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1

YEŞİLTAŞ, Erkan, and Gülşah ŞEKER. "A BIBLIOMETRIC ANALYSIS OF EDUCATIONAL RESEARCHES ABOUT SOCIAL MEDIA." Zeitschrift für die Welt der Türken / Journal of World of Turks 13, no. 2 (August 15, 2021): 169–89. http://dx.doi.org/10.46291/zfwt/130209.

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The purpose of this study is to examine the educational researches published about social media from a bibliometric perspective. The study used the case study design, which is a qualitative research design. The keyword “Social Media” was searched in research topics in the Web of Science (WoS) database. “Document title”, “abstract” and “keyword” were chosen as search criteria. Studies published between 2007 and 2021 were included in the analysis. The bibliometric data of 3861 academic studies contained in WoS educational researchs category constitute the data set of the study. The study found that educational researches on social media especially as of 2008 and this trend continued in the following years. The most frequent languages of publication in the field of social media in education are English, Spanish and Portuguese, respectively, and the most frequent types of academic research are articles, papers, and book chapters. Michigan State University, Florida State University System and University of North Carolina are the affiliations with the highest number of publishing researchers. In Turkey, Anadolu University is the affiliation with the biggest number of authors publishing research about social media in education. The USA, England and Australia are the three countries where studies about social media in education are published the most, respectively. The number of citations of academic studies published after 2010 is increasing every passing year. The most frequently used keywords in academic studies on media literacy in education are the concepts of “social media”, “higher education”, “Facebook”, “Twitter”, “e-learning”, “social networks” and "Web 2.0". Keywords: Social media, education, bibliometric analysis, Web of Science
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Upadhyay, Anima, and M. Chandrakala. "C orrosion Studies on Tinned Iron Plates From Infant Food Cans." Material Science Research India 13, no. 2 (November 26, 2016): 106–9. http://dx.doi.org/10.13005/msri/130207.

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The corrosion on smooth tinned iron material has been studied in different media. Solutions of sulphuric acid, hydrochloric acid, acetic acid and salt solutions of ammonium chloride and sodium chloride were prepared to investigate the corrosion on the metal plates. The plates was immersed in the solutions for a period of time same for all the solutions in order to determine the most aggressive environment. Weight loss technique was adopted to study the rate of corrosion. The result reveals that the material got corroded in this order sulphuric acid > hydrochloric acid > acetic acid > ammonium chloride > sodium chloride. It was therefore concluded that the rate of corrosion was high in strong acids compared to the weak acids and salts.
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Nair, Satheesh Balakrishnan, Rayaz Malik, and Rajdeep S. Khattar. "Carotid intima–media thickness: ultrasound measurement, prognostic value and role in clinical practice." Postgraduate Medical Journal 88, no. 1046 (July 3, 2012): 694–99. http://dx.doi.org/10.1136/postgradmedj-2011-130214.

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Hilhorst, Marc, Kristien Winckers, Benjamin Wilde, René van Oerle, Hugo ten Cate, and Jan Willem Cohen Tervaert. "Patients with Antineutrophil Cytoplasmic Antibodies Associated Vasculitis in Remission Are Hypercoagulable." Journal of Rheumatology 40, no. 12 (October 15, 2013): 2042–46. http://dx.doi.org/10.3899/jrheum.130200.

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Objectives.The risk of venous thromboembolism (VTE) is increased in patients with antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides (AAV) as compared to healthy subjects. The mechanisms underlying this increased occurrence of VTE are not completely understood. We hypothesize that AAV patients in remission are more procoagulant than healthy controls.Methods.Patients with AAV in remission and no VTE for the last 6 months were included. Patients with severe renal impairment (serum creatinine > 250 μmol/l) were excluded. Age and sex matched healthy controls were included. The endogenous thrombin potential (ETP) was determined together with hemostatic variables: fibrinogen, D-dimers, factor VIII (FVIII), tissue factor pathway inhibitor (TFPI), protein C, and free protein S.Results.Thirty-one patients were included. In 27 patients not taking anticoagulants, ETP was measured and found to be elevated: 137.1% as compared to a median of 90.0% for healthy controls (p < 0.01). Fibrinogen and D-dimer levels were not elevated in patients (median 3.5 g/l and 279 μg/l, respectively). FVIII and TFPI levels were also significantly increased in patients as compared to healthy controls (159% vs 137%; 122.5% vs 101%, respectively), whereas protein C and free protein S levels were not elevated (126.5% vs 118.6% and 124.6% vs 118.3%, respectively).Conclusion.Patients with AAV in remission are more procoagulant than healthy controls, as indicated by an increased ETP. The increased FVIII level measured in these patients suggests persistence of endothelial activation and/or dysfunction. This endothelial dysfunction may cause a continuous low-grade procoagulant state.
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Depue, Jacob B., Brian G. Southwell, Anne E. Betzner, and Barbara M. Walsh. "Encoded Exposure to Tobacco Use in Social Media Predicts Subsequent Smoking Behavior." American Journal of Health Promotion 29, no. 4 (March 2015): 259–61. http://dx.doi.org/10.4278/ajhp.130214-arb-69.

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MENTEŞ, Osman, and Mustafa TALAS. "THE INTERNATIONAL HUMANITARIAN AID DELIVERED FOR AFGHANISTAN ON PRIMARY AND SECONDARY EDUCATION AFTER 2001." Zeitschrift für die Welt der Türken / Journal of World of Turks 13, no. 1 (April 15, 2021): 61–73. http://dx.doi.org/10.46291/zfwt/130104.

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This study aims to scrutinize historical development, current situation, and main problems of the Afghanistan Education System and the political, social, and economic dimensions of international aid to the country that are made to solve these problems. Following a brief analysis of the historical progress of the Afghanistan education system; the current state of the system and primary, secondary, and community based educational activities in the country in the period ensuing the 2001 US intervention and lasting until 2020 and the place of the foreign aid in the education system and its effects on this system are explained. The resources of this study encompass books; articles; media broadcasts; direct observations in the field and the information obtained through interviews with students, teachers, bureaucrats, politicians, relief workers, and project beneficiaries; and websites, reports and periodical publications of the United Nations, international organizations, state-run institutions of the donor countries, Afghanistan Ministry of Education and Ministry of Economy, which carries out non-governmental organizations affairs in Afghanistan. Through the analysis of the data gathered from accessible sources, it has been revealed that the decades' lasting wars, internal conflicts, poverty, and disasters have destroyed the Afghan Education Sector and unfortunately, no permanent and sustainable solutions could be developed yet despite the significant gains accomplished thanks to intense efforts for nearly two decades. Lacking enough resources and means to solve these problems, Afghanistan remains dependent on aid. Hence, international aid should continue in the field of education as in the other fields more systematically and comprehensively for Afghanistan which is regrettably does not seem to be able to disentangle from this deadlock in the short or medium run and geographical imbalances in the distribution of both public services and international aid should be eliminated. Keywords: Afghanistan, education system, international aid, humanitarian aid, United Nations, Non-governmental Organization (NGO)
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Thrasher, James F., Sei-Hill Kim, India Rose, Ashley Navarro, Mary-Kathryn Craft, Kelly J. Davis, and Sharon Biggers. "Print Media Coverage around Failed and Successful Tobacco Tax Initiatives: The South Carolina Experience." American Journal of Health Promotion 29, no. 1 (September 2014): 29–36. http://dx.doi.org/10.4278/ajhp.130104-quan-11.

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Cicero, Kara, Mark L. Heaney, Todd L. Rosenblat, Nicole Lamanna, Joseph G. Jurcic, Mark G. Frattini, and Daniel J. Lee. "Combination Thioguanine and Decitabine Is Highly Active in Patients with Advanced Myeloid Malignancies: A Single Institution Experience." Blood 134, Supplement_1 (November 13, 2019): 3899. http://dx.doi.org/10.1182/blood-2019-130203.

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BACKGROUND: Despite recent advances, outcomes remain poor in secondary and relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We previously demonstrated that combination thioguanine (6TG) and decitabine restores therapeutic efficacy in vitro in R/R AML (O'Dwyer K et al. Blood 2010;114:2657). Based on these data, we completed a Phase I dose-escalation study of 6TG with decitabine in advanced myeloid malignancies with an overall response rate (ORR) of 67% and median progression-free survival (PFS) of 42 weeks in responding patients (Lee DJ, et al. Blood 2016;128:2816). Moreover, 5 of the 6 study participants who had previously received a hypomethylating agent (HMA) responded, suggesting that 6TG in combination with decitabine can overcome HMA resistance. Because of these results, a cohort of patients with high-risk and R/R AML and MDS were treated with combination 6TG and decitabine at Columbia University Irving Medical Center, and we now report our clinical experience with this regimen. METHODS: A retrospective chart review was performed of all adult patients at our institution with advanced myeloid malignancies who had received at least one cycle of 6TG and decitabine between 2013-2017. The treatment regimen utilized the maximum tolerated dose of 6TG identified in the phase I trial. Up to 2 cycles of induction with 6TG 80 mg/m2/day PO in 2 divided doses was given on Days 1-12. Decitabine 20 mg/m2 IV was given on Days 3-12. Following this, maintenance cycles consisted of 6TG on Days 1-7 and decitabine on Days 3-7 at the same doses. Treatment was continued until the time of hematopoietic stem cell transplant (HSCT), disease progression, or toxicity. The primary objective of this retrospective analysis was to determine the ORR. Secondary objectives were to evaluate PFS and overall survival (OS) in this population. RESULTS: Forty-two patients were identified, 55% of whom were female, with a median age of 68 years (range, 23-83 years). Thirty-three percent of the patients had secondary AML; 62% had R/R AML; 2% had R/R MDS; and 2% had chronic myelomonocytic leukemia. By ELN genetic risk stratification, 38% were adverse-risk, 43% were intermediate, and 17% were favorable, while 2% were unknown. However, 36 (86%) patients failed prior therapy, suggesting that nearly all of the treated patients were poor-risk. Nineteen (45%) patients had received prior HMA therapy, and 6 (14%) had undergone previous HSCT. Patients received a median of 2 cycles of therapy (range, 1-10). Five (12%) patients achieved complete remission (CR), 7 (16%) obtained a CR with incomplete count recovery (CRi/p), and 2 (5%) had morphologic leukemia-free state (MLFS), for an ORR of 33% (CR+CRi/p+MLFS). One notable patient who achieved CR was a 73-year-old with secondary AML, complex cytogenetics, and a TP53 mutation who subsequently went on to HSCT. Another 5 (36%) responders had complex karyotypes or poor-risk genetics. Ten of the 14 responders (71%) failed prior therapy. Of the 19 who had received prior HMA therapy, 6 (32%) responded. Six of 14 (43%) responders proceeded to HSCT. Two additional patients had significant blast reduction and underwent HSCT. Responses and maximum blast reduction were obtained after two cycles of therapy. For the responders, the median PFS was 38 weeks (range, 11-not reached), while the median OS was 43 weeks (range, 11-not reached). CONCLUSIONS: Combined 6TG and decitabine is a highly active regimen in advanced myeloid malignancies, with an ORR of 33% in this cohort, and median PFS and OS of 38 and 43 weeks, respectively, in responding patients. This compares favorably to the expected response rate of 10-20% with decitabine monotherapy in this poor-risk population consisting of mostly secondary and R/R AML. These data also confirm our prior phase I study findings that the addition of 6TG to decitabine can overcome prior HMA resistance, with 32% of those who had previously failed HMA therapy responding. This combination remains a viable therapeutic option for elderly and unfit patients with high-risk and R/R AML who cannot tolerate intensive chemotherapy. Disclosures Heaney: BMS: Research Funding; Partner Therapeutics: Consultancy; Roche: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Celgene: Research Funding; Novartis: Consultancy; AbbVie: Consultancy; Deciphera: Research Funding; Constellation: Research Funding; Blueprint: Research Funding; CTI: Research Funding. Lamanna:Ming: Research Funding; Celgene: Consultancy; Oncternal: Research Funding; TG Therapeutics: Research Funding; Infinity/ Verastem: Research Funding. Jurcic:Syros Pharmaceuticals: Research Funding; Astellas: Research Funding; AbbVie Inc: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Incyte: Consultancy; Kura Oncology: Research Funding; Forma Therapeutics: Research Funding; Genentech: Research Funding; Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Frattini:Celgene: Employment, Equity Ownership; Lin Bioscience: Consultancy. Lee:Abbvie: Research Funding; Roche: Research Funding; Tolero: Research Funding; Forty Seven, Inc.: Research Funding; Bayer: Research Funding.
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Heidenreich, Tobias, Fabienne Lind, Jakob-Moritz Eberl, and Hajo G. Boomgaarden. "Media Framing Dynamics of the ‘European Refugee Crisis’: A Comparative Topic Modelling Approach." Journal of Refugee Studies 32, Special_Issue_1 (December 1, 2019): i172—i182. http://dx.doi.org/10.1093/jrs/fez025.

