Journal articles: 'New York (N.Y.). Board of Police' – Grafiati (2024)

Abstract:

Background As drug-related morbidity and mortality continue to surge, police officers are on the front lines of the North American overdose (OD) crisis. Drug law enforcement shapes health risks among people who use drugs (PWUD), while also impacting the occupational health and wellness of officers. Effective interventions to align law enforcement practices with public health and occupational safety goals remain underresearched. Objective The Opioids and Police Safety Study (OPS) aims to shift police practices relating to PWUD. It adapts and evaluates the relative effectiveness of a curriculum that bundles content on public health promotion with occupational risk reduction (ORR) to supplement a web-based OD response and naloxone training platform (GetNaloxoneNow.org, or GNN). This novel approach has the potential to improve public health and occupational safety practices, including using naloxone to reverse ODs, referring PWUD to treatment and other supportive services, and avoiding syringe confiscation. Methods This longitudinal study uses a randomized pragmatic trial design. A sample of 300 active-duty police officers from select counties in Pennsylvania, Vermont, and New Hampshire with high OD fatality rates will be randomized (n=150 each) to either the experimental arm (GNN + OPS) or the control arm (GNN + COVID-19 ORR). A pre- and posttraining survey will be administered to all 300 officers, after which they will be administered quarterly surveys for 12 months. A subsample of police officers will also be qualitatively followed in a simultaneous embedded mixed-methods approach. Research ethics approval was obtained from the New York University Institutional Review Board. Results Results will provide an understanding of the experiences, knowledge, and perceptions of this sample of law enforcement personnel. Generalized linear models will be used to analyze differences in key behavioral outcomes between the participants in each of the 2 study arms and across multiple time points (anticipated minimum effect size to be detected, d=0.50). Findings will be disseminated widely, and the training products will be available nationally once the study is completed. Conclusions The OPS is the first study to longitudinally assess the impact of a web-based opioid-related ORR intervention for law enforcement in the U.S. Our randomized pragmatic clinical trial aims to remove barriers to life-saving police engagement with PWUD/people who inject drugs by focusing both on the safety of law enforcement and evidence-based and best practices for working with persons at risk of an opioid OD. Our simultaneous embedded mixed-methods approach will provide empirical evaluation of the diffusion of the naloxone-based response among law enforcement. Trial Registration ClinicalTrail.gov NCT05008523; https://clinicaltrials.gov/show/NCT05008523 International Registered Report Identifier (IRRID) DERR1-10.2196/33451

Abstract:

Lesbian, gay, bisexual, and other sexual minority (LGB+) South Asian Americans represent a disproportionately underserved and often invisible community in the United States. While issues of sexual violence have been documented in the South Asian American community, little is known on its impact among LGB+ individuals. This study explores the experience of sexual violence, related attitudes, and mental health outcomes among LGB+ South Asian Americans. A community-informed online survey of 18–34-year-old South Asian Americans living near the New York State region, recruited from online social media platforms, was conducted. Study design, implementation, and evaluation occurred in partnership with an advisory board of South Asian young adult representatives; data was analyzed both descriptively and through multivariable logistic regression models. Of the 385 participants who reported their sexuality, LGB+ participants comprised 24.1% (n = 93) of the sample. LGB+ participants were more likely to have experienced rape multiple times (17.2% vs. 9.6%) in bivariate analyses, and higher odds of depression (AOR:3.47, 95%CI:1.61–8.17) in adjusted analyses. Overall, LGB+ South Asian Americans displayed a disproportionate burden of sexual violence and depression. Findings identify policy and research pathways to address sexual violence among LGB+ South Asians.

Abstract:

This study provides a crime script analysis of fatal police shootings in New York from 2013 to 2020. This work examines incident rates and subject demographics, as well as the initial situation context, subject-officer encounter, and incident conclusion stages of fatal police shootings. Findings identify an average of 19 incidents per year (N = 152). Subjects were most commonly male, aged 26–35, and Black. Situations initiating police presence often involved violent crimes, mental health/welfare checks, and domestic disputes. During the subject-officer encounter, subjects were often armed with a weapon, and half were armed with a firearm. Despite these potentially dangerous weapons, incidents rarely concluded with non-subject deaths or victim injuries. A discussion of findings highlights implications for understanding and addressing fatal police shootings including curbing illegal gun obtainment, pairing officers with crisis intervention teams and mental health workers, using less-lethal devices, and strengthening officer field tactics.

Abstract:

The police reforms introduced in New York City by William Bratton are now hailed by Mayor Rudy Giuliani as the epitome of “zero-tolerance” policing, and he credits them for winning dramatic reductions in the city's crime rate. But the number of citizen complaints filed before the Civilian Complaint Review Board has jumped skyward, as has the number of lawsuits alleging police misconduct and abuse offorce. Comparison of crime rates, arrest statistics, and citizen complaints in New York with those in San Diego—where a more problem-oriented community policing strategy has been implemented—gives strong evidence that effective crime control can be achieved while producing fewer negative impacts on urban neighborhoods.

Abstract:

Currently, few studies have examined mediation programmes within independent police oversight agencies. Moreover, analyses of these programmes primarily focus on the degree of citizen satisfaction. This study adds to the existing research by examining possible characteristics linked to mediation selection within independent police oversight agencies. Specifically, this study considers the long-standing tension experienced between the police and certain groups (e.g. minorities, youths and residents of disadvantaged communities) and attempts to determined which groups are more or less likely to meet with officers to resolve police complaints. The data (obtained from the New York City Civilian Complaint Review Board and United States Census of 2010) allow for an analysis of complainant demographic characteristics and neighbourhood characteristics linked to the complainants. Bivariate and multivariate analyses uncovered group differences in mediation selection. Particularly, the results of this study demonstrate that minorities are more likely to select mediation.

Abstract:

Abstract Communities marginalized because of racism, heterosexism, and other systems of oppression have a history of being aggressively policed, and in those contexts, researchers have observed associations between a range of negative experiences with police and poor physical, mental, and behavioral health outcomes. However, past studies have been limited in that experiences of police contacts were aggregated at the neighborhood level and, if police contacts were self-reported, the sample was not representative. To address these limitations, we employed NYC Department of Health and Mental Hygiene 2017 Social Determinants of Health Survey (n = 2335) data to examine the associations of self-reported police contacts and discrimination by police and the courts with measures of physical (poor physical health), mental (poor mental health, serious psychological distress), and behavioral health (binge drinking). Residents marginalized because of racial, ethnic, and sexual minority status were more likely to be stopped, searched, or questioned by the police; threatened or abused by the police; and discriminated against by the police or in the courts; those experiences were associated with poor physical, mental, and behavioral health outcomes. The associations between experiences with police and poor health outcomes were strongest among Black residents and residents aged 25–44. Our findings suggest that the health of NYC residents who have had exposure to police and experienced discrimination by the police and courts is poorer than those who have not, and build on a growing body of evidence that aggressive policing practices have implications for public health.

Abstract:

Purpose The purpose of this paper is to understand the relationship among police legitimacy/trust and experiences of intimate partner violence (IPV), including victims’ decisions to report IPV to police and police responses to IPV. Design/methodology/approach Data were drawn from the 2017 Survey of Police–Public Encounters II – a cross-sectional, general population survey of adults from New York City and Baltimore (n=1,000). Regression analyses were used to examine associations among police legitimacy/trust, IPV exposure, police reporting of IPV, and perceived police responses to IPV and interaction effects. Findings Higher levels of IPV exposure were significantly associated with lower levels of police legitimacy/trust; however, this relationship was stronger among African–American participants than non-African–American participants. Higher levels of police legitimacy/trust were significantly associated with more positive police responses to IPV and this relationship was stronger among heterosexual participants than sexual minority participants. Research limitations/implications Future research should examine prospective relationships to understand causal mechanisms linking individual perceptions of police legitimacy/trust, experiences with IPV and victims’ interactions with police. Practical implications Low levels of legitimacy/trust between police and citizens may result, in part, if police are engaged in negative or inadequate responses to reports of IPV. Police–social work partnerships can enhance effective police responses to IPV, particularly to racial/ethnic and sexual minority individuals. Originality/value This study provides empirical evidence linking police legitimacy/trust to the experiences of IPV and perceived police responses to reports of IPV, including important group differences among victims based on race/ethnicity and sexual orientation.

Abstract:

In this article, we study the creation of two distinct but related developmental processes: a Downtown Revitalization Initiative (DRI) and Police Review Board (PRB) in the small city of Geneva, New York, to understand the sociopolitical and applied processes by which different core narratives shape development initiatives and outcomes. Beginning with the premise that “communities are intrinsically storied” (Maines and Bridger 1992:363), these two examples demonstrate the range of how stories about a community’s past, present, and future compete with each other to empower some community-based conceptions of development to coalesce while blocking others. We find that both act as place-makers—one through tangible construction and the other by the establishment of a law. In focusing on the power of narratives, these examples show how narratives drive contested interests and shape constructed resources through access to political, social, and cultural power in a small city in Central New York State.

Abstract:

Objectives: Crime reporting intentions have been associated with ratings of police legitimacy and effectiveness. Less is known about the role of personal encounters with police. We explore this issue by specifying associations between reporting intentions and type of contact (involuntary/voluntary), scope (cumulative/recent), and appraisal (respect/satisfaction with last encounter). Methods: This study draws on surveys of young adults in New York City ( N = 508) and uses structural equation modeling to examine correlates of crime reporting intentions. Results: Respondents with more stops are less willing to report, and this effect is both direct and indirect, operating primarily via legitimacy. The association between reporting intentions and variety of voluntary contacts is direct and positive. Negative appraisals of recent stops are associated with lower reporting intentions but only indirectly; feelings of disrespect in recent stops are mediated by perceptions of legitimacy. Dissatisfaction with a recent voluntary contact is related to negative views of police effectiveness, but effectiveness does not shape reporting intentions. Instead, disrespectful voluntary contact has a direct negative relationship with reporting attitudes. Conclusion: The results underscore the importance of better-specifying contact with the police, as reporting intentions and related perceptions of law enforcement vary across experience and appraisal mechanisms.

Abstract:

Knowledge about clean and healthy life in children needs to be given early to shape behavior in everyday life. Knowledge about healthy living can be provided at school through various learning programs. This study aims to find the effectiveness of health promotion programs (JUMSIH) to increase children's knowledge about clean and healthy living. The research method is a pre-experimental one-shot case study design. The respondents of this study were 68 students aged 7-8 years. The results showed that the JUMSIH program can help children have knowledge about healthy living. Based on data analysis, n = 15 generally obtained scores above 2.6. It was concluded that healthy living skills are often performed by students such as hand washing, bathing, and toothbrush behavior which are basic skills for children to be able to live healthy lives. Suggestions for further research which is the development of various programs to increase awareness of clean and healthy living from an early age. Keywords: Clean and healthy life Knowledge, Early Childhood, Health Promotion Program (JUMSIH) References: Akçay, N. O. (2016). Implementation of Cooperative Learning Model in Preschool. Journal of Education and Learning, 5(3), 83–93. https://doi.org/10.5539/jel.v5n3p83 Allport, B. S., Johnson, S., Aqil, A., Labrique, A. B., Nelson, T., KC, A., … Marcell, A. V. (2018). Promoting Father Involvement for Child and Family Health. Academic Pediatrics, 18(7), 746–753. https://doi.org/10.1016/j.acap.2018.03.011 Bonuck, K. A., Schwartz, B., & Schechter, C. (2016). Sleep health literacy in head start families and staff: Exploratory study of knowledge, motivation, and competencies to promote healthy sleep. Sleep Health, 2(1), 19–24. https://doi.org/10.1016/j.sleh.2015.12.002 Considerations, P., & Framework, N. Q. (2010). Health , Hygiene and Infection Control Strategies for Policy Implementation :2010(Vic). Conti, G., Heckman, J. J., & Pinto, R. (2016). The Effects of Two Influential Early Childhood Interventions on Health and Healthy Behaviour. Economic Journal, 126(596), F28–F65. https://doi.org/10.1111/ecoj.12420 Creswell, J. W. (2012). Educational Research Planning, Conducting, and Evaluating Quantitative and Qualitative Research(4th ed.; P. A. Smith, Ed.). Boston: Pearson. Duxbury, T., Bradshaw, K., Khamanga, S., Tandlich, R., & Srinivas, S. (2019). Environmental health promotion at a National Science Festival: An experiential-education based approach. Applied Environmental Education and Communication, 0(0), 1–16. https://doi.org/10.1080/1533015X.2019.1567406 Fernandez-Jimenez, R., Al-Kazaz, M., Jaslow, R., Carvajal, I., & Fuster, V. (2018). Children Present a Window of Opportunity for Promoting Health: JACC Review Topic of the Week. Journal of the American College of Cardiology, 72(25), 3310–3319. https://doi.org/10.1016/j.jacc.2018.10.031 Fung, C., Kuhle, S., Lu, C., et al. (2012). From “best practice” to “next practice”: the effectiveness of school-based health promotion in improving healthy eating and physical activity and preventing childhood obesity. Int. J. Behav. Nutr. Phys. Act., 9, 27. Gall, M. D., Gall, J. P., & Borg, W. R. (2007). Educational Research: An Introduction (4th ed.). New York: Longman Inc. Goldfeld, S., O’Connor, E., O’Connor, M., Sayers, M., Moore, T., Kvalsvig, A., & Brinkman, S. (2016). The role of preschool in promoting children’s healthy development: Evidence from an Australian population cohort. Early Childhood Research Quarterly, 35, 40–48. https://doi.org/10.1016/j.ecresq.2015.11.001 Hawe, P., Potvin, L. (2009). What is population health intervention research. Can. J. Public Health, 100 (Suppl I8–14). Julianti, R., Nasirun, M., & Wembrayarli. (2018). Pelaksanaan Perilaku Hidup Bersih dan Sehat (PHBS) di Lingkungan Sekolah. Jurnal Ilmiah Potensia, 3(1), 11–17. Kasnodihardjo, K. (2010). Metode pelembagaan perilaku hidup sehat kaitannya dengan kesehatan lingkungan dan hygiene perorangan pada keluarga di Subang Jabar. Keshavarz, N., Nutbeam, D., Rowling, L., Khavarpour, F. (2010). Schools as social complex adaptive systems: a new way to understand the challenges of introducing the health promoting schools concept. Soc. Sci. Med., (70), 1467–1474. Kobel, S., Wartha, O., Wirt, T., Dreyhaupt, J., Lämmle, C., Friedemann, E. M., … Steinacker, J. M. (2017). Design, implementation, and study protocol of a kindergarten-based health promotion intervention. BioMed Research International, 2017. https://doi.org/10.1155/2017/4347675 Langford, R., Bonell, C.P., Jones, H. E. (2014). The WHO health promoting school framework for improving the health and well-being of students and their academic achievement. Cochrane Database Syst, Rev. 4, CD008958. Manning, M. L., & Lucking, R. (1991). The what, why, and how of cooperative learning. The Clearing House. 64(3), 152–156. Marlina, R. L. (2011). Analisis Manajemen Promosi Kesehatan Dalam Penerapan Perilaku Hidup Bersih dan Sehat (PHBS) Tatanan Rumah Tangga di Kota Padang Tahun 2011. Padang: Universitas Andalas. Maryunani, A. (2013). Perilaku Hidup Bersih dan Sehat. Jakarta: Trans Info Media. McClure, M., Tarr, P., Thompson, C. M., & Eckhoff, A. (2017). Defining quality in visual art education for young children: Building on the position statement of the early childhood art educators. Arts Education Policy Review, 118(3), 154–163. https://doi.org/10.1080/10632913.2016.1245167 Mcisaac, J. D., Sim, S. M., Penney, T. L., & Kirk, S. F. L. (2012). School Health Promotion Policy in Nova Scotia: A Case Study. Revue PhénEPS / PHEnex Journal, 4(2). McIsaac, J. L. D., Penney, T. L., Ata, N., Munro-Sigfridson, L., Cunningham, J., Veugelers, P. J., … Kuhle, S. (2017). Evaluation of a health promoting schools program in a school board in Nova Scotia, Canada. Preventive Medicine Reports, 5, 279–284. https://doi.org/10.1016/j.pmedr.2017.01.008 Midcentraldhb. (2014). Health and Safety Guidelines for Early Childhood Education Services. https://doi.org/2014 Mikkonen, J., Raphael, D. (2010). Social Determinants of Health: The Canadian Facts. University School of Health Policy and Management Toronto. Proverawati, A. (2012). Perilaku Hidup Bersih dan Sehat. Yogyakarta: Nuha Medika. Reed, K.E., Warburton, D.E., Macdonald, H.M., Naylor, P.J., McKay, H. A. (2008). Action Schools! BC: a school-based physical activity intervention designed to decrease cardiovascular disease risk factors in children. Prev. Med, 46, 525–531. Samdal, O., Rowling, L. (2011). Theoretical and empirical base for implementation components of health-promoting schools. Health Educ., 111, 367–390. Syukriyah, E. (2011). Gambaran Pengetahuan, Sikap dan Tindakan Murid SD Tentang PHBS di SDN 06 Lubuk LayangPadang. Padang: Poletkkes Kemenkes Padang. Veugelers, P. J., & Schwartz, M. E. (2010). Comprehensive school health in Canada. Canadian Journal of Public Health = Revue Canadienne de Sante Publique, 101 Suppl(August), S5-8. https://doi.org/10.17269/cjph.101.1907 WHO. (2016). What is a health promoting school? WIjayanti, N. A. (2017). Implementation of Role Playing Method in the Hygiene Hadith Learning Toward Early CHildrens Healthy Behavior of Group B in Dabin Aggrek Gunungpati Semarang. Early Childhood Education Papers (Belia), 6(2).

Abstract:

Questions surrounding stop, question, and frisk (SQF) practices have focused almost exclusively on racial and ethnic disproportionality in the rate of stops, and whether police are engaged in racial profiling. This near-sole focus on the stop decision has overshadowed important questions about the use of force during Terry stops, resulting in a major gap in our understanding of the dynamics of SQF encounters. The current study addresses this issue through an examination of the nature, prevalence, and predictors of use of force during Terry stops using the 2012 SQF database of New York Police Department (NYPD; N = 519,948) and data from the U.S. Census Bureau. Results indicate that use of force was an infrequent event in NYPD stops (14%), and weapon force was quite rare (.01%). However, hierarchical multinomial logistic regression models show that Black and Hispanic citizens were significantly more likely to experience non-weapon force than White citizens, while controlling for other relevant situational and precinct-level variables. The findings suggest that minority citizens may be exposed to a racial or ethnic “double jeopardy,” whereby they are subjected to both unconstitutional stops and disparate rates of force during those stops. The study highlights the importance of expanding the focus on SQF beyond the racial profiling lens, as questions about the dynamics of police use of force decision-making raise equally important social and legal concerns.

