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Bracken, J., C. Coolens, and B. Driscoll. "Sci-Sat AM(1): Planning - 01: Volumetric 4D Computed Tomography with a 320 Multi-Slice Scanner." Medical Physics 37, no. 7Part3 (July 2010): 3907. http://dx.doi.org/10.1118/1.3476201.
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รัตนะ, วัชระ, ละมัย ร่มเย็น, and สัญญาศรณ์ สวัสดิ์ไธสง. "ปัจจัยที่ส่งผลต่อประสิทธิภาพการดำเนินงานกองทุนหมู่บ้านและชุมชนเมืองในเขตอำเภอวานรนิวาส จังหวัดสกลนคร." Interdisciplinary Academic and Research Journal 4, no. 2 (April 7, 2024): 507–28. http://dx.doi.org/10.60027/iarj.2024.274874.
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ภูมิหลังและวัตถุประสงค์: กองทุนหมู่บ้านมีวัตถุประสงค์เพื่อเป็นแหล่งเงินทุนหมุนเวียนสำหรับการลงทุนเพื่อพัฒนาอาชีพ สร้างงาน สร้างรายได้ เพิ่มรายได้และลดรายจ่าย หรือสำหรับการส่งเสริมและพัฒนาไปสู่การสร้างสวัสดิภาพ สวัสดิการ หรือประโยชน์ส่วนรวมอื่นใดให้แก่ประชาชนในหมู่บ้านหรือชุมชนเมือง รวมถึงเป็นแหล่งเงินทุนหมุนเวียนเพื่อบรรเทาความเดือดร้อนเร่งด่วนสำหรับประชาชนในหมู่บ้านหรือชุมชนเมือง ดังนั้นการวิจัยครั้งนี้มีวัตถุประสงค์เพื่อศึกษา (1) ระดับภาวะผู้นำเชิงกลยุทธ์ การมีส่วนร่วมของประชาชน และประสิทธิภาพการดำเนินงานกองทุนหมู่บ้านและชุมชนเมืองในเขตอำเภอวานรนิวาส (2) อิทธิพลของภาวะผู้นำเชิงกลยุทธ์ และการมีส่วนร่วมของประชาชน ที่ส่งผลต่อประสิทธิภาพการดำเนินงานกองทุนหมู่บ้านและชุมชนเมืองในเขตอำเภอวานรนิวาส ระเบียบวิธีการวิจัย: กลุ่มตัวอย่าง ได้แก่ สมาชิกกองทุนหมู่บ้านและชุมชนเมืองในเขตอำเภอวานรนิวาส จังหวัดสกลนคร จำนวน 395 คน โดยใช้แบบสอบถามเป็นเครื่องมือในการเก็บรวบรวมข้อมูล และสถิติที่ใช้ในการวิเคราะห์ข้อมูลได้แก่ ความถี่ ร้อยละ ค่าเฉลี่ย ส่วนเบี่ยงเบนมาตรฐาน และการวิเคราะห์การถดถอยพหุคูณ ผลการวิจัย: (1) ภาวะผู้นำเชิงกลยุทธ์ของผู้นำหมู่บ้าน โดยภาพรวมอยู่ในระดับมาก การมีส่วนร่วมของประชาชนในการดำเนินงานกองทุนหมู่บ้านและชุมชนเมือง โดยภาพรวมอยู่ในระดับมาก และประสิทธิภาพการดำเนินงานกองทุนหมู่บ้านและชุมชนเมืองของอำเภอวานรนิวาส จังหวัดสกลนคร โดยภาพรวมอยู่ในระดับมาก (2) ภาวะผู้นำเชิงกลยุทธ์ด้านการควบคุมองค์การให้สมดุล (β=.320) ด้านการปฏิบัติอย่างมีคุณธรรม (β=.315) ด้านการกำหนดทิศทางเชิงกลยุทธ์ (β=.180) และด้านการสนับสนุนวัฒนธรรมองค์การที่มีประสิทธิผล (β=.147) มีอิทธิพลต่อภาวะผู้นำเชิงกลยุทธ์ที่ส่งผลต่อประสิทธิภาพการดำเนินงานกองทุนหมู่บ้านและชุมชนเมืองอย่างมีนัยสำคัญทางสถิติที่ระดับ .01 โดยสามารถร่วมกันทำนายระดับประสิทธิภาพการดำเนินงานกองทุนหมู่บ้านและชุมชนเมืองในเขตอำเภอวานรนิวาส ได้ร้อยละ 70.80 (R2Adj=.708) การมีส่วนร่วมของประชาชน ด้านการมีส่วนร่วมในการรับผลประโยชน์ (β=.436) และด้านการมีส่วนร่วมในการประเมินผล (β=.178) มีอิทธิพลต่อภาวะผู้นำเชิงกลยุทธ์ที่ส่งผลต่อประสิทธิภาพการดำเนินงานกองทุนหมู่บ้านและชุมชนเมือง อย่างมีนัยสำคัญทางสถิติที่ระดับ .01 ด้านการมีส่วนร่วมในการตัดสินใจ (β=.123) มีอิทธิพลต่อภาวะผู้นำเชิงกลยุทธ์ที่ส่งผลต่อประสิทธิภาพการดำเนินงานกองทุนหมู่บ้านและชุมชนเมือง อย่างมีนัยสำคัญทางสถิติที่ระดับ .05 โดยสามารถร่วมกันทำนายระดับประสิทธิภาพการดำเนินงานกองทุนหมู่บ้านและชุมชนเมืองในเขตอำเภอวานรนิวาส ได้ร้อยละ 46.60 (R2Adj=.466) สรุปผล: ผลการศึกษาชี้ให้เห็นถึงภูมิทัศน์เชิงบวกในอำเภอวานรนิวาส ซึ่งความเป็นผู้นำเชิงกลยุทธ์ระหว่างผู้นำหมู่บ้านและการมีส่วนร่วมของประชาชนมีบทบาทสำคัญในการขับเคลื่อนประสิทธิภาพการดำเนินงานที่สูงของกองทุนหมู่บ้านและชุมชนเมือง ปัจจัยที่ระบุ รวมถึงการควบคุมองค์กรที่สมดุล ความประพฤติทางศีลธรรม และการสนับสนุนวัฒนธรรมองค์กรที่แข็งแกร่ง เน้นย้ำถึงความเชื่อมโยงระหว่างผู้นำเชิงกลยุทธ์กับการดำเนินงานของกองทุนที่มีประสิทธิผล การมีส่วนร่วมของสาธารณะ โดยเฉพาะอย่างยิ่งในกระบวนการรับผลประโยชน์ การประเมิน และการตัดสินใจ มีส่วนช่วยอย่างมากต่อประสิทธิภาพการดำเนินงานโดยรวม การค้นพบนี้เน้นย้ำถึงลักษณะองค์รวมและการทำงานร่วมกันของการเป็นผู้นำและการมีส่วนร่วมของชุมชนเพื่อให้มั่นใจว่าการดำเนินงานกองทุนหมู่บ้านและชุมชนเมืองในอำเภอวานรนิวาสประสบความสำเร็จ
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Hawley, John A., Louise M. Burke, Damien J. Angus, Kieran E. Fallon, David T. Martin, and Mark A. Febbraio. "Effect of altering substrate availability on metabolism and performance during intense exercise." British Journal of Nutrition 84, no. 6 (December 2000): 829–38. http://dx.doi.org/10.1017/s0007114500002440.
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The purpose of this study was to determine the effect of altering substrate availability on metabolism and performance during intense cycling. Seven highly trained men ingested a random order of three isoenergetic meals 90 min before cycling at 80 % maximal oxygen uptake (VO2max) for 20 min (about 310 W), followed by a 600 kJ time trial lasting about 30 min. Meals consisted of either 1·2 g saturated fat/kg body mass (BM) with 3500 U heparin intravenously (HIFAT) to elevate circulating plasma free fatty acid (FA) concentration, 2·5 g carbohydrate/kg BM (CHO) to elevate plasma glucose and insulin concentrations or 2·5 g carbohydrate+20 mg nicotinic acid/kg BM (NA) to suppress lipolysis and reduce free FA concentration. HIFAT elevated free FA concentration (HIFAT 1·3 (SEM 0·2), CHO 0·2 (sem 0·1), NA 0·1 (sem 0·1) mm; P<0·001), lowered the RER (HIFAT 0·94 (sem 0·01), CHO 0·97 (sem 0·01), NA 0·98 (sem 0·01); P<0·01) and increased the rate of fat oxidation (HIFAT 24 (sem 3), CHO 12 (sem 2), NA 8 (sem 3) μmol/kg per min; P<0·01) during the 20 min ride. Marked differences in fat availability and fuel utilisation, however, had little effect on performance in the subsequent time trial (HIFAT 320 (sem 16), CHO 324 (sem 15), NA 315 (sem 13) W). We conclude: (1) increased fat availability during intense cycling increases the rate of fat oxidation; but (2) the reduction in the rate of carbohydrate oxidation in the presence of high circulating plasma free FA is unlikely to enhance intense exercise performance lasting about 1 h; (3) substrate selection during intense (about 80 % VO2max) exercise is dominated by carbohydrate oxidation.
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Vučajnk, Filip, Valentina Spanic, Stanislav Trdan, Iztok Jože Košir, Miha Ocvirk, and Matej Vidrih. "Performance of Symmetric Double Flat Fan Nozzles against Fusarium Head Blight in Durum Wheat." Agriculture 14, no. 3 (February 21, 2024): 343. http://dx.doi.org/10.3390/agriculture14030343.
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Four types of nozzles were tested on large-scale trials with a 40 m2 plot unit size. The Avi Twin 110-01 (80 L ha−1), 110-02 (160 L ha−1), 110-03 (240 L ha−1), and 110-04 (320 L ha−1) symmetric double fan injector nozzles were tested during the 2020/2021 and 2021/2022 growing seasons. This study aimed to evaluate the performance of spray nozzles with regard to deoxynivalenol (DON) accumulation in durum wheat grains. Artificial inoculation with Fusarium spp. was performed after durum heads were protected with fungicide. The percentage of heads covered with fungicide droplets, grain yield, yield-related traits, technological quality parameters, and concentrations of DON were determined. Compared to the control (without fungicide treatment), the Avi Twin 04 nozzle caused a reduction of 45.0% in the DON concentration on average across both growing seasons. This positively corresponded to the percentage of heads covered with fungicide droplets, which was highest when this nozzle was utilized. In both trial years, the DON reduction caused by the 110-04 twin nozzle was higher than that caused by the 110-01 nozzle. Treatment with the 110-04 nozzle more effectively improved the grain yield, 1000-kernel weight, and test weight compared to treatment with the 110-01 nozzle and the untreated control. The differences in technological quality were less pronounced when different spray nozzles were used.
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Lynch, G. A., M. E. Hunt, and S. N. McCutcheon. "A note on the effect of monensin sodium administered by intraruminal controlled-release devices on productivity of dairy cows at pasture." Animal Science 51, no. 2 (October 1990): 418–21. http://dx.doi.org/10.1017/s0003356100005572.
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The effects of monensin sodium, administered by intraruminal controlled-release devices at a rate of 320 mglday, on milk and milk solids production and bloat score were examined in a trial with 90 lactating dairy cows given only mixed ryegrasslwhite clover pasture. Monensintreated cows had significantly greater yields of milk and milk protein than control cows (1397·2 (s.e. 22·9) v. 1296·9 (s.e. 16·3) kg milk, 49·6 (s.e. 0·9) v. 46·5 (s.e. 0·6) kg protein) over the 14-week period of treatment (P < 0·01). Yield of fat was similar in monensin-treated and control cows (62·9 (s.e. 1·5) v. 63·4 (s.e. 1·1) kg). Live weight, condition score and bloat score were not influenced by treatment but pasture conditions were not conducive to severe bloat challenge.
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Rondinone, Valeria, Lorenzo Pace, Antonio Fasanella, Viviana Manzulli, Antonio Parisi, Maria Rosaria Capobianchi, Angelo Ostuni, et al. "VOC 202012/01 Variant Is Effectively Neutralized by Antibodies Produced by Patients Infected before Its Diffusion in Italy." Viruses 13, no. 2 (February 11, 2021): 276. http://dx.doi.org/10.3390/v13020276.
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The coronavirus disease 2019 (Covid-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and presents a global health emergency that needs urgent intervention. Viruses constantly change through mutation, and new variants of a virus are expected to occur over time. In the United Kingdom (UK), a new variant called B.1.1.7 has emerged with an unusually large number of mutations. The aim of this study is to evaluate the level of protection of sera from 12 patients infected and later healed in Apulia Region (Italy) with Covid-19 between March and November 2020, when the English variant was not circulating in this territory yet, against the new VOC 202012/01 variant by seroneutralization assay. The sera of patients had already been tested before, using a virus belonging to the lineage B.1 and showed an antibody neutralizing titer ranging between 1:160 and 1:320. All the 12 sera donors confirmed the same titers of neutralizing antibodies obtained with a strain belonging to the lineage B.1.1.7 (VOC 202012/01). These data indicate that antibodies produced in subjects infected with variants of Sars-CoV-2 strain before the appearance of the English one, seem to have a neutralizing power also against this variant.
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Delaney, Kerri Z., Leandra Spatari, Mélanie Henderson, Sylvia Santosa, and Marie-Eve Mathieu. "Substrate Oxidation Is Altered by Obesity During Submaximal Cycling in Prepubertal and Early Pubertal Children: A Quality Study." Pediatric Exercise Science 33, no. 1 (February 1, 2021): 32–39. http://dx.doi.org/10.1123/pes.2020-0059.
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Background: To examine substrate oxidation in prepubertal and early pubertal children as a function of body weight, body composition, and sex during an exhaustive cycling test. Methods: This study included 320 children in prepubertal and early puberty (Tanner stage 1 or 2; n = 188 males) who completed a minimum of 4 stages (2–5 min/stage) of an adapted version of the McMaster exhaustive exercise protocol on an upright cycle ergometer. Substrate utilization, relative to individual VO2peak, was determined using VO2 and VCO2 data, obtained with breath-by-breath gas analysis during exercise. Results: Both peak (mg/kg lean body mass·min) and submaximal lipid oxidation (mg/kg lean body mass·min) were highest (P < .01) in children with healthy weight (HW), then overweight, and lowest in obese (OB). Both females with HW (compared with males with HW) and females with OB (compared with males with OB) had higher (P < .01) peak and submaximal lipid oxidation. In children with OB, fat-free mass correlated positively (P < .01) with submaximal lipid oxidation (r = .50). In contrast, in children with HW and overweight, fat-free mass correlated positively (P < .01) with carbohydrate oxidation (r = .52 and r = .47, respectively). Conclusion: Obesity during childhood may alter substrate oxidation during exercise. These results may have implications in the implementation of exercise programs in prepubertal or early puberty to control adiposity.
