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Schmitt, Thomas, Hartmut Goldschmidt, Kai Neben, Anja Freiberger, Johannes Huesing, Martina Gronkowski, Markus Thalheimer, et al. "Aprepitant, granisetrone, and dexamethasone for prevention of CINV after high-dose melphalan in autologous transplantation: Results of a randomized, placebo-controlled phase III trial." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 9612. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.9612.
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9612 Background: Aprepitant (A) is a NK1-antagonist approved for prevention of chemotherapy-induced nausea and vomiting (CINV). Though melphalan (M) is regarded only moderately emetogenic, CINV after high-dose M conditioning in autologous TPX can severely interfere with patients’ (pts) quality of life. Here we present the results of our monocentric, randomized (1:1), placebo-controlled, double-blind phase IIIb trial of A, granisetrone (G) and dexamethasone (D) in this setting. Methods: Pts were treated with A 125 mg po day 1, A 80 mg po days 2-4, G 2 mg po days 1-4 and D 4 mg po day 1, D 2 mg po days 2-3 (arm A) or placebo (P) days 1-4, G 2 mg po days 1-4 and D 8 mg day 1, D 4 mg days 2-3 (arm B). Melphalan 100 mg/m² iv was administered days 1-2. Episodes of emesis, modified functional living index – emesis questionnaire (FLIE) and intensity of nausea by visual analogue scale (VAS) were recorded between days 1-6. Primary endpoint was defined as no episode of vomiting and no additional antiemetic therapy within 120h of M administration. Results: Between 07/05 and 01/12 a total of 362 pts were randomized. 361 subjects (arm A=180; arm B=181; male n=229; female n=132; median age arm A=59.5 years; median age arm B=58 years) were available for the efficacy analysis. There were no significant differences in gender distribution and previous experience of CINV. Significantly less pts receiving A failed the primary endpoint (42% vs. 59%, OR=0.53 [0.34; 0.82], p=.0046). This effect was stressed in women (57% vs. 82%, OR=0.30) and patients with previous CINV (48% vs. 71%, OR=0.38). Emesis within 120h occurred in 22% of pts receiving A and 35% receiving P (OR=0.5 [0.31; 0.80], p=.0036). Though differences in overall nausea (16% vs. 22%, OR=0.65 [0.83; 1.10], p=.11) did not reach statistical significance, major nausea (VAS >25mm) was reduced (6% vs. 12%, OR=0.42 [0.19; 0.92], p=.026). Difference in FLIE score was -8.2 (p=.0007). Study medication was well tolerated. PK analyses showed no interaction between M and A. Conclusions: The combination therapy with A resulted in significantly less CINV compared to placebo. This effect was pronounced in women and pts with previous CINV. Clinical trial information: NCT00571168.
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Benavides-Villanueva, F., R. Fernández-Ramón, J. J. Gaitán-Valdizán, I. Gonzalez-Mazon, L. Sanchez-Bilbao, J. L. Martín-Varillas, D. Martínez-López, R. Demetrio-Pablo, and R. Blanco. "AB1636 CLINICAL PHENOTYPES IN SARCOIDOSIS USING CLUSTER ANALYSIS IN A COHORT OF 342 PATIENTS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 2052–53. http://dx.doi.org/10.1136/annrheumdis-2023-eular.5572.
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BackgroundSarcoidosis is a multi-system disease with unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and occurs at any time of life. This disease can affect any organ with a frequency varying according to ethnicity, sex and age most of the time affecting the pulmonary system with symmetrical bilateral hilar adenopathy. Extrapulmonary manifestations in skin, eyes, liver or lymphatic system can take a great morbimortality in patients.ObjectivesToa) indicate the phenotypes with similar characteristics with a cluster analysis andb) describe the principal features of those phenotypes.MethodsA model-based clustering was performed in a cohort of 342 sarcoidosis patients, diagnosed and follow-up from 1999 to 2019 at northern Spain hospital. Four homogeneous phenotypes were proposed in our study (C1: parenchymal lung involvement with dyspnea; C2: erythema nodosum and articular involvement with asthenia; C3: isolated hilar adenopathy; C4: miscellaneous extrapulmonary sarcoidosis). Chi-square test and ANOVA were used to compare, respectively, categorical, and continuous variables among groups. Two-sample t-tests and the partition of Pearson’s chi-square statistic for were used in pairwise comparisons.ResultsCluster analysis identified four groups: C1 (n=128; 37.4%), C2 (n=75; 21.9%), C3 (n=82; 24.0%), and C4 (n=57; 16.7%)(Table 1).Lung involvement was predominant in all clusters, ranged from 93.3% (C2) to 100% (C3). Extrapulmonary involvement was significantly higher in C2 (97.3%) and C4 (98.2%). Systemic steroids were significantly more used in cluster 1 (75.8%) compared to the rest (C2: 57.3%; C3: 48.8%; C4: 47.4%)(Figure 1).ConclusionSarcoidosis has a heterogenous disease, and a cluster analysis can be a useful tool to identify the clinical patterns and can be useful for the management.Reference[1]Sève P, Pacheco et al. Cells 2021;10. PMDI: 1739240.Table 1.Demographic and clinical characteristics of the study population. Data presented: n (%) or mean±SDCharacteristicsWhole cohort n=342C1 n=128C2 n=75C3 n=82C4 n=57p-valueq-valueGender (female)177 (51,8)45 (35.2)A,B,C47 (62.7)A46 (56.1)B39 (68.4)C<0.001<0.001Age at diagnosis (years)47.7±15.146.4±14.0A43.4±13.1B, C51.7±16.8A, B50.5±15.5C0.002<0.004Ethnicity0.80.8Caucasian322 (94.2)121 (94.5)70 (93.0)76 (92.7)56 (98.2)Hispanic15 (4.4)5 (3.9)4 (5.3)5 (6.1)1 (1.8)Black4 (1.2)2 (1.6)1 (1.3)1 (1.2)0Pulmonary involvement302 (88.3)120 (93.8)A70 (93.3)B82 (100)A,B30 (52.6)A,B<0.001<0.001Extrapulmonary involvement234 (68.6)68 (53.1)A,B73 (97.3)A,C37 (45.1)C,D56 (98.2)B,D<0.001<0.001Skin117 (34.2)26 (20.3)A56 (74.7)A3 (3.7)A32 (56.1)A<0.001<0.001Eye61 (17.8)22 (17.2)A15 (20.0)B21 (25.6)C3 (5.3)A,B,C0.020.04Liver33 (9.6)12 (9.4)5 (6.7)10 (12.2)6 (10.5)0.70.8Spleen7 (2.0)5 (3.9)1 (1.3)1 (1.2)00.30.4Bone4 (1.2)1 (0.8)2 (2.7)01 (1.8)0.40.5Joint95 (27.8)23 (18.0)A49 (65.3)A0A25 (43.9)A<0.001<0.001Parotid4 (2.3)2 (1.6)3 (4.0)2 (2.4)1 (1.8)0.70.8Kidney13 (3.8)2 (1.6)A0B0C11 (19.3)A,B,C<0.001<0.001Nervous system29 (8.5)6 (4.7)A16 (21.3)A,B,C6 (7.3)B1 (1.8)C<0.001<0.001Heart5 (1.5)3 (2.3)002 (3.5)0.20.3CIS: conventional synthetic immunosuppressants; SD: standard deviation.Groups sharing the same letter (A, B, C, D) have statistically significative differences (q>0.005) in the pairwise comparison.Abbreviation in alphabetical order: n=number; SD: standard deviation.Figure 1.Dendrogram of the hierarchical clustering leading to four clusters.C1: parenchymal lung involvement with dyspnea;C2: erythema nodosum and articular involvement with asthenia;C3: isolated hilar adenopathy;C4: miscellaneous extrapulmonary sarcoidosis.Acknowledgements:NIL.Disclosure of InterestsFabricio Benavides-Villanueva: None declared, Raúl Fernández-Ramón: None declared, Jorge Javier Gaitán-Valdizán: None declared, Iñigo Gonzalez-Mazon: None declared, Lara Sanchez-Bilbao: None declared, José Luis Martín-Varillas: None declared, David Martínez-López: None declared, Rosalía Demetrio-Pablo: None declared, Ricardo Blanco Speakers bureau: Speakers bureau: Abbvie, Pfizer, Roche, lilly, Bristol-Myers, Janssen, Galapagos and MSD, Consultant of: Consultant of: Abbvie, Pfizer, Roche, lilly, Bristol-Myers, Janssen and MSD, Grant/research support from: Grant/research support from: Abbvie, MSD, novartis and Roche.
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Kashif, Sanum, and Asia Hanif. "Comparison of Primary Outcomes in Extra-Abdominal Versus Intra-Abdominal Uterine Repair at Caesarean Section: A Comparative Study." Life and Science 3, no. 2 (April 7, 2022): 04. http://dx.doi.org/10.37185/lns.1.1.185.
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Objective: To compare extra-abdominal repair of uterine incision, in caesarean section with in situ repair, in terms of duration of surgery.Study Design: Comparative study. Place and Duration of Study: The study was conducted in Gynae and Obstetrics Department of CMH Abbottabad from May 2016 to Nov 2017.Materials and Methods: A total of 362 patients were randomized by creating permuted blocks of 6. In Group A (n=181), uterus was exteriorized, following delivery of baby and in Group B (n=181) in-situ repair of uterus was performed. Lower segment cesarean section (LSCS) with Pfannenstiel incision was made, with uterine repair in two layers. Data was collected by the trainee herself on the annexed pro forma. SPSS version 20 was used for data analysis.Results: The mean age of participants was 29.57 ± 5.79 years while mean age in group-A was 29.09 ± 5.52 years and in group-B was 30.04 ± 6.02 years. The mean gestational age in group-A and group-B was 37.26 ± 3.05 weeks and 37.24 ± 2.98 weeks respectively. The mean operative time in group-A was significantly lower (34.90 ± 5.84 minutes) then group-B (36.25 ± 6.36 minutes), p-value = 0.036 (< 0.05)Conclusion: The surgical time in extra abdominal uterine repair in caesarean sections was significantly short as compared to intra-abdominal repair, so exteriorization of uterus is more advantageous than in situ repair in terms of postoperative recovery.
How to cite this: Kashif S, Hanif A. Comparison of Primary Outcomes in Extra-Abdominal Versus Intra-Abdominal Uterine Repair at Caesarean Section: A Randomized Controlled Trial. Life and Science. 2022; 3(2): 79-82. doi: http://doi.org/10.37185/LnS.1.1.185
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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Desbiez, C., H. Lecoq, S. Aboulama, and M. Peterschmitt. "First Report of Cucurbit yellow stunting disorder virus in Morocco." Plant Disease 84, no. 5 (May 2000): 596. http://dx.doi.org/10.1094/pdis.2000.84.5.596c.
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In October, 1999, severe yellowing symptoms were observed in a melon (Cucumis melo L.) crop grown under plastic tunnels in the region of Agadir, Morocco. Large populations of whiteflies (Bemisia tabaci) were noticed during the early stages of the crop. At harvest, leaf samples were collected from two symptomatic plants and one symptomless plant. A mature yellow leaf was assayed from each symptomatic plant and for one of these two plants a younger leaf exhibiting only yellow spots. Cucurbit aphid-borne yellows virus, which causes similar symptoms in melons, was not detected by double-antibody sandwich enzyme-linked immunosorbent assay tests. Total RNA was extracted from fresh leaf tissues and submitted to reverse transcription and polymerase chain reaction with primers specific to two whitefly-transmissible viruses: Beet pseudo-yellows virus (BPYV) and Cucurbit yellow stunting disorder virus (CYSDV) (2). No amplification was obtained with BPYV-specific primers. In contrast, an expected 465-bp product was amplified in all samples from symptomatic plants with CYSDV-specific primers. No amplification was detected in samples from the symptomless plant nor from healthy control plants. B. tabaci-transmitted CYSDV has been reported in the Middle East, southwestern Europe, and North America (1,4). This is the first report of CYSDV in Morocco, and it follows the first report of another B. tabaci-transmitted virus, Tomato yellow leaf curl virus, in tomato (3), suggesting an important change in the viral pathosystem affecting vegetable crops in Morocco. References: (1) Kao et al. Plant Dis. 84:101, 2000. (2) Livieratos et al. Plant Pathol. 47:362, 1998. (3) Peterschmitt et al. Plant Dis. 83:1074, 1999. (4) Wisler et al. Plant Dis. 82:270, 1998.