Abstract:

In 2012, the Supreme Court of the United States decided Florence v. Board of Chosen Freeholders of the County of Burlington. The Court held that full strip searches, including cavity searches, are permissible regardless of the existence of basic reasonable suspicion that the arrestee is in possession of contraband. Further, the Court held that law enforcement may conduct full strip searches after arresting an individual for a minor offense and irrespective of the circumstances surrounding the arrest. These holdings upended typical search jurisprudence. Florence sanctions the overreach of state power and extends to law enforcement and corrections officers the unfettered discretion to conduct graphically invasive, suspicion-less strip searches. The Court’s dereliction of duty is enough to concern all citizens. However, the impact of this phenomenal lapse will not be felt equally in the age of what Bonilla-Silva has termed colorblind racism. In 2013, in the case of Floyd v. City of New York, Judge Shira A. Scheindlin found that between January 2004 and June 2012, the New York City Police Department (“NYPD”) made 4.4 million stops. She further found that more than eighty percent of these 4.4 million stops were of Blacks or Hispanics. Specifically, Judge Scheindlin found that in “52% of the 4.4 million stops, the person stopped was black, in 31% the person [stopped] was Hispanic, and in 10% the person stopped was white.” This rate of stops and frisks is grossly disproportionate to Black and Hispanic population representation in New York City and the United States in general. Further, as Judge Scheindlin astutely points out, “The NYPD’s policy of targeting ‘the right people’ for stops . . . is not directed toward the identification of a specific perpetrator, rather, it is a policy of targeting expressly identified racial groups for stops in general.” These findings make clear that Florence and colorblind racism enable law enforcement to wage war against the civil rights of minority citizens. This Article argues that the Court’s phenomenal lapse in Florence and its general abdication of law enforcement oversight inevitably subjects minorities, particularly Blacks and Latinos, to the blanket authority of law enforcement to harass and humiliate based on perfunctory arrests predicated on the slightest of infractions. Other legal analyses of Florence have largely ignored, and hence minimized, the salience of race when thinking about strip searches. In light of the significant consequential impacts of this decision on minority populations, this oversight is itself unreasonable. This paper will analyze the rationale and policy implications, particularly for people of color, in light of Florence. Finally, I will also propose policy recommendations to temper the projected negative impacts of the decision.

Abstract:

Although seatbelt use is known to reduce motor vehicle occupant crash injury and death, rear-seated adult occupants are less likely to use restraints. This study examines risk and protective factors associated with injury severity in front- and rear-seated adults involved in a motor vehicle crash in New York State. The Crash Outcome Data Evaluation System (CODES) (2016–2017) was used to examine injury severity in front- and rear-seated occupants aged 18 years or older (N= 958,704) involved in a motor vehicle crash. CODES uses probabilistic linkage of New York State hospitalization, emergency department, and police and motorist crash reports. Multivariable logistic regression models with MI analyze employed SAS 9.4. Odds ratios are reported as OR with 95% CI. The mortality rate was approximately 1.5 times higher for rear-seated than front-seated occupants (136.60 vs. 92.45 per 100,000), with rear-seated occupants more frequently unrestrained than front-seated occupants (15.28% vs. 1.70%, p < 0.0001). In adjusted analyses that did not include restraint status, serious injury/death was higher in rear-seated compared to front-seated occupants (OR:1.272, 1.146–1.412), but lower once restraint use was added (OR: 0.851, 0.771–0.939). Unrestrained rear-seated occupants exhibited higher serious injury/death than restrained front-seated occupants. Unrestrained teens aged 18–19 years old exhibit mortality per 100,000 occupants that is more similar to that of the oldest two age groups than to other young and middle-aged adults. Speeding, a drinking driver, and older vehicles were among the independent predictors of serious injury/death. Unrestrained rear-seated adult occupants exhibit higher severe injury/death than restrained front-seated occupants. When restrained, rear-seated occupants are less likely to be seriously injured than restrained front-seated occupants.

Abstract:

Financial information is one of the important information in decision making. However, many cases of fraud committed by management so that the information in the financial statements cannot be relied upon in decision making. Therefore, the auditor's job is to ensure that the company's financial statements are represented correctly (faithful representation) so that financial statement information becomes more quality and useful in making decisions. So this study aims to examine the effect of audit fee on audit quality. In addition, this study also examines important determinants of audit costs, namely company size, profitability, audit risk, complexity, and firm size. By using the purposive sampling method, samples of the financial and manufacturing industry in 2010-2017 used are 39 firms per year. This sample is used to examine the effect of audit fee on audit quality and the determinant of audit fee using simple linear regression analysis and multiple linear regression analysis. The result of this research shows that audit fees have a significant positive effect on audit quality. In addition, this study shows that firm size, complexity, and firm size are important determinants that determine audit fee. However, profitability and audit risk have not been proven to explain audit fees. Keywords: Audit Quality, Audit Fee, Firm Size, Profitability, Audit Risk, Complexity, Auditor Size Referencens: Al-Harshani, Meshari O. (2008), The pricing of audit services: Evidence from Kuwait. Managerial Auditing Journal, 23(7), 685–696. Al-Thuneibat, Ali. Abedalqader, Ream Tawfiq Ibrahim Al Issa, & Rana Ahmad Ata Baker, (2011), Do audit tenure and firm size contribute to audit quality? Empirical evidence from Jordan. Managerial Auditing Journal, 26(4), 317–334. Arens, Alvin A., Randal J. Elder,. Mark S. Beasley (2014), Auditing and Assurance Services: An Integrated Approach. United States: Pearson Education, Inc. Association of Certified Fraud Examiners (2018), Report to the Nations: 2018 Global Study on Occupational Fraud and Abuse, United States: ACFE. Bhandari, L. C. (1988), Debt/Equity Ratio and Expected Common Stock Returns : Empirical Evidence. The Journal of Finance, 43(2), 507–528. Bowerman, Bruce L., Richard T. O'Connell, Emily S. Murphree (2017), Business Statistics in Practice, Eighth Edition, New York: McGraw Hill Education. Brealey, Richard A., Myers, Stewart C. (2000), Principles of Corporate Finance, Boston: McGraw Hill Companies, Inc. Carey, P. J. (2008), The Benefits of Services Provided by External Accountants to Small and Medium Sized Enterprises. Carey, P., & Simnett, R. (2006), Audit partner tenure and audit quality. Accounting Review, 81(3), 653–676. Castro, Walther Bottaro de Lima, Ivam Ricardo Peleias, & Glauco Peres da Silva (2015), Determinants of Audit Fees: A Study in the Companies Listed on the BM&FBOVESPA, Brasil. Revista Contabilidade & Finanças, 26(69), 261–273. Chen, C. (2008), Audit Partner Tenure , Audit Firm Tenure , and Discretionary Accruals : Does Long Auditor Tenure Impair Earnings Quality ?, 25(2), 415–445. Cooper, D. R., & Schindler, P. S. (2014), Business Research Methods (Twelfth Edition). New York: McGraw-Hill/Irwin. DeAngelo, L. E. (1981), Auditor size and audit quality. Journal of Accounting and Economics, 3(3), 183–199. Dechow, Patricia. M., Richard. G. Sloan, & Amy P. Sweeney (1995), Detecting Earnings Management. The Accounting Review. DeFond, M., & Zhang, J. (2014), A review of archival auditing research. Journal of Accounting and Economics, 58(2–3), 275–326. Deis, Donald R., & Gary Giroux (1996), The effect of auditor changes on audit fees, audit hours, and audit quality. Journal of Accounting and Public Policy, 15(1), 55–76. Eilifsen, Aasmund, Jr William F Messier, Steven M Glover, Douglas F Prawitt (2014), Auditing & Assurance Services, Third Edition, London: McGraw-Hill. Ettredge, Michael., Elizabeth Emeigh Fuerherm, & Chan Li (2014), Fee pressure and audit quality. Accounting, Organizations and Society, 39(4), 247–263. Ferri, Michael G., & Wesley H. Jones (1979), Determinants of financial structure: a new methodological approach. The Journal of Finance, 34(3), 631–643. Francis, Jere. R. (2011), A Framework For Understanding And Researching Audit Quality. Auditing, 30(2), 125–152. Ghozali, H. Imam (2016), Aplikasi Analisis Multivariete dengan Program IBM SPSS 23, Edisi ke-8, Semarang: Badan Penerbit Universitas Diponegoro. Gitman, Lawrence J., Chad J. Zutter (2012), Principles Of Managerial Finance (Thirteenth). United States: Lawrence J. Gitman. Hoitash, Rani., Ariel Markelevich, & Charles A. Barragato (2007), Auditor fees and audit quality. Managerial Auditing Journal, 22(8), 761–786. Horngren, Charles T., L. Sundem, John A. Elliott (1999), Introduction to Financial Accounting, Seventh Edition, New Jersey: Prentice-Hall,Inc. Ikatan Akuntansi Indonesia (2017), Standar Akuntansi Keuangan (SAK), Jakarta: IAI International Accounting Standard Board (2018), The Conceptual Framework for Financial Reporting 2018. London : IASB. Jan, Chyan Long (2018), An effective financial statements fraud detection model for the sustainable development of financial markets: Evidence from Taiwan. Sustainability (Switzerland), 10(2). Jensen, Michael C., & William H. Meckling (1976), Theory Of The Firm : Managerial Behavior , Agency Costs And Ownership Structure, 3, 305–360. Joshi, P. L., & Hasan AL-bastaki (2000), Determinants of Audit Fees : Evidence from the Companies Listed in Bahrain, 138(November 1999), 129–138. Jubb. (1996), Audit fee determinants: The plural nature of risk. Managerial Auditing Journal, 11(3), 25–40. Kieso, Donald E., Jerry J. Weygandt, & Paul D. Kimmel (2013), Financial Accounting IFRS Edition. United States: John Wiley & Sons, Inc. Kieso, Donald E, Jerry J Weygandt, Terry D Warfield (2018), Intermediate Accounting: IFRS Edition Third Edition, United States: John Willey & Sons, Inc. Kikhia, Hassan Yahia (2014), Determinants of Audit Fees: Evidence from Jordan. Accounting and Finance Research, 4(1), 42–53. Knechel, Robert W., & Ann Vanstraelen (2007), The Relationship between Auditor Tenure and Audit Quality Implied by Going Concern Opinions. AUDITING: A Journal of Practice & Theory, 26(May), 113–131. Knechel, W. Robert, Gopal V. Krishnan, Mikhail Pevzner, Lori B Shefchik, & Uma K. Velury (2013), Audit quality: Insights from the academic literature. Auditing, 32(SUPPL.1), 385–421. Konrath, Larry F. (2002), Auditing A Risk Analysis Approach, Fifth Edition, South Western. Kusharyanti (2013), Analysis of the Factors Determining the Audit Fee. Journal of Economics, Business, and Accountancy | Ventura, 16(1), 147–160. Lennox, C. (1999), Are large auditors more accurate than small auditors? Accounting and Business Research, 29(3), 217–227. Lennox, C. S. (1999) Audit quality and auditor size: An evaluation of reputation and deep pockets hypotheses. Journal of Business Finance and Accounting, 26(7–8), 789–805. Liu, Siheng. (2017), An Empirical Study: Auditors’ Characteristics and Audit Fee. Open Journal of Accounting, 06(02), 52–70. Lobo, Gerald, & Yuping Zhao (2013), Relation between Audit Effort and Financial Report Misstatements: Evidence from Quarterly and Annual Restatements. Journal of International Accounting Research, 90(4), 1395–1435. Manry, David L, Theodore J. Mock, & Jerry L. Turner (2008), Does increased audit partner tenure reduce audit quality? Journal of Accounting, Auditing and Finance, 23(4), 553–572. Mohammed, Nishtiman Hashim, & Abdullah Saeed Barwari (2018), Determinants of Audit Fees : Evidence from UK Alternative Investment Market. Academic Journal of Nawroz University, 7(3), 34–47. Musah, A. (2017), Determinants of Audit fees in a Developing Economy: Evidence from Ghana. International Journal of Academic Research in Business and Social Sciences, 7(11). Newton, Nathan J., Dechun Wang, & Michael S. Wilkins (2013), Does a lack of choice lead to lower quality? evidence from auditor competition and client restatements. Auditing, 32(3), 31–67. Nikkinen, J., & Petri Sahlström (2004), Does Agency Theory Provide a General Framework for Audit Pricing ? International Journal of Auditing, 8, 253–262. Ohidoa, T., & Okun, O. O. (2018), Firms Attributes and Audit Fees in Nigeria Quoted Firms. International Journal of Academic Research in Business and Social Sciences, 8(3), 685–699. Pham, Ngoc Kim, Hung Nguyen Duong, Tin Pham Quang, & Nga Ho Thi Thuy (2017), Audit Firm Size, Audit Fee, Audit Reputation and Audit Quality: The Case of Listed Companies in Vietnam. Asian Journal of Finance & Accounting, 9(1), 429. Rahman, Dr Onaolapo Adekunle Abdul, Ajulo Olajide Benjamin, Onifade Hakeem Olayinka (2017), Effect of Audit Fees on Audit Quality: Evidence from Cement Manufacturing Companies in Nigeria. Effect of Audit Fees on Audit Quality: Evidence from Cement Manufacturing Companies in Nigeria., 5(1), 6–17. Rahmina, Listya Yuniastuti, & Sukrisno Agoes (2015), Influence of Auditor Independence, Audit Tenure, and Audit Fee on Audit Quality of Members of Capital Market Accountant Forum in Indonesia. Procedia - Social and Behavioral Sciences, 164(August), 324–331. Republik Indonesia (2008), Undang-Undang Republik Indonesia Nomor 20 tahun 2008 Tentang Usaha Mikro, Kecil, Dan Menengah. Sandra, & Patrick. (1996), The Deteminants of Audit Fees in HongKong: An Empirical Study. Asian Review of Accounting, 4(2), 32–50. Scott, William R (2015), Financial Accounting Theory, Seventh Edition, United States: Pearson Canada Inc. Shibano, T. (1990), Assessing Audit Risk from Errors and Irregularities. Journal of Accounting Research, 28(1990), 110. Sivathaasan, N., R. Tharanika, M. Sinthuja, V. Hanitha (2013), Factors determining Profitability: A Study of Selected Manufacturing Companies listed on Colombo Stock Exchange in Sri Lanka. European Journal of Business and Management, 5(27), 99-107–107. Subramanyam, K. R. (2014), Financial Statement Analysis, Eleventh Edition, New York: McGraw-Hill Education. Sun, Jerry, & Guoping Liu (2011), Client-specific litigation risk and audit quality differentiation. Managerial Auditing Journal, 26(4), 300–316. Tritschler, Jonas (2013), Audit Quality: Association Between Published Reporting Errors and Audit Firm Characteristics. Vu, Dinh Ha Thu Vu (2012), Determinants of audit fees for Swedish listed non-financial firms in NASDAQ OMX Stockholm. Whittington, Ray & Kurt Pany (2004), Principles of Auditing and Other Assurance Services, New York: McGraw-Hill/Irwin. Williams, David D. (1988), The Potential Determinants of Auditor Change. Journal of Business Finance & Accounting, 15(2), 243–261. Wooten, T. C. (2003), Research About Audit Quality. Wu, Shu-Hsing, Tsung-Che Wu, & Kun-Lin Yang (2017), Fair Value Information, Audit fees and Audit Committee in Taiwan. International Journal of Financial Research, 8(2), 124. Xu, Jiabing (2017), Analysis on the Relationship between Audit Fee Management and Audit Quality in China, 53(ICEM 2017), 530–533.

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Abstract: It is widely acknowledged that Herman Melville's Moby-Dick has been inspired by a variety of sources. One of these is the legend of Mocha Dick, about which Jeremiah N. Reynolds published the earliest known account in 1839. In his narration, Reynolds describes an evening he spent on board an unspecified whaling ship off Mocha Island, Chile, during which the whaler's first mate claimed to have killed Mocha Dick on a previous whaling voyage. This essay aims to substantiate the setting of Reynolds's account, in an attempt to identify the alleged murderer of Mocha Dick and eventually to investigate his previous voyages to seek any evidence of a large and / or white whale killed near Mocha Island. Overall, Reynolds's text was found to be consistent with the sources consulted: primarily, the logbook of the schooner Penguin . Reynolds's narration was identified as having taken place on April 3 or 4, 1830, on board the whaling ship Cincinnatus , which was built in New York in 1818. The identity of the whaling ship's first mate, however, could not be established due to a lack of supporting documentation, which in turn prevents further investigation into the origins of Mocha Dick's legend.

Abstract:

IntroductionUncontrolled hypertension (HTN) is prevalent in persons experiencing homelessness (PEH) and contributes to significant suffering and financial cost. Mobile health approaches such as short messaging service (SMS) texting have led to better control of HTN in the general population. Despite the high utilisation of mobile phones by PEH, SMS texting to support HTN control has not been evaluated among this population. We hypothesise that an SMS testing programme will enhance health communication, information management, outreach and care coordination, and provide behavioural support to address some barriers to HTN management in PEH.Methods and analysisThis study will use a mixed-methods study design to address two objectives: First, it will evaluate, in a randomised controlled trial, the efficacy of a 6-month SMS texting strategy vs an attention control on blood pressure reduction and adherence to medications and clinical appointments in 120 adults PEH with uncontrolled HTN. Outcomes will be measured at 0, 2, 4 and 6 months. Second, it will assess patients’ and providers’ acceptability and experience of SMS texting using semistructured interviews with PEH (n=30) and providers (n=10). The study will be conducted in shelter clinics in New York City in collaboration with community organisations. The primary statistical analysis will be on an intention-to-treat basis. The trial results will be reported as comparative summary statistics (difference in response rate or means) with 95% CIs and in accordance with the Consolidated Standards of Reporting Trials (CONSORT). Interviews will be transcribed, coded and analysed using an inductive grounded theory analysis.Ethics and disseminationThis study has been approved by the Institutional Review Board (IRB) at George Washington University. Written consent will be obtained from participants. The findings will be disseminated in peer-reviewed journals.Trial registration numberNCT05187013.

Abstract:

Three cohorts including the Fire Department of the City of New York (FDNY), the World Trade Center Health Registry (WTCHR), and the General Responder Cohort (GRC), each funded by the World Trade Center Health Program have reported associations between WTC-exposures and cancer. Results have generally been consistent with effect estimates for excess incidence for all cancers ranging from 6 to 14% above background rates. Pooling would increase sample size and de-duplicate cases between the cohorts. However, pooling required time consuming steps: obtaining Institutional Review Board (IRB) approvals and legal agreements from entities involved; establishing an honest broker for managing the data; de-duplicating the pooled cohort files; applying to State Cancer Registries (SCRs) for matched cancer cases; and finalizing analysis data files. Obtaining SCR data use agreements ranged from 6.5 to 114.5 weeks with six states requiring >20 weeks. Records from FDNY (n = 16,221), WTCHR (n = 29,372), and GRC (n = 33,427) were combined de-duplicated resulting in 69,102 unique individuals. Overall, 7894 cancer tumors were matched to the pooled cohort, increasing the number cancers by as much as 58% compared to previous analyses. Pooling resulted in a coherent resource for future research for studies on rare cancers and mortality, with more representative of occupations and WTC- exposure.

