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1
Khashila, Marwan, Mahmoud N. Hussien, Mourad Karray, and Mohamed Chekired. "Use of pore pressure build-up as damage metric in computation of equivalent number of uniform strain cycles." Canadian Geotechnical Journal 55, no. 4 (2018): 538–50. http://dx.doi.org/10.1139/cgj-2017-0231.
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The build-up of earthquake-induced excess pore-water pressure may be viewed as analogous to the cumulative damage of saturated granular materials caused by cyclic loading, and consequently as a damage metric when converting an irregular earthquake loading to an equivalent number of uniform cycles, Neq. In this paper, a comprehensive series of strain-controlled tests have been conducted using the new combined triaxial simple shear (TxSS) apparatus developed at Institute de Recherche d’Hydro-Quebec (IREQ) in collaboration with the geotechnical group at the Université de Sherbrooke to verify the hypothesis of adopting the pore-water pressure ratio, Ru, as a damage metric when converting earthquakes to an equivalently damaging number of uniform strain cycles. Different reconstituted saturated samples of Baie-Saint-Paul, Carignon, and Quebec sands have been tested under undrained conditions up to liquefaction. The experimental results from this study have been utilized to develop an empirical expression to compute Neqγ from both the number of cycles required to trigger liquefaction, Nliq, and the material parameter, r. The parameter r had been experimentally calibrated a priori from a separate set of tests using uniform strain cycles following the theoretical framework outlined by Green and Lee in 2006. The present results reveal that the measured pore-water pressure ratio, Ru, is in agreement with predicted cumulative damage using the Richart and Newmark (R–N) hypothesis. However, the Palmgren–Miner (P–M) hypothesis underestimates the cumulative damage (i.e., the generated pore-water pressure) during cyclic loading.
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Silvestre, Jason, Qing Z. Ruan, and Benjamin Chang. "Analysis of National Institutes of Health Funding in Hand Surgery." HAND 14, no. 4 (2018): 560–64. http://dx.doi.org/10.1177/1558944717751719.
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Background: Federal research dollars help investigators develop biomedical therapies for human diseases. Currently, the state of funding in hand surgery is poorly understood. This study defines the portfolio of National Institutes of Health (NIH) grants awarded in hand surgery. Methods: This was a cross-sectional study of hand surgeons in the US. Faculty members of accredited hand surgery fellowships and/or members of the American Society for Surgery of the Hand were queried in the NIH RePORT database for awards obtained during 2005-2015. Results: Of 2317 hand surgeons queried, only 18 obtained an NIH grant (0.8%). Thirty-eight unique grants were identified totaling $42 197 375. R01 awards comprised the majority of funding (78.0%) while K08 awards accounted for 1.1%. The K-to-R transition rate was zero. The National Institute of Arthritis and Musculoskeletal and Skin Disease supported the most funding (65.2%), followed by the National Institute of Neurological Disorders and Stroke (30.8%). There was no statistically significant difference in NIH funding totals with hand surgeon characteristics. Funding supported translational (46.0%), basic science (29.6%), clinical (21.0%), and education-based (3.4%) research. Peripheral nerve (33.3%) and bone and joint disease (30.1%) received the most research funding. Conclusions: Less than 1% of hand surgeons obtain NIH research grants. Of the 2 identified K08 awards, none led to a subsequent R award. Future research should identify barriers to grant procurement to design effective policies to increase NIH funding in hand surgery.
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Fári, Miklós Gábor. "The development of the scientific bases of horticulture and the history of horticultural innovation in the Northern Great Plain region and in Debrecen." Acta Agraria Debreceniensis, no. 17 (September 14, 2005): 17–20. http://dx.doi.org/10.34101/actaagrar/17/3264.
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It can be told about the second half of the XXth century that, apart from preferring the large-scale growing of field plants and the largescalelivestock farming, corresponding to the central political will of the communist era, the significance and innovation output ofhorticultural education in Debrecen was rather of follow-up trait, of secondary importance. The Tobacco Research Institute continued theresearch work, and then even this activity was stopped. According to a survey finished in 1997, the mentioned institute had no invention,granted patent, protection for registered model or any application for patent in progress at the Hungarian Patent Office. Until this time, invention activity at the University of Agricultural Sciences was of medium standard. In the National Patent Office, seven patent applications related to agricultural production and nine patent applications for other fields submitted under the inventors’ names were recorded. In the same period, the Cereal Research Institute (Szeged) led the absolute innovation list of Hungarian agricultural R+D institutions and university education institutes by submitting 164 own patent applications. Both in domestic and international terms, the horticultural innovation conducted at the University of Agricultural Sciences, despite the individual research results and achievements deserving recognition, without appropriate background – remained unnoticed. Let us put it this way: for the past decades, the light of the Debrecen Flower Carnival has not been thrown on the horticultural teachers and researchers of Debrecen.
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Ma, Dali. "Boundary repair: Science and enterprise at the Chinese Academy of Sciences." Social Studies of Science 49, no. 3 (2019): 381–402. http://dx.doi.org/10.1177/0306312719846560.
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In the 1980s, the Chinese state pushed the Chinese Academy of Sciences (CAS) to establish businesses. Some of these businesses did not engage in any research and development (R&D), and this resulted in scientists having concerns about the boundary around the institutionalizing scientific community. When the state supported CAS’s ‘Knowledge Innovation’ reform in the late 1990s, CAS’s organizing principle became centered on a more narrowly scientific logic, which led to less reliance on business income. Regression analysis indicates that CAS-owned enterprises without R&D were more likely to be discontinued during ‘Knowledge Innovation’. Moreover, businesses having no R&D were more likely to be discontinued (1) if they were making high profits and (2) if they were supervised by an institute in which Academicians had longer tenure, because these conditions heightened science-market conflict.
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Miller, Jeffrey, Frank Cichocki, Jianfang Ning, et al. "155 iPSC-derived NK cells mediate robust anti-tumor activity against glioblastoma." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (2020): A169. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0155.
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BackgroundGliomas represent the most common brain tumors within the central nervous system, with glioblastoma being the most aggressive type.1 Conventional treatment combines several approaches including surgery, chemotherapy, and radiation.2 However, the prognosis for glioblastoma remains unfavorable, with only 5% of patients surviving more than 5 years post-diagnosis.3 Thus, new treatment approaches are urgently needed. Natural killer (NK) cells directly lyse malignantly transformed or virally infected cells and secrete inflammatory cytokines that polarize cytotoxic immunity. Allogeneic NK cell adoptive transfer has shown clinical benefit in patients with advanced cancer.4–7 However, limitations of this approach include relatively low numbers of donor NK cells that can be isolated during an apheresis and variability in the quality of NK cells between donors. To overcome these limitations, we have developed a GMP manufacturing strategy to mass produce NK cells from induced pluripotent stem cells (iPSCs) as an approach to off-the-shelf cancer immunotherapy. We refer to these cells as ‘iNK’ (iPSC-derived NK) cells. Here, we provide preclinical data demonstrating the efficacy of iNK cells for immunotherapy against glioblastoma.Abstract 155 Figure 1Engineered iNK cells exhibit highly effective antitumor function in a xenogeneic model of glioblastoma. (A) Schematic of the experimental design to test iNK cell function against glioblastoma in vivo. (B) Kaplan Meier plots showing survival for groups of mice that received either vehicle alone or iNK cells after tumor engraftment (n=5 mice/group)MethodsWe generated iNK cells using previously published methods.8–10 iNK cells were used as effectors against an array of patient-derived glioblastoma lines in 2-dimensional live imaging IncuCyte assays where iNK cell-mediated killing was observed over the course of 48 hours. To investigate iNK cell infiltration and cytotoxicity in a more physiological context that accounts for the 3-dimensional architecture of the tumor, we also performed live imaging IncuCyte assays using iNK cells as effectors against glioblastoma spheroids. To test the anti-tumor function of iNK cells in vivo, we implanted patient-derived glioblastoma cells into mice via intracranial injection. Seven days later, 5 mice received intratumoral injections of iNK cells, and 5 mice received vehicle alone (as a control; figure 1A). All mice were monitored for weight and survival over 100 days.Results iNK cells exhibited strong and sustained cytotoxicity against 6 primary patient-derived mesenchymal glioblastoma lines in 2-dimensional IncuCyte assays and complete infiltration and destruction of glioblastoma spheroids in 3-dimensional IncuCyte assays. In xenogeneic adoptive transfer experiments, all mice receiving intratumoral injections of iNK cells survived out to day 100, while all mice in the vehicle group became moribund and had to be sacrificed by day 60 (figure 1B).ConclusionsiNK cells are highly cytotoxic against glioblastoma cells, and our preclinical in vivo data provides proof-of-concept for future clinical trials.Ethics ApprovalThis project has been approved by the University of Minnesota IACUC. Approval ID: 1812-36595AReferencesLouis D N, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee W K, Ohgaki H, Wiestler O D, Kleihues P, Ellison D W. The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 2016;131:803–820.Stupp R, Mason W P, van den Bent M J, Weller M, Fisher B, Taphoorn M J B, Belanger K, Brandes A A, Marosi C, Bogdahn U, Curschmann J, Janzer R C, Ludwin S K, Gorlia T, Allgeier A, Lacombe D, Cairncross J G, Eisenhauer E, Mirimanoff R O, European Organization for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–996.Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholz-Sloan JS, Villano JL. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev 2017;23:1985–1996.Miller J S, Soignier Y, Panoskaltsis-Mortari A, McNearney S A, Yun G H, Fautsch S K, McKenna D, Le C, Defor T E, Burns L J, Orchard P J, Blazar B R, Wagner J E, Slungaard A, Weisdorf D J, Okazaki J, McGlave P B. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005;105:3051–3057.Bachanova V, Cooley S, Defor T E, Verneris M R, Zhang B, McKenna D H, Curtsinger J, Panoskaltsis-Mortari A, Lewis D, Hippen K, McGlave P, Weisdorf D J, Blazar B R, Miller J S. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood 2014;123:3855.Ciurea S O, Schafer J R, Bassett R, Denman C J, Cao K, Willis D, Rondon G, Chen J, Soebbing D, Kaur I, Gulbis A, Ahmed S, Rezvani K, Scpall E J, Lee D A, Champlin R E. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplant. Blood 2017;130:1857–1868.Romee R, Rosario M, Berrien-Elliott M M, Wagner J A, Jewell B A, Schappe T, Leong J W, Abdel-Latif S, Schneider S E, Willey S, Neal C C, Yu L, Oh T, Lee S, Mulder A, Cooper M A, Fehniger T A. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukiemia. Sci Transl Med 2016:8;375ra123.Valamehr B, Abujarour R, Robinson M, Le T, Robbins D, Shoemaker D, Flynn P. A novel platform to enable the high-throughput derivation and characterization of feeder-free human iPSCs. Sci Rep 2012:2;213.Valamehr B, Robinson M, Abujarour R, Rezner B, Vranceanu F, Le T, Medcalf A, Lee T T, Fitch M, Robbins D, Flynn P. Platform for induction and maintenance of transgene-free hiPSCs resembling ground state pluripotent stem cells. Stem Cell Reports 2014;2:366–381.Zhu H, Blum R H, Bjordahl R, Gaidarova S, Rogers P, Lee T T, Abujarour R, Bonello G B, Wu J, Tsai P-F, Miller J S, Walcheck B, Valamehr B, Kaufman D S. Pluripotent stem cell-derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor immunity. Blood 2020;135:399–410.
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Conanec, Alexandre, Brigitte Picard, Denis Durand, et al. "New Approach Studying Interactions Regarding Trade-Off between Beef Performances and Meat Qualities." Foods 8, no. 6 (2019): 197. http://dx.doi.org/10.3390/foods8060197.
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The beef cattle industry is facing multiple problems, from the unequal distribution of added value to the poor matching of its product with fast-changing demand. Therefore, the aim of this study was to examine the interactions between the main variables, evaluating the nutritional and organoleptic properties of meat and cattle performances, including carcass properties, to assess a new method of managing the trade-off between these four performance goals. For this purpose, each variable evaluating the parameters of interest has been statistically modeled and based on data collected on 30 Blonde d’Aquitaine heifers. The variables were obtained after a statistical pre-treatment (clustering of variables) to reduce the redundancy of the 62 initial variables. The sensitivity analysis evaluated the importance of each independent variable in the models, and a graphical approach completed the analysis of the relationships between the variables. Then, the models were used to generate virtual animals and study the relationships between the nutritional and organoleptic quality. No apparent link between the nutritional and organoleptic properties of meat (r = −0.17) was established, indicating that no important trade-off between these two qualities was needed. The 30 best and worst profiles were selected based on nutritional and organoleptic expectations set by a group of experts from the INRA (French National Institute for Agricultural Research) and Institut de l’Elevage (French Livestock Institute). The comparison between the two extreme profiles showed that heavier and fatter carcasses led to low nutritional and organoleptic quality.
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Koshlyakov, M. N., A. G. Zatsepin, and S. A. Sviridov. "DOUBLE ANNIVERSARY OF PROFESSOR VLADIMIR STOKMAN." Journal of Oceanological Research 47, no. 5 (2019): 177–84. http://dx.doi.org/10.29006/1564-2291.jor-2019.47(5).13.
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In 2019, the 110th anniversary of the birth of the outstanding Soviet oceanologist – Professor Vladimir Shtokman, with whose name is closely connected to the formation and development of dynamic oceanology in our country, is celebrated. In the same year, another significant date is celebrated – 40 years from the date of the introduction of the R/V Professor Shtokman into the scientific fleet of the USSR Academy of Sciences. The research vessel is named after the outstanding scientist V.B. Shtokman, who led the theoretical research at the Shirshov Institute of Oceanology from 1946 to 1968.
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Lucas Prado, Clementina Corah. "A adoção do limite custo-efetividade na incorporação de tecnologias no SUS – o que se pode esperar." Revista Eletronica Gestão & Saúde 6, no. 4 (2015): 3127. http://dx.doi.org/10.18673/gs.v6i4.22103.
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Objetivo: Revisar o uso de avaliação custo-efetividade na incorporação de tecnologias em sistemas de saúde e informações sobre o limite custo-efetividade, especialmente embasadas na experiência do The National Institute for Health and Care Excellence – NICE no Reino Unido, a fim de pontuar os desafios que se apresentam ao caso brasileiro. Metodologia: Levantamento bibliográfico sobre o uso de avaliações econômicas na tomada de decisão em saúde e do Limite Custo-Efetividade (LCE) e suas consequências. Resultados: Há uma tendência atual de se adotar de forma explicita o LCE, sendo incipientes os métodos de cálculo empírico. A OMS estabeleceu, em 2002, que o LCE aceitável corresponde ao valor do PIB per capita por DALY, porém vários estudos buscaram estabelecer a disposição a pagar por QALY, obtidas diretamente com a população. Nimdet calculou a razão entre a disposição a pagar por QALY e o PIB per capita – por esta, o LCE a ser trabalhado pela CONITEC seria um valor entre R$ 1.361 a R$ 147.016. Além do LCE, há que se considerar o impacto orçamentário e o custo de oportunidade da incorporação, com a elaboração de um plano de desinvestimento que suporte o custo das novas tecnologias.
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Duran, Kevin. "Reviewer Acknowledgements for International Business Research, Vol. 11, No. 10." International Business Research 11, no. 10 (2018): 174. http://dx.doi.org/10.5539/ibr.v11n10p174.
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International Business Research wishes to acknowledge the following individuals for their assistance with peer review of manuscripts for this issue. Their help and contributions in maintaining the quality of the journal are greatly appreciated.
 