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Qiu, Chong-Rong, Qiang Fu, Jian Sui, Qian Zhang, Peng Wei, Yan Wu, Ke Zhu, Yi Lu, and Peng Wan. "Analysis of Serum Endothelial Cell-Specific Molecule 1 (Endocan) Level in Type 2 Diabetes Mellitus With Acute ST-Segment Elevation Myocardial Infarction and its Correlation." Angiology 68, no. 1 (September 29, 2016): 74–78. http://dx.doi.org/10.1177/0003319716634581.
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Endothelial cell-specific molecule 1 (ESM-1; endocan) is expressed by endothelial cells, and it can be overexpressed in diabetic patients. However, little is known concerning diabetic patients with acute ST-segment elevation myocardial infarction (STEMI). Therefore, we assessed serum ESM-1 level in patients having type 2 diabetes mellitus (T2DM) STEMI; 72 patients with DM (38 with and 34 without vascular disease) and 33 individuals as a control group were included. There was a significant difference in serum ESM-1 level between the T2DM group and the control group ( P = .03). There was also a significant difference in serum ESM-1 level between the T2DM with STEMI group and newly diagnosed T2DM group without vascular disease ( P = .01). In patients with T2DM, serum ESM-1 levels correlated positively with high-sensitivity C-reactive protein levels and the neutrophil to lymphocyte ratio ( r = .321, P = .006 and r = .320, P = .006). Our findings suggest that serum ESM-1 level may be a novel endothelial dysfunction biomarker and it may be related to vascular disease in T2DM.
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Zhao, Youshan, Feng Xu, Juan Guo, Sida Zhao, Chunkang Chang, and Xiao Li. "Dysregulation of ANKRD11 Influenced Hematopoisis By Histone Acetylation-Mediated Gene Expression in Myelodysplastic Syndrome." Blood 128, no. 22 (December 2, 2016): 4292. http://dx.doi.org/10.1182/blood.v128.22.4292.4292.
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Abstract Background and Object In addition to histone deacetylation, the importance of histone over-acetylation induced oncogene transcription in initiation and progression of myelodysplastic syndrome (MDS) has been proposed recently. Our previous whole-exome sequencing identified a new somatic mutation, ANKRD11, an important factor in histone acetylation regulation. Its roles in MDS pathophysiology need to be clarified. Methods The next generation target sequencing (Including ANKRD11) was carried out in 320 patients with MDS using the MiSeq Benchtop Sequencer. ANKRD11 mRNA expression in bone marrow of MDS was measured by real-time PCR. Loss and gain of function assay were carried out in myeloid cell lines K562, MEG-01£¬or SKM-1 to observe the influence on cell proliferation and differentiation . The levels of histone acetylation at H3 and H4 were detected by Western blot. Results Target sequencing in a cohort of 320 MDS patients identified 14 of ANKRD11 mutations (4.38%, Fig.1), which were confirmed by Sanger sequencing. Meanwhile, no ANKRD11 mutations in 100 normal controls were defined. ANKRD11 mutations occurred frequently in exons 10 and 9. The mRNA expression levels of ANKRD11 were significantly decreased in MDS patients, especially in ANKRD11mutant patients (Fig.2). ANKRD11 knockdown in K562 and MEG-1 resulted in growth inhibition, cell cycle arrest and erythroid/megakaryocytic differentiation retardant. In MDS cell line SKM-1, the arrested differentiation was rescued by over-expression of ANKRD11. Consistent with a role for ANKRD11 in histone acetylation, ANKRD11 KD increased acetylation of histones H3 and H4 at H3K14 and H4K5 and resulted in the upregulation of genes involved in differentiation inhibilation (SOX6, P21, et al). Finally, the ANKRD11 KD-mediated influence on cell proliferation and differentiation were reversed by inhibiting histone acetyltransferase activity. Conclusion Our assay defined that ANKRD11 was a crucial chromatin regulator that suppress histone acetylation and then decrease gene expression during myeloid differentiation, providing a likely explanation for its role in MDS pathogenesis. This study further support histone acetylase inhibitor as a potential treatment in MDS. Figure ANKRD11mutation distribution (a) and coexist with other mutations (b). Figure. ANKRD11mutation distribution (a) and coexist with other mutations (b). Figure The mRNA expression levels of ANKRD11in our MDS (A, C) subset and GEO data (B). Figure. The mRNA expression levels of ANKRD11in our MDS (A, C) subset and GEO data (B). Changes of histone acetylation in ANKRD11-KD cell line (MEG-01). ANKRD11 KD significantly increased acetylation of histones H3 and H4 at H3K14 and H4K5. Changes of histone acetylation in ANKRD11-KD cell line (MEG-01). ANKRD11 KD significantly increased acetylation of histones H3 and H4 at H3K14 and H4K5. Disclosures No relevant conflicts of interest to declare.
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Bell, Hazel. "As I was saying: essays on the international book business by Gordon Graham London: Hans Zell. 320 pp, 1993. paperback £16.95. ISBN 1-873836-01-5." Learned Publishing 7, no. 1 (January 1994): 63–64. http://dx.doi.org/10.1002/leap/70015br1.
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LORD, EVELYN. "Blasphemers & Blackguards: The Irish Hellfire Clubs. By DAVID RYAN. Dublin: Merrion. 2012. 320 p. £40 (hb). ISBN 978-1-908928-03-0. £16.99 (pb). ISBN 978-1-908928-01-6." Journal for Eighteenth-Century Studies 36, no. 4 (November 13, 2013): 594–95. http://dx.doi.org/10.1111/1754-0208.12026.
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Ndou, S. P., R. M. Gous, and M. Chimonyo. "Prediction of scaled feed intake in weaner pigs using physico-chemical properties of fibrous feeds." British Journal of Nutrition 110, no. 4 (January 23, 2013): 774–80. http://dx.doi.org/10.1017/s0007114512005624.
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The objective of the present study was to predict scaled feed intake (SFI) using the physico-chemical measurements of feed bulk, such that gut capacity can be estimated in weaner pigs. A basal feed with 13·7 MJ digestible energy and 180 g crude protein per kg DM was diluted to six inclusion levels (0, 80, 160, 240, 320 and 400 g/kg DM) using lucerne hay, maize cob, maize stover, sawdust, sunflower husks or grass hay (veld grass). A total of 124 pigs weighing 18·1 (sd1·37) kg body weight were used. Water-holding capacity (WHC; g water/g DM), bulk density (g DM/ml), neutral-detergent fibre (NDF) and acid-detergent fibre (ADF) influenced the SFI. The quadratic relationship between SFI and WHC was SFI = 19·1 (sem3·49)+10·04 (sem1·61) WHC–1·11 (sem0·17) WHC2(P< 0·01). SFI was also related (P< 0·01) to NDF and ADF by quadratic functions SFI = 24·3 (sem3·55)+0·12 (sem0·229) NDF − 0·00 012 (sem0·000036) NDF2and SFI = 30·2 (sem1·95)+0·112 (sem0·0232) ADF–0·000343 (sem0·0000612) ADF2, respectively. Using broken-stick analyses, the gut capacity was attained when WHC = 4·53 (sem1·25) g water/g DM, NDF = 367 (sem29) g/kg DM and ADF = 138 (sem77) g/kg DM. In conclusion, although threshold values for each were different, WHC, NDF and ADF contents of bulk feeds provide relationships with SFI that can be used to predict gut capacity in weaner pigs.
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Litvinova, Victoria R., Andrey P. Rudometov, Nadezhda B. Rudometova, Denis N. Kisakov, Mariya B. Borgoyakova, Lyubov A. Kisakova, Ekaterina V. Starostina, et al. "DNA Vaccine Encoding a Modified Hemagglutinin Trimer of Avian Influenza A Virus H5N8 Protects Mice from Viral Challenge." Vaccines 12, no. 5 (May 14, 2024): 538. http://dx.doi.org/10.3390/vaccines12050538.
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The development of a safe and effective vaccine against avian influenza A virus (AIV) H5N8 is relevant due to the widespread distribution of this virus in the bird population and the existing potential risk of human infection, which can lead to significant public health concerns. Here, we developed an experimental pVAX-H5 DNA vaccine encoding a modified trimer of AIV H5N8 hemagglutinin. Immunization of BALB/c mice with pVAX-H5 using jet injection elicited high titer antibody response (the average titer in ELISA was 1 × 105), and generated a high level of neutralizing antibodies against H5N8 and T-cell response, as determined by ELISpot analysis. Both liquid and lyophilized forms of pVAX-H5 DNA vaccine provided 100% protection of immunized mice against lethal challenge with influenza A virus A/turkey/Stavropol/320-01/2020 (H5N8). The results obtained indicate that pVAX-H5 has good opportunities as a vaccine candidate against the influenza A virus (H5N8).
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Razafindrainibe, Tanjonirina, Sidonie Rakotonomenjanahary, Mamitiana Andrianirina, and Nasolotsiry E. Ravel. "Congenital heart diseases and pregnancy, Universitary Hospital Center of Gynecology Obstetrical of Befelatanana, Madagascar." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 8, no. 8 (July 26, 2019): 3276. http://dx.doi.org/10.18203/2320-1770.ijrcog20193550.
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Background: Congenital heart diseases are malformations formed during the first weeks of life. Thanks to advances in medicine, they could be cared properly and pregnancies on heart diseases could be continued and completed. These malformations are sources of morbidity even high maternal fetal mortality. Whence our motivation to carry out this study and improve its care.Methods: This is a retrospective observational study reporting clinical cases of congenital heart disease pregnancies, only seen at the UHC-GOB over a seven years period (01 February 2007 - 28 February 2014).Results: We have identified 10 cases of congenital heart diseases out of 56 320 deliveries, that is, an incidence of 0.12 per 1000 deliveries. Isolated arterial canal persistence is predominant. The average age is 26±1. Four cases of congenital heart diseases diagnosed and repaired during childhood, have been noted as well as 02 cases of fortuitous discovery during pregnancy. No joint obstetric and cardiac follow up was performed for our patients. Delivery by high way is recommended in 70% of cases which 57% under peridural anesthesia. Half of the patients had peri-gestational cardiac decompensation such as dyspnea, pre-eclampsia and vacuo-shock progressively decreasing in post-partum. On the fetal side, we recorded 01 intra-uterine delayed growths, 03 premature births and 02 deaths.Conclusions: Pregnancy prognosis on congenital heart disease is based on the type of malformation, close follow up and a multidisciplinary care (Gyneco-obstetrician, Cardiologist, Reanimator, Pediatrician and Geneticist.
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Coberly, Jared, and Nitya Prabhakaran. "Evaluation of Forward Laser Light Scatter Technology as a Preculture Screen of Unpreserved Urine Specimens." American Journal of Clinical Pathology 152, Supplement_1 (September 11, 2019): S133. http://dx.doi.org/10.1093/ajcp/aqz125.012.
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Abstract Introduction Urine cultures are standard of care for the diagnosis of urinary tract infections. Reflexively culturing specimens only after an effective screening test could minimize the number of samples cultured, improving laboratory efficiency. We evaluated a commercial forward laser light scatter system as a screening tool for urine cultures. Methods One hundred ninety (190) consecutive unpreserved urine specimens were screened by the BacterioScan 216Dx system (BacterioScan) prior to urine culture. Performance characteristics were compared against traditional culture methods. Results Urine specimens from 40 men and 150 women were evaluated. In total, 182 specimens were obtained by clean-catch, 7 by catheter, and 1 via nephrostomy; 134 specimens were negative by urine culture (70%). Fifty-six were positive, with the most commonly identified organism being E coli (35 specimens, 62.5%). Compared to urine culture, forward laser light scatter identified 132 positives and 58 negatives (31%) for a sensitivity of 98%, specificity of 42%, positive predictive value of 42%, negative predictive value of 98%, and an overall accuracy of 59%. Average time from collection to result for light scatter analysis was 25 hours and 28 minutes (95% CI, ±74 minutes) versus 52:37 (±280 minutes) for urine culture (P < .01). Time to negative results was 25:51 (±77 minutes) for light scatter versus 53:17 (±320 minutes) for culture (P < .01). Time to positive results was 26:36 (±66 minutes) versus 51:02 (±146 minutes) for culture (P < .01). Conclusions Time to negative result and assay sensitivity showed an improvement over direct urine culture and could reduce number of cultures by ~30%; however, low positive predictive value and accuracy would lead to reflexive culture in the majority of specimens tested, limiting overall utility. Cost analyses may prove the modest efficiency gains do not outweigh the additional expense.
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Mahat, Hanifah, Muhammad Azizi Azri, Yazid Salleh, Nasir Nayan, and Mohamadisa Hashim. "The Use of Animated Elements to Increase Students’ Understanding in Geography Subjects." EDUCATUM Journal of Social Sciences 8, no. 2 (December 21, 2022): 1–13. http://dx.doi.org/10.37134/ejoss.vol8.2.1.2022.
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This study aims to analyze the level, relationship, and contribution among the variables of readiness, motivation, interest, and attitude towards animated elements application in the subject of geography among Form 1, secondary school students in Jempol district, Negeri Sembilan. This study used a quantitative approach with a survey design and questionnaires. The sample of the study consisted of 320 first grade students selected by simple random sampling, while the selection of the school was done by stratified random sampling. Descriptive analyzes (mean, percentage) and inferential analyzes (Pearson correlation, linear regression) were used to answer each study question. The results of the study show that willingness (M = 4.707, SP = .438), motivation (M = 4.750, SP = .421), interest (M = 4.784, SP = .388), and attitude toward the use of animation elements (M = 4.747 and SP = .469) are at a high level. The results of Pearson correlation analysis showed that there was a significant positive relationship between attitude toward using animation elements versus willingness r (.855) =. 000, p <.01, motivation r (.928) =. 000, p <.01, and interest r (.893) =. 000, p <.01. In addition, linear regression analysis showed that motivation and interest contributed 89.5 percent to students' attitudes toward using animated elements in the subject of geography with a value of R2 = .895, F = 896.596, p <.005. In conclusion, this study shows that students' willingness, motivation, and interest in using animated elements in the subject of geography are very high. This shows that the use of animated elements in the formal education of teachers in schools leads to changes in students' learning in the study area. The results of this study can be used by schoolteachers or subject teachers to improve the use of animated elements as a teaching tool in geography for students' learning.
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Kuruoglu, Tuba, Levent Sensoy, Aynur Atilla, Fatih Temocin, Demet Gur, and Esra Tanyel. "Evaluation of risk factors for the development of bacteremia and complications in patients with brucellosis: Is it possible to predict the clinical course?" Journal of Infection in Developing Countries 17, no. 09 (September 30, 2023): 1277–84. http://dx.doi.org/10.3855/jidc.18164.
