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1
Cash, Daniel. "Why the US Justice Department Must Act Against Moodys Corporation." Business Law Review 37, Issue 6 (December 1, 2016): 220–21. http://dx.doi.org/10.54648/bula2016040.
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This short note discusses the importance of the decision facing the US Justice Department in the near future regarding whether or not to take action against Moody’s Corp. for its actions in the lead up to the Financial Crisis. Having already fined Standard & Poor’s a record USD 1.375 billion for defrauding investors, the Justice Department faces a much different proposition. This note establishes just some of the reasons why it is imperative that Moody’s is punished, even if ultimately the punishment is less noticeable than that given to Standard & Poor’s.
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Debreceny, Roger S., Asheq Rahman, and Tawei Wang. "Corporate Network Centrality Score: Methodologies and Informativeness." Journal of Information Systems 31, no. 3 (May 1, 2017): 23–43. http://dx.doi.org/10.2308/isys-51797.
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ABSTRACT This research proposes a Corporation Network Centrality Score (CNCS) that exploits the social network implicit in Twitter interactions that are relevant to capital markets. The CNCS is the eigenvector network centrality score for interactions about corporations. The CNCS provides a summary numeric metric that captures a wide range of market-relevant information about the corporation it represents. The study asserts that the CNCS will assist the monitoring of corporations by auditors, regulators, and other market participants. The research calculates the CNCS for Standard & Poor's (S&P) 1500 firms and then tests the robustness of the metric by regressing CNCS on a set of variables that are known to convey firm fundamentals information to the capital markets. The study finds that CNCS is strongly associated with firm-led disclosures, market-based firm characteristics, and accounting-based firm fundamentals information. JEL Classifications: M41.
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Laskin, Alexander V. "The Narrative Strategies of Winners and Losers: Analyzing Annual Reports of Publicly Traded Corporations." International Journal of Business Communication 55, no. 3 (June 20, 2018): 338–56. http://dx.doi.org/10.1177/2329488418780221.
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This study focuses on the narrative strategies corporations utilize to communicate their annual results to investors and the financial community. Specifically, the study looks at the sample of overperforming and underperforming companies and analyzes how management shapes their performance results using a variety of narrative strategies in their annual reports. The study uses DICTION software in order to perform a computerized content analysis of annual reports of a purposive sample of Standard & Poor’s 500 corporations and identify and compare the usage of the 35 narrative strategies.
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Moya, Jorge, Marta Torres, and Manuel Uche-Soria. "An Analysis of the Long-Term Sustainability of the Large Companies Included in the Original Standard and Poor’s 500 Index." Discrete Dynamics in Nature and Society 2022 (September 1, 2022): 1–20. http://dx.doi.org/10.1155/2022/1558746.
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The changes generated by the natural economic and social development have configured a scenario where the companies’ survival is gradually decreasing. This process is also impacting on the big corporations that were strongly consolidated for many years. This research has analysed that which of these major companies of the Fortune 500 Index have adapted themselves over the years and have survived. After locating the surviving companies, this paper studied the presence of elements of business quality in each of these firms. Then, using a fuzzy set methodology, this study obtained results that identified some of the main elements that might be considered as inductors of the business durability in the case of the big corporations: the effectiveness of the companies, the coherence with the mission, and the capacity of organisation are essential for the long-term sustainability of the companies especially if they are associated with a formalised structure of governance. The results also conclude that the simple presence of these elements is not enough for the permanence of the companies and only the progresses and improvements in these variables can guarantee the sustainability of the companies.
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Schultz, Thomas D., and Kyle Scott. "Puerto Rico: The Evolution of America's Corporate Tax Haven." ATA Journal of Legal Tax Research 12, no. 1 (March 1, 2014): 17–40. http://dx.doi.org/10.2308/jltr-50746.
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ABSTRACT We examine the taxation of corporate income earned in the Commonwealth of Puerto Rico and how the repeal of the possession tax credit available under Internal Revenue Code (IRC) §936 resulted in many U.S. companies converting former possessions corporations into controlled foreign corporations. Although Puerto Rico is a U.S. territory, the conversions highlight that corporations organized under the laws of the Commonwealth generally are foreign corporations for U.S. tax purposes. A U.S. Senate Subcommittee reports Microsoft Corporation shifted offshore the recognition of nearly one-half of its U.S. net retail sales revenue for the period 2009–2011 by transferring intellectual property rights to a controlled subsidiary in Puerto Rico. We find that the corresponding U.S. tax benefits are significant compared to the credits once claimed under IRC §936, and over 20 percent of Standard & Poor's (S&P) 500 firms were in a similar position to avoid federal taxation by shifting income between political subdivisions of the United States.
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Miglietta, Nicola, Enrico Battisti, and Francesco Campanella. "Value maximization and open innovation in food and beverage industry: evidence from US market." British Food Journal 119, no. 11 (November 6, 2017): 2477–92. http://dx.doi.org/10.1108/bfj-04-2017-0213.
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Purpose The purpose of this paper is to examine listed companies, grouped by sector, that for decades have shown a dividend growth. Referring to the food and beverage (F&B) industry, the authors have investigated the adoption of an open innovation model in order to fill a gap in the existing literature. Design/methodology/approach This paper uses a multi-method design linking qualitative and quantitative approaches. The quantitative study was planned in order to identify some US-listed companies, called Dividend Champions that have distributed consistently growing dividends for over 50 years and have beaten the markets. The qualitative study was designed to provide insight into the adoption or not of an open innovation model by the listed companies in the F&B industry in the US market that were selected by the quantitative analysis. Findings The research is based on an empirical analysis undertaken with 816 listed companies in US markets. In particular, the authors underline 20 companies that over the past 50 years have systematically increased dividend paid, and at the same time, have beaten the market (Standard & Poor’s 500). In all, 30 per cent of the selected companies belong to the consumer goods sector, and F&B companies represent 50 per cent of them. All of these companies (The Coca-Coca Company, Hormel Foods Corporation, and Lancaster Colony Corporation) implement an open innovation model. Originality/value To the authors’ knowledge, this is the first exploratory study based on value maximisation and open innovation. An open innovation model increases competitiveness and the durability of competitive advantage, which are main sources of value creation. The paper highlights evidence from the F&B industry, referred to as Dividend Champions, and the adoption of an open innovation model.
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Wang, Wenjing, and Arthur S. Guarino. "The Impact of the Covid-19 Crisis on Common Stock Dividend Payout Policy." Research in Economics and Management 5, no. 4 (September 8, 2020): p68. http://dx.doi.org/10.22158/rem.v5n4p68.
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For many investors, dividends play a key role in evaluating the return of a common stock and the main reason for making the investment. For those investors, dividends are a necessary aspect since they are a vital source of income. But with the Covid-19 pandemic, many corporations have been adversely affected by a global economic slowdown. For publicly traded corporations, depending on its industry, dividends have been sharply affected to the point of either being reduced or suspended indefinitely. Using the Standard and Poor’s 500 stock index as a guide, stock analysts can possibly acquire a better understanding as to how reduced or suspended dividend income will affect different investors. The aim and purpose of this paper is to examine the affect the reduction and suspension of dividends will have as a source of needed income for private investors, pension funds, mutual funds, insurance companies, and real estate investment trusts.
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Vaziri, Mo, Rafiqul Bhuyan, and Ponkela Manue. "Alarming Factors in predictability of failure of financial institutions." International Journal of Business & Technology 1, no. 1 (October 1, 2012): 2–10. http://dx.doi.org/10.33107/ijbte.2012.1.1.01.
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The impact of failure of financial institutions is beyond just the failure of a public corporation. The failure of financial institutions in the USA, is a clear evidence that the greater macro impact is beyond just the failure of few financial institutions. It can bring down the entire economy and can have global devastating impact. By realizing the grave systemic risk of the failure, US government is forced to intervene and bail out many institutions for greater macro-economic reasons. It raises the view that perhaps the current regulating policies and methods are lacking efficiency in predicting the possibility of failure ahead of time and hence not effective in preventing that to happen. In this research we apply several existing methods of institutional failure and test the signaling ability of each method in predicting the bankruptcy well ahead of time. We apply Moody’s financial ratios, Standard and Poor’s financial ratio, vaziri’s financial ratio, Altman’s Z score and then applying logit model and discriminant analysis, we test each of these model’s predictive ability for future use. We analyze the reasons like changes in market, policy, economy, and political influence which have led to bankruptcy. Banks or financial institutions from Europe, United States and Asia are considered as samples. Samples are taken from same period to analyze the effect of different methods. The results from this analysis should help us find the most significant method that could be used to identify the risk, so that necessary action could be taken to prevent the effect or reject the project which could lead to bankruptcy in the future. This research would also offer policy recommendations for regulating agencies as to which factors should be analyzed deeply and how to implement a preventive measure ahead of any potential problems.
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França, Robério Dantas de, and Paulo Aguiar do Monte. "EFEITOS DA REPUTAÇÃO CORPORATIVA NA TAX AVOIDANCE DE EMPRESAS BRASILEIRAS DE CAPITAL ABERTO." Revista Universo Contábil 15, no. 4 (December 31, 2020): 109. http://dx.doi.org/10.4270/ruc.2019430.
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O objetivo do estudo é analisar o efeito da reputação corporativa na tax avoidance de empresas brasileiras de capital aberto. O tema é pouco explorado na área de contabilidade e tributos e, no Brasil não foi encontrado estudo que relacione de forma direta a reputação corporativa com a tax avoidance, o que garante o pioneirismo do estudo. Para alcançar tal propósito, utilizam-se regressões de dados em painel (estimadores FE-LSDV, RE e GMM) e testa-se a hipótese de associação da reputação corporativa com a tax avoidance. Utiliza a Effective Tax Rate – ETR e a ETR Diferencial como proxie de tax avoidance. A reputação corporativa é mensurada através de cinco proxies: (i) presença da firma no ranking Melhores e Maiores empresas do Brasil da revista Exame; (ii) ratings da Standard & Poor’s; (iii) Índice de Responsabilidade Empresarial – ISE; (iv) cobertura de analistas de mercado, e; (v) Índice de Reputação Corporativa – IRC, construída neste estudo para capturar a reputação estabelecida. A amostra de pesquisa contempla 225 empresas brasileiras de capital aberto, totalizando 1.575 observações/ano no período de 2010 a 2016. Em conjunto, os resultados confirmam parcialmente a hipótese de pesquisa, uma vez que nem todas as proxies de reputação se mostraram eficientes. Contudo, evidenciam a propensão das empresas com reputação forte a aumentarem a tax avoidance. Uma possível explicação para os achados é que essas empresas ignoram possíveis fatores de riscos fiscais e danos à reputação, sugerindo a existência do fenômeno do licenciamento moral no contexto dessas empresas.
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Ekopai, Joyce Margaret, Nathan Lubowa Musisi, Howard Onyuth, Benigna Gabriela Namara, and Celsus Sente. "Determination of Bacterial Quality of Water in Randomly Selected Swimming Pools in Kampala City, Uganda." New Journal of Science 2017 (June 14, 2017): 1–7. http://dx.doi.org/10.1155/2017/1652598.
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Swimming pools have become major recreation facilities for leisure and sports in cities across the world, but the standard guidelines, particularly in developing countries, are not adhered to because little is known about the contaminants in the pools and the possible health risks involved. This study provides a survey of bacterial quality of water from swimming pools in Kampala. A total of 26 water samples were collected from 13 outdoor swimming pools in Kampala between January and June 2016 and analysed for total aerobic plate count (TPC), Escherichia coli, coliforms, and Salmonella. The heterotrophic bacterial load ranged between 0 and 6.35 × 105 cfu/ml, where 6.35 × 105 cfu/ml was the highest load and 3 × 101 cfu/ml the least. The highest average TPC was 6.19 × 105 cfu/ml and the lowest 5.07 × 103 cfu/ml. 30.8% of the pools had TPC within acceptable limits (≤5 × 102 cfu/ml), whereas 69.2% were highly contaminated and did not conform to the Uganda National Water and Sewerage Corporation standards of recreational water quality for both treated (0 cfu/100 mls) water and untreated (10 cfu/100 mls) water. Although no positive results were yielded for E. coli, coliforms, and Salmonella, TPC represented the presence of heterotrophic bacteria which are often indicated in opportunistic infections.
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Sheveleva, G. I. "Corporate Governance in Russian electric power industry in terms of consumer requirements to its funding sources." E3S Web of Conferences 58 (2018): 02004. http://dx.doi.org/10.1051/e3sconf/20185802004.