 International Business Research is recruiting reviewers for the journal. If you are interested in becoming a reviewer, we welcome you to join us. Please find the application form and details at http://www.ccsenet.org/journal/index.php/ibr/editor/recruitment and e-mail the completed application form to ibr@ccsenet.org. 
 
 Reviewers for Volume 11, Number 10
 
  
 
 Andrea Carosi, University of Sassari, Italy
 
 Anna Paola Micheli, Univrtsity of Cassino and Southern Lazio, Italy
 
 Antônio André Cunha Callado, Universidade Federal Rural de Pernmabuco, Brazil
 
 Ashford C Chea, Benedict College, USA
 
 Aurelija Burinskiene, Vilnius Gediminas Technical University, Lithuania
 
 Benjamin James Inyang, University of Calabar, Nigeria
 
 Bruno Ferreira Frascaroli, Federal University of Paraiba, BrazilBrazil, 
 
 Celina Maria Olszak, University of Economics in Katowice, Poland
 
 Cheng Jing, eBay, Inc. / University of Rochester, USA
 
 Chokri Kooli, International Center for Basic Research applied, Paris, Canada
 
 Claudia Isac, University of Petrosani, Romania
 
 Dea’a Al-Deen Al-Sraheen, Al-Zaytoonah University of Jordan , Jordan 
 
 Eunju Lee, University of Massachusetts Lowell, USA
 
 Federica De Santis , University of Pisa , Italy
 
 Foued Hamouda, Ecole Supérieure de Commerce, Tunisia
 
 Francesco Ciampi, Florence University, Italy
 
 Gilberto Marquez-Illescas , University of Rhode Island, USA
 
 Giuseppe Granata, University of Cassino and Southen Lazio, Italy
 
 Giuseppe Russo, University of Cassino and Southern Lazio, Italy
 
 Guo Zi-Yi, Wells Fargo Bank, N.A., USA
 
 Imran Riaz Malik, IQRA University, Pakistan
 
 Janusz Wielki, Opole University of Technology, Poland
 
 Jerome Kueh, Universiti Malaysia Sarawak, Malaysia
 
 Joseph Lok-Man Lee, The Hong Kong Polytechnic University, Hong Kong
 
 Ladislav Mura, University of Ss. Cyril and Methodius in Trnava, Slovakia
 
 Luisa Pinto, University of Porto School of Economics, Portugal
 
 Manuel A. R. da Fonseca, Federal University of Rio de Janeiro (UFRJ), Brazil
 
 Manuela Rozalia Gabor, “Petru Maior” University of Tîrgu Mureş, Romania
 
 Marcelino José Jorge, Evandro Chagas Clinical Research Institute of Oswaldo Cruz Foundation, Brazil
 
 Maria-Madela Abrudan, University of ORADEA, Romania
 
 Maryam Ebrahimi, Azad University, Iran
 
 Mithat Turhan, Mersin University, Turkey
 
 Modar Abdullatif, Middle East University, Jordan
 
 Mohamed Abdel Rahman Salih, Taibah University, Saudi Arabia
 
 Ozgur Demirtas, Turkish Air Force Academy, Turkey
 
 Pascal Stiefenhofer, University of Brighton, UK
 
 Rafiuddin Ahmed, James Cook University, Australia
 
 Riaz Ahsan, Government College University Faisalabad, Pakistan
 
 Sumathisri Bhoopalan, SASTRA Deemed to be University, India
 
 Valeria Stefanelli, University of Salento, Italy
 
 Valerija Botric, The Institute of Economics, Zagreb, Croatia
 
 Wanmo Koo, Western Illinois University, USA
 
 Wejdene Yangui, Institute of High Business Studies of Sfax _ Tunisia (IHEC), Tunisia
 
