obtained in the ethylene glycol medium was studied and it was determined that nanoparticles of the Tl3AsS4 compound are formed at a temperature of 353 K.
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Kleinsorgen, Françoise, Luís Caetano, and Orlanda Torres. "Adesão em dentes hipomineralizados: uma revisão sistemática." RevSALUS - Revista Científica da Rede Académica das Ciências da Saúde da Lusofonia 5, Supii (January 15, 2024): 65. http://dx.doi.org/10.51126/revsalus.v5isupii.736.
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Introdução: Os defeitos do esmalte dentário são um achado prevalente na dentição decídua e permanente. Um dos principais desafios no tratamento da Hipomineralização Incisivo-Molar (MIH) é a adesão de materiais restauradores aos dentes afetados. É fundamental conhecer o quanto a MIH afeta esta adesão prevendo um selamento adequado que evite as microinfiltrações. Determinar a resistência de união dos sistemas adesivos aos substratos de dentes afetados com MIH, é de suma importância para a obtenção de um bom resultado clínico. Objetivos: O objetivo deste estudo é realizar uma revisão sistemática sobre a adesão em dentes afetados com MIH, de modo a identificar o melhor protocolo que otimize esta adesão. Materiais e Métodos: Foi realizada uma pesquisa na literatura nas bases de dados Pub MED, Biblioteca Cochrane e Science Direct dos últimos dez anos, sobre a adesão em dentes afetados com MIH, utilizando a combinação dos seguintes descritores: Hipomineralização Molar-Incisivo; Adesivo Dentário; Hipoclorito de sódio; Desproteinização; Restauração Resina Composta. A pesquisa realizada identificou 343 artigos, dos quais 23 foram considerados relevantes para este estudo. Resultados: A literatura descreve ao menos 4 protocolos que visam melhorara a adesão em dentes hipomineralizados. Destes 4 protocolos, 2 mostram-se eficientes em quase 50% dos casos. Sendo que o protocolo restaurador para MIH depende do grau de severidade do esmalte afetado. Conclusões: Conclui-se que a ligação ao esmalte hipomineralizado é um fator limitante à adesão. Uma desproteinização do esmalte com NaOCl a 5% ou com Papaína, antes do adesivo, pode melhorar o desempenho da adesão em esmalte hipomineralizado e a resistência da união.
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Neoptolemos, John P., Dan Palmer, Paula Ghaneh, Juan W. Valle, David Cunningham, Jonathan Wadsley, Tim Meyer, et al. "ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma." Journal of Clinical Oncology 34, no. 18_suppl (June 20, 2016): LBA4006. http://dx.doi.org/10.1200/jco.2016.34.18_suppl.lba4006.
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LBA4006 Background: The ESPAC-3 trial compared adjuvant GEM with 5-fluorouracil/folinic acid for resected pancreatic cancer. GEM is the standard of care based on similar survival and less toxicity. ESPAC-4 aimed to determine whether combination chemotherapy with GEM/CAP improved survival compared to GEM monotherapy. Methods: Patients with pancreatic ductal adenocarcinoma were randomized within 12 weeks of surgery (stratified for R0/R1 resection margin status and country) to have either six 4 week cycles of IV GEM alone or GEM with oral CAP. The primary endpoint was overall survival; secondary endpoints were toxicity, relapse free survival, 2 and 5 year survival and quality of life. 722 patients (480 expected events), 361 in each arm, were needed to detect a 10% difference in 2 year survival rates with 90% power (log-rank test with 5% two-sided alpha). Results: Between Nov 10 2008 and Sep 11 2014, 732 patients were randomized with 730 included in the full analysis set (366 GEM, 364 GEM/CAP). Median age was 65 years, 57% were men. WHO performance status was 0, 1 or 2 in 42% 55% and 3% respectively. Postoperative median CA19-9 was 19 kU/L. Median maximum tumor size was 30 mm, 60% were R1 resections, 80% were node positive and 40% were poorly differentiated. On Dec 11 2015 the Independent Trial Steering Committee requested that the trial proceed to full analysis. The data freeze was on March 2 2016. Median survival (months) for patients treated with GEM/CAP was 28.0 (95% CI, 23.5 – 31.5) and 25.5 (22.7 – 27.9) for GEM. Stratified log-rank analysis revealed an HR=0.82 [95% CI, 0.68 – 0.98]; χ2 (1) = 4.61, P=0.032. 196 out of 366 GEM patients in the safety set reported 481 grade 3/4 adverse events, while 226 out of 359 GEM/CAP patients reported 608 grade 3/4 adverse events ( P=0.242). Conclusions: Adjuvant GEM/CAP for pancreatic cancer had a statistically significant improvement in survival compared to GEM monotherapy. Clinical trial information: ISRCTN96397434.
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Makeev, M. I., M. A. Saidova, and T. E. Imaev. "Influence of mitral transcatheter edge-to-edge repair in patients with severe mitral regurgitation on left ventricle function." Russian Journal of Cardiology 29, no. 4 (March 11, 2024): 5634. http://dx.doi.org/10.15829/1560-4071-2024-5634.