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The paper highlights a strong interest of energy consumers in attracting investment in the development of Russian power generation companies. The importance of corporate governance for enhancing the investment attractiveness of these companies is emphasized. An in-depth evaluation of their current corporate practices was carried out within the framework of the existing ownership structure. The study identified the indicators of corporate governance quality for the benefit of modern investors that are the least observed by the overwhelming majority of power companies. The indicators were obtained on the basis of whether or not the companies satisfy the criteria of the new Russian Corporate Governance Code, and the criteria of the methodologies of Standard & Poor’s, Spencer Stuart and Transparency International. The study shows a slight increase in the transparency of the companies in the post-reform period and compares it with the information disclosure by the major corporations of Great Britain, the USA and Europe. The study shows high correlation of the approach and composition of the identified indicators of the corporate governance quality for Russian power generation companies with the 2017 Russian Corporate Governance Index. This Index is based on the international Good Governance Index methodology adapted to the Russian conditions.
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Ntsalaze, Zuziwe, Gideon Boako, and Paul Alagidede. "The impact of sovereign credit ratings on corporate credit ratings in South Africa." African Journal of Economic and Management Studies 8, no. 2 (June 12, 2017): 126–46. http://dx.doi.org/10.1108/ajems-07-2016-0100.
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Purpose The purpose of this paper is to examine the impact of sovereign credit ratings on corporations in South Africa by assessing whether the sovereign rating assigned to South Africa by credit rating agencies acts as a ceiling/constraint for credit ratings assigned to corporations that operate within the country. The question of whether sovereign ratings are significant in determining corporate ratings was also explored. Design/methodology/approach To test the hypothesis regarding the rating of corporates relative to sovereigns, a longitudinal panel design was followed. The analysis employed fixed effects and generalized method of moments techniques. Findings The main findings are that sovereign ratings both act as a ceiling for corporate ratings and are important determinants of corporate ratings in South Africa. The findings however indicated that company specific variables (accounting variables) are not significant in explaining credit risk ratings assigned to corporates. Research limitations/implications This study only looked at the rating activity done by Standard and Poor’s (S&P). A possible further study could explore the hypothesis tested in this research using data from multiple rating agencies and contrast the results across different agencies. Future studies could also look at crisis periods and how the transfer risk discussed in this paper manifests during the transfer period. Practical implications The results have implications for the borrowing costs incurred by corporates in South Africa when participating in the international debt market. The implication is that if the sovereign is poorly rated, the corporates may be limited in their ability to secure investor funding at competitive rates from the international financial markets. Thus, should South Africa be downgraded to non-investment grade by S&P, the implications may be that South African corporates on average may suffer the same fate. Originality/value Extant literature predominantly utilizes foreign currency ratings. To the extent that this study uses local currency ratings, it adds a new dimension in the body of related studies.
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Benjamin, Heather L., James M. Rossetti, Aaron J. Lampkin, Christie Hilton, Entezam Sahovic, Haifaa Abdulhaq, Richard K. Shadduck, Namratha Vemulapalli, Amanda Hercules, and John Lister. "Azacitidine in the Treatment of Elderly Patients with Acute Myelogenous Leukemia." Blood 114, no. 22 (November 20, 2009): 4164. http://dx.doi.org/10.1182/blood.v114.22.4164.4164.
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Abstract Abstract 4164 BACKGROUND Effective treatment of the elderly patient with acute myelogenous leukemia (AML) remains a challenging task. Elderly patients with AML usually respond poorly to standard induction chemotherapy. Response rates in elderly patients are in the range of 30–50% compared to 80–90% in younger patients. Moreover, prolonged hospitalization with treatment related mortality as high as 30% is typical in this older population. In a prior retrospective analysis done at our institution, azacitidine showed an overall response rate of 60% with limited toxicity when administered to patients older than 55 years of age with AML. We present an interim analysis of the first 13 patients enrolled in our prospective, phase II open label study using single agent azacitidine for elderly patients with AML. METHODS This is a prospective, phase II open label study using azacitidine in patients ≥ 60 years with AML. Inclusion criteria: Newly diagnosed AML (de novo or secondary, WHO criteria) and ECOG≤ 2. Promyelocytic (M3) phenotype was excluded. Patients with circulating blast count ≥ 30,000/mcl were treated with hydroxyurea until < 30,000/mcl. Azacitidine was given at a dose of 100 mg/m2 subcutaneously for 5 consecutive days every 28 days until disease progression or significant toxicity. G-CSF was given to patients with neutropenia (ANC < 1000/mcl) during all cycles excluding cycle one. RESULTS Thirteen patients have been enrolled to date. The mean age of patients is 75 years (range: 66–84). The mean baseline ECOG performance score was 1 with a mean during treatment of 1. Mean baseline bone marrow blast count was 57% (range: 21–100%). Overall response rate using the NCI response criteria (IWG criteria for patients with hematological improvement (HI) only) was 46% (6/13): complete response (CR; n=3; 23%), partial response (PR; n=1; 8%), and HI (n=2; 15%). One additional patient had a 94% reduction in marrow blasts, but failed to achieve transfusion independence. The mean number of days on treatment was 171+ (range: 13–606). The mean number of days hospitalized for diagnosis plus treatment or disease related complication was 21 (range: 7–72) with the majority of therapy being given in the outpatient setting. One patient required prolonged hospitalization after going on to allogeneic transplantation. The mean overall survival from diagnosis for all patients was 246+ days (range: 13–606). The mean overall survival for responders was 399+ days (range: 212–606). One patient continues on therapy with azacitidine at 606 days (CR). Of the other responders, one progressed at 420 days and is considering other options (CR), one died from an intra-cranial hemorrhage after receiving Mylotarg for disease progression at 454 days (CR), one progressed at 119 days and went on to another clinical trial (PR), and two died with disease at 212 and 347 days (HI). Non-hematological toxicity was limited to mild injection site skin reaction and fatigue in 77% (10/13) each. No treatment related deaths were observed. The dose and schedule of therapy remained constant in all but three patients: One patient required a 25% dose reduction after cycle 3 followed by another 25% reduction after cycle 11 due to drug induced marrow suppression, one patient required a 25% dose reduction after cycle 2 due to drug induced marrow suppression, and one patient required and tolerated a 25% dose escalation to recapture a CR after cycle 15. CONCLUSION This interim analysis suggests that the administration of subcutaneous azacitidine in an accelerated dosing schedule to elderly patients with acute myelogenous leukemia is a feasible and well-tolerated alternative to standard induction chemotherapy. Disclosures: Benjamin: Celgene Corporation: Research Funding. Off Label Use: Use of azacitidine in AML.. Rossetti:Celgene Corporation: Honoraria, Research Funding, Speakers Bureau. Sahovic:Celgene Corporation: Honoraria, Research Funding, Speakers Bureau. Abdulhaq:Celgene Corporation: Research Funding. Shadduck:Celgene Corporation: Honoraria, Research Funding, Speakers Bureau. Lister:Celgene Corporation: Research Funding.
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Xie, Jipan, Emily Goldmann, Anuja Roy, Chelsey Yang, Eric Q. Wu, and Carole Paley. "Comparison of Real-World Treatment Patterns and Clinical Outcomes in 18-59 Year-Old Patients with FLT3 Mutated Vs. FLT3 Wild Type Acute Myeloid Leukemia: A Medical Records Review." Blood 124, no. 21 (December 6, 2014): 5992. http://dx.doi.org/10.1182/blood.v124.21.5992.5992.
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Abstract Background: FMS-like tyrosine kinase-3 (FLT3) mutation is present in approximately one-third of AML patients. Internal tandem duplication mutations of FLT3 (FLT3-ITD) mutation in AML have been associated with poorer prognosis compared to FLT3 wild type (WT). Treatment patterns and outcomes among FLT3 mutated AML patients have not been well understood. Aims: To compare real-world treatment patterns and clinical outcomes in 18-59 year-old patients with FLT3 mutated vs. FLT3 WT AML. Methods: An online medical records review of 209 patients 18-59 years with a confirmed diagnosis of AML in 2010, 2011, or 2012 was conducted by US hematologists/oncologists. Physicians (n=112) with experience treating AML were chosen from a nationally-representative panel to conduct a review of patients’ medical charts. Charts of patients treated in a variety of practice settings (e.g., solo and group practices, teaching and community hospitals, hospital clinics) were abstracted using a secure online portal. Patient characteristics at diagnosis, treatment patterns (induction and consolidation chemotherapy and stem cell transplantation [SCT]) and clinical outcomes (complete remission [CR] and relapse) were compared between FLT3 mutated and WT patients using chi-square tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. Results: Medical records for 104 FLT3 mutated and 105 WT AML patients were reviewed. FLT3 mutation was associated with having poorer risk status at initial AML diagnosis based on National Comprehensive Cancer Network (NCCN) guidelines (p<0.0001). There was also a trend towards poorer Eastern Cooperative Oncology Group (ECOG) and Karnofsky performance scores among FLT3 mutated patients at diagnosis (Table 1). FLT3 mutated patients were numerically less likely to receive induction therapy compared to WT patients (92% vs. 98%, p=0.0586). Among patients who received induction therapy, FLT3 mutated patients were significantly less likely than WT patients to receive the standard 7+3 regimen vs. other treatment regimens, including cytarabine combinations without daunorubicin and idarubicin and non-cytarabine combinations (52% vs. 72%, p=0.0295). FLT3 mutated and WT patients who received induction therapy were similarly likely to receive consolidation therapy (77% vs. 80%, respectively, p=0.2488), but having FLT3 mutation was associated with receiving fewer cycles of consolidation therapy (p=0.0158). Similar proportions of FLT3 mutated and WT patients achieved CR (80% vs. 79%, p=0.8890). Forty-one percent of FLT3 mutated and 30% of WT patients received SCT (p=0.0740), the majority of whom received standard-intensity allogeneic SCT (88% of FLT3 mutated patients and 61% of WT patients). Compared to WT patients, FLT3 mutated patients were numerically more likely to relapse after achieving CR from induction therapy (12% vs. 7%, p=0.3639) and after SCT (14% vs. 6%, p=0.8674). Conclusions: FLT3 mutated patients were significantly more likely to have poorer risk status at diagnosis and were significantly more likely to receive fewer cycles of consolidation compared to WT patients. FLT3 mutated patients were as likely to achieve CR as WT patients, but results suggest a higher proportion of FLT3 mutated patients relapsed following induction and SCT. These results confirm that FLT3 mutation is associated with a poorer prognosis and suggest the need for improved treatment options for FLT3 mutated patients. Table 1. Patient disease characteristics at initial diagnosis Characteristic, n % FLT3 mutated patients (n=104) FLT3 WT patients (n=105) P-value Patient disease risk (based on NCCN guidelines) <0.0001* Better-risk 19 20% 40 41% Intermediate-risk 37 38% 46 47% Poor-risk 41 42% 12 12% Karnofsky Performance Score1 0.7309 100% 8 9% 11 12% 90% 22 24% 29 31% 80% 25 27% 23 24% 70% 7 8% 7 7% 60% 4 4% 3 3% 50% 5 5% 5 5% 40% 3 3% 5 5% 30% 8 9% 4 4% 20% 8 9% 7 7% 10% 3 3% 0 0% Eastern Cooperative Oncology Group performance status2 0.1594 0 28 27% 30 29% 1 52 50% 57 55% 2 13 13% 15 14% 3 7 7% 1 1% 4 4 4% 1 1% *p < 0.05 [1] Lower score indicates poorer performance; range from 100% = Normal, no complaints, no evidence of disease to 10% = Moribund, fatal processes progressing rapidly. [2] Higher score indicates poorer performance; range from 0 = Fully active, able to carry on all pre-disease performance without restriction to 4 = Completely disabled, cannot carry on any self-care, totally confined to bed or chair. Disclosures Xie: Novartis Pharmaceuticals Corporation: Consultancy, Research Funding. Goldmann:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding. Roy:Novartis Pharmaceuticals Corporation: Employment. Yang:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding. Wu:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding. Paley:Novartis Pharma: Employment.
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Ogoko, Emeka Chima, Stella Amarachi Onyemelukwe, Henrietta Ijeoma Kelle, Ifunanya Iroegbulem, Donard Emeziem, and Adebisi Akinyemi Fagbohun. "Health risk assessment of heavy metals in drinking water from Iponri water treatment plant, Lagos water corporation Nigeria." Ovidius University Annals of Chemistry 34, no. 1 (January 1, 2023): 41–49. http://dx.doi.org/10.2478/auoc-2023-0007.