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Introduction: Brucellosis is often confused with other diseases or accompanies the conditions it imitates. It causes treatment delays, failure, relapse, and complications. This study aimed to investigate bacteremia and complication predictors in Brucellosis patients. Early detection may help reduce relapse rates, length of hospital stay, and surgical intervention rates by providing appropriate treatment. Methodology: We examined 220 adult patients diagnosed with Brucellosis in our tertiary care hospital in the Black Sea Region between January 01, 2010, and January 01, 2022. Patients with and without bacteremia and complications were compared regarding demographic characteristics, clinical features, and laboratory parameters. Results: The mean age was 46.4 ± 15.8 years (18-96 years), and 61% were male. Low back pain and absence of muscle pain were independent risk factors for predicting bacteremia (p = 0.049, p = 0.043, respectively). Weakness /fatigue, weight loss, and 1/320 Standard Tube Agglutination Test (STAT) or Brucella Coombs Gel Test (BCGT) titers were independent risk factors that reduced the risk of complications; in contrast, low back pain and splenomegaly were independent risk factors for development of complications. (p = 0.025, p = 0.007, p = 0.008, p = 0.003, p = 0.021 respectively). Thrombocytopenia was related to complications. When the platelet cut-off value was taken as 160,000/µL in predicting complications, the sensitivity was 31.30%, and the specificity was 97.73% (p = 0.011). Conclusions: The risk of clinical progression and complications could be predicted with symptoms and signs such as myalgia, low back pain, weakness/fatigue, weight loss, splenomegaly, and easily accessible laboratory parameters such as serum STAT/BCGT titer and platelet level.
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Sinaga, Wulan Sari, Djoko Rahardjo, and Krismono Krismono. "Analisa Risiko Kesehatan Cemaran Krom dalam Beras di Kecamatan Jetis, Yogyakarta." Biospecies 16, no. 2 (July 3, 2023): 27–33. http://dx.doi.org/10.22437/biospecies.v16i2.20205.
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The distribution of chromium originating from industrial waste disposal activities into the Opak River can pollute the flow of rice irrigation water which has an impact on food safety, especially rice. This study aims to determine the concentration of hexavalent chromium, the daily intake rate of age groups, and the effect of chromium on health risks. This research was conducted in Jetis District, Bantul, Yogyakarta with 3 sub-district locations: Canden Village, Trimulyo Village, and Sumber Agung Village. The research samples used were 60 rice samples from their own harvest using irrigation water from the Opak River using a random sampling method. Analysis of hexavalent chromium in rice was carried out with a preparation of 15 grams and analyzed using a HACH DR 2700 Spectrophotometer. The results showed that 100% of rice samples in Jetis District were contaminated with hexavalent chromium. The chromium concentration in the 3 villages ranged from 0.054-0.604 mg/kg with the highest mean value of 0.224 mg/kg found in Canden village. The pattern of chromium intake from rice consumption in 3 sub-districts ranged from 0-1909 µg/day with a mean value of 971 µg/day. The average value of chromium intake patterns in 3 sub-districts is far beyond the safe limit set by WHO of 320 µg/day. From the health risk calculations, the Risk Quotient values obtained for the subdistricts of Canden, Trimulyo, and Sumber Agung villages were respectively 3.00, 2.00, and 2.00. The RQ value in 3 sub-districts is above the safe limit set by WHO at RQ > 1. Based on the calculation of the risk of cancer, seen from the ECR value, the results obtained range from 1.E-01 – 2.E-01, this ECR value is far beyond the set safe limit. by WHO is 10-4. Chromium concentration, daily intake rate, consumption patterns, and characteristics of respondents influence health risks. Keywords: Hexavalent Chromium, Rice, Health Risk Analysis Abstrak Distribusi kromium yang bersumber dari aktivitas pembuangan limbah industri ke Sungai Opak dapat mencemari aliran air irigasi persawahan yang berdampak pada keamanan pangan terutama beras. Penelitian ini bertujuan untuk mengetahui konsentrasi kromium heksavalen, laju asupan harian dari kelompok umur, dan pengaruh kromium terhadap risiko kesehatan. Penelitian ini dilakukan di Kecamatan Jetis, Bantul, Yogyakarta dengan 3 lokasi kelurahan yaitu Desa Canden, Desa Trimulyo dan Desa Sumberagung. Sampel penelitian yang digunakan adalah beras sebanyak 60 sampel yang berasal dari hasil panen sendiri yang memanfaatkan air irigasi sungai Opak dengan metode random sampling. Analisis kromium heksavalen pada beras dilakukan dengan preparasi sebanyak 15 gram dan dianalisis menggunakan alat Spektrofotometer HACH DR 2700. Hasil penelitian menunjukkan bahwa 100% sampel beras di Kecamatan Jetis telah terkontaminasi kromium heksavalen. Konsentrasi kromium pada 3 desa berkisar sebesar 0,054-0,604 mg/kg dengan nilai rerata tertinggi sebesar 0,224 mg/kg terdapat di desa Canden. Pola asupan kromium dari konsumsi beras pada 3 kelurahan berkisar 0-1909 µg/hari dengan nilai rerata sebesar 971 µg/hari. Nilai rerata pola asupan kromium di 3 kelurahan jauh melewati batas aman yang ditetapkan oleh WHO sebesar 320 µg/hari. Dari perhitungan risiko kesehatan, diperoleh hasil nilai Risk Quotient untuk kelurahan desa Canden, Trimulyo, Sumberagung secara berurutan sebesar 3,00, 2,00, 2,00. Nilai RQ pada 3 kelurahan diatas batas aman yang ditetapkan oleh WHO sebesar RQ > 1. Berdasarkan perhitungan risiko terjadinya kanker, dilihat dari nilai ECR diperoleh hasil berkisar1,E-01 – 2,E-01, nilai ECR ini jauh melewati batas aman yang ditetapkan oleh WHO sebesar 10-4. Konsentrasi kromium, laju asupan harian, pola konsumsi, karakteristik responden berpengaruh terhadap risiko kesehatan. Kata kunci: Kromium Heksavalen, Beras, Analisa Risiko Kesehatan
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BELL, M. J., J. M. CLOY, C. F. E. TOPP, B. C. BALL, A. BAGNALL, R. M. REES, and D. R. CHADWICK. "Quantifying N2O emissions from intensive grassland production: the role of synthetic fertilizer type, application rate, timing and nitrification inhibitors." Journal of Agricultural Science 154, no. 5 (January 6, 2016): 812–27. http://dx.doi.org/10.1017/s0021859615000945.
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SUMMARYIncreasing recognition of the extent to which nitrous oxide (N2O) contributes to climate change has resulted in greater demand to improve quantification of N2O emissions, identify emission sources and suggest mitigation options. Agriculture is by far the largest source and grasslands, occupying c. 0·22 of European agricultural land, are a major land-use within this sector. The application of mineral fertilizers to optimize pasture yields is a major source of N2O and with increasing pressure to increase agricultural productivity, options to quantify and reduce emissions whilst maintaining sufficient grassland for a given intensity of production are required. Identification of the source and extent of emissions will help to improve reporting in national inventories, with the most common approach using the IPCC emission factor (EF) default, where 0·01 of added nitrogen fertilizer is assumed to be emitted directly as N2O. The current experiment aimed to establish the suitability of applying this EF to fertilized Scottish grasslands and to identify variation in the EF depending on the application rate of ammonium nitrate (AN). Mitigation options to reduce N2O emissions were also investigated, including the use of urea fertilizer in place of AN, addition of a nitrification inhibitor dicyandiamide (DCD) and application of AN in smaller, more frequent doses. Nitrous oxide emissions were measured from a cut grassland in south-west Scotland from March 2011 to March 2012. Grass yield was also measured to establish the impact of mitigation options on grass production, along with soil and environmental variables to improve understanding of the controls on N2O emissions. A monotonic increase in annual cumulative N2O emissions was observed with increasing AN application rate. Emission factors ranging from 1·06–1·34% were measured for AN application rates between 80 and 320 kg N/ha, with a mean of 1·19%. A lack of any significant difference between these EFs indicates that use of a uniform EF is suitable over these application rates. The mean EF of 1·19% exceeds the IPCC default 1%, suggesting that use of the default value may underestimate emissions of AN-fertilizer-induced N2O loss from Scottish grasslands. The increase in emissions beyond an application rate of 320 kg N/ha produced an EF of 1·74%, significantly different to that from lower application rates and much greater than the 1% default. An EF of 0·89% for urea fertilizer and 0·59% for urea with DCD suggests that N2O quantification using the IPCC default EF will overestimate emissions for grasslands where these fertilizers are applied. Large rainfall shortly after fertilizer application appears to be the main trigger for N2O emissions, thus applicability of the 1% EF could vary and depend on the weather conditions at the time of fertilizer application.
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Faderl, Stefan, Meir Wetzler, David Rizzieri, Gary Schiller, Madan Jagasia, Robert Stuart, Siddhartha Ganguly, et al. "Clofarabine Plus Cytarabine Compared With Cytarabine Alone in Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia: Results From the CLASSIC I Trial." Journal of Clinical Oncology 30, no. 20 (July 10, 2012): 2492–99. http://dx.doi.org/10.1200/jco.2011.37.9743.
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Purpose To compare the receipt of clofarabine plus cytarabine (Clo+Ara-C arm) with cytarabine (Ara-C arm) in patients ≥ 55 years old with refractory or relapsed acute myelogenous leukemia (AML). Patients and Methods Patients were randomly assigned to receive either clofarabine (Clo) 40 mg/m2 or a placebo followed by Ara-C 1 g/m2 for five consecutive days. The primary end point was overall survival (OS). Secondary end points included event-free survival (EFS), 4-month EFS, overall remission rate (ORR; complete remission [CR] plus CR with incomplete peripheral blood count recovery), disease-free survival (DFS), duration of remission (DOR), and safety. Results Among 320 patients with confirmed AML (median age, 67 years), the median OS was 6.6 months in the Clo+Ara-C arm and 6.3 months in the Ara-C arm (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00). The ORR was 46.9% in the Clo+Ara-C arm (35.2% CR) versus 22.9% in the Ara-C arm (17.8% CR; P < .01). EFS (HR: 0.63; 95% CI, 0.49 to 0.80; P < .01) and 4-month EFS (37.7% v 16.6%; P < .01) favored the Clo+Ara-C arm compared with Ara-C arm, respectively. DFS and DOR were similar in both arms. Overall 30-day mortality was 16% and 5% for CLO+Ara-C and Ara-C arms, respectively. In the Clo+Ara-C and Ara-C arms, the most common grade 3 to 4 toxicities were febrile neutropenia (47% v 35%, respectively), hypokalemia (18% v 11%, respectively), thrombocytopenia (16% v 17%, respectively), pneumonia (14% v 10%, respectively), anemia (13% v 0%, respectively), neutropenia (11% v 9%, respectively), increased AST (11% v 2%, respectively), and increased ALT (10% v 3%, respectively). Conclusion Although the primary end point of OS did not differ between arms, Clo+Ara-C significantly improved response rates and EFS. Study follow-up continues, and the role of clofarabine in the treatment of adult patients with AML continues to be investigated.
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Afzalunnessa, Sharmin Sultana, and Shahina Tabassum. "HLA gene polymorphism among Bangladeshi patients with end-stage renal disease awaiting kidney transplantation." Bangabandhu Sheikh Mujib Medical University Journal 15, no. 1 (July 12, 2022): 1–10. http://dx.doi.org/10.3329/bsmmuj.v15i1.58420.
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Proper matching of HLA class I and class II antigens among donor and recipient is an important prerequisite for the long survival of a transplanted organ. To reveal the HLA gene polymorphism among end-stage renal disease (ESRD) patients and their donors, a total of 180 ESRD patients and 320 donors, referred by clinicians for HLA typing, were included in this study. HLA typing was performed using Polymerase Chain Reaction-Se- quence Specific Primer (PCR-SSP). The most frequent alleles reported from both groups were, A*11, A*02 and A*33 in A locus; B*15:02, B*35 and B*52 in B locus and DRB1*15, DRB1*07 and DRB1*04 in DR locus. Frequencies of four alleles, A*26, B*57, B*40 and DRB1*11 were found to be higher in ESRD patients. The three locus haplotypes A*24, B*15:02, DRB1*15 were observed more frequently among recipients than in donors. The results were found to be in genetic equilibrium. Higher frequencies of certain alleles in recipients may be indicative of risk factor for renal disease. Further studies are needed to corroborate the findings of this study. BSMMU J 2022; 15(1): 01-10
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Tan, Boonfei, Xiaoli Dong, Christoph W. Sensen, and Julia Foght. "Metagenomic analysis of an anaerobic alkane-degrading microbial culture: potential hydrocarbon-activating pathways and inferred roles of community members." Genome 56, no. 10 (October 2013): 599–611. http://dx.doi.org/10.1139/gen-2013-0069.
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A microbial community (short-chain alkane-degrading culture, SCADC) enriched from an oil sands tailings pond was shown to degrade C6–C10 alkanes under methanogenic conditions. Total genomic DNA from SCADC was subjected to 454 pyrosequencing, Illumina paired-end sequencing, and 16S rRNA amplicon pyrotag sequencing; the latter revealed 320 operational taxonomic units at 5% distance. Metagenomic sequences were subjected to in-house quality control and co-assembly, yielding 984 086 contigs, and annotation using MG-Rast and IMG. Substantial nucleotide and protein recruitment to Methanosaeta concilii, Syntrophus aciditrophicus, and Desulfobulbus propionicus reference genomes suggested the presence of closely related strains in SCADC; other genomes were not well mapped, reflecting the paucity of suitable reference sequences for such communities. Nonetheless, we detected numerous homologues of putative hydrocarbon succinate synthase genes (e.g., assA, bssA, and nmsA) implicated in anaerobic hydrocarbon degradation, suggesting the ability of the SCADC microbial community to initiate methanogenic alkane degradation by addition to fumarate. Annotation of a large contig revealed analogues of the ass operon 1 in the alkane-degrading sulphate-reducing bacterium Desulfatibacillum alkenivorans AK-01. Despite being enriched under methanogenic–fermentative conditions, additional metabolic functions inferred by COG profiling indicated multiple CO2 fixation pathways, organic acid utilization, hydrogenase activity, and sulphate reduction.
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MCCARTHY, JOHN P. "J. V. Fifer, The Master Builders: Structures of Empire in the New World, Spanish Initiatives and United States Invention (Durham: Durham Academic Press, 1996, £14.95). Pp. 320. ISBN 1 900838 01 X." Journal of American Studies 32, no. 3 (December 1998): 513–64. http://dx.doi.org/10.1017/s0021875898636033.
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MCCARTHY, JOHN P. "J. V. Fifer, The Master Builders: Structures of Empire in the New World, Spanish Initiatives and United States Invention (Durham: Durham Academic Press, 1996, £14.95). Pp. 320. ISBN 1 900838 01 X." Journal of American Studies 34, no. 2 (August 2000): 311–56. http://dx.doi.org/10.1017/s0021875899236419.