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Aim. To study the changes of left ventricular (LV) contractile function in patients with severe mitral valve (MV) insufficiency with assessment of global longitudinal strain (GLS) indicators and LV myocardial function after the mitral transcatheter edge-to-edge repair (TEER) within 12-month follow-up.Material and methods. The study consisted of 43 patients with severe mitral regurgitation (MR) as follows: 23 patients with functional MR (FMR), 20 patients with degenerative MR (DMR). A comprehensive echocardiographic study, including speckle tracking echocardiography, was performed at baseline, 4-5 days, 6 and 12 months after TEER. Standard structural and functional indicators of the LV, LV GLS and myocardial performance parameters were assessed.Results. The early postoperative period (4-5 days) was characterized by a decrease in global constructive work (GCW) (FMR group — from 977 [684; 1253] to 857 [736; 1488] mm Hg%, (p=0,038); DMR group — from 1458 [1283; 1848] to 1350 [1010; 1488] mm Hg% (p=0,011)), an increase in global wasted work (GWW) (FMR group — from 177 [130; 280] to 336 [242; 388] mm Hg% (p=0,004); DMR group — from 128 [81; 172] to 216 [164; 279] mm Hg% (p=0,043)), which was accompanied by a decrease in myocardial efficiency (FMR group — from 81,5 [77; 87] to 76 [73; 79]%, (p=0,021); DMR group — from 90 [85; 93] to 82 [79; 85]% (p=0,018)). After 12-month follow-up, there was a significant increase in GCW relative to the initial values in both cohorts of patients as follows: FMR group — to 1128 [890; 1711] mm Hg% (p=0,048); DMR group — to 1818 [1478; 2034] mm Hg% (p<0,001). There was also an increase in GWW in the FMR group to 255 [214; 363] mm Hg% (p=0,024) and in the DMR group to 230 [140; 270] mm Hg% (p=0,043). There were no significant improvement of LV GLS in both groups.Conclusion. The early postoperative period after TEER was characterized by a temporary deterioration in all LV performance parameters, which recovered by 6 and 12 months of follow-up. Myocardial function restoration by one year of follow-up was noted due to an increase in GCW. LV GLS and ejection fraction did not change significantly by 1 year of follow-up compared to baseline values.
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Duncan, Andrew W. "Book reviewsDiagnostic Imaging in Paediatrics. Ed. by GordonIsky, pp. xviii + 313, 1987 (Chapman and Hall Medical, London), £57.50. ISBN 0–412–22730–4." British Journal of Radiology 62, no. 736 (April 1989): 396. http://dx.doi.org/10.1259/0007-1285-62-736-396-a.
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Bartalucci, Giuditta, Stuart Fisher, John R. Helliwell, Madeleine Helliwell, Synnøve Liaaen-Jensen, John E. Warren, and James Wilkinson. "X-ray crystal structures of diacetates of 6-s-cis and 6-s-trans astaxanthin and of 7,8-didehydroastaxanthin and 7,8,7′,8′-tetradehydroastaxanthin: comparison with free and protein-bound astaxanthins." Acta Crystallographica Section B Structural Science 65, no. 2 (March 16, 2009): 238–47. http://dx.doi.org/10.1107/s0108768109004649.
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The crystal structures of the 6-s-cis [s-cis-(1)] and 6-s-trans [s-trans-(1)] conformers of the diacetates of astaxanthin (AXT) and those of (3S,3′S)-7,8-didehydroastaxanthin [(3S,3′S)-3,3′-dihydroxy-7,8-didehydro-β,β-carotene-4,4′-dione (2)] and (3S,3′S)-7,8,7′,8′-tetradehydroastaxanthin [(3S,3′S)-3,3′-dihydroxy-7,8,7′,8′-tetradehydro-β,β-carotene-4, 4′-dione (3)] are reported. The conformations of these four molecules vary in particular with the angle of twist of the end rings out of the plane of the polyene chain; for s-cis-(1), the end rings are twisted out of the plane of the polyene chain by an angle of −49.0 (5)°, and the conformation is therefore similar to that found for unesterified AXT as well as for the carotenoids, canthaxanthin and β,β-carotene. For s-trans-(1), the end rings are coplanar with the polyene chain and its conformation is much more similar to that of the protein-bound AXT in the blue protein, crustacyanin, which is found in the shell of lobsters, although s-trans-(1) shows much less bowing of the polyene chain. In (2) and (3) the end rings are also almost coplanar with the polyene chain with the end rings in (2) in the s-cis conformation, and in (3) in the s-trans conformation. Thus, an extensive ensemble of the possible β end-ring conformations has been determined. These structures are compared with one another as well as unbound, unesterified AXT and protein-bound AXT. Also, the effect of the end-ring conformations on the colour and UV–vis spectra of the crystals was established.
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Stogniy, Marina Yu, Sergey A. Anufriev, Akim V. Shmal'ko, Sergey M. Antropov, Aleksei A. Anisimov, Kyrill Yu Suponitsky, Oleg A. Filippov, and Igor B. Sivaev. "The unexpected reactivity of 9-iodo-nido-carborane: from nucleophilic substitution reactions to the synthesis of tricobalt tris(dicarbollide) Na[4,4′,4′′-(MeOCH2CH2O)3-3,3′,3′′-Co3(μ3-O)(μ3-S)(1,2-C2B9H10)3]." Dalton Transactions 50, no. 7 (2021): 2671–88. http://dx.doi.org/10.1039/d0dt03857a.
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Foster, Eugene P., and Lawrence R. Curtis. "2,2',4,4',5,5'- and 3,3',4,4',5,5'-Hexachlorobiphenyl pretreatments alter the biliary excretion of a challenge dose of 7,12-[3H]dimethylbenz[a]anthracene in rainbow trout (Oncorhynchus mykiss)." Canadian Journal of Fisheries and Aquatic Sciences 56, no. 4 (April 1, 1999): 642–49. http://dx.doi.org/10.1139/f99-065.