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Abstract The complexity and duration of the so-called ‘European refugee crisis’ created a climate of uncertainty, which left ample room for mass media to shape citizens’ understanding of what the arrival of these refugees meant for their respective country. This study analyses the national media discourses in Hungary, Germany, Sweden, the United Kingdom and Spain for this time period. Applying Latent Dirichlet Allocation topic modelling in five languages and based on N = 130,042 articles from 24 news outlets, we reveal country-specific media frames to track the overall course of the refugee debate and to uncover dynamics and shifts in discourses. While results show similarities across countries, due to media coverage responding to real-world developments, there are differences in media framing as well. Possible sources of these differences such as countries’ geographic location or status as receiving country are discussed.
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Paul, Shilpa, Koji Sasaki, J. Michael Savoy, Adam Dipippo, Nadya Jammal, Kayleigh Marx, Tapan M. Kadia, et al. "Title: 12 Versus 8 Prophylactic Intrathecal (IT) Chemotherapy Administration Decrease Incidence of Central Nervous System (CNS) Relapse in Patients (pts) with Newly Diagnosed Philadelphia (Ph)-Positive Acute Lymphocytic Leukemia (ALL)." Blood 134, Supplement_1 (November 13, 2019): 3810. http://dx.doi.org/10.1182/blood-2019-130284.

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Introduction: The addition of tyrosine kinase inhibitors to hyperfractionated cyclophosphamide, dexamethasone, vincristine, and doxorubicin alternating with high-dose methotrexate and cytarabine (HCVAD) for the treatment of Ph-positive ALL has significantly improved outcomes. However, with the increased median survival, an increased incidence of CNS relapses were documented over time, thus suggesting an increased risk among pts with Ph-positive disease (Ravandi et al, Cancer 2015).In order to reduce this incidence, treatment protocols for Ph-positive ALL were amended in 2012 to increase prophylactic IT chemotherapy from 8 to 12 at our institution. The aim of this study is to compare the incidence of CNS relapses in pts with Ph-positive ALL treated with 8 versus 12 ITs. Methods: We conducted a retrospective chart review of 156 pts with newly diagnosed Ph-positive ALL treated with Rituximab (R)± HCVAD plus imatinib (n=35), dasatinib (n=68), or ponatinib (n=53) between July 2001 and January 2019. Pts with CNS disease at initial diagnosis were excluded. Complete molecular response (CMR) at 3 months was defined as absence of a quantifiable BCR-ABL1 transcript. CNS relapse was identified by detection of blasts or rare atypical cells in the cerebrospinal fluid (CSF) in at least 2 successive evaluations and/or findings of leptomeningeal disease on imaging. Landmark analysis was performed at 6 months at the approximate time of completion of both systemic and IT therapy. Poor risk cytogenetic abnormality was defined as the presence of +der(22)t(9;22) and/or −9/9p in the absence of high hyperdiploidy (51‐65 chromosomes). CNS relapse-free survival (RFS) was defined from the start of therapy to the time of CNS relapse. Patients who died or relapsed in bone marrow were censored at the time of death and systemic relapse, respectively. Survival was assessed with and without the censoring of allogeneic stem cell transplantation (ASCT). Results: Pt characteristics are summarized in Figure A. One hundred and twelve pts (72%) received a median of 8 ITs (range, 2-8) and 44 pts (28%) received a median of 12 (range, 9-15). There were no statistically significant differences between groups in regards to baseline characteristics with the exception that more patients in the > 8 ITs cohort received ponatinib (66% vs 21%) and thus achieved a higher rate of 3-month CMR (70% vs 52%; p=0.04). CNS relapses were identified in 11 pts overall (7%, 4 treated with imatinib and 7 with dasatinib) and all of them received 8 or less prophylactic ITs (IT ≤8, 10% vs IT >8, 0%; p=0.023). The median follow-up of the entire population was 81 months, and 97 and 43 months for pts who received ≤8 and >8 ITs, respectively. The 3 and 6-year CNS RFS was 89% and 88% in pts with ≤8 ITs and 100% in pts with >8 Its, respectively (overall P=0.041; 3-yr CNS RFS P=0.049; 6-yr CNS RFS P=0.045) (Figure B). The outcomes remained statistically significant even after censoring for ASCT (P=0.048) (Figure C). In a multivariate analysis and after adjusting for the follow-up time, a median of 12 prophylactic IT chemotherapies was a prognostic factor significantly associated with a decrease rate of CNS relapses (P=0.03; HR=0.64 95%, CI: 0.43-0.96) (Figure D). Conclusion: In pts with newly diagnosed Ph-positive ALL, incorporation of 12 prophylactic IT chemotherapy in addition to systemic therapy is a very effective strategy to reduce the long-term incidence of CNS relapses. Figure Disclosures Paul: Pfizer: Consultancy; Agios: Consultancy. Sasaki:Otsuka: Honoraria; Pfizer: Consultancy. Kadia:BMS: Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioline RX: Research Funding; Celgene: Research Funding; Pfizer: 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: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding. Garcia-Manero:Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Amphivena: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Ravandi:Macrogenix: Consultancy, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Xencor: Consultancy, Research Funding; Menarini Ricerche: Research Funding; Selvita: Research Funding; Cyclacel LTD: Research Funding. Kantarjian:BMS: Research Funding; Novartis: Research Funding; AbbVie: Honoraria, Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ariad: Research Funding; Daiichi-Sankyo: Research Funding; Takeda: Honoraria; Pfizer: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Astex: Research Funding; Jazz Pharma: Research Funding; Cyclacel: Research Funding; Immunogen: Research Funding; Amgen: Honoraria, Research Funding. Jabbour:AbbVie: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Cyclacel LTD: Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding.
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11

Kern, Wolfgang, Manja Meggendorfer, Claudia Haferlach, and Torsten Haferlach. "Complemental Prognostic Impact of Flow Cytometric and Molecular Quantification of Minimal/Measurable Residual Disease in Acute Myeloid Leukemia." Blood 134, Supplement_1 (November 13, 2019): 4657. http://dx.doi.org/10.1182/blood-2019-130304.

