Bibliografias temáticas / 302/.13

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Literatura científica selecionada sobre o tema "302/.13"

Autor: Grafiati
Publicado: 25 de julho de 2024
Última modificação: 31 de julho de 2024

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Artigos de revistas sobre o assunto "302/.13"

1

Benito, Juliana M., Volgin Y. Andrei, Ye Chen, Lu Hongbo, Yuexi Shi, Teresa McQueen, Patrick A. Zweidler-McKay et al. "Leukemia Microenvironment and Pathologic Hypoxia: Sensitivity to Hypoxia-Activated Cytotoxin TH-302". Blood 120, n.º 21 (16 de novembro de 2012): 1523. http://dx.doi.org/10.1182/blood.v120.21.1523.1523.

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Abstract Abstract 1523 We have recently demonstrated that the leukemic bone marrow (BM) niche is highly hypoxic and that hypoxia promotes resistance of leukemic cells to chemotherapy (Benito et al., PLoS One 2011, e23108). Our preliminary data indicate that AML cells surviving chemotherapy in the human xenograft mouse models of leukemia reside within hypoxic areas of BM microenvironment as documented by staining with the hypoxia marker CAIX. These findings support utility of hypoxia-activated pro-drugs with the goal to eliminate leukemic blasts and leukemic stem cells residing in hypoxic BM microenvironment. TH-302 is a 2-nitroimidazole linked bromo-isophosphoramide mustard cytotoxin that upon hypoxia-dependent activation induces DNA cross-linking. TH-302 exhibited potent hypoxia-selective anti-leukemia activity in pre-B ALL (REH, NALM6), AML (OCI-AML3, MOLM-13, KG-1) and CML cell lines (KBM5), with IC50s at 1% O2 ranging from 0.04μM to 2.3μM and hypoxia cytotoxicity ratio (HCR) ranging from 116 for KBM5 to 11 for REH cells. TH-302 at 5–7.5μM also exhibited hypoxia-dependent anti-leukemia activity in primary ALL and AML samples (N=3; normoxia, 2–8%; hypoxia, 28–65% apoptotic cells).To better recapitulate the multidimensional BM niche we utilized co-cultures of GFP-labeled leukemic cells with bone marrow-derived RFP-labeled mesenchymal stromal cells (MSC) immobilized within Matrigel. MSC and leukemic cells generated three-dimensional (3D) structures- “spheroids”- and co-proliferated over time with colonies of leukemic cells firmly attached to MSC, as monitored by confocal microscopy (Fig. 1). Pimonidazole staining shows that vast hypoxia is present in the MSC/AML spheroids grown at normal oxygen tension, in contrast to what is observed in plastic-based (2-D) stromal co-cultures. Anti-leukemia activity of TH-302 was next determined in 2D vs 3D co-cultures of MSCs plus MOLM-13 or OCI-AML3 cells. In 2D co-cultures, MSC protected MOLM-13 and OCI-AML3 cells from TH-302-induced cytotoxicity, while extensive apoptosis was documented in hypoxic spheroid co-cultures (at 50nM TH-302, reduction in viability 10–15% vs >60%, Fig. 1). These findings suggest that culture conditions faithfully mimicking BM microenvironment promote pathologic hypoxia generated by rapidly proliferating AML cells, which in turn leads to their increased sensitivity to hypoxia-activated cytotoxins. To validate these findings in vivo, we next tested anti-leukemia efficacy of TH-302 in the in vivo model of primary AML established in NSG mice. TH-302 (50 mg/kg IP 3 times a week for three weeks) reduced the number of circulating AML cells (control, 13.2+/−5.7 ×106/ml; TH-302, 2.5+/−2.1 ×106/ml) and prolonged survival of NSG mice engrafted with primary AML cells compared to the vehicle treated mice (median survival time: TH-302=75 days; Control=56 days; P=0.003, n= 8 mice/group). To test the ability of hypoxia-activated prodrug to target leukemia-initiating cells, secondary transplant experiments were performed in which BM cells from control or TH-302 treated mice (collected after two weeks of therapy) were serially diluted and injected into secondary NSG recipient mice at 0.01, 0.005 or 0.0001×106̂ cells/mouse (N=5 mice/dilution). Although all mice transplanted with higher cell doses died from leukemia, we observed significantly prolonged survival of animals injected with 0.01×106 cells from TH-302-treated primary recipients compared with vehicle-treated controls (median survival control=68 days; TH-302=79 days; P=0.0031) or with 0.005×106 cells (control=79 days; TH-302=83 days; P=0.0462). In summary, our findings suggest that pathologic hypoxia is a prevalent condition of leukemic BM microenvironment that promotes survival of leukemic blasts and leukemia-initiating cells. The results support targeting hypoxia with hypoxia-activated cytotoxins such as TH-302 to enhance the efficacy of therapeutic regimens in AML. A Phase 1 single agent clinical trial of TH-302 in patients with relapsed/refractory hematologic malignancies is ongoing. Figure 1. Spheroids of MSCs and MOLM-13 cells were incubated with or without TH-302 for 72hr. Effect on cell viability was determined by WST-1 assay. Figure 1. Spheroids of MSCs and MOLM-13 cells were incubated with or without TH-302 for 72hr. Effect on cell viability was determined by WST-1 assay. Disclosures: Handisides: Threshold Pharmaceuticals: Employment. Hart:Threshold Pharmaceuticals: Employment. Konopleva:Threshold Pharmaceuticals: Research Funding.
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Wunder, Gerd, e Hans-Werner Goetz. "Rezension von: Goetz, Hans-Werner, Leben im Mittelalter". Württembergisch Franken 72 (2 de novembro de 2023): 381. http://dx.doi.org/10.53458/wfr.v72i.8223.

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Trierveiler-Pereira, Larissa, Matthew E. Smith, James M. Trappe e Eduardo R. Nouhra. "Sequestrate fungi from PatagonianNothofagusforests:Cystangium(Russulaceae, Basidiomycota)". Mycologia 107, n.º 1 (janeiro de 2015): 90–103. http://dx.doi.org/10.3852/13-302.

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Thomae, Heike. "Anmerkung zu Niedersächsisches OVG, Urt. v. 16.7.2020 – 13 LC 302/19 (VG Braunschweig)". Medizinrecht 39, n.º 2 (fevereiro de 2021): 174. http://dx.doi.org/10.1007/s00350-021-5800-7.