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Costa, Geraldo Márcio da, Rodrigo Alves Barros, Dircéia Aparecida da Costa Custódio, Ulisses de Pádua Pereira, Demétrio Junqueira Figueiredo, and Nivaldo da Silva. "Resistência a antimicrobianos em Staphylococcus aureus isolados de mastite em bovinos leiteiros de Minas Gerais, Brasil." Arquivos do Instituto Biológico 80, no. 3 (September 2013): 297–302. http://dx.doi.org/10.1590/s1808-16572013000300006.
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Staphylococcus aureus (S. aureus) destaca-se como um dos agentes etiológicos mais frequentes da mastite bovina, que causa os maiores prejuízos econômicos à pecuária leiteira brasileira. Visando avaliar o perfil de sensibilidade deste agente aos antimicrobianos, 352 isolados provenientes de 35 rebanhos leiteiros localizados em Minas Gerais foram submetidos a testes de antibiograma, utilizando-se a técnica de difusão em disco. Nitrofurantoína, bem como as associações de neomicina, bacitracina e tetraciclina (NBT) e penicilina, nafcilina e dihidroestreptomicina (PND), apresentaram 100% de eficiência in vitro. Foram verificados baixos índices de resistência no grupo das cefalosporinas, com valores de 0, 0,28 e 0,40% para cefquimona, cefalotina e ceftiofur, respectivamente. Entre os aminoglicosídeos, observou-se 1,69% de resistência para gentamicina e 3,35% para a neomicina. O maior índice de resistência foi observado para polimixina B (82%), seguido pelos betalactâmicos, ampicilina e penicilina, com índices de resistência de 80,92 e 80,45%, respectivamente. Níveis intermediários de resistência foram observados para tetraciclina, lincomicina, cefoperazona e sulfazotrim. Entre os isolados testados, 65 (18,15%), oriundos de 24 dentre os 35 rebanhos estudados, apresentaram multirresistência (índice MAR ≥ 0,2). Os resultados apontaram grande variação nos perfis de resistência aos antimicrobianos, assim como a ocorrência de múltipla resistência entre algumas cepas estudadas, salientando a necessidade de testes de antibiograma para a escolha dos antimicrobianos mais adequados para o tratamento ou prevenção de mastite causada por S. aureus.
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Li, Mingjia, Aziz Nazha, Paul Elson, Sean Hobson, Mikkael A. Sekeres, Matt E. Kalaycio, Ronald M. Sobecks, et al. "A Prognostic Scoring System for Newly Diagnosed Adult Acute Lymphocytic Leukemia Patients." Blood 124, no. 21 (December 6, 2014): 5252. http://dx.doi.org/10.1182/blood.v124.21.5252.5252.
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Abstract Introduction: Traditional prognostic factors for adult acute lymphocytic leukemia (ALL) include age, white blood count at diagnosis, and cytogenetic (CG) risk. We sought to identify a more detailed prognostic risk score for newly diagnosed adult patients (pts) based on these and other pre-treatment characteristics. Methods: 82 newly diagnosed ALL pts given induction chemotherapy (IC) at our institution between the years 2003-2011 were included, and data were obtained by chart review. Institutional review board approval was obtained. Variables examined included: gender, age, immunophenotype, CG risk, pre-IC body mass index (BMI), pre-IC and day 28 serum albumin, absolute lymphocyte (ALC) and neutrophil (ANC) counts, positive culture (blood or other) during IC, positive imaging suggestive of infection (during IC), and allogeneic hematopoietic cell transplant (AHCT). CG risk was ascribed by CALGB criteria (Blood 1999; 93: 3983). BMI was defined by: underweight (≤ 18.5), normal (> 18.5-25.0), overweight (> 25.0-30.0), moderately obese (> 30.0-35.0), severely obese (> 35.0-40.0), and very severely obese (> 40.0). The primary endpoint was overall survival (OS) which was measured from IC to death or last follow-up. Proportional hazards models were used for univariable and multivariable analyses. In the multivariable analysis stepwise variable selection was used to identify independent predictors. Results were internally validated using a bootstrap algorithm. For convenience measured factors were discretized using a recursive partitioning algorithm. Prognostic groups were formed by assigning “points” to each factor that were based on the magnitude of the estimated regression coefficients of the final model, and then summing the total number of points present. Results: Median age at diagnosis was 43 yrs (range 18-78); 58% male. 71% of pts (58/82) had a B-cell immunophenotype. CG risk included: normal: 15 pts (18%), high: 41 pts (50%), miscellaneous: 9 pts (11%), and unknown: 17 pts (21%). Twenty-four pts (29%) were Ph+. The majority of pts (70%: 57/82) received the CALGB 19802 regimen (Cancer 2013; 119: 90) for IC +/- a tyrosine kinase inhibitor (if they were Ph+). 27% of pts (22/ 82) received AHCT in CR1. Estimated median OS is 41.5 months (95% CI: 15.5-N/A). In univariable analysis age, pre-induction BMI, Day 28 ALC, pre- and Day 28 albumin, Day 28 ANC, Day 28 platelet count, evidence of infection, and CG risk were all seen to impact outcome. In multivariable analysis pre-IC BMI and albumin, age, and Day 28 ALC were identified as independent predictors. Assigning 1 “points” each for age >50, albumin prior to IC ≤ 3.2 g/dL, or Day 28 ALC ≤ 50 /uL and 2 points for BMI ≥ 35, 3 prognostic groups were defined: favorable (0 points) 32% of pts (26/80): estimated 5-yr OS of 68% +/-11%; intermediate (1 points) (29% of pts, 23/80): estimated 5 yr OS of 39% +/-11%, and unfavorable (≥ 2 points) (39% of pts, 31/80) with estimated 5 yr OS of 17% +/- 7% (Figure 1). Conclusion: We have constructed a simple prognostic model for newly diagnosed adults with ALL. This model will need to be validated in a larger group of uniformly treated patients. Table 1 Prognostic Factors for OS in Univariable and Multivariable Analysis Factor Univariable (HR (95% C.I.)) Multivariable (HR (95% C.I.)) Age at dx (≤50 vs. >50) 3.29 (1.80-5.99), p=.0001 2.83 (1.45-5.53), p=.002 Pre-IC BMI (<35 vs. >35) 2.95 (1.57-5.52), p=0.0008 3.88 (1.84-8.17), p=.0004 Pre-IC albumin (≥ 3.2 vs. < 3.2 g/dl) 2.61 (1.43-4.77), p=0.002 2.66 (1.33-5.30), p=.0006 Day 28 ALC (> 50/uL vs. ≤50/uL) 3.57 (1.61-7.91), p=0.002 3.11 (1.33-7.28), p=.009 CG risk 2.03 (0.98-4.22); p=0.06 ------ Day 28 albumin (>2.3 vs. ≤2.3 g/dl) 3.37 (1.66-6.83), p=0.0008 ------ Day 28 ANC (>200/uL vs. ≤200/uL) 4.51 (1.94-10.51), p=.0005 ------ Day 28 platelets (>75K/uL vs. ≤75K/uL) 2.44 (1.26-4.72), p=.008 ------ Any positive culture (no vs. yes) 2.19 (1.19-4.04), p=0.01 ------ Blood culture positive for bacteria (no vs. yes) 2.34 (1.28-4.30), p=0.006 ------ Positive imaging suggestive of infection (no vs. yes) 2.44 (1.34-4.46), p=0.004 ------ Positive blood culture and image (no vs. yes) 1.96 (1.07-3.57), p=0.03 ------ Figure 1 Prognostic Groups Figure 1. Prognostic Groups Disclosures No relevant conflicts of interest to declare.
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Desbiez, C., H. Lecoq, M. Girard, A. C. Cotillon, and L. Schoen. "First Report of Cucurbit yellow stunting disorder virus in Commercial Cucumber Greenhouses in France." Plant Disease 87, no. 5 (May 2003): 600. http://dx.doi.org/10.1094/pdis.2003.87.5.600c.
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In autumn 2001, severe yellowing symptoms were observed on greenhouse-grown cucumbers near Perpignan (southern France). Leaf samples were collected from two sites where plants displayed symptoms ranging from limited yellowing of the older leaves to severe, complete yellowing of the whole plant. Cucurbit aphid-borne yellows virus, a polerovirus that causes similar symptoms was not detected in doubleantibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) using a specific antiserum. Total RNA was extracted from fresh leaf tissues and used in reverse transcription-polymerase chain reaction (1) with primers specific for two whitefly-borne viruses also inducing yellows and occurring in the Mediterranean basin (1): Beet pseudo yellows virus (BPYV, genus Closterovirus) transmitted by Trialeurodes vaporariorum (West.) and Cucurbit yellow stunting disorder virus (CYSDV, genus Crinivirus) transmitted by Bemisia tabaci (Genn.). No BPYV was detected in this survey, but CYSDV was present in all samples. In subsequent surveys conducted in the spring and summer of 2002, BPYV and CYSDV were detected, sometimes in mixed infections, in samples collected from the same region. The complete CYSDV coat protein gene was amplified by PCR using specific primers (2), yielding the expected-size fragment of 756 bp. The French isolate (GenBank Accession No. AY204220) shared 99.6 to 100% nucleotide sequence identity in the sequenced CP fragments (700 nt) with isolates of the most common, highly homogenous subgroup of CYSDV that has emerged recently in the Middle East, southwestern Europe (Spain and Portugal), United States, and Morocco (2). To our knowledge, this is the first report of CYSDV in France and it shows the threat represented by the current emergence of B. tabaci-transmitted viruses. References: (1) I. C. Livieratos et al. Plant Pathol. 47:362, 1998. (2) L. Rubio et al. J. Gen. Virol. 82:929, 2001.
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Kopecna, M., I. Trcka, J. Lamka, M. Moravkova, P. Koubek, M. Heroldova, V. Mrlik, A. Kralova, and I. Pavlik. "The wildlife hosts of Mycobacterium avium subsp. paratuberculosis in the Czech Republic during the years 2002–2007." Veterinární Medicína 53, No. 8 (September 5, 2008): 420–26. http://dx.doi.org/10.17221/1931-vetmed.
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The objective of this study was to determine the wildlife hosts of Mycobacterium avium subsp. paratuberculosis (MAP) in the Czech Republic. A total of 8 796 wildlife animals were examined by culture of faecal or tissue samples during the years 2002–2007. MAP was isolated from 12 (0.5%) out of 2 296 red deer (Cervus elaphus), two (0.2%) out of 835 roe deer (Capreolus capreolus), 78 (5.7%) out of 1 381 fallow deer (Dama dama), 28 (3.2%)out of 866 mouflons (Ovis musimon), four (2.5%) out of 162 chamois (Rupicapra rupicapra) and from one (0.1%) out of 805 wild boar (Sus scrofa). MAP was not cultured from 82 badgers (Meles meles), 55 martens (Martes foina), one pine marten (Martes martes), 25 brown hares (Lepus europaeus), five rabbits (Oryctolagus cuniculus), nine European polecats (Mustela putorius), two steppe polecats (Mustela eversmannii), two American minks (Mustela vison), four raccoon dogs (Nyctereutes procyonoides) and four Eurasian otters (Lutra lutra). MAP was isolated from three (2.0%) out of 149 small terrestrial mammals: one (5.9%) out of 17 brown rats (Rattus norvegicus), one (1.7%) out of 59 common voles (Microtus arvalis) and one (2.6%) out of 39 lesser white-toothed shrews (Crocidura suaveolens). Culture examinations of 34 house mice (Mus musculus) and 2 113 pigeons (Columba livia f. domestica) were negative. All 123 in vitro growing MAP isolates from wild ruminants were of IS900 RFLP type B-C1. One mouflon infected with a MAP strain which did not grow on the tested media was after IS1311-PRA-PCR assessed as being infected with a “sheep” strain. The RFLP type of the MAP isolate from the wild boar was of the RFLP type A-C10. Although the detection of MAP in wildlife in the Czech Republic was not very high, their role as a potential risk factor for cattle should be considered.
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Baz, Rachid, Thomas G. Martin, Melissa Alsina, Kenneth H. Shain, Hearn J. Cho, Jeffrey L. Wolf, Anuj Mahindra, et al. "Pomalidomide, Cyclophosphamide, and Dexamethasone Is Superior to Pomalidomide and Dexamethasone in Relapsed and Refractory Myeloma: Results of a Multicenter Randomized Phase II Study." Blood 124, no. 21 (December 6, 2014): 303. http://dx.doi.org/10.1182/blood.v124.21.303.303.