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Background: Minimal/measurable residual disease (MRD) correlates with outcome in acute myeloid leukemia (AML). Flow cytometry (FC) and quantitative PCR (QPCR) both are recommended by ELN (Schuurhuis et al., Blood 2018) and NCCN guidelines. Comparative MRD data on FC and QPCR are limited. Aim: To assess the relative contribution of FC and QPCR in generating prognostically relevant MRD data in AML. Methods: 936 bone marrow samples of 305 AML patients in cytomorphologic CR were analyzed for MRD by both FC and QPCR (mainly fusion transcripts and NPM1 mutations) in parallel applying ELN guidelines. Patients´ages at diagnosis ranged from 20 to 89 years (median 57), sex ratio (f/m) was 155/150. As anticipated due to selection for MRD assessment risk according to ELN was favorable in 191 (63%), intermediate in 92 (30%) and poor in 18 (6%). Accordingly, 5 year event-free survival (EFS) was 68% and 5 year overall survival (OS) 68% at 2.4 years median follow-up. Samples for MRD assessment were drawn between 7 days and 8.5 years after diagnosis (median 5.8 months). MRD samples were categorized into 5 intervals: I1, <2 months after diagnosis, 189 cases (20%); I2, 2 to 6 months, 286 (31%); I3, 6 to 12 months, 167 (18%); I4, 1 to 2 years, 146 (16%); I5, >2 years, 148 (16%). Results: First, we focused on the percentages of MRD as determined by FC (%FC). %FC ranged from 0% to 5% (median, 0.003%). Overall, %FC strongly correlated with EFS (p<0.0001). Application of a cutoff of 0.1% %FC, as recommended by ELN, resulted in significant differences in 5 year EFS (76% vs. 49%, p<0.0001). Considering even lower %FC, also a cutoff of 0.01% had significant impact on 5 year EFS (79% vs. 63%, p<0.0001). Multivariate analysis considering both cutoff values revealed independent impact for both (0.1%, p=0.005; 0.01%, p<0.0001). Adding to the multivariate model the two relevant prognostic parameters determined at diagnosis, i.e. age and ELN poor risk, resulted in both cutoff values for %FC still being independently significant (0.1%, p=0.013; 0.01%, p<0.0001). Secondly, MRD levels determined by QPCR were evaluated. The ratios between target gene expression and ABL1 expression were determined for diagnosis and follow-up and the further divided by the latter resulting in a ratio QR for each MRD assessment. QR ranged from 0 to 8 (median, 0). QR was significantly related to EFS (p=0.015). Application of a cutoff of 0.01 QR (100-fold decrease) resulted in significant differences in 5 year EFS (79% vs. 42%, p<0.0001). Considering lower QR, also a cutoff of 0.001 (1000-fold decrease) had significant impact on 5 year EFS (81% vs. 50%, p<0.0001). Multivariate analysis considering both cutoff values revealed independent impact for both (0.01, p=0.022; 0.001, p<0.0001). Adding to the multivariate model age and ELN poor risk resulted in both cutoff values for QR still being independently significant (0.01, p=0.038; 0.001, p=0.002). Multivariate analysis for EFS considering %FC 0.1% and QR 0.01 confirmed independent significance for both methods (p<0.0001 each). Same was true for %FC 0.01% and QR 0.001 (p<0.0001 each). Multivariate analysis considering all four parameters (%FC 0.1%, %FC 0.01%, QR 0.01, QR 0.001) as well as age and ELN poor risk revealed independent significance for %FC 0.01% (p<0.0001) and QR 0.0001 (p=0.008). Subgroup analysis revealed impact on EFS for %FC at I1, I2 and I3 and for QR at I2 to I5. In detail, independent impact was demonstrated at I1 for %FC 0.01% (p=0.018), at I2 for %FC 0.1% (p=0.002) and at I3 for %FC 0.01% (p=0.016) while independent impact was demonstrated at I2 for QR 0.001 (p=0.014), at I3 for QR 0.001 (p=0.001), at I4 for QR 0.001 (p=0.006) and at I5 for QR 0.001 (p=0.002). MRD levels determined by both methods were also significantly related to OS. Application of %FC 0.01 resulted in significant differences in 5-year OS (87% vs. 76%, p<0.0001) as did application of QR 0.001 (89% vs. 68%, p<0.0001). Multivariate analysis for OS considering %FC 0.01% and QR 0.001 revealed independent impact for both (p=0.002 and p<0.0001, respectively). Adding age and ELN poor risk to the multivariate model still revealed independent impact for both %FC 0.01% (p=0.001) and QR 0.001 (p<0.0001) on OS. Conclusions: Quantification of MRD by both FC and QPCR reveals independent and prognostically highly relevant information. FC is more suitable early during course of disease while QPCR is so later. MRD by FC may be considered even at lower levels than recommended by ELN. Disclosures Kern: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Meggendorfer:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.
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Bhutani, Divaya, Siyang Leng, Samuel Pan, Amer Assal, Alexander Wei, Julia Gould, Markus Y. Mapara, and Suzanne Lentzsch. "Combination Chemotherapy with Carfilzomib, Bendamustine and Dexamethasone Is Highly Active for Therapy of Newly Diagnosed Multiple Myeloma-Results of Single Center Phase I/II Study." Blood 134, Supplement_1 (November 13, 2019): 3196. http://dx.doi.org/10.1182/blood-2019-130207.

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Background: Carfilzomib and Bendamustine are currently FDA approved for therapy of relapsed refractory multiple myeloma (MM). Bendamustine, in addition to interference with DNA replication, it can induce inhibition of mitotic checkpoints, inefficient DNA repair, and initiation of a p53-dependent DNA-damaging stress response leading to apoptosis of tumor cells (1). It has previously shown significant activity in relapsed myeloma (2). Carfilzomib is a second generation, irreversible proteasome inhibitor has demonstrated promising activity in first line therapy (3,4). we hypothesized that combining them will yield an effective induction regimen in the newly diagnosed MM. Study design: Inclusion criteria included newly diagnosed MM with measurable disease, age ≥18, ECOG PS 0-2, adequate renal (creatinine clearance >30 mL/min), cardiac and hepatic function. Carfilzomib was given IV on days 1, 2, 8, 9, 15, 16. All patients received 20 mg/m2 on days 1 and 2 of cycle 1, after which their dose was escalated to one of the following levels: 27, 36, 45, or 56 mg/m2. Bendamustine IVPB on days 1, 2, at 70 (dose levels 1 and 2) or 90 mg/m2 (dose levels 3-5). Dexamethasone 20 mg PO or IV D 1, 2, 8, 9, 15, 16, 22, 23. Each cycle of therapy was 28 days, and a total of 8 cycles was given. Stem cell harvest was done after 4 cycles and eligible patients proceeded to ASCT after 8 cycles. Maintenance was recommended - either carfilzomib (36mg/m2 D 1,2, 15, 16 of a 28-day cycle for 2 years, or investigator's choice. Primary objective was to determine the recommended phase 2 dose (RP2D) and additional objectives assessed efficacy and safety. Results: Between February 2014 and May 2018, 20 patients with newly diagnosed MM pts were accrued onto study (5 pts in phase I and 15 in phase II). Median age was 65 (range 48-74), and 14 (70%) patients were male. 7 (35%) were of Hispanic ethnicity. 3 patients (15%) were R-ISS stage 3, and 1 (5%) had high-risk cytogenetics. We did not observe any DLTs with our study treatment and established the RP2D as: carfilzomib 56 mg/m2, bendamustine 90 mg/m2 and dexamethasone 20 mg on the dosing schedule given above. The most common and severe toxicities were hematologic. Grade 3/4 hematologic toxicities were lymphocytopenia in 90% of patients, neutropenia 40%, anemia 20% and thrombocytopenia 20%. Notable non-hematologic toxicities were grade 3/4 infection in 20% of patients (typically upper respiratory and pneumonia), grade 1/2 acute kidney injury in 45% of patients, and grade 1/2 diarrhea in 40% of patients. No treatment emergent hypertension or heart failure were noted. 1 patient died while on study, from septic shock due to pneumonia 7 weeks after completion of induction. The regimen was highly effective, with an ORR of 100%. Best responses were: 2 (11%) PR, 5 VGPR (26%), and 12 CR (63%) (Figure 2). Among the CRs, 4 were MRD-positive, 5 were MRD-negative, and 3 did not have MRD testing. With a median follow-up of 28 months (range 11-71), 2 patients have progressed - 1 with del(17p) at 19 months after diagnosis, and the other with standard cytogenetic risk disease at 56 months. 2 patients have died - the patient with del(17p) from refractory myeloma at 37 months after diagnosis, and the other from septic shock as discussed above. Median PFS was 56 months, and median OS has not been reached. Conclusion: Carfilzomib, Bendamustine and Dexamethasone is safe and highly effective for newly diagnosed transplant eligible MM and should be further explored in a larger prospective trial for this patient population. References: 1. Leoni LM, Hartley JA. Mechanism of action: the unique pattern of bendamustine-induced cytotoxicity. Seminars in hematology 2011;48 Suppl 1:S12-23. 2. Lentzsch S, O'Sullivan A, Kennedy RC, et al. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood 2012;119:4608-13. 3. Dimopoulos MA, Goldschmidt H, Niesvizky R, et al. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. The Lancet Oncology 2017;18:1327-37. 4. Jakubowiak AJ, Dytfeld D, Griffith KA, et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood 2012;120:1801-9. Disclosures Bhutani: Sanofi: Membership on an entity's Board of Directors or advisory committees. Assal:Incyte corporation: Consultancy, Research Funding; boston biomedical: Consultancy. Lentzsch:Janssen: Consultancy; Takeda: Consultancy; BMS: Consultancy; Proclara: Consultancy; Abbvie: Consultancy; Clinical Care Options: Speakers Bureau; Sanofi: Consultancy, Research Funding; Multiple Myeloma Research Foundation: Honoraria; International Myeloma Foundation: Honoraria; Karyopharm: Research Funding; Columbia University: Patents & Royalties: 11-1F4mAb as anti-amyloid strategy; Caelum Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy. OffLabel Disclosure: Carfilzomib, Bendamustine and Dexamethasone for newly diagnosed multiple myeloma.
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He, Yuelin, Hua Jiang, Changgang Li, Yiping Zhu, Xuedong Wu, Liu Sixi, Qu Yuhua, et al. "A Busulfan Following Cyclophosphamide and Constant Cell Dose Protocol Improved Results in Alternative Donor Hematologic Stem Cell Transplantation in Thalassemia Major: A Result from Long-Term Large-Size Multi-Center Study." Blood 134, Supplement_1 (November 13, 2019): 970. http://dx.doi.org/10.1182/blood-2019-130202.

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Sibling donor transplantation (SDT) is a proven curative therapy for patients with thalassemia major (TM), NF-08-TM protocol improved the outcomes of unrelated donor transplantation (UDT) in single-center. This study aim was to determine whether outcomes of NF-08-TM protocol could be proved in multicenter and long-term follow-up and to compare the outcomes of full-matched (FM) and one-locus mismatch (WM) UDT. 586 patients from 4 pediatric BMT centers in China from Dec. 2008 to Jun. 2016 received NF-08-TM protocol, a newly designed Busulfan following Cyclophosphamide and constant cell dose protocol. With a median follow-up of 57 months (range, 21-116), the 9-year OS, TFS, GR, and TRM were 94.4%, 92.8%, 2.7%, and 5.6%, respectively, in total. The corresponding rates for SDTs (n=224) were 95.9%, 95.5%, 1.4% and 4.1%; for UDTs (n=275) were 92.4%, 89.9%, 4.3% and 7.6%; for parental donor transplantation (PDT, n=40) were 95.0%, 95.0%, 0% and 5.0%; and for cord blood transplantation (CBT, n=47) were 97.9%, 95.4%, 2.6% and 2.1%, respectively.The incidence of grade II-IV aGVHD, III-IV aGVHD, mild cGVHD and moderate/severe cGVHD of the entire cohort was 8.9%, 4.6%, 3.7%, and 1.4%, respectively. There was no statistically significant difference (SSD) in OS, TFS, TRM, and GR when comparing FM-SDTs with those of FM-PDTs, FM-UDTs or FM-CBTs. Among PDTs, no SSD was found in OS, TFS, TRM, GR, and GVHD in comparison of FM-PDTs and WM-PDTs. More moderate/severe cGVHD occurred in WM-UDTs than FM-UDTs. Compared FM-SDTs, WM-UDTs had worse OS, TFS, TRM, and a higher rate of grade II-IV aGVHD and cGVHD. Current study proved that Good outcomes of NF-08-TM protocol in single-center be proved in multicenter and long-term follow-up. Compared to the outcomes of FM-UDT) those of well-UDT was worse and was not recommended to thalassemia patients. Disclosures Wing: Miltenyi Biotec: Employment.
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Peresse, Clemence, Laurence Dedeken, Phu-Quoc Le, Laurence Rozen, Beatrice Gulbis, Sarah Wambacq, and Alina Ferster. "Did the Outcome of Sicke Cell Disease Babies Screened at Birth Improved from 2000? a Single Center Experience." Blood 134, Supplement_1 (November 13, 2019): 4847. http://dx.doi.org/10.1182/blood-2019-130294.