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Ahmed, Ahmed, Tariq Arshad e Stephen Neidle. "Abstract A079: The quadruplex-binding compound QN-302 in the MIA-PaCa2 pancreatic adenocarcinoma model shows no evidence of cardiac or neurological liabilities at therapeutic doses". Cancer Research 82, n.º 22_Supplement (15 de novembro de 2022): A079. http://dx.doi.org/10.1158/1538-7445.panca22-a079.

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Abstract The human genome contains multiple sites of quadruplex (G4) arrangements, with over-representation in promoter regions of many oncogenes. Small molecule G4 stabilization down-regulates the transcription of these genes, leading to selective inhibition of cancer cell growth and anti-tumor activity. We have developed a number of novel G4-binding small molecules. QN-302, the most potent, has significant in vivo activity in animal models for pancreatic cancer and is currently in pre-clinical development with Qualigen Therapeutics. The effects of QN-302 have been examined on (1) a panel of cardiac function receptors, (2) heart rate in vivo, and (3) on the histopathology of organs from treated animals. QN-302 was initially screened in a series of in vitro industry-standard CEREP receptor binding assays. The few apparent indications of significant receptor binding were examined in vivo by means of ELISA assays. Cardiac function was examined using a cardiac heart-beat monitor attached to animals treated with QN-302 and compared to animals dosed with a vehicle control. QN-302 gave negative results in CEREP assays, apart from micromolar inhibition of acetylcholinesterase (ACE) and muscarinic (MUSC) receptors. There was no significant hERG receptor inhibition. There was no significant inhibition of ACE and MUSC receptors in vivo. Heart rate experiments, run at both the proposed therapeutic dose of 1mg/kg and at elevated levels, did not show significant deviations from values for the vehicle control arm. Histopathology of heart, liver and brain tissues from QN-302 treated animals, did not show any deleterious effects from the drug. The lack of effects on ACE and MUSC receptors in vivo, together with the absence of effects on heart, liver and brain tissue from treated animals and the normality of heart rate during treatment, demonstrate that treatment of MIA-Paca2 tumor-bearing mice with QN-302 does not have a cardio-, nephro- or neurotoxic burden at therapeutic doses. QN-302 is bio-available at therapeutic doses and is currently in pre-clinical development with Qualigen Therapeutics Inc Citation Format: Ahmed Ahmed, Tariq Arshad, Stephen Neidle. The quadruplex-binding compound QN-302 in the MIA-PaCa2 pancreatic adenocarcinoma model shows no evidence of cardiac or neurological liabilities at therapeutic doses [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A079.
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Kim, Byung-Wook, Younghee Choe, Tae Ho Kim, Jun-Won Chung e Joon Sung Kim. "Optimal interval of surveillance gastroscopy after endoscopic resection for gastric neoplasia: A multicenter cohort study." Journal of Clinical Oncology 41, n.º 4_suppl (1 de fevereiro de 2023): 316. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.316.

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316 Background: Due to the possibility of metachronous recurrence of gastric neoplasia, surveillance gastroscopy is mandatory after endoscopic resection (ER) for gastric neoplasia. However, there is no consensus on the surveillance gastroscopy interval. This study aimed to find an optimal interval of surveillance gastroscopy and to investigate the risk factors for metachronous gastric neoplasia (MGN). Methods: Medical records were reviewed retrospectively in patients who underwent ER for gastric neoplasia in 3 teaching hospitals from June 2012 to July 2022. Patients were divided into 2 groups; annual surveillance vs. biannual surveillance. The incidence of MGN was identified, and the risk factors for MGN were investigated. Results: Among the 1,533 patients, 677 patients were included (annual surveillance 302, biannual surveillance 375). The median follow-up for all patients was 22 (range, 12‒91) months. MGN was observed in 61 patients and metachronous gastric cancer (MGC) in 26 patients, both of which were not significantly different between the annual and biannual surveillance groups (annual vs. biannual: 26/302 vs. 32/273, P=0.989 in MGN; 13/302 vs. 13/373, P=0.582 in MGC). All the lesions were removed by ER successfully. In a multivariate analysis, severe atrophic gastritis on endoscopy was an independent risk factor for MGC (odds ratio 3.8, 95% confidence interval 1.4‒10.1; P=0.008). H. pylori infection was not a significant risk factor in this study. Conclusions: Meticulous observation is necessary for patients with severe atrophic gastritis during follow-up gastroscopy after ER for gastric neoplasia. Annual surveillance gastroscopy might be enough after ER for gastric neoplasia.
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Ahmed, Ahmed, William Greenhalf, Tariq Arshad e Stephen S. Neidle. "Abstract B030: The quadruplex-binding compound QN-302 targets the S100P gene in PDAC". Cancer Research 82, n.º 22_Supplement (15 de novembro de 2022): B030. http://dx.doi.org/10.1158/1538-7445.panca22-b030.

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Abstract The compound QN-302, a tetra-substituted naphthalene diimide derivative has been previously disclosed to have single-digit nM anti-proliferative activity in a panel of human pancreatic ductal adenocarcinoma (PDAC) cell lines (Ahmed et al., ACS Med Chem Lett, 2020, 11, 1634-1644). It also has significant anti-tumor activity in the MIA-PACA2 xenograft model for PDAC as well as in the more demanding KPC model. Its novel mode of action involves the targeting of quadruplex (G4)-forming motifs in promoter regions of cancer-associated genes, where their prevalence is over-represented compared to other genes. The presence of a promoter G4 motif, stabilized by a ligand, presents an effective block to transcription. Transcriptome analyses of QN-302 in MIA-PACA2 cells has validated this concept, with the disclosure of a pattern of down-regulated genes involved in cancer-associated pathways and carrying G4 motifs in their promoters. We have also previously shown using RT-PCR and Western blots that a sub-set of these genes and their gene products are down-regulated in the MIA-PACA2 xenograft model following QN-302 treatment. We have now examined cellular changes in the expression of the 229 gene set associated with PDAC and compared these with data from cells and xenografts treated with QN-302. We find that expression of the key gene S100P, a prominent and well-authenticated marker of PDAC disease and progression, is highly down-regulated in QN-302 treated cells. The S100P gene contains 31 putative G4 motifs, including a classic G4 site in the S100P promoter, just upstream of the transcription start site. Transcriptome analyses have also been performed on tumor material from human patients, comprising a panel of poorly differentiated as well as more highly differentiated tumors, and has been compared with normal pancreas expression data. The S100P gene is statistically significantly highly over-expressed (especially in the poorly differentiated tumors), giving added confidence to the concept that the S100P gene is a therapeutic target and may also be useful as a marker of QN-302 response in future clinical use. We also find that the anti-tumor effect of QN-302 treatment in PDAC xenografts results in a high level of apoptosis, which is consistent with earlier reports that S100P in tumors binds to and suppresses p53 activity. The suppression of S100P transcription by QN-302 would thus be expected to remove this roadblock to apoptosis and cell death, in accordance with our observations. QN-302 is bio-available at therapeutic doses and is well tolerated at these levels in these animal models. It is being developed for clinical evaluation by Qualigen Therapeutics Inc and is currently at the pre-IND stage. Citation Format: Ahmed Ahmed, William Greenhalf, Tariq Arshad, Stephen S. Neidle. The quadruplex-binding compound QN-302 targets the S100P gene in PDAC [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B030.
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Makimoto, Hisaki, Roland Richard Tilz, Tina Lin, Andreas Rillig, Shibu Mathew, Sebastian Deiss, Erik Wissner et al. "Incidence and Anatomical Locations of Catheter Instability During Circumferential Pulmonary Vein Isolation Using Contact Force". International Heart Journal 55, n.º 3 (2014): 249–55. http://dx.doi.org/10.1536/ihj.13-302.