 Yasmin Tahira, Al Ain University of Science and Technology, Al Ain, UAE
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KITLV, Redactie. "Book Reviews." Bijdragen tot de taal-, land- en volkenkunde / Journal of the Humanities and Social Sciences of Southeast Asia 158, no. 2 (2002): 305–63. http://dx.doi.org/10.1163/22134379-90003783.
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-Greg Bankoff, Alfred W. McCoy, Lives at the margin; Biography of Filipinos obscure, ordinary and heroic. Madison, Wisconsin: Center for Southeast Asian Studies, University of Wisconsin-Madion, v + 481 pp. -Greg Bankoff, Clive J. Christie, Ideology and revolution in Southeast Asia 1900-1980; Political ideas of the anti-colonial era. Richmond, Surrey: Curzon Press, xi + 236 pp. -René van den Berg, Videa P. de Guzman ,Grammatical analysis; Morphology, syntax, and semantics; Studies in honor of Stanley Starosta. Honolulu: University of Hawai'i Press, xv + 298 pp. [Oceanic Linguistics Special Publication 29.], Byron W. Bender (eds) -Wayne A. Bougas, Daniel Perret ,Batu Aceh; Warisan sejarah Johor. Kuala Lumpour: École francaise d'Extrême Orient, Johor Baru: Yayasan Warisan Johor, xxxviii + 510 pp., Kamarudin Ab. Razak (eds) -Freek Colombijn, Benedict R. O.G. Anderson, Violence and the state in Suharto's Indonesia. Ithaca, New York: Cornell University, Southeast Asia Program, 247 pp. [Studies on Southeast Asia 30.] -Harold Crouch, Stefan Eklöf, Indonesian politics in crisis; The long fall of Suharto, 1996-98. Copenhagen: Nodic Institute of Asian Studies, 1999, xi + 272 pp. [NIAS Studies in Contemporary Asia 1.] -John Gullick, Kumar Ramakrishna, Emergency propaganda; The winning of Malayan hearts and minds 1948-1958. Richmond, Surrey: Curzon, 2002, xii + 306 pp. -Han Bing Siong, Daniel S. Lev, Legal evolution and political authority in Indonesia; Selected essays. The Hague: Kluwer Law International, 2000, 349 pp., The Hague, London, Boston: Kluwer International. -David Henley, Laura Lee Junker, Raiding, trading, and feasting; The political economy of Philippine chiefdoms. Honolulu: University of Hawai'i Press, 1999, ix + 477 pp. -R.D. Hill, Jonathan Rigg, Southeast Asia; The human landscape of modernization and development. London: Routledge, 1997, xxv + 326 pp. -Adrian Horridge, Gene Ammarell, Bugis navigation. New Haven, Connecticut: Yale University Press, xiv + 299 pp. [Yale Southeast Asia studies monograph 48.] 1999 -Bernice de Jong Boers, Peter Just, Dou Donggo justice; Conflict and morality in an Indonesian society. Lanham, Maryland: Rowman and Littlefield, 2001, xi + 263 pp. -Nico J.G. Kaptein, Howard M. Federspiel, Islam and ideology in the emerging Indonesian state; The Persatuan Islam (PERSIS), 1923 to 1957. Leiden: Brill, 2001, xii + 365 pp. -Gerrit Knaap, Els M. Jacobs, Koopman in Azië; De handel van de Verenigde Oost-Indische Compagnie tijdens de 18de eeuw. Zutphen: Walburg Pers, 2000, 304 pp. -Toon van Meijl, Bruce M. Knauft, From primitive to postcolonial in Melanesia and anthropology. Ann Arbor: University of Michigan Press, 1999, x + 320 pp. -Jennifer Nourse, Juliette Koning ,Women and households in Indonesia; Cultural notions and social practices. Richmond, Surrey: Curzon, 2000, xiii + 354 pp., Marleen Nolten, Janet Rodenburg (eds) -Sandra Pannell, Clayton Fredericksen ,Altered states; Material culture transformations in the Arafura region. Darwin: Northern Territory University Press, 2001, xiv + 160 pp., Ian Walters (eds) -Anne Sofie Roald, Alijah Gordon, The propagation of Islam in the Indonesian-Malay archipelago. Kuala Lumpur: Malaysian sociological research institute, 2001, xxv + 472 pp. -M.J.C. Schouten, Mary Taylor Huber ,Gendered missions; Women and men in missionary discourse and practice. Ann Arbor: The University of Michigan Press, 1999, x + 252 pp., Nancy C. Lutkehaus (eds) -Karel Steenbrink, Nakamura Mitsuo ,Islam and civil society in Southeast Asia. Singapore: Institute of Southeast Asian studies, 2001, 211 pp., Sharon Siddique, Omar Farouk Bajunid (eds) -Heather Sutherland, Robert Cribb, Historical atlas of Indonesia, Richmond, Surrey: Curzon, 2000, x + 256 pp. -Sikko Visscher, Lee Kam Hing ,The Chinese in Malaysia. Kuala Lumpur: Oxford University Press, 2000, xxix + 418 pp., Tan Chee-Beng (eds) -Edwin Wieringa, Jane Drakard, A kingdom of words; Language and power in Sumatra. Kuala Lumpur: Oxford University Press, 1999, xxi + 322 pp.
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Roberts, Andrew W., Shuo Ma, Danielle M. Brander, et al. "Determination of Recommended Phase 2 Dose of ABT-199 (GDC-0199) Combined with Rituximab (R) in Patients with Relapsed / Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)." Blood 124, no. 21 (2014): 325. http://dx.doi.org/10.1182/blood.v124.21.325.325.
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Abstract Introduction: ABT-199 is a selective, orally bioavailable BCL-2 inhibitor that rapidly induces responses in ~80% of patients (pts) with relapsed/refractory (R/R) CLL or small lymphocytic lymphoma (SLL) as a single agent (Seymour, EHA 2014). Rituximab (R) has only modest and short-lived activity as a single-agent in CLL; it can enhance the activity of other agents with minimal additional toxicity. ABT-199 and R demonstrate synergy in preclinical models of CD20-positive lymphoid malignancies, and the combination has the potential to improve efficacy. Methods: Primary objectives of this phase 1b, open-label, dose-escalation, multicenter study were to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RPTD) of ABT-199 + R in pts with R/R CLL/SLL and evaluate the safety profile; secondary objectives examine the pharmacokinetics (PK) and efficacy of the combination. Eligible pts began treatment with 20 or 50 mg ABT-199 (modified to 20 mg during the study) daily, with weekly increases in a ramp-up phase to a final cohort dose of 200 - 600 mg. After completion of the ramp-up phase, R was added starting at 375 mg/m2 and then 500 mg/m2 monthly for a total of 6 doses. ABT-199 was continued daily until progressive disease (PD) or unacceptable toxicity. Adverse events (AEs) were graded according to NCI-CTCAE v4.0. The MTD was determined using the Continual Reassessment Method. Responses were assessed using established criteria for CLL/SLL, including CT scan at month 3 and CT scan and bone marrow (BM) biopsy at the end of combination therapy. MRD was assessed using four color flow cytometry in peripheral blood (PB) and/or BM aspirate ≥2 months after response criteria were first met, and in PB every 12 weeks until MRD negativity was achieved. Results: As of July 6, 2014, 49 pts enrolled in 5 dose escalation cohorts (n = 41) and a safety expansion cohort (n = 8), with a median time on study of 201 days (1 – 624). Median age was 68 years (range 50–88) and 30 (61%) were male. The median number of prior therapies was 3 (1–10). Thirteen (27%) had fludarabine-refractory disease and 9 (18%) R-refractory. Nine (18%) had del (17p) and 19/27 (70%) with available data had unmutated IGVH. Thirteen pts have discontinued therapy: 6 due to PD; 3 after attaining complete remission; 2 due to AEs and 2 withdrew consent. Preliminary PK data suggest a negligible effect of R on ABT-199 exposure. The most common overall treatment-emergent AEs (>25% pts) were neutropenia (47%), nausea (41%), diarrhea (37%), pyrexia (31%), headache (31%), fatigue, upper respiratory tract infection, and cough (each 29%). The most common overall grade 3/4 AEs were neutropenia (47%), thrombocytopenia (16%), and anemia (14%). Treatment-emergent SAEs occurred in 20 (41%) pts; the most common were pyrexia (6%), and febrile neutropenia, infusion-related reaction, TLS, and Richter's Transformation (each 4%). Six pts experienced a DLT: 1 febrile neutropenia (200mg), 1 each thrombocytopenia, hematophagocytic syndrome, neutropenia (300mg), 1 neutropenia (600mg), and 1 pt experienced a fatal event of hyperkalemia in the setting of TLS after the first dose (50mg). That event led to a modified dosing scheme; no TLS was observed in the 32 subsequent pts using the revised ramp up dosing scheme. No MTD was identified. Of 34 pts who were evaluable for response in dose escalation cohorts, the overall response rate (ORR) was 88%, with 11 (32%) achieving a CR/CRi and 20 (56%) achieving a partial response (PR). MRD was quantified by local laboratory in 19 pts. Thirteen pts (7 in CR (6 at 10-4 and 1 at 10-3 sensitivity) and 6 in PR (10-4 sensitivity)) were MRD negative in bone marrow while one was MRD negative in peripheral blood (10-4 sensitivity). The RPTD of ABT-199 is 400 mg daily based on safety data; key safety and efficacy data for the dose selection are summarized in the table. Conclusions: The combination of ABT-199 and R is well-tolerated and achieves an overall response rate of 86% with 31% CRs in pts with CLL/SLL. Efficacy was observed across all dose cohorts. The RPTD of ABT-199 is 400mg daily, supported by a trend of lower rates of neutropenia and GI toxicity events in the absence of a clear difference in efficacy, compared to the higher doses. A phase 3 trial comparing ABT-199 and R versus bendamustine and R in pts with previously treated CLL is underway. Figure 1 Figure 1. Disclosures Roberts: Walter and Eliza Hall Institute of Medical Research : Employment, Research Funding; AbbVie: Research Funding; Genentech: Research Funding. Ma:Genentech: Consultancy; AbbVie: Research Funding. Kipps:AbbVie: Consultancy, Research Funding. Barrientos:Gilead: institutional funding Other; Pharmacyclics: Consultancy, institutional funding, institutional funding Other; AbbVie: institutional funding, institutional funding Other; Celgene: Consultancy. Davids:Genentech: Consultancy; Infinity Pharmaceuticals: Consultancy. Anderson:Walter and Eliza Hall Institute of Medical Research: Employment, milestone payments related to ABT-199 Other; AbbVie: Research Funding; Genentech: Research Funding. Tam:Roche: Honoraria. Mason-Bright:AbbVie : Employment. Rudersdorf:AbbVie: Employment. Gressick:AbbVie: Employment. Yang:AbbVie, Inc: Employment. Munasinghe:AbbVie: Employment. Zhu:AbbVie, Inc: Employment. Cerri:AbbVie: Employment. Enschede:AbbVie, Inc: Employment. Humerickhouse:AbbVie, Inc: Employment. Seymour:AbbVie: Research Funding; Genentech: Consultancy, Research Funding; Roche: Consultancy.
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White, Brian S., Suleiman A. Khan, Muhammad Ammad-ud-din, et al. "Comparative Analysis of Independent Ex Vivo functional Drug Screens Identifies Predictive Biomarkers of BCL-2 Inhibitor Response in AML." Blood 132, Supplement 1 (2018): 2763. http://dx.doi.org/10.1182/blood-2018-99-111916.
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Abstract Introduction: Therapeutic options for patients with AML were recently expanded with FDA approval of four drugs in 2017. As their efficacy is limited in some patient subpopulations and relapse ultimately ensues, there remains an urgent need for additional treatment options tailored to well-defined patient subpopulations to achieve durable responses. Two comprehensive profiling efforts were launched to address this need-the multi-center Beat AML initiative, led by the Oregon Health & Science University (OHSU) and the AML Individualized Systems Medicine program at the Institute for Molecular Medicine Finland (FIMM). Methods: We performed a comparative analysis of the two large-scale data sets in which patient samples were subjected to whole-exome sequencing, RNA-seq, and ex vivo functional drug sensitivity screens: OHSU (121 patients and 160 drugs) and FIMM (39 patients and 480 drugs). We predicted ex vivo drug response [quantified as area under the dose-response curve (AUC)] using gene expression signatures selected with standard regression and a novel Bayesian model designed to analyze multiple data sets simultaneously. We restricted analysis to the 95 drugs in common between the two data sets. Results: The ex vivo responses (AUCs) of most drugs were positively correlated (OHSU: median Pearson correlation r across all pairwise drug comparisons=0.27; FIMM: median r=0.33). Consistently, a samples's ex vivo response to an individual drug was often correlated with the patient's Average ex vivo Drug Sensitivity (ADS), i.e., the average response across the 95 drugs (OHSU: median r across 95 drugs=0.41; FIMM: median r=0.58). Patients with a complete response to standard induction therapy had a higher ADS than those that were refractory (p=0.01). Further, patients whose ADS was in the top quartile had improved overall survival relative to those having an ADS in the bottom quartile (p<0.05). Standard regression models (LASSO and Ridge) trained on ADS and gene expression in the OHSU data set had improved ex vivo response prediction performance as assessed in the independent FIMM validation data set relative to those trained on gene expression alone (LASSO: p=2.9x10-4; Ridge: p=4.4x10-3). Overall, ex vivo drug response was relatively well predicted (LASSO: mean r across 95 drugs=0.62; Ridge: mean r=0.62). The BCL-2 inhibitor venetoclax was the only drug whose response was negatively correlated with ADS in both data sets. We hypothesized that, whereas the predictive performance of many other drugs was likely dependent on ADS, the predictive performance of venetoclax (LASSO: r=0.53, p=0.01; Ridge: r=0.63, p=1.3x10-3) reflected specific gene expression biomarkers. To identify biomarkers associated with venetoclax sensitivity, we developed an integrative Bayesian machine learning method that jointly modeled both data sets, revealing several candidate biomarkers positively (BCL2 and FLT3) or negatively (CD14, MAFB, and LRP1) correlated with venetoclax response. We assessed these biomarkers in an independent data set that profiled ex vivo response to the BCL-2/BCL-XL inhibitor navitoclax in 29 AML patients (Lee et al.). All five biomarkers were validated in the Lee data set (Fig 1). Conclusions: The two independent ex vivo functional screens were highly concordant, demonstrating the reproducibility of the assays and the opportunity for their use in the clinic. Joint analysis of the two data sets robustly identified biomarkers of drug response for BCL-2 inhibitors. Two of these biomarkers, BCL2 and the previously-reported CD14, serve as positive controls credentialing our approach. CD14, MAFB, and LRP1 are involved in monocyte differentiation. The inverse correlation of their expression with venetoclax and navitoclax response is consistent with prior reports showing that monocytic cells are resistant to BCL-2 inhibition (Kuusanmäki et al.). These biomarker panels may enable better selection of patient populations likely to respond to BCL-2 inhibition than would any one biomarker in isolation. References: Kuusanmäki et al. (2017) Single-Cell Drug Profiling Reveals Maturation Stage-Dependent Drug Responses in AML, Blood 130:3821 Lee et al. (2018) A machine learning approach to integrate big data for precision medicine in acute myeloid leukemia, Nat Commun 9:42 Disclosures Druker: Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees; ALLCRON: Consultancy, Membership on an entity's Board of Directors or advisory committees; Fred Hutchinson Cancer Research Center: Research Funding; Celgene: Consultancy; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees; Aileron Therapeutics: Consultancy; Third Coast Therapeutics: Membership on an entity's Board of Directors or advisory committees; Oregon Health & Science University: Patents & Royalties; Patient True Talk: Consultancy; Millipore: Patents & Royalties; Monojul: Consultancy; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Leukemia & Lymphoma Society: Membership on an entity's Board of Directors or advisory committees, Research Funding; GRAIL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Beta Cat: Membership on an entity's Board of Directors or advisory committees; MolecularMD: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Henry Stewart Talks: Patents & Royalties; Bristol-Meyers Squibb: Research Funding; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Aptose Therapeutics: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; McGraw Hill: Patents & Royalties; ARIAD: Research Funding; Novartis Pharmaceuticals: Research Funding. Heckman:Orion Pharma: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Porkka:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Tyner:AstraZeneca: Research Funding; Incyte: Research Funding; Janssen: Research Funding; Leap Oncology: Equity Ownership; Seattle Genetics: Research Funding; Syros: Research Funding; Takeda: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Aptose: Research Funding; Agios: Research Funding. Aittokallio:Novartis: Research Funding. Wennerberg:Novartis: Research Funding.
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Lemaistre, Charles A. "R. lee clark." Cancer 74, no. 5 (1994): 1513–15. http://dx.doi.org/10.1002/1097-0142(19940901)74:5<1513::aid-cncr2820740502>3.0.co;2-b.
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Pretorius, Z. A., W. H. P. Boshoff, and G. H. J. Kema. "First Report of Puccinia striiformis f. sp. tritici on Wheat in South Africa." Plant Disease 81, no. 4 (1997): 424. http://dx.doi.org/10.1094/pdis.1997.81.4.424d.
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During August 1996, stripe (yellow) rust, caused by Puccinia striiformis f. sp. tritici, was observed for the first time on bread wheat (Triticum aestivum) in the Western Cape, South Africa. Ensuing surveys during the growing season indicated that stripe rust occurred throughout most of the wheat-producing areas in the winter rainfall regions of the Northern, Western, and Eastern Cape provinces. The disease was also observed on irrigated wheat in the summer rainfall area south of Kimberley. Stripe rust was most severe in the Western Cape, where prolonged cool and wet conditions favored epidemic development and necessitated extensive and often repeated applications of triazole fungicides. Due to spike infection and destruction of foliage, significant losses in grain quantity and quality occurred in certain fields. Avirulence/virulence characteristics of 32 stripe rust isolates, collected from commercial wheat fields, trap nurseries, and triticale, were determined on 17 standard differential wheat lines and seven supplementary testers supplied by C. R. Wellings, Plant Breeding Institute, Cobbitty, Australia. All isolates were representative of one pathotype, characterized by avirulence to Chinese 166 (Yr1), Vilmorin 23 (Yr3), Moro (Yr10), Strubes Dickkopf, Suwon 92/Omar, Clement (Yr2,9), Triticum aestivum subsp. spelta var. album (Yr5), Hybrid 46 (Yr4), Reichersberg 42 (Yr7), Heines Peko (Yr2,6), Nord Desprez (Yr3), Carstens V, Spaldings Prolific, Heines VII (Yr2), Federation*4/Kavkaz (Yr9), and Avocet-S/Yr15, and by virulence to Kalyansona (Yr2), Heines Kolben (Yr2,6), Lee (Yr7), Compair (Yr8), and Federation 1221. Cultivars Trident (Yr17), Avocet-R (YrA), and Selkirk (YrSk) appeared heterogeneous for stripe rust reaction. The pathotype resembled race 6E16, previously detected in East and North Africa, the Middle East, and western Asia. Pathotype identity was confirmed at IPO-DLO, Wageningen, using one South African isolate of P. striiformis f. sp. tritici. In view of the rapid dispersal of the pathogen during 1996, susceptibility of several high-yielding cultivars, and favorable climatic conditions in many wheat-growing areas, stripe rust is considered potentially damaging to South African wheat production. Field observations and seedling tests have shown, however, that certain cultivars are resistant to the introduced pathotype. At present the genetic basis of this resistance is largely unknown.