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Abstract Background: Pomalidomide-dexamethasone results in an overall response rate of 33% and median PFS of 4.2 months in patients with prior lenalidomide and bortezomib (Richardson et al. Blood 2014). In this randomized phase II trial, we compared pomalidomide-dexamethasone (arm B) versus the addition of oral weekly cyclophosphamide to pomalidomide-dexamethasone (arm C) in patients with lenalidomide-refractory multiple myeloma (MM). We have previously reported that the recommended phase II dose of cyclophosphamide with standard-dose pomalidomide + dexamethasone was 400 mg PO D1, 8, 15. Patients and Methods: Eligible patients had relapsed and refractory MM after at least 2 prior therapies and were lenalidomide refractory. Patients had a platelet count ≥ 50,000/mm3 and ANC ≥ 1,000/mm3 (patients with ≥50% bone marrow plasmacytosis were allowed if platelet count was ≥ 30,000/mm3and ANC could be supported with GCSF during screening and therapy). Patients were randomized (1:1) to receive pomalidomide 4 mg PO D1-21 and dexamethasone 40 mg PO D1, 8, 15, 22 (20 mg if older than 75 years) (arm B) with or without oral cyclophosphamide 400 mg PO D1, 8, 15 of a 28-day cycle (arm C). Patients randomized to arm B were allowed to cross over to arm C in the event of disease progression. Thromboprophylaxis was mandated with aspirin, warfarin, or LMWH. The primary endpoint was overall response rate using IMWG criteria. Secondary endpoints included an evaluation of PFS, OS and safety of the two arms. Results: Between 7/2012 and 3/2014, 36 patients were randomized to arm B and 34 to arm C. Patients characteristics were not different between the 2 arms (table below). The median number of prior therapies was 4 (2-12). All patients were lenalidomide refractory and none received prior pomalidomide. After a median follow up of 15 months, the overall response rate (partial response or better) was 39% and 65% (p=0.03) for arm B and C, respectively. The clinical benefit rate (minimal response or better) was 64% and 79% (p=0.2) for arm B and C, respectively. The median PFS was 4.4 months (95% CI 2.3-5.9) for arm B and 9.2 months (95% CI 4.6-16) for arm C (log rank p=0.04). As of July 2014, 28 patients had died (16 arm B, 12 arm C) with median overall survival of 10.5 versus 16.4 months (p=0.08) for arm B and C, respectively. Hematologic grade 3/4 adverse events were more frequent in arm C, although this was not statistically significant (see table). Thirteen patients crossed over and oral weekly cyclophosphamide was added to their tolerated dose of pomalidomide dexamethasone. For those patients, the best response was as follows: 2 PR, 2 MR, and 6 SD, 3 PD. Conclusions: Pomalidomide-dexamethasone in combination with oral weekly cyclophosphamide resulted in a superior response rate and PFS compared to pomalidomide-dexamethasone alone in patients with relapsed and refractory MM. The increased hematologic toxicities, as a result of the addition of oral cyclophosphamide, were manageable. Table Arm B (N=36) Arm C (N=34) P value Age, years, median (range) 63 (50-78) 64 (47-80) 0.7 Male, n (%) 23 (64) 18 (53) 0.3 Number of prior therapies, median (range) 4 (2-12) 4 (2-9) 0.5 Bortezomib refractory, n (%) 28 (78) 24 (71) 0.3 Carfilzomib refractory, n (%) 16 (44) 13 (38) 0.5 Prior high-dose therapy, n (%) 27 (75) 28 (82) 0.6 Prior alkylating agent, n (%) 32 (89) 32 (94) 1 B2-microglobulin, median (range) 3.2 (1.6-10) 3.6 (1.5-13.9) 0.5 Serum creatinine, median (range) 1 (0.5-2.3) 0.9 (0.6-2.1) 0.6 High-risk cytogenetics, n (%) 5 (24) 6 (28) 0.8 Deletion 17p, n (%) 3 (14) 4 (20) 0.8 t(4;14), n (%) 3 (14) 3 (14) 0.9 Trisomy or tetrasomy 1q, n (%) 11 (55) 6 (33) 0.4 Best response (partial response or better), n (%) 14 (39) 22 (65) 0.03 Clinical benefit rate (MR or better), n (%) 23 (64) 27 (79) 0.2 Grade 3/4 neutropenia, n (%) 12 (33) 17 (50) 0.2 Grade 3/4 febrile neutropenia, n (%) 4 (11) 6 (18) 0.5 Grade 3/4 thrombocytopenia, n (%) 2 (5) 5 (15) 0.2 Grade 3/4 anemia, n (%) 3 (8) 7 (20) 0.2 Grade 3/4 pneumonia, n (%) 4 (11) 3 (9) 1 Grade 3/4 fatigue, n (%) 2 (5) 4 (12) 0.4 Number of serious adverse events 17 20 Disclosures Baz: Celgene: Research Funding; Millenium: Research Funding; Bristol-Myers Squibb: Research Funding; Karypharm: Research Funding; Sanofi: Research Funding. Off Label Use: Pomalidomide cyclophosphamide dexamethasone in relapsed refractory myeloma. Martin:Sanofi: Research Funding; Novartis: Speakers Bureau. Alsina:Triphase: Research Funding; Millenium: Research Funding. Shain:Onyx / Amgen: Research Funding; Treshold: Research Funding. Chari:Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Array Biopharma: Membership on an entity's Board of Directors or advisory committees. Jagannath:Celgene: Honoraria; Millennium: Honoraria; Sanofi: Honoraria.
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Rocca, J., M. Beydon, V. Le Guern, E. Hachulla, J. J. Dubost, S. Jousse-Joulin, V. Devauchelle-Pensec, et al. "OP0233 IMPACT OF LYMPHOMA TREATMENT STRATEGY ON HEMATOLOGIC RESPONSE AND AUTOIMMUNE DISEASE ACTIVITY IN SJOGREN PATIENTS DEVELOPING LYMPHOMA." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 153–54. http://dx.doi.org/10.1136/annrheumdis-2023-eular.4525.
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BackgroundPrimary Sjögren Syndrome (pSS) patients have an increased risk of Non-Hodgkin lymphoma (NHL). There is no consensus on the therapeutic management of low-grade NHL. Two strategies can be proposed; either a ‘‘wait and see’’ strategy or an active therapeutic strategy.ObjectivesTo describe characteristics of NHL in pSS, therapeutic strategies and impact of these strategies on prognosis of lymphoma and of pSS.MethodsThis multicentric retrospective study included all lymphoma patients of the ASSESS cohort, enriched with patients recruited in Rheumatology and Internal Medicine departments. For each patient, we collected biological and clinical manifestations of pSS, lymphoma’s characteristics, and treatment strategy. Progression free survival (PFS) (lymphoma-PFS and pSS relapse free survival) and overall survival (OS) were analyzed.ResultsA total of 106 pSS patients who presented a B cell lymphoma between 1985 and 2019 were included. Among them 14 (13%) had diffuse large B cell lymphoma (DLBCL) and 82 pSS patients presented a low-grade B cell-NHL, mucosa-associated lymphoid tissue (MALT) lymphomas being the most frequent histologic subtype occurring in 68/82 (83%) patients.Among these 82 patients, a “wait and watch strategy” was chosen in 19 (23%) patients; 63 patients received a specific treatment for lymphoma at lymphoma diagnosis including systemic treatment (chemotherapy and/or immunotherapy) in 49 (60%) patients and local therapy (surgery or radiotherapy) in 14 (17%) patients; 10 patients further received rituximab (RTX) maintenance therapy.Comparison of treated versus not treated patients is presented in the Table 1. Untreated patients were older and had less pulmonary lymphoma location.We then analyzed the prognosis after a mean follow up of 6.5 years. Nine patients (11%) died during the follow-up. In multivariate analysis, age (HR= 1.16 [1.06-1.27], p = 0.001) and pulmonary location (HR= 8.15 [1.57-42.3], p = 0.013) were associated with death.Last, we compared OS, lymphoma PFS and pSS relapse PFS in treated versus not treated patients after propensity score weighting We observed that starting an active treatment for NHL at lymphoma diagnosis did not impact OS and lymphoma PFS (HR= 4.81 [0.48-47.9], p=0.2 and HR=1.12 |0.50- 2.48], p=0.8, respectively). Conversely, treating lymphoma had a protective effect on the risk of pSS relapse (HR 0.4 [0.17-0.95], p = 0.038). Last, among patients treated for lymphoma, we observed that no lymphoma relapse occurred in patients who received maintenance therapy with RTX (0/10 events vs 18/53, p = 0.04).ConclusionThis study based on a large number of pSS patients with lymphoma shows that age and pulmonary location are independently associated with the risk of death. The choice of treating lymphoma at its diagnosis or not does not affect OS and PFS for lymphoma. However treatment of lymphoma reduced the risk of pSS relapse. This should be taken into account when deciding therapeutic strategy in our pSS patients with lymphoma.Table 1.VariableWait and watch N=19Active treatment N=63p-val.F18/ 19 (95%)54/ 63 (86%)Age64.0 (54.0, 75.5)56.0 (47.0, 65.5)0.041Time between pSS and lymphoma diagnosis1.0 (0.0, 8.5)3.2 (0.1, 9.0)0.6ESSDAI6.0 (4.0, 8.0)8.0 (5.0, 14.0)0.2clinESSDAI4.0 (3.0, 7.0)6.5 (4.0, 12.8)0.091BiologySSA antibodies14/ 19 (74%)44/ 61 (72%)0.9SSB antibodies8/ 19 (42%)23/ 58 (40%)0.9Positive rheumatoid factor14/ 18 (78%)39/ 54 (78%)0.8Low C42/ 11 (18%)15/ 35 (43%)0.2Hypergammaglobulinemia9/ 16 (56%)30/ 45 (67%)0.5Lymphoma type0.7MALT lymphoma15/ 19 (79%)53/ 63 (84%)Nodal marginal zone lymphoma4/ 19 (21%)10/ 63 (16%)Lymphoma disseminationSalivary and/or ganglionar limited7/ 19 (37%)35/ 63 (56%)0.2Lymphoma spread ≥ 2 locations9/ 19 (47%)28/ 63 (44%)0.8Lymphoma localizationSalivary gland limited lymphoma4/ 19 (21%)20/ 63 (56%)0.4Pulmonary lymphoma involvement0/ 19 (0%)13/ 63 (21%)0.032Salivary gland lymphoma involvement11/ 19 (58%)36/ 63 (57%)>0.9OutcomeMedian follow-up7.0 (4.5, 8.5)6.0 (4.0, 13.5)0.7Death1/ 19 (5.3%)8/ 63 (13%)-REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Prajapati, Hasmukh J., James R. Spivey, Bassel F. El-Rayes, John S. Kauh, and Hyun Sik Kim. "Doxorubicin drug eluting beads transcatheter chemoembolization (DEB TACE) in patients with large hepatocellular carcinoma (HCC): Overall survival and a multivariate analysis (MVA) of prognostic factors." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e15033-e15033. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e15033.
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e15033 Background: To investigate the prognostic factors (PFs) associated with survival after DEB TACE in patients (pts) with at least > 5cm sized index HCC (iHCC). Methods: Consecutive pts with at least > 5cm sized iHCC, who received DEB TACE over last 82 months, were studied. Median overall survivals (mOSs) were analyzed according to different parameters from 1st DEB TACE. Kaplan Meier estimator by log rank test and Cox proportional Hazard model (for MVA) were used survival analyses using v20 SPSS. Results: 332 DEB TACEs (mean 3, medium 2) were performed in 112 pts (mean 62.1 years, SD 12), who had at least >5cm sized iHCC (mean 9.5 cm, SD 3.7). MOS from diagnosis and DEB TACE were 14.3 months (m) and 9.4 m respectively. MOS were 31.9 m, 11.1 m and 2.8 m in pts who received > 4, 2-4 and a 1 DEB TACEs respectively (p<0.001). Etiological factors for HCC were hepatitis C virus (54.4%), hepatitis B virus (12.5%), chronic alcoholism (7.1%), other causes of chronic liver disease (17%) and unknown with no chronic liver disease (9%); mOS were 8.8 m, 4.4 m, 5.8 m, 27 m, and 9.4 m respectively (p=0.01). MOS in pts with Child-Pugh Class A (58.9%), B (34.8%) and C (6.3%) were 17.2 m, 5.8 m and 1.6 m respectively (p<0.001). MOS in pts with BCLC stage B (17%), C (69.6%) and D (13.4%) were 20.9 m, 9.4 m, and 3.4 m respectively (p=0.003). 46.4% of pts had portal vein thrombosis (PVT) with mOS of 5.4 m vs. 17.1m in pts without PVT (p=0.006). Pts with serum alfa feto protein (sAFP) level>400 ng/dl (43.7%) had mOS of 5.4 m vs. 16.6 m in pts with sAFP<400ng/dl (p=0.008). 32.1% of pts received sorafenib systemic chemotherapy; mOS were 13.3m vs. 7.6m who did not receive the sorafenib (p=0.2). Pts with >5 HCCs (20.5%) had mOS of 5.4m vs. 13m in pts who had <5 HCCs (p=0.009). The following variables were independent significant PFs of survival on MVA: Child-Pugh class, etiology, number (no) of DEB TACEs, presence of vascular invasion and ECOG PS. Conclusions: Higher number of DEB TACE treatments correlates independently to improved OS in patients with at least >5cm sized index HCC. Other independent PFs of survival were etiology, Child-Pugh class, no of HCC tumors, ECOG PS and PVT.