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This study compared disposition of a polycyclic aromatic hydrocarbon (PAH) in rainbow trout after di-ortho and non-ortho polychlorinated biphenyl (PCH) pretreatments. Four weeks after intraperitoneal (i.p.) injection with 50 or 250 µg of the di-ortho 2,2',4,4',5,5'-hexachlorobiphenyl (2HxCB)·g-1 or 5 or 25 µg of the non-ortho 3,3',4,4',5,5'-hexachlorobiphenyl (3HxCB)·g-1, rainbow trout were i.p. injected with 10 nmol [3H]7,12-dimethylbenz[a]anthracene (DMBA)·g-1. Livers and gallbladders were removed 16 h later. Biliary excretion of [3H]DMBA decreased after i.p. injection of 2HxCB or 3HxCB. In a second experiment, rainbow trout were fed 60 or 220 ng 2HxCB·g fish-1·day-1 or 1.9 or 7.8 ng 3HxCB·g fish-1·day-1 for 4, 8, or 12 weeks. Fish were then i.p. injected with 10 nmol [3H]DMBA·g fish-1. Liver, bile, mesenteric fat, stomach, muscle, kidney, and plasma were sampled 16 h later. Fish fed 220 ng 2HxCB·g fish-1·day-1 for 4 weeks and 60 or 220 ng 2HxCB·g fish-1·day-1 for 8 weeks had greater biliary concentrations of [3H]DMBA than controls. Biliary [3H]DMBA increased for fish fed 7.8 ng 3HxCB·g fish-1·day-1 for 4 weeks. Thus, feeding both di-ortho and non-ortho PCBs transiently stimulated [3H]DMBA biliary excretion. Growth and survival data indicated no overt toxicity of the PCB doses used here via either exposure route. High i.p. doses that inhibited biliary excretion of [3H]DMBA were probably less environmentally relevant than the dietary doses fed here.
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Irons, D. W., P. H. Baylis, and J. M. Davison. "Effect of atrial natriuretic peptide on renal hemodynamics and sodium excretion during human pregnancy." American Journal of Physiology-Renal Physiology 271, no. 1 (July 1, 1996): F239—F242. http://dx.doi.org/10.1152/ajprenal.1996.271.1.f239.
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The effect of infused atrial natriuretic peptide (ANP) on sodium excretion (UNa), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF) was studied in 12 normotensive primigravidae at 32 wk gestation [late pregnancy (LP)] and again 4 mo postpartum [nonpregnant (NP)]. Three 20-min steady-state (renal) clearances of inulin and p-aminohippurate were used to measure GFR and ERPF, respectively, before and after infusion of ANP at 2 pmol.kg-1.min-1. Basal plasma ANP (pANP) was increased in LP compared with NP [7.8 +/- 0.6 vs. 3.3 +/- 0.4 pmol/l (P < 0.0001), respectively]. In LP, infusion of ANP increased pANP from 7.8 +/- 0.6 to 21.8 +/- 1.4 pmol/l (P < 0.00001), which produced a natriuresis [UNa of 0.18 +/- 0.02 vs. 0.25 +/- 0.03 mmol/min (P = 0.03), respectively], with no change in GFR (153 +/- 13 vs. 142 +/- 8 ml/min, P = 0.16) but a significant reduction in ERPF (766 +/- 52 vs. 660 +/- 31 ml/min, P = 0.002). In NP, ANP infusion increased pANP from 3.3 +/- 0.4 to 27.7 +/- 2.5 pmol/l (P < 0.00001), which produced no significant natriuresis [UNa of 0.22 +/- 0.07 vs. 0.26 +/- 0.09 mmol/min (P = 0.15), respectively] and no change in GFR (87 +/- 3 vs. 89 +/- 3 ml/min), but again a reduction in ERPF (486 +/- 17 vs. 414 +/- 9 ml/min, P < 0.001).
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Jiang, Xin Long, and Yi Hua Jiang. "Evaluation of the Adsorption of Cr(VI) by Modified Bamboo Shells." Applied Mechanics and Materials 361-363 (August 2013): 709–15. http://dx.doi.org/10.4028/www.scientific.net/amm.361-363.709.
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The adsorption of Cr(VI) by modified Bamboo shell has been investigated using chemical methods and IR spectrometry. The optimal condition for the adsorption of Cr(VI) by modified Bamboo shell is at 298 K and pH = 1.0, which gives a static saturated adsorption capacity of 12.68 mg·g-1, an apparent adsorption rate constant of k298 = 9.56 × 10-4 s-1, and an apparent adsorption activation energy of 7.38 kJ·mol-1. The adsorption follows the Langmuir and Freundlich isotherms and the liquid film diffusion is the controlling process of the adsorption. The adsorption thermodynamic parameters are ΔH = 66.04 kJ·mol-1, ΔS = 0.2974 kJ·mol-1·K-1, ΔG = −22.58~−28.52 kJ·mol-1. The anions HPO42-, H2PO4- and SO42- have negligible influence on the adsorption capacity. Small amount of desorption is observed only at pH > 11. The adsorption of Cr(VI) by modified bamboo shell is mainly a chemical process.
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Poonai, Naveen, Karina Burke, Shaily Brahmbhatt, Leslie Boisvert, Sheena Belisle, Brianna McKelvie, Kyna Patterson, Alison Stevenson, Donna Eull, and Stefan Friedrichsdorf. "35 Implementation of a quality improvement initiative to reduce pain and anxiety associated with needle-related procedures in a Canadian paediatric emergency department." Paediatrics & Child Health 26, Supplement_1 (October 1, 2021): e26-e27. http://dx.doi.org/10.1093/pch/pxab061.028.