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Newborn sreening (NS) for sickle cell disease (SCD) is effective in reducing early mortality and morbidity through education, prevention of infections and strategies to prevent stroke in children at risk of cerebral vasculopathy. Universal NS was implemented in all Brussels maternity wards since 2000. All identified children with SCD benefited from comprehensive medical care in dedicated centers. This retrospective study included all children with SCD diagnosed through NS and born between January 2000 and December 2005 (Group 1) and between January 2010 and December 2015 (Group 2) followed at Hôpital Universitaire des Enfants Reine Fabiola (Brussels, Belgium). Only patients whose parents consented to be recorded in the Belgian SCD database were eligible for this study. The aim of our study was to compare the outcome of 2 NS cohorts born at 10 years of interval. Demographic data, baseline hematological values and clinical events, occurrence of cerebral vasculopathy and prescription of disease-modifying treatments during the first 5 years of life were compared between both groups. Data were collected until March 1, 2019. 59 patients were identified for this study (35 in Group 1 and 24 in Group 2). Their characteristics are detailed in Table 1. Two patients in Group 2 did not completed the full 5-year evaluation period. Among these 59 patients, 77.9% patients developed at least one SCD clinical event before the age of 5. The number of patients who developed a specific clinical event as well as their age at this first event was the same between the 2 groups (Table 2). The hospitalization number and hospitalization days were not statistically different in the 2 groups (5 vs 4 hospitalizations during 5 years and 19 vs 17 days of hospitalization between Groups 1 and 2 respectively). 3 patients presented an overt stroke (1 in Group 1 and 2 in Group 2) with a global incidence of 1.02 stroke per 100 patient-years. No death was reported in both groups. The proportion of patients with abnormal transcranial doppler velocities decreased slightly in Group 2 (14.3% vs 8.3%, P=0.69) with more conditional velocities (5.7% vs 20.8%, P=0.10) but it was not statistically significant. 60% of patients in Group 1 were treated with hydroxyurea (HU) compared to 75% in Group 2 (P=0.27). HU was introduced at a median age of 2.5 (0.9-4.8) and 2.3 (0.8-4.8) in Groups 1 and 2 respectively (P=0.79). One patient from each group underwent an hematopoietic stem cell transplantation at 4.9 and 3.5 years. Hematological values were not different in the 2 groups excepted for platelets count, which were significantly lower in Group 2 (421 x 10³/µl vs 331 x 10³/µl, P=0.03). Moreover in patients under HU, platelet and reticulocytes count were statistically lower and HbF higher in Group 2 compared to Group 1 (Table 3). Nearly 80% of patients presented a clinical event before the age of 5. This is comparable to what is described in the literature. The Kaplan-Meier survival curves were not statistically different in both groups for the occurrence of a first dactylitis (P=0.52), a first vaso-occlusive crisis (P=0.22) and acute chest syndrome (P=0.37). No more difference was observed for acute anemia (P=0.43), severe infection (P=0.35) or patients under HU (P=0.40). Even if the number of patients on hydroxyurea is not statistically higher in Group 2, a better exposure to hydroxyurea is attested by the significant changes in some biological parameters. The limits of this study are the small size of our single center cohort and the exclusion of patients not recorded in the Belgian Registry because of lack of parental consent. This last point might create a bias by selecting patients whose parents are more prone to participate actively in the comprehensive care program. This periodic evaluation is essential to ensure the quality of care of patients and to measure possible changes in the management. Comprehensive care developed in our tertiary center had been already effective since 2000. Physicians not only tend to prescribe more hydroxyurea in young symptomatic patients, but also routinely adjust the dose to reach the maximal tolerated dose. Moreover adherence to treatment has been achieved through continuous education. Disclosures No relevant conflicts of interest to declare.
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15

Jurinovic, Vindi, Verena Passerini, Mikkel Z. Oestergaard, Andrea Knapp, Kirsten Mundt, Shamzah Araf, Julia Richter, et al. "Evaluation of the m7-FLIPI in Patients with Follicular Lymphoma Treated within the Gallium Trial: EZH2 mutation Status May be a Predictive Marker for Differential Efficacy of Chemotherapy." Blood 134, Supplement_1 (November 13, 2019): 122. http://dx.doi.org/10.1182/blood-2019-130208.

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Introduction : We have previously shown that a clinicogenetic risk model called the m7- Follicular Lymphoma (FL) International Prognostic Index (m7-FLIPI), which includes the mutation status of 7 genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), the FLIPI, and the ECOG performance status improves risk stratification in patients with advanced stage FL receiving frontline immunochemotherapy (Pastore, 2015). The m7-FLIPI was trained on a group of patients treated with R-CHOP and validated on an independent cohort treated with R-CVP. The aim of this study was to test the prognostic utility of the m7-FLIPI in patients treated within the GALLIUM trial. The GALLIUM trial enrolled 1202 patients with FL randomized to either receive Rituximab (R)- or Obinutuzumab (GA101, G)-based frontline treatment (Marcus, 2017). The chemotherapy consisted either of CHOP, CVP or Bendamustine and was allocated by the treating study center. All patients had previously untreated FL, advanced stage disease (stage III/IV or stage II with bulky disease) and ECOG performance status 0-2. All patients required treatment according to the GELF criteria. Methods: We performed targeted DNA sequencing of recurrently mutated genes, including the m7-FLIPI genes from diagnostic FL biopsies. We excluded cases with no available biopsies, insufficient DNA quantity/quality, or if patients did not sign informed consent for molecular studies. 418 patients were available for evaluation of the m7-FLIPI. The m7-FLIPI was calculated as previously described (http://www.glsg.de/m7-flipi/). Investigator-assessed progression-free survival (PFS), the primary endpoint in the GALLIUM trial, was the primary endpoint of this analysis. We performed Kaplan-Meier estimation and Cox proportional hazards regression to test the prognostic utility of the m7-FLIPI. The median follow up in the evaluable cohort was 4.7 years. 283 patients (68%) received Bendamustine (140 R, 143 G), 111 (27%) received CHOP (52 R, 59 G), and 24 (6%) received CVP (12 R, 12 G). Results : 104 patients (25%) had high-risk m7-FLIPI. 90 out of 194 patients with high-risk FLIPI (46%) were reclassified as low-risk by the m7-FLIPI. High-risk m7-FLIPI was associated with shorter PFS in the overall cohort (HR 1.52, P=0.030). Likewise, the m7-FLIPI was prognostic in patients treated with R-based regimens (HR 1.67, P=0.037). However, it was not prognostic in patients treated with G-based regimens (HR 1.24, P=0.49). When analyzed by different chemotherapy regimens, the m7-FLIPI was prognostic in patients receiving CHOP/CVP-based treatment (HR 2.05, P=0.013), validating the results from our original publication. The m7-FLIPI outperformed the FLIPI (HR 1.34, P=0.31) and had a significantly higher C-index (m7-FLIPI C=0.69, FLIPI C=0.57, P=0.021). However, the m7-FLIPI was not prognostic in patients receiving Bendamustine-based treatment (HR 1.23, P=0.42). Within the m7-FLIPI, mutations in EZH2 have the highest weight of all gene mutations. In this study, we found EZH2 mutations in 93 cases (22%). EZH2 mutations were associated with longer PFS (HR 0.25, P=0.0036) in CHOP/CVP-treated patients, but not in Bendamustine-treated patients (HR 1.11, P=0.71). Interaction analysis between the chemotherapy regimen and EZH2 mutation status showed a significant interaction term of 1.49 (P=0.011) for EZH2 mutations and Bendamustine. This increased the previously favorable HR in EZH2 unmutated patients (HR 0.55 for Bendamustine vs CHOP/CVP) to an unfavorable HR of 2.42 in EZH2 mutated patients. Overall, patients with EZH2 mutant FL appeared to benefit more from CHOP/CVP, whereas patients without EZH2 mutations had longer PFS with Bendamustine-based regimens, regardless whether chemotherapy was combined with R or G (see Figure). Conclusions: Here, we validated the prognostic utility of the m7-FLIPI for patients treated with R-CHOP/CVP. However, the m7-FLIPI was not prognostic in patients treated with Bendamustine-based regimens. While EZH2 mutation status was associated with longer PFS in patients receiving CHOP/CVP regimens (with either R or G), it did not impact treatment outcome of patients treated with Bendamustine, suggesting that EZH2 mutation status is a predictive marker for differential efficacy of the chemotherapy regimen. If confirmed, the EZH2 mutation status might be a highly useful biomarker to guide the selection of the preferred upfront chemotherapy. Figure Disclosures Oestergaard: F. Hoffmann-La Roche: Employment. Knapp:F. Hoffmann-La Roche Ltd: Employment. Mundt:F. Hoffmann-La Roche: Employment. Fitzgibbon:Gilead: Speakers Bureau; Epizyme: Membership on an entity's Board of Directors or advisory committees, Research Funding. Klapper:Roche, Takeda, Amgen, Regeneron: Honoraria, Research Funding. Marcus:Roche / Genentech: Honoraria, Speakers Bureau; Gilead: Consultancy. Davies:Karyopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Acerta Pharma: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; GSK: Research Funding; MorphoSys AG: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADCT Therapeutics: Honoraria, Research Funding; BioInvent: Research Funding. Herold:Roche: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Gilead: Honoraria; Celgene: Honoraria. Hiddemann:F. Hoffmann-La Roche: Research Funding. Unterhalt:F. Hoffmann-La Roche: Research Funding. Hoster:Roche Pharma AG: Other: Travel support; Janssen: Research Funding. Weigert:Novartis: Research Funding; F. Hoffmann-La Roche: Research Funding.
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16

Burd, Amy, Ross L. Levine, Amy S. Ruppert, Alice S. Mims, Uma Borate, Eytan M. Stein, Prapti A. Patel, et al. "Precision Medicine Treatment in Older AML: Results of Beat AML Master Trial." Blood 134, Supplement_1 (November 13, 2019): 175. http://dx.doi.org/10.1182/blood-2019-130201.