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Crabb, Simon J., Gareth Owen Griffiths, Ellice Marwood, Denise Dunkley, Nichola Downs, Karen Martin, Michelle Light, et al. "ProCAID: A randomized double-blind phase II clinical trial of capivasertib (C) in combination with docetaxel and prednisolone chemotherapy (DP) in metastatic castration-resistant prostate cancer (mCRPC)." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 5520. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.5520.
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5520 Background: DP extends survival in mCRPC, but clinical benefit is modest. PI3K/AKT/PTEN pathway activation is common in mCRPC contributing to disease progression and DP resistance. C is a pan-AKT inhibitor. Pre-clinical data indicate activity in prostate cancer and synergism with DP. This phase II trial combined C with DP in mCRPC. Methods: Key eligibility criteria: histologically or cytologically proven measurable or evaluable mCRPC, suitable for treatment with DP for PSA and/or radiographic disease progression, ECOG performance status 0-1, no prior chemotherapy for mCRPC, not requiring insulin or > 2 oral hypoglycaemic drugs for diabetes mellitus. Treatment: up to 10 cycles of DP (D: 75 mg/m2 IV, day 1; P: 5 mg bd oral, day 1 – 21) and random assignment (1:1, double blind) to oral C (320 mg twice daily, 4 days on/3 days off, from cycle 1, day 2) or matched placebo to disease progression. Primary endpoint: progression free survival (PFS; comprising PSA, radiographic or clinical progression, new cancer therapy or death; PCWG2 criteria) in the intent to treat (ITT) population. Secondary endpoints included overall survival (OS) and safety. PFS and OS were also assessed by composite biomarker (B) subgroup for PI3K/AKT/PTEN pathway activation status (NGS/IHC on archival tumour, contemporaneous ctDNA). Statistics: designed to detect a 50% increase in median PFS (6 to 9 months (mo)) between the placebo and C arms (90% power, 20% 1-sided alpha) by Cox proportional hazards model. Registration: ISRCTN 69139368. Results: 150 patients were randomised to 01/2019. Median follow up 16.77 months (IQR 12.0-26.5). PFS and OS by ITT and B status, are shown in the table (NR, not reached; CI confidence interval). Grade 3–4 adverse events (AE) were equally common between arms (62.2%). The most common AEs were diarrhoea, fatigue and nausea. Conclusions: Adding C to DP did not extend PFS. The OS secondary endpoint was significantly increased. PFS and OS results were consistent irrespective of PI3K/AKT/PTEN pathway activation status. Clinical trial information: 69139368 . [Table: see text]
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Silver, M., and A. L. Fowden. "Prepartum adrenocortical maturation in the fetal foal: responses to ACTH1–24." Journal of Endocrinology 142, no. 3 (September 1994): 417–25. http://dx.doi.org/10.1677/joe.0.1420417.
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Abstract The present study was carried out on 19 chronically catheterized mares and fetuses in late gestation (term >320 days). In six animals which were monitored up to the time of delivery of a live foal, plasma and amniotic fluid cortisol concentrations remained low until 4–5 days before parturition when there was a rapid, significant rise (P<0·05) which was not accompanied by any corresponding changes in maternal plasma cortisol. Circulating fetal ACTH concentrations became more variable close to delivery and ANOVA revealed no significant increases during this critical period, although a negative correlation between plasma ACTH and time to delivery was observed (P<0·05). Tests on fetal adrenal responsiveness to exogenous ACTH1–24 were carried out on ten animals. Before 295 days of gestation no significant increases in fetal plasma cortisol above its basal level of 20–30 nmol/l could be elicited by ACTH, administered as a single i.v. injection (1–2 μg/kg). By 304 ± 3 days (mean ± s.e.m.) small but significant (P<0·05) increments in plasma cortisol were detected after ACTH, while in the oldest group (313 ±2 days) significant (P<0·01) 50–60% increments were seen throughout the test period (2 h). Only one fetus was tested within 3 days of delivery and here a fourfold rise in plasma cortisol was evoked by ACTH. When changes in endogenous levels of circulating ACTH and cortisol were monitored every 15 min over 1·5- to 2-h periods in late gestation, rises in ACTH were only accompanied by concomitant increases in plasma cortisol in fetuses within 5 days of delivery (correlation coefficient r=0·58, P<0·01). Before this time, plasma cortisol concentrations remained at basal levels irrespective of any fluctuations in plasma ACTH. These findings indicate that the adrenal cortex of the fetal foal is relatively quiescent and insensitive to ACTH for most of the latter part of gestation, but that a short rapid escalation in circulating cortisol precedes its delivery. Journal of Endocrinology (1994) 142, 417–425
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Grivas, Petros, Scott T. Tagawa, Joaquim Bellmunt, Maria De Santis, Ignacio Duran, Peter-Juergen Goebell, Andrea Necchi, et al. "TROPiCS-04: Study of sacituzumab govitecan in metastatic or locally advanced unresectable urothelial cancer that has progressed after platinum and checkpoint inhibitor therapy." Journal of Clinical Oncology 39, no. 6_suppl (February 20, 2021): TPS498. http://dx.doi.org/10.1200/jco.2021.39.6_suppl.tps498.
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TPS498 Background: Treatment options are limited for patients with locally advanced unresectable or metastatic urothelial carcinoma (mUC) who progress following prior platinum-based and checkpoint inhibitor (CPI) therapy. Sacituzumab govitecan (SG) is an antibody-drug conjugate consisting of an anti–Trop-2 monoclonal antibody coupled to SN-38 (an active metabolite of irinotecan, a topoisomerase-I inhibitor) via a unique hydrolyzable linker. A phase II registrational study, TROPHY-U-01 study, confirmed the initial positive efficacy signal in mUC. SG demonstrated an objective response rate (ORR) of 27% and median overall survival (OS) of 10.5 months in patients with mUC (median 3 prior lines of therapy and 87% with ≥1 Bellmunt risk factors) who progressed after prior platinum-based and CPI therapies (n=113; Loriot ESMO 2020). The results compared favorably with historic single-agent chemotherapy (ORR ~10%; OS ≤7 months). A phase III trial has been initiated to confirm these findings. Methods: TROPiCS-04 (NCT04527991) is a global, multicenter, open-label, randomized, controlled trial in patients with locally advanced unresectable or mUC who progressed after prior platinum-based and CPI therapies (with Eastern Cooperative Oncology Group performance status 0–1 and adequate hematologic, hepatic, and renal function). Patients will be randomized 1:1 to receive SG 10 mg/kg intravenously (IV) on day 1 and 8 of 21-day cycles or single-agent treatment of physician’s choice (paclitaxel 175 mg/m2, docetaxel 75 mg/m2, or vinflunine 320 mg/m2 IV on day 1 of 21-day cycles) until progressive disease, unacceptable toxicity, or withdrawal of consent. Treatment beyond progressive disease may be permitted in patients deemed to be receiving clinical benefit per investigator assessment. Approximately 482 patients will be enrolled to provide 90% power on the primary endpoint of OS. Secondary endpoints include progression-free survival, ORR, clinical benefit rate, duration of response (all per Response Evaluation Criteria in Solid Tumors v1.1), safety, and quality of life. Study initiation is ongoing and enrollment begins in Q4 2020 across ~90 sites. Clinical trial information: NCT04527991.
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Xue, Jinqi, Nan Niu, Shuo Wang, Guanglei Chen, Fang Qiu, Yi Zhao, Fei Xing, et al. "Neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer: A pilot trial." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): e12603-e12603. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e12603.
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e12603 Background: Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib plus dalpiciclib (cyclin dependent kinase 4/6 inhibitor) and letrozole in patients with triple-positive breast cancer (TPBC), but the efficacy still needs improvement. This pilot study explored the efficacy and safety of adding trastuzumab to this neoadjuvant regimen in TPBC. Methods: Patients received five 28-day cycles of pyrotinib (320 mg once daily), dalpiciclib (125 mg once daily on days 1-21) and letrozole (2.5 mg once daily), plus six 21-day cycles of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg maintenance dose on day 1), followed by surgery. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Secondary endpoints were objective response rate (ORR), breast pathological complete response (bpCR; ypT0/is) rate, residual cancer burden (RCB), change in Ki-67 level from baseline to surgery, and safety. Results: Between February 16, 2022 and June 2, 2022, 12 patients were enrolled. Seven (58%; 95% CI, 27.7-84.8) patients achieved tpCR and bpCR. The rate of RCB 0-I was 75% (95% CI, 46.8-91.1%). ORR was 92% (95% CI, 64.6-98.5%). Mean Ki-67 level was significantly reduced from 45.0% (95% CI, 19.5% - 70.5%) at baseline to 17.2% (95% CI, 0.7% - 33.7%) after neoadjuvant therapy (P<0.05). The most common grade 3 adverse events were diarrhea (4 [33%]) and decreased neutrophil count (3 [25%]). No grade 4 events or treatment-related deaths occurred. Conclusions: This four-drug neoadjuvant regimen shows promising pathological response in patients with TPBC, with an acceptable safety profile. The results warranted further validation. Clinical trial information: NCT05228951 .
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Welmer, Anna-Karin, Linda Sandberg, Christina Sandlund, Caroline Björck, Maria Hagströmer, Julia Hamilton, Gunilla Helgstrand, et al. "Study protocol for the ‘preventing functional decline in acutely hospitalised older patients (PREV_FUNC)’ study: effects of two multicomponent exercise programmes on physical function – a three-armed randomised controlled trial." BMJ Open 13, no. 8 (August 2023): e070885. http://dx.doi.org/10.1136/bmjopen-2022-070885.
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IntroductionAcutely hospitalised older patients often live with frailty and have an increased risk of impaired physical function. Previous studies suggest that exercise might mitigate the risk of physical impairment; however, further research is needed to compare the effect of different types of exercise interventions. In this paper, we report a protocol for a trial that aims to examine (1) if multicomponent exercise interventions (interventions that include both mobility and strengthening exercises) have effects on physical function compared with usual care in older adults and (2) if a comprehensive multicomponent exercise programme is more effective than a simple multicomponent exercise programme that only include walking and sit-to-stand exercises.Methods and analysisThis is a three-armed randomised controlled trial, with two intervention groups (comprehensive and simple exercise programme) and a control group receiving usual care. We will include 320 participants aged ≥75 years from geriatric medical departments of four hospitals in Stockholm, Sweden. Assessments will be conducted at hospital admission, discharge and 3 months thereafter concerning physical function (primary outcome), activities of daily living, health-related quality of life, sarcopenia and falls. The number of readmissions will be registered up to 1 year after discharge. Data will be analysed with linear mixed effects models, according to the intention-to-treat approach.Ethics and disseminationEthical approval for this trial has been granted by the Swedish Ethical Review Authority (approval number 2022-03032-01). Data collection will consider the information requirement, the requirement of consent, confidentiality obligations and the utilisation requirement. Trial findings will be disseminated through multiple channels, including scientific publications and conferences, and workshops with healthcare professionals and the public.Trial registration numberNCT05366075
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Verhoef, Sanne P. M., Diederick Meyer, and Klaas R. Westerterp. "Effects of oligofructose on appetite profile, glucagon-like peptide 1 and peptide YY3-36 concentrations and energy intake." British Journal of Nutrition 106, no. 11 (June 17, 2011): 1757–62. http://dx.doi.org/10.1017/s0007114511002194.
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In rats, oligofructose has been shown to stimulate satiety hormone secretion, reduce energy intake and promote weight loss. The present study aimed to examine the effect of oligofructose supplementation on appetite profiles, satiety hormone concentrations and energy intake in human subjects. A total of thirty-one healthy subjects (ten men and twenty-one women) aged 28 (sem 3) years with a BMI of 24·8 (sem 0·3) kg/m2 were included in a randomised double-blind, cross-over study. The subjects received 10 g oligofructose, 16 g oligofructose or 16 g placebo (maltodextrin) daily for 13 d, with a 2-week washout period between treatments. Appetite profile, active glucagon-like peptide 1 (GLP-1) and peptide YY3-36 (PYY) concentrations and energy intake were assessed on days 0 and 13 of the treatment period. Time × treatment interaction revealed a trend of reduction in energy intake over days 0–13 by oligofructose (P = 0·068). Energy intake was significantly reduced (11 %) over time on day 13 compared with day 0 with 16 g/d oligofructose (2801 (sem 301) v. 3217 (sem 320) kJ, P < 0·05). Moreover, energy intake was significantly lower with 16 g/d oligofructose compared with 10 g/d oligofructose on day 13 (2801 (sem 301) v. 3177 (sem 276) kJ, P < 0·05). Area under the curve (AUC) for GLP-1 on day 13 was significantly higher with 16 g/d oligofructose compared with 10 g/d oligofructose (45 (sem 4) v. 41 (sem 3) pmol/l × h, P < 0·05). In the morning until lunch, AUC0–230 min for PYY on day 13 was significantly higher with 16 g/d oligofructose compared with 10 g/d oligofructose and placebo (409 (sem 35) v. 222 (sem 19) and 211 (sem 20) pg/ml × h, P < 0·01). In conclusion, 16 g/d and not 10 g/d oligofructose may be an effective dose to reduce energy intake, possibly supported by higher GLP-1 and PYY concentrations.
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Halim, Timotheus Y., Julye C. Lavoie, Michael J. Barnett, Stephen H. Nantel, Thomas J. Nevill, John D. Shepherd, Heather J. Sutherland, et al. "High Risk AML Outpatient Management: A Retrospective Analysis of Bacteremia Incidence Following Chemotherapy." Blood 104, no. 11 (November 16, 2004): 884. http://dx.doi.org/10.1182/blood.v104.11.884.884.