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Matsuoka, Hideaki, Koichiro Nakano, Norimasa Takatani, Tomonori Yoshida, Shizunobu Igimi e Mikako Saito. "Flow Cytometric Method for in situ Preparation of Standard Materials of a Small Defined Number of Microbial Cells with Colony-Forming Potentiality". Journal of AOAC INTERNATIONAL 97, n.º 2 (1 de março de 2014): 479–83. http://dx.doi.org/10.5740/jaoacint.13-302.

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Abstract Standard materials of a small defined number of cells with colony-forming potentiality are essential for the rational validation of food microbiological methods. An in situ flow cytometric method using viable staining with 6-carboxyfluorescein diacetate (CFDA) and tryptic soy agar (TSA) was previously proposed and its feasibility was demonstrated with five strains. In this study, this method was applied to 16 strains to support its broad applicability. The cellsorting gate was previously determined based on the CFDA stainability alone. Now the structural properties of cells designated by forward and side-scattering intensities have been introduced as the second gating criteria. Under the optimum gate condition, 100 cells have been selected and sorted on TSA. Consequently, a 95% or higher colony-forming rate has been attained for every strain. A successful application to microaerophilic Campylobacter spp. is especially of great importance because it suggests further broader applicability.
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Bendell, J. C., G. J. Weiss, J. R. Infante, E. G. Chiorean, M. Borad, R. Tibes, S. F. Jones, V. K. Langmuir, S. Kroll e H. A. Burris. "Final results of a phase I study of TH-302, a hypoxia-activated cytotoxic prodrug (HAP)". Journal of Clinical Oncology 27, n.º 15_suppl (20 de maio de 2009): 2573. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.2573.

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2573 Background: TH-302 is a 2-nitroimidazole prodrug of the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM). TH-302 is essentially inactive under normoxia but in severe hypoxia and in the presence of certain reductases, it is reduced and Br-IPM is released. Methods: Eligible patients (pts) had ECOG ≤1, advanced or metastatic solid tumors, evaluable by RECIST, and acceptable hematologic, liver and renal function. A modified accelerated titration design was used. TH-302 was administered intravenously over 30–60 minutes on Day 1, 8 and 15 of a 28-day cycle. CT scans were obtained after every 2 cycles. Detailed pharmacokinetic sampling was performed on Days 1 and 15. The primary objectives of this study were to determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). Results: Twenty-nine pts enrolled at 3 sites at 9 dose levels from 7.5–670 mg/m2. Median age: 64y. 20 male/9 female. ECOG 0/1: 16/13. Primary tumor: prostate (8), colorectal (8), lung (5) other (8). Two of 5 pts at 670 mg/m2 had DLT: Herpes simplex perianal/rectal ulcers and dehydration due to mucositis. Reversible skin and mucosal adverse events (AE) occurred in 12 of 15 (80%) pts at ≥480 mg/m2 including grade 3 events in 3 pts. The most common TH-302-related AEs were nausea, skin lesions, vomiting and fatigue. Hematologic toxicity was mild and limited: two pts with grade 1 and one pt with grade 2 neutropenia and five pts with grade 1 thrombocytopenia. Five pts had grade 3 and one grade 4 lymphopenia. Four pts have enrolled at an intermediate dose of 575 mg/m2 with no DLT so this is likely the MTD and is well above the predicted biologic effective dose of 100 mg/m2. One pt with SCLC treated at 480 mg/m2 and one with melanoma treated at 670 mg/m2 had unconfirmed partial responses; 12 pts had stable disease (6 continuing after 4 or more cycles), 7 had PD, 4 were unevaluable and 4 are too early to assess. Cmax and AUC for TH-302 and Br-IPM increased linearly with no accumulation at Day 15. Conclusions: Weekly TH-302 has remarkably little hematologic toxicity. Skin and mucosal AEs have developed at the higher dose levels. Skin/mucosa are known to have hypoxic regions. TH-302 is the first HAP to demonstrate tumor responses in Phase I. The MTD is likely 575 mg/m2. Studies in combination with chemotherapy are ongoing. [Table: see text]
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Livros sobre o assunto "302/.13"

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United States. Congress. House. Committee on the Budget., ed. Report of the Committee on the Budget, House of Representatives: Pursuant to section 13 of S. Con. Res. 120, concurrent resolution on the budget--fiscal year 1987, 302(a) allocations. Washington: U.S. G.P.O., 1986.

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United States. Congress. House. Committee on the Budget., ed. Report of the Committee on the Budget, House of Representatives: Pursuant to section 13 of H. Con. Res. 93, concurrent resolution on the budget, fiscal year 1988, 302(a) allocations. Washington: U.S. G.P.O., 1987.

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3

Strong, Janet Adams, 1951- author, ed. Hearst Magazine Building, 951-69 Eighth Avenue/301-13 West 56th Street/302-12 West 57th Street, Borough of Manhattan: Built 1927-28; architects, Joseph Urban and George B. Post & Sons. New York, N.Y.]: Landmarks Preservation Commission, 1988.

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1973-, Heath Dan, ed. Made to stick: Why some ideas survive and others die. New York: Random House, 2007.

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House, United States Congress, ed. Report on subdivision of budget totals agreed to in the Concurrent Resolution on the budget (S. Con. Res. 120) for fiscal year 1987: Pursuant to section 302(b)(2) of the Congressional Budget and Impoundment Control Act of 1974, as amended, and section 13 of the joint explanatory statement of the committee of conference on S. Con. Res. 120 (Report 99-666). Washington: U.S. G.P.O., 1986.