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*equal contribution of AB, RLL, BD and JCB Background: Acute myeloid leukemia (AML) is common with increasing age, and older adults with AML rarely achieve long-term remission with chemotherapy. Gene discovery studies in older adults with AML have shown that this malignancy is characterized by a multitude of somatic genomic alterations beginning with initiating somatic events followed by acquisition of collaborative transforming mutations. Despite these important biologic insights, current therapeutic approaches to AML remain limited, particularly in adults ≥ 60 years of age. The Beat AML trial was designed to assess the feasibility of using genetic profiling to assign patients (pts) to molecularly defined, subtype-specific therapies within 7 days of the initial diagnosis in a multi-center clinical trial setting, and to delineate the role of molecularly informed first-line treatment of AML with mechanism based novel therapies. Methods: Treatment-naïve patients with AML were enrolled in this prospective trial which offered accelerated cytogenetic and comprehensive mutational testing within 7 days followed by treatment assignment using these molecular data. Pt eligibility included age ≥ 60 years with non-APML AML, no known CNS leukemia, no prior hypomethylating agent (HMA) therapy and no clinical need for emergent therapy. Eligible pts were profiled by local cytogenetics analysis and using a central next generation sequencing (NGS) assay (Foundation Medicine, Inc.) with all molecular data required for treatment assignment (TA) obtained &lt; 7 days. TA was made centrally using a pre-determined algorithm considering somatic cytogenetic and molecular alterations in the dominant clone, available targeted therapeutics for specific AML subsets, and the likelihood of cure with intensive chemotherapy. Results: From November 2016 to January 2019, 487 pts with a suspected diagnosis of AML had enrolled at 14 clinical sites; 395 were eligible for the study (77% of the patients not eligible for the study had an alternative diagnosis). The median age of eligible patients was 72 years (range: 60 to 92) with 38% being≥ 75 years and 16% with treatment-related AML. From the 395 eligible patients, 374 (94.7%) were centrally assigned to the different cytogenetic/genomic groups within 7 days. The most common groups were TP53 mutated (19%) and marker negative (18%) molecular groups. The Beat AML trial is dynamic by design, thereby allowing different arms to open over time; all trial arms are designed to evaluate for substantial clinical efficacy in small, molecularly defined patient subsets. As shown in Figure 1, 224 patients (57%) had a TA and consented to a BEAT AML sub-study. Of the remaining 171 patients, 103 received standard therapy defined as induction therapy (7+3) or hypomethylation agent (25 before TA and 78 after TA), 28 received an alternative investigational agent (5 before TA and 23 after TA), 38 received palliative care, and 2 had an unknown treatment status and are grouped with the palliative care patients in subsequent analyses; 9 patients died before TA (2 who received standard therapy and 7 in the palliative care group). Demographic, clinical, performance and molecular characteristics were not largely different between pts who elected targeted therapy as part of the BEAT AML trial versus those who elected standard therapy. As shown in Figure 2, the overall survival was significantly longer for patients enrolled in a targeted therapy arm as part of the BEAT AML trial compared to those who elected standard therapy. (p&lt;0.0001). The 30-day estimated death rate was 3.7% (95% CI: 1.9-7.2) for patients electing treatment on a BEAT AML sub-study, 20.4% (95% CI: 13.0-31.2) for those receiving standard therapy, 0% for those receiving an investigational therapy, and 72.6% (95% CI: 57.8-85.7) for the palliative care group. Conclusion: Our data support the feasibility of a rapid precision medicine approach in older patients with previously untreated AML. Patients with AML who elected treatment assigned based upon cytogenetic and molecular alterations in the dominant clone using a novel precision medicine approach had significantly improved overall survival versus those who elected standard of care treatment. Disclosures Levine: Gilead: Consultancy; Prelude Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Isoplexis: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Research Funding; Qiagen: Membership on an entity's Board of Directors or advisory committees; Loxo: Membership on an entity's Board of Directors or advisory committees; Imago Biosciences: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Lilly: Honoraria. Mims:Abbvie: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Astellas Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Borate:Novartis: Consultancy; Takeda: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; AbbVie: Consultancy. Stein:Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas Pharma US, Inc: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, Inc.: Membership on an entity's Board of Directors or advisory committees; Bioline: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Patel:France Foundation: Honoraria; Dava Oncology: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Baer:Takeda: Research Funding; Incyte: Research Funding; Kite: Research Funding; Forma: Research Funding; AI Therapeutics: Research Funding; Abbvie: Research Funding; Astellas: Research Funding. Stock:Daiichi: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria; UpToDate: Honoraria; Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Deininger:Pfizer: Consultancy, Honoraria, Research Funding; Ascentage Pharma: Consultancy, Honoraria; TRM: Consultancy; Sangoma: Consultancy; Fusion Pharma: Consultancy; Adelphi: Consultancy; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Humana: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Sangamo: Consultancy; Blueprint: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Blum:Boehringer Ingelheim: Research Funding; Celgene: Research Funding; Astellas,: Research Funding; Xencor: Research Funding; Forma: Research Funding; AmerisourceBergen: Consultancy. Schiller:Amgen: Other, Research Funding; Agios: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Constellation Pharmaceutical: Research Funding; Daiichi Sankyo: Research Funding; Eli Lilly and Company: Research Funding; FujiFilm: Research Funding; Genzyme: Research Funding; Gilead: Research Funding; Incyte: Research Funding; J&J: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Karyopharm: Research Funding; Novartis: Research Funding; Onconova: Research Funding; Pfizer Pharmaceuticals: Equity Ownership, Research Funding; Sangamo Therapeutics: Research Funding; Bristol Myer Squibb: Research Funding; Astellas: Research Funding; Biomed Valley Discoveries: Research Funding. Olin:Daiichi Sankyo: Research Funding; Astellas: Research Funding; Genentech: Consultancy, Research Funding; Pfizer: Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria; Revolution Medicine: Consultancy; AstraZeneca: Research Funding; Clovis: Research Funding; Ignyta: Research Funding; MedImmune: Research Funding; Mirati Therapeutics: Research Funding; Novartis: Research Funding; Spectrum: Research Funding. Foran:Agios: Honoraria, Research Funding. Lin:Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria. Traer:AbbVie: Consultancy; Agios: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Notable Labs: Equity Ownership. Odenike:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Astra Zeneca: Research Funding; Astex Pharmaceuticals: Research Funding; NS Pharma: Research Funding; Gilead Sciences: Research Funding; Janssen Oncology: Research Funding; Oncotherapy: Research Funding; Agios: Research Funding; CTI/Baxalta: Research Funding. Arellano:Gilead: Consultancy. Vergilio:Roche Holding AG: Equity Ownership; Foundation Medicine: Employment. Brennan:Foundation Medicine: Employment. Vietz:Foundation Medicine: Employment. Druker:ALLCRON: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Aileron Therapeutics: #2573, Constructs and cell lines harboring various mutations in TNK2 and PTPN11, licensing fees , Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Patents & Royalties, Research Funding; Burroughs Wellcome Fund: Membership on an entity's Board of Directors or advisory committees; Cepheid: Consultancy, Honoraria; The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; GRAIL: Equity Ownership, Other: former member of Scientific Advisory Board; Patient True Talk: Consultancy; Dana-Farber Cancer Institute (antibody royalty): Patents & Royalties: #2524, antibody royalty; Pfizer: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Research Funding; Merck & Co: Patents & Royalties: Dana-Farber Cancer Institute license #2063, Monoclonal antiphosphotyrosine antibody 4G10, exclusive commercial license to Merck & Co; OHSU (licensing fees): Patents & Royalties: #2573, Constructs and cell lines harboring various mutations in TNK2 and PTPN11, licensing fees ; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Aptose Biosciences: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Beta Cat: Membership on an entity's Board of Directors or advisory committees, Other: Stock options; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees, Other: Stock options; Beat AML LLC: Other: Service on joint steering committee; CureOne: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Gilead Sciences: Other: former member of Scientific Advisory Board; ICON: Other: Scientific Founder of Molecular MD, which was acquired by ICON in Feb. 2019; Monojul: Other: former consultant; Novartis: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Patents & Royalties: Patent 6958335, Treatment of Gastrointestinal Stromal Tumors, exclusively licensed to Novartis, Research Funding; Bristol-Myers Squibb: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Research Funding. Byrd:Novartis: Other: Travel Expenses, Speakers Bureau; BeiGene: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Acerta: Research Funding; Ohio State University: Patents & Royalties: OSU-2S; Genentech: Research Funding; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau.
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17

Uriens, S., K. Rezai, V. Girre, V. Dieras, and F. Lokiec. "Population pharmacokinetics of docetaxel in elderly patients." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 13020. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.13020.

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13020 Background: Elderly patients (>70 years) may present different pharmacokinetic profile for many drugs , mainly because of altered elimination due to renal function or metabolic decreases. Methods: Docetaxel, 50 to 85 mg/m2, median 70 mg/m2, was infused during 1 hr to 44 patients, aged 70 to 83 years, median 76.5 years. Three blood samples per patient were obtained according to a limited sampling strategy (Baille et al. Clin Cancer Res 1997, vol. 3, 1535–38). Covariates of interest were carefully recorded, age, body weight, body surface area, gender, serum creatinine, orosomucoid, serum albumin. These data were then analysed using NONMEM V to a) obtain individual Bayesian estimates of docetaxel clearance, b) re-analyse the data in order to estimate population parameters for this elderly population, c) show possible covariate effects on the pharmacokinetic parameters. Results: Median docetaxel CL from Bayesian estimation was 29.1 (2.5–97.5% quantiles 12–49) L/h. When the population was re-analysed per se, docetaxel CL was 29.2 (2.5–97.5% quantiles 17–35) L/h. The inter- subject variability for CL was 25% (precision 32%).. No covariate effect was observed on CL. Conclusions: Docetaxel clearance in elderly patients is slightly decreased, 29 L/h versus 36.8 L/h (reported in 547 patients, mean age 56 years, 5–95% quantiles 39–71 years). The inter-subject-variability of CL in elderly patients was decreased to 25% versus 47.5% in the 547 patients population. A pharmacokinetic- pharmacodynamic modelling of neutrophil counts versus time will be performed in these elderly patients in order to point a possible different sensitivity of this population to the myelosuppressive effects of docetaxel. No significant financial relationships to disclose.
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18

Gates, George A. "Acute and secretory otitis media, edited by j. sade, 580 pp, kugler publications, berkeley, ca, 1986, $130.00." Laryngoscope 97, no. 11 (November 1987): 1368. http://dx.doi.org/10.1288/00005537-198711000-00027.