Abstract:

IntroductionGrowing evidence supports combining social, behavioural and biomedical strategies to strengthen the HIV care continuum. However, combination interventions can be resource-intensive and challenging to scale up. Research is needed to identify intervention components and delivery models that maximise uptake, engagement and effectiveness. In New York City (NYC), a multicomponent Ryan White Part A-funded medical case management intervention called the Care Coordination Programme (CCP) was launched at 28 agencies in 2009 in order to address barriers to care and treatment. Effectiveness estimates based on >7000 clients enrolled by April 2013 and their controls indicated modest CCP benefits over ‘usual care’ for short-term and long-term viral suppression, with substantial room for improvement.Methods and analysisIntegrating evaluation findings and CCP service-provider and community-stakeholder input on modifications, the NYC Health Department packaged a Care Coordination Redesign (CCR) in a 2017 request for proposals. Following competitive re-solicitation, 17 of the original CCP-implementing agencies secured contracts. These agencies were randomised within matched pairs to immediate or delayed CCR implementation. Data from three 9-month periods (pre-implementation, partial implementation and full implementation) will be examined to compare CCR versus CCP effects on timely viral suppression (TVS, within 4 months of enrolment) among individuals with unsuppressed HIV viral load newly enrolling in the CCR/CCP. Based on current enrolment (n=933) and the pre-implementation outcome probability (TVS=0.54), the detectable effect size with 80% power is an OR of 2.75 (relative risk: 1.41).Ethics and disseminationThis study was approved by the NYC Department of Health and Mental Hygiene Institutional Review Board (IRB, Protocol 18–009) and the City University of New York Integrated IRB (Protocol 018–0057) with a waiver of informed consent. Findings will be disseminated via publications, conferences, stakeholder meetings, and Advisory Board meetings with implementing agency representatives.Trial registration numberRegistered with ClinicalTrials.gov under identifier: NCT03628287, V.2, 25 September 2019; pre-results.

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Background Globally, the most important human rights and public health issue that sex workers face is their experience of high levels of violence (Kinnell, 2006, Kinnell, 2008, Alexander, 1999). Deering’s systematic review estimated levels of sexual violence in sex working populations as being between 14% and 54% (Deering et al, 2014). Aims This international, robust mixed methods study will explore the frequency of sexual violence against sex workers, barriers in criminal justice and the legal consciousness of sex workers regarding their rights and consent. The hypothesis to be tested is that the safety of sex workers from sexual violence is mediated by the differing legal contexts of sex work environments. We will compare experiences across research sites in the context of legalisation (Nevada USA), client criminalisation (Northern Ireland), decriminalisation (New Zealand) and partial criminalisation (England, Scotland and Wales) [henceforth ESW]. Methods An international survey (n = 1,000) will be translated into several languages, to disaggregate experiences by demographic categories (gender, ethnicity, sexual orientation) and sex work sector (including online, street-based and brothels). Interviews (n = 100) with sex workers, police, prosecutors and service providers will be thematically analysed to explore legal consciousness, why the patterns occur and contextualise the statistical findings. These data will be supplemented with comparative legislative, policy and case analysis. Research study data will be used to compare the social factors and legal norms shaping sex workers experiences of sexual violence, justice and support interventions. Recommendations for a ‘best practice’ review of legal improvements and support interventions will be produced following completion of the study. Given the sensitive nature of the research, robust ethical and data protection mechanisms are in place. The research has ethical approval from each research site, an Advisory Board and trained, paid peer researchers to assist with data gathering, analysis and dissemination. The study will report findings in 2023/2024.

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Abstract Introduction Plasmacytoid dendritic cells (pDCs) express CD123/IL-3Rα and promote tumor growth and immunosuppression in multiple myeloma (MM) (Chauhan et al, Cancer Cell 2009, 16:309-323; Ray et al, Leukemia, 2018, 32:843-846). Tagraxofusp is a novel targeted therapy directed against CD123, and is FDA-approved for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm [BPDCN]). Tagraxofusp can also trigger anti-MM activity by reducing the viability of immunologically defective and tumor-promoting pDCs in MM. Furthermore, tagraxofusp synergistically enhances the anti-MM activity of anti-MM agents bortezomib and pomalidomide. Our preclinical findings led to a recently completed phase 1/2 clinical trial of tagraxofusp with pomalidomide/dexamethasone in relapsed/refractory MM patients (NCT02661022). Results demonstrated preliminary safety and efficacy, with 5 of 9 heavily pretreated patients achieving durable partial response (PR) (ASH 2019). Here, we report the early results of our translational correlative studies using bone marrow (BM), peripheral blood (PB), and serum from the study cohort. Methods Tagraxofusp is a bioengineered targeted therapy directed to CD123 comprised of human IL-3 fused to a truncated diphtheria toxin (DT) payload (Stemline Therapeutics, NY). pDCs and patient MM cells were purified from BM/PB samples after informed consent, and quantified using FACS, as described (Ray et al, Leukemia, 2018). A novel high throughput seroproteomics platform SOMAscan was used to analyze 1,310 protein analytes in serum samples from MM patients (n = 9). SOMAscan data were subjected to meta-analysis to generate heatmaps, followed by hierarchical cluster analysis. SOMAscan results were validated with ELISA using supernatants from MM patient pDCs cultured with or without tagraxofusp. Results Analysis of BM/PB samples from MM patients receiving tagraxofusp therapy showed a distinct reduction in the frequency of viable pDCs [average 2% at screening vs 0.75% post-tagraxofusp; n = 6; p = 0.036]. Of note, pDCs isolated from tagraxofusp-treated patients showed decreased ability to trigger MM cell growth. SOMAscan analysis of patient serum before and after tagraxofusp therapy showed alterations in the levels of 100 proteins [Median Fold Change in expression: 0.39 to 4.5; n = 6; 3 each; p &lt; 0.05]. Importantly, tagraxofusp treatment reduced pDC-related soluble proteins including IFN-α (fold change: 0.8, treated vs untreated; p &lt; 0.05). Pathway analysis further show that treatment affected immune signaling. For example, tagraxofusp decreased the levels of immunosuppressive proteins, soluble CD40L and IL1R2 (0.071-fold and 0.088 fold vs untreated; p = 0.02 and p = 0.013, respectively), promoting immune response. Moreover, analysis of end of treatment samples showed decreased soluble C-reactive protein, affecting the complement cascade after treatment (0.53-fold, p = 0.0173) via the downregulation of several C-C motif soluble chemokines (p &lt; 0.05). Our earlier study showed that pDC-MM interactions triggered secretion of IL-3, which in turn promotes both pDC survival and MM cell growth. Importantly, tagraxofusp in this trial decreased serum IL-3 levels (fold change 0.75, treated vs untreated; p &lt; 0.05). Conclusions In the present study, we validate the target specificity of tagraxofusp against MM pDCs in relapsed and refractory MM patients enrolled in a phase 1/2 clinical trial. A future clinical trial of tagraxofusp in combination with bortezomib and pomalidomide will examine the utility of tagraxofusp to improve outcome in patients with relapsed refractory MM. Disclosures Mo: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Consultancy; BMS: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy. Olguin: Stemline Therapeutics, New York, NY: Current Employment. Chen: Stemline Therapeutics, New York, NY: Current Employment. Brooks: Stemline Therapeutics: Current Employment. Mughal: Stemline: Current Employment, Current holder of stock options in a privately-held company; Oxford University Press, Informa: Other: financial benefit and/or patents . Richardson: Janssen: Consultancy; Celgene/BMS: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Secura Bio: Consultancy; GlaxoSmithKline: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy, Research Funding; AstraZeneca: Consultancy; Takeda: Consultancy, Research Funding; AbbVie: Consultancy; Protocol Intelligence: Consultancy; Regeneron: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding. Chauhan: Oncopeptides: Consultancy; C4 Therapeutics: Current equity holder in publicly-traded company; Stemline Therapeutics: Consultancy. Anderson: Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Abstract:

e18603 Background: Rectal cancer has a well-established volume-outcome relationship. However, the impact of fellowship training on outcomes following colorectal cancer resection is unknown. Methods: Patients who underwent stage I-III colorectal adenocarcinoma resection (2004-2014) were identified in the New York State Cancer Registry and Statewide Planning & Research Cooperative System. Hierarchical analyses assessed the association between surgeon American Board of Colorectal Surgery (ABCRS) certification and postoperative outcomes and survival. Derived from volume tertiles, surgeons who performed ≥15 annual colon cancer resections or ≥10 annual rectal cancer resections were characterized as high-volume colon (HVCSs) or rectal (HVRSs) surgeons, respectively. Results: 47,491 colorectal cancer resections (right colon = 23,824, 50.2%; left colon = 18,154, 38.2%; rectal cancer = 5,513, 11.6%) met inclusion criteria. ABCRS-certified HVCSs (N = 92) comprised only 5.5% of the surgeon cohort but performed 20.6% of the colon cancer resections. Similarly, ABCRS-certified HVRSs (N = 31) comprised only 3.8% of the surgeon cohort but performed 16.5% of the rectal cancer resections. Despite no significant difference in complications, ABCRS-certified HVCS/HVRSs overall had better postoperative outcomes and were associated with improved survival following colorectal cancer resection. Conclusions: These results suggest that for the best outcomes and long-term survival following colon and rectal cancer resection, referral to high-volume, ABCRS-certified surgeons may be the best choice.[Table: see text]

Abstract:

Abstract Background Respiratory syncytial virus (RSV) vaccines are in clinical development for older adults. We described RSV infections among adults requiring hospitalization and risk factors for severe outcomes using a population-based platform, the Influenza Hospitalization Surveillance Network (FluSurv-NET). Methods Surveillance occurred October 1–April 30 (2014–2017) at sites located in seven states (California, Georgia, Michigan, Minnesota, New York, Oregon, and Tennessee) covering an annual catchment population of up to 13 million adults ≥18 years. Laboratory-confirmed RSV cases were identified using hospital and state public health laboratories, hospital infection preventionists, and/or reportable condition databases. Medical charts were reviewed for demographic and clinical data. International Classification of Diseases (ICD) discharge codes were abstracted. Odds ratios (Oregon) and 95% confidence intervals (CIs) were determined to assess risk factors for ICU hospitalization and deaths. Results A total of 2,326 hospitalized RSV cases were identified. Over half were ≥65 years (62%, n = 1,438/2,326), female (59%, n = 1,362/2,326), white (70%, n = 1,301/1,855), and had ≥3 underlying medical conditions (52%, n = 1,204/2,326). 20% (n = 398/2,000) were hospitalized in the ICU (median length of stay, 3 days; interquartile range, 1–6 days), and 5% (n = 96/2,001) died in the hospital. Congestive heart failure (CHF; OR: 1.4, 95% CI: 1.1–1.8) and chronic obstructive pulmonary disease (COPD; OR: 1.3, 95% CI: 1.1–1.7) were associated with ICU admission, while age ≥80 years (OR: 4.1, 95% CI: 1.8–12.1) and CHF (OR: 2.4, 95% CI: 1.6–3.6) were associated with in-hospital deaths. RSV-specific ICD codes were listed in the first 9 positions in only 44% (879/1,987) of cases. Conclusion To our knowledge, this is the largest US case series of RSV-infected hospitalized adults. Most cases were ≥65 years and had multiple underlying medical conditions. Older age, CHF, and COPD were associated with the most severe outcomes. Few cases had RSV-specific ICD codes, suggesting that administrative data underestimate adult RSV-related hospitalizations. Continued surveillance is needed to understand the epidemiology of RSV among adults as vaccine products move toward licensure. Disclosures E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support. H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

Abstract:

Abstract Abstract 2239 Introduction: Socioeconomic, environmental, lifestyle and genetic factors play a role in the etiology of ITP but are poorly understood. A self-reported questionnaire was designed to study these relationships and how these factors prior to the diagnosis of ITP relate to treatment response and disease progression in order to gain insight into the etiology of ITP. Methods: To design the questionnaire that would address topics of interest: 1) 60 ITP patient interviews were performed and 2) the questionnaire was reviewed by project coordinators, nurse practitioners, Platelet Disorder Support Association (PDSA) members, and hematologists. The input was incorporated into a further-revised questionnaire, which was then administered to both “pediatric” (patients <18 years of age at the time of diagnosis) and adult ITP patients from the Platelet Disorders Center at Weill Cornell - New York Presbyterian Hospital. Formal statistical analysis to relate responses to one question to responses of another to define sub-groups of patients is ongoing. Results: 109 patients were enrolled. Ages ranged from 2–78 years of age; median age was 55 years, with 21 females and 33 “pediatric” patients. The most frequent environmental exposures in adults were automotive exhaust (n=14) and Teflon (n=12). In pediatrics, preservatives and insecticides (n=8) and Teflon (n=7) were most common. The most prevalent hazardous substances in both groups were cleaning supplies (n=16 adults, n=9 “pediatric”) and chlorinated water (n=13 adult, n=9 “pediatric”). 13 adults also had exposure to gasoline or diesel fumes. Refer to figure 1. 51(47%) patients reported at least one infection prior to diagnosis with ITP. The most common were Strep throat (n=12); influenza (n=9), and respiratory tract infections (n=8). Twenty-four (22%) patients reported at least one autoimmune disease, including celiac (n=2) and discoid lupus (n=2).Twenty-one patients reported a family history of Type II diabetes, 12 Type I diabetes, 13 osteoarthritis and 10 rheumatoid arthritis. Eight (7%) patients reported at least one inflammatory disease including: Crohn's disease (n=3), Inflammatory bowel disease (n=7), Systemic lupus erythematous and Vitiligo(each n=1). Thirty-seven (34%) patients reported surgeries prior to diagnosis of ITP, especially: appendectomy (n=8) and tonsil removal (n=8). Twenty-three patients traveled close to date of diagnosis, 58 patients reported more stress than usual (i.e. death of a relative, loss of employment); 13 patients reported a drastic change in diet (i.e. decreasing calories (n=7) or becoming vegetarian (n=5)). Vitamin supplementation for vitamin C and D (each n=17), E (n=12) and B (n=11) were common. In addition, 11 vitamin deficiencies were reported, vitamin D (n=5), vitamin B12 (n=3) and other (n=3). The most frequent allergic reactions included: 31 (28%) patients with hay fever, 9 patients with allergies to milk, 7 patients with poison ivy or skin irritation, 6 patients with eczema, and 4 with allergic rhinitis. Other medical conditions reported were: hypothyroidism (n=10), hyperthyroidism (n=9), high blood pressure (N=16), high cholesterol (N=14), and anemia (N=13) [9 additional patients included 4 with iron deficiency anemia and 5 with a family history of iron deficiency anemia]. Seven patients reported a lack of prenatal care in their mothers' pregnancy and 7 were premature. Medications reported include: acetaminophen (n=53), antibiotics (n=36), antihistamines (n=22), and hormone therapy (n=17). Vaccinations received close to date of diagnosis include: flu vaccine (n=10) and T-dap (n=9). Prednisone was reported most frequently as both the best therapy to minimize symptoms (n=18) and the worst (n=16). Conclusion: Our pilot study intended to capture critical information and to further development of the questionnaire. We can see if there are groups of patients in whom onset and other characteristics relate to outcomes including response to treatment. Following formal statistical analysis of the material acquired (in progress and anticipated by early September), the next step will be for a final updated version of the questionnaire to be posted on the PDSA web site in order to accrue responses from a much larger number of patients. The questionnaire will also be given to a non-ITP patient population to serve as controls. Disclosures: Bussel: Amgen: Family owns Amgen stock Other, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; GlaxoSmithKline: Family owns GSK stock, Family owns GSK stock Other, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; IgG of America: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sysmex: Research Funding; Portola: Consultancy. Off Label Use: The use of romiplostim in pediatric patients was examined in this study.

Abstract:

Increasing evidence demonstrates that an online Diabetes Prevention Program (DPP) can delay the onset of type 2 diabetes. However, little has been done for Chinese Americans. This study, using Community-Based Participatory Research and Intervention Mapping approaches, describes a formative research process in the development of a culturally and linguistically tailored online DPP program among Chinese Americans with prediabetes living in New York City. Using a triangulation approach, data were collected to inform the development of an online DPP curriculum through (1) a literature review, (2) three focus groups (n = 24), and (3) a community advisory board meeting among 10 key informants knowledgeable in community needs, diabetes care, and lifestyle interventions. Participants indicated online DPPs would be very useful and easily accessible. However, key barriers including low computer skills/literacy and technology self-efficacy were identified. In addition, taking meal photos and tracking pedometer steps daily were found to be acceptable self-motoring tools for sustaining a healthy lifestyle. Furthermore, the integration of features such as text message reminders and the creation of social support groups into the online DPP curriculum was proposed to minimize attrition. This theory-based formative research to develop a culturally and linguistically appropriate web-based DPP curriculum was well-received by Chinese Americans and warrants testing in future intervention studies.