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Abstract Primary Subject area Emergency Medicine - Paediatric Background Needle-related procedures such as intravenous (IV) insertion, venipuncture, and lumbar puncture (LP) are commonly performed in children, particularly in the emergency department (ED). Children consistently rate these needle-related procedures as very distressing. While topical anesthetics have been shown to be highly effective and are available, they are inconsistently used. The Children’s Comfort Promise was originally developed at the Minnesota Children’s Hospital. It requires nursing staff to use four strategies for children undergoing needle-related procedures: (1) topical anesthetic, (2) sucrose or breastfeeding if ≤ 12 months, (3) Comfort positioning (swaddling, skin-to-skin, or facilitated tucking if ≤ 12 months and sitting upright for children > 12 months), and (4) age-appropriate distraction. Objectives We sought to evaluate compliance with all 4 Comfort Promise strategies for managing children’s pain and anxiety during needle-related procedures in a Canadian paediatric ED. Design/Methods Implementation of The Comfort Promise in March 2020 included a focus group to perform a root cause analysis, designation of nurse champions, monthly steering committee and ED working group meetings, and didactic education sessions. Our institution’s decision support unit identified all encounters of children 0-17 years who underwent at least one needle-related procedure at our paediatric ED from January 1 to November 30, 2020. The outcome was compliance with all 4 Comfort Promise strategies. Balancing measures included adverse drug reactions and vasoconstriction. We used statistical process control to analyze the outcome from 2 months preceding and 7 months following implementation. Results From January 1 to November 30, 2020, 21,600 encounters were identified, of which 10,294/21,600 (47.7%) were female. Age ranged from 0-17 years with a mean (SD) of 6.9 (5.5) years. Needle-related procedures were performed in 730/21,600 (3.4%) encounters, most commonly IV insertion (289/730, 39.6%) and venipuncture for blood sampling (232/730, 31.8%). Half of all encounters had no compliance strategies electronically recorded (363/730, 49.7%). Compliance with all Comfort Promise strategies increased over the study period (Figure 1). Topical anesthetic increased from 3/35 (8.6%) to 35/83 (42.2%). Sucrose or breastfeeding increased from 0/6 (0%) to 2/16 (12.5%). Comfort positioning increased from 0/35 (0%) to 26/83 (31.3%). Distraction increased from 0/35 (0%) to 22/83 (26.5%). There were no adverse drug reactions or vasoconstriction. Conclusion Implementation of The Comfort Promise in a Canadian paediatric ED resulted in greater use of strategies, particularly topical anesthetic, to reduce needle-related distress in children. Ongoing compliance will depend on consistent electronic recording and provider education.
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Afifah, Dini Nur, Pujiati Utami, Suwarti Suwarti, Endar Puspawiningtiyas, Itsna Nurrahma Mildaeni, Yeti Rusmiati Hasanah, and Adam Mufarij. "Pelatihan pemanfaatan sampah dapur sebagai bahan pembuatan pupuk organik cair (POC) bagi anggota relawan lembaga lingkungan hidup dan penanggulangan bencana Kabupaten Banyumas." Transformasi: Jurnal Pengabdian Masyarakat 17, no. 2 (December 31, 2021): 185–96. http://dx.doi.org/10.20414/transformasi.v17i2.3924.
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[Bahasa]: Pengelolaan sampah dapur merupakan salah satu upaya untuk mengurangi volume sampah yang masuk ke Tempat Pembuangan Sampah Akhir (TPA). Namun, hal tersebut masih jarang dilakukan oleh masyarakat. Rendahnya minat masyarakat dalam mengolah sampah disebabkan oleh: keterbatasan lahan, kerumitan proses, pengetahuan yang terbatas, dan kesibukan. Merujuk pada masalah tersebut, maka dalam pengabdian masyarakat ini ditawarkan pemanfaatan sampah rumah tangga sebagai bahan pupuk organik cair (POC). Inovasi yang dihadirkan adalah pemanfaatan kotoran sapi dan urin kambing untuk meningkatkan nutrisi POC. Sasaran kegiatan ini adalah anggota relawan Lembaga Lingkungan Hidup dan Penanggulangan Bencana (LLHPB) Banyumas. Tujuan kegiatan ini adalah mengedukasi mitra sasaran agar dapat menerapkan sistem pengolahan sampah secara benar dan ramah lingkungan melalui konversi sampah dapur menjadi POC dengan decomposer EM-4. Pengetahuan dan teknologi ditransfer melalui simulasi ipteks dengan sosialisasi daring, video tutorial, dan poster yang berkaitan dengan tema yang dipilih. Hasil evaluasi menunjukkan bahwa kegiatan IbM ini mampu meningkatkan kesadaran anggota mitra untuk mengolah sampah sebesar 91,7%. Pupuk Organik Cair yang dibuat dengan teknik yang diusulkan memiliki kadar nitrogen, fosfor, dan kalium masing-masing sebesar 3,3%; 6,2% dan 7,8%. Nilai tersebut telah sesuai dengan syarat mutu kadar N,P,K yang diatur dalam Peraturan Menteri Pertanian Nomor 70/Permentan/SR.140/10/2011.
Kata Kunci: sampah organik, pengomposan, pupuk organik cair
[English]: Kitchen waste management is one of the efforts to reduce the volume of waste that enters final disposal sites. Unfortunately, this is still rarely done by people. A low interest of the people in processing waste is caused by: limited land, the complexity of the process, limited knowledge, and business. Referring to this problem, in this community service program,, the use of household waste as liquid organic fertilizer (LOF) is offered. The innovation presented in this program is the uses of cow dung and goat urine to increase POC nutrition. The partner of this program was a volunteer member of the Banyumas Institute for the Environment and Disaster Management. The objective is to educate partners to implement a proper and environmentally friendly waste management system through the conversion of kitchen waste into POC with the EM-4 decomposer. Methods used in this program were science and technology simulation, through: online outreach, video tutorials, and posters related to the chosen theme, and the transfer of knowledge and technology. The evaluation results show that this program is able to increase the awareness of partner members to process waste by 91.7%. Liquid Organic Fertilizer made by the proposed technique comprises nitrogen 3.3%, phosphorus 6.2%, and potassium 7.8%. This value is in accordance with the quality requirements for the levels of N, P, K regulated in the Regulation of the Minister of Agriculture Number 70/Permentan/ SR.140/10/2011
Keywords: organic waste, composting, liquid-organic fertilizer
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Zhang, Renshi, and Wayne L. Mattice. "Atomistic modeling of the diffusion of small penetrant molecules in the bulk amorphous polyimide of 3,3′,4,4′-benzophenonetetracarboxylic dianhydride and 2,2-dimethyl-1,3-(4-aminophenoxy) propane." Journal of Membrane Science 108, no. 1-2 (December 1995): 15–23. http://dx.doi.org/10.1016/0376-7388(95)00146-3.