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Tenkouano, Abdou, Niéyidouba Lamien, Josephine Agogbua, et al. "Promising High-Yielding Tetraploid Plantain-Bred Hybrids in West Africa." International Journal of Agronomy 2019 (April 21, 2019): 1–8. http://dx.doi.org/10.1155/2019/3873198.
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The devastating threat of black leaf streak disease caused by Pseudocercospora fijiensis on plantain production in West Africa spurred the development of resistant hybrids. The goal of this research and development (R&D) undertaken was assessing the development and dissemination of two plantain hybrids PITA 3 and FHIA 21 bred in the 1980s by the International Institute of Tropical Agriculture (IITA, Nigeria) and the Fundación Hondureña de Investigación Agrícola (FHIA, Honduras), respectively. In Côte d’Ivoire, plantain growers selected PITA 3 and FHIA 21 based on their improved agronomic characteristics and, between 2012 and 2016, they were massively propagated and distributed to farmers in Benin, Burkina Faso, Côte d’Ivoire, and Togo under the West Africa Agricultural Productivity Program (WAAAP) coordinated by the West and Central Africa Council for Agricultural Research and Development (CORAF). In 2016, the Centre National de Recherche Agronomique in Côte d’Ivoire included the hybrids in the improved cultivar directory. This R&D activity illustrates how three decades of crossbreeding, selection, and distribution led to local acceptance. It also highlights how a CORAF-led partnership harnessed CGIAR research for development. The dissemination and acceptance of these plantain hybrids will enhance the sustainable intensification in plantain-based farming systems across the humid lowlands of West and Central Africa.
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Munoz-Martin, Joan Francesc, Adrian Perez, Adriano Camps, et al. "Snow and Ice Thickness Retrievals Using GNSS-R: Preliminary Results of the MOSAiC Experiment." Remote Sensing 12, no. 24 (2020): 4038. http://dx.doi.org/10.3390/rs12244038.
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The FSSCat mission was the 2017 ESA Sentinel Small Satellite (S⌃3) Challenge winner and the Copernicus Masters competition overall winner. It was successfully launched on 3 September 2020 onboard the VEGA SSMS PoC (VV16). FSSCat aims to provide coarse and downscaled soil moisture data and over polar regions, sea ice cover, and coarse resolution ice thickness using a combined L-band microwave radiometer and GNSS-Reflectometry payload. As part of the calibration and validation activities of FSSCat, a GNSS-R instrument was deployed as part of the MOSAiC polar expedition. The Multidisciplinary drifting Observatory for the Study of Arctic Climate expedition was an international one-year-long field experiment led by the Alfred Wegener Institute to study the climate system and the impact of climate change in the Arctic Ocean. This paper presents the first results of the PYCARO-2 instrument, focused on the GNSS-R techniques used to measure snow and ice thickness of an ice floe. The Interference Pattern produced by the combination of the GNSS direct and reflected signals over the sea-ice has been modeled using a four-layer model. The different thicknesses of the substrate layers (i.e., snow and ice) are linked to the position of the fringes of the interference pattern. Data collected by MOSAiC GNSS-R instrument between December 2019 and January 2020 for different GNSS constellations and frequencies are presented and analyzed, showing that under general conditions, sea ice and snow thickness can be retrieved using multiangular and multifrequency data.
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Takagi, Hiroshi. "History and Future Prospect of Electro-ceramics in Japan and Asia." Additional Conferences (Device Packaging, HiTEC, HiTEN, and CICMT) 2012, CICMT (2012): 000002–9. http://dx.doi.org/10.4071/cicmt-2012-kn2_murata.
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On the background of a long history of Japanese ceramics, various electro-ceramic materials have been studied and many kinds of electronic components using them have been developed in Japan. The first invention of electro-ceramics in Japan should be a ferrite at Tokyo Institute of Technology in 1930, and the mass production of ferrite started in 1937. Then, Japanese electro-ceramic industry has led the world on electro-ceramic materials and components until now, especially in the fields of BaTiO3, PZT, PTC thermistor, ZnO varistor and insulating ceramics. In recent years, new electro-ceramic materials, their processes and new devices using them have been still studied actively in Japan. Currently, R&D activities in Asia outside of Japan, and electro-ceramic industries in those areas have been grown steadily.
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Ahsani, S. A. H. "The State of Research on Islamic Spain." American Journal of Islam and Society 9, no. 4 (1992): 556–62. http://dx.doi.org/10.35632/ajis.v9i4.2541.
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The era of Muslim rule in Spain (711-1491 CE) witnessed great contributionsin many areas of knowledge and learning. Rapid strides weremade in such diverse fields as art and architecture, agriculture and handicrafts,linguistics and literature, humanities and Social studies, music andpoetry, and the physical and mechanical sciences. In fact, Islamic Spain,known to the Muslim world as al Andalus, served as a bridge for thetransfer of the knowledge and wisdom of Classical Greece to Europe, aprocess that eventually led to the European Renaissance.The achievements of al Andalus will not be discussed in this paper.Rather, a survey of current research activities focusing on al Andaluswill be presented. The areas covered are Europe, North America, NorthAfrica, and parts of Asia. Latin American activities have not been surveyeddue to the nonavailability of sources.EuropeEurope has been the center of research on al Andalus. Various periodicalshave served as major sources of information: Al-Andalus (Madrid1933), Hesperis (Paris 1921-59), Hesperis-Tamuda (Rabat 1960), Miscellanceade Estudios Arabes y Hebraicos (Granda 1952), Revista de InstitutoEgypcio de Studios Islamicos (Madrid 1953), Revue de la OccidentMusulman et la Mediterranee (Aix-en-Provence 1966), Boletin de laAssociation Espaniola de Orientalistas (Madrid 1965), and Cuadernos dela Alhambra (Granada 1965).Certain important books have also appeared, such as Peres: la PoisieAndalousie, which includes a history of that period. Introductions to editionsof texts and translations relate important infonnation about al Andalusunder the al Murabitun and the al Mu’ahhidun dynasties. Hourani(1961) has written an excellent book: Averroes: On the Harmony of Religionand Philosophy. Memorial volumes in honor of E. Levi-Provencal,G. and W. Marcais, Menendes Pidal, Millas Vallicrosa y Parya, A. H. andR. Basset, H. A. R. Gibb and H. Wehr also contain much valuable data.Mention must be made of translations by institutes devoted to thestudy of al Andalus: Dar al Thaqafah (Beirut) has published valuablebooks, as have several Spanish and North African organizations (i.e.,Conjeyo Superior de Investigaciones Cientificas Madrid], Instituto deStudios Islambs [Madrid], Institute des Haut-Etudes Marocaines Paris ...
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Moujalled, Donia M., Fiona C. Brown, Giovanna Pomilio, et al. "Acquired Mutations in BAX Confer Resistance to BH3 Mimetics in Acute Myeloid Leukemia." Blood 136, Supplement 1 (2020): 7–8. http://dx.doi.org/10.1182/blood-2020-136872.
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Background: Recent randomized trials have demonstrated improvements in overall survival (OS) for the BCL-2 inhibitor venetoclax (VEN) in combination with azacitidine and low dose cytarabine in older unfit patients with AML. Pre-clinical studies identified BAX deficiency as a potential mechanism of VEN resistance in AML, but this has not been observed in patients to date (Chen, Cancer Disc 2019). Methods: Patient samples were derived from studies approved by the Alfred Ethics Committee. BAX sequencing was performed using targeted sequencing. In vivo studies used NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. S63845 and S55746 were obtained from Servier/Novartis, A1155463 from G. Lessene (WEHI), venetoclax and cytarabine from Selleckchem. OCI-AML cells were used for protein, viability and competition studies. Results: We used targeted sequencing to assess BAX among 44 patients relapsing after attaining initial remission on VEN-containing regimens for AML. BAX variants at relapse were identified in 6 patients (13.6%), with a variant allelic frequency (VAF) of 0.75% - 48% (Fig A). This included missense, frameshift (fs), nonsense and splice site mutations (Fig A). One variant, P168A, residing in the linker region prior to the α9 helix is known to reduce BAX translocation and activity. The emergence of BAX mutations at AML progression implicated its role in adaptive resistance (Fig B). In contrast, no BAX mutations were identified in a control cohort of 35 patients with AML relapsing after conventional chemotherapy (Fig A). To explore mechanisms of acquired resistance to BH3 mimetics, OCI-AML3 cells were exposed to increasing concentrations of BCL-2 and MCL1 inhibitors over 3-months. Acquired resistance (OCI-AML3-R) was associated with loss of BAX expression, with no changes observed in other BCL-2 family members (Fig C). In contrast, BAX expression was preserved in OCI-AML3 cells exposed to similar concentrations of DMSO (OCI-AML3 DMSO). Targeted BAX NGS revealed a BAX E41Gfs variant in exon 3 at baseline (VAF 46%). In OCI-AML3-R cells, this variant was detected at a VAF of 86%, with no copy number change detected on sequencing-based copy number assessment, consistent with development of loss of heterozygosity in OCI-AML3-R cells. OCI-AML3-R cells were also cross-resistant to an MCL1 inhibitor (S63845), combination of VEN with S63845 or triple combination with VEN, S63845 and a BCL-X inhibitor A1155463 (not shown). In a xenograft model of AML, cohorts transplanted with OCI-AML-R cells lacking wildtype BAX displayed reduced survival compared to mice transplanted with OCI-AML3-DMSO cells after combined treatment with VEN and S63845 (Fig D). As mitochondrial apoptosis is mediated by pro-apoptotic effectors BAX and BAK, we generated OCI-AML3 cells deficient in BAX or BAK by CRISPR/CAS9 gene editing. Only BAX-/- but not BAK-/- cells were resistant to cell death induced by inhibitors of BCL-2 and MCL1 (not shown). This specificity was confirmed in xenograft models of BAX-/- or BAK-/- AML, which confirmed resistance of BAX deficient cells to combined therapy with VEN and S63845 in vivo (Fig E). Finally, to determine if BAX deficiency confers generalized chemoresistance, a competition assay compared proportions of wildtype BAX expressing and BAX-/- OCI-AML3 cells during a 14-day exposure to either 1) VEN, 2) S63845, 3) combined VEN and S63845 or 4) Ara-C. VEN therapy led to expansion of BAX-/- deficient cells, which was enhanced in combination with S63845. In contrast, treatment with Ara-C depleted BAX-/- cells over 4 days, with death of both BAX and BAX-/- populations seen by day 7 (Fig F). Conclusion: We identified the presence of BAX mutations in AML samples from patients progressing on VEN-containing regimens. We show that BAX, but not BAK loss in an AML cell line is associated with resistance to BH3-mimetic drug combinations resulting in reduced survival in AML xenograft models. In contrast, BAX deficiency does not impede the cytotoxic actions of conventional chemotherapy. We conclude that selection of BAX deficient cells may represent a novel mechanism of resistance to BH3-mimetics in the treatment of AML and that the emergence of BAX variants should be considered in patients developing adaptive resistance to VEN-based therapies. Disclosures Moujalled: Walter and Eliza Hall Institute: Patents & Royalties: milestone and royalty payments related to venetoclax.; Servier: Research Funding. Brown:Servier: Research Funding. Anstee:Walter and Eliza Hall Institute: Patents & Royalties: milestone and royalty payments related to venetoclax.. Banquet:Servier: Current Employment. Chanrion:Servier: Current Employment. Maragno:Servier: Current Employment. Schoumacher:Servier: Current Employment. Lessene:Servier: Research Funding; Walter and Eliza Hall Institute: Patents & Royalties: milestone and royalty payments related to venetoclax.. Geneste:Servier: Current Employment. Huang:Genentech: Research Funding; Walter and Eliza Hall Institute: Patents & Royalties: milestone and royalty payments related to venetoclax.; Servier: Research Funding. Roberts:Servier: Research Funding; Janssen: Research Funding; Genentech: Patents & Royalties: for venetoclax to one of my employers (Walter & Eliza Hall Institute); I receive a share of these royalties; AbbVie: Research Funding. Blombery:Janssen: Honoraria; Invivoscribe: Honoraria; Amgen: Consultancy; Novartis: Consultancy. Wei:Genentech: Honoraria, Other: Advisory committee; Servier: Consultancy, Honoraria, Other: Advisory committee; Walter and Eliza Hall Institute: Patents & Royalties; Macrogenics: Honoraria, Other: Advisory committee; AMGEN: Honoraria, Other: Advisory committee, Research Funding; Astra-Zeneca: Honoraria, Other: Advisory committee, Research Funding; Janssen: Honoraria, Other; Abbvie: Honoraria, Other: Advisory committee, Research Funding, Speakers Bureau; Astellas: Honoraria, Other: Advisory committee; Pfizer: Honoraria, Other: Advisory committee; Celgene: Honoraria, Other: Advisory committee, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.
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Li, Hong, Si-Yu Li, Yang Liu, et al. "Probing primordial gravitational waves: Ali CMB Polarization Telescope." National Science Review 6, no. 1 (2018): 145–54. http://dx.doi.org/10.1093/nsr/nwy019.
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Abstract In this paper, we will give a general introduction to the Ali CMB Polarization Telescope (AliCPT) project, which is a Sino–US joint project led by the Institute of High Energy Physics and involves many different institutes in China. It is the first ground-based Cosmic Microwave Background (CMB) polarization experiment in China and an integral part of China's Gravitational-wave Program. The main scientific goal of the AliCPT project is to probe the primordial gravitational waves (PGWs) originating from the very early Universe. The AliCPT project includes two stages. The first stage, referred to as AliCPT-1, is to build a telescope in the Ali region of Tibet at an altitude of 5250 meters. Once completed, it will be the highest ground-based CMB observatory in the world and will open a new window for probing PGWs in the northern hemisphere. The AliCPT-1 telescope is designed to have about 7000 transition-edge sensor detectors at 95 GHz and 150 GHz. The second stage is to have a more sensitive telescope (AliCPT-2) with more than 20 000 detectors. Our simulations show that AliCPT will improve the current constraint on the tensor-to-scalar ratio r by one order of magnitude with three years' observation. Besides the PGWs, AliCPT will also enable a precise measurement of the CMB rotation angle and provide a precise test of the CPT symmetry. We show that three years' observation will improve the current limit by two orders of magnitude.
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Nelson Wekha, Wafula, Nicholas Kibet Korir, Moses Siambi, Henry F. Ojulong, and Joseph P. Gweyi-Onyango. "Agromorphological Performance and Character Association of Finger Millet under Varying Phosphorus Regimes." Journal of Agricultural Studies 5, no. 1 (2017): 90. http://dx.doi.org/10.5296/jas.v5i1.10809.
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Finger millet production on more than 30% of world arable land is limited by P availability and more than 70% in the semi-arid and marginalized areas which covers most of the Sub-Saharan Africa. Phosphorus is one of the most important elements significantly affecting plant growth and metabolism. Three finger millet varieties (U-15, P-224 and Ikhulule) were evaluated under four P fertilizer levels (0, 12.5, 25 and 37.5 kg ha-1 P2O5) at the International Crops Research Institute for the Semi-Arid Tropics Station, Alupe and the Kenya Agricultural and Livestock Research Organization Station, Kakamega during the long and short rainy seasons of 2015 with the aim of determining their agromorphological response and trait associations. The on-station experiments were laid out in Randomized Complete Block Design in factorial arrangement with three replications. The statistical analysis of phosphorus levels and variety exhibited significant differences (P<0.05) to stand vigor, plant height, leaf blade length, number of leaves and lodging. The results revealed that application of 25 kg ha-1 P2O5 rate led to the tallest plants (65.0 cm), longest leaf blades (58.0 cm) and highest number of leaves per plant (16) at Alupe site while 37.5 kg ha-1 P2O5 rate eliciting the tallest plants (58.79 cm), longest leaf blades (51.44 cm) and highest number of leaves per plant (13) at Kakamega site. The highest rate led to the greatest vigor in both sites for both seasons while the control had the poorest vigor. Variety P-224 showed the highest lodging count with 32 out of 246 plants per experimental unit during the rainy season at Kakamega. The unit increase in grain yield was positively and significantly correlated with increased values of the harvest index (r=0.375), number of leaves (r=0.393) and plant height (r=0.431) but negatively and significantly correlated to the 1000-grain mass (r=-0.578) and lodging (r=-0.233). The best phosphorus treatment for most of the parameters was 25 kg ha-1 P2O5 at Alupe while maximum levels of the study parameters were realized under the 37.5 kg ha-1 P2O5 rate at Kakamega.