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6

United States. Congress. House. Committee on Foreign Affairs. Consideration of miscellaneous bills and resolutions: Full committee markup before the Committee on Foreign Affairs, House of Representatives, One Hundred Third Congress, second session, on H. Res. 323, H. Con. Res. 180, H. Con. Res. 124, H.R. 3813, H.R. 4429, H. Con. Res. 111, H.R. 4635, H.J. Res. 388, H. Res. 476, H. Res. 471, H. Con. Res. 151, H.R. 2826, S.J. Res. 204, proposed legislative language to implement the Uruguay Round, H. Con. Res. 250, H.R. 5030, H.R. 5034, H.R. 4541, H. Con. Res. 257, H.R. 4950, H.R. 5108, H. Con. Res. 286, H. Con. Res. 279, H.R. 5155, H. Con. Res. 302, H. Res. 561, S. Con. Res. 74, H. Con. Res. 216, H. Con. Res. 278, and H. Res. 560, January 25, February 9, March 16, May 18, June 23, July 19, August 3, September 13 and 28, and October 3, 1994. Washington: U.S. G.P.O., 1994.

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7

Rational choice. Cambridge, MA: MIT Press, 2010.

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De Giusti, Armando, Guillermo Simari e Patricia Pesado, eds. Computer Science & Technology Series. Editorial de la Universidad Nacional de La Plata (EDULP), 2013. http://dx.doi.org/10.35537/10915/58940.

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CACIC’12 was the eighteenth Congress in the CACIC series. It was organized by the School of Computer Science and Engineering at the Universidad Nacional del Sur. The Congress included 13 Workshops with 178 accepted papers, 5 Conferences, 2 invited tutorials, different meetings related with Computer Science Education (Professors, PhD students, Curricula) and an International School with 5 courses. CACIC 2012 was organized following the traditional Congress format, with 13 Workshops covering a diversity of dimensions of Computer Science Research. Each topic was supervised by a committee of 3-5 chairs of different Universities. The call for papers attracted a total of 302 submissions. An average of 2.5 review reports were collected for each paper, for a grand total of 752 review reports that involved about 410 different reviewers. A total of 178 full papers, involving 496 authors and 83 Universities, were accepted and 27 of them were selected for this book.
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Report of the Committee on the Budget, House of Representatives: Pursuant to section 13 of H. Con. Res. 93, concurrent resolution on the budget, fiscal year 1988, 302(a) allocations. Washington: U.S. G.P.O., 1987.

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10

Report of the Committee on the Budget, House of Representatives: Pursuant to section 13 of S. Con. Res. 120, concurrent resolution on the budget--fiscal year 1987, 302(a) allocations. Washington: U.S. G.P.O., 1986.

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Capítulos de livros sobre o assunto "302/.13"

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"13 La Pensée sérielle dans le théâtre de Calderón 302". In La pensée sérielle, du Moyen Age aux Lumières, 302–15. Brill | Rodopi, 2018. http://dx.doi.org/10.1163/9789004386006_015.

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Zubchenko, O. S. "Sociological aspects of military occupation (on the example of Southern Ukraine)". In MILITARY OFFENCES AND WAR CRIMES: BACKGROUND, THEORY AND PRACTICE, 294–315. Izdevnieciba “Baltija Publishing”, 2023. http://dx.doi.org/10.30525/978-9934-26-302-6-13.

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Fried, Johannes. "13. Um Deutschland ist mir gar nicht bang: Jetzt und heute". In Die Deutschen, 302–23. Verlag C.H.BECK oHG, 2018. http://dx.doi.org/10.17104/9783406720390-302.

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Taber, Douglass F. "Preparation of Substituted Benzenes: The Beaudry Synthesis of Arundamine". In Organic Synthesis. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190646165.003.0064.

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Stephen G. DiMagno of the University of Nebraska developed (Chem. Eur. J. 2015, 21, 6394) a protocol for the clean monoiodination of 1 to 2. The bromomethylation (or chloromethylation, with HCl) of a benzene derivative is straightforward with formal­dehyde and HBr. Naofumi Tsukada of Shizuoka University designed (Organometallics 2015, 34, 1191) a Cu catalyst that mediated the coupling of an alkyne with the benzyl bromide so produced, effecting net propargylation of 3 with 4 to give 5. Triazenes such as 7, versatile intermediates for organic synthesis, are usually prepared by diazotization of the corresponding aniline. Kay Severin of the Ecole Polytechnique Fédérale de Lausanne established (Angew. Chem. Int. Ed. 2015, 54, 302) an alternative route from the aryl Grignard reagent 6. Ping Lu and Yanguang Wang of Zhejiang University showed (Chem. Commun. 2015, 51, 2840) that dimethylformamide could serve as the carbon source for the conversion of 8 to the nitrile 9. Junha Jeon of the University of Texas at Arlington effected (J. Org. Chem. 2015, 80, 4661; Chem. Commun. 2015, 51, 3778) the reductive ortho silylation of 10 to give 11. Vladimir Gevorgyan of the University of Illinois at Chicago found (Angew. Chem. Int. Ed. 2015, 54, 2255) that the phenol derivative 12 could be ortho carboxylated, leading to 13. Lutz Ackermann of the Georg-August-Universität Göttingen, starting (Chem. Eur. J. 2015, 21, 8812) with the designed amide 14, effected ortho metala­tion followed by coupling, to give the methylated product 15. Tetsuya Satoh and Masahiro Miura of Osaka University used (Org. Lett. 2015, 17, 704) the dithiane of 16 to direct ortho metalation. Coupling with acrylate followed by reductive desulfu­rization led to the ester 17. Jin-Quan Yu of Scripps/La Jolla designed (Angew. Chem. Int. Ed. 2015, 54, 888) the phenylacetamide 18 to direct selective meta metalation, leading to the unsat­urated aldehyde 19. In an extension of the Catellani protocol, Guangbin Dong of the University of Texas prepared (J. Am. Chem. Soc. 2015, 137, 5887) the biphenyl 21 by net meta metalation of the benzylamine 20. Several methods for the de novo assembly of benzene derivatives have recently been put forward. Rajeev S. Menon of the Indian Institute of Chemical Technology condensed (Org. Lett. 2015, 17, 1449) the unsaturated aldehyde 22 with the sulfonyl ester 23 to give 24.
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"Bastiaan C.J. Zoeteman, Wouter C. Kersten, Wiebe F. Vos, Lieke van de Voort and Ben J.M. Ale (2010), 'Communication Management during Risk Events and Crises in a Globalised World: Predictability of Domestic Media Attention for Calamities', Journal of Risk Research, 13, pp. 279-302". In Emergency Policy, 223–46. Routledge, 2017. http://dx.doi.org/10.4324/9781315256641-22.