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Van der Heijde, D., X. Baraliakos, M. Dougados, M. Brown, D. Poddubnyy, F. Van den Bosch, N. Haroon, et al. "OP0019 BIMEKIZUMAB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: 24-WEEK EFFICACY & SAFETY FROM BE MOBILE 2, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO-CONTROLLED STUDY." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 12–13. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2441.
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BackgroundBimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. In a phase 2b study, BKZ showed rapid and sustained efficacy and was well tolerated up to 156 weeks (wks) in patients (pts) with active ankylosing spondylitis (AS).1,2ObjectivesTo assess efficacy and safety of BKZ vs placebo (PBO) in pts with active AS up to Wk 24 in the ongoing pivotal phase 3 study, BE MOBILE 2.MethodsBE MOBILE 2 (NCT03928743) comprises a 16-wk double-blind, PBO-controlled period and 36-wk maintenance period. Pts were aged ≥18 yrs, met modified New York criteria and had active AS (BASDAI ≥4, spinal pain ≥4) at BL. Pts were randomised 2:1, BKZ 160 mg Q4W:PBO. From Wk 16, all pts received BKZ 160 mg Q4W. Primary and secondary efficacy endpoints were assessed at Wk 16.ResultsOf 332 randomised pts (BKZ: 221; PBO: 111), 322 (97.0%) completed Wk 16 and 313 (94.3%) Wk 24. BL characteristics were comparable between groups: mean age 40.4 yrs, symptom duration 13.5 yrs; 72.3% pts male, 85.5% HLA-B27+, 16.3% TNFi-experienced. At Wk 16, the primary (ASAS40: 44.8% BKZ vs 22.5% PBO; p<0.001) and all ranked secondary endpoints were met (Table 1). Responses with BKZ were rapid, including in PBO pts who switched to BKZ at Wk 16, and increased to Wk 24 (Figure 1; Table 1). Substantial reductions of hs-CRP by Wk 2 and MRI SIJ and spine inflammation by Wk 16 were achieved with BKZ vs PBO (Table 1). At Wk 24, ≥50% pts had achieved ASDAS <2.1 (Figure 1).Table 1.Efficacy at Wks 16 and 24BLWk 16Wk 24PBO N=111BKZ 160 mg Q4W N=221PBO N=111BKZ 160 mg Q4W N=221p valuePBO→BKZ 160 mg Q4W N=111BKZ 160 mg Q4W N=221Ranked endpoints in hierarchical orderASAS40* [NRI] n (%)--25 (22.5)99 (44.8)<0.00163 (56.8)119 (53.8)ASAS40 in TNFi-naïve† [NRI] n (%)--22 (23.4)a84 (45.7)b<0.00156 (59.6)a100 (54.3)bASAS20† [NRI]n (%)--48 (43.2)146 (66.1)<0.00185 (76.6)159 (71.9)BASDAI CfB† [MI] mean (SE)6.5 (0.1)6.5 (0.1)–1.9 (0.2)–2.9 (0.1)<0.001–3.3 (0.2)–3.3 (0.1)ASAS PR† [NRI]n (%)--8 (7.2)53 (24.0)<0.00128 (25.2)56 (25.3)ASDAS-MI† [NRI] n (%)--6 (5.4)57 (25.8)<0.00143 (38.7)67 (30.3)ASAS 5/6† [NRI]n (%)--16 (14.4)94 (42.5)<0.00157 (51.4)107 (48.4)BASFI CfB† [MI] mean (SE)5.2 (0.2)5.3 (0.2)–1.1 (0.2)–2.2 (0.1)<0.001–2.2 (0.2)–2.4 (0.2)Nocturnal spinal pain CfB† [MI]mean (SE)6.8 (0.2)6.6 (0.1)–1.9 (0.2)–3.3 (0.2)<0.001–3.7 (0.3)–3.8 (0.2)ASQoL CfB† [MI] mean (SE)8.5 (0.4)9.0 (0.3)–3.2 (0.3)–4.9 (0.3)<0.001–4.9 (0.4)–5.4 (0.3)SF-36 PCS CfB† [MI] mean (SE)34.6 (0.8)34.4 (0.6)5.9 (0.8)9.3 (0.6)<0.00110.6 (0.8)10.8 (0.6)BASMI CfB† [MI] mean (SE)3.8 (0.2)3.9 (0.1)–0.2 (0.1)–0.5 (0.1)0.005–0.5 (0.1)–0.6 (0.1)Other endpointsnEnthesitis-free state†c [NRI]n (%)--22 (32.8)d68 (51.5)e-33 (49.3)d70 (53.0)eASAS40 in TNFi-experienced [NRI]n (%)--3 (17.6)f15 (40.5)g---ASDAS-CRP CfB [MI]mean (SE)3.7 (0.1)3.7 (0.1)–0.7 (0.1)–1.4 (0.1)-–1.7 (0.1)–1.6 (0.1)hs-CRP (mg/L) [MI] geometric mean (median)6.7 (6.3)6.5 (8.2)6.0 (6.3)2.4 (2.4)-1.9 (2.2)2.1 (2.3)MRI spine Berlin CfBh [OC] mean (SD)3.3 (4.9)i3.8 (5.3)j0.0 (1.4)k–2.3 (3.9)l---SPARCC MRI SIJ score CfBh [OC] mean (SD)5.8 (7.7)i7.4 (10.7)m1.1 (6.9)k–5.6 (9.9)l---Randomised set. *Primary endpoint; †Secondary endpoint; an=94; bn=184; cMASES=0 in pts with BL MASES >0; dn=67; en=132; fn=17; gn=37; hIn pts in MRI sub-study; in=45; jn=82; kn=43; ln=79; mn=83; nNominal p values not shown.Over 16 wks, 120/221 (54.3%) BKZ pts had ≥1 TEAE vs 48/111 (43.2%) PBO; three most frequent on BKZ were nasopharyngitis (BKZ: 7.7%; PBO: 3.6%), headache (4.1%; 4.5%) and oral candidiasis (4.1%; 0%). No systemic candidiasis was observed. Up to 16 wks, incidence of SAEs was low (1.8%; 0.9%); no MACE or deaths were reported; 2 (0.9%) IBD cases occurred in pts on BKZ.ConclusionDual inhibition of IL-17A and IL-17F with BKZ in pts with active AS resulted in rapid, clinically relevant improvements in efficacy outcomes vs PBO. No new safety signals were observed.1,2References[1]van der Heijde D. Ann Rheum Dis 2020;79:595–604; 2. Gensler L. Arthritis Rheumatol 2021;73(suppl 10):0491.AcknowledgementsThis study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of InterestsDésirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Employee of: Imaging Rheumatology BV (Director), Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma, Maxime Dougados Consultant of: AbbVie, Eli Lilly, Novartis, Merck, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Matt Brown Speakers bureau: Novartis, Consultant of: Pfizer, Clementia, Ipsen, Regeneron, Grey Wolf Therapeutics, Grant/research support from: UCB Pharma, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, and UCB Pharma, Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GSK, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB Pharma, Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Filip van den Bosch Speakers bureau: AbbVie, Bristol Myers-Squibb, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Amgen, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB Pharma, Nigil Haroon Consultant of: AbbVie, Amgen, Janssen, Merck, Novartis and UCB Pharma, Huji Xu: None declared, Tetsuya Tomita Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Mitsubishi-Tanabe, Novartis, and Pfizer, Consultant of: AbbVie, Eli Lilly, Gilead, Novartis, and Pfizer, Lianne S. Gensler Consultant of: AbbVie, Eli Lilly, Gilead, GSK, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Novartis, Pfizer, and UCB Pharma; paid to institution, Marga Oortgiesen Employee of: UCB Pharma, Carmen Fleurinck Employee of: UCB Pharma, Thomas Vaux Employee of: UCB Pharma, Alexander Marten Employee of: UCB Pharma, Atul Deodhar Speakers bureau: Janssen, Novartis, and Pfizer; consultant of AbbVie, Amgen, Aurinia, BMS, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB Pharma.
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Talati, Chetasi, Aaron D. Goldberg, Amanda Przespolewski, Onyee Chan, Najla Al Ali, Christopher Famulare, David A. Sallman, et al. "Comparison of Induction Strategies and Responses for Acute Myeloid Leukemia Patients after Resistance to Hypomethylating Agents for Antecedent Myeloid Malignancy." Blood 132, Supplement 1 (November 29, 2018): 665. http://dx.doi.org/10.1182/blood-2018-99-119879.
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Abstract Background Outcomes in patients (pts) with secondary acute myeloid leukemia (sAML) (therapy related myeloid neoplasms and AML with myelodysplasia related changes (MRC) per WHO 2016 classification (Arber et al, Blood 2016)) are poor. Pts treated with hypomethylating agents (HMAs) have suboptimal responses to induction chemotherapy (IC) upon transformation to AML. Previously, it was retrospectively demonstrated that the IC with cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M) yields significantly higher response rates (64%) than 7+3 (cytarabine and anthracycline) (29%) in pts with prior HMA exposure (Jaglal et al, Leukemia Research 2014). Following the recent approval of CPX-351 for induction in sAML subgroup, we investigated outcomes after CPX-351 to cladribine based regimens and 7+3 in pts with sAML with prior HMA exposure. Methods We identified pts with sAML who had prior HMA treatment for an antecedent hematologic malignancy (AHM) and later received induction chemotherapy upon AML transformation from Moffitt Cancer Center (MCC) (n=229), Memorial Sloan Kettering Cancer Center (n=11) and Roswell Park Comprehensive Cancer Center (n=2). Patients were divided into 3 cohorts based on induction regimen: (A) cladribine based (CLA+/-G+/-M) (B) standard 7+3 and (C) CPX-351. Demographics, disease-specific variables, and outcomes were collected in accordance with the institutional review board approved protocol. Responders (R) were defined as pts achieving CR or CRi as defined by the 2003 International Working Group (IWG) criteria after 1 or 2 cycles of the either induction regimen whereas non-responders (NR) were defined as responses other than CR/CRi. Pts receiving a second induction with a different regimen were considered NR. Fisher's exact test and the ANOVA test were used to determine significance for continuous and categorical variables. Kaplan-Meier analysis with log-rank test was performed to estimate overall survival (OS). Results Among 242 pts who received IC for AML after HMA failure for prior AHM, 114 were treated with (A) cladribine based regimen (B) 94 pts with standard 3+7 and (C) 34 pts with CPX-351 (Cohort C). Baseline characteristics for all 3 cohorts are outlined in Table 1A. Median age for cohort A, B, and C were 65 (33-82), 66 (26-81), and 69 (36-82), respectively. Males comprised of 68.4%, 63% and 52.9% of the cohorts A, B and C, respectively. No pts had favorable-risk karyotype as defined by European LeukemiaNet (ELN) 2017 criteria. Adverse risk karyotype was noted in 42.1% of cohort A, 34.6% of cohort B and 22.7% of cohort C (p=.337). The majority of pts received azacitidine as their HMA for their AHM (88.7%, 84.9% and 82.4% in cohorts A, B, C, respectively) and median number of cycles administered prior to transformation to AML were 6, 4 and 5 for cohorts A, B, and C, respectively. Response rates in each cohort are summarized in Table 1B. The CR/CRi rate was 53% in cohort A, 32% in cohort B and 41.1% in cohort C (p=.005 between cohort A and B) (p=.329 between cohorts A and C) (p=.526 between cohorts B and C). The early death rates (<60 days of induction) were not significantly different among the 3 cohorts, at 12%, 8% and 2.9% in cohorts A, B and C respectively (p=.200). In pts who received ≤ 4 cycles of HMAs prior to AML transformation, response rates to CPX-351 were higher (64.3%) than in pts who received >4 cycles of HMAs (25.0%) (p=.0397). Cohort A (56.5% vs. 50.0%, p=.288) and B (39.1% vs. 25.5%, p=.175) did not demonstrate such a difference (Table 1C and 1D). There was a trend towards better OS (19.9 vs. 5.5mo) with CPX-351 treated pts with ≤ 4 cycles of HMAs compared to >4 cycles (p=.092) (Figure 1). To date, 70.0% of responding pts in cohort A have undergone an allogeneic stem cell transplant compared to 31.0% in cohort B and 28.6% in cohort C (p=.15). There was no significant difference in median OS among the 3 groups, cohort A (7.27 months), cohort B (7.63 months) and cohort C (7.07 months) (p=.887). Among responders, the mOS did not differ (12.93, 21.7, and 19.9 months for cohorts A, B, and C respectively, p=.635). Conclusions We demonstrate that cladribine-based induction regimens and CPX-351 yield higher CR/CRi rates compared to 7+3 in pts with sAML after HMA failure. Prolonged duration of HMA exposure may lower response potential with CPX-351 upon AML transformation. Median OS remains poor and did not differ among the 3 groups illustrating the unmet need for therapy for sAML pts after HMA failure. Disclosures Goldberg: AROG: Research Funding; Abbvie: Research Funding; Celgene: Research Funding; Pfizer: Research Funding. Sallman:Celgene: Research Funding, Speakers Bureau. List:Celgene: Research Funding. Wang:Amgen: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; Jazz: Speakers Bureau; Amgen: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Novartis: Speakers Bureau. Tallman:AROG: Research Funding; Cellerant: Research Funding; AbbVie: Research Funding; ADC Therapeutics: Research Funding; Orsenix: Other: Advisory board; Daiichi-Sankyo: Other: Advisory board; BioSight: Other: Advisory board. Komrokji:Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Sweet:Celgene: Honoraria, Speakers Bureau; Jazz: Speakers Bureau; Agios: Consultancy; Astellas: Consultancy; Phizer: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau; Phizer: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau; Astellas: Consultancy; Jazz: Speakers Bureau; BMS: Honoraria; Agios: Consultancy; Celgene: Honoraria, Speakers Bureau; BMS: Honoraria.