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Carvalho, Roberto L. da S., and Angel R. S. Delgado. "Estimates of reference evapotranspiration in the municipality of Ariquemes (RO) using neural networks GMDH-type." Revista Brasileira de Engenharia Agrícola e Ambiental 23, no. 5 (2019): 324–29. http://dx.doi.org/10.1590/1807-1929/agriambi.v23n5p324-329.
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ABSTRACT Reference evapotranspiration is a climatological variable of great importance for water use dimensioning in irrigation methods. In order to contribute to the climatic understanding of Ariquemes, Rodônia state, Brazil, the study aims to model the behavior of the time series of reference evapotranspiration using a GMDH-type (Group Method of Data Handling) artificial neural network (ANN) and to compare it with the SARIMA (Seasonal Autoregressive Integrated Moving Average) methodology. Data from the National Institute of Meteorology - INMET, obtained at the Automatic Weather Station of Ariquemes, from January 2011 to January 2014, were used. Data analysis was performed using software R version 3.3.1 through the GMDH-type ANN package. Modeling by GMDH-type ANN led to results similar to the results of the SARIMA model, thus constituting an option to predict climatic time series. GMDH-type models with larger numbers of inputs and layers presented lowest mean square error.
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Choi, C. B., T. Y. Lee, K. S. Kim, and S. C. Bae. "AB0370 SAFETY OF CS20AT04, A HAPLOIDENTICAL ALLOGENEIC BONE MARROW-DERIVED MESENCHYMAL STEM CELLS, IN A PHASE 1 STUDY IN LUPUS NEPHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1485.2–1485. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3287.
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Background:Mesenchymal stem cells are known to have immunomodulatory properties and may potentially have therapeutic effect in lupus nephritis. Mesenchymal stem cells form a haploidentical donor are an attractive cell sourceObjectives:CS20AT04, a haploidentical allogeneic bone marrow-derived mesenchymal stem cell, was evaluated in patients with lupus nephritis for safety and tolerability.Methods:This was a single-arm phase 1 dose-escalation trial of CS20AT04 in adult patients with lupus nephritis (NCT03174587). A 3 + 3 design was used for dose escalation. The starting dose was 2.0 x 106 cells/kg and was escalated to 3.0 x 106 cells/kg if there no dose-limiting toxicity. The primary objective was to determine the maximum tolerated dose and evaluate the safety and tolerability at 28 days after the infusion.Results:Seven patients were enrolled in the study. Patients received CS20AT04 through intravenous infusion. The initial dose of 2.0 x 106 cells/kg was administered for the first 3 patients without any dose limiting toxicity. There was 1 patient who were not administered the full 2.0 x 106 cells/kg dose due to technical error during infusion. The patient did not show dose limiting toxicity, but 1 additional patient was enrolled to have 3 patients who received the full 2.0 x 106 cells/kg dose before escalating to the next level dose. The dose of 3.0 x 106 cells/kg was administered for the next 3 patients without any dose limiting toxicity. Three adverse events were reported (1 diarrhea, 1 toothache, and 1 arthralgia) and they were all NCI-CTC grade I events.Conclusion:CS20AT04 was well tolerated in single dose up to 3.0 x 106 cells/kg in patients with lupus nephritis.Acknowledgments:This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C0778).Disclosure of Interests:Chan-Bum Choi: None declared, Tae Yong Lee Shareholder of: Corestem Inc, Employee of: Corestem Inc, Kyung Suk Kim Shareholder of: Corestem Inc, Employee of: Corestem Inc, Sang-Cheol Bae: None declared
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Heathershaw, Tony. "Computational ocean acoustics. by F. B. Jensen, W. A. Kuperman, M. B. Porter and H. Schmidt. American institute of physics. 1994. pp. 634. price £70.00 (hardback). isbn 1 56396 209 8. Oceanography and acoustics: Prediction and propagation models. Edited by A. R. Robinson and D. Lee. American Institute of Physics. 1994. Pp. 300. Price £53.00 (hardback). ISBN 1 56396 203 9." Quarterly Journal of the Royal Meteorological Society 121, no. 525 (1995): 1179–81. http://dx.doi.org/10.1002/qj.49712152515.
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Diamant, Betinio. "The Elements of Roman Law, With a Translation of the Institutes of Justinian. 4th edn. by R. W. Lee. [London: Sweet & Maxwell. 1956, 5th impression 1990. 499 pp. ISBN 0-421-01780-5. £18.50]." International and Comparative Law Quarterly 41, no. 2 (1992): 507–8. http://dx.doi.org/10.1093/iclqaj/41.2.507.
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Reed, Kaye E. "Quantitative Paleozoology. R. Lee Lyman." Journal of Anthropological Research 65, no. 4 (2009): 677–78. http://dx.doi.org/10.1086/jar.65.4.25608290.
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Shipman, Pat. "Response to R. Lee Lyman." American Anthropologist 89, no. 3 (1987): 715–17. http://dx.doi.org/10.1525/aa.1987.89.3.02a00150.
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O’Shea, Laura E., James E. Hawkins, Jonathan Lord, et al. "Access to and sustainability of abortion services: a systematic review and meta-analysis for the National Institute of Health and Care Excellence—new clinical guidelines for England." Human Reproduction Update 26, no. 6 (2020): 886–903. http://dx.doi.org/10.1093/humupd/dmaa026.
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Abstract BACKGROUND Induced abortion is a common procedure. However, there is marked variation in accessibility of services across England. Accessing abortion services may be difficult, particularly for women who live in remote areas, are in the second trimester of pregnancy, have complex pre-existing conditions or have difficult social circumstances. OBJECTIVE AND RATIONALE This article presents a two-part review undertaken for a new National Institute of Health and Care Excellence guideline on abortion care, and aiming to determine: the factors that help or hinder accessibility and sustainability of abortion services in England (qualitative review), and strategies that improve these factors, and/or other factors identified by stakeholders (quantitative review). Economic modelling was undertaken to estimate cost savings associated with reducing waiting times. SEARCH METHODS Ovid Embase Classic and Embase, Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), PsycINFO, Cochrane Library via Wiley Online, Cinahl Plus and Web of Science Core Collection were searched for articles published up to November 2018. Studies were included if they were published in English after 2001, conducted in Organization for Economic Co-operation and Development (OECD) countries and were: qualitative studies reporting views of patients and/or staff on factors that help or hinder the accessibility and sustainability of a safe abortion service, or randomized or non-randomized studies that compared strategies to improve factors identified by the qualitative review and/or stakeholders. Studies were excluded if they were conducted in OECD countries where abortion is prohibited altogether or only performed to save the woman’s life. One author assessed risk of bias of included studies using the following checklists: Critical Appraisal Skills Programme checklist for qualitative studies, Cochrane Collaboration quality checklist for randomized controlled trials, Newcastle-Ottawa scale for cohort studies, and Effective Practice and Organization of Care risk of bias tool for before-and-after studies. Qualitative evidence was combined using thematic analysis and overall quality of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Confidence in the Evidence from Reviews of Qualitative Research (CERQual). Quantitative evidence was analysed in Review Manager 5.3 and overall quality of evidence was assessed using GRADE. OUTCOMES Eight themes (service level barriers; financial barriers; logistical barriers; personal barriers; legal and policy barriers; privacy and confidentiality concerns; training and education; community prescribing and telemedicine introduce greater flexibility) and 18 subthemes were identified from 23 papers (n = 1016) included in the qualitative review. The quality of evidence ranged from very low to high, with evidence for one theme and seven subthemes rated as high quality. Nine studies (n = 7061) were included in the quantitative review which showed that satisfaction was better (low to high quality evidence) and women were seen sooner (very low quality evidence) when care was led by nurses or midwives compared with physician-led services, women were seen sooner when they could self-refer (very low quality evidence), and clinicians were more likely to provide abortions if training used an opt-out model (very low quality evidence). Economic modelling showed that even small reductions in waiting times could result in large cost savings for services. WIDER IMPLICATIONS Self-referral, funding for travel and accommodation, reducing waiting times, remote assessment, community services, maximizing the role of nurses and midwives and including practical experience of performing abortion in core curriculums, unless the trainee opts out, should improve access to and sustainability of abortion services.
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Sklodowski, Kamil, Vito Dozio, Silvia Lopez-Lastra, Andrés Lanzós, Kristina Beeler, and Emanuela Romano. "59 Integrating deep proteomics profiling with survival analysis to identify novel biomarkers of response to PD-1 blockade in NSCLC patients." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (2020): A64. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0059.
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BackgroundImmune checkpoint inhibitors have improved clinical responses and overall survival for patients with non-small cell lung cancer (NSCLC). However, the response is not equal and known NSCLC biomarkers are not sufficient in predicting therapy outcome. Deep proteomic analysis of NSCLC patient‘s plasma treated with anti-PD-1-blockade using a state-of-the-art data independent acquisition mass spectrometry (DIA-MS) is a powerful and unbiased way of identifying protein signatures associated with disease stage or response to treatment. However, to unravel these associations large-scale omics data should be analyzed with respect to available clinical information. To achieve this goal, we have used an approach previously applied by Uhlen et al., 20171 for transcriptomic datasets. In this approach survival data is used to set the most optimal thresholds for candidate biomarkers.Methods125 plasma samples were analyzed by capillary flow liquid chromatography coupled to DIA-MS. Data were extracted with latest SpectronautTM and proteins were quantified. Each recorded protein intensity was used as a threshold for two groups of samples for which Kaplan-Meier estimates were generated using ‘survival’2 package in R. Benjamini-Hochberg correction was applied and p-values with corresponding intensity cut-offs were extracted to generate panels of potential biomarkers.Results125 plasma samples (in total 75 baseline and 50 after 8-weeks treatment) from advanced NSCLC patients treated with an anti-PD-1 inhibitor following at least 1 prior line of treatment were analyzed. 727 unique proteins were quantified across all samples. Data analysis was performed separately for each line of treatment and treatment status resulting in more than 100’000 p-values. For each group, panels of proteins with best performance in separating progression free survivals were defined at FDR of 0.10, giving 64 unique proteins which were mapped to acute phase response, platelet degranulation and complement activation. Several of these proteins were listed in the Early Detection Research Network database of the National Cancer Institute, and one of them – LYPD3, was a potential therapeutic target in a preclinical study for NSCL treatment.3 Selected proteins were then used to cluster patients into cohorts that showed association with the response to therapy.ConclusionsDeep proteomic profiling of plasma samples using DIA-MS in conjunction with clinical outcome enables a holistic and stringent analysis of potential circulating biomarkers. Such analysis generates functional insights into the plasma proteome that enable deeper understanding and comprehensive integration of clinical data with proteomics markers at different disease stages and treatment phases.ReferencesUhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z, Edfors F, Sanli K, von Feilitzen K, Oksvold P, Lundberg E, Hober S, Nilsson P, Mattsson J, Schwenk J.Therneau TM, Grambsch PM. Modeling Survival Data: Extending the Cox Model. Springer. 2000, New York, ISBN 0-387-98784-3.Willuda J, Linden L, Lerchen H, Kopitz C, Stelte-Ludwig B, Pena C, Lange C, Golfier S, Kneip C, Carrigan P E, Mclean K, Schuhmacher J, von Ahsen O, Müller J, Dittmer F, Beier R, El Sheikh S, Tebbe J, Leder G, Apeler H, Jautelat R, Ziegelbauer K, Kreft B, Preclinical Antitumor Efficacy of BAY 1129980-a Novel Auristatin-Based Anti-C4.4A (LYPD3) Antibody-Drug Conjugate for the Treatment of Non-Small Cell Lung Cancer. Mol Caner Ther 2017;16(5):893–904
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DENICOFF, K. D., G. S. LEVERICH, W. A. NOLEN, et al. "Validation of the prospective NIMH-Life-Chart Method (NIMH-LCMTM-p) for longitudinal assessment of bipolar illness." Psychological Medicine 30, no. 6 (2000): 1391–97. http://dx.doi.org/10.1017/s0033291799002810.
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Background. Systematic and accurate depiction of a patient's course of illness is crucial for assessing the efficacy of maintenance treatments for bipolar disorder. This need to rate the long-term prospective course of illness led to the development of the National Institute of Mental Health prospective Life Chart Methodology (NIMH-LCMTM-p or LCM). The NIMH-LCMTM-p allows for the daily assessment of mood and episode severity based on the degree of mood associated functional impairment. We have previously presented preliminary evidence of the reliability and validity of the LCM, and its utility in clinical trials. This study is a further and more extensive validation of the clinician rated NIMH-LCMTM-p.Methods. Subjects included 270 bipolar patients from the five sites participating in the Stanley Foundation Bipolar Network. Daily prospective LCM ratings on the clinician form were initiated upon entry, in addition to at least monthly ratings with the Inventory of Depressive Symptomatology-clinician rated (IDS-C), the Young Mania Rating Scale (YMRS) and the Global Assessment of Functioning (GAF). We correlated appropriate measures and time domains of the LCM with the IDS-C, YMRS and GAF.Results. Severity of depression on the LCM and on the IDS-C were highly correlated in 270 patients (r = −0·785, P < 0·001). Similarly, a strong correlation was found between LCM mania and the YMRS (r = 0·656, P < 0·001) and between the LCM average severity of illness and the GAF (r = −0·732, P < 0·001).Conclusions. These data further demonstrate the validity and potential utility of the NIMH- LCMTM-p for the detailed daily longitudinal assessment of manic and depressive severity and course, and response to treatment.
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Cai, Xichen, and D. C. Neckers. "Photoresponsive Polymers I Photoresponsive Polymers I . Edited by Seth R. Marder (Georgia Institute of Technology, Atlanta, USA) and Kwang-Sup Lee (Hannam University, Daejeon, South Korea). From the series Advances in Polymer Science, 213. Springer-Verlag: Berlin, Heidelberg. 2008. xii + 210 pp. $229. ISBN 978-3-540-69448-9 ." Journal of the American Chemical Society 131, no. 9 (2009): 3407. http://dx.doi.org/10.1021/ja900878r.
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Nell, Victor. "Interpretation and Misinterpretation of the South African Wechsler-Bellevue Adult Intelligence Scale: A History and a Prospectus." South African Journal of Psychology 24, no. 2 (1994): 100–109. http://dx.doi.org/10.1177/008124639402400208.
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The South African Wechsler is based on the 1939 Wechsler-Bellevue Adult Intelligence Scale. However, the name under which it was published by the National Institute of Personnel Research in 1969, the ‘South African Wechsler Adult Intelligence Scale’, has led a generation of South African psychologists to believe that this instrument is a local verson of the 1955 WAIS, a fundamentally revised and renormed Wechsler-Bellevue. It is argued that the continued use of the South African Wechsler-Bellevue, with its outdated norms and unknown statistical properties, is not in the public interest, and that diagnostic conclusions based on this instrument may be misleading. It is then argued that if a new adult intelligence scale is to be developed, this should be based on the 1981 revision of the Wechsler (WAIS-R), rather than the local scale now under development by the Human Sciences Research Council; and finally, that in psychology, South Africa is not a beggar at the world's door, and that the capability exists for the development of an innovative and culturally appropriate ability assessment device. One such possibility is described.
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Afriansyah, Afriansyah. "ANALISIS DAN DESAIN SISTEM INFORMASI ADMINISTRASI KEGIATAN PENELITIAN DAN PENGABDIAN MASYARAKAT MENGGUNAKAN METODE WORK SYSTEM FRAMEWORK DENGAN PEMODELAN UNIFIED MODELING LANGUAGE." INTECOMS: Journal of Information Technology and Computer Science 1, no. 2 (2018): 168–82. http://dx.doi.org/10.31539/intecoms.v1i2.292.
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University can’t be separated from the Tri Dharma namely in the fields of education, research and community service. Institute for Research and Community Services Lancang Kuning University has launched a strategic framework for research through the Research Master Plan (RIP) and the Roadmap Research to support research results and superior quality. One of them by building an Information Systems Research Activities Administration and Community Services seeks to streamline the work of the staff LPPM and also makes it easy for researchers in particular lecturers and reviewers in their duties. In this system, the researchers register their proposals online. Furthermore, staff LPPM recaps the number of proposals on all types of grants that is then distributed to the reviewer to assess. Administration Information System Research Activities and Community Service is used method of analysis Work System Framework. Methods of work system framework, expected later able to provide a description of the process or activity system that uses information technology or other resources. Modeling design methodology using Unified Modeling Language (UML) and MySql database.
 