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Trabalhos de conferências sobre o assunto "302/.13"

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Scheff, Jerry J., e Roger H. L. Chen. "Bridge Decks Inspection Using Chain Drag and Ground Penetrating Radar". In Engineering Mechanics Conference 2000. Reston, VA: American Society of Civil Engineers, 2000. http://dx.doi.org/10.1061/40495(302)13.

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Souza, Guilherme, Julian Santos, Gabriel SantClair, Janaina Gomide e Luan Santos. "A Comparative Analysis of Countries' Performance According to SDG Indicators based on Machine Learning". In Encontro Nacional de Inteligência Artificial e Computacional. Sociedade Brasileira de Computação - SBC, 2021. http://dx.doi.org/10.5753/eniac.2021.18248.

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The Sustainable Development Goals (SDGs) are part of a global effort to reduce the impacts of climate change, promoting social justice and economic growth. The United Nations provides a database with hundreds of indicators to track the SDGs since 2016 for a total of 302 regions. This work aims to assess which countries are in a similar situation regarding sustainable development. Principal Component Analysis was used to reduce the dimension of the dataset and k-means algorithm was used to cluster countries according to their SDGs indicators. For the years of 2016, 2017 and 2018 were obtained 11, 13 and 11 groups, respectively. This paper also analyses clusters changes throughout the years.
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3

Romanenko, O. G., S. B. Kislitsin, O. P. Maksimkin, Sh B. Shiganakov, Ye V. Chumakov e I. V. Dumchev. "The Application of Structural Materials Data From the BN-350 Fast Reactor to Life Extension of Light Water Reactors". In 14th International Conference on Nuclear Engineering. ASMEDC, 2006. http://dx.doi.org/10.1115/icone14-89028.

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This paper describes the results of investigations of 08Cr16Ni11Mo3 (AISI 316 steel analogue) austenitic stainless steel irradiated in BN-350 breeder reactor at irradiation conditions close to that for Light Water Reactor (LWR) Internals. The pores were found in 08Cr16Ni11Mo3 steel irradiated at temperature 280°C up to rather low damage 1.3 dpa and with dose rate 3.9×10−9 dpa/s. There were obtained dose rate dependencies of yield strength, ultimate strength and ductility for 08Cr16Ni11Mo3 steel irradiated up to 7–13 dpa at 302–311°C. These dependencies show a decrease in both yield strength and ultimate strength when dose rate decreases. There was observed an apparent decrease in total elongation when dose rate decreases, which was presumably connected with the pores formation in the steel at low dose rates.
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4

Lishchenko, Pavel, Maria Draganskaya e Inna Savvicheva. "Assessment of grain productivity and adaptability yellow lupine on soddy-podzol sandy soil". In Multifunctional adaptive feed production 27 (75). ru: Federal Williams Research Center of Forage Production and Agroecology, 2022. http://dx.doi.org/10.33814/mak-2022-27-75-52-59.

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The article presents the results of a comparative assessment of grain productivity and adaptability indicators of various varieties of yellow lupine cultivated on soddy-podzolic sandy soil. We studied 8 varieties of lupine of domestic selection of the All-Russian Research Institute of Lupine, Novozybkovskaya SHOS; neighboring countries - Belarus and foreign selection (Germany), as well as the hybrid material of the Novozybkovskaya SHOS for 2016–2020. The adaptability of variety samples was comprehensively tested in terms of environmental stability and plasticity, using the criterion of "yield". Changes in meteorological conditions over the years of research made it possible to objectively assess the variation in the productivity of lupine by grain. For five years of testing, the grain yield varied from 6.4 c/ha Vladko (Belarus) to 11.8 c/ha, Novozybkovsky 100 (Novozybkovskaya SHOS). On average, changes in the productivity of varieties of VNII lupine from 9.7 to 11.3 c/ha, Novozybkovskaya SHOS – 10.7–11.8 c/ha, Belarusian breeding – 6.4–9.1 c/ha, foreign – 8.3–8.7 q/ha. Samples 5-10-84 (13.2 c/ha), 1-08-7-75 and 2-13-33 (12.7 c/ha) and 7-13-65 (12,5 q/ha). According to the set of indicators of adaptability, the All-Russian Research Institute of Lupine Nadezhny and Bulat turned out to be the best among the varieties; Belarusian selection Kastrychnik; Novozybkovskoy SHOS – Druzhny 165 and Novozybkovsky 100. From the hybrid material of the Novozybkovskaya SHOS promising numbers 1-08-7-75, 5-10-84, 4-12-302, 2-13-33, which have genetic flexibility, adaptability and stability in conditions of sandy and sandy loamy soils of the South-West of the Bryansk region.
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5

Федоренко, М. В. "Становлення української системи державної служби за часів державницької роботи В. І. Вернадського в Україні (1917–1921)". In І МІЖНАРОДНА НАУКОВО-ПРАКТИЧНА КОНФЕРЕНЦІЯ ТАВРІЙСЬКОГО НАЦІОНАЛЬНОГО УНІВЕРСИТЕТУ ДО 160-РІЧНИЦІ ВІД ДНЯ НАРОДЖЕННЯ В. І. ВЕРНАДСЬКОГО. ЧАСТИНА 1. Liha-Pres, 2023. http://dx.doi.org/10.36059/978-966-397-302-9-13.

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6

Ковальчук, В. І. "РОЛЬ ПЕДАГОГА В УМОВАХ ЦИФРОВІЗАЦІЇ". In I Міжнародна науково–практична конференція «Інноваційні рішення в сучасній науці, освіті та практиці». Національний транспортний університет, 2020. http://dx.doi.org/10.33744/978-966-632-302-9-2020-13-15.

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7

Poeppelmann, M. "“Hinterm Horizont geht’s weiter”: Auszeit für verwaiste Familien auf der ostfriesischen Insel Spiekeroog [302]". In 13. Kongress der Deutschen Gesellschaft für Palliativmedizin. © Georg Thieme Verlag KG, 2020. http://dx.doi.org/10.1055/s-0040-1715271.