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TOGAWA, Hiroki, Naruhiro HAYASHI, Tomoyuki FUKAI, Shiroh ITAI, and Yoshiyuki MIWA. "1304 Spatial Design of Playground with Shadow Media : Development of Shadow Media System Focused on Movement of Light Source." Proceedings of Design & Systems Conference 2012.22 (2012): _1304–1_—_1304–4_. http://dx.doi.org/10.1299/jsmedsd.2012.22._1304-1_.

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Seefeld, M., S. El Tarhouny, A. X. C. Fan, S. Hahn, W. Holzgreve, and X. Y. Zhong. "Parallel Assessment of Circulatory Cell-Free DNA by PCR and Nucleosomes by ELISA in Breast Tumors." International Journal of Biological Markers 23, no. 2 (April 2008): 69–73. http://dx.doi.org/10.1177/172460080802300202.

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Objectives In order to assess the potential biomolecules for breast cancer, we analyzed in parallel the levels of cell-free glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and cell-free nucleosomes in serum samples from patients with benign and malignant breast tumors. The levels of cell-free DNA obtained by quantitative PCR were compared with those obtained by enzyme-linked immunosorbent assay (ELISA). Methods Twenty-three patients with benign breast tumors, 27 patients with breast cancer, and 32 age-matched healthy women were recruited. The amounts of serum nucleosomes were analyzed by ELISA and the levels of cell-free GAPDH were measured by real-time quantitative PCR. The correlation between nucleosome and cell-free GAPDH levels was examined using the Spearman rank test. Results The levels of cell-free GAPDH were significantly higher in the serum samples of patients with benign and malignant breast tumors than in those of the control group (median 37,966 GE/mL, range 3,802–130,104 versus 11,770 GE/mL, range 2,198–73,522, p=0.035 and median 40,698 GE/mL, range 3,644–192,482 versus 11,770 GE/mL range 2,198–73,522, p=0.001). The concentration of cell-free GAPDH correlated significantly with the quantities of nucleosomes in serum samples (r=0.451, p=0.000). There was, however, no significant difference between healthy individuals and women with benign breast tumors or breast cancer in terms of nucleosomes determined by ELISA. Conclusion Our data suggest that the cell-free serum GAPDH DNA assayed by quantitative PCR is a better biomarker than nucleosomes assayed by ELISA in patients with breast tumors.
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Lasso, Erika Tay, Anjali Herekar, Clara Riggle, Sheng Li, Hui Hwang, Mariko Horie, Kenneth S. Phelps, et al. "619 Pain Management in Burn and Wound Patients: Effects of Acupuncture in Pain Score and Medication." Journal of Burn Care & Research 43, Supplement_1 (March 23, 2022): S150—S151. http://dx.doi.org/10.1093/jbcr/irac012.247.

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Abstract Introduction Pain management in burn patients is a complex ongoing problem. Opioid and non-opioid medications have historically been used as the primary pain management modality in burn care. Considering the ongoing opioid epidemic, a multidisciplinary holistic approach is needed for pain management. Acupuncture has been recognized to help in different settings such as chronic back pain, neurological problems, depression, and anxiety. We hypothesize that burn and wound patients receiving acupuncture will have a decrease in opioids and non-opioid medications on acupuncture day (ACd) compared to non-acupuncture day (n-ACd) and a reduction of pain scores before and after acupuncture. Methods A prospective observational study in all patients admitted to the burn service was made. We exclude patients that were unable to provide consent or age 6 years and younger. A numeric pain score (1-10) was collected from the patients before and after each acupuncture session; if patients were sleeping after acupuncture pain score was collected when they woke up. A prospective collection of daily opioids and non-opioids medications was made. Opioids were converted to daily morphine equivalents (MME). Results From February to August 2021, 53 patients on the burn service were treated with acupuncture for a total of 185 sessions. The median age was 49 years (IQR:32.5-63.0). Median TBSA for burn patients was 3.3% (IQR:1.5-8.1). The number of sessions per patient ranged from 1-12 with a median of 3 (IQR1.7-4). Before acupuncture, the median pain score was 5 (IQR:2.6-6.4), and after treatment was it was 1.5 (IQR:0.2-2.8). Of 185 sessions, 49 (26%) of those sessions, patients fell asleep afterward. Median morphine use on ACd was 26.6 MME (15.8-62.1) vs. n-ACd 27.35 MME (15.5-65.3). For non-opioid medication, the median of acetaminophen on ACd 1007.5mg (313.39 -1950) vs. n-ACd 1381.25mg (642.5-2535). After adjusting for TBSA and chronic opioid use, patients were given a daily mean of 391 MME CI: (1201.12-419.12 p=0.334) less in ACd vs. n-ACd. In addition, acetaminophen had a daily mean of 395.12mg CI: (130.05, 660.19 p=0.005) less in ACd vs. n-ACd. Overall, acupuncture was associated with a significant lower pain score with a mean of 2.799 points less. Conclusions Acupuncture seems to abrogate pain in burn and wound patients, as demonstrated by doses of pain medication. While there was no significant difference in opioid medications, there was a significant difference in acetaminophen, indicating that additional education of a tiered approach to pain medications is essential to reduce unnecessary opioid use.
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Campone, M., C. Charbonnel, F. Magrangeas, S. Minvielle, J. Genève, A. Martin, R. Deporte, R. Bataille, L. Campion, and P. Jézéquel. "Establishment of a predictive classifier of node-positive breast cancer patients treated by FEC100 chemotherapy using gene expression profiling." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 13004. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.13004.

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13004 Background: In breast cancer treatment, biomarkers providing information about chemotherapy sensitivity are needed. FEC100 combination, frequently prescribed in Europe, is still applied empirically to patients. Our study’s goal was to establish a classifier of sensitivity to this regimen using gene expression data and classical clinicopathologic parameters. Methods: The study retrospectively included 151 patients belonging to the FEC100 arms of two multicentric phase III clinical trials: PACS01 (n = 128) and PEGASE01 (n = 23) (FNCLCC). Patients had unilateral breast cancer, showed no evidence of distant metastasis, were node-positive, aged less than 65-year-old. Median follow-up was 5 years. The number of relapses were respectively 23 and 10. We used cDNA nylon microarrays containing 7,000 genes to analyze gene expression profiles of tumor. Patients were split into a training set and a test set. A 3-step analysis based on Cox regression was applied: 1) elimination of non discriminant genes, 2) robust (resampling) univariate selection of discriminant genes and 3) development of multivariate models combining the discriminant genes, the Nottingham Prognostic Index (NPI) (developed in 2 binary variables) and the hormonal receptors. As a final step, after dichotomization of the retained genes, a risk score was built and applied first on the test set, and then on the whole cohort. Kaplan-Meier curves and logrank tests were performed to assess the new risk score. Results: The new risk score (one gene [G6224] and NPI) permitted to separate patients from the test set in 3 significantly different groups; it was also an improvement on NPI (test set: NPI, p = 0.0005; risk score p = 0.0001 - whole cohort: NPI, p = 2.10−5; risk score, p = 1.10−10). Conclusions: We identified G6224 whose expression combined with NPI showed a good capacity for classifying breast cancer patients who received FEC100 chemotherapy. Our results strengthen the interest of G6224 since it was previously described in various solid tumors as a prognostic biomarker with a tumor-suppressor activity. No significant financial relationships to disclose.
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Torres, M. Gabriela. "Sarah England, Writing Terror on the Bodies of Women: Media Coverage of Violence against Women in Guatemala (Lanham, MD: Lexington, 2018), pp. xiv + 419, $130.00; £100.00, hb." Journal of Latin American Studies 52, no. 4 (November 2020): 837–38. http://dx.doi.org/10.1017/s0022216x20001054.

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Smallman, Lesley A. "Pathology and Surgery of the Salivary GlandsR. A. Cawson, M. J. Gleeson, J. W. Eveson Isis Medical Media Ltd, 1997 ISBN 1 899066 61 6 Price: £130.00." Journal of Laryngology & Otology 112, no. 7 (July 1998): 694. http://dx.doi.org/10.1017/s0022215100141490.

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Gupta, Manju, Pankaj Kumar Mishra, Amit Bathla, Mohd Shoeb, and Jagdish Prasad. "Thoracic approaches in atrial septal defect closure a comparative study." International Surgery Journal 4, no. 5 (April 22, 2017): 1619. http://dx.doi.org/10.18203/2349-2902.isj20171608.

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Background: Atrial septal defects (ASD) are one of the most common cardiac malformations. Being asymptomatic, diagnosis is not always made in childhood and may be delayed to adolescence or adulthood. The incidence of ASD in female is twice that of male, so greater emphasis has been placed on the cosmetic results of the operation.Methods: In this study, we retrospectively compare results 100 patients of ASD closure through a right anterolateral thoracotomy incision and median sternotomy incision. Between August 2011 to August 2016, out of total 100 patients with ostium secundum ASD, 50 patients operated by right anterolateral thoracotomy have mean age 16.74 yrs, mean weight 28.77 kg, mean Height 122.06 cm and 50 patients with midline sternotomy have mean age 17.07 year, mean weight 29.24 kg, mean height 122.20cm.Results: There was no mortality in both groups. Per operatively mean operating time, mean CPB time, mean cross clamp time in thoracotomy was 130.08±8.16min, 48.68±5.10min, 29.70±4.21 min while in sternotomy was 121.34±8.30 min, 45.62±4.10 min, 28.28±2.82 min respectively. When compared, there is significant increased duration in operating and CPB time in thoracotomy while cross clamp time was non-significant. Mean duration of ICU and Hospital stay in thoracotomy group was 1.78±0.58days and 6.74±1.77 days when compared to sternotomy group in which it was 2.40±0.495 days and 7.66±1.40 days which is significantly less when compared. Postoperatively and in follow up thoracotomy group have better cosmesis when compared.Conclusions: Surgical treatment of osteum secondum ASD using right anterolateral thoracotomy approach has low operative risk better cosmetic results and patient satisfaction.
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Abbassi-Ghadi, N., and H. Hafez. "Ultrasound-guided foam sclerotherapy within a rolling treatment programme is an effective low-cost treatment for superficial venous insufficiency." Phlebology: The Journal of Venous Disease 28, no. 4 (February 22, 2012): 195–200. http://dx.doi.org/10.1258/phleb.2011.011099.