 Keywords : Information Systems, Administration, Work System Framework, UML
 Alter, S. (2013). Work system theory: overview of core concepts, extensions, and challenges for the future. Journal of the Association for Information Systems, 72.
 DIKTI. (2016). Panduan Pelaksanaan Penelitian dan Pengabdian Masyarakat di Perguruan Tinggi. Direktorat Jenderal Penguatan Riset dan Pengembangan Kementerian Riset, Teknologi, dan Pendidikan Tinggi. Edisi X.
 Hamzah. (2016). Sistem Informasi Kegiatan Penelitian dan Pengabdian Kepada Masyarakat Universitas Respati. Jurnal Teknologi dan Sistem Informasi(TEKNOSI), 2(2): 17-26.
 Lee, S. Unified Modeling Language (UML) for Database Systems and Computer Applications.
 Rohman, N. (2009). Sistem Pengolahan Data Kp Dan Ta Pada Program Studi If, Mi Dan Ka Stmik Mardira Indonesia Bandung. Jurnal Computech & Bisnis, 3(1), 1-13.
 Rosa, A. S., dan Shalahuddin, M. (2013). Rekayasa Perangkat Lunak Terstruktur Dan Berorientasi Objek. Informatika. Bandung
 Williandy, I., Fitriawan, H., & SP, R. A. (2016). Rancang Bangun Sistem Informasi Penelitian dan Pengabdian Kepada Masyarakat Fakultas Teknik Universitas Lampung Menggunakan PHP dan MySQL. Jurnal Rekayasa dan Teknologi Elektro(ELECTRICIAN), 10(3) : 192-200.
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Nacef, L., H. Ferjani, H. Riahi, et al. "AB0191 ON WHICH FACTOR TO ACT TO REDUCE CARDIOVASCULAR RISK IN PATIENTS WITH RHEUMATOID ARTHRITIS?" Annals of the Rheumatic Diseases 80, Suppl 1 (2021): 1119.3–1120. http://dx.doi.org/10.1136/annrheumdis-2021-eular.4183.
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Background:Patients with rheumatoid arthritis (RA) are at higher cardiovascular risk (CVR) than the general population due to chronic inflammation. Several factors, both modifiable and non-modifiable, can increase this risk. Intima-media thickness (IMT) was considered as a marker for atherosclerosis.Objectives:This study aimed to identify predictor factors of increasing IMT.Methods:The prospective study was carried out on patients with RA who met the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria. These patients were followed in the rheumatology department of the Kassab Institute. The socio-demographic data, biological and immunological parameters were collected.Framingham’s score quantified the cardiovascular risk at 10-years. Carotid Ultrasonography (US) using a high resolution B mode carotid measured intima-media thickness (IMT) as a subclinical marker of atherosclerosis. Carotid US was performed in the supine position, according to American Society of Echocardiography guidelines. IMT was measured in the left (LCC) and right (RCC) common carotid arteries, the left (LIC) and right (RIC) internal carotid arteries, and the left (LEC) and right (RIC) internal carotid arteries. An increased IMT was defined as ≥0.9 mm.We analyzed data by the SPSS statistical package. A p-value <0.05 was considered significant.Results:Of the 47 patients surveyed, 78.7% were female. The mean age was 52.5 ±11.06 [32-76]. The duration disease was 86.25 ±63 months [5-288] and was erosive in 81.6% of cases. The rheumatoid factor (RF) was positive in 57.8% of patients, and citrullinated antipeptide antibodies (ACPA) were present in 62.2%. Eight patients had a previous CV history (hypertension, diabetes or dyslipidemia) and 16.4% were active smokers. Among women, 43.6% were postmenopausal. ITM was significantly higher in men at LIC (0.037) and LEC (0.025). Older age was associated with increased ITM in LIC (p=0.046; r=0.295), LEC (p=0.05; r=0.412), RCC (p=0.034; r=0.317), and REC (p=0.009; r=0.382). The ITM for LCC, LIC, LEC, RCC, RIC, and REC was higher in postmenopausal women, with no significant difference (p=0.782, p=0.208, p=0.877, r=0.734, p=0.808, p=0.437, respectively).Among the modifiable factors, active smoking was associated with a higher ITM at the REC level (p=0.047). However, weight was not associated with an increased ITM (LCC: p=0.092; LIC: p=0.985; LEC: p=0.952; RCC: p=0.744; RIC: p=0.210; REC: p=0.510). In our study, there was no significant association between DAS28 disease activity or inflammatory marks and ITM (LCC: p=0.784; LIC: p=0.316; LEC: p=0.420; RCC: p=0.784; RIC: p=0.484; REC: p=0.754).Conclusion:In our study, the non-modifiable factors associated with increased ITM were advanced age and male gender. The modifiable factor impacting ITM was primarily active smoking. Surprisingly, disease activity and biological inflammation did not influence ITM.References:[1]S. Gunter and al. Arterial wave reflection and subclinical atherosclerosis in rheumatoid arthritis. Clinical and experimental rheumatology 2018; 36: clinical e.xperimental.[2]Aslan and al. Assessment of local carotid stiffness in seronegative and seropositive rheumatoid Arthritis. Scandinavian cardiovascular journal, 2017.[3]Martin i. Wah-suarez and al, carotid ultrasound findings in rheumatoid arthritis and control subjects: a case-control study. Int j rheum dis. 2018;1–7.Disclosure of Interests:None declared
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Wührl, Peter. "Im Gespräch mit ... R. Paul Lee." DO - Deutsche Zeitschrift für Osteopathie 5, no. 2 (2007): 4–6. http://dx.doi.org/10.1055/s-2007-981508.
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Mekel, Crystalinda T. O., Jenny ,. Baroleh, and Caroline B. D. Pakasi. "PROFIL USAHA KLAPERTAART MANADO." AGRI-SOSIOEKONOMI 11, no. 3 (2015): 25. http://dx.doi.org/10.35791/agrsosek.11.3.2015.9860.
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This study aims to provide a description of the Petra klapertaart business in terms of raw materials, capital, labor, production, costs, and the amount of profit earned.This research was conducted for one mounth on October 2015. The data used are primary data get from the owner. Petra klapertaart is one of the home industries that can give value added to coconut plants, particularly coconuts, so it can help coconut farmers to improve their economy. Constraints limited capital to run the business, get solution from the Ministry of Agriculture that is Petra klapertaart registered as one of a member the Independent Institute Rooted in the Community (LM3), which receive capital assistance in the form of funds. This led to make a research to see the description of the business profile Petra klapertaart after getting financial aid from the Ministry of Agriculture. Data obtained with primary data taken by researchers from business owners as the the main source. Data collection techniques were done by direct observation and interviews with business owners. The results showed that the Petra klapertaart business is a small-scale business that uses coconut raw materials that processed into klapertaart and became one of the members of the Independent Institute Rooted in the Community (LM3) which get funding. On Klapertaart marketing activities, business owners deal directly with consumers to sell klapertaart. Based on the results, the amount of production, the amount of production in September 2015, which is 12 times the production made two recipes in each production, produce 348 klapertaart cup aluminum foil, make a profit with the ratio of R / C> 1 is equal to 1.84 in September 2015 means, Petra business get the benefits, so this business is effort to develop
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Buchanan, J. Grant. "Sir James Baddiley. 15 May 1918 — 19 November 2008." Biographical Memoirs of Fellows of the Royal Society 56 (January 2010): 3–23. http://dx.doi.org/10.1098/rsbm.2010.0010.
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James Baddiley was a biochemist who used the methods and insight of the organic chemist to answer important questions in biology, notably coenzyme structure and the structure and function of bacterial cell walls. A graduate of Manchester University, he moved to Cambridge in 1944 with A. R. Todd, where he synthesized adenosine triphosphate, the nucleotide concerned with essential energy transformations in all forms of life. As an independent researcher at the Lister Institute in London he elucidated the structure of coenzyme A and other coenzymes. He was appointed Professor of Organic Chemistry in Newcastle, where the exploration of the structures of two cytidine nucleotides led to the discovery of the teichoic acids, major components of the cell walls and membranes of Gram-positive bacteria. These discoveries were extended to cover the structures, biosynthesis, function and immunology of the teichoic acids. Baddiley became Professor of Chemical Microbiology in 1977. Moving to Cambridge after his retirement, he was able to continue his researches in the Department of Biochemistry. He was elected a Fellow of Pembroke College and as an elder statesman undertook extensive committee work, often as chairman, both in Cambridge University and nationally. He was knighted in 1977.
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Duran, Kevin. "Reviewer Acknowledgements for International Business Research, Vol. 12, No. 3." International Business Research 12, no. 3 (2019): 174. http://dx.doi.org/10.5539/ibr.v12n3p174.
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International Business Research wishes to acknowledge the following individuals for their assistance with peer review of manuscripts for this issue. Their help and contributions in maintaining the quality of the journal are greatly appreciated.
 