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8

Miller, Kathy, Patricia M. LoRusso, Pamela Munster, Ian Krop, Cynthia Ma, Helen Lee, Joe Reynolds et al. "Abstract P4-15-04: Effect of pre-treatment with cyclophosphamide on MM-302 (HER2-targeted liposomal doxorubicin) deposition in HER2-positive metastatic breast cancer patients assessed by64Cu-MM-302 PET/CT". In Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, TX. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.sabcs14-p4-15-04.

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9

Vinatoru, Mircea. "MICROWAVE AND ULTRASOUNDS TOGETHER – A CHALLENGE". In Ampere 2019. Valencia: Universitat Politècnica de València, 2019. http://dx.doi.org/10.4995/ampere2019.2019.9822.

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The literature related to microwave and ultrasound working simultaneously is rather infrequent. The reason is obvious: microwave irradiation is of electromagnetic origin while ultrasound is a mechanical vibration energy. Moreover, the optimal settings for ultrasound propagation throughout a reaction media do not coincide with the conditions required for application of microwaves. Therefore, the challenge is to find a way to best combination of these sources of energy into one apparatus to allow researchers to take advantage of the features of each technology. The oldest paper describing such a combination – microwave and ultrasound is having just 20 years [1] and describe an apparatus which uses a probe system delivering ultrasound through decalin to a vessel holding the reagents dipped in the MW cavity (fig. 1a). Another possibility using a normal MW oven is described by Peng [2] (fig.1b), but this setup is having radiation leakage problems and needs a proper protection. Ragaini et all proposed another type of setup [3] (fig. 1c), not easy to reproduce, but describing calibration and parameters which show an additive increase of thermal energy delivered when MW and US works simultaneous. Insert here uploaded pictures Figure 1. Some MW-US simultaneous setups Few years ago, Cravotto and Cintas [4], disccussed for the first time the potential of using MW and US in sequential or tandem setups. Their paper discuss all possible setups for using mostly glass probe for devlivery of ultrasonic energy or classical setup (fig. 1a). Slowly the concept gain popularity and the paper of Lionelly and Mason [5] prompts to the potential industrial applications, naming the combination of microwave with ultrasound a hybrid technology. The challenge in using this “hybrid technology” is to find a vesatile and reproducible apparatus able to deliver both microwave and ultrasound at a full controlable parameters. In our laboratory we have and use the setup like in the fig. 1a, but the ultrasonic energy is delivered by an ultrasonic cleaning device attached to microwave device (SAIREM Miniflow 200SS). To achieve the above mentioned outcome launched a project to build a device which could work with MW and US in tandem (as Cravotto mentioned [4]) using an US device able to deliver more than a single ultrasonic frequency at a full controlled power. It is our believe that such a device could significantly contribute to MW-US tandem equipment development. Based on our expertise and potential proposed interaction of US with reagents [6] we will investigate the influence (if any) of ultrasound upon MW field. In this paper we will present the earlier results of “Tandem Microwave Ultrasound” energy influence on chemical reagents. References 1. Lagha, A., et al., Analusis, 1999. 27(5): p. 452-457. 2. Peng, Y. and G. Song, Green Chemistry, 2001. 3(6): p. 302-304. 3. Ragaini, V., et al., Ultrasonics Sonochemistry, 2012. 19(4): p. 872-876. 4. Cravotto, G. and P. Cintas, Chemistry - A European Journal, 2007. 13(7): p. 1902-1909. 5. Leonelli, C. and T.J. Mason, Chemical Engineering and Processing: Process Intensification, 2010. 49(9): p. 885-900. 6. Vinatoru, M. and T.J. Mason, Ultrasonics Sonochemistry, 2018.
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10

Starodub, Alexander, Daniel Vaena, Kenneth L. Pennington, Ebenezer A. Kio, Daniel Bruetman, Tracy Thorne, Stewart Kroll e Mohammed M. Milhem. "Abstract B77: Phase I study of TH-302, an investigational hypoxia-targeted drug, in combination with sunitinib." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-b77.

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Relatórios de organizações sobre o assunto "302/.13"

1

McDonagh, Marian S., Jesse Wagner, Azrah Y. Ahmed, Rongwei Fu, Benjamin Morasco, Devan Kansagara e Roger Chou. Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain. Agency for Healthcare Research and Quality (AHRQ), outubro de 2021. http://dx.doi.org/10.23970/ahrqepccer250.