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Aims To review the results and cost of a rolling ultrasound-guided foam sclerotherapy (UGFS) treatment programme for patients with chronic superficial venous insufficiency. Method A prospective study of a rolling treatment programme where patients were offered unlimited follow-up at intervals of 6–8 weeks and further (top up) UGFS when necessary, until occlusion criteria were met. Results A total of 213 lower limbs with complete follow-up were included in the study. Median (range) age was 57 (16–94) years, maximum diameter of varicose vein was 10 (3–18) mm, C of CEAP (clinical, aetiological, anatomical and pathological elements) was 4 (2–6), number of treatment sessions was one (1–4) and follow-up was three (1.5–33) months. Satisfactory occlusion could not be achieved in nine (4%) limbs. The ratio of odds (95% CI) for requiring more than one treatment session was 3.58 (1.46–8.77), P = 0.002 for great saphenous varicosity and 2.11 (1.13–3.94), P = 0.015 for age 50 or more. There were 20 (9.3%) immediate and 63 (29.5%) delayed adverse effects. All were minor except for one cutaneous nerve injury, one pulmonary embolism and one infected haematoma. The ratio for odds (95% CI) for post-treatment skin discolouration was 2.59 (1.14–5.87), P = 0.017 for women and 1.32 (1.02–1.71), P = 0.032 for increasing sclerosant volume used. Service line costing per completed treatment episode was £115.22 (€130.07, $188.60). Conclusion UGFS in a rolling treatment programme is safe and can achieve high occlusion rates at a low cost. Patients above the age of 50 with great saphenous varicosity are likely to require more than one treatment session.
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Ahiamadu, Nnamdi Michael, Ify L. Nwaogazie, and Yusuf O. L. Momoh. "Empirical Characterization of Heavy Metals in Crude Oil Spill Sites in Emohua, Rivers State, Nigeria." European Journal of Environment and Earth Sciences 2, no. 5 (September 29, 2021): 24–28. http://dx.doi.org/10.24018/ejgeo.2021.2.5.161.

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The study assessed the concentration of heavy metals in three oil spill sites in Emohua local government area in Rivers State, Nigeria. Soil samples were collected at depth 0-30cm for surface soil samples and up to 10m for sub-surface soil samples depending on the depth of borehole. Groundwater samples were collected from drilled boreholes while the surface water samples were collected from fishponds or water bodies (rivers) close to the oil spill sites. The samples taken from the oil spill sites were analysed to determine the level of concentration of 10 Department of Petroleum Resource (DPR) specified heavy metals (Cd, Zn, Cu, Pb, Cr, Ba, Ni, Hg, As, and Co). BUCK Scientific Atomic Absorption Spectrophotometer (AAS) was used in detecting the concentration of the heavy metals. For the surface soil, Pb concentration in site A and B were significantly higher than what was obtained at site C, with a mean concentration of 219.70, 130.01 and 3.41mg/kg respectively for the three sites. The mean lead (Pb) concentration obtained in the surface soil was within DPR and United State Environmental Protection Agency (USEPA) acceptable limits. Barium also has significant concentration in both the surface soil and sub-surface soil. Kruskal Wallis test indicated significant difference in the Pb, Cd, Zn, Cu, Cr and Ba concentration in surface/topsoil among the three sites and also indicated significant difference in the concentrations of Pb, Cd, Cr, Ni, Ba and As in sub-surface soil among the sites. Little heavy metal concentration was found in both the groundwater and surface water. The study showed that even if some heavy metals were detected at the oil spill sites, they do not pose any serious health risk, as all the heavy metals in the four environmental media at the three sampling sites were below the national limit stipulated by the Department of Petroleum Resource (DPR), Nigeria.
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Ankersen, Dorit Vedel, Petra Weimers, Mette Bennedsen, Anne Birgitte Haaber, Eva Lund Fjordside, Moritz Emanuel Beber, Christian Lieven, et al. "Long-Term Effects of a Web-Based Low-FODMAP Diet Versus Probiotic Treatment for Irritable Bowel Syndrome, Including Shotgun Analyses of Microbiota: Randomized, Double-Crossover Clinical Trial." Journal of Medical Internet Research 23, no. 12 (December 14, 2021): e30291. http://dx.doi.org/10.2196/30291.

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Background The long-term management of irritable bowel syndrome (IBS) poses many challenges. In short-term studies, eHealth interventions have been demonstrated to be safe and practical for at-home monitoring of the effects of probiotic treatments and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). IBS has been linked to alterations in the microbiota. Objective The aim of this study was to determine whether a web-based low-FODMAP diet (LFD) intervention and probiotic treatment were equally good at reducing IBS symptoms, and whether the response to treatments could be explained by patients’ microbiota. Methods Adult IBS patients were enrolled in an open-label, randomized crossover trial (for nonresponders) with 1 year of follow-up using the web application IBS Constant Care (IBS CC). Patients were recruited from the outpatient clinic at the Department of Gastroenterology, North Zealand University Hospital, Denmark. Patients received either VSL#3 for 4 weeks (2 × 450 billion colony-forming units per day) or were placed on an LFD for 4 weeks. Patients responding to the LFD were reintroduced to foods high in FODMAPs, and probiotic responders received treatments whenever they experienced a flare-up of symptoms. Treatment response and symptom flare-ups were defined as a reduction or increase, respectively, of at least 50 points on the IBS Severity Scoring System (IBS-SSS). Web-based ward rounds were performed daily by the study investigator. Fecal microbiota were analyzed by shotgun metagenomic sequencing (at least 10 million 2 × 100 bp paired-end sequencing reads per sample). Results A total of 34 IBS patients without comorbidities and 6 healthy controls were enrolled in the study. Taken from participating subjects, 180 fecal samples were analyzed for their microbiota composition. Out of 21 IBS patients, 12 (57%) responded to the LFD and 8 (38%) completed the reintroduction of FODMAPs. Out of 21 patients, 13 (62%) responded to their first treatment of VSL#3 and 7 (33%) responded to multiple VSL#3 treatments. A median of 3 (IQR 2.25-3.75) probiotic treatments were needed for sustained symptom control. LFD responders were reintroduced to a median of 14.50 (IQR 7.25-21.75) high-FODMAP items. No significant difference in the median reduction of IBS-SSS for LFD versus probiotic responders was observed, where for LFD it was –126.50 (IQR –196.75 to –76.75) and for VSL#3 it was –130.00 (IQR –211.00 to –70.50; P>.99). Responses to either of the two treatments were not able to be predicted using patients’ microbiota. Conclusions The web-based LFD intervention and probiotic treatment were equally efficacious in managing IBS symptoms. The response to treatments could not be explained by the composition of the microbiota. The IBS CC web application was shown to be practical, safe, and useful for clinical decision making in the long-term management of IBS. Although this study was underpowered, findings from this study warrant further research in a larger sample of patients with IBS to confirm these long-term outcomes. Trial Registration ClinicalTrials.gov NCT03586622; https://clinicaltrials.gov/ct2/show/NCT03586622
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Lind, Margaret L., Alexander J. Robertson, Julio Silva, Frederick Warner, Andreas C. Coppi, Nathan Price, Chelsea Duckwall, et al. "Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case–control analysis." PLOS Medicine 19, no. 12 (December 1, 2022): e1004136. http://dx.doi.org/10.1371/journal.pmed.1004136.

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Background The benefit of primary and booster vaccination in people who experienced a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains unclear. The objective of this study was to estimate the effectiveness of primary (two-dose series) and booster (third dose) mRNA vaccination against Omicron (lineage BA.1) infection among people with a prior documented infection. Methods and findings We conducted a test-negative case–control study of reverse transcription PCRs (RT-PCRs) analyzed with the TaqPath (Thermo Fisher Scientific) assay and recorded in the Yale New Haven Health system from November 1, 2021, to April 30, 2022. Overall, 11,307 cases (positive TaqPath analyzed RT-PCRs with S-gene target failure [SGTF]) and 130,041 controls (negative TaqPath analyzed RT-PCRs) were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 5.9% and 8.1% had a documented prior infection (positive SARS-CoV-2 test record ≥90 days prior to the included test), respectively. We estimated the effectiveness of primary and booster vaccination relative to SGTF-defined Omicron (lineage BA.1) variant infection using a logistic regression adjusted for date of test, age, sex, race/ethnicity, insurance, comorbidities, social venerability index, municipality, and healthcare utilization. The effectiveness of primary vaccination 14 to 149 days after the second dose was 41.0% (95% confidence interval (CI): 14.1% to 59.4%, p 0.006) and 27.1% (95% CI: 18.7% to 34.6%, p < 0.001) for people with and without a documented prior infection, respectively. The effectiveness of booster vaccination (≥14 days after booster dose) was 47.1% (95% CI: 22.4% to 63.9%, p 0.001) and 54.1% (95% CI: 49.2% to 58.4%, p < 0.001) in people with and without a documented prior infection, respectively. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds of infection among boosted (≥14 days after booster dose) and booster-eligible people (≥150 days after second dose). The odds ratio (OR) comparing boosted and booster-eligible people with a documented prior infection was 0.79 (95% CI: 0.54 to 1.16, p 0.222), whereas the OR comparing boosted and booster-eligible people without a documented prior infection was 0.54 (95% CI: 0.49 to 0.59, p < 0.001). This study’s limitations include the risk of residual confounding, the use of data from a single system, and the reliance on TaqPath analyzed RT-PCR results. Conclusions In this study, we observed that primary vaccination provided significant but limited protection against Omicron (lineage BA.1) infection among people with and without a documented prior infection. While booster vaccination was associated with additional protection against Omicron BA.1 infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection. These findings support primary vaccination in people regardless of documented prior infection status but suggest that infection history may impact the relative benefit of booster doses.
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Dolzhenko, M. M., and S. A. Bondarchuk. "Comparative efficacy and predictive value of fixed combination of amlodipine and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in patients with coronary heart disease, post-infarction cardiosclerosis and hypertension." Zaporozhye Medical Journal 23, no. 6 (October 29, 2021): 791–99. http://dx.doi.org/10.14739/2310-1210.2021.6.240999.