Abstract:

Background. HSC dose and HLA match are independent risk factors that impact non-relapse mortality in children and adults undergoing umbilical cord blood (UCB) transplant for acute leukemia (Eapen et al. Blood 2014 123:133-140). Low number of CD34+ HSCs results in prolonged periods of cytopenia and higher risk of graft failure. To reduce these risks, a minimum cell dose threshold, e.g. 3.0 x 107 total nucleated cells (TNC)/kilogram (kg), has generally been required in CBU selection. While beneficial in terms of hematopoietic recovery, this cell dose threshold markedly limits the number of available cord blood units (CBUs) particularly for larger adolescent and adult recipients, thus reducing the probability of identifying a 7-8/8 HLA-matched graft. In addition, a second UCB unit is often required for adults as a single unit may not meet the cell dose threshold. MGTA-456 is an expanded CD34+ HSC product utilizing an AHR antagonist in the presence of SCF, Flt-3L, IL-6 and TPO. In previous studies with fresh MGTA-456, 36 patients with hematologic malignancies demonstrated rapid neutrophil recovery and sustained engraftment in all patients. The aims of this study (NCT03674411) were to evaluate the safety and efficacy of cryopreserved MGTA-456 as well as the effectiveness of lowering the minimum cell dose threshold of the selected CBU from 3.0 x 107 to 1.0 x 107 TNC/kg to improve donor-recipient HLA match. Patients and Methods: Ten patients with high-risk hematologic malignancy were enrolled with 9 transplanted to date. Conditioning consisted of cyclophosphamide 120 mg/kg, fludarabine 75 mg/m2 and total body irradiation 1320 cGy (total doses) with cyclosporine and mycophenolate mofetil as immunoprophylaxis. G-CSF was initiated on the day after infusion and continued until the neutrophil count exceeded 2500/uL for 3 consecutive days. Results: Cryopreserved MGTA-456 contained a median of 1.9 x 109 CD34+ cells (range, 1.1-6.2) after expansion culture (a 491-fold expansion of CD34+ cells [range, 219-672]). As shown in Table 1, neutrophil recovery occurred in 100% of patients (with one pending after recent transplant) at a median of 15 days (range, 0-31), similar to recipients of fresh MGTA-456 in a prior study (median 14 days, range 7-32) and significantly faster than in recipients of unmodified UCB (median 25 days). Platelet recovery (&gt;20,000/uL for 7 days without transfusion) was also comparable in recipients of cryopreserved and fresh MGTA-456 (median 42 [range 27-53] vs 45 days [range 28-54], respectively), and again faster relative to recipients of unmodified CBUs (median 64 days). In line with preclinical experiments in NSG murine recipients that demonstrates all engrafting cells are retained in the CD34+CD90+ subpopulation, CD34+CD90+ content strongly correlated with speed of neutrophil recovery in recipients of MGTA-456 (cryopreserved and fresh) as shown in Figure 1. As expected, lowering the cell dose requirement from 3.0 x 107 to 1.0 x 107 TNC/kg for UCB unit selection prior to expansion culture improved HLA match and/or eliminated the need for double UCB transplant in 5 of 6 adults (Table 1). As a result, all but one patient received an 8/8 (n=5) and 7/8 (n=4) HLA matched UCB graft, potentially contributing to the low incidence of acute GVHD with only one patient of the 7 out &gt;42 days having grade 2 acute GVHD. This low rate of GVHD compares favorably to that observed in the prior study of fresh MGTA-456. With a follow-up of 19-187 days (median 89), all patients are alive. Conclusion: Transplantation of cryopreserved MGTA-456 resulted in complete engraftment and rapid recovery with speed of neutrophil recovery correlating with the CD34+CD90+ cell dose. Based on the marked expansion that is now possible, units with fewer cells can now be considered, increasing the probability of finding a better HLA matched unit, particularly for adults. Availability of MGTA-456 could reduce the barriers associated with cell dose and poor HLA match previously limiting the successful use of UCB in transplantation. Disclosures Stefanski: Novartis: Consultancy, Speakers Bureau. Brunstein:Magenta: Research Funding; Gamida: Research Funding; Astex: Research Funding. McKenna:Icahn School of Medicine, New York, New York: Consultancy; CIBMTR BMT CTN (NIH): Other: Medical Monitor; National Eye Institute (NIH): Other: DSMB (2); Magenta Therapeutics: Research Funding; Gamida: Research Funding; NMDP: Other: Donor and Patient Safety Monitoring Advisory Group; Fate Therapeutics: Research Funding; Intima: Patents & Royalties: Royalities, Research Funding. Miller:Dr. Reddys Laboratory: Membership on an entity's Board of Directors or advisory committees; Moderna: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics, Inc: Consultancy, Research Funding; GT BioPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CytoSen: Membership on an entity's Board of Directors or advisory committees; OnKImmune: Membership on an entity's Board of Directors or advisory committees. Blazar:KidsFirst Fund: Research Funding; Childrens' Cancer Research Fund: Research Funding; Abbvie Inc: Research Funding; Leukemia and Lymphoma Society: Research Funding; Kamon Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics and BlueRock Therapeuetics: Membership on an entity's Board of Directors or advisory committees; Five Prime Therapeutics Inc: Co-Founder, Membership on an entity's Board of Directors or advisory committees; Regeneron Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Alpine Immune Sciences, Inc.: Research Funding; RXi Pharmaceuticals: Research Funding; Fate Therapeutics, Inc.: Research Funding; Tmunity: Other: Co-Founder; BlueRock Therapeutics: Membership on an entity's Board of Directors or advisory committees. Boitano:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Cooke:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Raffel:Magenta Therapeutics: Employment, Equity Ownership. Davis:Magenta Therapeutics: Employment, Equity Ownership. Wagner:Rocket Pharmaceuticals: Consultancy; Magenta: Consultancy, Research Funding; BlueRock: Research Funding; Gadeta: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding.

Abstract:

Abstract Background: Assessment of malignant plasma cell cycling via plasma cell labeling index (PCLI) has been a validated prognostic tool in multiple myeloma (MM) but the test requires specialized technical expertise and is not widely available. Ki67 is a well-known protein marker of cellular proliferation on immunohistochemical (IHC) staining with prognostic utility in other malignancies. In an effort to develop a simpler system to provide analogous information to PCLI, we used a novel IHC co-staining technique for CD138 and Ki67 to quantify plasma cells in active cycling. We then performed a retrospective analysis of the ratio of Ki67/CD138 (Ki67%) in newly diagnosed patients with multiple myeloma receiving 1st-line therapy to correlate with clinical outcomes. Methods: A retrospective cohort study of patients (pts) with treated symptomatic MM was performed by interrogation of the clinical database at the Weill Cornell Medical College / New York Presbyterian Hospital. For inclusion in the analysis, subjects must have started first-line treatment in the period of 2005-2010, and had available bone marrow biopsies. Double-staining with Ki67 and CD138 was performed by IHC. The Ki67% was calculated as the percent of plasma cells expressing CD138 that were also found to express Ki67. Treatment outcomes were stratified and compared based on %Ki67. Response was determined by monthly serum protein electrophoresis / immunofixation (IFX) with free light chain analysis according to International Multiple Myeloma Working Group (IMWG) guidelines. Pts who were IFX negative but had no subsequent bone marrow biopsy were classified as being in unconfirmed complete remission. Results: We identified 151 patients with newly diagnosed MM and available %Ki67 expression who received first-line therapy over the period of 2005-2010. Patient were subdivided into two groups based on %Ki67: Low: %ki67 <= 5%, n = 87; and High: %Ki67 >5, n=64, to allow for comparison of treatment response and survival analysis. Specific therapeutic agent exposure history did not differ significantly between patients. Both groups had similar depth of response rates (ORR) to front-line therapy, Table 1. Median progression-free survival for the high versus low %Ki67 groups approached statistical significance at 54 months (95% CI 30.8,67.4) versus 26.9 months (95% CI 21.6,40.2), respectively (P = 0.083). At data cut-off, there were 30 deaths in the low %Ki67 group (1-yr OS 93%, 5-yr OS 71%) and 36 deaths in the high %Ki67 group (1-yr OS 94%, 5-yr OS 62%). Median overall survival (OS) was not reached for Ki67% <= 5% (95% CI 97.3,NR) vs. 78.9 months (95% CI 55.9,93.1) for Ki67% > 5%, (P = 0.0434), Figure 1. Multivariate cox regression for factors with influence on OS showed that only high-risk cytogenetics (HR 2.05, 95% CI 1.17, 2.92, P = 0.027), ISS (HR 1.835, 95% CI 1.33, 3.60, P = 0.000), and %Ki67 group status had an independent effect on survival outcome. Low (<=5%) versus high (>5%) %Ki67 influenced overall survival with a hazard ratio of 1.76 (CI 1.07,2.92, P = 0.027). Survival after ASCT was significantly longer in the low %Ki67 group with median OS not reached (95%CI, 97.3, NR) versus 86.9 months (95% CI 43.9, NR) for high %Ki67 group (P = 0.04). Discussion: The ratio of IHC double positive Ki67 and CD138 of > 5% is an independent prognostic marker for overall survival in newly diagnosed MM undergoing 1st line therapy. The %Ki67 serves as a simpler and widely available analog to PCLI that can be presently performed in most hematopathology laboratories. Table 1: First Line Treatment and Best Response (modified IMWG Criteria) Ki67% <= 5(N = 87)n (%) Ki67% > 5(N = 64)n (%) P Treatment Exposure* Lenalidomide 59 (67.8) 48 (75) 0.34 Thalidomide 30 (34.5) 14 (21.9) 0.09 Bortezomib 25 (28.7) 14 (21.9) 0.34 Alkylating agent 11 (12.6) 4 (6.3) 0.19 ASCT 27 (31) 22 (34.4) 0.66 Best Response Overall Response (>= Partial response) 77 (88.4) 57 (89.1) 0.41 Complete response 15 (17.2) 22 (34.4) Unconfirmed complete response** 14 (16.1) 8 (12.5) Very good partial response 23 (26.4) 15 (23.4) Partial response 25 (28.7) 12 (18.8) Stable disease 9 (10.3) 5 (7.8) Progressive disease 1 (1.2) 2 (3.1) * Percentages do not add to 100% due to instances of concurrent therapy use ** Unconfirmed complete response: immunofixation negative, but no confirmatory bone marrow biopsy available Figure 1 Overall Survival by %Ki67 Figure 1. Overall Survival by %Ki67 Disclosures Mark: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Rossi:Celgene: Speakers Bureau. Pekle:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Perry:Celgene: Speakers Bureau. Coleman:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Honoraria. Niesvizky:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Abstract:

This research focuses on the efforts made by supporters of Berni in establishing her group's identity. By strengthening group solidarity and building networks with various parties, Berni's supporters have the goal of building a supporting character without conflict and making Jember a safe area for all supporters. Researchers use social capital theory to analyze the beliefs, norms, and social networks formed by Berni's supporters. This study uses a qualitative method with an ethnographic approach. The findings of this study include solidarity among members created through activities carried out by supporters of Berni, namely meeting, drinking coffee together, and coming to the stadium to provide support to Persid during the competition. While in the bridging aspect, Berni's supporters have succeeded in building a secure and reciprocal network with various parties such as the management of the Persid Jember club, the regional government, the police, supporters outside the region, and with the community. Berni's supporters also build trust in the broader community by not engaging in clashes or destruction that can disturb the community. Keywords: social capital, trust, norms, identity. Referensi: Afrizal. (2015). Metode Penelitian Kualitatif: Sebuah Upaya Mendukung Penggunaan Penelitian Kualitatif dalam Berbagai Disiplin Ilmu. Jakarta: PT. Raja Grafindo Persada Hasbullah, J. (2006). Social Capital: Menuju Keunggulan Budaya Manusia Indonesia. Jakarta: MR-United Press Lucky, N. dan Setyowati, N. (2013). Fenomena Perilaku Fanatisme Suporter Sepak Bola (Studi Kasus Suporter Persebaya Bonek di Surabaya). Jurnal Kajian Moral dan Kewarganegaraan No. 1 Vol. 1. Surabaya: Universitas Negeri Surabaya diakses pada 4 Juni 2018 melalui https://jurnalmahasiswa.unesa.ac.id/index.php/jurnal-pendidikan kewarganegaraa/article/view/1474 Maarif, S. (2011). Bahan Ajar Sosiologi: Kapital Sosial. Yogyakarta: Gress Publishing Narwoko, J. & Suyanto, B. (2006). Sosiologi: Teks Pengantar dan Terapan.Jakarta: Kencana Putnam, R. D. (1995). Bowling Alone: American’s Declining Social Capital. Journal of Democracy No. 1 Vol. 6. Maryland: Johns Hopkins University Press diakses pada 17 Oktober 2017 melalui https://muse.jhu.edu/article/16643 Putnam, R. D. (2000). Bowling Alone: The Collapse and Revival of American Community. New York: Simon and Schuster Paperbacks Soekanto, S. (2013).Sosiologi Suatu Pengantar. Jakarta: Rajawali Pers Sunoto, H. (2014). Modal Sosial: Definisi, Konsep-konsep Utama Dari Pemikiran Modal Sosial, dan Analisis Terhadap Masalah Kemasyarakatan. Bandung: Sekolah Tinggi Kesejahteraan Sosial diakses pada 29 Maret 2017 melalui https://www.academia.edu/8894781/Modal_Sosial_penjelasan_singkat_para_pakar Syahra, R. (2003). Modal Sosial: Konsep dan Aplikasi. Jurnal Masyarakat dan Budaya Vol. 5 No. 1. Jakarta: LIPI diakses pada 11 Maret 2018 melalui http://jmb.lipi.go.id/index.php/jmb/article/view/256 Wirawan, A. O. 2014. Berni Pride of The City: Kisah Sebuah Kelompok Suporter Sepak Bola. Jember: Berni

Abstract:

Abstract Introduction: Despite improved outcomes for children with Hodgkin lymphoma (HL), relapsed and refractory disease remain a challenge for a subset of patients. High dose therapy followed by autologous stem cell transplantation (ASCT) is the standard of care for relapsed disease, largely based on data from studies in adults. As new therapies emerge for HL, risk stratification of pediatric patients with relapsed disease will be essential to determine which patients are likely to benefit from ASCT and which patients should be selected for alternative therapy. In this study we report the long-term outcome of 34 pediatric patients with HL who underwent ASCT at a single institution. Methods: We conducted a retrospective analysis of 34 consecutive pediatric patients with HL who underwent ASCT at Memorial Sloan Kettering Cancer Center from 1989-2013. Data collected included age, histology, treatment prior to ASCT, disease status at the time of transplant, conditioning regimen, and outcome after ASCT. Given recent data supporting a Childhood Hodgkin International Prognostic Score (CHIPS) for risk stratification in first-line therapy(Schwartz et al, ASH Abstract #3649, 2011), this score was calculated at the time of relapse to evaluate its prognostic relevance in the relapse setting. One point was awarded for each of the following: stage IV disease, bulky mediastinal adenopathy, albumin <3.5, and fever. Kaplan-Meier survival analysis was used to estimate the probability of overall survival (OS) and disease-free survival (DFS). Patient Characteristics: Pathologic classification included nodular sclerosis (n=30), mixed cellularity (n=1), lymphocyte predominant (n=2), or subtype unspecified (n=1). The median age was 17.9 yrs (range 9.7-21) and 47% of patients were male. Thirty-three patients had relapsed disease; one patient had primary refractory disease. The median time from diagnosis to first relapse was 13 months (range 5-60). Twenty-five patients (73.5%) had chemotherapy responsive disease at the time of transplant (CR or PR). Others had stable disease (n=6), mixed response (n=2) or progressive disease (n=1). Thirty-one of 34 patients received radiation therapy either during initial treatment or as part of a salvage regimen. Four patients received brentuximab vedotin at the time of relapse. ASCT preparative regimen consisted of cyclophosphamide-etoposide + total lymphoid irradiation (n=14) or + carmustine (n=16), while 4 patients received the BEAM regimen. All but two patients treated after 1997 received chemotherapy-only preparative regimens. Results: The median follow up for the cohort was 70.5 months (range 2.5-144). The 12-year OS and DFS were 65.1% and 63.6% respectively. The cause of death included HL (n=7), sepsis (n=1) and end stage renal disease (n=1). Patient age, stage at diagnosis, and time from diagnosis to relapse were not associated with differences in DFS. Patients who received an ASCT after 1997 had a better outcome than those who received an ASCT before 1997 (DFS 44.9% vs. 81.8%, p=0.012). Patients with chemotherapy sensitive disease at the time of transplant had a superior DFS (74.5% vs. 33.3%, p=0.005). Although not statistically significant, there was a trend toward improved outcome among patients with early stage disease at relapse (stage I/II) compared to advanced stage (III/IV) (DFS 81.3% vs. 54.2%, p=0.098). Among 21 patients with data available to calculate CHIPS at time of relapse, there was a superior OS among those with a lower CHIPS with OS of 100%, 70%, 50%, and 0% for patients with a CHIPS of 0, 1, 2, and 3 respectively (p=0.021). There were no patients with a CHIPS of 4. There was a trend toward improved DFS among patients with a low CHIPS, however this was not statistically significant (DFS of 100%, 70%, 66.7%, and 0% in patients with a CHIPS of 0, 1, 2, and 3 respectively, p=0.176). Conclusions: ASCT offers the prospect of durable, disease free survival for a significant proportion of pediatric patients with relapsed HL. The outcome among patients who received an ASCT in recent years (1997-2013) was high (DFS 81.8%). Chemotherapy sensitive disease at the time of transplant was associated with superior DFS. To our knowledge this is the first report evaluating the potential utility of CHIPS in the relapse setting. Despite the small sample size (n=21) CHIPS was predictive of OS, suggesting that this measure should be studied further as a potential prognostic marker in relapsed HL. Disclosures Trippett: Seattle Genetics, Inc.: Research Funding; OSI Pharmaceuticals: Research Funding. Kernan:Gentium S.p.A.: Research Funding. Prockop:Atara Biotherapeutics: Other: I have no financial disclosures, but Atara Biotherapeutics has exercised a licensing agreement with Memorial Sloan Kettering Cancer Center and MSKCC and some investigators at MSKCC have a financial interest in Atara.. Scaradavou:National Cord Blood Program- New York Blood Center: Employment. Moskowitz:Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding.

Abstract:

BackgroundThyroid dysfunction is a well known side effect of immune checkpoint blockade (ICB) and is one of the most common causes of immune-related adverse events (IRAE). The incidence varies with each individual therapy but generally estimated to be in the range between 6–18% per one study. Hypothyroidism and thyroiditis are the most common manifestations. Initial hyperthyroidism followed by hypothyroidism is another manifestation. Hypothyroidism is more common with an incidence of 10% whereas hyperthyroidism has an incidence of 5%. Less is known about the incidence of worsening thyroid dysfunction in patients with pre-existing thyroid dysfunction treated with ICB.MethodsA retrospective analysis was collected on 370 patients who received immunotherapy from April 2015 to April 2019. Of those, 212 had abnormal thyroid function tests. We analyzed a subgroup of these patients who had baseline thyroid dysfunction for worsening thyroid dysfunction after they were given ICB. Fifty-three patients were included in the analysis and had an abnormal baseline TSH at the start of immunotherapy. Type of immunotherapy, worst TSH, duration between initiation of immunotherapy to worst TSH, treatment type, and grade of abnormality as per Immune Checkpoint Inhibitor Related Adverse Events Common Terminology Criteria for Adverse Events (IRAE-CTCAE) were also recorded. Analysis was done for patients to compare likelihood of worsening TSH resulting in change in treatment for thyroid disorder.ResultsOf the identified patients (N=53) with abnormal TSH screening values outside of the institution’s normal reference range 0.35 - 4.95 uIU/ml, 45.7% (N=16) were hypothyroid and 54.3% (N=19) were hyperthyroid at baseline. Of those who were hypothyroid, 50% (N=8) had worsening TSH and 50% (N=8) had unchanged TSH during treatment. Of those who were hyperthyroid, 31.6% (N=6) had unchanged TSH, 52.6% (N=10) had worsened TSH, and 15.8% (N=3) had normalization of TSH compared to baseline. Overall 26.4% had worsening and of those 11.3% required treatment change.ConclusionsThyroid dysfunction is one of the most common IRAE’s associated with immune checkpoint inhibitors. Little is known about the impact of immunotherapy on patients with existing thyroid dysfunction. Patients who have underlying thyroid dysfunction are at an increased risk for worsening thyroid dysfunction with the use of ICB but though not unduly above the risk general population. Of those with change, only a modest percentage required an alteration of their endocrine therapy. Of interest, our data suggests a potential increased risk in patients with baseline hyperthyroidism compared to hypothyroidism which may be clinically relevant.Ethics ApprovalThe study was approved by ECU Brody School of Medicine Institution’s Ethics Board, approval number 19-000710.ReferencesBarroso-Sousa R, Barry WT, Garrido-Castro AC, et al. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA oncology. 2018;4:173–182.Fessas P, Possamai LA, Clark J, et al. Immunotoxicity from checkpoint inhibitor therapy: clinical features and underlying mechanisms. Immunology. 2019; 2020;159:167–177.Brody HM, Macherla S, Bulumulle A, Namireddy P, Cherry CR. The real-world incidence of immunotherapy-related thyroid dysfunction: A retrospective analysis of a single center’s experience over five years. Journal of clinical oncology. 2020;38:98–98.Iyer PC, Cabanillas ME, Waguespack SG, et al. Immune-Related Thyroiditis with Immune Checkpoint Inhibitors. Thyroid (New York, N.Y.). 2018;28:1243–1251.Presotto EM, Rastrelli G, Desideri I, et al. Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study. Journal of endocrinological investigation. 2019; 2020;43:337–345.Chalan P, Di Dalmazi G, Pani F, De Remigis A, Corsello A, Caturegli P. Thyroid dysfunctions secondary to cancer immunotherapy. Journal of endocrinological investigation. 2017; 2018;41:625–638.Mangla A, Paydary K, Yadav U, Liu J, Lad TE. Predictors and outcomes of thyroid dysfunction with immunotherapy: A single institution observational experience. Journal of clinical oncology. 2019;37:e14134-e14134.Basak EA, van der Meer, Jan W M, Hurkmans DP, et al. Overt Thyroid Dysfunction and Anti-Thyroid Antibodies Predict Response to Anti-PD-1 Immunotherapy in Cancer Patients. Thyroid (New York, N.Y.). 2020;30:966–973.Kassi E, Angelousi A, Asonitis N, et al. Endocrine-related adverse events associated with immune-checkpoint inhibitors in patients with melanoma. Cancer medicine (Malden, MA). 2019;8:6585–6594.