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Abstract Urban water supplied from treatment plants can constitute public health problems if poorly treated or accidentally contaminated. Water quality and health risk assessment of water supplied from Lagos State water treatment plant was performed. Heavy metal concentration was determined using Atomic Absorption Spectrophotometer. The mean concentrations of Pb, Cu, Zn, Fe, Mn, Cd, Ni, As and Cr were within the standard maximum permissible limits for drinking water quality. The mean estimated daily intake through oral ingestion of drinking water for Pb, Cu, Zn, Fe, Mn, Cd, Ni, As and Cr were 0.00024, 0.00117, 0.00158, 0.00665, 0.00736, 0.000271, 0.00148, 0.000563 and 0.000834 mg/kg bw/day respectively, but were within acceptable tolerable daily intake standards for adult population. The values of hazard quotients for the heavy metal in water samples were below one for adult population. Hazard indices of treated water samples were below the threshold value of one (HI ˂ 1) while hazard indices of untreated and pre-treated water samples exceeded one, indicating possible associated potential health risks as a result of combined effects of the heavy metals through oral consumption water. Incremental life cancer risk values of Cd, Ni, As and Cr in all the three categories of water samples exceeded the safe limit for cancer risk while the cumulative cancer risk (ΣILCR) also exceeded the proposed threshold safe risk limit (> 1x10−4), indicating potential carcinogenic lifetime health risk in adult population through oral consumption of the heavy metal in water. Conclusively, the treated water had lowest levels of heavy metals, hazard quotient, incremental life cancer risks values and unsafe for drinking purposes compared to the untreated and pre-treated water.
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Shiah-Hou, Shin-Rong. "The effect of analyst coverage on CEO compensation structure: evidence from the S & P 1500." Managerial Finance 42, no. 3 (March 14, 2016): 191–211. http://dx.doi.org/10.1108/mf-10-2014-0273.
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Purpose – What is the role of analysts in reducing agency problems and information asymmetry between stockholders and managers? The purpose of this paper is to confirm the analyst’s role by examining his or her influence on CEO compensation structure. Design/methodology/approach – The major population for this study consists of publicly traded corporations of the S & P 1500 for which data on CEO compensation is available from Standard & Poor’s Execucomp database, along with the proxy statements of these firms. Regression analysis is used to test hypotheses about the effect of analyst coverage on CEO compensation. Findings – The evidence shows that CEOs of firms with greater analyst coverage or higher analyst coverage quality (analyst coverage index) have higher pay-for-performance (Delta), more compensation incentives to increase firm risk (Vega), more total compensation, and more excess compensation. Even after controlling for the effect of other types of corporate governance, including internal governance and institutional holdings, analysts’ activities still have an incremental effect on CEO compensation structure. Practical implications – The authors findings may be useful to investors who use analyst coverage to evaluate the firm’s CEO compensation, as it suggests that investors may reference the information about analyst coverage of firms to craft appropriate CEO compensation structures. Originality/value – The authors results contribute by showing that the extra effect of analyst activities on CEO compensation structure exists, even after controlling for other types of governance mechanisms, such as internal governance and institutional investors’ holdings.
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Bataineh, Khaled. "Return and volatility spillovers between FTSE All-Share Index and S&P 500 Index." Investment Management and Financial Innovations 19, no. 2 (April 26, 2022): 107–18. http://dx.doi.org/10.21511/imfi.19(2).2022.09.
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This paper explores the effect of the return and volatility spillover between the Standard and Poor’s 500 index and FTSE All-Share index using the AG-DCC_ Dynamic Conditional Correlation model over the sample period from April 1995 to April 2019. It demonstrates that the Standard and Poor’s 500 return and volatility are crucial in forecasting the market’s future dynamics of the FTSE All Shares where it finds a significant spillover effect for both return and volatility from the Standard and Poor’s 500 to FTSE All Shares, while weak evidence has been found in the opposite direction, that is, an insignificant spillover effect for both return and volatility from FTSE All Shares to the Standard and Poor’s 500. In addition, the paper also finds high Dynamic Conditional Correlation (DCC) between both the Standard and Poor’s 500 and FTSE All Shares. Therefore, it finds asymmetric correlation and transmission mechanisms between the Standard and Poor’s 500 and FTSE All Shares, which means there is an asymmetric interconnectedness between two markets, so allocating assets between two markets will not benefit investor portfolios as investing in high-yielding shares do.
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Bataineh, Khaled. "Return and volatility spillovers between FTSE All-Share Index and S&P 500 Index." Investment Management and Financial Innovations 19, no. 2 (April 26, 2022): 107–18. http://dx.doi.org/10.21511/imfi.19(2).2022.09.
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This paper explores the effect of the return and volatility spillover between the Standard and Poor’s 500 index and FTSE All-Share index using the AG-DCC_ Dynamic Conditional Correlation model over the sample period from April 1995 to April 2019. It demonstrates that the Standard and Poor’s 500 return and volatility are crucial in forecasting the market’s future dynamics of the FTSE All Shares where it finds a significant spillover effect for both return and volatility from the Standard and Poor’s 500 to FTSE All Shares, while weak evidence has been found in the opposite direction, that is, an insignificant spillover effect for both return and volatility from FTSE All Shares to the Standard and Poor’s 500. In addition, the paper also finds high Dynamic Conditional Correlation (DCC) between both the Standard and Poor’s 500 and FTSE All Shares. Therefore, it finds asymmetric correlation and transmission mechanisms between the Standard and Poor’s 500 and FTSE All Shares, which means there is an asymmetric interconnectedness between two markets, so allocating assets between two markets will not benefit investor portfolios as investing in high-yielding shares do.
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Moreau, Philippe, Antonio Palumbo, Paolo Corradini, Michele Cavo, Michel Delforge, Katja C. Weisel, Enrique M. Ocio, et al. "Analysis of Patient (Pt) Outcomes By Prior Treatment and Depth of Response in Stratus (MM-010), a Phase 3b Study of Pomalidomide + Low-Dose Dexamethasone (POM + LoDEX) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM)." Blood 126, no. 23 (December 3, 2015): 1834. http://dx.doi.org/10.1182/blood.v126.23.1834.1834.
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Abstract Introduction: The introduction of newer agents, such as lenalidomide (LEN) and bortezomib (BORT), has resulted in improved survival outcomes in pts with RRMM (Kumar, Leukemia, 2012), and a greater depth of response has been associated with improved efficacy outcomes in RRMM (Harousseau, Haematologica, 2010). However, once pts become refractory to these newer agents, they experience poorer outcomes, with short overall survival (OS; Kumar, Leukemia, 2012). POM + LoDEX is approved for the treatment of pts with RRMM with ≥ 2 prior treatments, including LEN and BORT. A previous subanalysis of pts treated with POM + LoDEX in the MM-003 trial demonstrated that pts with a deeper response, as measured by a reduction in serum M protein, experienced longer OS and progression-free survival (PFS; San Miguel, ASH 2013). POM + LoDEX was shown to be safe and effective in the phase 3b STRATUS trial (MM-010; Dimopoulos, EHA 2015); here, we present the outcomes in this pt population by prior treatment and depth of response. Patients and Methods: Pts with RRMM (progressive disease [PD] on or within 60 days of last prior treatment) with prior adequate alkylator therapy in whom LEN and BORT treatment failed were eligible. POM 4 mg was administered on days 1 to 21 of a 28-day cycle in combination with LoDEX (40 or 20 mg for pts aged ≤ 75 or > 75 yrs, respectively) on days 1, 8, 15, and 22. Treatment was continued until PD or unacceptable toxicity, and thromboprophylaxis was required for all pts. For this efficacy analysis, pts were grouped according to prior treatment history or reduction in serum M protein level. Results: As of May 4, 2015, 682 pts were enrolled and 676 have received POM + LoDEX. In the intent-to-treat population, the median age was 66 yrs, 56% of pts were male, the median time since diagnosis was 5.3 yrs, and pts had received a median of 5 prior regimens. Approximately half of all pts (54.5%) had received prior thalidomide (THAL), and 186 vs 496 pts had received ≤ 3 vs > 3 prior regimens of therapy, respectively. Most pts were refractory to LEN (96%), BORT (84%), or both LEN and BORT (80%). The overall response rates (ORRs) were generally similar regardless of prior THAL, number of prior regimens, and LEN/BORT refractoriness. Pts who received prior THAL had an ORR of 30.4% compared with 35.2% for pts who did not receive prior THAL (Table). Similarly, for pts with a history of ≤ 3 vs > 3 prior antimyeloma regimens, ORR was 28.5% vs 34.1%. ORR did not appear to be impacted by refractory status to LEN and/or BORT (ORR, 32.1%-32.9%). PFS was comparable and independent of prior THAL exposure, number of prior regimens, and LEN/BORT refractoriness (PFS, 3.9-4.6 mos). Median OS was also similar for pts with or without prior THAL exposure (11.4 mos vs 12.0 mos, respectively), as was OS for pts with ≤ 3 vs > 3 prior regimens (12.8 mos vs 11.9 mos, respectively). Pts with LEN and/or BORT refractoriness had the same median OS of 11.9 mos. Analysis of PFS by serum M protein levels showed that a greater reduction in these levels was associated with a longer median PFS: for pts with a serum M protein reduction of < 25%, ≥ 25% to < 50%, and ≥ 50%, median PFS was 3.0, 4.8, and 7.6 mos, respectively. Conclusions: The efficacy of POM + LoDEX in this heavily pretreated population was independent of treatment history. ORR, OS, and PFS were not significantly impacted by treatment history with THAL, having ≥ 3 prior regimens, or refractoriness to LEN and/or BORT. As shown previously with POM + LoDEX, there was a clear trend toward prolonged PFS in pts with a greater reduction in serum M protein levels. This analysis supports POM + LoDEX as a standard of care for pts with RRMM. Figure 1. Figure 1. Disclosures Moreau: Celgene: Honoraria, Other: Adboard; Takeda: Other: Adboard; Janssen: Other: Adboard; Amgen: Other: Adboard; Novartis: Other: Adboard. Palumbo:Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria; Novartis, Sanofi Aventis: Honoraria. Cavo:Janssen-Cilag, Celgene, Amgen, BMS: Honoraria. Delforge:Novartis: Honoraria; Celgene Corporation: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Weisel:Amgen: Consultancy, Honoraria, Other: Travel Support; Noxxon: Consultancy; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Travel Support, Research Funding; Novartis: Other: Travel Support; Onyx: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Other: Travel Support. Knop:Celgene Corporation: Consultancy. de Arriba:MundiPharma: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene Corporation: Consultancy, Honoraria, Speakers Bureau. Simcock:Celgene Corporation: Employment. Miller:Celgene Corporation: Employment, Equity Ownership. Slaughter:Celgene Corporation: Employment, Equity Ownership. Watkins:Celgene Corporation: Employment. Herring:Celgene Corporation: Employment. Biyukov:Celgene: Employment, Equity Ownership. Peluso:Celgene Corporation: Employment, Equity Ownership. Zaki:Celgene Corporation: Employment, Equity Ownership. Dimopoulos:Amgen: Honoraria; Novartis: Honoraria; Genesis: Honoraria; Janssen-Cilag: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Onyx: Honoraria.
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Ravandi, Farhad, Srdan Verstovsek, Zeev Estrov, Jan A. Burger, Solly George, Carol Bivins, Jorge Cortes-Franco, William M. Garrett, Robert C. Newton, and Hagop Kantarjian. "Significant Activity of the JAK2 Inhibitor, INCB018424 in Patients with Secondary, Post-Myeloproliferative Disorder (MPD) Acute Myeloid Leukemia (sAML): Results of An Exploratory Phase II Study." Blood 114, no. 22 (November 20, 2009): 631. http://dx.doi.org/10.1182/blood.v114.22.631.631.