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Zektser, Miri, Katrina Hueniken, Michael Crump, Anca Prica, John Kuruvilla, Robert Kridel, Rodger E. Tiedemann, Armand Keating, and Vishal Kukreti. "Considering Older Patients As Candidates for Auto Stem Cell Transplants: A Comprehensive Study on Toxicities and Survival Analysis." Blood 142, Supplement 1 (November 28, 2023): 4964. http://dx.doi.org/10.1182/blood-2023-174816.
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Introduction: High-dose chemotherapy and autologous stem cell transplantation (ASCT) are commonly used for relapsed/refractory (R/R) Hodgkin (HL) and non-Hodgkin lymphoma (NHL). However, concerns about treatment-related mortality (TRM) and toxicity limit its use in older patients (pts). Existing evidence suggests higher rates of complications and inferior overall survival (OS) in older pts, but conflicting findings suggest that outcomes may be influenced by comorbidities rather than age ( Lahoud O, Curr Oncol Rep. 2015). Our study comparing ASCT outcomes and toxicities in lymphoma pts in younger and older age groups. Methods: In this retrospective study, we analyzed lymphoma pts who underwent ASCT at the Princess Margaret Cancer Centre from January 2015 to December 2019. After Institutional Review Board approval, clinical data was collected from institutional databases and patient charts. The hematopoietic cell transplantation comorbidity index (HCT-CI) and Charlson Comorbidity Index (CCI) were retrospectively calculated. Response assessment was done by Lugano 2014 classification. Grade 3-5 nonhematologic toxicities were collected from admission to day 100 using Common Terminology Criteria for Adverse Events version 5. Overall survival (OS) and progression-free survival (PFS) were calculated from date of transplant to death or disease progression. OS and PFS assessed via Kaplan-Meier; log rank tests and Cox regression performed. The patients were divided into two age groups: Group A (<65 years) and Group B (≥65 years). Results: There were 334 pts who underwent ASCT. 332 pts were analyzed; 2 pts were lost to follow-up and 16 pts were day 1 transfers, making acute toxicity data unavailable. The median age was 53 (range: 18-71), 17% of pts being aged ≥65. The majority of pts (69%) had NHL (table 1). The Eastern Cooperative Oncology Group (ECOG) performance status was ≤1 for 91%. Group B had a higher proportion of pts with ECOG score =2 (18% vs 7%, p < 0.001 ) and higher CCI (88% vs 27% , p < 0.001). NHL and mantle cell lymphoma (MCL) were more prevalent in Group B (93%, 23% vs 68%, 12% respectively, p< 0.001). Thirteen percent of NHL pts were transformed disease. Both groups had similar percentage of pts with central nervous system (CNS) lymphoma (~ 5%). Conditioning regimens varied based on lymphoma type: most of the HL/aggressive lymphomas: Etoposide+Melphalan (ML), CNS lymphoma: Thiotepa based regimen, and MCL Cytarabine + ML+/- Total Body Irradiation. The majority (83%) were treated for R/R disease, while 17% received it as first-line treatment. Prior to transplant, 76% of pts were in CR. Median follow-up was 38 months. Median OS was not reached for Group A, and 73 months for Group B. Five year OS were 82% and 74% respectively (p = 0.05). Median PFS was 75.2 months for Group A and 43.0 months for Group B, with 5-year PFS of 54% and 47% respectively (p = 0.2). Twenty percent of pts died during follow-up, with only 4% being NRM. From the entire cohort 3% of patients died within 100 days post-transplant, with no difference between groups. Three pts died within 100 days of ASCT with 2 deaths from sepsis (Group A) and 1 death from Respiratory failure (Group B). Common transplant-related toxicities did not differ significantly between groups (figure 1). Group B had significantly higher rates of Renal (7%vs 18%), Respiratory (16% vs 6%), and Metabolism abnormalities (14% vs 5%) (p = 0.021-0.028). Group B needed more blood product transfusions by 100 days post-transplant: Packed Cells (mean) 1.7 vs 1.1 units (p 0.08), Platelets (mean) 3 vs 1.9 units (p 0.002). Group B had a longer average length of stay 18 days vs. 14 days (p < 0.001). About 6% of pts required ICU admission, and 4% were discharged to rehabilitation/long-term care facilities, with no group differences. Conclusions: The study concludes that ASCT can be safely performed in appropriately selected elderly pts. TRM rates were not significantly higher in older compared to younger pts with lymphoma. However, older pts did experience higher rates of specific toxicities including renal failure, pulmonary complications, metabolism abnormalities, longer hospital stays, and increased transfusion requirements. In the multivariate analysis, older pts exhibited shorter OS, influenced by lymphoma type and treatment response. Further research is needed to develop risk stratification and geriatric assessments to improve toxicity prediction in elderly pts undergoing ASCT.
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Sirohi, Bhawna, David Cunningham, Andy Norman, Michele Trumper, Sheela Rao, Tracey Murray, Yvonne Prior, Geoffrey Chong, Kim Last, and Andrew Wotherspoon. "Use of Gemcitabine, Cisplatin and Methylprednisolone (GEM-P) with or without Rituximab in Relapsed and Refractory Patients with Diffuse Large B Cell Lymphoma (DLBCL)." Blood 106, no. 11 (November 16, 2005): 939. http://dx.doi.org/10.1182/blood.v106.11.939.939.
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Abstract There is currently no standard salvage chemotherapy regimen in patients with relapsed/ refractory DLBCL. We have previously shown that GEM-P is an effective salvage regimen in patients with relapsed/refractory lymphoma; 10 patients in this study had DLBCL (Br J Cancer2005;92:1352–7). The aim of this study was to evaluate the combination of GEM-P in a larger subset of DLBCL patients. This has not been reported before. Between 1/01 and 3/05, 39 (10 patients had transformed lymphoma) heavily pre-treated relapsed and refractory DLBCL patients received GEM-P; 24 (61%) of these patients also received Rituximab (R). The median age was 49 y (range, 18–68); 28 males; 64% patients had Stage III/IV disease; 69% had IPI ≥2. The median time from diagnosis to start of GEM-P ± R was 17 mo (range, 2mo-7 yrs). All patients had previously received an anthracycline-based regimen. The disease status at start of GEM-P ± R was: 24 patients were in 1st relapse, 7 had primary refractory disease, 5 were in 2nd relapse and 3 in 3rd relapse. Median number of cycles of GEM-P ± R received were 2 (range, 1–4). The overall response rate (RR) was 59% (95% CI 42.1–74.4). 11 (28%) patients attained complete response, 12 partial response and 15 patients did not respond; 1 patient died of progressive disease. The median response duration to GEM-P ± R in 23 responding patients was 332 days (range, 36–1530) compared to 170 days (range, 26–2264) in 32 responding patients to 1st-line chemotherapy. Of the 24 patients who received R (not randomised; given when available via NHS funding network) with GEM-P, the overall RR was 67% (95% CI 45–84) compared to 47% (95% CI 21–73) in those who did not receive R (P=0.2). Eight patients were consolidated with high-dose therapy which was an autologous stem cell transplant (ASCT) in 7 (all are alive and well except one who relapsed 4 mo later and died of progressive disease) and a reduced intensity conditioning matched unrelated donor transplant in 1 patient who died of transplant-related complications. The remaining patients did not undergo an ASCT due to treatment failure (n=16), cardiac insufficiency (n=2) and subclavian vein thrombosis (n=1). ASCT was not planned in the other 12 patients because of indolent histology (n=2), inadequate stem cell collection (n=1), lost-to follow-up (n=1), previous high-dose therapy (n=3) and stage 1 disease (n=1), physicians decision (n=1), patients choice (n=1) multiply relapsed disease (n=2). Progression-free survival (PFS) and overall surveival (OS) are shown in the Table. 23 patients are alive at a median follow-up of 543 days (range, 76–1598). In conclusion, GEM-P is an effective salvage regimen with long response duration in patients with relapsed or refrcatory DLBCL. The additional benefit with Rituximab on outcome warrants further studies in new and relapsed patients with DLBCL in a prospective, randomised trial. Survival OS PFS GEM-P (n=15) 3-y 40%(95%CI 16–63) 1-y 27%(95%CI 8–49) GEM-P +R (n=24) 3-y 65%(95%CI 40–82) 1-y 51% (95%CI 28–69) GEM-P ±R (n=39) 3-y 53.4% (95% CI 35–69) Median 157d (95% CI 42–271) PFS by rituximab use PFS by rituximab use
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Shaw, E. G., B. Berkey, S. W. Coons, D. Brachman, J. C. Buckner, K. J. Stelzer, G. R. Barger, P. D. Brown, M. R. Gilbert, and M. Mehta. "Initial report of Radiation Therapy Oncology Group (RTOG) 9802: Prospective studies in adult low-grade glioma (LGG)." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 1500. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.1500.
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1500 Background: Treatment of adult LGG is controversial. Favorable patients (pts) (age <40 years [yrs] who undergo gross total resection [GTR]) are typically observed. Unfavorable pts (age ≥40 who have subtotal resection [STR] or biopsy [B]) are usually given initial radiation therapy (RT), reserving chemotherapy (historically procarbazine, CCNU and vincristine [PCV]) for recurrence. In 1998, the RTOG, in conjunction with SWOG, NCCTG, and ECOG initiated prospective studies of adult LGG, the results of which are reported herein. Methods: Favorable pts were observed postoperatively in a single arm Phase II study (Arm 1). Unfavorable pts were stratified by age, histology, KPS, and presence/absence of contrast enhancement on preoperative magnetic resonance imaging and randomized to either RT alone (54Gy in 30 fractions to a local treatment field) (Arm 2) or RT followed by 6 cycles of standard dose PCV (Arm 3). Reported results include overall survival (OS) rate, median overall survival time (MOST), progression-free survival (PFS) rate, and median progression-free survival time (MPFST). Survival data are compared using Wilcoxon p-values. Results: A total of 362 eligible/analyzable pts were accrued between 1998 and 2002. Median follow-up time is 4 years. For the 111 favorable pts observed on Arm 1, OS at 2- and 5-yrs is 99% and 94%. PFS at 2- and 5-yrs is 82% and 50%. For the 251 unfavorable pts on Arms 2 (RT alone) and 3 (RT+PCV), there was no difference in OS or PFS. OS at 2- and 5-yrs was 87% and 61% with RT alone versus (vs) 86% and 70% with RT+PCV (p=0.72). MOST was not reached in RT alone pts and was 6.0 yrs in RT+PCV pts. PFS at 2- and 5-yrs was 73% and 39% with RT alone vs 72% and 61% with RT+PCV (p=0.38). MPFST was 4.0 yrs with RT alone vs 6.0 yrs with RT+PCV. Acute grade 3–4 toxicity occurred in 9% of pts who received RT alone, 67% who received RT+PCV (mostly hematologic). There were no treatment deaths on either arm. Conclusions: 5-yr PFS was poor in all three arms ranging from 39% to 61%. Only half of favorable pts were disease-free at 5 yrs. In unfavorable pts, there was no OS advantage with the addition of PCV to RT. Both PFS and MPFST were better with the addition of PCV, but not significantly. Analysis of outcome by 1p19q status is pending. No significant financial relationships to disclose.