Abstract:

Background: Gastrointestinal dysbiosis has been associated with unfavorable clinical outcomes after allogeneic stem cell transplantation, but its clinical significance in patients receiving induction chemotherapy for AML has not been well defined. We therefore explored changes in microbial diversity and their potential impact on clinical outcomes in patients with newly-diagnosed AML undergoing standard intensive induction chemotherapy. Methods: Stool samples were obtained from 64 newly-diagnosed AML patients receiving induction chemotherapy at Weill Cornell Medicine/The New York Presbyterian Hospital from November 2015 to May 2019. A total of 140 serial samples were analyzed and categorized into three treatment time-points (±7 days): Baseline (n=64), Day 14 after chemotherapy initiation (n=51), and Day 30 after chemotherapy initiation (n=25). Clinical characteristics and treatment outcomes were collected. DNA was extracted from stool samples and sequencing of the V4 region of the bacterial 16S rRNA genes was performed using an Illumina MiSeq platform. Alpha microbial diversity was measured by the Shannon Index, Simpson Index, and the observed number of Operational Taxonomic Units (OTUs). The Friedman test was used to assess for changes in alpha diversity from baseline to Day 14 to Day 30 samples. Wilcoxon rank-sum tests were used to compare alpha diversities between groups of dichotomized clinical variables, including gender, age, early antibacterial use, diarrhea, bloodstream infections, and achieving a complete response (CR). The Kruskal Wallis one-way test of variance was used to compare differences in microbial diversity between ELN risk categories. A multivariate logistic regression model was applied to assess associations between the degree of change in diversity from baseline to day 14 and clinical outcomes. Results: Clinical characteristics are summarized in Table 1. Intensive chemotherapy consisted of 7+3 (cytarabine/anthracycline), CPX-351, or 7+3 combined with other therapies. 49 (77%) patients achieved CR or CRi (CR with incomplete count recovery) and 24 (38%) had bloodstream infections during their hospital course. Shannon and Simpson diversity indices and OTUs are shown in Figure 1. There was a significant decline in median microbiome alpha diversities measured by all indices among baseline, day 14, and day 30 samples (Shannon: p = 0.0003; Simpson: p = 0.0003; OTU: p&lt;0.0001). The median change in diversity from baseline to day 14 samples were: Shannon (median: -0.932, range: -3.714 to +1.96), Simpson (median: -0.210, range: -0.947 to +0.689), and OTU (median -62, range: -270 to 93). 24 patients (38%) received antibacterial treatment prior to day 14. However, antibacterial therapy during this time was not associated with change in diversity using any of the indices. Decrease in alpha diversity from baseline to day 14 samples by Shannon index was associated with the achievement of CR/CRi (p = 0.023) (Figure 2). Subsequent multivariate regression analysis showed significant correlations between amount of Shannon diversity decrease from baseline to day 14 and CR/CRi, independent of age, ELN risk, and baseline diversity (Odds ratio: 0.053, (95% CI: 0.001 to 0.467, p = 0.049). Achievement of CR/CRi was significantly correlated with a decrease of microbiome diversity from baseline to day 14 (Median = -1.111), whereas failure to achieve CR/CRi was correlated with an increase in microbiome diversity from baseline to day 14 (Median = +0.199). There were no significant correlations between levels of baseline, day 14, or day 30 microbiome diversity and age (&gt;60 vs. ≤60), ELN risk categories, diarrhea, bloodstream infections, or CR/CRi using any of the indices. There were no significant correlations between decrease in diversity from baseline to Day 14 samples and diarrhea or bloodstream infections. (Figure 2) Conclusion: Gut microbial diversity declines in patients receiving intensive induction chemotherapy for AML throughout their hospitalization, even in the absence of antibacterial therapy. Overall decrease in diversity at day 14 is associated with achievement of remission, independent of age, ELN risk, and baseline diversity. In this cohort, neither decreased microbial diversity nor a decline in microbial diversity was associated with adverse clinical outcomes. Additional study of the impact of the gut microbiome on outcomes in patients with AML is warranted. Disclosures Lee: Roche Molecular Systems: Consultancy; Jazz Pharmaceuticals, Inc: Consultancy; Helsinn: Consultancy; Karyopharm Therapeutics: Consultancy; Ai Therapeutics: Research Funding; AstraZeneca Pharmaceuticals: Consultancy. Ritchie:Genentech: Other: Advisory board; Celgene: Other: Advisory board; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Celgene, Novartis: Other: travel support; Jazz Pharmaceuticals: Research Funding; Pfizer: Other: Advisory board, travel support; agios: Other: Advisory board; Tolero: Other: Advisory board; Celgene, Incyte, Novartis, Pfizer: Consultancy; Ariad, Celgene, Incyte, Novartis: Speakers Bureau. Desai:Sanofi: Consultancy; Celgene: Consultancy; Cellerant: Consultancy; Astex: Research Funding; Astellas: Honoraria. Roboz:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Actinium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amphivena: Consultancy, Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astex: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Eisai: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orsenix: Consultancy, Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trovagene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Abstract:

IntroductionWith progress in the ‘diagnose’, ‘link’ and ‘retain’ stages of the HIV care continuum, viral suppression (VS) gains increasingly hinge on antiretroviral adherence among people with HIV (PWH) retained in care. The Centers for Disease Control and Prevention estimate that unsuppressed viral load among PWH in care accounts for 20% of onward transmission. HIV intervention strategies include ‘data to care’ (D2C)—using surveillance to identify out-of-care PWH for follow-up. However, most D2C efforts target care linkage, not antiretroviral adherence, and limit client-level data sharing to medical (versus support-service) providers. Drawing on lessons learnt in D2C and successful local pilots, we designed a ‘data-to-suppression’ intervention that offers HIV support-service programmes surveillance-based reports listing their virally unsuppressed clients and capacity-building assistance for quality-improvement activities. We aimed to scale and test the intervention in agencies delivering Ryan White HIV/AIDS Programme-funded behavioural health and housing services.Methods and analysisTo estimate intervention effects, this study applies a cross-sectional, stepped-wedge design to the intervention’s rollout to 27 agencies randomised within matched pairs to early or delayed implementation. Data from three 12-month periods (pre-implementation, partial implementation and full implementation) will be examined to assess intervention effects on timely VS (within 6 months of a report listing the client as needing follow-up for VS). Based on projected enrolment (n=1619) and a pre-implementation outcome probability of 0.40–0.45, the detectable effect size with 80% power is an OR of 2.12 (relative risk: 1.41–1.46).Ethics and disseminationThis study was approved by the New York City Department of Health and Mental Hygiene’s institutional review board (protocol: 21–036) with a waiver of informed consent. Findings will be disseminated via publications, conferences and meetings including provider-agency representatives.Trial registration numberNCT05140421.

Abstract:

Abstract Abstract 2066 Poster Board II-43 From 1999 to 2009, 298 adults, age 60 yrs and above, received initial induction therapy for untreated AML at Weill-Cornell Medical College/New York Presbyterian Hospital. Based on physician/patient preference and/or protocol eligibility, patients received either a traditional cytosine arabinoside/anthracycline-based induction regimen (n= 103) or an alternative, low-intensity regimen(n=195); either low-dose ara-C +/- arsenic trioxide (n=88) or tipifarnib +/- oral etoposide (n=107). Overall the median age was 72 yrs (range 60-89), 47% had an antecedent hematological disorder (AHD) and 42% had an unfavorable karyotype. Patients treated with low-intensity regimens were significantly older compared to those given standard induction (median age 75 vs 67 yrs) and had a higher percentage of unfavorable karyotypes (46% vs 33%). Complete remissions (CR) were achieved in 23% of patients receiving low-intensity regimens and 53% of patients treated with standard therapy. Thirty and 60 day mortality rates were 9.7% and 20.5% versus 14.5% and 25% for low-intensity and standard regimens respectively (p=0.29). Seventy two of the initial 195 patients (37%) treated with a low-intensity regimen received a second induction regimen for primary resistance or relapse; either a standard ara-C-anthracycline regimen (n=38) or a second non-intensive regimen (decitabine +/- gemtuzumab ozogamicin, low-dose ara-c, SGN-33,) (n=34). Overall 25/72 (35%) achieved a CR with salvage therapy; 16/38 CR's (42%) with standard induction and 9/34 CR's (26%) with a second low-intensity regimen. Median overall survival for all 298 patients was 6.7 months. By univariate analysis, no significant difference in survival was seen for patients initially treated with a low-intensity regimen compared to those receiving standard induction (median 6.2 vs 7.7 months; p=0.82 by log-rank test). By multivariate analysis, age over 75, prior AHD, unfavorable karyotype, ECOG performance status > 2, and male gender all predicted for shorter survival, whereas intensity of initial treatment did not. These results suggest that older patients with AML may receive initial therapy with a non-traditional, low-intensity induction regimen and have similar survival outcomes compared to patients given standard induction. A comparison of the quality of life of patients, as manifested by the percentage of days spent in hospital, frequency of transfusion support, and number of outpatient visits, will be presented. Death due to resistant disease remains the major problem for older patients with AML Disclosures: Off Label Use: arsenic trioxide to be used to enhance the effects of low-dose ara-C as part of a clinical trial.

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IntroductionThe COVID-19 pandemic is forcing changes to clinical practice within traditional addiction treatment programmes, including the increased use of telehealth, reduced restrictions on methadone administration (eg, increased availability of take-home doses and decreased requirements for in-person visits), reduced reliance on group counselling and less urine drug screening. This paper describes the protocol for a mixed-methods study analysing organisational-level factors that are associated with changes in clinic-level practice changes and treatment retention.Methods and analysisWe will employ an explanatory sequential mixed-methods design to study the treatment practices for opioid use disorder (OUD) patients in New York State (NYS). For the quantitative aim, we will use the Client Data System and Medicaid claims data to examine the variation in clinical practices (ie, changes in telehealth, pharmacotherapy, group vs individual counselling and urine drug screening) and retention in treatment for OUD patients across 580 outpatient clinics in NYS during the pandemic. Clinics will be categorised into quartiles based on composite rankings by calculating cross-clinic Z scores for the clinical practice change and treatment retention variables. We will apply the random-effects modelling to estimate change by clinic by introducing a fixed-effect variable for each clinic, adjusting for key individual and geographic characteristics and estimate the changes in the clinical practice changes and treatment retention. We will then employ qualitative methods and interview 200 key informants (ie, programme director, clinical supervisor, counsellor and medical director) to develop an understanding of the quantitative findings by examining organisational characteristics of programmes (n=25) representative of those that rank in the top quartile of clinical practice measures as well as programmes that performed worst on these measures (n=25).Ethics and disseminationThe study has been approved by the Institutional Review Board of NYU Langone Health (#i21-00573). Study findings will be disseminated through national and international conferences, reports and peer-reviewed publications.

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Abstract Background: Monoclonal immunoglobulin deposition disease (MIDD) is a rare complication of plasma cell dyscrasias in which deposition of immunoglobulin light and/or heavy chains results in organ dysfunction, most commonly affecting the kidneys. MIDD can present with new onset hypertension, hematuria, renal insufficiency and proteinuria. The rarity of MIDD contributes to the uncertainty regarding optimal therapy (typically targeting the clonal plasma cells), and the relationship between hematologic response and renal outcome. We report here the experience at Memorial Sloan Kettering Cancer Center and New York Presbyterian Hospital/Weill Cornell Medical Center. Methods: An electronic query of pathology records was performed to identify patients with a biopsy-proven diagnosis of MIDD. Patients were eligible for inclusion in this analysis if they had received treatment and had been subsequently followed at either institution. A retrospective review of clinical records extracted patients' baseline characteristics and treatment history. Hematologic responses were assessed according to International Myeloma Working Group uniform response criteria (Kumar, S. et al 2016 Lancet Oncol 17(8): e328-346) and renal organ responses were evaluated based on changes in serum creatinine (SCr), and proteinuria, a modification of criteria previously reported (Kourelis, T. V., et al 2016, Am J Hematol 91(11): 1123-1128.; Nasr, S.H. et al. 2009, J Am Soc Nephrol 20(9): 2055-2064. The primary objective was to determine the rate of hematologic response after initial therapy. Secondary objectives included: (i) Estimation of renal response rate; (ii) Identification of risk factors associated with renal response using the Wilcoxon Rank Sum and Fisher's Exact Tests. Results: Among 54 patients identified who were diagnosed and started treatment between 1/1999 and 1/2016, 29 met criteria for inclusion. Baseline characteristics at diagnosis included: Median age of 50 (range, 32-79); 17 (59%) were male; 22 (75%) had hypertension. Renal parameters at diagnosis: median SCr of 2.4 mg/dl (range, 0.4-19), median CrCl 23 ml/min (range, 4-131), median proteinuria 2383.7mg/24h (range 4.7-13,000), nephrotic-range proteinuria syndrome in 13 (45%), hematuria in 4/25 pts (16%; 4 unknown), 7 were on hemodialysis (HD) prior to initiation of therapy, and 26 (90%) patients had monoclonal kappa light chain deposits. Hematologic parameters included median free light chain ratio of 67.9 (2.8-1179.0), detectable M-spike in 11 pts with a mean level of 0.6 g/dL and median bone marrow plasmacytosis of 20% (range, 0-90%). Induction treatment regimens included bortezomib in 18 (62%), lenalidomide in 6 (21%), cyclophosphamide in 8 (28%), and 21 (73%) underwent autologous stem cell transplant (ASCT) during the course of their treatment. Outcomes are shown in Table 1. Hematologic response among the 29 pts at completion of first line therapy included an overall response rate (ORR) of 93% with sCR (N=14, 48%); CR (N=5, 17%), VGPR (N=6, 20%), PR (N=2, 6.9%), Not available (N=2, 7%). Renal response (Table 1) among 29 patients included CR (N=9, 31%), PR (N=14, 48%) and End Stage Renal Disease (ESRD) (N=6, 21%). Among 7 patients on HD at baseline, 3 remained on HD despite treatment, while 4 stopped HD after treatment, 2 as a result of the treatment and 2 after renal transplant. 3 patients progressed to ESRD and required HD during treatment. Baseline beta-2 microglobulin (B2M), SCr, and eGFR at diagnosis were factors associated with renal response (p<0.05). Hematologic response (CR vs. non-CR) was not associated with renal response (p=0.68) in this cohort. Conclusions: In this cohort, we observed a high rate of hematologic response (65.5% reaching CR) to upfront treatment regimens. A majority of patients received bortezomib-based regimens and ASCT. We observed a large proportion of patients whose renal impairment from MIDD improved significantly after receiving therapy directed at the underlying clonal neoplasm, with 75.8% reaching PR or better, nearly a third of patients achieving a renal CR, and 2/7 patients on HD at diagnosis discontinuing HD after treatment. Our experience presented here serves to inform the treatment approach of patients with MIDD. Given the scarcity of outcome data in MIDD, especially in the era of novel anti-myeloma therapy, prospective studies to optimize the management of these patients are needed. Disclosures Rossi: Celgene: Consultancy. Smith:Celgene: Consultancy, Patents & Royalties: CAR T cell therapies for MM, Research Funding. Korde:Amgen: Research Funding. Mailankody:Janssen: Research Funding; Juno: Research Funding; Physician Education Resource: Honoraria; Takeda: Research Funding. Lesokhin:Squibb: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Genentech: Research Funding; Janssen: Research Funding; Serametrix, inc.: Patents & Royalties: Royalties. Landgren:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy; Merck: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Hassoun:Oncopeptides AB: Research Funding.