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Abstract Abstract 631 Background: Mutations of JAK2 gene have been identified in a significant proportion of patients with MPDs with the selective JAK2 inhibitors demonstrating significant activity. Patients with AML following prior MPD (sAML) respond poorly to standard cytotoxic chemotherapy and have a poor outcome. Abnormalities of the Jak-Stat signaling pathway have also been identified in a number of other hematological malignancies; chromosomal translocations resulting in TEL-JAK2 constructs lead to the constitutive activation of STAT5, IL-3-independent cellular proliferation, and leukemogenesis. Similarly, infection with oncogenic viruses such as human T-cell lymphotrophic virus, type I, and Abelson murine leukemia viruses results in enhanced kinase activity of Jaks, possibly accounting for their leukemogenic potential. Furthermore, disrupted Jak-Stat signaling has been reported in a number of leukemias. Aim: To identify potential activity of INCB018424 in patients with advanced hematological cancers. Methods: We are conducting a phase II study of INCB018424 in patients with relapsed/refractory leukemias for which no standard therapies are anticipated to result in a durable remission. Patients with performance status 0,1,and 2 with adequate organ function and no active, uncontrolled intercurrent illness or infection receive INCB018424 orally at 25 mg BID daily for 4 weeks (cycle #1). Response is assessed after 2 cycles of treatment. Responding patients or patients with stable disease are allowed to continue until progression. Predetermined dose modifications to 15 mg or 10 mg BID are allowed for drug related toxicities. Results: Eighteen patients [median age, 68 years; (range, 53-88] with relapsed and refractory leukemias (9 de novo AML, 3 sAML, 2 ALL, 1 MDS, 2 CMML, 1 CML) have been treated. The median number of prior therapies is 2 (range,1 to 6). Five patients (1 with AML, 2 with sAML, and 3 with CMML) had the JAK2 V617F mutation. Cytogenetic abnormalities include diploid in 7, chromosome 5 and 7 in 5, t(2;9) in 1, and the Philadelphia chromosome in 2. Pts have received a median of 1 cycle of therapy (range, 1-5 cycles) with 8 pts having stable disease (3 for 2 cycles, 2 for 3 cycles, 1 for 4 cycles, and 2 for 5 cycles). Three patients (including 2 with sAML and 1 with CMML, all with JAK2 mutation) have had significant declines in their bone marrow blasts (to <5%) associated with significant decrease in the size of the spleen and clinical improvement. The regimen has been very well tolerated with only grade 3 side effects being elevation of liver enzymes in 2 patients (thought not to be related to the study drug) and grade 3 thrombocytopenia in 1 patient. Conclusion: INCB018424 has significant activity in sAML and CMML associated with JAK2 V617F mutation. Clinical studies combining it with chemotherapy in sAML are warranted. Disclosures: Ravandi: Incyte Corporation: Research Funding. Verstovsek:Incyte: Research Funding. Garrett:Incyte Corporation: Employment. Newton:Incyte Corporation: Employment.
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Gee, Harold. "Standard & Poor’s Capital IQ NetAdvantage." Charleston Advisor 18, no. 4 (April 1, 2017): 49–52. http://dx.doi.org/10.5260/chara.18.4.49.
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Muglia, Camilla, Luca Santabarbara, and Stefano Grassi. "Is Bitcoin a Relevant Predictor of Standard & Poor’s 500?" Journal of Risk and Financial Management 12, no. 2 (May 31, 2019): 93. http://dx.doi.org/10.3390/jrfm12020093.
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The paper investigates whether Bitcoin is a good predictor of the Standard & Poor’s 500 Index. To answer this question we compare alternative models using a point and density forecast relying on Dynamic Model Averaging (DMA) and Dynamic Model Selection (DMS). According to our results, Bitcoin does not show any direct impact on the predictability of Standard & Poor’s 500 for the considered sample.
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Costello, Michele R. "Standard & Poor’s Capital IQ NetAdvantage Revisited." Charleston Advisor 25, no. 4 (April 1, 2024): 57–62. http://dx.doi.org/10.5260/chara.25.4.12.
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Standard & Poor’s (S&P) Capital IQ NetAdvantage is an integrated Web-based market intelligence platform. NetAdvantage offers global news, market analytics, counterparty analytics, fund analytics, industry research, powerful screening tools, and people search capabilities, offered separately in many competitor products, under one platform using transparent and trusted industry-standard sources. Users can analyze the global business operating environment with information on public markets and indices, basic information on foreign exchange rates and interest rates, sovereign profiles, peer groups generated with S&P Capital IQ’s proprietary relevancy score, and detailed CFRA Industry Research Reports. The streamlined interface with mostly intuitive menus and links plus a free-text search bar make this platform more accessible than its more sophisticated counterparts. Limitations include lack of depth in some content areas, certain ADA compliance issues, and some clunky aspects of the search interface despite significant improvements over the years.
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Corley-Lay, Judith B. "Friction and Surface Texture Characterization of 14 Pavement Test Sections in Greenville, North Carolina." Transportation Research Record: Journal of the Transportation Research Board 1639, no. 1 (January 1998): 155–61. http://dx.doi.org/10.3141/1639-17.
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Three locked-wheel skid trailers, International Cybernetics Corporation (ICC) Model MOR 5041 and K. J. Law Models M 1270 and M 1290, were tested at three speeds on 14 test sections located in Greenville, North Carolina. The test sections included a heavy-duty surface course, polymer-modified heavy-duty surface course, rubber-modified heavy-duty surface course, heavy-duty surface course with carbon black, stone mastic with fibers, polymer-modified stone mastic, and large-stone surface course. Multivariate regression analysis of friction number versus speed for the three test vehicles was performed. Despite having been load cell calibrated 1 day before testing, the ICC MOR 5041 results were statistically different from those of the other skid trailers on all but one test section. The two K. J. Law skid trailers were statistically different from each other, either on intercept or slope, on more than half of the test sections. Each individual skid trailer provided repeatable results with a standard deviation of about 2 when testing was done at 64 km/h, with a higher standard deviation for testing at lower speed. The frictional resistance of the test sections was compared by ranking frictional number at 64 km/h and rate of decline of friction number with speed. The best frictional performance was provided by the heavy-duty surface course and the large-stone surface course, and stone mastic with fibers and stone mastic with polymer were ranked poorest. None of the test sections had an average friction number less than 40, even when tested at 80 km/h.
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Smirnov, Veniamin, and Dimitri Volchenkov. "Five Years of Phase Space Dynamics of the Standard & Poor’s 500." Applied Mathematics and Nonlinear Sciences 4, no. 1 (June 28, 2019): 209–22. http://dx.doi.org/10.2478/amns.2019.1.00019.
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AbstractInhomogeneous density of states in a discrete model of Standard & Poor’s 500 phase space leads to inequitable predictability of market events. Most frequent events might be efficiently predicted in the long run as expected from Mean reversion theory. Stocks have different mobility in phase space. Highly mobile stocks are associated with less unsystematic risk. Less mobile stocks might be cast into disfavor almost indefinitely. Relations between information components in Standard & Poor’s 500 phase space resemble of those in unfair coin tossing.
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Hodigere, Renuka, and Diana Bilimoria. "Human capital and professional network effects on women’s odds of corporate board directorships." Gender in Management: An International Journal 30, no. 7 (October 5, 2015): 523–50. http://dx.doi.org/10.1108/gm-07-2015-0063.
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Purpose – The purpose of this study is to examine the importance of human capital and professional networks for women’s and men’s appointment to the boards of directors of public companies. The study provides an in-depth analysis of how human capital and professional networks contribute to women’s as compared with men’s odds of corporate board membership. Design/methodology/approach – The study analyzes the human capital and professional networks of 494 male and female corporate outside (non-executive) directors appointed between 2005 and 2010 to the boards of US public companies listed in the Standard & Poor’s 500 index. Human capital was measured as director age, education and professional experience (function and role). Professional network variables measured included composition of professional network, network centrality, constraint and cohesion. Findings – The study’s findings reveal that the characteristics that impact the appointment of women as outside directors to public company boards differ from those of men. Relative to men, certain professions such as government relations and education improve the odds of appointment of women to corporate boards, while age lowers women’s odds. The number of network ties and the degree of network cohesion were also significant in predicting the likelihood of female board appointment to public corporations relative to men’s odds. The final model was able to predict female board membership correctly only in 28 per cent of the cases, while male board membership was predicted in 89 per cent of the cases, suggesting that factors other than human capital and professional networks (e.g. their gender) impact women’s appointment to corporate boards. Originality/value – To the authors ' knowledge, this study is the first to comprehensively examine the professional network components of female and male directors along with their human capital in the analysis of their prospects for board appointment. The conceptualization of professional networks as well the depth of quantitative analysis of the network components of the study advance the extant literature on the composition of corporate boards.
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Ocran, Matthew. "South Africa and United States stock prices and the Rand/Dollar exchange rate." South African Journal of Economic and Management Sciences 13, no. 3 (September 3, 2010): 362–75. http://dx.doi.org/10.4102/sajems.v13i3.106.
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This paper seeks to examine the dynamic causal relations between the two major financial assets, stock prices of the US and South Africa and the rand/US$ exchange rate. The study uses a mixed bag of time series approaches such as cointegration, Granger causality, impulse response functions and forecasting error variance decompositions. The paper identifies a bi-directional causality from the Standard & Poor’s 500 stock price index to the rand/US$ exchange rate in the Granger sense. It was also found that the Standard & Poor’s stock price index accounts for a significant portion of the variations in the Johannesburg Stock Exchange’s All Share index. Thus, while causality in the Granger sense could not be established for the relationship between the price indices of the two stock exchanges it can argued that there is some relationship between them. The results of the study have implications for both business and Government.
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Venter, Pierre J., and Eben Maré. "Pricing collateralised options in the presence of counterparty credit risk: An extension of the Heston–Nandi model." South African Statistical Journal 56, no. 1 (2022): 37–51. http://dx.doi.org/10.37920/sasj.2022.56.1.3.
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In this paper, a closed-formexpression for a collateralised European option in the presence of counterparty credit risk and stochastic volatility is derived. The model is applied to Standard and Poor’s 500 index options. The model prices obtained are consistent with expectations.
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Maingot, Michael, and Tony K. Quon. "Sampling Practices of Internal Auditors at Corporations on the Standard & Poor's Toronto Stock Exchange Composite Index*." Accounting Perspectives 8, no. 3 (August 2009): 215–34. http://dx.doi.org/10.1506/ap.8.3.2.
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Slichter, Sherrill J., Larry J. Dumont, Jose A. Cancelas, Terry Gernsheimer, Zbigniew Szczepiorkowski, Nancy M. Dunbar, Stephen Medlin, et al. "Treatment of Bleeding in Severely Thrombocytopenic Patients with Transfusion of Dimethyl Sulfoxide (DMSO) Cryopreserved Platelets (CPP) Is Safe - Report of a Phase 1 Dose Escalation Safety Trial." Blood 128, no. 22 (December 2, 2016): 1030. http://dx.doi.org/10.1182/blood.v128.22.1030.1030.