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Abstract Treatment of acute myeloid leukemia (AML) involves aggressive remission inducing (IND) chemotherapy, and consolidation (CON) chemotherapy aimed at preventing or delaying relapse. Since September 2001, our institution has implemented a selective discharge protocol, which allows the majority of CON cycles, and some selected IND cycles, to be administered entirely on outpatient (OP), or early discharge (ED: prior to ANC >0.5 x 109/L or before d+15) basis. One of the primary concerns associated with this novel practice is the prompt management of infections in these high-risk neutropenic patients, requiring immediate administration of empirical broad spectrum parenteral antibiotics. Our group previously reported the safety and feasibility of OP management (Savoie Blood 2002, 100:11 p766a). We now present a comparative review of the incidence of septicemia over a 5 year period, encompassing the change in management policy. We investigated the impact of selective discharge on infectious morbidity, and the spectrum of bacterial pathogens and their resistance profile. OP received all standard chemotherapy and supportive care in outpatient settings. Supportive care was modified for OP, adding Ciprofloxacin 500mg po BID as antimicrobial prophylaxis d+1 from the start of chemotherapy. Universal supportive care for all pts consisted of Acyclovir 600mg po qid or Valacyclovir 500mg po od (if HSV IgG positive) and Fluconazole 200–400mg po od or Itraconazole 200mg po bid (if previously aspergillus infection). The prophylaxis was stopped upon ANC recovery. Pts were not routinely treated with G-CSF. Between Feb 1999 and Feb 2004, 328 IND and 295 CON cycles of chemotherapy (total=623) were given to 295 patients. Following guidelines adopted in Sep 1, 2001 the majority of CON cycles [84% (133/159)] were administered to pts in our OP day-care clinic, also a smaller number of CON and some IND cycles were candidates for ED. Analysis of trends indicated a minor decrease in overall bacteremia incidence following the implementation of OP protocol. [21% (65/303) before 1-Sept-01, 19% (61/320) after 1-Sept-01),NS]. However, a significant decrease in bacteremia was observed in the CON cycle subgroup (which included the largest OP population), from 31% (42/136) before, to 19% (29/159) after 1-Sept-01 (p=0.01). In addition, a notable shift in incidence of gram-ve bacteremia occurred in IP (-cipro prophylaxis) compared to OP (+cipro prophylaxis) from 49% to 27% of total bacterial infections. Nevertheless, a larger fraction of gram-ve isolates from OP exhibited resistance to ciprofloxacin. No treatment related deaths occurred as a result of infection in the OP population. This report constitutes the first comparative study of bacteremial complications in high risk neutropenic AML patients treated in OP settings. OP management in conjunction with prophylactic antibiotherapy is safe, and results in a significant decrease in bacteremia. However, the use of gram-ve coverage prophylaxis introduced a shift in pathogenic microorganisms and emergence of resistance. Supported by our findings we propose that selective OP management of AML pts should be encouraged, keeping in mind the change in the spectrum of infections.
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Hartmane, Ilona, Ingmārs Mikažāns, Iveta Ivdra, Andra Dērveniece, and Ināra Ančupāne. "Experience of Phototherapy in Dermatological Praxis in Complex Therapy of Psoriasis Patients." Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences. 70, no. 1 (February 1, 2016): 7–12. http://dx.doi.org/10.1515/prolas-2016-0002.
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Abstract Psoriasis is a chronic relapsing skin disease presenting with erythematous and papulous lesions with infiltration and extensive desquamation on the skin surface. It is a genetically determined, multifactorial dermatosis where genetic, immune, and environmental factors play significant roles in its development. In Latvia in treatment of different forms of extensively spreading psoriasis, PUVA (psoralen and ultraviolet A light therapy), a combined method, is administered, applying long-wave UVA radiation with wavelength 320–400 nm in combination with photosensibilisator 8-metoxypsoralen and medium wave length UVB radiation narrow-band phototherapy — 311 nm using specialised TL-01 lamps. The aim of our clinical investigation was to determine the efficacy of narrow-band phototherapy (UVB 311 nm) in the complex treatment of patients with different severity of extensive psoriatic lesions treated in the Clinical Centre of Skin and Sexually Transmitted Diseases. Cases of clinical data of 260 patients with widely spread psoriasis were analysed. In the Group 1 (n = 102) receiving narrow-band UVB therapy, the mean and cumulative UVB dosage was 1.8 ± 0.6 and 21.5 ± 3.8 J/cm2, respectively, whereas in Group 2 (n = 91) it was 2.2 ± 0.1 and 27.7 ± 8.0 J/cm2. To obtain clinical recovery, 18 to 30 procedures were necessary (average 22 ± 4.1) with total irradiation dose received 110 ± 4.6 J/cm2. In 67 patients of the control group, PUVA therapy was administered, and positive therapeutic efficacy was observed in all patients. Clinical recovery was obtained in 86.2% in patients of the Group 1, in 82.4% — of Group 2, and in 80% — in 67 patients of the control group. Narrow-band (311 nm) UVB phototherapy is currently one of the leading pathogenetical methods of treatment of patients with widespread psoriasis. It has high efficacy, good tolerability, does not have severe side effects and restrictions in use, in comparison with traditional PUVA therapy.
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Fang, Michele, Eric Hume, and Said Ibrahim. "Race, Bundled Payment Policy, and Discharge Destination After TKA: The Experience of an Urban Academic Hospital." Geriatric Orthopaedic Surgery & Rehabilitation 9 (January 1, 2018): 215145931880322. http://dx.doi.org/10.1177/2151459318803222.
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Background: Total knee arthroplasty (TKA) provides good clinical outcomes for the treatment of end-stage osteoarthritis; however, discharge destination after TKA has major implications on postoperative adverse outcomes and readmissions. With the initiation of Bundled Payments for Care Improvement (BPCI), it is unclear how racial disparities in discharge destination after TKA will be affected by the new bundled payment for TKA. Methods: Bundled Payments for Care Improvement was implemented in July 01, 2014, at the University of Pennsylvania. We compared differences during early implementation (July 1, 2014, to, March 30, 2016) and during late policy implementation (April 1, 2016, to February 28, 2017) in patient characteristics (including race: African American [AA], white, and other race), discharge destination (skilled nursing facility [SNF], inpatient rehabilitation facility, home, home with home health, or other), and outcomes. Results: We identified 2276 patients who underwent TKA (43.8% AA, 48.2% white, and 8.0% other race). African American patients were more likely to be discharged to SNF as opposed to home than white patients both during the early BPCI (AA: 53.0%, n = 320; white: 32.4%, n = 210, P < .05) and late BPCI implementation (AA: 44.4%, n = 169, white: 26.9%, n = 120, P < .05), though all races showed trends to decreasing SNF use during the late BPCI implementation. Discussion: There were no significant differences in readmissions, length of stay, mortality, or intensive care unit days during early and late implementation of BPCI or when AA patients were compared to white patients. Conclusion: We found no significant changes in racial variations in discharge destination and outcomes after elective TKA. Bundled Payments for Care Improvement has encouraged better preoperative preparation of patients and discharge planning; however, payment reforms alone might not be sufficient to address variation in post-op management following elective surgery.
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Koenecke, Christian, Gudrun Göhring, Liesbeth de Wreede, Anja van Biezen, Christof Scheid, Liisa Volin, Johan Maertens, et al. "Prognostic Value Of Five-Group Cytogenetic Risk Classification In Patients With MDS After Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study Of The Chronic Malignancies Working Party Of The EBMT." Blood 122, no. 21 (November 15, 2013): 2092. http://dx.doi.org/10.1182/blood.v122.21.2092.2092.
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Abstract Introduction The only curative treatment approach for patients with myelodysplastic syndromes (MDS) is allogeneic hematopoietic stem cell transplantation (HSCT), but disease relapse after transplantation is a major concern. Predictors for disease outcome after HSCT are limited. However, unfavorable cytogenetic abnormalities have been shown to serve as predictors for MDS-relapse after transplantation. Similar to the data available in MDS-patients not undergoing HSCT (Schanz et al. J Clin Oncol 2012), there is evidence that the novel 5-group cytogenetic classification has a better predictive value for outcome after HSCT than standard IPSS cytogenetics (Deeg et al. Blood 2012). The aim of this large multicentric, international study was to retrospectively determine the impact of the new 5-group cytogenetic MDS classification on outcome after HSCT. Patients and Methods Patients were selected from the EBMT database who had received HSCT for the treatment of MDS between 1982 and 2010 and for whom sufficient cytogenetic information was available. In total, 903 patients were included into the study. At time of HSCT, 97 (10.7%) patients had untreated MDS, 218 (24.1%) patients had advanced MDS or AML evolving from MDS in complete remission, and 227 (25.1%) patients were not in remission after treatment (in 12.3% information on stage of the disease was not available). Median time between diagnosis and transplant was 6.6 months (range 0.2-359.3). Matched related donor HSCT was performed in 574 patients (63.6%), and matched unrelated donor HSCT in 329 patients (36.4%). Bone marrow (35.4%) or peripheral blood (64.6%) served as stem cell graft. Myeloablative preparative regimens were used in 582 patients (64.5%), and a non-myeloablative regimen was given to 320 patients (35.4%). Impact of cytogenetic classification was analyzed in uni- and multivariate models regarding overall survival (OS) and relapse free survival (RFS) after HSCT. Predictive performance of the 2 classifications was compared by means of the cross-validated log partial likelihood. Results Estimated 5-year RFS and OS were 32% and 36% respectively. According to the 5-group cytogenetic classification 19 (2.1%) patients had very good risk cytogenetics, 204 (22.6%) normal risk cytogenetics, 438 (48.5%) intermediate risk cytogenetics, 178 (19.7%) poor risk cytogenetics, and 64 (7.1%) very poor risk cytogenetics. Good, intermediate, and poor risk cytogenetics according to IPSS were found in 192 (38.0%), 500 (40.2%), and 211 (23.7%) patients, respectively. In univariate analysis 5-group cytogenetic information was found to be strongly associated with OS and RFS (OS: log-rank test P<.01, RFS: P<.01) (Figure 1). Further clinicopathologic factors showed a significant impact on impaired OS and RFS: Disease status at HSCT (RA/RARS no pretreatment; RAEB(t)/sAML in CR; RAEB(t)/sAML not in CR, RAEB(t)/sAML untreated) (OS: P<.01, RFS: P<.01) and IPSS cytogenetics (good; intermediate; poor) (OS: P<.01, RFS: P<.01). Patient age showed an impact for RFS (P=.05), but not for OS (P=.09). In multivariate analysis, statistically significant predictors for RFS and OS at HSCT were 5-group cytogenetics, IPSS-cytogenetics, disease status and patient's age. Using 5-group cytogenetics classification, patients with poor risk [(RFS: P=.001, HR=1.40 (95% CI: 1.15-1.71); OS: P=.003, HR=1.38 (95% CI: 1.12-1.70)] or very poor risk cytogenetics [(RFS: P<.001, HR=2.14 (95% CI: 1.6-2.9); OS: P<.001, HR=2.14 (95% CI: 1.59-2.87)] had worse RFS and OS than patients in the other 3 risk groups. Patients with very poor risk cytogenetics had worse RFS and OS compared to patients with poor risk cytogenetics [(RFS: P<.01, HR=1.53 (95-% CI: 1.11-2.11), OS: P<.01, HR=1.55 (95-% CI: 1.11-2.15)]. When comparing the predictive performance of a series of 3 models both for OS and for RFS – (1) with only classical risk factors, (2) these extended with IPSS cytogenetics, (3) extended with 5-group classification instead-, the model with 5-group cytogenetics performed best. Conclusion In this international, multicentric analysis we confirm that MDS patients with poor and very poor risk cytogenetics had significantly worse RFS and OS after HSCT than patients in the other risk groups of the 5-group cytogenetic classifier. New therapeutic strategies to prevent relapse after HSCT in patients with poor or very poor cytogenetics are urgently needed. Disclosures: No relevant conflicts of interest to declare.
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Martins Figueiredo, L., F. Correia, M. A. Rafael, L. Lourenço, A. M. Oliveira, J. C. Branco, L. Santos, and A. Martins. "P112 Impact of the SARS-COV2 pandemic on patients with inflammatory bowel disease - Preliminary results of a prospective, single-center study." Journal of Crohn's and Colitis 15, Supplement_1 (May 1, 2021): S204—S205. http://dx.doi.org/10.1093/ecco-jcc/jjab076.239.
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Abstract Background The real impact of COVID-19 infection on patients with Inflammatory Bowel Disease (IBD) is unknown. It was speculated that this population could be a risk group. The aim of this study is to evaluate the incidence of SARS-CoV2 infection, the impact of initiation/change of IBD therapy and its morbidity and mortality, during the COVID-19 pandemic in Portugal. Methods Prospective cross-sectional study. Patients with IBD followed at a Gastroenterology Department in an area with a high incidence rate of SARS-CoV2 were included, from 01/03/2020 to 31/08/2020. Data was obtained through telephonic appointments, hospital inpatients admissions, Emergency Department Service and Day Hospital episodes. Results 335 patients were included, 194 female, with a mean age of 47.4 years (18–88). 200 had Crohn’s disease (CD), 132 Ulcerative Colitis, 3 unclassified colitis. 320 were on therapy (95.5%): salicylates n=230 (71.9%), systemic corticosteroids n=34 (10.6%) (18 started during the pandemic), thiopurines/methotrexate n=117 (36.6%) (8 started in this period), biological n=148 (46.3%) (14 started in this period). 7 patients (2.2%) triple immunosuppressed. 75 patients had disease in remission, 232 mild/moderate, 28 severe disease (requiring hospitalization). SARS-CoV2 infection was observed in 3 patients (incidence rate: 0.89%), treated as an outpatient basis. 2 male, mean age 58 years, 2 with CD. Comorbidities: 0: n = 1; 2: n = 1; 4: n = 1. 2 patients were on salicylates and one on adalimumab (monotherapy, before the pandemic). There were no deaths. Conclusion All patients started or maintained their IBD therapy according to current international guidelines. A significantly higher incidence of COVID-19 infection than that of the local and Portuguese population in general has not been documented. According to our preliminary results, the population with IBD does not appear to be a risk group for acquiring infection or having a severe course of the disease.
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Egorov, Evgeny N., Nikolay I. Kol'tsov, and Nikolay F. Ushmarin. "TECHNOLOGICAL ADDITIVES FOR OIL AND PETROL RESISTANCE RUBBERS BASED ON BUTADIENE-NITRILE CAOUTCHOUCS." IZVESTIYA VYSSHIKH UCHEBNYKH ZAVEDENII KHIMIYA KHIMICHESKAYA TEKHNOLOGIYA 64, no. 6 (May 15, 2021): 41–46. http://dx.doi.org/10.6060/ivkkt.20216406.6169.
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The article investigated the influence of various technological additives (zincolet BB 222, lubstab-01 and MA-L22) on the technological properties of the rubber mixture, physical, mechanical and operational characteristics of rubber based on nitrile butadiene caoutchouc BNKS-40AMN. Basic rubber mixture studied included caoutchouc, BC-FF percadox, zinc monomethacrylate, maleide F, triallyl isocyanurate, acetonanil N, MGF-9 and THM-3 oligoester acrylates, carbon black P 514 and other ingredients. The rubber mixture was prepared on laboratory rolls LB 320 160/160 in two stages. At the first stage, BNKS-40AMN caoutchouc was mixed with ingredients and processing aids. As technological additives, zincolet BB 222, lubstab-01 and MA-L22 were used. In the second mixing step, BC-FF percadox and vulcanization coagents were introduced. For the obtained variants of the rubber mixture the vulcanization characteristics were studied on an MDR 3000 Basic rheometer at a temperature of 170 °C. The rubber mixture prepared was vulcanized in a P-V-100-3RT-2-PCD type vulcanizing press at 150 °C for 40 min. Determination of elastic-strength and operational properties of rubber were carried out according to the standards existing for the rubber industry. The oil resistance of the vulcanizates was evaluated by changing their elastic strength after exposure to standard liquid SZHR-1 at a temperature of 125 °C, as well as by changing the mass of the samples after exposure to a mixture of isooctane with toluene at room temperature. It was found that the introduction of technological additives in the rubber compound improves the distribution of carbon black P 514 and powdered ingredients (zinc monomethacrylate, maleide F, triallyl isocyanurate, acetonanil H) in the caoutchouc matrix. Increased elastic strength indicators and their smallest changes after exposure to aggressive hydrocarbon media is characterized a rubber containing technological additive MA-L22. A comparison of technological, elastic-strength properties and resistance to aggressive media for rubbers containing butadiene-nitrile caoutchoucs BNKS-18AMN, BNKS-28AMN and BNKS-40AMN with optimal technological additives for them was done. It has been established that rubber containing BNKS-40AMN and technological additive MA-L22 is characterized by improved vulcanization properties, increased elastic strength indicators and their smallest changes after exposure to aggressive hydrocarbon media.