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Background: NK cells have the capacity to kill tumor targets, representing a novel immunotherapeutic approach to cancer. We have shown promising clinical activity in AML with a previous NK cell preparation. Limitations of NK therapies have included specificity, persistence after infusion, and potential for maximal activity of NK cells in vivo. GDA-201 is a cellular product composed of natural killer (NK) cells from healthy donors expanded ex vivo with nicotinamide (NAM) and IL-15; this is a unique ex vivo activation strategy to induce persistence of potent anti-tumor activity. Prior in vitro studies and pre-clinical models demonstrated that NAM-exposed NK cells exhibited augmented resistance against exhaustion and improved killing function, proliferation, and organ retention. We now report safety and efficacy from a phase 1 clinical trial of GDA-201 in patients (pts) with relapsed or refractory (R/R) NHL or MM. Methods: Following donor apheresis, CD3-depleted mononuclear cells were cultured for 14-16 days with NAM (5mM) and IL-15 (20ng/ml), resulting in a 40-fold increase in NK cells and increased expression of CD62L from 2.9% to 21%. GDA-201 contained ~98% NK cells, and CD3 content was maintained at &lt;0.5% (&lt;5x105/kg/dose). Pts with R/R CD 20-positive NHL or refractory MM received cyclophosphamide (400mg/m2 IV x 3d) and fludarabine (30 mg/m2 /d IV x 3d), followed by two doses of GDA-201 (Days 0 and 2) and low-dose IL-2 (6 million units sc). Pts with NHL or MM received rituximab (375 mg/m2 x 4 weekly or elotuzumab (10 mg/kg x 3 weekly), respectively, to enhance NK cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Results: 20 pts were enrolled: 7 with NHL (4 follicular, 2 transformed, 1 diffuse large cell lymphoma) and 13 with MM, in 3 cohorts of escalating GDA-201 dose; 11 pts received the maximum target dose (median 1.7 x 108 cells/kg, range 1.6-2.0 x 108 cells/kg). There were no dose limiting toxicities. The most common grade 3/4 adverse events were neutropenia and thrombocytopenia, febrile neutropenia (n=2), increased creatinine, hyponatremia, pulmonary edema; all events were transient. One pt had grade 2 cytokine release syndrome at day 18, presenting with fever, hypoxemia and hypotension, responding to tocilizumab; pt later died of E Coli sepsis. There were no neurotoxic events, GVHD or marrow aplasia. Among 7 NHL pts, there were 3 CR and 2 PR with overall response rate of 71%. Median duration of response was 12 months (CR patients) and 5 months (PR patients). Figure 1A illustrates a 57-year-old man with history of CLL and Richter's transformation (large cell lymphoma), pre- GDA-201 and 6 months post therapy; the pt had continued response with 80% tumor shrinkage at 6 months. In MM patients, 1 patient with extramedullary disease had CR and 4 had SD with median duration 2.5 months. In our previous study using overnight-activated NK cells, persistence 7 days after adoptive transfer was limited. Using GDA-201, flow cytometry confirmed persistence of donor NAM-NK in peripheral blood up to day 7-10 (day 7 range 2-55% donor NK cells; Figure 1B), as well as enhanced in vivo proliferation (median Ki67 99%). Conclusions: Cellular therapy using GDA-201 with monoclonal antibodies was safe, and demonstrated early evidence of clinical activity in heavily pre-treated pts with advanced NHL and MM. The recommended dose of GDA-201 for phase 2 is 2.0 x 108 cells/kg. The clinical responses showed that NK cell targeting through ADCC can be efficacious and increase response. Laboratory studies showed that GDA-201 had better persistence than observed in our previous studies using overnight activated cytokine alone stimulated NK cells. This study demonstrated that GDA-201 has an efficacy signal, and larger phase II studies are warranted. Disclosures Bachanova: Incyte: Research Funding; Gamida Cell: Research Funding; Novartis: Research Funding; GT Biopharma: Research Funding; Celgene: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. McKenna:Fate Therapeutics: Research Funding; Magenta Therapeutics: Research Funding; CIBMTR BMT CTN (NIH): Other: Medical Monitor; Icahn School of Medicine, New York, New York: Consultancy; National Eye Institute (NIH): Other: DSMB (2); Gamida: Research Funding; NMDP: Other: Donor and Patient Safety Monitoring Advisory Group; Intima: Patents & Royalties: Royalities, Research Funding. Brachya:Gamida Cell: Employment, Equity Ownership. Peled:Gamida Cell: Employment, Equity Ownership. Miller:GT BioPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CytoSen: Membership on an entity's Board of Directors or advisory committees; Dr. Reddys Laboratory: Membership on an entity's Board of Directors or advisory committees; Moderna: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics, Inc: Consultancy, Research Funding; OnKImmune: Membership on an entity's Board of Directors or advisory committees.

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Resumen: El presente artículo se encuentra dividido en cinco apartados que permiten que su lectura y comprensión sea mucho más amigable. Es interesante y entender que el tema del terrorismo es un tema de naturaleza dinámica y cambiante, en el artículo se estudiara los diferentes tipos de terrorismo que existe y el impacto que ha tenido en el establecimiento de los estados de seguridad pública, así como la afectación a los derechos humanos de las personas y los regímenes jurídicos en los cuales se tipifica esta figura. Abstract: This article is divides into five sections that allow its reading and understanding to be much more user-friendly. It is interesting to understand that the issue of terrorism is a dynamic and changing issue, the article will study the different types of terrorism that exist and the impact it has had on the establishment of states of publica security as well as the impact to the human rights of persons and the legal regimes in which this figure is typified. Fuentes de consulta: Arendt H. (2006) Sobre la revolución, Madrid: Alianza. Báez Corona, J. F. (2015). El realismo mágico jurídico (recreación legal de una ficción literaria con especial referencia a Latinoamérica). Justicia. (28), 15-31. doi:http://dx.doi.org/10.17081/just.20.28.1032 Báez, J. (2021). Tradición contra innovación en los modelos de formación jurídica universitaria en México. Revista de Derecho. (56). 137-153. https://dx.doi.org/10.14482/dere.56.340 Bakke E. (2015) Terrorism and Conterterrorism studies, comparing theory and practice, Netherlands, Leiden University Press. Bobbio N. (2004) Estado, Gobierno y Sociedad por una teoría general de la política, México, Fondo de Cultura Económica. Caillois R. (1973) La cuesta de la guerra (trad.) Rufina Bórquez, México, Fondo de Cultura Económica. Coteño Muñoz A. (2018) “Terrorismo individual los atentados perpetrados por actores solitarios” Eunomía. Revista en Cultura de la Legalidad, número 15 Madrid, Universidad Carlos III. Donner, F. (2007) “Fight for God- But Do So with Kindness: Reflections on War, Peace, and Communal Identity in Early Islam”. In War and Peace in the Ancient World, Oxford. Blackwell. Durham M. (2000) The Christian right, the far right and the Boundaries of American Conservatism. Manchester: Manchester University Press. Dworkin R, (2013) “Foreword”, in Extreme Speech and Democracy, Oxford, Oxford University Press. Essig, C. (2001). Terrorism: Criminal Act of Act of War? Implications for National Security in the 21st Century. Pennsylvania: US Army War College. Foucault, M. (2009) Historia de la sexualidad 1. La voluntad de saber, México, Siglo XXI. Friedman B, H., Harper J, Preble C. (2010) Terrorizing ourselves. Why U.S. Counterterrorism Policy is Failing and How to Fix It. Washington D.C. Instituto Cato. Gallego, C. (2012). El concepto de seguridad jurídica en el Estado social. Revistas jurídicas. Vol 2, Núm 9, Recuperado de http://juridicas.ucaldas.edu.co/downloads/Juridicas9(2)_6.pdf Griset, P. L., Mahan, S. (2003) Terrorism in perspective, United States of America. Sage Publications Inc. González Calleja, E. (2013). El Laboratorio del Miedo, Madrid, Crítica. Habermas J. (1998) Derechos humanos y soberanía popular. Las versiones liberal y republicana, en Rafael del Águila, Fernando Val, Madrid, Alianza Habermas J. (1994) La desobediencia civil, piedra de toque del Estado democrático de Derecho, en Ensayos políticos, Barcelona, Península. Heydar S. (2017) Islamic Peace Ethics. Legitimate and Illegitimate Violence in Contemporary Islamic Thought. United States of America, Baden-Baden: NomosAschendorff Verlag. Hoffman B., Howard R. (2011) Terrorism and counterterrorism: Understandin the new security environment readings and interpretations: 4a eth, United States of America, Mcgraw-Hill. Hoffman, B. (2006). Inside Terrorism. New York: Columbia University Press. Jackson, R, et al., (2011) Terrorism. A Critical Introduction, New York, Palgrave Macmillian Jassies N. (2009) Mrinus Van Der Lubbe y el incendio del Reichstag. Trad., García Velasco C., España, Editorial Alikornio. Jellinek G (1954) Teoría Geenral de los Estados. Trad. Fernando de los Ríos. Buenos Aires, ed. Albatroz. Jenkins, B.M. (1975), "International Terrorism: A New Mode of Conflict", in Garitón D, y Schaerf C. Internactional Terrorism and World Security, Londres, Cromm Helm. Johnston, T. D. (1981). Selective costs and benefits in the evolution of learning. En J. S. Rosenblatt, R .A. Hinde, C. Beer y M. C. Busnel (Eds.). Advances of the study of behavior. New York: Academic Press Kilpatrick J (2020) Quand un état d’urgence temporarire devient permanent, le cas de la France. París, Transnational Institute. Khadduri, M. (1955) War and Peace in the Law of Islam. Baltimore, The Johns Hopkins Press. Kyrou, A. (2012). L’imaginaire des Anonymous, des luddites à V pour Vendetta. París Folis esssays Lasoen, K. (2018). “War of Nerves: The Domestic Terror Threat and the Belgian Army”. In Studies in Conflict & Terrorism, vol. 42, no. 11. Le Goff J. (1984) La Civilisation d l’occident médiéval, París, Foils Essay. Lillich, B. R. (1985) Paris Minimum Standards of Human Rights Norms in a State of Emergency, The American Journal of International Law, Vol. 79, No. 4 Locke J. (1997), Segundo tratado sobre el gobierno civil, Madrid, Alianza. Loubet Del Bayle, J. L. (1992) La Police. Approche socio-politique. Paris, Montchrestien. Luhmann, N. (2005) El derecho de la sociedad, 2a ed., México, Herder, Universidad Iberoamericana. Majoran, A. (2015). The illusion of war: Is terrorism a criminal act or an act of war? International Politics Reviews, Vol.3 Issue 1 Martin J-C, (2006) Les règles internationales relatives à la lutte contre le terrorismo. París, edición Bruylant. Nateras González M, E. (2018) Colombia Las autodefensas en Michoacán, México: ¿rescate de la ciudadanía ante la violencia? Revista Opinión Jurídica, Universidad de Medellín, Vol. 17, Núm. 33 Placido A. P., y Perkins L K. (2010) Drug Trafficking violence in México implications for the United States. Washington D.C. U.S. Senate Caucus on International Narcotics Control Departmente of Justice Poczynok, I. (2019). Fuerzas armadas y contraterrorismo. Apuntes para renovar un “debate crónico” en la Argentina. Revista Relaciones Internacionales, Estrategia Y Seguridad, vol. 2, Núm. 14 Poland J. (2004) Understanding Terrorism: Groups, Strategies and responses. New York. Pretince Hall. Rawls J (1999) La justificación de la desobediencia civil, en Justicia como equidad. Materiales para una teoría de la justicia, Madrid, Tecnos. Reinares, F y García-Calvo, C. (2016) Estado Islámico en España. Madrid: Real Instituto Elcano. Rivas, P., y Rey, P. (2008) Las autodefensas y el paramilitarismo en Colombia (1964-2003), Bogotá, CON Fines. Rapoport, D. (2004). “The four waves of modern terrorism”. En Audrey, C. y James, L. Attacking Terrorism: Elements of a Grand Strategy. Washington D.C. George town University Press Rodley N. (1985) International Human Rights Law, dans Evans, M. D, International Law, Oxford, Oxford University Press. Reitberger M (2013) “License to kill: is legitimate authority a requirement for just war? in International Theory, Cambridge, Cambridge University Press, Vol. 5, Issue 1. Robespierre Maximilien (2005) Por la felicidad y por la libertad, discursos. España, El viejo topo. Rousseau J. J., (2013) Discurso sobre el origen y fundamento de la desigualdad entre los hombres, Madrid, Calpe. Tinnes J. (2020) Bibliography: Defining and Conceptualizing Terrorism Compiled PERSPECTIVES ON TERRORISM Volume 14, Issue 6, The Netherlands Universiteit Leiden. recuperado de https://www.universiteitleiden.nl/perspectives-on-terrorism/archives/2020#volume-xiv-issue-6 Toboso Buezo M. (2020) Colección Segmentos de Seguridad Terrorismo y antiterrorismo. España. Institut de Seguretat Pública de Catalunya.. Saint Thomas Aquinas (2003) On law, morality and Politics, translated by Regan Richard United States of America, Hackett publishing company. Sinai, J. (2008) “How to Define Terrorism”, Perspectives on Terrorism, Journal of the Terrorism Research Initiative and the Center for Terrorism and Security Studies, The Netherlands, Universiteit Leiden, Vol. 2, No.4, recuperado de http://www.terrorismanalysts.com/pt/index.php/pot/article/view/33/html Skinner, B. F. (1953) Science and human behavior. New York, The Macmillan Company. United States Department of State. (2004) Patterns of Global Terrorism 2003 Washington, DC: Office of the Secretary of State, Office of the Coordinator for Counterterrorism. Valadés D. (1974) La dictadura constitucional en América Latina, México, UNAM. Walther T C., Höhn A., (2020) El ejército alemán y sus graves problemas con la ultraderecha. DW noticiero recuperado de https://www.dw.com/es/el-ej%C3%A9rcito-alem%C3%A1n-y-sus-graves-problemas-con-la-ultraderecha/a-54044495 Wallace, D. (2008). Combatiendo el terrorismo bajo las leyes de la guerra. Military Review Hispan-American, Vol. 88, Issue 2 Weber M. (1986) El político y el científico. (trad) Francisco Rubio Llorente, Madrid, Alianza Editorial.

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Background In the United States, transgender women (TW) are disproportionately burdened by HIV infection. Cohort studies are needed to evaluate factors driving HIV acquisition among TW over time. These will require implementation strategies that are acceptable to the TW community and feasible to implement. Objective This study aims to investigate the rate and correlates of HIV acquisition and other health outcomes among TW in eastern and southern United States. Methods LITE is a multisite prospective cohort in 6 eastern and southern US cities, which will be followed across 24 months of technology-enhanced biobehavioral follow-up. Adult TW, regardless of HIV status, are recruited via convenience sampling (eg, peer referrals, social media, and dating apps). Participants are enrolled in a baseline study visit, complete a sociobehavioral survey, and test for HIV and sexually transmitted infections. Participants who are not living with HIV at baseline are offered enrollment into the cohort (N=1100); follow-up assessments occur quarterly. Results Cohort assembly was informed by synchronous Web-based focus group discussions with TW (n=41) and by continuing engagement with community advisory board members from each site. Enrollment launched in March 2018. The study is underway in the Atlanta; Baltimore; Boston; Miami; New York City; and Washington, DC, metro areas. As of March 2019, 795 TW completed a baseline visit (mean age 35 years). The majority of the participants are racial/ethnic minorities, with 45% of the TW identifying as black and 28% of the TW identifying as Hispanic/Latinx. More than one-quarter (28%) of the TW are living with HIV infection (laboratory-confirmed). Online recruitment methods support engagement with TW, although peer referral and referral through trusted health facilities and organizations remain most effective. Conclusions This study is responsive to increasing research interest in technology-enhanced methods for cohort research, particularly for hard-to-reach populations. Importantly, the diversity of literacy, technology use, and overall socioeconomic situations in this sample of TW highlights the need to leverage technology to permit a flexible, adaptive methodology that enhances engagement of potential participants living in marginalized contexts while still ensuring rigorous and sound study design. International Registered Report Identifier (IRRID) DERR1-10.2196/14704

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Object Patients undergoing placement of an external ventricular drain (EVD) are at increased risk for development of venous thromboembolisms (VTEs). Early chemical prophylaxis has been shown to decrease rates of embolism formation, but the risks for bleeding and the optimal time to initiate prophylaxis have not been clearly defined for this patient population. The authors evaluated the safety and risks for bleeding when chemical prophylaxis for VTEs was started within 24 hours of EVD placement. Methods To compare rates of hemorrhage among patients who received prophylaxis within 24 hours and those who received it later than 24 hours after admission, the authors conducted an institutional review board–approved retrospective review. Patients were those who had had an EVD placed and postprocedural imaging conducted at Bellevue Hospital, New York, from January 2009 through April 2012. Data collected included demographics, diagnosis, coagulation panel results, time to VTE prophylaxis and imaging, and occurrence of VTEs. The EVD-associated hemorrhages were classified as Grade 0, no hemorrhage; Grade 1, petechial hyperdensity near the drain; Grade 2, hematoma of 1–15 ml; Grade 3, epidural or subdural hematoma greater than 15 ml; or Grade 4, intraventricular hemorrhage or hematoma requiring surgical intervention. Results Among 99 patients, 111 EVDs had been placed. Low-dose unfractionated heparin had been given within 24 hours of admission (early prophylaxis) to 56 patients and later than 24 hours after admission (delayed prophylaxis) to 55 patients. There were no statistical differences across all grades (0–4) among those who received early prophylaxis (n = 45, 5, 5, 1, and 0, respectively) and those who received delayed prophylaxis (n = 46, 4, 1, 1, and 3, respectively) (p = 0.731). In the early prophylaxis group, 3 VTEs were discovered among 32 of 56 patients screened for clinically suspected VTEs. In the delayed prophylaxis group, 5 VTEs were discovered among 33 of 55 patients screened for clinically suspected VTEs (p = 0.71). Conclusions Hemorrhagic complications did not increase when chemical prophylaxis was started within 24 hours of admission. Also, the incidence of VTEs did not differ between patients in the early and delayed prophylaxis groups. Larger randomized controlled trials are probably needed to assess decreases in VTEs with earlier prophylaxis.