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Abstract Availability of platelets (plts) is severely limited by shelf life in some military as well as civilian settings. Additionally, some bleeding, thrombocytopenic patients do not have a therapeutic response to a standard plt transfusion. Methods for cryopreservation of apheresis plts for up to two years in 6% DMSO at <-65°C (CPP) have been developed and evaluated by in vitro assays and by in vivo infusions in non-human primates, in a few controlled human trials, and in field military operations. However, FDA has not yet approved CPP for routine use. Autologous radiolabeled CPP in healthy volunteers (n=32) had average plt recoveries of 33 ± 10% and survivals of 7.5 ± 1.2 days, and these results were 52 ± 12% and 89 ± 15%, respectively, of the same volunteers' fresh radiolabeled plts. The in vitro phenotype of CPP showed higher granule secretion, phosphotidylserine expression, and plt microparticles and poorer responses to common plt agonists compared to standard room temperature stored plts. These data suggest that transfused CPP might lead to an accelerated and enhanced clotting process in vivo. Our objective was to evaluate the safety of transfused CPP in a Phase-1 dose escalation trial. Eligibility criteria were hospitalized thrombocytopenic hematology/oncology patients with active World Health Organization (WHO) Grade 2 or greater bleeding that was, in most patients, uncontrolled by standard plts, no history of unprovoked thrombotic events, and no indication of active DIC. Fifty-nine patients consented and 28 were transfused with ½ CPP unit (n=5), one CPP unit (n=7), two CPP units (n=6), and three CPP units (n=6). One thawed single apheresis CPP unit contained 2.5 x 1011 ± 4.2 x 1010 plts in 50 ± 4 ml. In addition, one standard apheresis plt unit was randomly given to patients enrolled in each cohort (n=4). The study conformed to the Declaration of Helsinki and was listed on clinical trials.gov (NCT02078284). Patients were monitored for six days post-transfusion for adverse events (AEs) including clinical assessments for signs or symptoms of thrombosis and specific laboratory assays: prothrombin time (PT), partial thromboplastin time (aPTT), D-dimer, fibrinogen, prothrombin fragments 1 + 2 (F1+2), antithrombin, thrombin antithrombin (TAT), thrombin generation (TGT), and thromboelastography (TEG). All safety data were reviewed by an independent data safety monitoring committee prior to escalation to the next higher dose cohort. No thrombotic events occurred after transfusion of CPP units. Five serious AEs were reported, and none were associated with the CPP transfusion but, rather, were related to worsening of the patients' underlying medical conditions. Of 38 AEs, 5 were, at least, possibly related to a CPP transfusion and included DMSO skin odor following a ½ CPP unit and three CPP units (n=2), mild fever and chills in the same patient after one CPP unit (n=2), and moderate headache the next day following transfusion of three CPP units (n=1). As expected in this clinically-ill patient population, D-dimer, fibrinogen, F1+2, aPTT, and TAT averaged higher than the upper limit of normal prior to transfusion and remained similar following transfusion. TGT and TEG were suppressed pre-transfusion and were improved towards normal levels following transfusion of either CPP or standard plts. There was no induction of a post-transfusion hypercoagulable state in any patient based on laboratory results. Modest increases in corrected plts count increments (x 103/mm3) were observed following CPP transfusion (one CPP unit gave CCI's of 2.3 ± 3.5; two CPP units 4.2 ± 2.8; and three CPP units 5.6 ± 2.3) compared with 21.1 ± 3.6 after one unit of standard apheresis plts. Notably, all patients had stabilization or improvement of their bleeding following a CPP transfusion including one patient with Grade 4 CNS bleeding who had resolution of neurologic symptoms with no further plt transfusions, and four patients (17%) had WHO bleeding downgraded. In conclusion, the infusion of up to three sequential units of CPP in patients with severe thrombocytopenia and active bleeding was safe without any evidence of thrombotic complications despite CPP having a procoagulant phenotype resulting from the cryopreservation process. CPP may be efficacious to stop bleeding in thrombocytopenic patients as suggested by stabilization or downgrading of WHO bleeding grades. Phase 2/3 efficacy clinical trials are now indicated. Disclosures Slichter: NHLBI / NIH: Research Funding; Genentech: Research Funding; Cerus Corporation: Research Funding; Terumo BCT: Research Funding; Cellphire: Research Funding; Department of Defense / US Army Medical Research and Material Command: Research Funding; Megakaryon: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Stock options. Dumont:US Army Medical Research and Material Command (Award W81XWH-15-C-0047) / Department of Defense: Research Funding. Cancelas:New Health Sciences, Inc.: Membership on an entity's Board of Directors or advisory committees; US Army Medical Research and Material Command (Award W81XWH-15-C-0047) / Department of Defense: Research Funding; National Institutes of Health: Research Funding; Terumo BCT: Research Funding; Cerus Corporation: Research Funding; Haemonetics, Inc.: Research Funding; Citra Labs, Inc.: Research Funding; Cellphire, Inc.: Membership on an entity's Board of Directors or advisory committees; William & Lawrence Hughes Foundation: Research Funding; Leukemia & Lymphoma Society of North America: Research Funding. Gernsheimer:Department of Defense: Research Funding; NHLBI / NIH: Research Funding. Szczepiorkowski:Fresenius Kabi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Grifols: Consultancy, Research Funding; Terumo BCT: Consultancy; Cerus Corporation: Research Funding; Erydel: Research Funding; Citra Labs: Research Funding; US Army Medical Research and Material Command (Award W81XWH-15-C-0047) / Department of Defense: Research Funding; American Association of Blood Banks: Other: President-Elect. Dunbar:Verax Biomedical: Membership on an entity's Board of Directors or advisory committees; US Army Medical Research and Material Command (Award W81XWH-15-C-0047) / Department of Defense: Research Funding. Jones:US Army Medical Research and Material Command (Award W81XWH-15-C-0047) / Department of Defense: Research Funding. Rugg:US Army Medical Research and Material Command (Award W81XWH-15-C-0047) / Department of Defense: Research Funding. Prakash:US Army Medical Research and Material Command (Award W81XWH-15-C-0047) / Department of Defense: Research Funding. Hmel:US Army Medical Research and Material Command (Award W81XWH-15-C-0047) / Department of Defense: Research Funding. Ransom:US Army Medical Research and Material Command (Award W81XWH-15-C-0047) / Department of Defense: Research Funding.
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Pratta, Michael A., Hao Liu, Sherry Owens, Ying Yan, Michael C. Arbushites, and Michael D. Howell. "A Biomarker Signature to Predict Complete Response to Itacitinib and Corticosteroids in Acute Graft Versus Host Disease." Blood 134, Supplement_1 (November 13, 2019): 3279. http://dx.doi.org/10.1182/blood-2019-124069.
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BACKGROUND: Acute graft versus host disease (aGVHD) represents a serious and potentially life-threatening condition in patients receiving hematopoietic stem cell transplantation (HSCT). Development of aGVHD is characterized by increased levels of inflammatory mediators and activated T cells in circulation, leading to tissue and organ damage. Previously, we demonstrated that a panel measuring ST2, REG3A, and TNFR1 poorly predicted response to the combination of corticosteroids and itacitinib, a potent and highly selective JAK1 inhibitor, in a parallel-cohort phase 1 trial (NCT02614612). In this study, we utilized broad proteomic analysis to identify potentially predictive biomarkers of therapeutic response to the combination treatment. METHODS: Plasma samples were collected from 25 patients enrolled in the Phase 1 clinical trial prior to and at designated times following treatment. Broad proteomic analysis was conducted by OLINK Proteomics using a proximity extension assay. Selected biomarkers were quantitated by the same method based on standard curves generated using recombinant proteins. Statistical differences were identified using unpaired T tests and significance conferred when p<0.05. All participants provided written consent before enrollment. RESULTS: The 25 patients in this study were stratified based on overall response to treatment with itacitinib and corticosteroid at day 28 (based on CIBMTR). Patients included 10 complete responders (CR), 1 very good partial responder (VGPR), 8 partial responders (PR) and 6 patients with progressive disease and/or death (PD/death) prior to day 28. Novel biomarkers were identified and associated with therapeutic response by comparing the levels of approximately 1000 proteins in the CR (N=10) and PD/Death (N=6) cohorts specifically. The initial analysis identified 50 proteins significantly upregulated (P<.05) and 52 proteins significantly down-regulated (P<.05) in the CR cohort at baseline compared with the PD/Death cohort. The list of candidates were further screened based on correlation to known aGVHD biomarkers, degree of separation between the populations, as well as reliable and consistent testing (ie, coefficient of variation <20%). From these analyses, candidate biomarkers were identified and representative examples are shown in table 1. Novel biomarkers include macrophage chemotactic protein 3 (MCP3/CCL7), stem cell factor (SCF/KIT-L), interleukin 8 (IL8), and tumor necrosis factor receptor super family 6B (TNFRSF6B). Each of these candidate biomarkers demonstrated a significant (P<.05) difference between CR and PD/death cohorts, with intermediate levels detected in patients with an intermediate (VGPR/PR) response to treatment. Because MCP3, IL8, and TNFRSF6B presumably associate with inflammation, elevation of these biomarkers in the PD/Death cohort that poorly respond to a JAK inhibitor (JAKi) is not surprising. In addition, elevation of SCF in responders to JAKi is consistent with supporting hematopoiesis. CONCLUSION: Potentially novel biomarkers may be useful in predicting complete responses to treatment with a combination of corticosteroids and itacitinib in patients with aGVHD post HSCT. Disclosures Pratta: Incyte Research Institute: Employment. Liu:Incyte: Employment, Equity Ownership. Owens:Incyte Corporation: Employment, Equity Ownership. Yan:Incyte Corporation: Employment. Arbushites:Incyte: Employment. Howell:Incyte: Employment.
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Vychytilová, Jana. "Intermarket Technical Research of the U.S. Capital Markets and the Czech Stock Market Performance." Acta Universitatis Agriculturae et Silviculturae Mendelianae Brunensis 62, no. 6 (2014): 1509–19. http://dx.doi.org/10.11118/actaun201462061509.
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Globalization of the capital markets increasingly leads the investors to understand the fundamentals and technicals of asset cross-correlations and the global asset allocation seems to be an important task. The paper measures product momentum correlations between the four leading global benchmarks Standard & Poor’s stock index, Thomson Reuters/Jefferies CRB index, 30-Year U.S. Treasury Bond Price index and Dollar Index and between these indices and the Czech stock PX index. Empirical results illustrate that statistically significant correlations between U.S. indices existed over some past period at the 95.0% confidence level. In addition, the significant relation between indices Standard & Poor’s stock index, Thomson Reuters/Jefferies CRB index and the Czech stock market PX during the past fifteen years has been detected. These conclusions were reached from an analysis of monthly data in the United States and the Czech Republic, from January 1999 to April 2014. The empirical results offer beneficial applications not only for investors to diversify their risk but also for policy-makers to allocate resources more efficiently.
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Facon, Thierry, Cyrille Hulin, Meletios A. Dimopoulos, Andrew Belch, Nathalie Meuleman, Mohamad Mohty, Wen-Ming Chen, et al. "A Frailty Scale Predicts Outcomes of Patients with Newly Diagnosed Multiple Myeloma Who Are Ineligible for Transplant Treated with Continuous Lenalidomide Plus Low-Dose Dexamethasone on the First Trial." Blood 126, no. 23 (December 3, 2015): 4239. http://dx.doi.org/10.1182/blood.v126.23.4239.4239.
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Abstract Background: Many patient (pt) and disease factors have been shown to impact prognosis in multiple myeloma (MM). A recently described frailty scale categorized pts with MM into 3 groups: fit, intermediate, and frail based on age, comorbidities, and physical and cognitive functioning (Palumbo, Blood, 2015). These groups were predictive of risk of death. The pivotal phase 3 FIRST trial examined the impact of continuous therapy with lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) on outcomes in transplant-ineligible pts with newly diagnosed MM (NDMM; Benboubker, N Engl J Med, 2014). In this study, Rd continuous resulted in progression-free survival (PFS) and overall survival (OS) benefits compared with melphalan-prednisone-thalidomide (MPT). This analysis examined outcomes in pts by severity of frailty score in the FIRST trial, the largest clinical trial of transplant-ineligible NDMM to date. Methods: Pts with NDMM who were ineligible for transplant were randomized to treatment with Rd continuous, Rd for 18 cycles (Rd18; 72 weeks), or MPT for 12 cycles (72 weeks). Pts were categorized into 3 severity groups using a score based on age, Charlson Comorbidity Index score, and the Activities of Daily Living (measures of self-care) and Instrumental Activities of Daily Living (measures of usual activities) scales from the EQ-5D questionnaire at baseline, as previously described (Palumbo, Blood, 2015). This analysis examined PFS and OS outcomes by severity group in the overall pt population and between the Rd continuous and MPT arms, which were the primary comparators in this study, using an updated data cutoff of March 3, 2014. Results: This analysis included 1517 of 1623 pts from the intent-to-treat population; 106 pts were excluded because they did not have the required baseline data from the EQ-5D. The majority of pts enrolled in the FIRST trial were frail (54%) compared with fit (17%) or intermediate (30%). Similar breakdowns were observed across treatment arms (Figure 1). Frail pts were older and had higher Eastern Cooperative Oncology Group performance status scores, higher International Staging System (ISS) stage, higher lactate dehydrogenase levels, and worse renal function than fit or intermediate pts. In the overall pt population, better fitness was associated with significantly improved OS compared with worse fitness: fit vs intermediate (hazard ratio [HR] = 0.66; P = .004), fit vs frail (HR = 0.42; P < .0001), intermediate vs frail (HR = 0.62; P < .0001). Rd continuous treatment prolonged PFS compared with MPT for all pt severity groups (Figure 2). Rd continuous reduced the risk of progression or death vs MPT by 44%, 38%, and 21% in fit, intermediate, and frail groups, respectively. OS was also extended with Rd continuous vs MPT for all pt severity groups (Figure 2). Risk of death was reduced by 48%, 28%, and 20% in the fit, intermediate, and frail groups, respectively, with Rd continuous compared with MPT. Causes of death were primarily MM or complications of MM in fit (62% of deaths) and intermediate (57% of deaths) pts; while they were the cause of death in half of frail pts. Pts were further categorized within each fitness group by ISS stage: fit pts were classified by stage I vs II/III and intermediate and frail pts were classified by stage I/II vs III. Addition of ISS stage further improved prognostic classification within each severity group for both PFS and OS. Discussion: Results validated the feasibility of using the frailty scale for predicting risk of death in pts with NDMM and further demonstrated an association with PFS outcomes. The majority of pts fell into the frail category, which was associated with the poorest outcomes, indicating a need to further improve outcomes for a large proportion of pts with MM. Rd continuous resulted in PFS and OS benefits compared with MPT regardless of severity of frailty level, with the greatest benefits observed in fit pts. Poor outcomes of frail pts are likely further impacted by a higher proportion of deaths due to causes independent of MM compared with fit and intermediate pts, such as pre-existing comorbidities. These data support the use of Rd continuous as a standard frontline treatment option, even for frail pts with NDMM who are older and may have comorbidities or physical or cognitive impairments. Figure 1. Breakdown of Severity Group by Treatment Arm Figure 1. Breakdown of Severity Group by Treatment Arm Figure 2. PFS and OS by Pt Severity Group Figure 2. PFS and OS by Pt Severity Group Disclosures Facon: Celgene: Membership on an entity's Board of Directors or advisory committees; Jansen: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Hulin:Celgene Corporation: Honoraria; Bristol Myers Squibb: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Dimopoulos:Janssen-Cilag: Honoraria; Genesis: Honoraria; Amgen: Honoraria; Genesis: Honoraria; Janssen: Honoraria; Onyx: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Mohty:Celgene Corporation: Honoraria, Research Funding. Zamagni:Celgene Corporation: Honoraria, Speakers Bureau; Janssen Pharmaceuticals: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Renwick:Amgen: Other: Travel; Bayer: Speakers Bureau. Tempescul:Gilead: Other: Export Board Committee. Palumbo:Novartis, Sanofi Aventis: Honoraria; Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria. Sturniolo:Celgene Corporation: Employment. Ervin-Haynes:Celgene Corporation: Employment.