 International Business Research is recruiting reviewers for the journal. If you are interested in becoming a reviewer, we welcome you to join us. Please find the application form and details at http://www.ccsenet.org/journal/index.php/ibr/editor/recruitment and e-mail the completed application form to ibr@ccsenet.org.
 
 Reviewers for Volume 12, Number 3
 
 &nbsp;
 
 Alireza Athari, Eastern Mediterranean University, Iran
 
 Anca Gabriela Turtureanu, &ldquo;DANUBIUS&rdquo; University Galati, Romania
 
 Andrea Carosi, University of Sassari, Italy
 
 Anna Paola Micheli, Univrtsity of Cassino and Southern Lazio, Italy
 
 Ant&ocirc;nio Andr&eacute; Cunha Callado, Universidade Federal Rural de Pernmabuco, Brazil
 
 Ashford C Chea, Benedict College, USA
 
 Bruno Marsigalia, University of Casino and Southern Lazio, Italy
 
 Chokri Kooli, International Center for Basic Research applied, Paris, Canada
 
 Christopher Alozie, Tansian University, Nigeria
 
 Cristian Marian Barbu, &ldquo;ARTIFEX&rdquo; University, Romania
 
 Duminda Kuruppuarachchi, University of Otago, New Zealand
 
 Essia Ries Ahmed, Universiti Sains Malaysia, Malaysia
 
 Federica Caboni, University of Cagliari, Italy
 
 Federica De Santis, University of Pisa, Italy
 
 Florin Ionita, The Bucharest Academy of Economic Studies, Romania
 
 Foued Hamouda, Ecole Sup&eacute;rieure de Commerce, Tunisia
 
 Francesco Ciampi, Florence University, Italy
 
 Francesco Scalera, University of Bari &quot;Aldo Moro&quot;, Italy
 
 Gianluca Ginesti, University of Naples &ldquo;FEDERICO II&rdquo;, Italy
 
 Hillary Odor, University of Benin, Nigeria
 
 Ivana Tomic, IT Company CloudTech, Republic of Serbia
 
 Joanna Katarzyna Blach, University of Economics in Katowice, Poland
 
 Joseph Lok-Man Lee, The Hong Kong Polytechnic University, Hong Kong
 
 Khaled Mokni, Northern Border University, Tunisia
 
 L. Leo Franklin, Bharathidasn University, India
 
 Ladislav Mura, University of Ss. Cyril and Methodius in Trnava, Slovakia
 
 Leow Hon Wei, SEGi University, Malaysia
 
 Manuel A. R. da Fonseca, Federal University of Rio de Janeiro (UFRJ), Brazil
 
 Marcelino Jos&eacute; Jorge, Evandro Chagas Clinical Research Institute of Oswaldo Cruz Foundation, Brazil
 