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Abstract Background: Multiple myeloma (MM) is characterized by the neoplastic proliferation of plasma cells that most often produce a single monoclonal immunoglobulin (M-protein). In approximately 2% of cases however, two or more distinct M-proteins of different immunoglobulin isotype are noted at diagnosis. The International Myeloma Working Group (IMWG) does not provide specific guidelines for determination of treatment response for MM with multiple M-proteins (MMP) and evidence comparing response and treatment outcomes of patients (pts) with MMP to those with a single M-protein (SMP) is lacking. The current tacit convention for assessing treatment response is to sum all M-proteins to get an aggregate M-protein value to compare to subsequent aggregate M-proteins over time. This approach has not been formally validated; it is unknown whether pts with MMP have a different natural history of the disease or response to treatment. We therefore conducted a retrospective analysis comparing clinical outcomes of 1st-line therapy of patients with MMP vs SMP. Methods: A retrospective cohort study of MM pts undergoing first-line therapy was performed by interrogation of the clinical database at the Weill Cornell Medical College / New York Presbyterian Hospital. Subjects diagnosed with active MM who received first-line treatment were included. MMP status was assigned to any patient (pt) with two or more distinct bands appearing on a serum protein electrophoresis with different isotypes on serum immunofixation prior to receiving any therapy. Baseline pt characteristics, therapy received, treatment, and survival outcomes were collected and compared. For pts with MMP, response was determined by following the change in sum of all M-proteins and following the sum as a SMP when applying IMWG criteria. Results: 170 pts were identified in the period of 2005-2014 and included in the analysis: 159 pts (93.5%) with SMP and 11 (6.5%) with MMP. Pts with MMP were older (median age 72 vs 62, P = 0.01) with a lower degree of bone marrow plasmacytosis (median 19% vs 45%, P = .003), with a trend towards a higher rate of extramedullary presentation (18.2% vs 4.5%, P = 0.051). Staging by ISS and Durie-Salmon, presence of adverse cytogenetics, sex, lactate dehydrogenase, C-reactive protein, baseline hemoglobin, and serum creatinine were similar in the two groups. The M-protein isotype distribution for SMP and MMP are shown below in Table 1, with no clear pattern emerging for the SMP group. Pts with SMP were more likely to have been treated with thalidomide (32% vs 0 pts, P = .025) and less with alkylating agents (8.8 vs 27.2%, p = 0.49), however were equally likely to have received treatment with lenalidomide, bortezomib, or autologous stem cell transplant. Overall response to therapy appeared deeper in SMP vs MMP (Table 2) but was not statistically different (P = 0.053). Median PFS was similar for SMP and MMP at 148 vs 135 weeks, respectively (log rank P = 0.87). Overall survival was also unaffected by the presence of MMP: median OS for SMP and MMP was 411 and 423 weeks, (log rank P = .42). A logistic regression model showed higher age (OR 1.15, 95% CI 1.04,1.28) and lower percent plasmacytosis (OR 0.92, 95% CI 0.87, 0.98) to be associated with the presence of MMP at diagnosis. Discussion: The presence of more than one distinct M-spike isotype at diagnosis of active MM was not associated with adverse treatment or survival outcomes. The current convention of following the sum of all M-proteins in these pts is valid. The IMWG criteria should be amended to formally clarify this method of determination of response in pts with MMP. Table 1: Multiple M-protein isotypes M-Protein Isotypes N = 170 (%) IgG-kappa 60 (35.3) IgG-lambda 33 (19.4) IgA-kappa 16 (9.4) IgA-lambda 16 (9.4) Free kappa 24 (14.1) Free lambda 9 (5.3) IgD-lambda 1 (0.6) IgG lambda and IgG kappa 2 (1.1%) IgG kappa and IgA kappa 2 (1.1%) IgA kappa and IgG lambda 2 (1.1%) IgG kappa and free mu heavy chains 1 (0.6%) IgG lambda and IgA lambda 1 (0.6%) IgG kappa and IgG lambda and IgM kappa 1 (0.6%) Biclonal IgG kappa, monoclonal IgA kappa 1 (0.6%) IgG kappa, IgM kappa, and IgA kappa 1 (0.6%) Table 2: Overall response for SMP vs MMP IMWG Response SG(N = 159) PG(N = 11) P Overall Response Rate N = 155 N = 11 .053 PD 3 2 SD 14 0 PR 38 5 VGPR 63 3 CR 3 0 SCR 38 1 Disclosures Mark: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Niesvizky:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Abstract Abstract 1800 Poster Board I-826 Background The prevalence of peripheral neuropathy (PNP) during the treatment of MM with Bortezomib is high. About 20% of patients develop a grade 3-4 PNP due to this treatment, and as a result Bortezomib treatment is stopped or a reduced dose is given. Therefore, there is a strong need to find markers which predict the susceptibility of a patient to develop Bortezomib related PNP. Materials and methods: Bortezomib treated patients from the Dutch/German Hovon 65 GMMG-HD4 trial and the French IFM-2005/01 trial were used for this analysis. In both trials, the efficacy of Bortezomib as induction treatment prior to high-dose therapy is evaluated and PNP status was recorded. Samples were genotyped using a custom-built molecular inversion probe (MIP)-based single nucleotide polymorphism (SNP) chip containing 3404 SNPs (Bank on a Cure program; Van Ness et al., 2008). In total, 232 patients who did not develop PNP were compared to 210 PNP cases (grade 1, n=82; grade 2 n=86, grade 3, n=31, grade 4, n=11). Results The data were processed on the basis of the following criteria. First, SNPs genotyped in less than 75% of the samples were removed (n=155). This resulted in elimination of 59% of the data with unknown genotype while only 1% of the genotyped data were lost. The remaining 41% of the missing data were imputed using BIMBAM (Guan et al., PLoS Genet. 4:e1000279, 2008). As reference panels, the data sets of the BOAC chips from this study, 500 random samples from the Rotterdam ERGO study (Köttgen et al., Nat. Genet. 41, 712–717, 2009) and 60 phased CEU HAPMAP samples were used. Secondly, SNPs were excluded which did not show any genotype variance and which were not in Hardy Weinberg equilibrium. As a last step the data was adjusted for stratification using Eigenstrat (Price et al., Nat. Genet. 38: 904–909, 2006). By removing 21 SNPs and 14 samples the variance between the IFM and Hovon was reduced to an acceptable level (p = 0.011). The resulting combined IFM/Hovon dataset now contained 2764 SNP and 428 samples. The data set was divided in 6/7 (n=367) part as a learning set and 1/7 (n=61) as a validation set. Possibly informative SNPs were selected using information gain as a feature selection method (Cover et al., Elements of information theory. New York, John Wiley, 1991). 66 SNPs with an information gain in allele and genotype frequency were selected (p value < 0.05 after permutation test (n=10000)). Classifiers generated by Partial C4.5 decision tree (PART), support vector machine (SVM) and Random forest learned on this set reached a better than random performance. Sensitivity, specificity, positive predictive value and negative predictive value were respectively 55%, 70%, 60%, and 66% for the PART classifier. Conclusion Preliminary classifiers generated by this dataset suggest that building a classifier with clinically relevant performance may be within reach. To this end, we will report on the outcome of different combinations of existing classifier methods and feature selection methods. Van Ness, B, Ramos, C, Haznadar, M, Hoering, A,Haessler, J, Crowley, J, Jacobus, S, Oken, M, Rajkumar, V, Greipp, P, Barlogie, B, Durie, B, Katz, M, Atluri, G, Ganf, G, Gupta, R, Steinbach, M, Kumar, V, Mushlin, R, Johnson, D, and Morgan, G. (2008). Genomic Variation in Myeloma: Design, content, and initial application of the Bank On A Cure SNP Panel to analysis of survival. BMC Medicine. 6:26. Disclosures Hanifi-Moghaddam: Skyline Diagnostics: Employment.

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Abstract The pathogenesis of immune thrombocytopenia (ITP) is multifactorial, with both cellular and humoural immune dysfunction. The role of NK cells has not been well defined in ITP but in other diseases NK cells have a role in rejecting “foreign” eg transplanted organ or tumor, and also acting against self as occurs in autoimmunity. NK cell activity is orchestrated by the balance of activating vs. inhibitory signalling, in particular via the killer cell immunoglobulin-like receptor (KIR) family of receptors. Significant variation exists in KIR allelic subtype and copy number for the KIR between individuals, and associations have been made with certain haplotypes and a number of autoimmune disorders including rheumatoid arthritis, scleroderma and diabetes. Previous reports have demonstrated a reduction in natural killer (NK) cell number and function in ITP and expression of inhibitory KIR genes is increased in patients in remission vs. active ITP. Methods To explore whether a particular KIR haplotype might predispose to ITP, and also affect response to ITP treatment, we performed KIR genotyping using the Invitrogen SSP kit on 92 patients attending a haematology centre in New York and compared the results to data from 213 controls taken from the USA Eastern Database. Genomic DNA was typed for the inhibitory KIR genes KIR2DL1, KIR2DL2, KIR2DL5A (alleles 001 and 002), KIR2DL5B (alleles 002-004, 06, and 007), KIR3DL1, KIR3DL3; the activating KIR genes KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DS1; the framework genes KIR2DL3, KIR2DL4, KIR3DL2, KIR3DP1; and the pseudogene KIR2DP1. The patients with ITP had been or were receiving treatment with IVIG (n=64), corticosteroids (72) and rituximab (37). Bleeding symptoms were recorded. Response to treatment was defined as complete - platelet count increase to > 100 x 109/mL; partial - platelet count increase to > 50 x 109/mL; or no response. For the purpose of analysis, PRs and CRs were combined. A comprehensive database allowed a logistic regression, assessing both responses to treatments, platelet counts, neutrophil counts, CRP, lymphocyte subsets and bleeding symptoms. Results The expression of two inhibitory KIR genes, 2DL1 and 3DL1, was significantly lower in the patients with ITP as compared to controls (87% 2DL1 and 87% 3DL1 compared to 99% in controls - P < 0.02). Response to rituximab was strongly related to KIR haplotype expression. 2DL1 expression was higher among nonresponders to Rituximab (100% of non responders compared to 82% of responders), whereas 2DL3 expression was significantly lower (79% compared to 90%) (P < 0.05, Figure 1B). Separately, patients with the 2DS3 allele, an activatory KIR, were 5.5 times more likely to have experienced significant bleeding. Conclusions Although these findings are preliminary and require further investigation, these data suggest that increased cytotoxic autoimmunity due to reduced KIR inhibition may be associated with the development of ITP and possibly contribute importantly to the pathogenesis. Anti-CD20 targeting therapy directed at B cells was strongly influenced by 2 different KIRs (1 upregulated and one down-regulated) emphasizing the potential role of NK cells in elimination of tissue-based (nodal) B cells. Finally a more pronounced clinical phenotype with a markedly higher incidence of severe bleeding associated with an increased activatory KIR expression demonstrates the role of NK cells in bleeding presumably via their effects on either endothelial cells or platelet function. These exciting findings will be pursued for confirmation in a larger number of patients. Disclosures: Bussel: Amgen: Family owns stock Other, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Genzyme: Research Funding; GlaxoSmithKline: Family owns stock, Family owns stock Other, Membership on an entity’s Board of Directors or advisory committees, Research Funding; IgG of America: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Sysmex: Research Funding; Symphogen: Membership on an entity’s Board of Directors or advisory committees.

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Objective Ensuring the transmurality of the mitral isthmus lesion, a critical component of the cryomaze, entails mirror-image application of the cryoprobe both on endocardial and epicardial surfaces when carrying out ablation. Concerns of circumflex artery injury have been expressed during the epicardial application of the cryoprobe over the coronary sinus as the artery courses on the posterior surface of the sinus in the atrioventricular (AV) groove. The objective of this study was to analyze the incidence of significant injury to the circumflex artery and its impact on outcomes, if any, in those patients who have undergone cryomaze. Methods Between August 2004 and December 2009, a total of 223 patients underwent argon-based cryoablation (120-second application at −140°C). After Western Institutional Review Board approval, 20 consecutive patients with normal results of preoperative coronary angiograms (right dominance, 75%; left dominance, 15%; codominant circulation, 10%) and who were at least 6 months postablation were enrolled in this study. The mean ± SD age was 60.74 ± 14.99 years, 35% were men, and 50% belonged to New York Heart Association class III/IV. The mean ± SD atrial fibrillation duration was 23.83 ± 36.28 months (65% were paroxysmal). Ten percent (n = 2) underwent primary cryomaze, 40% (n =8) underwent cryomaze plus mitral valve repair, and 50% (n = 10) underwent two or more concomitant valvular procedures. Twelve patients underwent biatrial cryomaze, and eight underwent only left-sided cryomaze. All patients underwent a 24-hour Holter monitoring, electrocardiogram stress test, and a coronary computed tomographic angiogram, as per the protocol of this study. Results At discharge, 85% had normal sinus rhythm, whereas 15% of the patients were paced. On a mean ± SD follow-up at 32.57 ± 19.51 months, the Holter and/or pacemaker interrogation revealed AV synchrony in all patients—16 in sinus rhythm and 4 with heart block who converted to AV synchrony after subsequent pacemaker implantation. The stress test was available for 18 patients, and its results were negative in all of them. On the computed tomographic angiogram, 95% of the patients had a completely patent circumflex artery. Stenosis was noticed in only one patient (right dominant circulation), with a 30% to 40% tubular stenosis of the circumflex artery. However, this lesion corresponded to the P1 area of the mitral annulus and was significantly proximal on the circumflex to the P3 area, where the cryoprobe was applied during the cryomaze procedure. Conclusions Barring one case of partial circumflex stenosis, likely due to the ongoing normal progression of coronary artery disease, these data derived from a limited prospective trial suggest that epicardial application during the cryomaze procedure does not cause anatomic or physiological compromise of the circumflex artery. Nevertheless, laboratory and anecdotal evidence exist that conflict with this conclusion, and caution should be exercised when applying cryothermy in the vicinity of coronary arteries.

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Abstract Introduction: In systemic light chain (AL) amyloidosis free light chains produced by clonal plasma cells form amyloid fibrils that are deposited in tissues and organs resulting in organ dysfunction. Cardiac involvement by AL amyloidosis is frequent and the most critical prognostic factor. Prognostic evaluation in AL is based on cardiac biomarkers and patients with very high levels of both NTproBNP (≥8500 pg/ml) and cardiac Troponins (Mayo stage 3B) are at high-risk of early death and have a median survival of just 3-6 months in most series. The outcome of stage 3B patients has not improved despite the introduction of bortezomib-based therapies and there is an urgent need for new non-toxic treatments which can also lead to rapid and deep hematologic responses. Daratumumab, an IgGκ monoclonal antibody targeting CD38, has proved highly effective either alone or in combination with bortezomib, cyclophosphamide and dexamethasone and with good tolerability in AL amyloidosis patients. Methods: EMN22 is a phase 2, open-label, multicenter study planning to enroll 40 newly diagnosed patients with stage 3B AL amyloidosis from 5 sites in Greece, the Netherlands, Italy and France. Eligible patients should have high-sensitivity troponin T (hsTnT) &gt;54 pg/mL and NT-proBNP ≥8500 pg/mL. Primary treatment consists of daratumumab monotherapy, initially administered intravenously at 16 mg/mL, and since February 2020 administered subcutaneously at a fixed dose of 1800 mg; weekly during Cycles 1-2, every 2 weeks for Cycles 3-6 and every 4 weeks thereafter. Patients who do not achieve a hematologic VGPR or better by Cycle 4 may also receive at investigator's discretion weekly bortezomib and low dose dexamethasone. Treatment continues until disease progression according to major organ deterioration progression-free survival criteria, start of new therapy, or for a maximum of 2 years. The current analysis includes patients who started treatment at least 3 months prior to the cut-off date (16 June 2021). Results: Among 17 patients included in this analysis, 9 (53%) are still on treatment and 8 (47%) have discontinued, either due to an adverse event (n=5, 29%), or due to disease progression (n=3, 18%). Most patients were males (n=12, 71%) and median age was 65 years (range 45-84). Eastern Cooperative Oncology Group performance status was 1 for 5 (29%), 2 for 11 patients (65%), and 3 for one patient (6%). Eight (47%) patients had New York Heart Association (NYHA) class II symptoms, and 9 (53%) NYHA class IIIA. At screening, median NT-proBNP was 13,994 pg/mL (range 8,816-40,428), median hsTnT 119.1 pg/mL (range 59.8-692) and median difference of involved to uninvolved free light chains (dFLC) was 553 mg/L (range 49-2823). Apart from the heart, the median number of other organs involved was 1 (range 0-5), with nervous system (n=8, 47%) and kidneys (n=7, 41%) most commonly affected. The median number of daratumumab infusions was 13 and the median duration of therapy with daratumumab therapy was 3.7 months. Overall, 5 patients (29%) started additional treatment with bortezomib after completion of 3 cycles of daratumumab monotherapy. All 17 patients had at least one treatment-emergent adverse event. Eleven patients (65%) had a serious adverse event (SAE); 9 (53%) had at least one cardiac-related serious adverse event, and one SAE (fatigue) was related to bortezomib. Six patients (35%) suffered a fatal SAE: sepsis (n=1), sudden death (n=3), and cardiac failure (n=2). Most common grade 3 or 4 non-serious AEs were peripheral edema (n=4, 24%), dyspnea (n=3, 18%), and atrial fibrillation (n=2, 12%), and only one non-serious neutropenia grade 3 was related to daratumumab. The overall response rate was 71%, with 3 patients (18%) achieving CR, 6 (35%) VGPR, and 3 (18%) a PR, with a combined CR+VGPR rate of 53% (9/17). One-, two-, and three-month overall response rates were 65% (n=11), 71% (n=12), and 71% (n=12), and the median time to first response was 7 days while the median time to at least VGPR was 14 days. The 6-month and 12-month OS rate were 70% and 53% respectively (median OS has not been reached). Conclusions: In this prospective phase 2 study, in patients with high-risk AL amyloidosis (stage 3B), daratumumab monotherapy shows a favorable safety profile and induced very rapid and deep hematologic responses with a median time to first response of 7 days, with 53% of the patients achieving VGPR or better and a 6-month OS of 70%. Figure 1 Figure 1. Disclosures Kastritis: Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Genesis Pharma: Honoraria. Minnema: Jansen-Cilag: Consultancy; Kite/Gilead: Consultancy; Alnylam: Consultancy; Celgene: Other: Hospitality; BMS: Honoraria. Dimopoulos: Amgen: Honoraria; Beigene: Honoraria; BMS: Honoraria; Takeda: Honoraria; Janssen: Honoraria. Huart: Janssen: Honoraria. Leonidakis: Health Data Specialists: Current Employment. Manousou: Health Data Specialists: Current Employment. Sonneveld: Amgen: Consultancy, Honoraria, Research Funding; Celgene/BMS: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; SkylineDx: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Palladini: Pfizer: Honoraria; Siemens: Honoraria; Janssen Global Services: Honoraria, Other: advisory board fees.

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Abstract Abstract 2230 Introduction: Thrombopoietic agents (TPO-A) are widely used in adults for difficult ITP. However only 1 study has been published describing the use of a TPO mimetic (Nplate) in 22 children with ITP. This study is a post hoc analysis of 32 children (<21yr) who received clinical treatment (off study) with either Nplate or Promacta. Methods: All children described are from 2 centers:,Weill Cornell in New York (n=22, 9 on Nplate, 13 on Promacta) and Childrens Hospital Orange County (10, all on Nplate). All patients in this abstract were treated off study although some had previously participated in the AMGEN195 (Pediatric) followed by AMGEN 213 (long term maintenance) studies. Responses (taken from the published study) were defined as platelet count (plt ct) > 50k on 2 consecutive weeks, plt increase ≥ 20k on 2 consecutive weeks, and the percent of weeks at ≤ 50k independent of rescue therapy. Rescue therapy e.g. IVIG, steroids, plt transfusion, resulted in counts being considered “non-responder” for 2 full weeks after initiation of treatment. Bone marrows were evaluated for reticulin fibrosis (RF) using consensus grades 0–3. Several patients had more than one marrow during treatment; in these cases, the most recent on-therapy marrow was used. Results: The median age of patients on Nplate was 10 years of age (2–19) while for those on Promacta it was 16 years (5–19). Of the 32 patients treated with TPO-A, 24 responded with a plt ct ≥ 50k twice; 19/32 received Nplate and 15/19 responded; 13/32 received Promacta and 9/13 responded. Plt increases ≥ 20k were seen in 23 of 32 patients. The number of patients whose platelet count was ≥ 50k for at least 50 percent of visits was 20/32. The mean number of previous treatments for responders to Nplate was 3.2 while for Nplate non-responders it was 2.25. For Promacta, the mean for responders was 2.9 treatments and for non-responders 3 treatments. Younger patients did not seem to respond as well to treatment with either TPO-A (see table). Nplate patients received treatment for a mean of 19.2 weeks; for patients treated with Promacta it was 13.7 weeks. Baseline bone marrows were available in 17 patients of whom 6 had grade 1 reticulin fibrosis (RF). There were 10 children with marrows performed after the start of TPO-A: 2 with RF score=0, 7 with score=1+, and 1 with score=2+ Adverse events (AEs) other than bone marrow fibrosis and bleeding (lack of efficacy) were all 1–2+ and not related to TPO-A. In particular, no thrombosis or development of malignancy was seen. In conclusion, TPO-A were an effective treatment of chronic ITP in the 32 consecutive children retrospectively analyzed here from 2 centers. Younger children in this study seemed not to respond as well as older children, in contrast to small numbers of young children in published data who responded very well. No major changes were seen in the bone marrows but a formal baseline and on therapy study in children is needed to assess this issue. AEs were infrequent and tolerable. Additional studies with both Nplate and Promacta, either planned or in progress, are needed to clarify the response rates, AEs eg bone marrow fibrosis, and effects in subgroups of children. Disclosures: Bussel: Portola: Consultancy; Eisai: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cangene: Research Funding; Genzyme: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sysmex: Research Funding.