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Peffault De Latour, Regis, Lynn Huynh, Jasmina I. Ivanova, Todor Totev, Mehmet Bilginsoy, Joseph H. Antin, Anuja Roy, and Mei Sheng Duh. "A Retrospective Chart Review to Assess Burden of Illness Among Patients with Severe Aplastic Anemia with Insufficient Response to Immunosuppressive Therapy." Blood 130, Suppl_1 (December 7, 2017): 678. http://dx.doi.org/10.1182/blood.v130.suppl_1.678.678.
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Abstract Background: Aplastic anemia (AA) is a rare disease, with an incidence of 1-2 new cases per million per year in Europe and North America. Primary therapies for AA for patients who do not have a sibling or matched unrelated donor or are unfit for allogeneic hematopoietic stem cell transplantation (HSCT) include immunosuppressive therapy (IST) with the combination of antithymocyte globulin (ATG) and calcineurin inhibitors. Therapeutic options beyond IST are limited and include eltrombopag, which was approved by the US FDA for use in patients with severe AA who fail to respond adequately to IST. The health economic burden of this rare and debilitating condition is poorly understood, especially for refractory cases. Objective: To examine health resource utilization associated with severe AA among patients with insufficient response to IST in real-world practice settings in a recent time period. Methods: We conducted a retrospective, longitudinal chart review of patients with severe AA treated at clinical centers in the US (Dana-Farber Cancer Institute [DFCI]) and France (Service d'Hématologie Greffe, Hôpital Saint-Louis [AGRAH]). Severe AA in this study was identified as having bone marrow cellularity <25%, or 25-50% with <30% residual hematopoietic cells; and at least two of the following laboratory findings: neutrophil count <500 cell/µL, platelets <20,000/µL, reticulocyte count <20,000/µL. Eligible patients were ≥18 years old, first diagnosed with severe AA between January 1, 2006 and January 31, 2016, had insufficient response to at least one course of IST following severe AA diagnosis, and had ≥12 months of medical data after first diagnosis with severe AA. Patients with congenital disorders of hematopoiesis were excluded. Kaplan-Meier method was used to analyze time from first IST to time of HSCT. Cumulative incidence and incidence rates were used to summarize frequency of blood transfusions and AA-related health care resource utilization. The study was approved by local IRB. Results: The study included 34 refractory severe AA patients (NDFCI=20; NAGRAH =14). Mean age at severe AA diagnosis was 43.3 (standard deviation [SD]: 16.8) years and 52.9% (18/34) of patients were women. Median follow-up time after severe AA diagnosis was 56.1 (range: 12.0-118.7) months. Thirty-three (97.1%) patients received ATG in combination with calcineurin inhibitor (cyclosporine or tacrolimus) with or without corticosteroid as primary therapy. Among patients treated with ATG, 51.5% (17/33) patients received only one course of ATG and 48.5% (16/33) patients received ≥2 courses of ATG. The most common secondary AA therapy included eltrombopag (17.6%, N=6) and androgens (8.8%, N=3). The median treatment duration for eltrombopag was 6.4 (range: 5.6-53.4) months. The average frequency of transfusions per patient per month was 2.8 (SD: 2.8) red blood cell (RBC) and 3.3 (SD: 3.5) platelet transfusions. The mean AA-related health care utilization rates per patient per year were 0.8 (95% confidence interval [CI]: 0.6, 1.0) for inpatient visits, 0.5 (95% CI: 0.4, 0.8) for emergency room visits, and 19.1 (95% CI: 17.9, 20.5) for office visits prior to undergoing HSCT. Among the subgroup of patients treated with eltrombopag, the mean number of RBC transfusions per patient per month was reduced from 2.4 (SD: 2.0) before to 0.9 (SD: 0.8) after eltrombopag treatment, and from 3.0 (SD: 2.3) to 1.3 (SD: 1.6) for platelet transfusions. Similarly, AA-related health care utilization rates were lower after eltrombopag initiation (∆inpatient visits: -0.3 (95% CI: -1.1, 0.5); ∆emergency room visits: -0.6 (95% CI: -1.5, 0.4); ∆office visits: -11.7 (95% CI: -16.2, -7.1) per patient per year). Thirty (88.2%) patients received HSCT with a median time of 12.9 (95% CI: 7.9, 17.3) months after first IST initiation. During the follow-up period, 29.4% (10/34) patients died; nine patients died after HSCT. Two (5.9%) patients transformed to myelodysplastic syndrome and/or acute myeloid leukemia. Conclusion: This is one of the first studies to quantify the transfusion and health resource burden of refractory severe AA. In a small subgroup of patients receiving eltrombopag, there was a trend toward reduction in blood transfusion frequency, AA-related hospitalization rate, and outpatient office and emergency room visits after eltrombopag initiation. Disclosures Peffault De Latour: Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Amgen: Research Funding. Huynh: Novartis Pharmaceuticals Corporation: Research Funding. Ivanova: Novartis, GSK, Teva, Lilly: Research Funding. Totev: Novartis Pharmaceuticals Corporation, Shire Pharmaceuticals Inc.: Research Funding. Bilginsoy: Novartis Pharmaceuticals Corporation: Research Funding. Roy: Novartis: Employment, Equity Ownership. Duh: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding.
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Buser, Andreas S., Laura Infanti, Andreas Holbro, Joerg Halter, Sabine Gerull, Dominik Heim, Michael Medinger, et al. "Impact of Amotosalen/UVA Pathogen Inactivated Platelet Components on Outcomes after Allogeneic Hematopoetic Stem Cell Transplantation: A Single Center Analysis." Blood 134, Supplement_1 (November 13, 2019): 1167. http://dx.doi.org/10.1182/blood-2019-122330.
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Background: Platelet component (PC) transfusion is required for allogeneic hematopoietic stem cell transplantation (HCT) recipients. Contamination with infectious pathogens (bacteria, viruses, or protozoa) and T-cells is a risk factor for transfusion-transmitted infection (TTI) and transfusion associated graft-versus-host disease (TA-GVHD). Pathogen inactivation (PI) treatment of PC with amotosalen-UVA (PI-PC, INTERCEPT Blood System, Cerus Corp) in platelet additive solution (PAS) without bacterial screening, gamma irradiation, CMV serology, and with 7-day storage has been the standard of care in Switzerland since 2011 to manage risk of TTI and TA-GVHD. PI-PC have replaced conventional PC (C-PC) prepared in PAS with gamma irradiation and 5 day storage. We previously reported platelet usage in two consecutive five year periods at the University Hospital of Basel. Mean PI-PC dose was higher (3.0 vs. 2.8 x 1011, p=0.001) and mean storage duration longer (4.2 vs. 3.4 days: p=0.001) than with C-PC. PC expiration wastage was reduced with 7-day PI-PC storage vs. 5-day storage (1.5% vs. 8.7%). For HCT recipients, days of PC support; PC use per patient; and RBC use per patient were similar, despite 24.3% lower corrected count increments (CCI) with PI-PC. Now, we report the impact of these observations on treatment related mortality (TRM) and overall survival (OS) 100 days after HCT. Patients and Methods: A two-period retrospective cohort study was conducted to evaluate PI-PC impact on outcomes of consecutive first allogeneic HCT recipients from January 2006 to December 2010 (Period 1, P1), when gamma-irradiated apheresis C-PC were used, and Period 2 (P2) from January 2011 to December 2017, when apheresis and whole blood-derived PI-PC were used. The review utilized 100-day OS and 100-day TRM to determine the impact of PI-PC on HCT outcomes. Descriptive statistics were used for continuous variables and log-rank analysis for survival outcomes. Univariate analysis was performed using Pearson χ2 statistics. Multivariate Cox regression modelling analyses included: PC period (P1, P2), donor match (HLA identical/twin, matched related, matched unrelated), disease state (early, intermediate, late), and conditioning regimen (reduced intensity, myeloablative) with TRM as the outcome. This was an IRB approved single-center analysis. Results: In P1 and P2, 256 and 557 consecutive first-time allogeneic HCT recipients were included, respectively. By univariate analysis, the distribution of European Group for Bone Marrow Transplantation (EBMT) risk scores (grouped 0-2, 3-4, 5-7) and mean patient age were higher during P2 (p = 0.001 and p <0.001, respectively). Primary disease status (p = 0.039); stem cell source (p <0.001); GVHD prophylaxis with ATG (p <0.001); total body irradiation (p <0.001); and conditioning regimen (p <0.001) were different between P1 and P2. Donor match (p=0.084) and disease status (p = 0.628) were similar in P1 and P2. TRM at day 100 post HCT was significantly less (31/557, 5.5%) for PI-PC recipients in P2 vs. C-PC recipients in P1 (37/256, 14.5%, p<0.001). Overall proportion of survivors at day 100 post HCT was significantly greater for PI-PC recipients (507/557, 91.0 %) compared to C-PC recipients (209/256, 81.6%, p <0.001). By multivariate Cox regression analysis, P2 with PI-PC component support was associated with improved TRM (p = 0.001; adjusted hazard ratio 0.433; 95% confidence interval: 0.262, 0.716). Donor match (p = 0.019), disease state (p = 0.022), and myeloablative conditioning (p = 0.034) were associated with significantly poorer TRM (Table). Stem cell source was not significant (p=0.157) in the model. Hemorrhage was reported as cause of death in 1/50 (2.0%) patients during P2 with PI-PC and 4/47 (8.5%) patients during P1 with C-PCs. Conclusions: Universal implementation of PI-PC in routine with extended storage to 7 days in P2 was associated with reduced TRM and better overall survival 100 days post HCT, despite transplantation of older patients with higher EBMT risk scores. Multivariate analysis revealed an adjusted hazard ratio of 0.433 (95% C.I. 0.262, 0.716) for TRM by 100 days, suggesting better outcomes in P2. This retrospective analysis at a single site indicated that PI-PC treated with amotosalen /UVA stored up to 7 days did not have a negative impact on TRM and OS in HCT recipients, and was an integral part of improving clinical outcomes at our institution. . Table. Disclosures Heim: Novartis: Research Funding. Irsch:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.
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Cheng, C. S. Agnes, Denton L. Collins, and Henry He Huang. "The market response to the Standard & Poor’s transparency and disclosure rankings." Corporate Ownership and Control 5, no. 2 (2008): 244–55. http://dx.doi.org/10.22495/cocv5i2c2p1.
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This paper investigates whether the Standard & Poors (S&P) transparency and disclosure (T&D) rankings represented new information to the financial markets when the results of the study were released by S&P on October 15, 2002. The S&P T&D rankings report the relative levels of three disclosure dimensions (ownership structure and investor rights, financial transparency and information disclosure, and board and management structure and process) provided by firms in their annual reports (annual report rankings) and complete regulatory filings (composite rankings). The results suggest that the S&P T&D rankings provided new information to the markets on cross-sectional differences in disclosure, and the market responds unfavorably during the event period to firms with large difference in disclosure levels across annual report and other regulatory filings. Further analyses reveal that the results are driven by the subcategory of ownership structure and investor rights.
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Mulugetta, Abraham, Hormoz Movassaghi, and Raquib Zaman. "The influence of standard and poor’s ranking changes on stock price performance." Managerial Finance 28, no. 4 (April 2002): 19–30. http://dx.doi.org/10.1108/03074350210767807.
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Goldberg, Aaron D., Chetasi Talati, Pinkal Desai, Christopher Famulare, Sean M. Devlin, Noushin Farnoud, David A. Sallman, et al. "TP53 Mutations Predict Poorer Responses to CPX-351 in Acute Myeloid Leukemia." Blood 132, Supplement 1 (November 29, 2018): 1433. http://dx.doi.org/10.1182/blood-2018-99-117772.