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George III, Qiuhong Zhao, Timothy Voorhees, Nathan Denlinger, Narendranath Epperla, Audrey M. Sigmund, Gabriela Sanchez-Petitto, et al. "Association between post-CART terminal complement complex (TCC) levels and clinically significant immune effector cell–associated neurotoxicity syndrome (ICANS)." Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024): 7036. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.7036.
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7036 Background: The cornerstone of ICANS pathogenesis is endothelial dysfunction leading to blood-brain barrier disruption driven by inflammatory cytokines. Endothelial dysfunction is often associated with complement activation as in thrombotic microangiopathy, but the association between complement and ICANS has not yet been investigated. Herein, we describe the association between TCC levels (sC5b-9) and ICANS after CART. Methods: We retrospectively included 42 patients (pts) with B-cell non-Hodgkin lymphoma treated with axi-cel or brexu-cel from 03/2022 - 09/2023 at Ohio State University who had had sC5b-9 levels available pre-lymphodepletion (pre-LD), pre-CART and post-CART infusion. sC5b-9 levels were measured once in each of the timepoints: pre-LD (between D-7 and D-4), pre-CART (between D-3 and D0) and post-CART (between D2 and D8). We defined clinically significant ICANS as peak grade ≥2 (G≥2). Median and interquartile range (IQR) were used to describe the biomarkers levels, and Wilcoxon-rank sum test was used to compare values between groups. Results: Median age was 64 years (26-76), 30 (71%) pts had large B-cell lymphoma and 6 (14%) had untransformed follicular lymphoma who received axi-cel (36, 86%), and 6 (14%) had mantle cell lymphoma who received brexu-cel. Following CART, cytokine-release syndrome (CRS) peak grade was 2 and 1 in 16 (38%) and 22 (52%) of the pts, respectively, and 4 pts (10%) had no CRS. The ICANS peak grade was 4, 3, 2 and 1 in 4 (10%), 2 (5%), 6 (14%) and 6 (14%) of the pts, respectively, and 24 (57%) of the pts had no ICANS. The median time from CART to ICANS peak was 6 days (2-12). Tocilizumab and steroids were used in 28 (67%) and 20 (48%) of the pts, respectively. We compared sC5b-9 levels pre-LD, pre-CART and post-CART between pts that had ICANS peak G≥2 (N = 12) vs. grade 1 or did not have ICANS (G0-1, N = 30). We found that the post-CART sC5b-9 levels were significantly higher among pts who had ICANS G≥2 [median (IQR) 254 (129) vs. 183 (82) ng/mL, p = 0.013]. There was no statistical difference in the levels pre-LD and pre-CART between pts who had ICANS G≥2 vs. G0-1, median (IQR) 176 (103) vs. 159 (94) ng/mL, p = 0.37, and 152 (64) vs. 143 (69) ng/mL, p = 0.89, respectively. We also compared levels of other biomarkers associated with tumor burden, inflammation, and endothelial dysfunction at the same time points sC5b-9 was measured between pts with ICANS G≥2 vs. G0-1 and there were no statistically significant differences: median (IQR) pre-LD LDH 171 (73) vs. 180 (115) U/L, p =0.54, post-CART ferritin 262 (546) vs. 297 (333) ng/mL, p = 0.92 and post-CART fibrinogen 302 (221) vs. 405 (146) mg/dL, p = 0.29. Conclusions: Our findings support an association between post-CART sC5b-9 levels and clinically significant ICANS warranting further investigation of the role of complement in the ICANS pathogenesis and as a therapeutic target.
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Chen, C. C., C. A. Chang, H. T. Tsai, and H. T. Hsu. "Identification of a Potyvirus Causing Latent Infection in Calla Lilies." Plant Disease 88, no. 9 (September 2004): 1046. http://dx.doi.org/10.1094/pdis.2004.88.9.1046a.
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A new potyvirus designated as Calla lily latent virus (CLLV) was isolated from apparently healthy calla lilies (Zantedeschia spp.) collected from nurseries in Taichung County, Taiwan. Different from most calla lily-infecting potyviruses, CLLV infects Chenopodium quinoa and develops local lesions on inoculated leaves (3). Typical potyvirus particles approximately 780 nm long were detected from CLLV-induced C. quinoa local lesions. CLLV was transmitted readily to and established in C. quinoa. Attempts to establish CLLV infection in calla lilies from extracts of C. quinoa lesions were not successful. The virus was transmitted from infected to healthy calla lilies with difficulty. A 1.3-kb cDNA product was amplified by reverse transcription-polymerase chain reaction (RT-PCR) from CLLV-infected calla lilies and C. quinoa using potyvirus degenerate primers (2). The PCR product was cloned and sequenced. It was found to consist of 1,339 nucleotides (nt) (GenBank Accession No. AF469171) corresponding to the genome organization of the 3′terminal region of potyviruses. The deduced amino acid sequence contains 362 residues encoding the 3′terminal region of the nuclear inclusion b gene (80 residues) and the complete coat protein (CP) gene (282 residues). A 253-nt noncoding region (NCR) was found at the 3′terminal region of the cDNA. By comparing with known sequences of potyviruses, CLLV was identified as a new species of Potyvirus based on the uniqueness in the CP gene and 3′ NCR. Soybean mosaic virus and Watermelon mosaic virus 2 are the potyviruses most similar to CLLV, but they share only approximately 80% nucleotide identity with CLLV in the CP and NCR regions. Attempts to purify sufficient CLLV from C. quinoa for antiserum preparation were not successful. Alternatively, polyclonal antibodies were produced using E. coli-expressed CLLV CP (1). The antibodies were useful for detection of CLLV and its CP in calla lilies using enzyme-linked immunosorbent assay, sodium dodecyl sulfate-immunodiffusion, immuno-specific electron microscopy, and western blot. Field surveys showed that calla lily plants found positive for CLLV by serological methods always remained symptomless throughout the six-month growing season. Occasionally, CLLV was detected in symptomatic calla lilies, but these plants were consistently confirmed dually infected by other viruses (Dasheen mosaic virus and Konjak mosaic virus found most commonly). Infection of CLLV alone in calla lilies may not have a direct impact on the production and marketing of the crop. Synergism is not currently known when calla lilies are coinfected with other viruses. CLLV is spread by vegetative propagation through infected rhizomes or tubers. References: (1) C. C. Chen et al. Plant Dis. 87:901–905, 2003. (2) S. S. Pappu et al. Plant Dis. 82:1121–1125, 1998. (3) F. W. Zettler and R. D. Hartman. Pages 464–470 in: Virus and Virus-like Diseases of Bulb and Flower Crops. G. Loebenstein et al., eds. John Wiley and Sons Inc., UK, 1995.
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Herrera, Alex F., Haesook T. Kim, Malek Faham, Heather Sun, Aliyah R. Sohani, Edwin P. Alyea, Yi-Bin Chen, et al. "Sequencing-Based Detection of Minimal Residual Disease Is Associated with Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Lymphoid Malignancies." Blood 124, no. 21 (December 6, 2014): 3961. http://dx.doi.org/10.1182/blood.v124.21.3961.3961.
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Abstract Introduction: Monitoring for minimal residual disease (MRD) in hematologic malignancies can identify patients at high risk of relapse after standard therapy and hematopoietic stem cell transplantation (HSCT). However, techniques are limited for MRD monitoring of most lymphoma subtypes. The LymphoSIGHTTM method (Sequenta, Inc.) is a high-throughput sequencing-based MRD assay that detects small amounts of circulating tumor DNA (CTD) in patients with lymphoid malignancies. This assayhas shown promise in the monitoring of patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL). We evaluated whether CTD measured by LymphoSIGHTTM pre- and post-allogeneic HSCT predicts relapse and outcome in patients with lymphoid malignancies. Methods: We retrospectively studied patients enrolled between 2009-2012 on a multicenter phase 3 trial comparing sirolimus-containing to non-sirolimus containing GVHD prophylaxis regimens in patients with lymphoma undergoing allogeneic HSCT. Only patients with available archival tumor tissue were included. Patients underwent conventional restaging at 3, 6, 12, 18 and 24 months per protocol. Genomic tumor DNA was extracted from formalin-fixed paraffin-embedded tissue or bone marrow aspirate mononuclear cells. PCR amplification of IGH and IGK regions was performed followed by high-throughput sequencing to determine the tumor clonotype(s). As part of the trial, peripheral blood mononuclear cell (PBMC) and plasma samples were collected pre-HSCT and at days 30, 60, 100, 180, 270, 365, 545 and 730 after HSCT. DNA from plasma (DLBCL) and PBMCs (other histologies) was amplified and sequenced to determine the level of CTD per million diploid genomes. Results: We studied 68 patients with B-cell non-Hodgkin lymphoma, classical Hodgkin lymphoma (HL), or CLL. Clonotype calibration was successful in 51 patients (75%; 82% when excluding diagnostic samples with insufficient DNA). MRD evaluation was performed at >=1 time point in 40 patients (13 CLL, 4 DLBCL, 4 transformed indolent lymphoma (TIL), 8 follicular lymphoma (FL), 7 MCL, 4 HL). Overall, 9/40 patients in the cohort relapsed, with a 2y cumulative incidence of relapse/progression (CIR) of 18%. Thirteen of 26 patients (50%) tested were MRD+ pre-HSCT, including 27% of patients in complete remission (CR) and 71% of patients in partial remission (PR) by conventional criteria. The 2y CIR in MRD+ vs MRD- patients at baseline was 38% vs 7% (p=0.2), 2y non-relapse mortality (NRM) was 15% vs 8% (p=0.6), and 2y progression-free survival (PFS) was 46% vs 85% (p=0.12). At day 100, 12 of 32 patients (38%) tested were MRD+. The 2y CIR in day 100 MRD+ patients was 25% vs 0% for MRD- patients (p=0.25), 2y NRM was 25% vs 5% (p=0.05), and 2y PFS was 50% vs 95% (p=0.01). In multivariable models with histology and disease status at HSCT as covariates, the hazard ratio (HR) for progression or death associated with baseline MRD+ was 2.8 (p=0.3); for day 30 MRD+, HR=6.0 (p=0.1); and for day 100 MRD+, HR=8.3 (p=0.07). When entered into the models as a time-dependent covariate, MRD-positivity was associated with a significantly increased risk of progression or death (HR 5.2, 95% CI 1.8-15.4; p=0.03) and of disease relapse/progression (HR 12.7, 95% CI 2.5-64.3, p=0.002). Histology and disease status were not significantly associated with either outcome in the models. Nine patients relapsed or progressed at a median of 4 (range 1-28) months post-HSCT and 7 (78%) had an MRD+ PB sample at a median of 6 months prior to relapse (Figure). Five patients were persistently MRD+ in all PB samples tested prior to relapse and 2 were initially MRD- then became MRD+. All 5 patients who relapsed after day 100 were MRD+ prior to relapse. Among 31 patients who did not relapse: 16 were MRD- in all PB samples tested; 9 were initially MRD+ then became MRD- by day 365 (4 by d100, 3 by d180, 2 by d365); 2 had a mixed MRD pattern, initially MRD-, then MRD+, then MRD- thereafter; the remaining 4 patients, all of whom had CLL, were persistently MRD+ but had marrow or PB evidence of persistent disease without progression at MRD+ time points. Conclusions: MRD status based on CTD detection in patients with lymphoid malignancies is predictive of outcome after allogeneic HSCT. This technique may provide important prognostic information throughout the HSCT course and identify a target population for early intervention to prevent disease relapse. Figure 1 Figure 1. Disclosures Faham: Sequenta, Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.
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Woyach, Jennifer, Shanmugapriya Thangavadivel, David Weiss, Lai Wei, Eric McLaughlin, Kerry Rogers, Seema A. Bhat, et al. "Final Results of a Phase 2 Trial of Early Intervention Ibrutinib with Vaccinations in Patients with Asymptomatic, High-Risk CLL." Blood 134, Supplement_1 (November 13, 2019): 1759. http://dx.doi.org/10.1182/blood-2019-131099.