Abstract:

The proponents of this research developed their interests to look into every good points a community-based relapse prevention program being implemented by a particular local community among low-risk drug-users surrenderers. This included appreciating the design of the program and how it impacted the participants and the community of Barangay Salapan, San Juan City. All these being viewed from the underlying principles of restorative justice, in the pursuit of describing how the sanctity and dignity of human life is being restored using the five stages of appreciative inquiry as method of analysis. The rehabilitation program being implemented by the local community and supported by the local government provided a silver lining for the victims of the prohibited drugs. Initially, it helped redeem their lost personal sense of dignity, social respect and acceptance, and become a productive and significant individual members of their particular families and their beloved community. It was emphasized that the restoration of the sanctity and dignity of life demands greater openness, volunteerism, respect sincerity and discipline from each of the persons involved in the rehabilitation program. It was noted also that all the sectors of the local community should be united and unselfishly support the program regardless of political color or affiliation, religious background, economic interests and social biases, so that the sacredness and dignity of life which is very primal as a value will be constructively attained. References Brabant, K. V. (2015). Effective advising in state building and peacebuilding contexts-how: appreciative inquiry. Geneva,International Peacebuilding Advisory Team Byron, W. (1998). The building blocks of catholic social teaching. AmericaCaday, F. (2017). Causes of drug abuse among college students: The Philippine experience. Ifugao State University, Philippines. The International Journal of Social Sciences and Humanities InventionCoghlan, A., Preskill, H. and Catsambas, T.T. An overview of appreciative inquiry in evaluation. Retrieved from http://www.rismes.it/pdf/Preskill.pdf.Cooperrider, D. and Whitney, D. (2005). A positive revolution in change: Appreciative inquiry. Case Western Reserve University, The Taos InstituteDangerous Drugs Board, Office of the President. (2016). Oplan Sagip, Guidelines on voluntarily surrenderer of drug users and dependents and monitoring mechanism of barangay anti-drug abuse campaigns. Board Regulation No. 4. Office of the President. Republic of the Philippines.Gómez, M.P.M., Bracho, C.A. and Hernández, M. (2014). Appreciative inquiry, a constant in social work. Social Sciences, SciencePublihing Group. Spain John Paul II. (1987). Solicitudo Rei Socialis. Libreria Editrice Vaticana Helliwell, J. F. (2011). Institutions as enablers of wellbeing: TheSingapore prison case study. British Columbia. University of British Columbia. International Journal of WellbeingHimes, K. (2001). Responses to 101 questions on social catholic teaching manwah. Paulist Press St. Columban’s Mission Society. Mazo, G. N., (2017). Transformational rehabilitation: Communitybased intervention to end the drug menace. International Journal of Research - Granthaalayah, 5(12), 183-190. https://doi.org/10.5281/zenodo.1133854.Morales, S.,Corpus, R. and Oliver, R. (2013). Appreciative inquiry approach on environmental stewardship on the issues of the West Philippine Sea. Polytechnic University of the Philippines. National Youth Congress 2013 of the PhilippinesMikulich, A. (2012). Catholic social thought and restorative justice. Jesuit Social Research InstitutePloch, A. (2012). Why dignity matters: Dignity and the right (or not) to rehabilitation from international and national perspectives. New York University Journal of International Law and Politics. New York University School of Law.Pope Francis. (2015). Laudato si. Vatican City. Leberia Editrice Vaticana.Sakai, K.(2005). Research on the trends in drug abuse and effective measures for the treatment of the drug abusers in asian countries an analysis of innovative measures for the treatment of drug abusers. Tokyo, Japan. United Nations Asia and Far East Institute (UNAFEI)Sanchez, Z.M. and Nappo, S.A. (2008). Religious intervention and recovery from drug addiction. Rev Saúde Pública. Universidade Federal de São Paulo. São Paulo, SP, BrasilSandu, A. and Damian, S. (2012). Applying appreciative inquiry principles in the restorative justice field. Romania. Lumen Publishing House.Shuayb, M., Sharp, C., Judkins, M. and Hetherington M. (2009). Using appreciative inquiry in educational research: possibilities and limitations. Report. Slough: NFER.Yip, P., Cheung, S.L., Tsang, S.,Tse, S., Ling, W.O., Laidler, K., Wong, P., Law, and F., Wong, L.(2011). A study on drug abuse among youths and family relationship. University of HongKong

Abstract:

BackgroundInterleukin 8 (IL-8) is a C-X-C chemokine that exerts protumorigenic effects in the tumor microenvironment, including recruiting immunosuppressive PMN-MDSCs and promoting angiogenesis.1–3 Elevated serum IL-8 (sIL-8) is a negative prognostic indicator in patients with solid tumors and may have predictive value in patients treated with immunotherapies.2 4 5 BMS-986253, a fully human-sequence IgG1κ anti–IL-8 monoclonal antibody, binds IL-8 and prevents signaling through CXCR1/CXCR2 and has been shown to be safe in patients with advanced cancers.3 We present initial results of BMS-986253 + NIVO from a phase 1/2a trial in patients with advanced cancers who had detectable sIL-8 levels, the majority of whom had progressed on/after prior anti–PD-(L)1 (NCT03400332).MethodsDuring safety evaluation/dose exploration, patients with advanced metastatic solid tumors (melanoma, NSCLC, SCCHN, RCC, or UCC) and detectable sIL-8 (>10 pg/mL at screening) received BMS-986253 600 (n=16), 1200 (n=15), or 2400 mg (n=18) Q4W, or 1200 (n=12) or 2400 mg (n=59) Q2W, + NIVO 480 mg intravenously Q4W. Safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity were evaluated (investigator-assessed, RECIST v1.1).ResultsAs of March 20, 2020, 120 patients (median age, 63 years [range, 35–87 years]) received BMS-986253 + NIVO; 97% of patients received prior anti–PD-(L)1 therapy, and 25% received prior anti–CTLA-4 therapy. BMS-986253 + NIVO was well tolerated with no dose-limiting toxicities observed. Most TRAEs were grade 1–2. The most common (≥5% of patients) TRAEs (any grade; grade 3–4) were fatigue (9%; 1%), nausea (7%; 0%), rash/rash maculopapular (6%; 0%), pruritus (5%; 0%), and decreased appetite (5%; 0%). Grade 3–4 serious TRAEs were reported in 2 patients (infusion-related reaction, BMS-986253 2400 mg Q2W + NIVO; AST/ALT increased, BMS-986253 1200 mg Q4W + NIVO). BMS-986253 exposure increased dose proportionally and was not altered with NIVO. BMS-986253 resulted in dose-dependent reductions in free sIL-8 levels, with tumor IL-8 suppression detected in most patients evaluated; additional pharmacodynamic endpoints will be presented. Partial responses were observed in multiple tumor types, including 5 of 28 patients with melanoma who had progressed on/after prior anti–PD-(L)1; 4 of the 5 patients were also previously treated with anti–CTLA-4.ConclusionsBMS-986253 + NIVO demonstrated a tolerable safety profile with dose-proportional pharmacokinetics and robust sIL-8 suppression. Preliminary antitumor activity was observed across a range of doses/regimens in this biomarker-enriched, anti–PD-(L)1–experienced, heterogeneous patient population with advanced cancers. These findings support further evaluation of BMS-986253 in select advanced tumors.AcknowledgementsThe authors acknowledge Dr Charles Drake while at Columbia University Medical Center, New York, NY, USA, for his contributions to the study.Trial RegistrationNCT03400332Ethics ApprovalThis study was approved by the WCG Independent Review Board, approval number 20172711.ReferencesDavid JM, Dominguez C, Hamilton DH, et al. The IL-8/IL-8R axis: a double agent in tumor immune resistance. Vaccines (Basel) 2016;4:22.Schalper KA, Carleton M, Zhou M, et al. Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors. Nat Med. 2020;26:688–692.Bilusic M, Heery CR, Collin JM, et al. Phase I trial of HuMax-IL-8 (BMS-986253), an anti–IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors. J Immunother Cancer 2019;7:240.Yuen KC, Liu L-F, Gupta V, et al. High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade. Nat Med 2020;26:683–698.Sanmamed MF, Perez-Gracia JL, Schalper KA, et al. Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti–PD-1 treatment in melanoma and non-small-cell lung cancer patients. Ann Oncol 2017;28:1988–1995.

Abstract:

In 1918 into a peasant family, was born A. A. Shalimov, who, after finishing school and technical school he enrolled in the Kuban medical Institute (1936-1941), he worked as a doctor in hospitals near Krasnodar, in Chita oblast (1941), in the cities of Bryansk and the eagle; chief surgeon of the Orel region (1949). In 1951, A. A. Shalimov returned to Bryansk, he defended his dissertation and received the title of Honored doctor of the RSFSR. Later A. A. Shalimov moved to Kharkov, he defended his doctoral dissertation (1957) and was appointed head of the Department of thoracic surgery and anesthesiology of the Ukrainian Institute of advanced training of physicians (1959), Director of the Kharkiv Institute of General and urgent surgery (1965), head of the Department of thoracoabdominal surgery of the Kiev Institute of improvement of doctors, as head of the surgical Department, the Director of Kiev research Institute of Hematology and blood transfusion (1970) and Kyiv Sri of clinical and experimental surgery (1971), chief surgeon of the Ministry of health of Ukraine (1980). A. Shalimov was elected a corresponding member of the Academy of Sciences of Ukraine (1969), academician of the National Academy of Sciences of Ukraine (1978). A. A. Shalimova awarded the title Hero of Socialist Labor of the USSR (1982), Hero of Ukraine with the order of Powers (2005). Alexander Shalimov 870 author of scientific papers, including 35 monographs, 112 inventions, he has trained 50 doctors and nearly 100 candidates of medical Sciences. A. A. Shalimov was awarded two orders of Lenin and red banner of Labor, order of the October Revolution, the order of the Ukrainian State (2005) and "For merits" of three degrees, medals and orders and medals of foreign States. Oleksandr Shalimov was a member of the Board of the Association of surgeons im. N. And. Pirogov, the International Association of surgeons, the all-Union scientific society of surgeons, gastroenterologists and cardiologists, Chairman of the Ukrainian Republican scientific society of surgeons, full member of the new York Academy of Sciences, editor-in-chief of the journal "Clinical surgery", Deputy of the Supreme Soviet of the Ukrainian SSR 8-10 convocations. The international chamber of the American biographical Institute, he was elected "Man of the year – 1997", awarded diploma of the International biographical centre of Cambridge University for achievements in medicine of the twentieth century. Died Alexander Shalimov February 28, 2006.

Abstract:

ABSTRAKPenelitian bertujuan untuk mengetahui bagaimana pengaruh dari variabel pangkat dan golongan, jenis kelamin, jumlah tanggungan keluarga, lama pendidikan, frekuensi pengajian, serta pendapatan lain selain gaji sebagai determinan terhadap pembayaran zakat profesi di kalangan Pegawai Negeri Sipil (PNS) di Kota Banjarmasin. Penelitian ini menggunakan pendekatan kuantitatif dengan teknik analisis regresi logistik untuk menganalisis data. Penelitian ini melibatkan data primer atas 126 responden yang diambil menggunakan teknik convenience sampling dengan kriteria PNS Golongan III dan IV di mana golongan tersebut memiliki gaji yang telah memenuhi nisab zakat profesi. Diperoleh hasil bahwa variabel pangkat dan golongan, jenis kelamin, dan pendapatan lain selain gaji masing-masing berpengaruh negatif signifikan terhadap pembayaran zakat profesi sedangkan variabel jumlah tanggungan keluarga, lama pendidikan, dan frekuensi pengajian masing-masing ditemukan memiliki pengaruh positif signifikan terhadap pembayaran zakat profesi.Kata Kunci: pembayaran zakat profesi, pangkat dan golongan, jenis kelamin, jumlah tanggungan keluarga, lama pendidikan, frekuensi pengajian, pendapatan lain selain gaji ABSTRACTThis study aims to determine how the influence from titles and ranks, gender, number of family dependents, education history, frequency of communal Qur’an reading, and other forms of income apart from the actual salary itself as a determinant of professional zakat payments paid by State Civil Servants (PNS) in Banjarmasin City. This study uses a quantitative approach with logistic regression analysis techniques to analyze data. This study involved primary data on 126 respondents who were taken using a convenience sampling technique with the criteria of PNS Group III and IV where the group had a salary that met the professional zakat nisab. The results show that the variables of titles and ranks, gender, and other forms of income have a significant negative effect on the payment of zakat on profession, while the variables of the number of family dependents, education history, and the frequency of communal Qur’an reading are found to have a significant positive effect on zakat on profession payments.Keywords: zakat on profession, titles and ranks, gender, numbers of family dependents, education history, the frequency of communal Qur’an reading, other forms of income apart from the actual salary itself. DAFTAR PUSTAKAAbdullah, M., & Sapiei, N. S. (2018). Do religiosity, gender and educational background influence zakat compliance? The case of Malaysia. International Journal of Social Economics, 45(8), 1250–1264. https://doi.org/10.1108/IJSE-03-2017-0091Ahmad, S., Nor, N. G. M., & Daud, Z. (2011). Tax-based modeling of zakat compliance. Jurnal Ekonomi Malaysia, 45, 101-108.Al Qardhawi, Y. (2011). Fiqh Al Zakah. Beirut: Muassasah al-RisalahAndam, A. C., & Osman, A. Z. (2019). Determinants of intention to give zakat on employment income: Experience from Marawi City, Philippines. Journal of Islamic Accounting and Business Research, 10(4), 528–545. https://doi.org/10.1108/JIABR-08-2016-0097Anshori, M., & Iswati, S. (2009). Metodologi penelitian kuantitatif. Surabaya: Airlangga University Press (AUP).Arsyianti, L. D., Kassim, S., & Adewale, A. (2017). Socio-demographic and economic factors affecting regular charity-giving: A case of low-income households in Indonesia. International Journal of Zakat, 2(1), 21-29. https://doi.org/https://doi.org/10.37706/ijaz.v2i1.12Azen, R., & Walker, C.M. (2010). Categorical data analysis for the behavioral and social sciences. London: Routledge. https://doi.org/10.4324/9780203843611Azman, F. M. N., & Bidin, Z. (2015). Zakat compliance intention behavior on saving. International Journal of Business and Social Research, 5(1), 118–128.Badan Kepegawaian Daerah Provinsi Kalimantan Selatan. (2020). Jumlah PNS berdasarkan jenis kelamin. Diakses dari https://data.kalselprov.go.id/?r=JmlPns/index BAZNAS. (2021). Laporan kinerja badan amil zakat nasional tahun 2020. Jakarta: BAZNAS.BAZNAS Kota Banjarmasin. (2020). Infografik penerimaan BAZNAS Kota Banjarmasin 2019. Diakses dari https://baznas.banjarmasinkota.go.id/detailpost/infografik-penerimaan-baznas-kota-banjarmasin-2019Direktorat Jenderal Pajak. (2020). Penghasilan Tidak Kena Pajak. Diakes dari https://www.pajak.go.id/id/penghasilan-tidak-kena-pajakDinas Komunikasi dan Informatika Provinsi Kalimantan Selatan. (2020). Produktivitas Perkebunan Karet Menurun. Diakses dari https://diskominfomc.kalselprov.go.id/2020/06/09/produktivitas-perkebunan-karet-menurunDSN MUI. (2003). Fatwa MUI nomor 3 tahun 2003 tentang zakat penghasilan. Jakarta: DSN MUI.Eagly, A.H. (2013). Sex differences in social behavior: A social-role interpretation. New York: Psychology Press. https://doi.org/10.4324/9780203781906Hilbe, J.M. (2015). Practical guide to logistic regression. New York: Chapman and Hall/CRC. https://doi.org/10.1201/b18678Top of FormHosmer, D. W., Lemeshow, S., & Sturdivant, R. X. (2013). Applied logistic regression. Hoboken (N.J.): Wiley.Kastlunger, B., Dressler, S. G., Kirchler, E., Mittone, L., & Voracek, M. (2010). Sex differences in tax compliance: Differentiating between demographic sex, gender-role orientation, and prenatal masculinization (2D:4D). Journal of Economic Psychology, 31 (4), 542-552. https://doi.org/10.1016/j.joep.2010.03.015Bottom of FormLaLumia, S. (2008). The effects of joint taxation of married couples on labor supply and non-wage income. Journal of Public Economics, 92(7), 1698–1719. https://doi.org/10.1016/j.jpubeco.2008.01.009Lind, D. A., Marchal, W. G., & Wathen, S. A. (2011). Statistical techniques in business & economics. Boston: McGraw-Hill/Irwin.Medias, F. (2018). Ekonomi mikro Islam. Magelang: UNIMMA Press.Pemerintah RI. (2017). Peraturan Pemerintah nomor 11 tahun 2017 tentang manajemen pegawai negeri sipil.Pusat Kajian Strategis Badan Amil Zakat Nasional. (2019). Outlook Zakat Indonesia 2020. Jakarta: Puskas BAZNAS.Putri, K. M., Fahmi, M. Y., & Handayani, L. (2019). Factors affecting community trust to pay zakay at the national board of zakat (BAZNAS) of South Kalimantan Province. International Conference of Zakat 2019 Proceedings.Pribadi, Y., Saat, N., & Burhani, A. N. (2020). The new santri: Challenges to traditional religious authority in Indonesia. Singapore: ISEAS - Yusof Ishak Institute.Rahmani, & Yanti. (2018). Penyelenggara syariah ajak PNS tunaikan zakat profesi. Diakses dari https://kalsel.kemenag.go.id/berita/515581/Penyelenggara-Syariah-Ajak-PNS-Tunaikan-Zakat-ProfesiSobana, D. H., Husaeni, U. A., Jamil, I., & Saepudin, D. (2016). The variables that affect compliance of muslim merchants for zakat maal in the district of Cianjur. International Journal of Zakat, 1(1), 78-87. https://doi.org/10.37706/ijaz.v1i1.8Sohag, K., Mahmud, K. T., Alam, MD. F. & Samargandi, N. (2015). Can zakat system alleviate rural poverty in Bangladesh? A propensity score matching approach. Journal of Poverty, 19(3), 261-277. DOI: 10.1080/10875549.2014.999974Undang-Undang Nomor 5 Tahun 2014 tentang Aparatur Sipil Negara.Undang-Undang Nomor 20 Tahun 2003 tentang Sistem Pendidikan Nasional.Wahid, H., Ahmad, S., & Noor, M. A. M. (2007). Kesedaran membayar zakat pendapatan di Malaysia. Islamiyyat, 29, 53–70.Yang, N., Chen, C. C., Choi, J., & Zou, Y. (2000). Sources of work-family conflict: A sino-U.S. Comparison of the effects of work and family demands. Academy of Management Journal, 43(1), 113–123. https://doi.org/10.2307/1556390