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Abstract Background: CPX-351 (Vyxeos) is a liposomal combination of daunorubicin and cytarabine that was FDA approved in 2017 for treatment of adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). Genomic predictors of response to CPX-351 have not been described. TP53 mutations are uncommon in de novo AML, but relatively enriched in the t-AML and AML-MRC populations for which CPX-351 is approved (Christiansen DH et al. JCO 2001; Devillier R et al. Oncotarget 2015). As TP53 mutations confer resistance to conventional daunorubicin and cytarabine chemotherapy, we sought to determine whether TP53 mutations confer resistance to CPX-351. Methods: This is a retrospective, multi-center review of patients who received at least 1 cycle of induction chemotherapy with CPX-351 at Memorial Sloan Kettering Cancer Center (MSKCC), Moffitt Cancer Center (MCC), and Weill Cornell Medical College (WCMC). 101 patients were identified at MSKCC (n=22), MCC (n=44), and WCMC (n=35). Responses to CPX-351 were graded using European Leukemia Net (ELN) response criteria. (Döhner H et al Blood 2017) Immunophenotypic minimal residual disease (MRD) was identified in bone marrow aspirates (BMA) by multiparameter flow cytometry in 43 patients (MSKCC n=22, WCMC n=21). Any level of residual disease was considered MRD+. Molecular analysis was obtained from pre-induction BMA by next-generation sequencing using 21, 32, 49, or 400 gene panels, all of which included TP53. Cytogenetics/FISH were performed using standard techniques. Fisher's exact tests were used to determine significance and are two-tailed. Kaplan-Meier (KM) analysis with log-rank test was performed to estimate overall survival (OS). Results: Patient characteristics are in Table 1. 84/101 (83.1%) had baseline molecular profiling prior to CPX-351. TP53 mutations were identified in 18/84 (21.4% of patients). Analysis of additional co-mutations and responses will be presented by our collaborators (Talati et al., ASH 2018 submitted). TP53 mutations (19/20 distinct mutations) clustered in the DNA binding domain (Figure 1A). TP53 mutations are significantly associated with complex or monosomal karyotypes (p<0.001, see Table 1). Following 1-2 cycles of CPX-351 induction, complete responses (CR) combined with complete responses with incomplete blood count recovery (CRi) were significantly higher in TP53 wild-type (WT) patients compared to TP53 mutant patients. 62% WT (41/66) achieved CR/CRi, in comparison to 33% (6/18) TP53 mutant CR/CRi, p=0.0353, odds ratio=0.3049 (95 % CI:0.1016 to 0.9150). (Figure 1B). Responses for CR alone also trended in favor of TP53 WT patients. 45.5% (30/66) WT achieved CR, while 27.8% TP53 mutant (5/18) achieved CR, P=0.2806. Responses for MRD negative CR also favored WT patients, 36% MRD-CR WT (9/25), 8.3% MRD-CR TP53 mutant (1/12), although these results were not statistically significant likely due to low numbers of (n=37) who underwent molecular profiling and later MRD analysis. OS was not significantly different (Figure 3B, p=0.093), but also trended towards favoring WT over TP53 mutant patients. Additional data with longer-term follow-up will be presented. Conclusion: Our data demonstrate that AML patients with TP53 mutations have lower rates of CR/CRi than WT patients after 1-2 cycles of CPX-351. While our study is retrospective and limited by small numbers, our data overall support the hypothesis that resistance to liposomal daunorubicin and cytarabine chemotherapy is common in AML patients with TP53 mutations. Future clinical studies are needed to determine optimal therapy for these patients. Figure 1. A) Map of TP53 mutations in patients treated with CPX-351. Black circles represent truncating mutations; purple circles represent non-synonymous single nucleotide variants or splice site mutations. B) Rates of CR/CRi (left), CR (middle), and MRD negative CR in WT (n=66) and TP53 mutant (n=18) patients treated with CPX-351. C) OS for WT and TP53 mutant patients treated with CPX-351. Table 1. Patient Characteristics. Disclosures Goldberg: AROG: Research Funding; Celgene: Research Funding; Abbvie: Research Funding; Pfizer: Research Funding. Desai:Argenx: Consultancy; Cellerant Inc: Consultancy. Sallman:Celgene: Research Funding, Speakers Bureau. Roboz:Novartis: Consultancy; Celltrion: Consultancy; Novartis: Consultancy; Orsenix: Consultancy; Eisai: Consultancy; Sandoz: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy; AbbVie: Consultancy; Celgene Corporation: Consultancy; Aphivena Therapeutics: Consultancy; Orsenix: Consultancy; Bayer: Consultancy; Celltrion: Consultancy; Daiichi Sankyo: Consultancy; Bayer: Consultancy; Argenx: Consultancy; Celgene Corporation: Consultancy; Otsuka: Consultancy; AbbVie: Consultancy; Daiichi Sankyo: Consultancy; Eisai: Consultancy; Janssen Pharmaceuticals: Consultancy; Astex Pharmaceuticals: Consultancy; Pfizer: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Jazz Pharmaceuticals: Consultancy; Astex Pharmaceuticals: Consultancy; Cellectis: Research Funding; Roche/Genentech: Consultancy; Sandoz: Consultancy; Jazz Pharmaceuticals: Consultancy; Cellectis: Research Funding; Argenx: Consultancy; Aphivena Therapeutics: Consultancy. Sweet:Celgene: Honoraria, Speakers Bureau; BMS: Honoraria; Agios: Consultancy; Phizer: Consultancy; Agios: Consultancy; Celgene: Honoraria, Speakers Bureau; Astellas: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Jazz: Speakers Bureau; BMS: Honoraria; Astellas: Consultancy; Phizer: Consultancy; Jazz: Speakers Bureau. Tallman:Cellerant: Research Funding; AROG: Research Funding; Orsenix: Other: Advisory board; AbbVie: Research Funding; ADC Therapeutics: Research Funding; BioSight: Other: Advisory board; Daiichi-Sankyo: Other: Advisory board.
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Chen, Jian, Shangbin Yang, Spero R. Cataland, and Haifeng M. Wu. "Time-Dependent Activation of Complement system during Storage of Platelet Product." Blood 124, no. 21 (December 6, 2014): 4287. http://dx.doi.org/10.1182/blood.v124.21.4287.4287.
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Abstract Platelet transfusion is known for carrying a high incidence of clinically significant transfusion reactions such as febrile nonhemolytic transfusion reaction. The mechanism responsible for these transfusion-associated adverse events, however, is poorly understood. In this study, we hypothesize that prolonged in vitro storage activates the complement system in the platelet product that in turn causes a high frequency of transfusion reactions. Fresh platelet units obtained from three blood donors were stored on a temperature controlled platelet rotator between 22-24 C°. An aliquot of platelet product was obtained using sterile techniques from each unit on day 2 through day 7. The platelet product from each collection was then immediately centrifuged to obtain platelet poor plasma for the study of complement activation levels. For all study samples, C4d levels were assayed to evaluate the activation of the classical pathway, factor Bb levels were measured to determine the status of the complement alternative pathway, C3a levels were used to examine common pathway activation, and C5a and C5b-9 were assayed for determination of the terminal pathway activation of the complement system. The reference range for each complement factor was determined using citrated plasma from 40 healthy donors. As shown in table 1, both C4d and C3a demonstrated time-dependent increases relevant to storage time. On day 7, C4d and C3a levels were five-fold higher than their baseline levels measured on day 2. In contrast, factor Bb levels remained stable and within the normal range throughout the study. Over a storage span of seven days, the terminal complement factors C5a and C5b-9 were also significantly increased, although not as dramatically as C4d and C3a. Figure 1 illustrates a progressive increase of C3 activation in all three study donors over the time of storage (2-7 days). This report, for the first time, provides strong evidence that substantial complement activation occurs in the platelet products under standard storage conditions. A longer storage time of platelet product in vitro is accompanied by a remarkable elevation of complement activation biomarkers. By examining the pattern of complement profiles in the stored platelets, we further demonstrated that the activation of the classic pathway, rather than alternative pathway, appears to be the driving event that leads up to a level of over-reactivity of the complement system. Given the fact that complement hyperactivation is known to disrupt host homeostasis and cause disease, the adverse reactions seen in platelet recipients is likely related to the infusion of C3a and C5a which are known to be potent inflammatory cytokines. The observations from this study therefore provide a new perspective in understanding the pathophysiology responsible for adverse reactions from platelet transfusions. Further studies will be required to fully evaluate the clinical impact of complement activation in transfused platelet products. Figure 1 Figure 1. Disclosures Cataland: Alexion Corporation: Honoraria, Research Funding, Speakers Bureau. Wu:Alexion Corporation: Honoraria, Research Funding, Speakers Bureau.
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Brauers, Willem K. M., and Natalija Lepkova. "IS CREDIT RATING RESERVED TERRITORY FOR CREDIT RATING AGENCIES? A MULTIMOORA APPROACH FOR EUROPEAN FIRMS AND COUNTRIES." Technological and Economic Development of Economy 25, no. 6 (October 16, 2019): 1259–81. http://dx.doi.org/10.3846/tede.2019.10722.
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Credit Rating Agencies rate firms and countries by internal experts but with a final qualitative judgment by their management acting as decision makers. These ratings on their turn influence the countries credit rating and ipso facto of their enterprises. The work of the CRA is in fact double: credit rating of firms and other organizations at one side and countries on the other. Considering the credit rating of firms, the CRA made significant mistakes during the Recession 2007−2009 and their judgment is too much American oriented, in any way from a European point of view. Consequently, in Europe many efforts were made to come to a new agency, but all efforts failed. It could be different for the rating of countries. Is a more scientific approach, eventually on a quantitative and structural basis, not possible? Therefore, MULTIMOORA, a quantitative method, is suggested. The study was made for all countries of the European Continent. Based on data available in 2013 and on their extrapolation, the results are quite comparable to the results of Standard & Poor’s Credit Rating System of the moment. As the classifications of Moody’s and Fitch are very similar to those of Standard & Poor’s the outcome would be similar for these other Credit Rating Agencies.
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Labrecque, Sébastien. "Les agences de notation dans la gouvernance financière internationale." Potentia: Journal of International Affairs 5 (October 1, 2014): 47–66. http://dx.doi.org/10.18192/potentia.v5i0.4405.
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Le département de la Justice des États-Unis a déposé en février 2013 une poursuite contre l’agence de notation financière Standard and Poor’s. Celle-ci est accusée par le gouvernement américain d’avoir tourné les coins ronds en attribuant de bonnes notations à des titres financiers adossés à des hypothèques qui présentaient pourtant de grands risques et, ainsi, d’avoir contribué au déclenchement de la crise financière de 2008 aux États-Unis (Eaglesham, Neumann et Perez 2013).
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Boreiko, Dmitri, Serguei Kaniovski, Yuri Kaniovski, and Georg Ch Pflug. "Business Cycles and Conditional Credit-Rating Migration Matrices." Quarterly Journal of Finance 08, no. 04 (September 24, 2018): 1840005. http://dx.doi.org/10.1142/s2010139218400050.
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To quantify the impact of business cycles on the dynamics of credit ratings, conditional migration matrices and probabilities of the corresponding macroeconomic scenarios are estimated. The approach is tested on a Standard and Poor’s (S&P’s) dataset that covers the period from 1991 to 2013. The difference between the conditional probabilities and their unconditional counterparts is evaluated. It is the greatest, up to [Formula: see text], for contraction periods and downgrading probabilities.
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Johnson, Travis L. "Risk Premia and the VIX Term Structure." Journal of Financial and Quantitative Analysis 52, no. 6 (December 2017): 2461–90. http://dx.doi.org/10.1017/s0022109017000825.
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The shape of the Chicago Board Options Exchange Volatility Index (VIX) term structure conveys information about the price of variance risk rather than expected changes in the VIX, a rejection of the expectations hypothesis. The second principal component, SLOPE, summarizes nearly all this information, predicting the excess returns of synthetic Standard & Poor’s (S&P) 500 variance swaps, VIX futures, and S&P 500 straddles for all maturities and to the exclusion of the rest of the term structure. SLOPE’s predictability is incremental to other proxies for the conditional variance risk premia, economically significant, and inconsistent with standard asset pricing models.
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Jadid Abdulkadir, Said, Hitham Alhussian, Muhammad Nazmi, and Asim A Elsheikh. "Long Short Term Memory Recurrent Network for Standard and Poor’s 500 Index Modelling." International Journal of Engineering & Technology 7, no. 4.15 (October 7, 2018): 25. http://dx.doi.org/10.14419/ijet.v7i4.15.21365.
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Forecasting time-series data are imperative especially when planning is required through modelling using uncertain knowledge of future events. Recurrent neural network models have been applied in the industry and outperform standard artificial neural networks in forecasting, but fail in long term time-series forecasting due to the vanishing gradient problem. This study offers a robust solution that can be implemented for long-term forecasting using a special architecture of recurrent neural network known as Long Short Term Memory (LSTM) model to overcome the vanishing gradient problem. LSTM is specially designed to avoid the long-term dependency problem as their default behavior. Empirical analysis is performed using quantitative forecasting metrics and comparative model performance on the forecasted outputs. An evaluation analysis is performed to validate that the LSTM model provides better forecasted outputs on Standard & Poor’s 500 Index (S&P 500) in terms of error metrics as compared to other forecasting models.