 Maria do C&eacute;u Gaspar Alves, University of Beira Interior, Portugal
 
 Maria Teresa Bianchi, University of Rome &ldquo;LA SAPIENZA&rdquo;, Italy
 
 Miriam Jankalov&aacute;, University of Zilina, Slovakia
 
 Mongi Arfaoui, University of Monastir, Tunisia
 
 Muath Eleswed, American University of Kuwait, USA
 
 Ozgur Demirtas, Turkish Air Force Academy, Turkey
 
 Pascal Stiefenhofer, University of Brighton, UK
 
 Prosper Senyo Koto, Dalhousie University, Canada
 
 Rafiuddin Ahmed, James Cook University, Australia
 
 Razana Juhaida Johari, Universiti Teknologi MARA, Malaysia
 
 Riccardo Cimini, University of Tuscia, Viterbo, Italy
 
 Roberto Campos da Rocha Miranda, University Center Iesb, Brazil
 
 Sang- Bing Tsai, University of Electronic Science and Technology of China, China
 
 Sara Saggese, University of Naples Federico II, Italy
 
 Shun Mun Helen Wong, The Hong Kong Polytechnic University, Hong Kong
 
 Slavoljub M. Vujović, Economic Institute, Belgrade, Serbia
 
 Tariq Tawfeeq Yousif Alabdullah, University of Basrah, Iraq
 
 Valerija Botric, The Institute of Economics, Zagreb, Croatia
 
 Velia Gabriella Cenciarelli, University of Pisa, Italy
 
 Yan Lu, University of Central Florida, USA
 
 Yasmin Tahira, Al Ain University of Science and Technology, Al Ain, UAE
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Стоюхина, Н. Ю. "GEORGY IVANOVICH CHELPANOV AND LABOR PSYCHOLOGY." Институт психологии Российской Академии Наук. Организационная психология и психология труда, no. 1(18) (April 12, 2021): 162–83. http://dx.doi.org/10.38098/ipran.opwp.2021.18.1.008.
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В статье анализируются результаты поездки Г.И. Челпанова в Америку в 1911 г., куда он направился во время строительства Психологического института при Московском университете для ознакомления с организацией психологических институтов и лабораторий, в которых работали виднейшие ученые Дж.М. Кеттелл, Р. Вудвортс, Э.Б. Титченер, Д.Р. Энджелл, Х.А. Карр, Ч.Х. Джадд, Д.Ф. Шепард, У.Б. Пиллсбери, С. Холл, Г. Мюнстерберг и др. Устройство и принципы работы руководимых ими научно-исследовательских подразделений оставили большое впечатление. По приезде в Москву в своих выступлениях он неоднократно возвращался к своим американским воспоминаниям. Начало ХХ в. характеризовалось зарождением прикладной психологии, а одним из ее направлений была психология труда. Американский ученый немецкого происхождения Г. Мюнстерберг - признанный в мире основатель прикладной психологии, за трудами которого внимательно следил Г.И. Челпанов. Именно ее развитие стала предметом обсуждения в его выступлениях в 1911 - 1912 гг. Главные вопросы, требовавшие незамедлительного ответа - области приложения прикладной психологии и кто будет этим заниматься в России. Именно Психологический институт, оснащенный самыми современными приборами, должен был готовить к будущим научным исследованиям тех молодых людей, которые в скором времени займутся прикладной психологией. Так и произошло - с 1912 г. заработал Психологический институт, где воплощались замыслы Г.И. Челпанова. В 1921 г., т.е. ровно 100 лет назад, уже в Советской России, он возвращается к теме прикладной психологии, имевшей конкретное имя - психология труда. Он наметил задачи, требовавшие незамедлительного решения, которые, как показала практика 1920-30-х гг., решались советскими учеными. The article addresses G. I. Chelpanov’s trip to the USA in 1911, where he went during the construction of the Psychological Institute at Moscow University to get acquainted with the organization of psychological institutes and laboratories, where the most prominent scientists J. M. Cattell, R. Woodworth, E. B. Titchener, J.R. Angell, H. A. Carr, C. H. Judd, J. F. Shepard, W. B. Pillsbury, S. Hall, G. Münsterberg and many others worked, the structure and principles of the research led by them left a great impression. Speaking upon his arrival in Moscow, he repeatedly returns to his American memories. The beginning of the twentieth century was marked by the emergence of applied psychology, and one of the areas was labor psychology. The American scientist of German origin G. Münsterberg is the internationally recognized founder of applied psychology, whose works G. I. Chelpanov knew and followed. It was its development that became the subject of discussion in his speeches in 1911 and 1912. The main questions that demanded an immediate answer were the areas of application of applied psychology and personalities who would implement this in Russia. It was the modern and equipped with the most modern devices Psychological Institute that was supposed to prepare for future scientific research those young people who would soon be engaged in applied psychology. And so, it happened - since 1912 the Psychological Institute was opened, where G. I. Chelpanov’s ideas were manifested. In 1921, already in Soviet Russia, he returned to the topic of applied psychology, which already had a specific name - labor psychology. He outlined the tasks that needed to be addressed in the near future, which, as the practice of the 1920s and 1930s showed, were solved by Soviet scientists.
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Hickey, Robert C., and Gerald P. Murphy. "R. Lee Clark, Jr., M.D. 1906–1994." Journal of Surgical Oncology 56, no. 2 (1994): i—ii. http://dx.doi.org/10.1002/jso.2930560202.
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Baravik-Munsell, Erica. "Dr. William R. Lee (“Bill”) (1978-2016)." Veterinary Radiology & Ultrasound 58, no. 4 (2017): 487. http://dx.doi.org/10.1111/vru.12498.
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Hosain, Suman Nazmul, Farzana Amin, and Shahnaz Ferdous. "The Anesthesia & Anesthetists of the First Open Heart Surgery of Bangladesh." Bangladesh Heart Journal 36, no. 1 (2021): 55–60. http://dx.doi.org/10.3329/bhj.v36i1.55518.
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Although a few closed heart operations were performed in the late 1960s, well organized approach to open heart surgery began in Bangladesh only after establishment of Institute of Cardiovascular Diseases (ICVD) in 1978. A Japanese team of surgeons, anesthetists, nurses and technicians provided extensive support in capacity building of the local human resources. Ultimately the first open heart surgery of Bangladesh, the direct closure of Atrial Septal Defect of an 18 year old college student, was performed on 18th September 1981. It was great news of that time. People came to know about the success story of the ICVD director then Colonel M Abdul Malik, a renowned cardiologist cum team leader and the Bangladeshi surgeon duo Dr M Nabi Alam Khan and Dr S R Khan. But somehow the anesthetists, an important part of the team were out of focus and have been forgotten over time. Led by Prof Khalilur Rahman, the anesthetist team of the day included Dr Nurul Islam, Dr Abdul Hadi, Dr Delowar Hossain, Dr A Y F Ellahi Chowdhury and Dr Monir Hossain. This article is an attempt to remind their contribution and expressing respect and gratitude to the anesthetists of that pioneering team. Bangladesh Heart Journal 2021; 36(1) : 55-60
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Laba, I. Nengah. "Developing Students’ Essay Writing about Tourism Topics through Word Clustering Technique." Journal of Business on Hospitality and Tourism 3, no. 1 (2017): 96. http://dx.doi.org/10.22334/jbhost.v3i1.94.
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This study aimed to analyze the effectiveness of developing students’ essay writing about tourism topics through word clustering technique. The subjects under study were students sitting on semester 6 at Sekolah Tinggi Pariwisata Bali Internasional (International Bali Institute of Tourism). This classroom action research (CAR) was basically triggered by the fact that the subjects under study have still low capability in English essay writing about Tourism Topics. This study made use of pre-test or initial reflection (IR) and post-test research design using descriptive analysis. There were two cycles in this CAR and each cycle consists of four successive sessions. The IR was intended to establish the real pre-existing English essay writing capability of the subject under study. The Mean of the Pre-test or IR score obtained by the subjects under study was 3.63. The Mean of the Post-test or R scores both in Cycle I and in Cycle II showed an increasing figure which is 4.12 in S1, 5.06 in S2, 5.78 in S3, 6.34 in S4, 6.76 in S5, 7.14 in S6, 7.44 in S7 and 7.82 in S8. These figures showed that the Mean of the Post-test or R scores in each session was much higher than the Mean of Pre-test or IR in essay writing. The data analysis further led to the computation of the Grand Mean score for both Cycles I and Cycle II. The computation of the Grand Mean resulted in Cycle I (XI) was 5.32. The computation of the Grand Mean resulted in Cycle II was 7.29. The difference Mean of Cycle I and cycle II is 1.97 (XII – XI = 7.29 – 5.32 = 1.97). These research findings revealed that developing students’ essay writing about the tourism topics through word clustering technique was very effective.
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Mau, Theresa, Martin O’Brien, Amiya K. Ghosh, Richard A. Miller, and Raymond Yung. "Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging." Journals of Gerontology: Series A 75, no. 1 (2019): 89–98. http://dx.doi.org/10.1093/gerona/glz177.
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Abstract The National Institute on Aging (NIA)-sponsored Interventions Testing Program (ITP) has identified a number of dietary drug interventions that significantly extend life span, including rapamycin, acarbose, and 17-α estradiol. However, these drugs have diverse downstream targets, and their effects on age-associated organ-specific changes are unclear (Nadon NL, Strong R, Miller RA, Harrison DE. NIA Interventions Testing Program: investigating putative aging intervention agents in a genetically heterogeneous mouse model. EBioMedicine. 2017;21:3–4. doi:10.1016/j.ebiom.2016.11.038). Potential mechanisms by which these drugs extend life could be through their effect on inflammatory processes often noted in tissues of aging mice and humans. Our study focuses on the effects of three drugs in the ITP on inflammation in gonadal white adipose tissue (gWAT) of HET3 mice—including adiposity, adipose tissue macrophage (ATM) M1/M2 polarization, markers of cellular senescence, and endoplasmic reticulum stress. We found that rapamycin led to a 56% increase of CD45+ leukocytes in gWAT, where the majority of these are ATMs. Interestingly, rapamycin led to a 217% and 106% increase of M1 (CD45+CD64+CD206−) ATMs in females and males, respectively. Our data suggest rapamycin may achieve life-span extension in part through adipose tissue inflammation. Additionally, HET3 mice exhibit a spectrum of age-associated changes in the gWAT, but acarbose and 17-α estradiol do not strongly alter these phenotypes—suggesting that acarbose and 17- α estradiol may not influence life span through mechanisms involving adipose tissue inflammation.
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Phillips, Tycel J., Adam J. Olszewski, Javier Munoz, et al. "Mosunetuzumab, a Novel CD20/CD3 Bispecific Antibody, in Combination with CHOP Confers High Response Rates in Patients with Diffuse Large B-Cell Lymphoma." Blood 136, Supplement 1 (2020): 37–38. http://dx.doi.org/10.1182/blood-2020-136295.
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Introduction: Despite the curative intent of the R-CHOP regimen in the first-line treatment of diffuse large B-cell lymphoma (DLBCL), 35-40% of patients who received R-CHOP will eventually succumb to their disease (Coiffier, et al. Blood 2010; Sarkozy and Sehn. Ann Lymphoma 2019). As such, improved treatments are needed. Mosunetuzumab (Mosun) is a T-cell-engaging bispecific antibody that redirects T cells to eliminate malignant B cells by binding to CD3 on T cells and CD20 on B cells. Mosun monotherapy has a manageable safety profile and promising efficacy, including durable complete responses (CR), in patients (pts) with relapsed and/or refractory (R/R) non-Hodgkin lymphoma (NHL) (Schuster, et al. ASH 2019). This is the first report describing the safety and efficacy of Mosun plus CHOP (M-CHOP) in pts with R/R NHL and newly diagnosed DLBCL in the ongoing GO40515 (NCT03677141) study. Methods: Pts with R/R NHL and with newly diagnosed DLBCL received six 21-day cycles of M-CHOP. In Cycle (C) 1, Mosun was administered in step-up doses on Day (D) 1 (1mg), D8 (2mg), and D15 (13.5mg and 30mg in R/R NHL; 30mg in newly diagnosed DLBCL) to mitigate cytokine release syndrome (CRS). Full dose Mosun (C1D15 dose) was given on D1 of subsequent cycles in addition to CHOP. Interim and primary response assessments were obtained after C4 and C6, respectively. Primary prophylaxis with granulocyte colony-stimulating factor was mandatory for all pts. Pts with a partial response or stable disease at the end of C6 could continue Mosun monotherapy for up to 11 additional cycles. Response rates were based on the Lugano criteria (Cheson, et al. J Clin Oncol 2014). Results: As of June 3, 2020, 43 pts had received M-CHOP: seven patients with R/R NHL, and 36 pts with newly diagnosed DLBCL. Pts with disease stage II-IV were enrolled, with a median IPI score of 3 (range: 2-4) and ECOG performance status between 0 and 2. Median age was 66 (range: 39-87) and 17 pts (42%) were female. In pts with R/R NHL treated with M-CHOP (n=7), the overall response rate (ORR) was 86%, with 71% of pts achieving a CR. Twenty-seven out of 36 pts with previously untreated DLBCL started treatment at least three months prior to data cut-off date; in these pts the ORR was 96%, with a CR rate of 85% (Table). Grade (Gr) ≥3 adverse events (AEs) occurred in 37 pts (86%) and serious AEs in 19 pts (44%). Two pts (29%) with R/R NHL experienced CRS (one with Gr 1 and one with Gr 2; ASTCT grading, Lee et al. Biol Blood Marrow Transplant 2019); one pt received tocilizumab. Nineteen pts (53%) with previously untreated DLBCL had CRS events (14 with Gr 1, five with Gr2); one pt received tocilizumab. No pts required vasopressors or high-flow oxygen. All CRS events occurred in C1, resolved without sequelae, and did not result in discontinuation or delay in treatment. No immune effector cell-associated neurotoxicity syndrome (ICANS) events were observed. Neutropenia occurred in two pts with R/R NHL (29%; Gr 4 n=2) and 23 pts with newly diagnosed DLBCL (64%; Gr 3 n=3, Gr 4 n=20). Febrile neutropenia occurred in two pts (29%) with R/R NHL, and six pts (17%) with newly diagnosed DLBCL. Gr 5 AEs, excluding disease progression, were reported in two pts: one due to Pneumocystis jirovecii pneumonia in a pt with R/R NHL, and one due to pneumonia in a pt with newly diagnosed DLBCL. All pts with R/R NHL have completed treatment. Among pts with newly diagnosed DLBCL, four have completed treatment and 29 remain on treatment; one pt died on-study (Gr 5 pneumonia), and two withdrew from the study treatment due to AEs (one due to treatment-unrelated esophageal perforation; one due to treatment-related pneumonitis). Linear pharmacokinetics (PK) were observed for Mosun. No differences were seen in Mosun exposure for pts with R/R NHL and previously untreated DLBCL. Similar PK characteristics were seen with M-CHOP as with Mosun monotherapy, indicating no impact when co-administered with CHOP. Conclusions: Preliminary data show that Mosun, a novel CD20/CD3 bispecific antibody, when combined with CHOP confers high response rates and a manageable safety profile in pts with R/R NHL and previously untreated DLBCL. End of treatment response rate data for pts with previously untreated DLBCL, and correlative studies of T-cell response, will be presented. Disclosures Phillips: Incyte: Consultancy, Other: travel expenses; AstraZeneca: Consultancy; Seattle Genetics: Consultancy; Bayer: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Pharmacyclics: Consultancy; Cardinal Health: Consultancy; BMS: Consultancy; Beigene: Consultancy; Karyopharm: Consultancy. Olszewski:TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding; Spectrum Pharmaceuticals: Research Funding; Genentech, Inc.: Research Funding. Munoz:Alexion: Consultancy; Portola: Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy; Bayer: Consultancy, Research Funding, Speakers Bureau; Kyowa: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Verastem: Speakers Bureau; Juno/Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Beigene: Consultancy, Speakers Bureau; Fosunkite: Consultancy; Innovent: Consultancy; Acrotech/Aurobindo: Speakers Bureau; AstraZeneca: Speakers Bureau; Genentech/Roche: Research Funding, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Merck: Research Funding; Incyte: Research Funding; Millenium: Research Funding. Kim:AstraZeneca: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy; Voronoi: Consultancy; Boryung: Consultancy; AstraZeneca and Korea Health Industry Development Institute: Research Funding. Yoon:Celltrion: Honoraria; Samyang: Research Funding; Amgen, Chongkundang, Celgene, Astrazeneca: Consultancy. Greil:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; MSD Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; BMS/celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; Daiichi Sankyo, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; Astra zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding. Westin:Novartis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; 47: Research Funding; Janssen: Consultancy, Research Funding; Amgen: Consultancy; Kite: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; BMS: Consultancy, Research Funding. Jaeger:Novartis: Consultancy, Honoraria, Research Funding; Amgen: Honoraria; Infinity: Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; True North: Honoraria, Research Funding; Miltenyi: Consultancy, Honoraria; CDR Life AG: Consultancy, Research Funding; Karyopharm: Honoraria; Gilead: Honoraria, Research Funding; Takeda: Honoraria; AbbVie: Honoraria; F. Hoffmann-La Roche: Honoraria, Research Funding. Canales:Celgene, Gilead, iQone, Janssen, Karyopharm, Novartis, F. Hoffmann-La Roche, Sandoz: Honoraria; Janssen, F. Hoffmann-La Roche, Sandoz, Takeda: Speakers Bureau. Chen:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; Bristol-Myer Squibb: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Janssen Pharmaceuticals: Current equity holder in publicly-traded company. Althaus:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. O'Hear:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Negricea:F. Hoffmann-La Roche: Current Employment. Xie:F. Hoffmann-La Roche: Current Employment. McCord:Genentech, Inc.: Current Employment; F. Hoffman-La Roche: Current equity holder in publicly-traded company. Purev:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Vallurupalli:Received Research funding to University of Kansas to conduct the ongoing GO40515 clinical trial for which the abstract is being submitted.: Research Funding; On Kite speaker Bureau but do not receive any honorarium.: Speakers Bureau. OffLabel Disclosure: Mosunetuzumab (RG7828; CD20-TDB) is a full-length, fully humanized immunoglobulin G1 (IgG1) bispecific antibody targeting both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). Mosunetuzumab redirects T cells to engage and eliminate malignant B cells. Mosunetuzumab is an investigational agent.
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Huang, Xiaoyu. "Preface." Pure and Applied Chemistry 77, no. 12 (2005): iv. http://dx.doi.org/10.1351/pac20057712iv.
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The 7th IUPAC International Conference on Heteroatom Chemistry (ICHAC-7) was held in Shanghai, China, on 21-25 August 2004. This conference was co-organized by Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences (CAS); Chinese Chemical Society; Shanghai Society of Chemistry and Chemical Industry; and State Key Laboratory of Organometallic Chemistry and State Key Laboratory of Elemento-organic Chemistry. Three hundred participants attended the conference, with about 150 attendants from 23 different countries other than China. The scientific program consisted of 8 plenary lectures, 1 keynote lecture, 38 invited lectures, 56 p, and 120 posters. This conference focused on the following 6 major themes:- Organocatalysis- Heteroatom chemistry directed toward organic synthesis- Mechanistic and structural aspect of heteroatom chemistry- New heteroatom-containing materials- Biologically relevant heteroatom chemistry- Supramolecular chemistry of heteroatom.All the lecture sessions were held in Everbright Exhibition Center. The following highlighted lectures are representative of the quality of material presented at the conference:- Robert R. Holmes, University of Massachusetts, "Phosphoryl transfer enzymes and hypervalentphosphorus chemistry"- Christopher A. Reed, University of California at Riverside, "Strongest but gentlest: New acids fororganic and inorganic chemistry"- Xiyan Lu, Shanghai Institute of Organic Chemistry, CAS, "Synthetic methodologies using tertiaryphosphines as nucleophilic catalysts"- Tetsuo Otsubo, Hiroshima University, "Functional oligothiophenes as advanced molecular electronicsmaterials"- Dao-Ben Zhu, Institute of Chemistry, CAS, "Recent advances of molecular material in theOrganic Solid Laboratory, CAS"- Ian Manners, University of Toronto, "Catalytic routes to rings, chains, and macromolecules basedon inorganic elements"- Masaaki Yoshifuji, Tohuku University, "Recent develpments in the chemistry of low-coordinatedorganophosphorus compounds"- Peter Jutzi, University of Bielefeld, "Cyclopentadienyl and ferrocenyl chemistry of some p-blockelements"- Andreas Pfaltz, University of Basel, "Design of heterocyclic ligands for asymmetric catalysis"The organizers also prepared a series of rich social programs for the participants of the conference, which included a welcome party and a city sightseeing tour of Shanghai. ICHAC-7 was a fruitful meeting for all participants, in particular, the young scientists and students who found a world forum to present and discuss their results, meet scientists from other countries, exchange experiences, and socialize with scientists from all fields of heteroatom chemistry. Many of these contacts have led to new cooperation and exchanges among students and young and senior scientists. In addition to the lectures in this issue, six lectures of this conference have been documented in the Chinese Journal of Chemistry, Vol. 23, Nos. 8,9 (2005).The 8th IUPAC International Conference on Heteroatom Chemistry will be held in 2007 in Riverside, CA and will be hosted by Prof. Christopher A. Reed of the University of California at Riverside.Xiaoyu HuangConference Editor
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Hillmen, Peter, Hope Qamoos, Anne Uyei, et al. "A Phase 1b-2 Study of KRT-232, a First-in-Class, Oral, Small Molecule Inhibitor of Murine Double Minute 2 (MDM2), in Combination with Acalabrutinib for the Treatment of Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) or R/R Diffuse Large B-Cell Lymphoma (DLBCL)." Blood 136, Supplement 1 (2020): 23–24. http://dx.doi.org/10.1182/blood-2020-134901.
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Background: Insights into molecular biology and signaling pathways have led to the development of innovative therapeutic strategies to treat B-cell malignacies. In R/R CLL, targeted agents including Bruton tyrosine kinase inhibitors (BTKi) and B-cell lymphoma 2 inhibitors (Bcl-2i) have emerged as new standard of care (Ghia, 2019; Seymour, 2018). More recently, the combination of these two agents has shown impressive and synergistic clinical results with significantly higher complete response (CR) rates reported compared with either agent alone (Jain, 2019). This combination leverages the ability of BTKi to mobilize and egress malignant B-cells from the protective tumor microenvironment and to disrupt cell adhesion-mediated resistance; thereby increasing B-cell sensitivity to novel pro-apoptotic mechanisms (e.g. Bcl-2i). KRT-232 is a potent and highly selective second-generation inhibitor of MDM2 which rapidly activates p53 to induce apoptosis in malignant hematopoetic stem cells and progenitor cells. Studies in CLL and DLBCL cell lines showed MDM2i overcame Bcl-2 overexpression leading to induction of apoptosis through the upregulation of p21, BAX, and PUMA and downregulation of Bcl-xL (Drakos, 2011; Ciardullo, 2019). As such, targeting the p53-driven apoptotic pathway may be a novel mechanism, independent of Bcl-2 inhibition, to treat B-cell malignacies. KRT-232-driven apoptosis requires tumor cells to express the wild-type encoding p53 gene (TP53WT) found in ~60% and ~80% of pts with R/R CLL and R/R DLBCL, respectively (Miao, 2019; Lazarian, 2017). Acalabrutinib is a potent and highly selective second-generation inhibitor of BTK with established efficacy in R/R CLL and an improved safety profile (Ghia, 2020). In pts with R/R DLBCL, acalabrutinib monotherapy was well tolerated and demonstrated promising clinical activity (24% overall response rate [ORR], 19% CR; Dyer 2018). Aberrant signaling through BTK drives malignant B-cell proliferation, trafficking and sequestering into protective niches causing lymphadenopathy. BTK signaling plays a critical role in CXCR4-CXCL12 driven chemotaxis and integrin-mediated adhesion. Stromal interactions within the protective microevironment have been associated with aberrant B-cell proliferation, treatment resistance and protection against apoptosis (Montresor, 2018). The combinination of KRT-232, a novel cell-death pathway agent, with acalabrutinib, a selective and potent cell trafficking modulator, has the potential to demonstrate synergistic clinical activity across a broad range of B-cell malignancies with a differentiated safety profile compared with similar targeted combinations. To this effect, nonclinical synergy has been demonstrated with combinations of MDM2i and BTKi in CLL (Voltan, 2016) and DLBCL (Gu, 2019). Study Design and Methods: KRT-232 + acalabrutinib is being evaluated in a Phase 1b-2 open-label, global, multicenter study in pts with R/R TP53WT DLBCL (Cohort 1) or R/R TP53WT CLL (Cohort 2; Figure). Pts aged ≥18 years with histologically confirmed disease and ECOG PS of 0-2 will be enrolled. Pts with known CNS involvement, prior exposure to MDM2i or BTKi and recent prior therapy (anticancer treatment &lt;28 days [d], allogenic stem cell transplantation [SCT] &lt;6 mo, autologous SCT &lt;3 mo) are excluded. Phase 1b will determine the maximum tolerated dose and recommended phase 2 dose (RP2D) for KRT-232 in combination with standard dose of acalabrutinib (100 mg BID) using a 3+3 dose escalation design (Figure). KRT-232 will be administered d1-7 of 28-d cycles with 3-6 pts per dose level. Phase 2 will include expansion arms (Cohort 1: N≈40; Cohort 2: N=19) where pts will be treated with the RP2D of KRT-232 + acalabrutinib. For phase 2, the primary end points are CR (Cohort 1) and CR/CR with incomplete hematologic recovery (Cohort 2). Secondary end points include ORR, duration of response, MRD (Cohort 2 only), PFS, OS, safety/tolerability, and pharmacokinetics. [NCT04502394]. Figure Disclosures Hillmen: F. Hoffmann-La Roche: Honoraria, Research Funding; Astra Zeneca: Honoraria; Gilead: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Pharmacyclics: Research Funding. Qamoos:Kartos Therapeutics: Current Employment, Current equity holder in private company. Uyei:Kartos Therapeutics: Current Employment. Rothbaum:Quogue Capital: Current Employment; Iovance Biotherapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Acerta Pharma: Current equity holder in private company; Kartos Therapeutics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Telios Pharma: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Quogue IP Holdings: Patents & Royalties. Jurczak:Roche: Research Funding; Takeda: Research Funding; Pharmacyclics: Research Funding; MeiPharma: Research Funding; Janssen: Research Funding; Bayer: Research Funding; Acerta: Research Funding; Jagiellonian University, Krakow, Poland: Ended employment in the past 24 months; Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland: Current Employment; TG Therapeutics: Research Funding. Thieblemont:Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Bristol-Myers Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Incyte: Honoraria; Bayer: Honoraria; Hospira: Research Funding. Byrd:Vincera: Research Funding; Novartis: Research Funding; Trillium: Research Funding; Leukemia and Lymphoma Society: Other; Janssen: Consultancy; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, BeiGene: Research Funding; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, Novartis, Janssen: Speakers Bureau; Pharmacyclics LLC, an AbbVie Company, Janssen, Novartis, Gilead, TG Therapeutics: Other; Acerta Pharma: Research Funding; Syndax: Research Funding; Kartos Therapeutics: Research Funding. OffLabel Disclosure: KRT-232 is an investigational small molecule MDM2 inhibitor. This trial-in-progress abstract describes a clinical trial that will evaluate the safety and efficacy of KRT-232 + acalabrutinib for patients with R/R DLBCL or R/R CLL.
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Zeidan, Amer M., Cynthia Z. Qi, Bhavik J. Pandya, Andy Garnham, Hongbo Yang, and Manasee V. Shah. "Cost-Effectiveness Analysis of Gilteritinib Versus Salvage Chemotherapy (SC) for the Treatment of Relapsed or Refractory (R/R) FLT3-Mutated (FLT3mut+) Acute Myeloid Leukemia (AML)." Blood 134, Supplement_1 (2019): 3859. http://dx.doi.org/10.1182/blood-2019-123819.
Full textAbstract:
Introduction: FLT3 is a frequently mutated gene in approximately one-third of AML cases and is associated with a poor prognosis. Few effective therapeutic options exist for patients with R/R FLT3mut+ AML. In 2018, gilteritinib was approved in the US as the first targeted therapy indicated for R/R FLT3mut+ AML. The efficacy of gilteritinib was established in the ADMIRAL trial, a phase 3 randomized trial, in comparison with SC (i.e., low-dose cyctarbine [LDAC], azacitidine, mitoxantrone + etoposide + cytarabine [MEC], and fludarabine + cytarabine + granulocyte colony stimulating factor + idarubicin [FLAG-IDA]). The results from the trial indicated that gilteritinib significantly improved overall survival (OS) compared to SC with 1-year survival rates of 37% vs. 17%. To inform the value of gilteritinib, this study aimed to assess the cost-effectiveness of gilteritinib for the treatment of R/R FLT3mut+ AML from a US third-party payer's perspective. Methods: A cost-effectiveness analysis (CEA) model was developed using monthly cycles and a 3% discount rate to assess the incremental cost effectiveness of gilteritinib compared to SC over a lifetime horizon. The model structure comprised a decision tree followed by two three-state partitioned survival models. The decision tree component stratified patients based on whether they received allogeneic hematopoietic stem cell transplantation (HSCT) following treatment initiation. The partitioned survival components included three health states: event-free survival (EFS), alive and post-event, and death. The selected model structure was chosen because HSCT is a key clinical event that has a significant impact on treatment outcomes for the target population. The efficacy inputs (OS and EFS) varied by HSCT status. The efficacy inputs for OS and EFS without HSCT were estimated based on the ADMIRAL trial. The efficacy inputs for OS and EFS with HSCT were assumed to be the same for both gilteritinib and SC and were based on available literature (Evers 2018). Parametric survival models or HRs were used to predict probabilities of being in different health states until year 3. Afterwards, all patients who remained alive were considered long-term survivors and their mortality risk was twice that of the general population based on literature. Treatment costs (drug, administration, and hospitalization), adverse event (AE) costs, subsequent HSCT costs, medical costs for each health state, FLT3 mutation testing, post-progression treatment, and terminal care costs were obtained from public databases and literature. For SC, the same regimen composition (i.e., LDAC, azacitidine, MEC, and FLAG-IDA) as the ADMIRAL trial was considered to estimate the treatment costs. All costs were inflated to 2018 US dollar (USD). Utilities for each health state were derived from the ADMIRAL trial and disutilities for AEs were derived from the literature. Total incremental costs, total incremental LYs, and total incremental QALYs were calculated. Incremental cost-effectiveness ratios (ICERs), defined as the incremental cost per additional gain in health effect (i.e., LY and QALY), were used to assess the economic value of gilteritinib relative to SC. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also performed to test the robustness of the base-case results. Results: Over a lifetime horizon, the base-case model estimated that treatment with gilteritinib led to an increase of 1.55 discounted LYs and an increase of 1.29 discounted QALYs at an additional cost of $141,097 relative to SC; the corresponding incremental cost per LY gained was $90,761, and incremental cost per QALY gained was $109,741. Cost-effectiveness was most sensitive to gilteritinib cost, HSCT rate, and discount rate. In the PSA, the estimated probability that gilteritinib is cost-effective was 93.5% at an acceptable willingness-to-pay threshold of $150,000/QALY. Conclusions: Gilteritinib demonstrated greater LY and QALY improvements compared with SC. With an ICER of $109,741/QALY, gilteritinib is a cost-effective strategy from a US third-party payer's perspective, based on the $150,000/QALY threshold recommended by the US Institute for Clinical and Economic Review. Compared to SC, gilteritinib represents a new active treatment option for R/R FLT3mut+ AML patients that provides better health outcomes with a favorable cost-effectiveness profile. Disclosures Zeidan: Trovagene: Consultancy, Honoraria, Research Funding; Medimmune/AstraZeneca: Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Ariad: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Daiichi Sankyo: Honoraria; Cardinal Health: Honoraria; Seattle Genetics: Honoraria; BeyondSpring: Honoraria; Incyte: Consultancy, Honoraria, Research Funding; Acceleron Pharma: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Otsuka: Consultancy, Honoraria, Research Funding; Agios: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Research Funding; Jazz: Honoraria. Qi:Astellas: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Astellas for the conduct of this study; Analysis Group, Inc.: Employment. Pandya:Astellas Pharmaceuticals: Employment. Garnham:Astellas: Employment. Yang:Analysis Group, Inc.: Employment; Astellas: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Astellas for the conduct of this study. Shah:Astellas: Employment.
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Senfield, Jeffrey J., Theresa Hahn, Swami Padmanabhan, Philip L. McCarthy, and Minoo Battiwalla. "Analysis of Donor Age and Absolute Lymphocyte Count Recovery as Prognostic Indicators of Survival after Allogeneic Blood or Marrow Transplantation." Blood 108, no. 11 (2006): 5252. http://dx.doi.org/10.1182/blood.v108.11.5252.5252.
Full textAbstract:
Abstract Absolute lymphocyte count (ALC) recovery ≥500 cells/mL at day 15 or 30 post-autologous (autoBMT) transplantation has been reported in many studies as an independent prognostic indicator of overall survival (OS) and progression free survival (PFS) in non-Hodgkin lymphoma (NHL), Hodgkin Disease (HD), multiple myeloma (MM) and breast cancer patients. ALC recovery has also been reported in the allogeneic blood and marrow transplant (alloBMT) setting as an important factor in predicting risk of relapse of acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML). It has been shown in previous reports that donor age is critically important for OS after alloBMT. In addition, increased donor age correlates with a reduction of common lymphoid progenitor (CLP) differentiation potential which led us to hypothesize that donor age might predict ALC recovery time in related and unrelated alloBMT recipients. We reviewed 76 related and 36 unrelated HLA-matched consecutive patients with hematological malignancies who underwent first alloBMT at Roswell Park Cancer Institute between 4/20/2000 and 3/17/2006. The patient population included 53 males and 59 females with a median (range) age of 44 (4–68) years. Conditioning regimens were FluMel (n=33), CyTBI (n=32), BuCy (n=19), FluCy (n=13), VCT (n=11), and other (n=4). The stem cell source was bone marrow (n=34), peripheral blood (n=77) or both (n=1). Hematologic engraftment was defined as absolute neutrophil count (ANC) reaching 500 cells/ml or more for 3 consecutive days. ALC at day 30 and time to ALC ≥ 500 cells/mL were analyzed. Our results show that peripheral blood (p=0.04) and a higher CD34+ dose (p=0.05) were significantly associated with day 30 ALC ≥ 500. Time to ALC recovery ≥500 cells/mL was not significantly related to donor age for related alloBMT (p=0.340). However, in unrelated alloBMT patients, there was a trend toward increasing donor age associated with a longer time to ALC recovery ≥ 500 cells/mL (p=0.087). ANC recovery correlates with ALC recovery in related (R=0.237, p=0.02) and unrelated (R=0.514, p<0.001) alloBMT recipients. Recipient and donor age were strongly correlated in related alloBMT patients (R=0.89, p<0.001) and weakly correlated in unrelated alloBMT patients (R=0.236, p=0.09). ALC recovery ≥ 500 at day 30 post alloBMT was not a significant predictor of OS in either the related or unrelated subgroups. We will further examine donor-recipient age disparities in unrelated alloBMT patients and present multivariate analyses of predictors for time to ALC recovery.
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Schwartz, Adelheid. "Andre R. Prévot. Manual for the Classification and Determination of the Anaerobic Bacteria Monograph of the Pasteur Institute). Übersetzt von V. Fredette nach der III. ergänzten französischen Auflage. 402 S. Philadelphia 1966: Lea und Febiger. $ 15,-." Zeitschrift für allgemeine Mikrobiologie 7, no. 4 (2007): 331. http://dx.doi.org/10.1002/jobm.19670070418.
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