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Floudas, Charalampos S., Changqing Xie, Gagandeep Brar, Maria Pia Morelli, Suzanne Fioravanti, Melissa Walker, Donna Mabry-Hrones, et al. "Combined immune checkpoint inhibition (ICI) with tremelimumab and durvalumab in patients with advanced hepatocellular carcinoma (HCC) or biliary tract carcinomas (BTC)." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 336. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.336.
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336 Background: Prognosis in advanced HCC and BTC is unfavorable, and 5-year overall survival (OS) rate is less than 20% and 10%, respectively. Single agent ICI in HCC has response rates (RR) of 20%, while early data in BTC reported 17.4% RR. Dual ICI has increased RR in other malignancies. The purpose of this study was to explore the efficacy of the combination of anti-CTLA4 (tremelimumab) with anti-PD-L1 (durvalumab) in advanced HCC and BTC. Methods: Eligible patients with advanced HCC or BTC who had received (or refused) at least one prior therapy, received monthly tremelimumab 75 mg in combination with durvalumab 1500 mg for 4 doses followed by monthly durvalumab 1500 mg monotherapy until progression of disease or unacceptable toxicity. Response was assessed with CT scan every 8 weeks. Adverse events (AEs) were recorded and managed. The primary endpoint is 6-month progression free survival (PFS). Results: Twenty-two patients were enrolled, 10 with advanced HCC and 12 with advanced BTC. Male to female ratio was 14:8, with median age of 62.5 years (range 19-80). Grade 3/4 treatment-related AEs included lymphocytopenia, hyponatremia, bullous dermatitis, maculopapular rash, mucositis, hypophosphatemia, anaphylaxis, dyspnea, pleural effusion, and pain. Twenty patients were evaluable for response analysis. Two patients (2/10, 20%) achieved a confirmed partial response (both with HCC, lasting 6.9 and 17.6 months), while 9 patients (4 [40%] with HCC and 5 [41.7%] with BTC) had stable disease, with the longest duration of 9.3 months (in an HCC patient). Disease control rate is 60% in HCC and 41.7% in BTC, respectively. In this small pilot cohort, median PFS was 3.1 months (95% CI 0.8 to 4.6 months) and median OS was 5.45 months (95% CI 4.60 to 8.3 months) among BTC patients, while HCC patients median PFS was 7.8 months (95% CI 2.6 to 10.6 months) and median OS was 15.9 (95% CI 7.1 to 16.3 months). Conclusions: Combined ICI with tremelimumab and durvalumab is well tolerated and demonstrates promising activity in patients with advanced HCC and BTC. Clinical trial information: NCT02821754.
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Wang, Wen-Zhen, Kai-Yue Zhang, Xin-Gang Jia, Li Wang, Lei-Lei Li, Wei Fan, and Li Xia. "A New Dinuclear Cobalt Complex for Copolymerization of CO2 and Propylene Oxide: High Activity and Selectivity." Molecules 25, no. 18 (September 8, 2020): 4095. http://dx.doi.org/10.3390/molecules25184095.
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Based on the ligand H4Salen-8tBu (salen-4), a new dinuclear cobalt complex (salen-4)[Co(III)TFA]2 (salen-4 = 3,5-di-tert-butylsalicylaldehyde-3,3′-diaminobiphenylamine; TFA = trifluoroacetic acid) has been firstly synthesized and characterized. It shows high catalytic activity for the copolymerization of propylene oxide (PO) and carbon dioxide (CO2), yielding regioregular poly(propylene carbonate) (PPC) with little generation of propylene carbonate (PC) by-product. It has been found that (salen-4)[Co(III)TFA]2 shows higher activity at milder conditions, generating a polymer with maximum Mn of 293 kg/mol and a narrow molecular weight distribution PDI of 1.35. The influences of reaction time, CO2 pressure, reaction temperature, nature of the cocatalyst, catalyst dosage and substrate concentration on the molecular weight, yield and selectivity of the polymer were explored in detail. The results showed that the (salen-4)[Co(III)TFA]2/[PPN]TFA catalyst system demonstrated a remarkable TOF as high as 735 h–1. In addition, a hypothetical catalytic reaction mechanism was proposed based on density functional theory (DFT) calculations and the catalytic reaction results of the (salen-4)[Co(III)TFA]2.
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de Launoit, Y., and J. Adamski. "Unique multifunctional HSD17B4 gene product: 17beta-hydroxysteroid dehydrogenase 4 and D-3-hydroxyacyl-coenzyme A dehydrogenase/hydratase involved in Zellweger syndrome." Journal of Molecular Endocrinology 22, no. 3 (June 1, 1999): 227–40. http://dx.doi.org/10.1677/jme.0.0220227.
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Six types of human 17beta-hydroxysteroid dehydrogenases catalyzing the conversion of estrogens and androgens at position C17 have been identified so far. The peroxisomal 17beta-hydroxysteroid dehydrogenase type 4 (17beta-HSD 4, gene name HSD17B4) catalyzes the oxidation of estradiol with high preference over the reduction of estrone. The highest levels of 17beta-HSD 4 mRNA transcription and specific activity are found in liver and kidney followed by ovary and testes. A 3 kb mRNA codes for an 80 kDa (737 amino acids) protein featuring domains which are not present in the other 17beta-HSDs. The N-terminal domain of 17beta-HSD 4 reveals only 25% amino acid similarity with the other types of 17beta-HSDs. The 80 kDa protein is N-terminally cleaved to a 32 kDa enzymatically active fragment. Both the 80 kDa and the N-terminal 32 kDa (amino acids 1-323) protein are able to perform the dehydrogenase reaction not only with steroids at the C17 position but also with D-3-hydroxyacyl-coenzyme A (CoA). The enzyme is not active with L-stereoisomers. The central part of the 80 kDa protein (amino acids 324-596) catalyzes the 2-enoyl-acyl-CoA hydratase reaction with high efficiency. The C-terminal part of the 80 kDa protein (amino acids 597-737) facilitates the transfer of 7-dehydrocholesterol and phosphatidylcholine between membranes in vitro. The HSD17B4 gene is stimulated by progesterone, and ligands of PPARalpha (peroxisomal proliferator activated receptor alpha) such as clofibrate, and is down-regulated by phorbol esters. Mutations in the HSD17B4 lead to a fatal form of Zellweger syndrome.