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Objectives. To evaluate the evidence on benefits and harms of cannabinoids and similar plant-based compounds to treat chronic pain. Data sources. Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Library, and SCOPUS® databases, reference lists of included studies, submissions received after Federal Register request were searched to July 2021. Review methods. Using dual review, we screened search results for randomized controlled trials (RCTs) and observational studies of patients with chronic pain evaluating cannabis, kratom, and similar compounds with any comparison group and at least 1 month of treatment or followup. Dual review was used to abstract study data, assess study-level risk of bias, and rate the strength of evidence. Prioritized outcomes included pain, overall function, and adverse events. We grouped studies that assessed tetrahydrocannabinol (THC) and/or cannabidiol (CBD) based on their THC to CBD ratio and categorized them as high-THC to CBD ratio, comparable THC to CBD ratio, and low-THC to CBD ratio. We also grouped studies by whether the product was a whole-plant product (cannabis), cannabinoids extracted or purified from a whole plant, or synthetic. We conducted meta-analyses using the profile likelihood random effects model and assessed between-study heterogeneity using Cochran’s Q statistic chi square and the I2 test for inconsistency. Magnitude of benefit was categorized into no effect or small, moderate, and large effects. Results. From 2,850 abstracts, 20 RCTs (N=1,776) and 7 observational studies (N=13,095) assessing different cannabinoids were included; none of kratom. Studies were primarily short term, and 75 percent enrolled patients with a variety of neuropathic pain. Comparators were primarily placebo or usual care. The strength of evidence (SOE) was low, unless otherwise noted. Compared with placebo, comparable THC to CBD ratio oral spray was associated with a small benefit in change in pain severity (7 RCTs, N=632, 0 to10 scale, mean difference [MD] −0.54, 95% confidence interval [CI] −0.95 to −0.19, I2=28%; SOE: moderate) and overall function (6 RCTs, N=616, 0 to 10 scale, MD −0.42, 95% CI −0.73 to −0.16, I2=24%). There was no effect on study withdrawals due to adverse events. There was a large increased risk of dizziness and sedation and a moderate increased risk of nausea (dizziness: 6 RCTs, N=866, 30% vs. 8%, relative risk [RR] 3.57, 95% CI 2.42 to 5.60, I2=0%; sedation: 6 RCTs, N=866, 22% vs. 16%, RR 5.04, 95% CI 2.10 to 11.89, I2=0%; and nausea: 6 RCTs, N=866, 13% vs. 7.5%, RR 1.79, 95% CI 1.20 to 2.78, I2=0%). Synthetic products with high-THC to CBD ratios were associated with a moderate improvement in pain severity, a moderate increase in sedation, and a large increase in nausea (pain: 6 RCTs, N=390 to 10 scale, MD −1.15, 95% CI −1.99 to −0.54, I2=39%; sedation: 3 RCTs, N=335, 19% vs. 10%, RR 1.73, 95% CI 1.03 to 4.63, I2=0%; nausea: 2 RCTs, N=302, 12% vs. 6%, RR 2.19, 95% CI 0.77 to 5.39; I²=0%). We found moderate SOE for a large increased risk of dizziness (2 RCTs, 32% vs. 11%, RR 2.74, 95% CI 1.47 to 6.86, I2=0%). Extracted whole-plant products with high-THC to CBD ratios (oral) were associated with a large increased risk of study withdrawal due to adverse events (1 RCT, 13.9% vs. 5.7%, RR 3.12, 95% CI 1.54 to 6.33) and dizziness (1 RCT, 62.2% vs. 7.5%, RR 8.34, 95% CI 4.53 to 15.34). We observed a moderate improvement in pain severity when combining all studies of high-THC to CBD ratio (8 RCTs, N=684, MD −1.25, 95% CI −2.09 to −0.71, I2=50%; SOE: moderate). Evidence on whole-plant cannabis, topical CBD, low-THC to CBD, other cannabinoids, comparisons with active products, and impact on use of opioids was insufficient to draw conclusions. Other important harms (psychosis, cannabis use disorder, and cognitive effects) were not reported. Conclusions. Low to moderate strength evidence suggests small to moderate improvements in pain (mostly neuropathic), and moderate to large increases in common adverse events (dizziness, sedation, nausea) and study withdrawal due to adverse events with high- and comparable THC to CBD ratio extracted cannabinoids and synthetic products in short-term treatment (1 to 6 months). Evidence for whole-plant cannabis, and other comparisons, outcomes, and PBCs were unavailable or insufficient to draw conclusions. Small sample sizes, lack of evidence for moderate and long-term use and other key outcomes, such as other adverse events and impact on use of opioids during treatment, indicate that more research is needed.
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2

Chou, Roger, Jesse Wagner, Azrah Y. Ahmed, Benjamin J. Morasco, Devan Kansagara, Shelley Selph, Rebecca Holmes e Rongwei Fu. Living Systematic Review on Cannabis and Other Plant-Based Treatments for iii Chronic Pain: 2022 Update. Agency for Healthcare Research and Quality (AHRQ), setembro de 2022. http://dx.doi.org/10.23970/ahrqepccer250update2022.

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Objectives. To update the evidence on benefits and harms of cannabinoids and similar plant-based compounds to treat chronic pain using a living systematic review approach. Data sources. Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Library, and SCOPUS® databases; reference lists of included studies; and submissions received after Federal Register request were searched to April 4, 2022. Review methods. Using dual review, we screened search results for randomized controlled trials (RCTs) and observational studies of patients with chronic pain evaluating cannabis, kratom, and similar compounds with any comparison group and at least 1 month of treatment or followup. Dual review was used to abstract study data, assess study-level risk of bias, and rate the strength of evidence (SOE). Prioritized outcomes included pain, overall function, and adverse events. We grouped studies that assessed tetrahydrocannabinol (THC) and/or cannabidiol (CBD) based on their THC to CBD ratio and categorized them as comparable THC to CBD ratio, high-THC to CBD ratio, and low-THC to CBD ratio. We also grouped studies by whether the product was a whole-plant product (cannabis), cannabinoids extracted or purified from a whole plant, or a synthetic product. We conducted meta-analyses using the profile likelihood random effects model and assessed between-study heterogeneity using Cochran’s Q statistic chi square test and the I2 statistic. Magnitude of benefit was categorized as no effect or small, moderate, and large effects. Results. From 3,283 abstracts, 21 RCTs (N=1,905) and 8 observational studies (N=13,769) assessing different cannabinoids were included; none evaluated kratom. Studies were primarily short term, and 59 percent enrolled patients with neuropathic pain. Comparators were primarily placebo or usual care. The SOE was low unless otherwise noted. Compared with placebo, comparable THC to CBD ratio oral spray was associated with a small benefit in change in pain severity (7 RCTs, N=632, 0 to10 scale, mean difference [MD] −0.54, 95% confidence interval [CI] −0.95 to −0.19, I2=39%; SOE: moderate) and overall function (6 RCTs, N=616, 0 to 10 scale, MD −0.42, 95% CI −0.73 to −0.16, I2=32%). There was no effect on study withdrawals due to adverse events. There was a large increased risk of dizziness and sedation, and a moderate increased risk of nausea (dizziness: 6 RCTs, N=866, 31.0% vs. 8.0%, relative risk [RR] 3.57, 95% CI 2.42 to 5.60, I2=0%; sedation: 6 RCTs, N=866, 8.0% vs. 1.2%, RR 5.04, 95% CI 2.10 to 11.89, I2=0%; and nausea: 6 RCTs, N=866, 13% vs. 7.5%, RR 1.79, 95% CI 1.19 to 2.77, I2=0%). Synthetic products with high-THC to CBD ratios were associated with a moderate improvement in pain severity, a moderate increase in sedation, and a large increase in nausea (pain: 6 RCTs, N=390, 0 to 10 scale, MD −1.15, 95% CI −1.99 to −0.54, I2=48%; sedation: 3 RCTs, N=335, 19% vs. 10%, RR 1.73, 95% CI 1.03 to 4.63, I2=28%; nausea: 2 RCTs, N=302, 12.3% vs. 6.1%, RR 2.19, 95% CI 0.77 to 5.39; I²=0%). We also found moderate SOE for a large increased risk of dizziness (2 RCTs, 32% vs. 11%, RR 2.74, 95% CI 1.47 to 6.86, I2=40%). Extracted whole-plant products with high-THC to CBD ratios (oral) were associated with a large increased risk of study withdrawal due to adverse events (1 RCT, 13.9% vs. 5.7%, RR 3.12, 95% CI 1.54 to 6.33) and dizziness (1 RCT, 62.2% vs. 7.5%, RR 8.34, 95% CI 4.53 to 15.34); outcomes assessing benefit were not reported or insufficient. We observed a moderate improvement in pain severity when combining all studies of high-THC to CBD ratio (8 RCTs, N=684, MD −1.25, 95% CI −2.09 to −0.71, I2=58%; SOE: moderate). Evidence (including observational studies) on whole-plant cannabis, topical or oral CBD, low-THC to CBD, other cannabinoids, comparisons with active products or between cannabis-related products, and impact on use of opioids was insufficient to draw conclusions. Other important harms (psychosis, cannabis use disorder, and cognitive effects) were not reported. Conclusions. Low to moderate strength evidence suggests small to moderate improvements in pain (mostly neuropathic), and moderate to large increases in common adverse events (dizziness, sedation, nausea) with high- and comparable THC to CBD ratio extracted cannabinoids and synthetic products during short-term treatment (1 to 6 months); high-THC to CBD ratio products were also associated with increased risk of withdrawal due to adverse events. Evidence for whole-plant cannabis and other comparisons, outcomes, and plant-based compounds was unavailable or insufficient to draw conclusions. Small sample sizes, lack of evidence for moderate and long-term use and other key outcomes, such as other adverse events and impact on use of opioids during treatment, indicate that more research is needed.
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3