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Adrangi, Bahram, Arjun Chatrath, Madhuparna Kolay, and Kambiz Raffiee. "Dynamic Responses of Standard and Poor’s Regional Bank Index to the U.S. Fear Index, VIX." Journal of Risk and Financial Management 14, no. 3 (March 10, 2021): 114. http://dx.doi.org/10.3390/jrfm14030114.
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This study examines the reaction of the Standard and Poor’s Regional Bank Index (SPRB) to the U.S. equity market fear index (i.e., the Chicago Board of Trade Volatility Index [VIX]). The VIX is designed to perform as a leading indicator of the volatility in equity markets. However, practitioners observe many periods of divergence between the VIX and S&P 500. Our paper examines the daily data for the period of 2009 through 2019. We show that once the effects of consumer confidence and capacity utilization are accounted for, there is a negative association between the VIX and regional bank performance.
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Antia, Murad J. "The Standard & Poor’s Guide to Selecting Stocks (a review): The Standard & Poor’s Guide to Selecting Stocks 2005 Kaye Michael McGraw-Hill (877) 833-5524, www.books.mcgraw-hill.com . 244 pages, $24.95." Financial Analysts Journal 64, no. 3 (June 2008): 102–3. http://dx.doi.org/10.2469/faj.v64.n3.14.
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Карминский, Александр Маркович. "Модели корпоративных рейтингов для развивающихся рынков." Journal of Corporate Finance Research / Корпоративные Финансы | ISSN: 2073-0438 5, no. 3 (November 7, 2011): 19–29. http://dx.doi.org/10.17323/j.jcfr.2073-0438.5.3.2011.19-29.
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Автор: Александр Маркович Карминский - Национальный Исследовательский Университет "Высшая Школа Экономики". Электронная почта: akarminsky@hse.ru
В работе рассматриваются особенности существующей системы корпоративных рейтингов и специфика развития соответствующих эконометрических моделей рейтингов для предприятий на развивающихся рынках. В качестве объясняющих переменных используются финансовые индикаторы, индикаторы финансового рынка, а также макроэкономические и отраслевые факторы в разрезе отдельных стран. Рассматриваются и моделируются рейтинги международных агентств Standard & Poor’s, Moody’s Investors Service и Fitch Ratings. Оценивается предсказательная сила полученных моделей. Обсуждаются результаты сравнения рейтингов трех ведущих международных агентств.
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Зинкевич, Надежда В. "Прозрачность раскрытия информации российскими компаниями: обзор докладов, представленных на Второй Международной конференции «Корпоративное управление и устойчивое развитие бизнеса: стратегические роли советов директоров»." Journal of Corporate Finance Research / Корпоративные Финансы | ISSN: 2073-0438 1, no. 4 (December 31, 2010): 76–85. http://dx.doi.org/10.17323/j.jcfr.2073-0438.1.4.2007.76-85.
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В последние годы все больше российских компаний выходят на международные рынки капитала. Для привлечения средств зарубежных инвесторов компании необходимо соответствовать высоким стандартам корпоративного управления, одной из составляющей которого является информационная прозрачность. Тем не менее проведенное специалистами агентства Standard&Poor’s исследование свидетельствует, что уровень прозрачности российских компаний стагнирует. Возможным объяснением этой тенденции служит феномен «ресурсного проклятия», описанный Дурневым А. и Гуриевым С. С другой стороны, как показывает в своей работе Сеттлз А., успешность размещения ценных бумаг за рубежом положительно зависит от уровня раскрытия информации российскими компаниями.
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Ewanchuk, Logan, and Christoph Frei. "Recent Regulation in Credit Risk Management: A Statistical Framework." Risks 7, no. 2 (April 14, 2019): 40. http://dx.doi.org/10.3390/risks7020040.
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A recently introduced accounting standard, namely the International Financial Reporting Standard 9, requires banks to build provisions based on forward-looking expected loss models. When there is a significant increase in credit risk of a loan, additional provisions must be charged to the income statement. Banks need to set for each loan a threshold defining what such a significant increase in credit risk constitutes. A low threshold allows banks to recognize credit risk early, but leads to income volatility. We introduce a statistical framework to model this trade-off between early recognition of credit risk and avoidance of excessive income volatility. We analyze the resulting optimization problem for different models, relate it to the banking stress test of the European Union, and illustrate it using default data by Standard and Poor’s.
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Harada, Naonori, Hiroshi Okamura, Takahiko Nakane, Shiro Koh, Satoru Nanno, Mitsutaka Nishimoto, Asao Hirose, et al. "Pretransplant Plasma Brain Natriuretic Peptide and N-Terminal Pro-Brain Natriuretic Peptide Are More Useful Prognostic Markers of Overall Survival after Allogeneic Hematopoietic Cell Transplantation Than Echocardiography." Blood 136, Supplement 1 (November 5, 2020): 38–39. http://dx.doi.org/10.1182/blood-2020-134223.
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Background: There are several prognosis prediction models about allogeneic hematopoietic cell transplantation (allo-HCT) such as the hematopoietic cell transplantation specific comorbidity index (HCT-CI) and the refined disease risk index (R-DRI). Although HCT-CI and R-DRI are valuable and commonly used, further improvement of these models is desirable because the prognostic predictive abilities for post-allo-HCT survival remain suboptimal. Both brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP), are released from the ventricular and atrial walls, in response to the walls stretch into the blood. Plasma BNP and NT-proBNP levels are well-known biomarkers of the predictors of death in patients with cancer and heart disease. However, it is unclear whether these biomarkers are useful predictors for prognosis after allo-HCT. The main aim of our study was to evaluate the potential role of plasma BNP and NT-proBNP levels in predicting the mortality in allo-HCT patients. Methods: We retrospectively registered consecutive patients who underwent allo-HCT from January 2011 to December 2018. Plasma BNP and NT-proBNP examinations and echocardiography within 1 month from the start of conditioning regimen were performed in all transplant candidates as pretransplant work-up in our institution. Cox regression models were used to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CI) in the univariate and multivariate analyses. Relapse/progression (Rel/Prog) and non-relapse mortality (NRM) were considered competing events. The Fine-Gray proportional hazard regression model was used for the univariate and multivariate analyses with competing risks. A p value < 0.050 was considered statistically significant. We estimated the two models using c-statistics on the basis of time to event, using the total follow-up period to compare the predictive accuracy of R-DRI or HCT-CI with BNP or NT-proBNP added models. Standard errors (SEs) for the c-statistics were estimated by applying a bootstrap procedure using 1000 bootstrap samples to confirm the reproducibility. The SEs for the difference in c-statistics between these two models were compared with the above bootstrap samples and used to compute a z-score and a p value for the difference, similar to that in several previous studies. Results: We enrolled 174 consecutive patients. The median age was 49 (range: 16-68) years. During the follow-up period, 64 patients died (36.8%). Both plasma BNP and NT-proBNP levels showed a significant association with OS and NRM, but not Rel/Prog in the univariate analysis. Next, we conducted multivariable analysis to evaluate the independence of plasma BNP and NT-proBNP levels by adjusting for not only those variables that were reported as prognostic factors in the previous research for OS, but also diastolic dysfunction that can be associated with plasma BNP and NT-proBNP levels. We constructed each two and three multivariable model, including either BNP or NT-proBNP to assess the effects of these biomarkers on OS and NRM according to the one-in-ten rule 6 to avoid overfitting (Table 1). The adjusted models for OS showed that higher plasma BNP and NT-proBNP levels were significantly associated with poorer outcomes. Moreover, the adjusted models for NRM showed that a higher plasma BNP level was significantly associated with the outcome. We also evaluated the prognostic significance of BNP, NT-proBNP, HCT-CI, or echocardiographic parameters, including ejection fraction (EF) and diastolic dysfunction, by adding to R-DRI via computation of the c-statistic. BNP or NT-proBNP showed significantly higher c-statistic estimates for OS as compared with R-DRI alone (c-statistic estimate 0.741, 0.759, and 0.674, respectively), but not EF or diastolic dysfunction (Table 2). Both plasma BNP and NT-proBNP levels had higher HRs for OS [HR per standard deviation (SD) 2.57 (95% CI: 1.75-3.76), p < 0.001, and HR per SD 1.95 (95% CI: 1.39-2.73), p < 0.001] and NRM [HR per SD 2.10 (95% CI: 1.11-3.97), p < 0.024, and HR per SD 2.57 (95% CI: 1.92-3.44), p < 0.001] even in the normal heart function group. Conclusion: Plasma BNP and NT-proBNP levels are easy to perform and cost-effective; thus, these could be useful independent biomarkers for predicting allo-HCT prognosis than echocardiography. They enable clinical decision regarding allo-HCT. Disclosures Okamura: NIPPON SHINYAKU CO.,LTD: Honoraria. Nakane:Pfizer Japan Inc.: Research Funding; Janssen Pharmaceutical K.K.: Research Funding; Bayer Yakuhin, Ltd: Research Funding; Novartis: Honoraria, Research Funding; DAIICHI SANKYO COMPANY, LIMITED: Honoraria; Mundipharma K.K: Honoraria. Nanno:Otsuka Pharmaceutical Co., Ltd: Honoraria. Nishimoto:Bayer Yakuhin, Ltd:: Research Funding; Janssen Pharmaceutical K.K.:: Research Funding. Nakamae:Shire Japan KK: Honoraria; Celgene Corporation: Honoraria; DAIICHI SANKYO COMPANY, LIMITED: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Chugai Pharmaceutical Co., Ltd: Honoraria; Japan Blood Products Organization: Honoraria; NIPPON SHINYAKU CO.,LTD: Honoraria; Novartis: Honoraria; Pfizer Japan Inc.: Honoraria; Bristol-Myers Squibb: Honoraria; Kyowa-Hakko Kirin Co.,Ltd: Honoraria; Amgen Astellas BioPharma K.K: Honoraria; Astellas Pharma Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria. Nakashima:Amgen Astellas BioPharma K.K: Honoraria; Novartis: Honoraria, Research Funding; Eisai Co., Ltd: Honoraria, Research Funding; Amgen Inc: Honoraria; Kyowa-Hakko Kirin Co.,Ltd: Honoraria; Kyowa Kirin Co., Ltd: Honoraria; JCR Pharmaceuticals Co., Ltd: Honoraria; Pfizer Japan Inc: Honoraria; Astellas Pharma Inc: Research Funding; SymBio Pharmaceuticals Limited: Research Funding; Celgene Corporation: Research Funding; AbbVie GK: Research Funding; M S D K. K: Research Funding. Koh:Takeda Pharmaceutical Company Limited: Honoraria, Research Funding; Sumitomo Dainippon Pharma Co., Ltd: Honoraria; M S D K. K: Honoraria; NIHON PHARMACEUTICAL CO., LTD: Honoraria; Chugai Pharmaceutical Co., Ltd: Research Funding; Asahi Kasei Corporation: Research Funding; Amgen Astellas BioPharma K.K: Research Funding; IQVIA Services Japan K.K.: Research Funding; Takeda Science Foundation: Research Funding. Hino:Kyowa-Kirin: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Astellas: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Taiho: Research Funding; Teijin: Research Funding; MSD: Honoraria, Research Funding; Sumitomo Dainippon: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Daiichisankyo: Honoraria, Research Funding; Eisai: Research Funding; Jansenn: Honoraria; Celgene: Honoraria; Mochida: Honoraria; Ono: Honoraria; Sanofi: Honoraria; Japan Blood Products Organization: Research Funding; Nippon Shinyaku: Honoraria; Nihon Pharmaceutical: Research Funding; Mundi Pharma: Honoraria; Alexion: Honoraria. Nakamae:Pfizer Japan Inc: Honoraria, Research Funding; Astellas Pharma Inc: Honoraria, Research Funding; Otsuka Pharmaceutical Co., Ltd: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Amgen Astellas BioPharma K.K: Honoraria; ONO PHARMACEUTICAL CO., LTD: Honoraria; Kyowa-Hakko Kirin Co.,Ltd: Honoraria; Shire Japan KK: Honoraria; Celgene Corporation: Honoraria; DAIICHI SANKYO COMPANY, LIMITED: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Chugai Pharmaceutical Co., Ltd: Honoraria; Japan Blood Products Organization: Honoraria; NIPPON SHINYAKU CO.,LTD: Honoraria; Novartis: Honoraria; PPD-SNBL K.K: Research Funding.