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Johansson, Magnus, Andrew J. Brooks, David A. Jans, and Subhash G. Vasudevan. "A small region of the dengue virus-encoded RNA-dependent RNA polymerase, NS5, confers interaction with both the nuclear transport receptor importin-β and the viral helicase, NS3." Journal of General Virology 82, no. 4 (April 1, 2001): 735–45. http://dx.doi.org/10.1099/0022-1317-82-4-735.
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The dengue virus RNA-dependent RNA polymerase, NS5, and the protease/helicase, NS3, are multidomain proteins that have been shown to interact both in vivo and in vitro. A hyperphosphorylated form of NS5 that does not interact with NS3 has been detected in the nuclei of virus-infected cells, presumably as the result of the action of a functional nuclear localization sequence within the interdomain region of NS5 (residues 369–405). In this study, it is shown by using the yeast two-hybrid system that the C-terminal region of NS3 (residues 303–618) interacts with the N-terminal region of NS5 (residues 320–368). Further, it is shown that this same region of NS5 is also recognized by the cellular nuclear import receptor importin-β. The interaction between NS5 and importin-β and competition by NS3 with the latter for the same binding site on NS5 were confirmed by pull-down assays. The direct interaction of importin-β with NS5 has implications for the mechanism by which this normally cytoplasmic protein may be targetted to the nucleus.
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Nukui, Hiroshi, Michio Murakami, Sanae Midorikawa, Minako Suenaga, Yuichi Rokkaku, Hirooki Yabe, and Akira Ohtsuru. "Mental Health and Related Factors of Hospital Nurses." Asia Pacific Journal of Public Health 29, no. 2_suppl (March 2017): 161S—170S. http://dx.doi.org/10.1177/1010539516682589.
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The mental health of hospital nurses is a key health issue in public health promotion during the recovery phase following the Fukushima disaster. In this study, conducted 4 years after the disaster, we analyzed the overall mental health, knowledge, risk perception of radiation, and work and daily life burdens of nurses working at medical institutions in the Fukushima Prefecture (collection rate = 89.6%; response number = 730). Overall mental health status was estimated using the 12-item version of the General Health Questionnaire, and 333 respondents (45.6%) scored above the 12-item General Health Questionnaire threshold point (≥4), indicating probable emotional distress compared with the general population under normal circumstances. Multivariate logistic analysis suggested that the ability to cope with daily life and work-related stressors were more important than risk perception and acquisition of knowledge regarding radiation and its control methods for supporting the mental health of nurses following the Fukushima disaster.
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McKellar, A. R. W. "Interference effects in the spectrum of HD: IV: the pure rotational band at room temperature." Canadian Journal of Physics 64, no. 3 (March 1, 1986): 227–31. http://dx.doi.org/10.1139/p86-041.
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The rotational spectrum of HD has been studied in absorption at room temperature for a density range of 6–57 amagat. Spectra were obtained in the 170- to 360-cm−1 region, including the R0(1), R0(2), and R0(3) transitions, with a 1-m path length and a spectral resolution varying from 0.05 to 0.20 cm−1. The observed line strengths were used to determine values for the dipole transition moments of HD in the range of 7.4 to 7.8 × 10−4 D, which is somewhat lower than currently accepted theoretical values of about 8.3–8.4 × 10−4 D. Only very small effects (≈0.2% per amagat) were found due to collisional interference on the line strengths; this result contrasts with much larger interference effects observed in the fundamental band, and it also casts some doubt on other recent studies of the rotational spectrum where larger interference effects were reported.
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Savio, V., Y. Tissera, M. I. Quaglia, J. A. Albiero, C. G. Alonso, M. Demarchi, C. Maldini, et al. "AB0830 LIPID PROFILE IN PSORIATIC ARTHRITIS. FREQUENCY AND ASSOCIATION WITH DISEASE ACTIVITY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1719.1–1720. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2185.
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Background:Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with higher risk of cardiovascular events and metabolic syndrome. The inflammation not only accelerates atherosclerosis, but also may influence cardiovascular (CV) risk factors such as lipid profile, blood pressure and insulin resistance. Lipid profile has previously been studied in PsA, however this association is still controversial.Objectives:To study the frequency of altered lipid profile in patients with PsA and its association with disease activity.Methods:We studied all the patients with diagnosis of PsA who consecutively attended to Rheumatology Unit at Cordoba Hospital from July 2018 to December 2019. PsA was diagnosed according CASPAR criteria. Clinical and laboratory data were collected. The activity of the disease was evaluated by PASI, MDA and DAPSA. Quantitative variables will be expressed in median and 1st and 3rd interquartile; qualitative variables expressed in frequency and percentage. Correlation analysis was calculated using Spearman’s rank correlation coefficient. P<0.05 was considered statistically significant.Results:42 PsA patients were included. Mean age was 56 years old (47.25-62.75) and 54.76% were female (n=23). 92.86% (n=39) of the patients had plaque Psoriasis and 87.8% (n=36) had peripheral joint involvement.Frequency of comorbidities in PsA are shown in Graphic 1. 