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Introduction: The Bruton's Tyrosine Kinase (BTK) inhibitor ibrutinib (IB) is a standard therapy for previously untreated CLL patients. While therapy is currently indicated only for patients with progressive, symptomatic disease, the introduction of targeted therapies in CLL has re-opened the question of whether asymptomatic high risk patients would benefit from early intervention. As well, even in early stages CLL is associated with profound cellular, humoral and innate immune suppression and patients with CLL respond poorly to routine vaccinations. IB has been shown to reverse disease mediated immune dysfunction partly through Th1 skewing. We undertook a phase 2 study of IB in asymptomatic high risk CLL patients who did not otherwise require therapy to evaluate: 1) the safety and efficacy of 2 years of IB in this clinical setting and 2) ability of IB to improve the efficacy of routine vaccines. Methods: This is a single-stage phase II study of IB in previously untreated asymptomatic, genetically high-risk patients with CLL, who did not meet IWCLL treatment criteria. High risk genomics were defined as del(11)(q22.3), del(17)(p13.1), unmutated IGHV, and/or complex karyotype (≥3 cytogenetic abnormalities). Patients were randomized to receive IB 420mg PO daily either concurrent with the pneumococcal (PCV13), influenza and TdaP vaccines (Arm A) or following vaccination (Arm B) for a total of 27 cycles (2 years). The primary objective of the study was to determine the safety and 2-year progression-free survival (PFS) of asymptomatic, high-risk CLL patients treated with IB. Secondary objectives include determination of safety and immune responses to vaccines in relation to IB administration, development of resistance, and quality-of-life (QOL). QOL measures assessed general QOL (SF-12, EORTC), anxiety (GAD-7) and depression (PHQ-9). Results: Forty-four patients (pts; 21 in Arm A, 23 in Arm B) were enrolled from 1/2016 to 6/2017, with a median age of 58 (range 35-82). Sixty-six percent of pts were male and all were high-risk: 91% with unmutated IGHV, 14% with del(17)(p13.1), 34% with del(11)(q22.3), and 24% with complex karyotype (≥ 3 abnormalities). Median follow-up is 2.6 years (range: 0.2-3.2). Excluding 2 patients in Arm B who progressed prior to receipt of IB, 2-year PFS was 92%. From a landmark of 2-years and including 33 patients who reached this point and discontinued IB, 6-month PFS was 87% (95% CI: 69-95%; Figure 1). Of 9 pts who progressed after IB discontinuation, 3 have not required further treatment, 5 restarted IB or acalabrutinib, and 1 started venetoclax/rituximab, and all responded. For PCV13, in Arm A, 15/16 patients showed a significant increase in antibody titer 2 cycles following vaccination, but response disappeared by cycle 12. In Arm B, 3/13 patients had an increase in antibody titer, with no increase following second vaccination. For influenza, patients in Arm B showed a significant response to influenza A vaccination, while patients in both arms responded to influenza B vaccination. IB was generally well tolerated, and only one pt discontinued treatment due to toxicity (atrial fibrillation). Grade 3+ toxicities that occurred in >2% of patients included anemia (7%), atrial fibrillation (11%), dental caries (7%), hyperglycemia (7%), hypertension (43%), and neutropenia (7%). At baseline, patients' reports of physical health-related (M=48.52, SD=7.96) and mental health-related quality of life (M=52.20, SD=8.57) similar to U.S population norms, along with moderately high global health (M=78.49 of 100, SD = 20.51). Additionally, patients' anxiety (M=3.56, SD=4.71) and depressive symptom reports (M=3.65, SD=4.46) were in the "none/mild" range. There was no significant change in the latter measure from baseline to 12 months (p>0.25), excepting anxiety which slightly decreased (M=1.31, SD=2.33; F(3,44)=5.94, p<0.01). Conclusions Early intervention with IB was well tolerated and significantly improved patient disease status. Vaccine response to PCV13 was improved by concurrent ibrutinib, but lost at 12 months, suggesting re-vaccination might be helpful. Quality of life remained good throughout treatment, with improvement in patient anxiety. Extended follow-up will be required to determine how long remissions can be maintained after drug discontinuation in this population. Disclosures Woyach: Verastem: Research Funding; Loxo: Research Funding; Morphosys: Research Funding; Karyopharm: Research Funding; AbbVie: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding. Rogers:AbbVie: Research Funding; Acerta Pharma: Consultancy; Genentech: Research Funding; Janssen: Research Funding. Bhat:Pharmacyclics: Consultancy; Janssen: Consultancy. Grever:Acerta Pharma, LLC: Membership on an entity's Board of Directors or advisory committees. Lozanski:Beckman Coulter: Research Funding; Stemline Therapeutics Inc.: Research Funding; Boehringer Ingelheim: Research Funding; Genentec: Research Funding. Byrd:TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Acerta: Research Funding; Novartis: Other: Travel Expenses, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; BeiGene: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau. Awan:Gilead: Consultancy; Sunesis: Consultancy; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy; Genentech: Consultancy. OffLabel Disclosure: Clinical trial of ibrutinib used in an off-label setting
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Metzeler, Klaus H., Heiko Becker, Kati Maharry, Michael D. Radmacher, Jessica Kohlschmidt, Krzysztof Mrózek, Deedra Nicolet, et al. "ASXL1 Mutations Identify a High-Risk Subgroup of Older Patients with Primary Cytogenetically Normal Acute Myeloid Leukemia within the European LeukemiaNet ‘Favorable' Genetic Category." Blood 118, no. 21 (November 18, 2011): 417. http://dx.doi.org/10.1182/blood.v118.21.417.417.
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Abstract Abstract 417 Mutations in the additional sex combs like-1 (ASXL1) gene have been identified in patients (pts) with myelodysplastic syndromes, myeloproliferative neoplasms, and acute myeloid leukemia (AML). We present here the first study on ASXL1 mutations in adult primary cytogenetically normal (CN-)AML, and report their associations with clinical and molecular characteristics, treatment outcomes, and gene- and microRNA- (miR-)expression profiles. We studied 423 primary CN-AML pts, aged 18–83 years (y) and treated on cytarabine/daunorubicin-based frontline protocols, for ASXL1 exon 12 mutations (frame shift and nonsense changes) and other prognostic gene mutations [FLT3-internal tandem duplications (ITD) and tyrosine kinase domain mutations, MLL partial tandem duplications, and mutations in NPM1, CEBPA, WT1, IDH1, IDH2 and TET2]. ASXL1mutations were 5 times more common in older (≥60y) than in younger (<60y) pts [38/234 (16.2%) vs 6/189 (3.2%); P<.001], and subsequent analyses therefore focused on older CN-AML pts. Compared to ASXL1-wild type (-wt) pts, ASXL1-mutated (-mut) pts very rarely carried NPM1 mutations (P<.001) or FLT3-ITD (P=.002), but more often had CEBPA mutations (P=.01). ASXL1-mut pts also had lower white blood counts (P=.02), lower blast percentages in blood (P<.001) and bone marrow (P=.04), and tended to have higher platelet counts (P=.06) and more frequently be male (P=.08) than ASXL1-wt pts. Among older primary CN-AML pts, those with mutated ASXL1 had a lower complete remission (CR) rate (53% vs 71%; P=.04) and shorter disease-free survival (DFS; P=.03; 3y rates, 10% vs 19%), overall survival (OS; P=.006; 3y rates, 5% vs 23%) and event-free survival (EFS; P=.002; 3y rates, 5% vs 14%; Fig. A) than ASXL1-wt pts. Due to the strong associations of ASXL1 mutations with NPM1-wt, absent FLT3-ITD and mutated CEBPA, we studied their prognostic impact within the genetic categories defined in the European LeukemiaNet (ELN) guidelines [ELN Favorable (Fav): CN-AML with mutated CEBPA and/or mutated NPM1 without FLT3-ITD; ELN Intermediate-I: all remaining CN-AML pts]. ELN Fav/ASXL1-mut pts had a lower CR rate (50%) compared with ELN Fav/ASXL1-wt pts (82%; P=.04). All 6 ELN Fav/ASXL1-mut pts who achieved CR relapsed within 13 months, while 27% of ELN Fav/ASXL1-wt pts were alive and disease-free at 3y. All ELN Fav/ASXL1-mut pts died within 18 months after enrollment, whereas 34% of ELN Fav/ASXL1-wt pts were alive at 3y (OS, P<.001). EFS of ELN Fav/ASXL1-mut pts also was significantly worse than for ELN Fav/ASXL1-wt pts (P<.001; 3y rates, 0% vs 22%; Fig. B). Multivariable analyses confirmed that ASXL1 mutations associated with lower CR rates (P=.03), shorter DFS (P<.001), OS (P<.001) and EFS (P<.001) only among ELN Fav pts, after adjusting for other risk factors. In contrast, ASXL1 mutations were not associated with outcomes in the ELN Intermediate-I group. Further exploratory analyses in molecular subgroups suggested that ASXL1 mutations may be associated with particularly unfavorable outcomes [ie, shorter OS (P<.001) and EFS (P=.02)] among CEBPA-mut pts. Gene- and miR-expression profiles were derived using Affymetrix HG-U133 plus 2.0 and custom-made miR microarrays. We identified an ASXL1 mutation-associated gene-expression signature comprising 67 differentially expressed genes (92 probe-sets), including upregulation of WNT pathway co-receptor LRP6, cytochrome P450 enzyme CYP1B1, and GJA1 (connexin 43, mediating stem cell-stroma interactions in the bone marrow). No significant signature of differentially expressed miRs was found. In conclusion, in this first study of ASXL1 mutations focusing on primary CN-AML, we demonstrate that they associate with inferior outcomes in older pts, particularly within the ELN Fav genetic group. We also report the first ASXL1-mutation associated gene-expression signature in CN-AML that may provide useful insight into the biology of ASXL1-mut AML, and help design novel treatment approaches for this high-risk group of older pts.FigureFigure. Disclosures: No relevant conflicts of interest to declare.
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Pangestuti, Retno, Anissa Lestari Kadiyono, Surya Cahyadi, and Hendriati Agustiani. "A Modifying the Instrument of Self-Regulation in Early Childhood Assessment." JPUD - Jurnal Pendidikan Usia Dini 13, no. 1 (April 30, 2019): 114–27. http://dx.doi.org/10.21009/10.21009/jpud.131.09.
Full textAbstract:
Self-regulation for pre-school children is very important to support children’s adjustments in all situations and conditions. The current problem is the instrument of self-regulation is more focused on regulation in learning which is not suitable for young children. This study aims to examine the validity and reliability of Preschool Self-Regulation Assessment (PSRA) in Indonesia by modifying several children self-regulation theories. The instrument was translated from English into Indonesian and it retranslated into the native language by linguists. The questions, then, were validated through a process of professional judgment and cognitive de-briefing. The study was carried out to 179 children aged 6 to 7 years old. Data were analyzed by using confirmatory factor analysis (CFA). It showed that there are 5 dimensions of children's self-regulation, namely: attentional focus, behavioral control, self-motivated, self-autonomy and emotional control. The result showed that the five-dimensional model is agreed with the data and prove to measure children’s self-regulation. Cronbach’s alpha coefficient value was 0.899, indicating high scale reliability. Thus, the pre-school children’s self-regulation assessment has well psychometric for further use.
Keywords: Children’s self-regulation, Confirmatory Factor Analysis, Construct validation, Pre-school self-regulation assessment, Reliability
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Hampel, Paul J., Kari G. Rabe, Yucai Wang, Steven R. Hwang, Saad S. Kenderian, Eli Muchtar, Jose F. Leis, et al. "Incidence of Richter Transformation in Patients with Chronic Lymphocytic Leukemia (CLL) /Small Lymphocytic Lymphoma (SLL): A Cohort Study Evaluating Different Therapeutic Eras." Blood 142, Supplement 1 (November 28, 2023): 3271. http://dx.doi.org/10.1182/blood-2023-185076.