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The aim of the work – to analyze the effectiveness of a fixed combination of amlodipine and angiotensin-converting enzyme (ACE) inhibitor (lisinopril) or angiotensin II receptor blocker (valsartan) in patients with coronary heart disease (CHD), post-infarction cardiosclerosis (PIC), arterial hypertension (AH) regarding the blood pressure (BP) control and impact on a composite endpoint. Materials and methods. General clinical examination of 108 patients with PIC and AH was done at the Cardiology Department of Shupyk National Healthcare University of Ukraine within 12 months. Patients were divided into two groups. The first group patients (n = 50) were assigned to receive a fixed combination of valsartan and amlodipine (160 mg and 5 mg, respectively), and the second group patients (n = 58) were treated with a fixed combination of lisinopril and amlodipine (10 mg and 5 mg, respectively). Patients were followed-up for 12 months, including general clinical examination, office BP measurements, 24-hour BP monitoring, echodopplerography, monitoring of the composite endpoint. Exclusion criteria were hemodynamically significant heart valve lesions, permanent or temporary cardiac pacing, acute heart failure and implanted cardioverter-defibrillator, permanent form of atrial fibrillation, acute cerebrovascular disorder, decompensation of severe somatic pathology. Statistical analysis of the data obtained was performed using Microsoft Excel, IBM SPSS Statistics v. 23. Descriptive data were presented as arithmetic mean ± standard deviation (M ± SD) in the case of normal distribution of variables, data with distribution other than normal were presented in Me format (Q25; Q75), where Me was the median, Q25, Q75 – lower and upper quartiles (Q25; Q75), or as a percentage for categorical values with Pearson’s Chi-square (χ2) calculation. Differences in mean values were considered statistically significant at a level of Р < 0.05. Results. According to all statistical criteria, BP indicators did not differ in both patient groups. Systolic office BP in the first group was 133.00 (123.00; 140.25) mm Hg., in the second group – 130.00 (122.00; 140.00) mm Hg. In the first group, diastolic office BP was 81.00 (79.50; 81.00) mm Hg and in the second group – 80.00 (75.00; 86.00) mm Hg. No statistically significant differen­ces were found in the study groups when assessing mean BP levels during the 24-hour monitoring. In the assessment of index values, systolic BP load was higher than normal in 58 % of patients in the first group and in 56.9 % of patients in the second group (χ2 = 0.01; P = 0.53). The assessment of diastolic BP load indices revealed increased diastolic BP index in 72 % of patient in the first group and in 75.9 % – in the second group (χ2 = 0.2; P = 0.4). The number of patients with BP higher or less than 130/80 mm Hg was compared. Systolic BP was above and below 130 mm Hg in 56 % and 44 %, respectively, of the first group patients; the distribution was 37.9 % and 62.1 % in the second group. Therefore, the percentage of patients with target systolic BP was higher in the second group (χ2 = 3.52; P = 0.046). Analyzing the composite endpoint, a statistically significant difference in the Kaplan–Meier curves via the statistical criterion using a log-rank test (P = 0.007) was detected. Conclusions. No statistically significant differences were found in the analysis of office blood pressure and 24-hour blood pressure monitoring between amlodipine with lisinopril and amlodipine with valsartan groups. The detailed analysis revealed a greater percentage of patients with target blood pressure below 130/80 mm Hg among those under 65 years of age receiving amlodipine with lisinopril (χ2 = 3.52; P = 0.046). The better prognostic value of the fixed combination of amlodipine with lisinopril compared to the combination of amlodipine with valsartan (P = 0.007) was demonstrated by the endpoint analysis.
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Lundmark, Evelina. "Practical Spiritualities in a Media Age, edited by Curtis D. Coats and Monica M. Emerich." International Journal for the Study of New Religions 11, no. 1 (August 5, 2021). http://dx.doi.org/10.1558/ijsnr.20636.

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Harada, Kenji, and Yukiko Harada. "Abstract 13020: Obesity-related Vascular Functional Change Becomes Apparent in Early Childhood." Circulation 142, Suppl_3 (November 17, 2020). http://dx.doi.org/10.1161/circ.142.suppl_3.13020.

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Background: Obesity is associated with structural and functional changes in the artery, but there is little information when arterial dysfunction begins to appear. The purpose of this study is to investigate the relationship between body mass index (BMI) z-score and arterial function from childhood to adolescence. Methods: Echocardiography was performed in 779 healthy children. Subjects were divided into 3 age groups: pre-school children group, 4 to 6 year (n =236); school children group, 7 to 12 years (n = 385); adolescents group, 13 to 20 years (n = 158). Stroke volume was calculated using aortic diameter and pulsed Doppler velocity profile. SV was indexed for body surface area (SVI). Effective arterial elastance (Ea) was estimated by end-systolic pressure/SVI and total arterial compliance (Ca) by pulse pressure/SVI. Quantitative B-mode ultrasound scans were used to measure intima-media thickness and diameters of the common carotid artery. Results: Intima-media thickness of carotid artery did not change with BMI z-score in the pre-school and school children groups (r = 0.09 and 0.11, p > 0.05, respectively), but a weak but significant correlation between intima-media thickness of carotid artery and BMI z-score was found in the adolescents group (r = 0.20, p < 0.05). In the pre-school children group, Ea and Ca did not correlate with BMI z-score, but there were significant relationships between BMI z-score and Ea and Ca in the school children (r = 0.27 and 0.16, p < 0.01, respectively) and in the adolescents groups (r = 0.38 and 0.29, p < 0.01, respectively). The slope of the relationship between BMI z-score and Ea in the adolescents group was significantly steeper compared with the school children group (p<0.05). Conclusion: Obesity-related arterial functional changes begin to appear in younger school children, however, remodeling of the common carotid artery is not yet present. With advancing age, negative effects of obesity on vascular functional and morphological changes become apparent. Our findings suggest that primary prevention programs should be initiated in early childhood.
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Wahyudin Purba, Deddy, and Fikri Padhilah. "Pengaruh Konsentrasi Nutrisi-Ab Mix Dan Variasi Media Terhadap Hasil Cabai Merah Dengan Hidroponik Sistem Wick." Jurnal Agrium 18, no. 2 (September 22, 2021). http://dx.doi.org/10.29103/agrium.v18i2.5339.

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Penelitian ini disusun berdasarkan Rancangan Acak Kelompok (RAK) Faktorial dengan 2 faktor perlakuan dan 3 ulangan. Faktor pertama adalah pemberian nutrisi AB Mix (A) terdiri dari tiga taraf yaitu A1 = 1000 ppm/plot, A2 = 1500 ppm/plot, A3 = 2000 ppm/plot. Faktor kedua adalah variasi media tanam (M) terdiri dari 3 jenis yaitu M1 = Rockwool, M2 = Arang Sekam Padi + Serbuk Gergaji, M3 = Arang Sekam Padi + Cocopeat. Hasil penelitian pemberian Pemberian Pupuk Ab-Mix menunjukkan tidak berpengaruh nyata pada pengamatan tinggi tanaman, menunjukkan pengaruh nyata pada pengamatan jumlah daun, jumlah daun terbanyak yaitu konsentrasi AB Mix 1000 ppm/plot (A1) yaitu 40,22 helai. Menunjukkan tidak berpengaruh nyata pada pengamatan jumlah bunga, dan produksi pertanaman sampel, tetapi menunjukkan pengaruh nyata pada pengamatan produksi per plot, dengan produksi terbanyak yaitu pemberian konsentrasi AB Mix 1000 ppm/plot (A1) menunjukkan jumlah produksi yaitu 130,44 g. Pemberian berbagai jenis media tanam menunjukkan tidak berpengaruh nyata pada semua parameter amatan. Interaksi pemberian AB Mix dan media tanam menunjukkan tidak berpengaruh nyata pada parameter pengamatan tinggi tanaman, tidak menunjukkan pengaruh nyata pada parameter pengamatan jumlah daun 2 dan 6 MST, tetapi berpengaruh yata pada umur 4 MST, tidak menunjukkan pengaruh yang nyata pada parameter pengamatan jumlah bunga, produksi per tanaman sampel dan produksi per plot
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Yagi, Tsukasa, Eizo Tachibana, Yasushi Ueki, Kazuo Sakamoto, Hiroshi Imamura, Takamichi Miyamoto, Hiroshi Takahashi, et al. "Abstract 13004: The Effect of Vasopressor Agents in the Treatment of Cardiovascular Shock." Circulation 132, suppl_3 (November 10, 2015). http://dx.doi.org/10.1161/circ.132.suppl_3.13004.

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Abstract:
Background: Various vasopressor agents are used for the treatment of cardiovascular shock. According to a randomized double-blind comparison study reported in 2010, norepinephrine is more useful than dopamine for patients in cardiovascular shock. In Japan, although both norepinephrine and dopamine are used as first-line vasopressor agents, the status of use and usefulness of the two agents have not yet been clarified. Methods: The Japanese Circulation Society (JCS) Shock Registry was a prospective, observational, multi-center, cohort study between May 2012 and June 2014.Of the patients registered in the JCS-Shock Registry, data of those who received norepinephrine or dopamine as a vasopressor agent, without the use of intra-aortic ballon pumping or cardiopulmonary bypass, were examined. The primary end point of the study was the rate of death at 30 days. Results: Of the 980 patients registered in the JCS-Shock Registry, the data of 320 patients were included in this analysis, after exclusion of patients who had not received the two agents and patients meeting the exclusion criteria. Of the 320 patients, 98 had received norepinephrine (N group), 142 had received dopamine (D group), and 80 had received both agents (N+D group). The acute mortality rates were 26.5, 25.4 and 46.2% in the N, D and N+D groups, respectively (p = 0.003). In a stratified analysis according to the renal function (eGFR [median: 43] ≥43 [normal renal function] versus eGFR <43 [reduced renal function]) at the time of admission, the acute mortality rates in the patients of the N, D and N+D groups with normal renal function were 7.8, 21.1 and 41.2%, respectively (p = 0.001), being significantly lower in the N group. On the other hand, the acute mortality rates in the patients of the N, D and N+D groups with reduced renal function were 46.8, 29.6 and 50.0%, respectively (p = 0.049), being significantly lower in the D group. Conclusion: Although norepinephrine is recommended as the first-line treatment, a trend towards more frequent use of dopamine was found in Japan. In addition, norepinephrine appeared to contribute to a reduction of the acute mortality in patients with normal renal function, while dopamine appeared to contribute to a reduction of the acute mortality in patients with reduced renal function.
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