31 (73.8%) of the patients were treated with topical therapy, 3 (7.14%) with phototherapy, 31 (73.8%) with Methotrexate and 17 (41.46%) with biologics and JAK inhibitor. Activity Disease Index and Lipid profile are shown in Table 1 and 2.There was not association between Apo B/Apo A coefficient with DAPSA (rho=0.013; p=0.940) and MDA (rho=-0.029; p=0.867).Conclusion:In spite of the presence of cardiovascular factors in the majority of PsA patients, lipid profile is not correlated with disease activity in this population.References:[1]Ahlehoff O, Gislason GH, Charlot M, et al. Psoriasis is associated with clinically significant cardiovascular risk: A Danish nationwide cohort study. J Intern Med 2011;270:147-57.[2]Mallbris, L., Ritchlin, C.T., Ståhle, M. “Metabolic disorders in patients with psoriasis and psoriatic arthritis.” Curr RheumatolRep.8(5): 355–363. 2006[3]Ng CY, Tzeng I-S, Liu S-H, Chang Y-C, Huang Y-H. Metabolic parameters in psoriatic patients treated with interleukin-12/23 blockade (Ustekinumab). J Dermatol 2018; 45:309–313[4]Kaur S, Kingo K, Zilmer M. Psoriasis and cardiovascular risk – do promising new biomarkers have clinical impact? Mediators Inflamm 2017; 2017: 7279818[5]Gentile M, Peluso R, Di Minno MN, et al. Association between small dense LDL and sub-clinical atherosclerosis in patients with psoriatic arthritis. ClinRheumatol 2016; 35: 2023-9.Graphic 1.Comorbidities in PsATable. 1.Activity Disease Index in PsAACTIVITY INDEXn=42DAPSA14.45 (9.72-23.92)DAPSA≤4 REMISSION3>4 y ≤14 low disease activity16>14 y ≤28 moderate disease activity17>28 high disease activity3cDAPSA14.00 (8.00-23.00)/41*MDA9 (25)/36PASI2.20 (0.20-6.80)/41**Expressed in median and interquartiles.Qualitative variables expressed in frequency and percentage.Table. 2.Lipid Profile in PsA patients.Cholesterol (mg/dl)194.5 (164.8-218.2)HDL (mg/dl)48.00 (37.00-57.00)LDL (mg/dl)114.5 (78.5-140.8)TG (mg/dl)139.50 (89.25-191.20)Expressed in median and interquartiles.Disclosure of Interests:None declared
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Liu, X., Z. Sun, W. Guo, F. Wang, L. Song, J. Li, Q. Liu, and Q. Shu. "POS0647 EFFICACY, SAFETY AND CHARACTERISTICS OF IGURATIMOD-BASED THERAPY IN THE TREATMENT OF UA, ERA AND RA PATIENTS FOR 24 WEEKS: A PROSPECTIVE COHORT STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 561.2–562. http://dx.doi.org/10.1136/annrheumdis-2021-eular.91.
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Background:Experts emphasize early diagnosis and treatment in RA, but the widely used diagnostic criterias fail to meet the accurate judgment of early rheumatoid arthritis. In 2012, Professor Zhanguo Li took the lead in establishing ERA “Chinese standard”, and its sensitivity and accuracy have been recognized by peers. However, the optimal first-line treatment of patients (pts) with undifferentiated arthritis (UA), early rheumatoid arthritis (ERA), and rheumatoid arthritis (RA) are yet to be established.Objectives:To evaluate the efficacy and safety of Iguratimod-based (IGU-based) Strategy in the above three types of pts, and to explore the characteristics of the effects of IGU monotherapy and combined treatment.Methods:This prospective cohort study (ClinicalTrials.gov Identifier NCT01548001) was conducted in China. In this phase 4 study pts with RA (ACR 1987 criteria[1]), ERA (not match ACR 1987 criteria[1] but match ACR/EULAR 2010 criteria[2] or 2014 ERA criteria[3]), UA (not match classification criteria for ERA and RA but imaging suggests synovitis) were recruited. We applied different treatments according to the patient’s disease activity at baseline, including IGU monotherapy and combination therapies with methotrexate, hydroxychloroquine, and prednisone. Specifically, pts with LDA and fewer poor prognostic factors were entered the IGU monotherapy group (25 mg bid), and pts with high disease activity were assigned to combination groups. A Chi-square test was applied for comparison. The primary outcomes were the proportion of pts in remission (REM)or low disease activity (LDA) that is DAS28-ESR<2.6 or 3.2 at 24 weeks, as well as the proportion of pts, achieved ACR20, Boolean remission, and good or moderate EULAR response (G+M).Results:A total of 313 pts (26 pts with UA, 59 pts with ERA, and 228 pts with RA) were included in this study. Of these, 227/313 (72.5%) pts completed the 24-week follow-up. The results showed that 115/227 (50.7%), 174/227 (76.7%), 77/227 (33.9%), 179/227 (78.9%) pts achieved DAS28-ESR defined REM and LDA, ACR20, Boolean remission, G+M response, respectively. All parameters continued to decrease in all pts after treatment (Fig 1).Compared with baseline, the three highest decline indexes of disease activity at week 24 were SW28, CDAI, and T28, with an average decline rate of 73.8%, 61.4%, 58.7%, respectively. Results were similar in three cohorts.We performed a stratified analysis of which IGU treatment should be used in different cohorts. The study found that the proportion of pts with UA and ERA who used IGU monotherapy were significantly higher than those in the RA cohort. While the proportion of triple and quadruple combined use of IGU in RA pts was significantly higher than that of ERA and UA at baseline and whole-course (Fig 2).A total of 81/313 (25.8%) pts in this study had adverse events (AE) with no serious adverse events. The main adverse events were infection(25/313, 7.99%), gastrointestinal disorders(13/313, 4.15%), liver dysfunction(12/313, 3.83%) which were lower than 259/2666 (9.71%) in the previous Japanese phase IV study[4].The most common reasons of lost follow-up were: 1) discontinued after remission 25/86 (29.1%); 2) lost 22/86 (25.6%); 3) drug ineffective 19/86 (22.1%).Conclusion:Both IGU-based monotherapy and combined therapies are tolerant and effective for treating UA, ERA, and RA, while the decline in joint symptoms was most significant. Overall, IGU combination treatments were most used in RA pts, while monotherapy was predominant in ERA and UA pts.References:[1]Levin RW, et al. Scand J Rheumatol 1996, 25(5):277-281.[2]Kay J, et al. Rheumatology 2012, 51(Suppl 6):vi5-9.[3]Zhao J, et al. Clin Exp Rheumatol 2014, 32(5):667-673.[4]Mimori T, et al. Mod Rheumatol 2019, 29(2):314-323.Disclosure of Interests:None declared
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L. M., Abramova, and Golovanov Ya. M. "Regularities of cemetery flora formation in towns of the Southern Cis-Urals, Republic of Bashkortostan." Povolzhskiy Journal of Ecology 16, no. 4 (2017): 323–34. http://dx.doi.org/10.18500/1684-7318-2017-4-323-334.