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Vardi, Anna, Andreas Agathangelidis, Evangelia Stalika, Millaray Marincevic, Maria Karypidou, Achilles Anagnostopoulos, Chrysoula Belessi, Nikos Darzentas, Richard Rosenquist, and Kostas Stamatopoulos. "T Cell Receptor Gene Repertoire Restriction in Chronic Lymphocytic Leukemia with Stereotyped IGHV4–34/IGKV2–30 Antigen Receptors." Blood 120, no. 21 (November 16, 2012): 3908. http://dx.doi.org/10.1182/blood.v120.21.3908.3908.
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Abstract Abstract 3908 Chronic lymphocytic leukemia (CLL) exhibits a remarkably skewed immunoglobulin (IG) gene repertoire mainly evident in the existence of subsets of patients with quasi-identical IGs in their B cell receptors (BcRs), collectively accounting for one-third of CLL patients. BcR stereotypy is strongly suggestive of clonal selection by a restricted set of antigens. However, it is not yet clear at which phase of clonal evolution these antigens act, or whether the stimulation is persistent. Furthermore, the possible role of antigens in the selection and activation of cognate T lymphocytes remains obscure yet highly relevant, given recent data about T cell interactions with CLL B cells and their tolerized behavior. Here, we analyzed the repertoire of T cell receptor β chain genes (TRB) in CLL expressing stereotyped IGHV4–34/IGKV2–30 BcR IGs (subset #4), which exhibit a series of immunogenetic features, such as pronounced intraclonal diversification of IG genes, suggestive of ongoing interactions with (auto)antigens. Furthermore, subset #4 CLL cells have distinctive functional responses to BcR and/or Toll-like receptor triggering, rendering this subset a paradigmatic example for seeking evidence of antigen selection also within the T cell population. We analyzed 18 peripheral blood samples of 12 untreated subset #4 patients (samples from different time points were analyzed in 4 cases). No case had evidence of infection at sampling. PCR amplicons for TRBV-TRBD-TRBJ gene rearrangements (BIOMED2 protocol) were subcloned by transformation into E. coli/TOP10F bacteria and randomly chosen individual colonies were subjected to Sanger sequencing. Only productive rearrangements (n=320, ranging from 14–52/case) were analyzed. All cases were found to carry clusters of identical rearrangements (≥2) corresponding to distinct clonotypes; the number of expanded clonotypes/case ranged from 1–13 (median 5). The relative frequency of each clonotype/case was determined by dividing the number of the corresponding identical sequences by the total number of subcloned sequences analyzed. The frequency of the most expanded (immunodominant) clonotype/case ranged from 8.1–70.4%. Collectively, the frequency of all expanded clonotypes/case ranged from 29.7–93.3%. In 2/4 cases that were analyzed at different time points, at least one clonotype was found to persist. Importantly, cluster analysis of the TRB CDR3 sequences of all cases identified ‘public’ clonotypes: 2 identical clonotypes (TRBV15*02/TRBD1*01/TRBJ2–2*01 and TRBV30*01/TRBD1*01/TRBJ2–2*01) each shared by a pairs of different patients and a highly similar clonotype shared by an additional pair of patients. In conclusion, the present study provides clear evidence of repertoire skewing among T cells in CLL patients belonging to subset #4, strongly supporting antigen selection. The finding of ‘public’ clonotypes raises the possibility that shared antigenic epitopes may be relevant for clonal selection of T cells in different subset #4 cases. Whether the antigens that drive T cell repertoire restriction are identical/related to those implicated in the selection of CLL progenitors of subset #4 or even the malignant cells themselves or whether they are tumor-associated antigens remains to be clarified. Disclosures: No relevant conflicts of interest to declare.
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DerSarkissian, Maral, Deepshekhar Gupta, Jasmina Ivanova, Alexander Niyazov, Enrico Zanardo, Tracy Guo, Jingru Wang, Mei Sheng Duh, and Stephen J. Freedland. "Racial differences in survival and healthcare resource utilization among Medicaid-insured adults with metastatic castration-resistant prostate cancer." Journal of Clinical Oncology 41, no. 6_suppl (February 20, 2023): 29. http://dx.doi.org/10.1200/jco.2023.41.6_suppl.29.
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29 Background: Prostate cancer (PC) disproportionately affects Black or African American (BAA) men in the United States (US), but racial disparities in outcomes are not well understood. This study analyzed racial disparities in OS, healthcare resource utilization (HRU), and PC treatments in Medicaid-insured metastatic castration resistant PC (mCRPC) patients. Methods: This retrospective longitudinal cohort study evaluated de-identified data from the Centers for Medicare and Medicaid Services 100% Medicaid data files from 01/01/2010 – 12/31/2018. The study included adult patients with a diagnosis of PC and metastasis, and a claim for at least one of the following drugs prior to 9/30/2018, which is specific to mCRPC (date defined index): ≥1 claim for cabazitaxel, mitoxantrone, enzalutamide, radium-223, or sipuleucel-T, ≥1 claim for abiraterone acetate before June 2017, ≥1 claim for docetaxel at least 90 days after initiation of hormone therapy, or evidence of castration resistance. Patients were required to be continuously enrolled for ≥6 months pre-index (i.e., baseline period) and ≥3 months post-index. Outcomes were assessed from the index date to the earliest of end of continuous enrollment, data availability, or death. A multivariable Cox proportional hazards model of OS, and a multivariable Poisson model of HRU were implemented and controlled for age, plan type, region, median state income, residence in a state with Medicaid expansion, index year, Charlson comorbidity index, baseline HRU, baseline PC treatments, and clinical characteristics. Results: The study included 1,095 mCRPC patients (320 [29%] White [W], 278 [25%] BAA, 190 [17%] Hispanic [H], 307 [28%] Other races [O]). H had the highest mean age of 69 years, followed by 68 years for O, and 63 years for both W and BAA. Median unadjusted OS was 46.7 months in H, 40.5 months in BAA, 35.3 months in O, and 32.3 months in W. After adjustment, H had significantly lower risk of death vs. W (hazard ratio [95% confidence interval (CI)]: 0.62 [0.42, 0.90]) and BAA had comparable survival to W (0.85 [0.62, 1.16]). BAA had significantly fewer PC-related outpatient (OP) visits vs. W (adjusted incidence rate ratios [IRR] [95% CI]: 0.67 [0.48, 0.93]), but significantly more PC-related emergency room (ER) visits (5.03 [2.03, 12.47]) per patient per year. Race cohorts differed in the proportions of patients treated with novel hormonal therapy (70% W, 63% BAA, 58% H, 67% O) and chemotherapy use (29% BAA, 26% H, 24% W, 19% O). Conclusions: Among Medicaid-insured adult mCRPC patients, H were more likely to live longer than W patients, while BAA and W patients had similar OS. BAA patients had a higher rate of PC-related ER visits but fewer PC-related OP visits as compared to W, showing differential use of PC-related healthcare resources.
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Knauer, Mark, Terry Armstrong, Brandon Barnes, Austin Jones, Bo Mobley, Tyler O'Dell, Lee Tyre, and Matthew Wynn. "254 Impact of Preweaning Factors on Nursery Throughput." Journal of Animal Science 100, Supplement_2 (April 12, 2022): 119. http://dx.doi.org/10.1093/jas/skac064.201.
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Abstract The objective was to evaluate factors associated with nursery throughput. Data consisted of 3,260 piglets from 320 litters at the NCDA Tidewater Research Station. At weaning, piglets were housed nine per pen (0.23m2 per pig) in onsite nursery facilities for 35 d. Using linear models, farrowing batch (BATCH), gender, litter size (LS), average piglet birth weight (BWT), birth weight CV (BWT_CV), piglet weaning weight (WWT), weaning weight CV (WWT_CV) and weaning age (WEANAGE) were associated with nursery average daily gain (NurADG), nursery exit weight (NurEXITWT), nursery survival (SURVIVAL) and full-value nursery pigs (FULLVALUE, pigs >13.6kg at nursery exit). Litter was the experimental unit. Average WEANAGE, WWT, SURVIVAL and FULLVALUE were 28.1 (±4.7 d), 7.8kg, 98.7% and 94.3%, respectively. Correlations between NurADG with gender, LS, BWT, BWT_CV, WWT, WWT_CV and WEANAGE were zero, -0.04, 0.24, 0.09, 0.81, 0.10 and 0.73, respectively. Factors related (P < .01) to NurADG included BATCH, BWT, WWT and WEANAGE (R2 = 0.80). Within these factors, WWT and WEANAGE explained 70% of the variation in NurADG. A 1kg increase in BWT and WWT increased (P < 0.01) NurADG by 60.3 and 19.4g per pig per d, respectively. A 1 d older WEANAGE increased (P < 0.01) NurADG by 9.36g per pig per d. Increased NurEXITWT was associated (P < 0.05) with BATCH and greater BWT, WWT and WEANAGE (R2=0.88). Within these, WWT and WEANAGE explained 83% of the variation in NurEXITWT. A 1kg increase in BWT and WWT increased (P < 0.01) NurEXITWT by 2.09 and 1.68kg per pig, respectively. A 1 d older WEANAGE increased (P < 0.01) NurEXITWT by 323g per pig. Increased BWT was associated (P < 0.01) with greater SURVIVAL, explaining 4% of the variation. Improved FULLVALUE was associated with (P < 0.05) BATCH and generally greater BWT, WWT and WEANAGE (R2 = 0.44). Of the factors studied, WWT had the greatest impact on the percentage of FULLVALUE at nursery exit (R2 = 0.36).
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Hannan, Kellie Arensman, Paul Frykman, Eric Mathiowetz, Jill Sathre, Nou Cheng Yang, and Kelsey Jensen. "Reducing the rate of guideline-discordant therapy for inpatients with community-acquired pneumonia." Antimicrobial Stewardship & Healthcare Epidemiology 3, S2 (June 2023): s24. http://dx.doi.org/10.1017/ash.2023.244.
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Background: Despite guidelines recommending shorter durations of therapy and empiric coverage of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) only for patients with certain risk factors, optimizing therapy for community-acquired pneumonia (CAP) remains a challenge for antimicrobial stewardship (AMS) teams. We investigated the impact of a multimodal AMS initiative on the rate of guideline-discordant empiric antibiotic selection and total duration of therapy for CAP. Methods: A quality improvement initiative was implemented at 9 community hospitals in 2022 to optimize CAP therapy. Education was provided to pharmacists and providers. Alerts were implemented within the electronic medical record to prompt the AMS team to review fluoroquinolones, antipseudomonal β-lactams, and anti-MRSA agents ordered for CAP. Clinical pharmacists reviewed antibiotic orders for CAP at hospital discharge and encouraged providers to prescribe a total antibiotic duration of 5–7 days. For the preintervention period (July– September 2021) and the postintervention period (July to September 2022), a random sample of 320 patients with an antibiotic order for CAP were evaluated retrospectively via chart review. Patients treated for an indication other than CAP were excluded. The primary outcome was the proportion of patients with a total duration of therapy >7 days. Secondary outcomes included average duration of therapy, rate of guideline-discordant empiric therapy, and type of guideline discordance. Results: In total, 317 patients were included. The proportion of patients with a total duration of therapy >7 days decreased from 29% to 14% (P < .01). Average duration of therapy and guideline-discordant empiric therapy also decreased significantly (Table 1). Conclusions: This multifaceted AMS initiative was associated with decreased guideline-discordant empiric therapy and decreased total duration of therapy for CAP.Disclosures: None
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Al-Batran, Salah-Eddin, Ingeborg Roetzer, Luisa Wohn, Wolfgang Blau, Thomas Zander, Kim Barbara Luley, Philipp Ivanyi, et al. "Home parenteral nutrition (HPN) using individually compounded PN administered via multi-chamber Eurotubes versus PN administered via 2/3-chamber bags in patients with metastatic or localized solid tumors requiring HPN: The randomized IKF-010 PEKANNUSS trial of AIO." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): e24123-e24123. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e24123.
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e24123 Background: Cancer patients (pts) often experience malnutrition and some of them require HPN. However, HPN is associated with challenges, including the need for nursing service to prepare PN bags and add supplements, severely limiting patient autonomy and flexibility. Moreover, HPN is a major risk factor for catheter-related infections (CRI). Eurotubes is a 7/8/9-multi-chamber system that offers fully individualized PN compounding without need for further line or bag manipulation outside GMP environment. This study evaluates whether HPN via Eurotubes improves patient autonomy compared with HPN via traditional 2/3-chamber bags. Methods: This is a randomized, multicenter, investigator-initiated, phase IV trial. Pts with metastatic/locally advanced tumors and need for HPN were stratified according to ECOG PS, the modified Glasgow Prognostic Score (mGPS) and concurrent systemic treatment and randomized 2:1 to receive HPN via Eurotubes (Arm A) or HPN via 2/3-chamber bags (Arm B). Primary endpoint was patient autonomy defined as the proportion of pts with ≥70% of HPN administrations done without nursing service assistance (self-administration or with help of relatives) as provided in pts diaries in the intent to treat population (ITT). A total of 192 pts were required to show a significant improvement in proportions of pt autonomy from 5 to 20% (80% power; 2-sided α < .05 [Fisher’s exact]). Secondary endpoints included CRI, safety, body weight and serum albumin. Results: Study was terminated for slow recruitment after enrollment of 142 pts of which 131 pts qualified for ITT. Baseline criteria were well balanced regarding ECOG PS, body weight, albumin, mGPS, and nutritional risk score, but more pts in Arm A had metastatic disease (78% vs 61%). In median, pts received HPN for 48 days (1 - 320 days) and median cumulative macronutrients of glucose, 3805g; amino acids, 2100g; and lipids, 2250g. Injections of additional supplements into PN bag at home were required in 11% v 96% of pts for Arm A vs B (p < .01). The primary endpoint was met, with patient autonomy being 52% vs 33% in Arm A vs B (p = .04) and the difference was more pronounced in pts with ECOG PS ≤1 (68% vs 42%). Relative changes in body weight and serum albumin favored the Arm A until visit 5. All grade adverse events related to HPN were lower in Arm A (27% vs 55%; p < .01) as were CRI rates (13% vs 22%; p = .22). Device deficiency (8% vs 7%) and PN related death (1% vs 2%), and median overall survival (6.6 vs 6.8 months) were similar. Conclusions: Eurotubes significantly improved patient autonomy, compared with 2/3-chamber bags and were associated with significantly less HPN-related adverse events. HPN via Eurotubes represents a treatment option that is safe and renders pts more able to self-manage their treatment. Clinical trial information: NCT04105777 .