Chou, Roger, Azrah Y. Ahmed, Christina Bougatsos, Benjamin J. Morasco, Rebecca Holmes, Terran Gilbreath e Rongwei Fu. Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain: 2022 Update—Surveillance Report 2. Agency for Healthcare Research and Quality (AHRQ), janeiro de 2023. http://dx.doi.org/10.23970/ahrqepccer250.2022updatesr2.

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Objectives. To update the evidence on benefits and harms of cannabinoids and similar plant-based compounds to treat chronic pain using a living systematic review approach. Data sources. Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Library, and SCOPUS® databases; reference lists of included studies; and submissions received after Federal Register request were searched to October 24, 2022. Review methods. Using dual review, we screened search results for randomized controlled trials (RCTs) and observational studies of patients with chronic pain evaluating cannabis, kratom, and similar compounds with any comparison group and at least 1 month of treatment or followup. Dual review was used to abstract study data, assess study-level risk of bias, and rate the strength of evidence (SOE). Prioritized outcomes included pain, overall function, and adverse events. We grouped studies that assessed tetrahydrocannabinol (THC) and/or cannabidiol (CBD) based on their THC to CBD ratio and categorized them as comparable THC to CBD ratio, high-THC to CBD ratio, and low-THC to CBD ratio. We also grouped studies by whether the product was a whole-plant product (cannabis), cannabinoids extracted or purified from a whole plant, or a synthetic product. We conducted meta-analyses using the profile likelihood random effects model and assessed between-study heterogeneity using Cochran’s Q statistic chi square test and the I2 statistic. Magnitude of benefit was categorized as no effect or small, moderate, and large effects. Results. From a total of 3,568 abstracts, 21 RCTs (N=1,905) and 9 observational studies (N=15,079) assessing different cannabinoids were included; none evaluated kratom. Studies were primarily short term, and 60 percent enrolled patients with neuropathic pain. Comparators were primarily placebo or usual care. The SOE was low unless otherwise noted. Compared with placebo, comparable THC to CBD ratio oral spray was associated with a small benefit in pain severity (7 RCTs, N=632, 0 to 10 scale, mean difference [MD] −0.54, 95% confidence interval [CI] −0.95 to −0.19, I2=39%; SOE: moderate) and overall function (6 RCTs, N=616, 0 to 10 scale, MD −0.42, 95% CI −0.73 to −0.16, I2=32%). There was no effect on study withdrawals due to adverse events. There was a large increased risk of dizziness and sedation, and a moderate increased risk of nausea (dizziness: 6 RCTs, N=866, 31.0% vs. 8.0%, relative risk [RR] 3.57, 95% CI 2.42 to 5.60, I2=0%; sedation: 6 RCTs, N=866, 8.0% vs. 1.2%, RR 5.04, 95% CI 2.10 to 11.89, I2=0%; and nausea: 6 RCTs, N=866, 13% vs. 7.5%, RR 1.79, 95% CI 1.19 to 2.77, I2=0%). Synthetic products with high-THC to CBD ratios were associated with a moderate improvement in pain severity, a moderate increase in sedation, and a large increase in nausea (pain: 6 RCTs, N=390, 0 to 10 scale, MD −1.15, 95% CI −1.99 to −0.54, I2=48%; sedation: 3 RCTs, N=335, 19% vs. 10%, RR 1.73, 95% CI 1.03 to 4.63, I2=28%; nausea: 2 RCTs, N=302, 12.3% vs. 6.1%, RR 2.19, 95% CI 0.77 to 5.39; I²=0%). We also found moderate SOE for a large increased risk of dizziness (2 RCTs, 32% vs. 11%, RR 2.74, 95% CI 1.47 to 6.86, I2=40%). Extracted whole-plant products with high-THC to CBD ratios (oral) were associated with a large increased risk of study withdrawal due to adverse events (1 RCT, 13.9% vs. 5.7%, RR 3.12, 95% CI 1.54 to 6.33) and dizziness (1 RCT, 62.2% vs. 7.5%, RR 8.34, 95% CI 4.53 to 15.34); outcomes assessing benefit were not reported or insufficient. We observed a moderate improvement in pain severity when combining all studies of high-THC to CBD ratio (8 RCTs, N=684, MD −1.25, 95% CI −2.09 to −0.71, I2=58%; SOE: moderate). Evidence (including observational studies) on whole-plant cannabis, topical or oral CBD, low-THC to CBD, other cannabinoids, comparisons with active products or between cannabis-related products, and impact on use of opioids was insufficient to draw conclusions. Other important harms (psychosis, cannabis use disorder, and cognitive effects) were not reported. Conclusions. Low to moderate strength evidence suggests small to moderate improvements in pain (mostly neuropathic), and moderate to large increases in common adverse events (dizziness, sedation, nausea) with high and comparable THC to CBD ratio extracted cannabinoids and synthetic products during short-term treatment (1 to 6 months); high-THC to CBD ratio products were also associated with increased risk of withdrawal due to adverse events. Evidence for whole-plant cannabis and other comparisons, outcomes, and plant-based compounds was unavailable or insufficient to draw conclusions. Small sample sizes, lack of evidence for moderate and long-term use and other key outcomes, such as other adverse events and impact on use of opioids during treatment, indicate that more research is needed.
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