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Le Moigne, Ronan, Paul Pearson, Veronique Lauriault, Nan Hyung Hong, Peter Virsik, Han-Jie Zhou, and Alessandra Cesano. "Preclinical and clinical pharmacology of EPI-7386, an androgen receptor N-terminal domain inhibitor for castration-resistant prostate cancer." Journal of Clinical Oncology 39, no. 6_suppl (February 20, 2021): 119. http://dx.doi.org/10.1200/jco.2021.39.6_suppl.119.
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119 Background: EPI-7386 is the newest of the “anitens”, a new class of compounds designed to inhibit androgen receptor activity by binding to the N-terminal domain (NTD) of the AR. Through this novel method of AR inhibition, anitens can block AR transcription even in the presence of AR ligand-binding domain (LBD) resistance mechanisms including point mutations and splice variants. Compared to the first generation aniten, EPI-506, which showed poor pharmacokinetic properties in patients, EPI-7386 is metabolically stable in vitro and in vivo. A Phase 1 clinical trial of EPI-7386 in metastatic castration-resistant prostate cancer patients failing standard of care therapies is ongoing and the pharmacokinetic properties of the drug in preclinical models as well as in the initial cohort of patients are presented. Methods: The metabolic stability of EPI-7386 was evaluated in vitro in mouse, rat, dog, monkey, and human hepatocytes. Projected PK parameters in humans were estimated from in vitro and in vivo clearance correlation (IVIVC). Induction of CYP isoforms was evaluated in human hepatocyte cultures. In patients, plasma concentrations of EPI-7386 were determined by LC-MS-MS, and 4-beta-hydroxycholesterol levels in plasma were followed over time as an indirect indicator of CYP3A induction. Results: In vitro hepatocyte studies demonstrated good metabolic stability for EPI-7386 with an in vitro half-life > 360 min. In animal PK studies, the terminal half-life of EPI-7386 was approximately 5.8 hours in mouse, 4.9 hours in rat, 13.4 hours in dog and the plasma clearance was low across species. The oral bioavailability of EPI-7386 ranged from 33–112% in mouse to > 100% in rat and dog. Using IVIVC, a predicted human clearance of 0.16–0.39 mL/min/kg was calculated for EPI-7386, which was in line with allometric scaling from animal PK parameters. Human PK profiles of different doses of EPI-7386 were simulated using predicted oral bioavailability, clearance, and volume of distribution. Cmax and AUC0–24h for the Phase 1 first-in-human study (NCT04421222) starting dose of 200 mg dose were predicted to be 6,915 ng/mL and 137,278 ng•h/mL respectively. A comparison between estimated PK parameters and actual values observed in the first patient cohort will be presented. Human hepatocyte CYP induction studies showed that EPI-7386 is not an inducer of CYP1A2 but may have the potential to induce CYP2B6 and CYP3A4. A comparison of 4-beta-hydroxy cholesterol levels measured during the phase 1 will be presented along with a comparison drawn from in vitro models. Conclusions: Pre-clinical characterization predicts that EPI-7386 has the appropriate PK and metabolic properties to afford exposure in patients at potentially efficacious levels following once-daily oral administration. PK measurements in the initial cohort of patients treated in the Phase 1 study will be presented. Clinical trial information: NCT04421222.
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Landewé, Robert BM, Désirée van der Heijde, Maxime Dougados, Xenofon Baraliakos, Filip E. Van den Bosch, Karl Gaffney, Lars Bauer, et al. "Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction." Annals of the Rheumatic Diseases 79, no. 7 (May 7, 2020): 920–28. http://dx.doi.org/10.1136/annrheumdis-2019-216839.
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BackgroundThe best strategy for maintaining clinical remission in patients with axial spondyloarthritis (axSpA) has not been defined. C-OPTIMISE compared dose continuation, reduction and withdrawal of the tumour necrosis factor inhibitor certolizumab pegol (CZP) following achievement of sustained remission in patients with early axSpA.MethodsC-OPTIMISE was a two-part, multicentre phase 3b study in adults with early active axSpA (radiographic or non-radiographic). During the 48-week open-label induction period, patients received CZP 200 mg every 2 weeks (Q2W). At Week 48, patients in sustained remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 at Weeks 32/36 and 48) were randomised to double-blind CZP 200 mg Q2W (full maintenance dose), CZP 200 mg every 4 weeks (Q4W; reduced maintenance dose) or placebo (withdrawal) for a further 48 weeks. The primary endpoint was remaining flare-free (flare: ASDAS ≥2.1 at two consecutive visits or ASDAS >3.5 at any time point) during the double-blind period.ResultsAt Week 48, 43.9% (323/736) patients achieved sustained remission, of whom 313 were randomised to CZP full maintenance dose, CZP reduced maintenance dose or placebo. During Weeks 48 to 96, 83.7% (87/104), 79.0% (83/105) and 20.2% (21/104) of patients receiving the full maintenance dose, reduced maintenance dose or placebo, respectively, were flare-free (p<0.001 vs placebo in both CZP groups). Responses in radiographic and non-radiographic axSpA patients were comparable.ConclusionsPatients with early axSpA who achieve sustained remission at 48 weeks can reduce their CZP maintenance dose; however, treatment should not be completely discontinued due to the high risk of flare following CZP withdrawal.Trial registration numberNCT02505542, ClinicalTrials.gov.