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Vulsteke, Christof, Petros Grivas, Scott T. Tagawa, Joaquim Bellmunt, Maria De Santis, Ignacio Duran, Peter-Juergen Goebell, et al. "TROPiCS-04: Study of sacituzumab govitecan (SG) in patients (pts) with locally advanced (LA) unresectable or metastatic urothelial cancer (mUC) that has progressed after prior platinum (PLT) and checkpoint inhibitor (CPI) therapy." Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022): TPS582. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.tps582.
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TPS582 Background: Treatment options are limited for pts with LA unresectable or mUC who progress after prior PLT-based and CPI therapies. SG is an antibody-drug conjugate (ADC) composed of an anti-trophopblast cell surface antigen 2 (Trop-2) antibody coupled to SN-38 (a topoisomerase-I inhibitor) via a proprietary hydrolyzable linker. In the phase 2 registrational study TROPHY-U-01 (NCT03547973), SG demonstrated an objective response rate (ORR) of 27% and median overall survival (OS) of 10.9 months in pts with mUC who progressed after prior PLT-based and CPI therapies (n = 113; median, 3 prior lines of therapy; 84% with ≥1 Bellmunt risk factors; Tagawa et al, J Clin Oncol. 2021). These results compared favorably with historic data for single-agent chemotherapy (ORR, ̃18%; OS, 9 months; Powles et al. J Clin Oncol. 2021) and led to accelerated approval of SG by the US Food and Drug Administration for pts with LA or mUC who previously received a PLT-containing chemotherapy and CPI. The phase 3 TROPiCS-04 trial has been initiated to confirm these findings. Methods: TROPiCS-04 (NCT04527991) is a global, multicenter, open-label, randomized, controlled trial in pts with LA unresectable or mUC who progressed after prior PLT-based and CPI therapies. Key eligibility requirements include Eastern Cooperative Oncology Group performance status 0-1; no prior CPI or ADC therapy within 4 weeks of study drug initiation; no history of active interstitial lung disease or noninfectious pneumonitis; and adequate hematologic, hepatic, and renal function. Pts will be randomly assigned 1:1 to receive SG 10 mg/kg intravenously (IV) on days 1 and 8 of 21-day cycles or single-agent treatment of physician’s choice (paclitaxel 175 mg/m2, docetaxel 75 mg/m2, or vinflunine 320 mg/m2 IV on day 1 of 21-day cycles) until progressive disease, unacceptable toxicity, or withdrawal of consent. Treatment beyond progressive disease may be permitted in pts deemed to be receiving clinical benefit per investigator assessment. Approximately 600 pts will be enrolled across ̃280 sites in 3 regions (North America, Europe, and Asia-Pacific) to provide 90% power on the primary endpoint of OS. Secondary endpoints include progression-free survival, ORR, clinical benefit rate, duration of response (all per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review and investigator assessment), safety, and quality of life. Study enrollment started in January 2021 and is ongoing with pts currently enrolled at 30 sites across all 3 regions. Clinical trial information: NCT04527991.
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Palani, Manoj Kumar. "Monte Carlo tree search for generating vectors of lattice rules." ANZIAM Journal 62 (February 24, 2022): C225—C241. http://dx.doi.org/10.21914/anziamj.v62.16070.
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Lattice rules are widely studied in the context of quasi-Monte Carlo methods as a means to achieve a small integration error. The rules themselves are determined completely by so called generating vectors, so there is an interest in methods for constructing vectors that perform well. This article introduces a new component-wise construction of a generating vector using the principles of Monte Carlo tree search, with the goal of avoiding local optima. Error bounds are proven for the vectors obtained from this method, which are analogous to existing results for the popular component by component construction. References J. Dick. On the convergence rate of the component-by-component construction of good lattice rules. J. Complex. 20 (2004), pp. 493–522. doi: 10.1016/j.jco.2003.11.008 J. Dick, F. Y. Kuo, and I. H. Sloan. High-dimensional integration: The quasi-Monte Carlo way. Acta Numer. 22 (2013), pp. 133–288. doi: 10.1017/S0962492913000044 M. Giles, F. Y. Kuo, I. H. Sloan, and B. J. Waterhouse. Quasi-Monte Carlo for finance applications. ANZIAM J. 50 (2008), pp. C308–C323. doi: 10.21914/anziamj.v50i0.1440 N. M. Korobov. Approximate evaluation of repeated integrals. Doklady Akademii Nauk SSSR 124 (1959), pp. 1207–1210 F. Y. Kuo. Component-by-component constructions achieve the optimal rate of convergence for multivariate integration in weighted Korobov and Sobolev spaces. J. Complex. 19 (2003), pp. 301–320. doi: 10.1016/S0885-064X(03)00006-2 D. Nuyens and R. Cools. Fast algorithms for component-by-component construction of rank-1 lattice rules in shift-invariant reproducing kernel Hilbert spaces. Math. Comput. 75 (2006), pp. 903–920. doi: 10.1090/S0025-5718-06-01785-6 I. H. Sloan and A. V. Restzov. Component-by-component construction of good lattice rules. Math. Comput. 71 (2002), pp. 263–273. doi: 10.1090/S0025-5718-01-01342-4 I. H. Sloan and H. Woźniakowski. When are quasi-Monte Carlo algorithms efficient for high-dimensional integrals? J. Complex. 14 (1998), pp. 1–33. doi: 10.1006/jcom.1997.0463 X. Wang and I. H. Sloan. Efficient weighted lattice rules with applications to finance. SIAM J. Sci. Comput. 28 (2006), pp. 728–750. doi: 10.1137/S1064827502418197
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Van der Heijde, D., A. Deodhar, L. S. Gensler, D. Poddubnyy, A. Kivitz, M. Dougados, N. De Peyrecave, et al. "POS0226 BIMEKIZUMAB LONG-TERM SAFETY AND EFFICACY IN PATIENTS WITH ANKYLOSING SPONDYLITIS: 3-YEAR RESULTS FROM A PHASE 2B STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 332–33. http://dx.doi.org/10.1136/annrheumdis-2021-eular.156.
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Background:Bimekizumab (BKZ), a monoclonal antibody that selectively inhibits interleukin (IL)-17A and IL-17F, has demonstrated clinical efficacy and safety in patients with ankylosing spondylitis (AS) treated over a period up to 96 weeks.1,2Objectives:To report 3-year interim safety and efficacy of BKZ in patients with active AS from a phase 2b dose-ranging study (BE AGILE; NCT02963506) and its ongoing open-label extension (OLE; NCT03355573).Methods:BE AGILE study design has been described previously.1 Patients treated with BKZ 160 mg or 320 mg every 4 weeks (Q4W) at Week 48 in BE AGILE were eligible for OLE entry. All OLE patients received BKZ 160 mg Q4W. Treatment-emergent adverse events (TEAEs) are reported for the BE AGILE safety set (patients who received ≥1 dose of BKZ on study entry) for total exposure to BKZ across BE AGILE and the OLE. Efficacy outcomes are reported for the OLE full analysis set (patients who entered the OLE and had ≥1 dose of BKZ and ≥1 valid efficacy variable measurement in the OLE), and include: ASAS40, ASAS20, ASAS PR, ASDAS, ASDAS-CII, ASDAS-MI, ASDAS-ID (<1.3) and ASDAS <2.1. Data are reported as imputed (multiple imputation [MI] based on the missing at random assumption, or non-responder imputation [NRI]) and as observed case (OC).Results:262/303 (86%) patients randomised at BE AGILE study baseline completed Week 48 on BKZ 160 mg or 320 mg. At Week 48, 255/262 (97%) patients entered the OLE (full analysis set: 254); 219 patients had an efficacy assessment at Week 156. Over the 156 weeks, the exposure-adjusted incidence rate (EAIR) per 100 patient-years (PY) of TEAEs was 143.5, with an EAIR of 5.8 for serious TEAEs, 1.3 for serious infections, and 3.8 for Candida infections (Table 1). All Candida infections were mild or moderate; none were systemic or led to study discontinuation. Over 156 weeks, the EAIR of inflammatory bowel disease (1.2), anterior uveitis (0.8), and injection site reactions (0.5) remained low. Efficacy demonstrated at Week 48 in BE AGILE was maintained or improved up to Week 156 (Figure 1). Mean ASDAS improved from 3.9 at BE AGILE baseline to 2.0 and 1.8 at Weeks 48 and 156 respectively (by MI). At Week 156 in the NRI analyses, ASAS40 and ASAS PR were achieved by 62.6% (OC: 72.6%) and 32.7% (OC: 37.9%) patients respectively. ASDAS-ID and ASDAS <2.1 responder rates (NRI) were maintained or continued to increase from Week 48, and by Week 156, responses were achieved by 28.0% (OC: 33.0%) and 57.1% (OC: 67.4%) patients respectively. ASDAS-MI responder rates (NRI) continued to increase from 44.9% at Week 48 to 46.5% at Week 156 (OC: 52.9%).Table 1.Safety for total exposure to BKZ across BE AGILE and the OLEBE AGILEWeeks 0–48BE AGILE + OLEWeeks 0–156n (%) [EAIR/100 PY]BKZ 160 mg(n=149;114.2 PY)BKZ 320 mg(n=150;119.6 PY)All BKZ(N=303;261.3 PY)All BKZ(N=303;781.0 PY)Any TEAE103 (69.1) [168.7]122 (81.3) [221.1]235 (77.6) [186.2]280 (92.4) [143.5]Serious TEAEs5 (3.4) [4.4]6 (4.0) [5.1]13 (4.3) [5.1]43 (14.2) [5.8]Key TEAEs of special monitoringSerious infections3 (2.0) [2.7]1 (0.7) [0.8]4 (1.3) [1.5]10 (3.3) [1.3]Candida infections10 (6.7) [9.1]9 (6.0) [7.9]19 (6.3) [7.5]28 (9.2) [3.8]Inflammatory bowel disease1 (0.7) [0.9]2 (1.3) [1.7]4 (1.3) [1.5]9 (3.0) [1.2]Anterior uveitis1 (0.7) [0.9]1 (0.7) [0.8]2 (0.7) [0.8]6 (2.0) [0.8]Study discontinuations due to TEAEs7 (4.7)10 (6.7)20 (6.6)38 (12.5)Drug-related TEAEs48 (32.2)54 (36.0)110 (36.3)149 (49.2)Deaths1 (0.7)01 (0.3)2 (0.7)TEAEs are reported for the BE AGILE safety set for total exposure to BKZ across BE AGILE and the OLE. There was one death in BE AGILE (cardiac arrest) and one in the OLE (road traffic accident); neither was considered treatment-related.Conclusion:The safety profile of BKZ in patients with AS was in line with previous observations.1.2 Patients treated with BKZ demonstrated sustained and consistent efficacy over 156 weeks.References:[1]van der Heijde D. Ann Rheum Dis 2020;79:595–604; 2. Baraliakos X. Arthritis Rheumatol 2020;72 (suppl 10).Acknowledgements:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Employee of: Director of Imaging Rheumatology, Atul Deodhar Speakers bureau: Janssen, Novartis, Pfizer, Consultant of: AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB Pharma, Lianne S. Gensler Consultant of: AbbVie, Eli Lilly, Gilead, GSK, Novartis, Pfizer, UCB Pharma, Grant/research support from: Pfizer, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GSK, MSD, Novartis, Pfizer, Samsung Bioepis, UCB Pharma, Grant/research support from: AbbVie, MSD, Novartis, Pfizer, Alan Kivitz Shareholder of: Pfizer, Novartis, Speakers bureau: Amgen, Eli Lilly, Pfizer, Novartis, Consultant of: Novartis, UCB Pharma, Maxime Dougados Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, Novartis, Pfizer, UCB Pharma, Natasha de Peyrecave Employee of: UCB Pharma, Marga Oortgiesen Employee of: UCB Pharma, Thomas Vaux Employee of: UCB Pharma, Carmen Fleurinck Employee of: UCB Pharma, Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma
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Okhawere, Kennedy E., Gediwon Milky, I.-Fan Shih, Yanli Li, and Ketan K. Badani. "Comparison of 1-Year Health Care Expenditures and Utilization Following Minimally Invasive vs Open Nephrectomy." JAMA Network Open 5, no. 9 (September 16, 2022): e2231885. http://dx.doi.org/10.1001/jamanetworkopen.2022.31885.
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ImportanceGiven the widespread adoption and clinical benefits of minimally invasive surgery approaches (MIS) in partial nephrectomy (PN) and radical nephrectomy (RN), assessment of long-term cost implications is relevant.ObjectiveTo compare health care utilization and expenditures within 1 year after MIS and open surgery (OS).Design, Setting, and ParticipantsThis cohort study was conducted using a US commercial claims database between 2013 and 2018. A total of 5104 patients aged 18 to 64 years who underwent PN or RN for kidney cancer and were continuously insured for 180 days before and 365 days after surgery were identified. An inverse probability of treatment weighting analysis was performed to examine differences in costs and use of health care services.ExposuresSurgical approach (MIS or OS).Main Outcomes and MeasuresOutcomes assessed included 1-year total health care expenditure, health care utilizations, and estimated days missed from work.ResultsOf the 5104 patients, 2639 had PN (2008 MIS vs 631 OS) and 2465 had RN (1816 MIS vs 649 OS) and most were male (PN: 1657 [62.8%]; RN: 399 [63.1%]) and between 55 and 64 years of age (PN: 1034 [51.3%]; RN: 320 [55.7%]). Patients who underwent MIS had lower index hospital length of stay compared with OS (mean [95% CI] for PN: 2.45 [2.37-2.53] vs 3.78 [3.60-3.97] days; P < .001; for RN: 2.82 [2.73-2.91] vs 4.62 [4.41-4.83] days; P < .001), and lower index expenditure for RN ($28 999 [$28 243-$29 796] vs $31 977 [$30 729-$33 329]; P < .001). For PN, index expenditure was lower for OS than MIS (mean [95% CI], $27 480 [$26 263-$28 753] vs $30 380 [$29614-$31 167]; P < .001). Patients with MIS had lower 1-year postdischarge readmission rate (PN: 15.1% vs 21.5%; odds ratio [OR], 0.65; 95% CI, 0.52-0.82; P < .001; RN: 15.6% vs 18.9%; OR, 0.79; 95% CI, 0.63-1.00; P = .05), and fewer hospital outpatient visits (mean [95% CI] for PN: 4.69 [4.48-4.90] vs 5.25 [4.84-5.66]; P = .01; RN: 5.50 [5.21-5.80] vs 6.71 [6.12-7.30]; P < .001) than those with OS. For RN, MIS was associated with 1.47 fewer missed workdays (95% CI, 0.57-2.38 days; P = .001). The reduction in health care use in MIS was associated with lower or similar total cumulative expenditures compared with OS (mean difference [95% CI] for PN: $331 [–$3250 to $3912]; P = .85; for RN: –$11 265 [–$17 065 to –$5465]; P < .001).Conclusions and RelevanceIn this cohort study, MIS was associated with lower or similar total cumulative expenditure than OS in the period 1 year after discharge from the index surgery. These findings suggest that downstream expenditures and resource utilization should be considered when evaluating surgical approach for nephrectomy.
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Kelvin, Joanne F., Bridgette Thom, Catherine Benedict, Jeanne Carter, Stacie Corcoran, Maura N. Dickler, Karyn A. Goodman, et al. "Cancer and Fertility Program Improves Patient Satisfaction With Information Received." Journal of Clinical Oncology 34, no. 15 (May 20, 2016): 1780–86. http://dx.doi.org/10.1200/jco.2015.64.5168.
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Purpose A cancer and fertility program was established at a large cancer center to support clinicians in discussing treatment-related fertility risks and fertility preservation (FP) options with patients and in referring patients to reproductive specialists. The program provides resources, clinician education, and fertility clinical nurse specialist consultation. This study evaluated the program’s impact on patient satisfaction with information received. Patients and Methods Retrospective cross-sectional surveys assessed satisfaction before (cohort 1 [C1]) and after (cohort 2 [C2]) program initiation. Questionnaires were investigator-designed, gender-specific, and anonymous. Results Most C1 (150 males, 271 females) and C2 (120 males, 320 females) respondents were 2 years postdiagnosis; the most frequently reported cancers were testicular, breast, and lymphoma. A significant difference in satisfaction with the amount of information received was seen between C1 and C2. For males, satisfaction with information on fertility risks was high in both cohorts but significantly greater in C2 for information on sperm banking (χ2 = 9.3, P = .01) and finding a sperm bank (χ2 = 13.3, P = .001). For females, satisfaction with information was significantly greater in C2 for information on fertility risks (χ2 = 62.1, P < .001), FP options (χ2 = 71.9, P < .001), help with decision making (χ2 = 80.2, P < .001), and finding a reproductive endocrinologist (χ2 = 60.5, P < .001). Among patients who received and read information materials, 96% of males and 99% of females found them helpful. Among C2 females, fertility clinical nurse specialist consultation was associated with significantly greater satisfaction with information on FP options (χ2 = 11.2, P = .004), help with decision making (χ2 = 10.4, P = .006), and finding a reproductive endocrinologist (χ2 = 22.6, P < .001), with 10% reporting lack of knowledge as a reason for not pursuing FP. Conclusion Improvements in patient satisfaction with information received demonstrate the potential for fertility programs in cancer care settings to improve the quality of clinician-patient discussions about fertility.
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Bracey, Daniel N., Tunc C. Kiymaz, David C. Holst, Kamran S. Hamid, Johannes F. Plate, Erik C. Summers, Cynthia L. Emory, and Riyaz H. Jinnah. "An Orthopedic-Hospitalist Comanaged Hip Fracture Service Reduces Inpatient Length of Stay." Geriatric Orthopaedic Surgery & Rehabilitation 7, no. 4 (August 19, 2016): 171–77. http://dx.doi.org/10.1177/2151458516661383.
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Introduction: Hip fractures are common in the elderly patients with an incidence of 320 000 fractures/year in the United States, representing a health-care cost of US$9 to 20 billion. Hip fracture incidence is projected to increase dramatically. Hospitals must modify clinical models to accommodate this growing burden. Comanagement strategies are reported in the literature, but few have addressed orthopedic-hospitalist models. An orthopedic-hospitalist comanagement (OHC) service was established at our hospital to manage hip fracture patients. We sought to determine whether the OHC (1) improves the efficiency of hip fracture management as measured by inpatient length of stay (LOS) and time to surgery (TTS) and (2) whether our results are comparable to those reported in hip fracture comanagement literature. Methods: A comparative retrospective–prospective cohort study of patients older than 60 years with an admitting diagnosis of hip fracture was conducted to compare inpatient LOS and TTS for hip fracture patients admitted 10 months before (n = 45) and 10 months after implementation (n = 54) of the OHC at a single academic hospital. Secondary outcome measures included percentage of patients taken to surgery within 24 or 48 hours, 30-day readmission rates, and mortality. Outcomes were compared to comanagement study results published in MEDLINE-indexed journals. Results: Patient cohort demographics and comorbidities were similar. Inpatient LOS was reduced by 1.6 days after implementation of the OHC ( P = .01) without an increase in 30-day readmission rates or mortality. Time to surgery was insignificantly reduced from 27.4 to 21.9 hours ( P = .27) and surgery within 48 hours increased from 86% to 96% ( P = .15). Discussion: The OHC has improved efficiency of hip fracture management as judged by significant reductions in LOS with a trend toward reduced TTS at our institution. Conclusion: Orthopedic-hospitalist comanagement may represent an effective strategy to improve hip fracture management in the setting of a rapidly expanding patient population.
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Niu, Nan, Fang Qiu, Tong Liu, Wenbin Guo, Guijin He, Yi Zhao, Yong Li, et al. "Primary analysis of MUKDEN 01: A multicenter, single-arm, prospective, phase 2 study of neoadjuvant treatment with pyrotinib and letrozole plus dalpiciclib in triple-positive breast cancer." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): 588. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.588.
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588 Background: Despite the use of multiple lines of targeted therapy has revolutionized treatment for HER2-positive breast cancer, these methods still have limited efficacy for triple-positive breast cancer (TPBC), which calls for persistent exploration for optimized treatment strategy. This MUKDEN-01 prospective trial aimed to evaluate the efficacy of oral, chemo-sparing neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib, which also meet the need for treatment convenience under COVID-19 pandemic, for patients with TPBC. Methods: The MUKDEN 01 was an investigator-initiated, multicentre, single arm, prospective phase II trial, which was performed at twelve hospitals in China(NCT04486911). Treatment-naïve patients with stage II-III tumors that according to the AJCC 8th edition criteria were eligible. Patients were treated with each cycle of 4 weeks with oral administration of pyrotinib 320 mg, and letrozole 2.5mg once daily for 4 weeks, and dalpiciclib 125 mg once daily for three weeks, followed by one week off, for five cycles. The primary endpoint was pathological complete response (pCR) in the breast and axilla (ypT0/is ypN0). Secondary endpoints included pCR in the breast (ypT0/is). residual cancer burden (RCB) score, Ki67 index change at surgery compared with baseline, and safety. Safety was analyzed in all patients, who received treatment. The study is still ongoing, and the enrollment has been completed. Results: Between June 20, 2020 and Sep. 6, 2021, 68 patients were screened for eligibility and 61 patients were recruited into this first stage of study. After surgery, 18 (29.5%, 95% CI 18.5-42.6) out of 61 patients achieving tpCR(ypT0/is ypN0), 21 (34.4%, 95% CI 22.7-47.7) patients achieved bpCR(ypT0/is). The patients with excellent pathologic response (RCB 0-1) to the combined therapy accounted for 54.1% (33/61, 95% CI 40.9-66.9). Mean Ki67 expression was reduced from 38.7% (95%CI: 31.3-46.0) at baseline to 19.3% (95% CI:13.6-25.0; p=0.0001) in the surgical samples. The most frequent grade 3 AE were neutropenia (35 [57%]), leukopenia (13 [21%]), diarrhea (9 [15%]) and oral mucositis (4 [7%]). There were five grade 4 neutropenia (8%) and one grade 4 increased AST (2%), but without other SAE and death throughout the study. Conclusions: Neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib yielded a pCR rate comparable to standard chemotherapy plus dual HER2 blockade in TPBC patients. The combined therapy was also well-tolerated and provided a chemo-sparing neoadjuvant approach for TPBC patients. To our knowledge, this is the first study to evaluate the therapeutic efficacy of a chemo-free neoadjuvant treatment with HER2 TKI pyrotinib and letrozole plus CDK4/6 inhibitor dalpiciclib for TPBC patients. Further validation in a large-scale randomized controlled trial is warranted. Clinical trial information: NCT04486911.
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Tortonese, D. J., and G. A. Lincoln. "Photoperiodic modulation of the dopaminergic control of pulsatile LH secretion in sheep." Journal of Endocrinology 143, no. 1 (October 1994): 25–32. http://dx.doi.org/10.1677/joe.0.1430025.
Full textAbstract:
Abstract This study was conducted to investigate whether the photoperiodic regulation of the seasonal changes in pulsatile LH secretion in the ram involves changes in the activity of inhibitory hypothalamic dopaminergic (DA) pathways. To test this hypothesis, a series of experiments was carried out in Soay rams in which the effects of a DA-D2 receptor antagonist (sulpiride) or a DA-D2 receptor agonist (bromocriptine) on the pulsatile secretion of LH were determined under both long and short days. In each experiment blood samples were collected every 10 min for 8 h starting at the time of vehicle, sulpiride or bromocriptine injections to assess concentrations of LH. Sulpiride (0·59 mg/kg, s.c.) administered to rams under long days induced an immediate and sustained increase in the secretion of LH that lasted for approximately 4 h (P<0·05; ANOVA); this LH response reflected both a rise in mean concentrations (0·247 ± 0·03 vs.0·452 ± 0·1 μg/1) and an increase in the frequency of LH pulses (0·5±0·5 vs. 2·33±0·42 pulses/8 h; P<0·01). In contrast, under short days sulpiride had no effect. Bromocriptine (0·06 mg/kg, s.c.) administered to rams under long days, when LH concentrations were low, was without effect, but when given to rams under short days significantly (P<0·05) suppressed mean LH concentrations (0·627 ±0·08 vs. 0·320 ± 0·02 μg/l) and LH pulse frequency (4·86 ±0·46 vs. 2·43 ±0·37 pulses/8 h). In an additional experiment, pimozide (total dose: 0·16 mg/kg, i.m.), a DA antagonist less specific for DA-D2 receptors than sulpiride, was ineffective in modifying LH secretion in sexually inactive rams exposed to long days. These results are consistent with the hypothesis that an inhibitory dopaminergic system is involved in the regulation of pulsatile LH secretion in the ram. The induced changes in LH pulse frequency under long days (increased by sulpiride) and under short days (decreased by bromocriptine) indicate that, under both photoperiods, DA acts within the hypothalamus, via a specific DA-D2 receptor, to influence pulsatile GnRH secretion. A photoperiodic-induced activation of this inhibitory system may therefore represent the mechanism whereby long days suppress LH secretion and lead to the sexually inactive state characteristic of the non-breeding season. Journal of Endocrinology (1994) 143, 25–32
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Hamid, Omid, Anja Williams, Juanita Suzanne Lopez, Daniel Olson, Takami Sato, Heather May Shaw, Claire Frances Friedman, et al. "Phase 1 safety and efficacy of IMC-F106C, a PRAME × CD3 ImmTAC bispecific, in post-checkpoint cutaneous melanoma (CM)." Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024): 9507. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.9507.
Full textAbstract:
9507 Background: IMC-F106C is a novel ImmTAC bispecific protein (PRAME × CD3). Dose escalation results showed robust T cell activation, T cell infiltration into tumor, and clinical activity in various solid tumors (NCT04262466; Hamid 2022). We present updated CM data from monotherapy (mono) and anti-PD1 combination (combo) cohorts. Methods: HLA-A*02:01+ unresectable/metastatic (m) CM patients (pts) previously treated with immune checkpoint inhibitors (ICI) were eligible. Primary objectives were safety and selection of recommended dose; additional objectives were efficacy and ctDNA response (Natera, Guardant). Stable disease (SD) with any tumor reduction confirmed with ≥ 1 subsequent scan was analyzed based on association with overall survival (OS) for tebentafusp. Molecular response was defined ≥ 0.5 log [68%] ctDNA reduction by week 9. PRAME was tested by immunohistochemistry (IHC; PRAME+ defined as H-score ≥1). Efficacy is presented by PRAME− and PRAME+ (documented + and unknown) groups. IMC-F106C dosed IV with 2 step-up doses and weekly target dose (20-320 mcg mono, 160 mcg combo). Pembrolizumab (pembro) dosed at IV 400 mg Q6W. Data cutoff: Dec 2023. Median follow-up of mono was 11 months. Results: 46 mCM pts (40 mono, 6 combo) received IMC-F106C ≥ 20 mcg. All mono pts received prior ICI (100% anti-PD1, 88% anti-CTLA4); 25% had prior BRAF/MEK inhibitors. 35/40 mono pts were grouped by IHC as positive (25 PRAME+, 10 unknown) vs. 5 PRAME−. Adverse events (AEs) were consistent with prior experience. Most common AE was Grade 1/2 CRS (50%); mostly in first 3 weeks. No drug related AEs led to treatment discontinuation or death. Safety for pembro combo to date was consistent with the individual agents. 31/40 mono pts had a RECIST evaluable tumor assessment. The clinical benefit rate (CBR) of PR + SD was 61% (19/31). 35% (11/31) had any tumor reduction that was confirmed on ≥ 1 subsequent scan, including 4 PR (ORR 13%) and 7 SD (26 of 31 pts were PRAME+; the CBR in these was 65% and included all 11 (42%) with confirmed tumor reduction. In 5 PRAME−, there was no tumor reduction. Both median progression free survival (PFS) and 6-month OS rates were higher in PRAME + vs –: 4.5 vs 2.1 months and 94% vs 40%, respectively. 12/40 mono pts received therapy for > 6 months and 14/40 mono pts remain on therapy. 41% of ctDNA-evaluable, PRAME+ mono pts had a molecular response (9/22); this was associated with longer PFS and OS. Correlative biomarkers will be shared. Conclusions: IMC-F106C was well tolerated with promising clinical activity in ICI-pretreated, mCM patients without clinical options. Clinical activity, measured by any confirmed tumor reduction and ctDNA molecular response, is enriched in PRAME+ patients at ~40% and associated with longer PFS and OS. IMC-F106C can be combined with anti-PD1. A Ph 3 trial of IMC-F106C with nivolumab in 1st line mCM has been initiated (PRISM-MEL301; NCT06112314). Clinical trial information: NCT04262466 .