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INTRODUCTION Richter transformation (RT) is the histologic transformation of CLL/SLL into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). We previously reported an incidence of 0.5% per year of RT in patients with newly diagnosed CLL and an incidence of 1% per year following initiation of therapy (Parikh, BJH, 2013). It is unknown whether these incidences have changed in the novel agent era. METHODS We identified patients with previously untreated CLL/SLL in the Mayo Clinic CLL Database who were seen within 12 months of diagnosis. Only patients with biopsy-proven DLBCL with histopathology confirmation at Mayo Clinic were included. Cumulative incidence methodology was used to display the time to development of RT with death as a competing risk (both from time of initial CLL/SLL diagnosis, and from start of CLL directed therapy). We defined the time period prior to February 2014 (FDA approval of ibrutinib for CLL) as the pre-novel agent era and the time period starting February 2014 as the novel agent era. Using Cox regression analysis, we compared the incidence of RT, both after initial CLL diagnosis and after initiation of CLL therapy, between patients diagnosed with CLL in the pre-novel agent era versus the novel agent era. RESULTS Between 1/2000 and 4/2023, 3347 patients were seen at Mayo Clinic. The median age at diagnosis was 65 years (range 21-97 years), and 66% patients were male. Baseline characteristics of patients at the time of CLL and RT diagnoses between the two treatment eras were similar, including distance in miles of primary residence from Mayo Clinic ( Table 1). The median follow-up for the entire cohort was 5.6 years (9.5 years for the pre-novel agent era cohort and 3.2 years for the novel agent era cohort). A total of 82 patients were diagnosed with RT (69 in the pre-novel agent era and 13 in the novel agent era). Overall, the 1-, 5- and 10-year cumulative incidence rates for RT from the time of CLL/SLL diagnosis were 0.6% (95% CI: 0.4-0.9%), 1.8% (95% CI: 1.3-2.3%), and 3.0% (95% CI: 2.4-3.8%), respectively. Among the patients who received CLL/SLL therapy (n=1382), the 1-, 5-, and 10-year incidence rates for RT from the time of treatment start were 0.3% (95% CI: 0.1-0.8%), 3.3% (95% CI: 2.4-4.5%), and 4.9% (95% CI: 3.7-6.5%), respectively. Among 1981 patients diagnosed with CLL/SLL in the pre-novel agent era, the 1- and 5-year incidence rates for RT from the time of diagnosis were 0.6% (95% CI: 0.4-1.1%) and 2.1% (95% CI: 1.5-2.8%), respectively. Among 1366 patients diagnosed with CLL/SLL in the novel agent era, the 1- and 5-year incidence rates following CLL/SLL diagnosis were 0.5% (95% CI: 0.2-1.1%) and 1.1% (95% CI: 0.6-2.2%), respectively. The RT incidence from time of CLL/SLL diagnosis was not significantly different between the pre-novel agent and novel agent era patients (hazard ratio [HR] 1.6, 95%CI 0.9-3.0, p=0.13). Patients who received CLL/SLL treatment in the pre-novel agent era (n=926) and novel agent era (n=456) had subsequent 1-year incidence rates of RT of 0.3% (95% CI: 0.1-1.0%) and 0.2% (95% CI: 0.0-1.8%), respectively. The 5-year incidence rates for these groups were 3.7% (95% CI: 2.6-5.2%) and 1.9% (95% CI: 0.7-5.0%), respectively. Although an increased risk of RT after CLL/SLL directed therapy was observed in the pre-novel agent era compared to the novel agent era (HR 2.4, 95%CI: 0.9-6.1, p=0.07; Figure 1), this did not cross the threshold of statistial significance. Among patients diagnosed in the pre-novel agent era who developed RT (n=69), CLL treatment prior to RT included: none, n=19 (28%); chemoimmunotherapy only, n=36 (52%); and novel agent, n=14 (20%; includes 11 treated with prior chemoimmunotherapy also). In contrast, among patients diagnosed in the novel agent era who developed RT (n=13), CLL treatment prior to RT included: none, n=8 (62%); and novel agent, n=5 (38%). CONCLUSIONS Patients who received CLL/SLL directed treatment appear to have a lower risk of RT in the novel agent era. This may be driven by the fact that none of the patients who developed RT in the novel agent era received chemoimmunotherapy. Whether novel agent use for CLL/SLL suppresses the development of RT or avoids the risk associated with cytotoxic chemotherapy-induced clonal evolution requires further study. Although limited by length of follow-up, our findings challenge the notion that RT incidence will increase in parallel with CLL patients living longer with novel agent treatments.
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Rugo, Hope S., Patrick Neven, Isabel Saffie, Yeon Hee Park, Michelino De Laurentiis, Florence Lerebours, Eva Maria Ciruelos, et al. "Abstract PD13-05: Alpelisib + fulvestrant in patients with PIK3CA-mutated, HR+, HER2— advanced breast cancer (ABC) who received chemotherapy or endocrine therapy (ET) as immediate prior treatment: BYLieve Cohort C primary results and exploratory biomarker analyses." Cancer Research 82, no. 4_Supplement (February 15, 2022): PD13–05—PD13–05. http://dx.doi.org/10.1158/1538-7445.sabcs21-pd13-05.
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Abstract Introduction: Alpelisib (ALP), an inhibitor and degrader of phosphatidylinositol-3-kinase α (PI3Kα), + fulvestrant (FUL) demonstrated efficacy in PIK3CA-mutated, HR+, HER2- ABC in the phase 3 SOLAR-1 trial, which included only 20 patients (pts) with prior CDK4/6 inhibitor (CDKi) in the PIK3CA-mutated cohort. BYLieve (NCT03056755), a phase 2, open-label, 3-cohort noncomparative study, evaluates ALP + endocrine therapy (ET; FUL or letrozole [LET]) in pts with PIK3CA-mutated, HR+, HER2- ABC, progressing on/after prior therapies, including CDKi + ET. Cohorts A and B were restricted to pts receiving CDKi + (aromatase inhibitor [AI] or FUL), respectively, as immediate prior therapy, but Cohort C included pts whose cancer progressed on/after AI (in adjuvant or metastatic setting), and who received chemotherapy (CT; any line), or ET (FUL or LET monotherapy or with targeted therapy, including CDKi + FUL, but not CDKi + AI) as immediate prior treatment. Cohorts A and B demonstrated efficacy and safety of ALP + ET after prior CDKi. Here, we report primary results and biomarker analyses from Cohort C.. Methods: Pts in Cohort C received ALP 300 mg orally QD + FUL 500 mg intramuscular Q28D + C1D15. The primary endpoint was assessed in each cohort separately and is the proportion of pts with centrally confirmed PIK3CA mutation alive and without disease progression at 6 mo per local assessment; 95% CIs are calculated using Clopper and Pearson (1934) exact method. The 95% CI lower bound of the primary endpoint >30% is clinically meaningful evidence of treatment effect. In an exploratory analysis of baseline biomarkers using ctDNA, progression-free survival (PFS) was estimated in pt subgroups per high (≥10%) or low (<10%) ctDNA fraction and ESR1 mutational status via Kaplan-Meier estimation.. Results: 127 pts were enrolled in Cohort C (1 pt discontinued prior to treatment start) with ≥6 mo follow-up by the cutoff date (14 Jun 2021); 115 had a centrally confirmed PIK3CA mutation. Median follow-up was 11.4 mo (range, 0-23 mo); 79 (62.7%) pts had ≥2 prior lines of therapy in the metastatic setting, 58 (46.0%) pts had prior CT exposure in the metastatic setting, and 41 (32.5%) pts had prior FUL exposure in the metastatic setting. The primary endpoint was met, with 48.7% (95% CI, 39.3%-58.2%) of pts alive and without disease progression at 6 mo. Median PFS (mPFS) was 5.6 mo (95% CI, 5.4-8.1 mo). The most common all-grade adverse events (AEs) by preferred term were hyperglycemia (n=82, 65.1%), diarrhea (n=66, 52.4%), nausea (n=51, 40.5%), and rash (n=49, 38.9%). Grade ≥3 AEs (≥10%) included hyperglycemia (n=30, 23.8%) and rash (n=17, 13.5%). AEs leading to discontinuation occurred in 15.1% (n=19) of pts; most frequent AEs leading to discontinuation were rash (n=5, 4.0%) and hyperglycemia (n=4, 3.2%). Exploratory biomarker analyses in 74 pts who had available baseline biomarker samples at data cutoff showed that pts with a low ctDNA fraction (n=23) had longer mPFS than pts with high ctDNA fraction (n=51; 16.7 [95% CI, 10.4-19.5] vs 5.4 [95% CI, 2.9-7.2] mo; p<0.001, HR=0.31 [95% CI, 0.2-0.6]). Efficacy was similar in pts with (n=20) and without (n=54) ESR1-mutated tumors (6.3 [95% CI, 2.8-8.3] vs 8.3 [95% CI, 5.5-16.7] mo; p=0.095, HR=0.59 [95% CI, 0.3-1.1]).. Conclusion: In Cohort A of BYLieve, efficacy of ALP + FUL suggests clinical benefit immediately after CDKi + AI; Cohort C confirms clinically relevant activity of ALP + FUL in a heterogeneous population, primarily treated in the third line or later, and potentially regardless of ESR1 status or ctDNA fraction, with no new safety signals detected. Together, these data confirm that ALP targets the effects of the PIK3CA-driver oncogene in HR+, HER2- ABC. Citation Format: Hope S Rugo, Patrick Neven, Isabel Saffie, Yeon Hee Park, Michelino De Laurentiis, Florence Lerebours, Eva Maria Ciruelos, Nicholas Turner, Dejan Juric, Ennan Gu, Christina H Arce, Mukta Joshi, Estelle Roux, Murat Akdere, Stephen Chia. Alpelisib + fulvestrant in patients with PIK3CA-mutated, HR+, HER2— advanced breast cancer (ABC) who received chemotherapy or endocrine therapy (ET) as immediate prior treatment: BYLieve Cohort C primary results and exploratory biomarker analyses [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD13-05.
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Di Blasi, Roberta, Steven Le Gouill, Emmanuel Bachy, Guillaume Cartron, David Beauvais, Fabien Le Bras, Francois Xavier Gros, et al. "Outcome of Relapsed/Refractory Aggressive B-Cell Lymphoma Patients Relapsing after Anti-CD19 CAR T-Cells and Enrolled in the Descar-T French National Registry." Blood 138, Supplement 1 (November 5, 2021): 885. http://dx.doi.org/10.1182/blood-2021-150994.
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Abstract Background . Anti-CD19 Chimeric Antigen Receptor (CAR) T-cells are a major therapeutic advance in the management of patients (pts) with relapsed/refractory aggressive B-cell lymphoma (R/R aggressive BCL) with reported overall response rates between 40% and 83% in the pivotal trials (ZUMA1, JULIET, TRANSCEND) as well as in the real-life cohorts with either axicabtagene ciloleucel (axi-cel, Yescarta) or tisagenlecleucel (tisa-cel, Kymriah). However, a significant number of pts will experience progression or relapse after infusion with an estimated 24-month progression-free survival (PFS) of between 33% and 42%. DESCAR-T is a nationwide registry that aims to collect real-life data for all pts treated with commercialized CAR T-cells in France. It represents a unique opportunity to investigate the outcome of pts who relapse after CAR T-cell therapy. Patients and Methods . In all, 680 pts with R/R aggressive BCL were registered in DESCAR-T from August 2018 and 550 were infused at the time of the present analysis (April 12, 2021) with either axi-cel (n=350) or tisa-cel, n=200). All pts gave informed informed consent before DESCAR-T registration. Progression and relapse after CAR T-cells were defined based on the Cheson 2014 response assessment criteria. Results . With a median follow-up (F-up) of 7.9 months, 238 pts (43.3%) out of 550 treated pts relapsed, after axi-cel in 136 pts (F-up = 9.0 months [5.1 - 9.7]) and after tisa-cel in 102 pts (F-up = 7.8 months [5.9 - 10.4]). Histological subtypes were DLBCL (n 178, 74.8%), PMBL (n=11, 4.6%), HGBCL (n= 3, 1.3%), transformed follicular lymphoma (tr FL) (n=31, 13%), or other histologies (FL n=2, PCNSL n=1, tr MZL n=3, unclassifiable hodgkin/DLBCL n=9). At time of registration, median age was 62 years (range 18;77), 43.6% were aged >65 yrs, and 67.2% were male; 184 (79.7%) presented with advanced disease (stage III or IV), and 13 (5.9%) with low age-adjusted International Prognostic Index (aaIPI), 82 (37.1%) with low-intermediate aaIPI, 110 (49.8%) with high-intermediate aaIPI, and 16 (7.2%) with high aaIPI. At time of CAR T-cell infusion, 36 (18.9%) pts presented with ECOG PS >=2 and 72 (38.9%) with an elevated LDH level. The median number of lines prior to CAR T-cell infusion was 3 (range 2-9), including 48 (20.1%) transplant (46 auto-HSCT and 2 allo-HSCT). Median time between order and infusion was 50 days (IQR 43; 59). Bridging therapy was administered to 87.8% of the pts, with a high-dose regimen including combined immunochemotherapy for 84.5% of the pts. Failure after CAR T-cells occurred after a median time of 2.71 months (range 0.2; 21.5), 54 (22.7%) being during the first month after infusion (< M1) and 156 (65.5%) during the first-three months after infusion (<M3). At failure, 154 (64%) patients received treatments that maybe combined and described as followed : 70 (45.5%) lenalidomide, 70 (45.5%) various immunotherapies (rituximab, daratumomab, polatuzumab), 31 (20.1%) a combined immunochemotherapy with various regimens (R-DHAX, RICE, Pola-R-Benda,...), 21 (13.6%) an anti-PD1 immune checkpoint inhibitor (Nivolumab, pembrolizumab), 11 (7.1%) bi-specific T-cell engagers (TCE), 18 (11.7%) radiotherapy, and 3 a transplant (1 an auto-HSCT and 2 an allo-HSCT). The overall response rate to the salvage therapy after CAR T-cells was 11% (complete response rate 5.2%). The median PFS was 2.8 months (95% CL, 2.4 -3.1). The median overall survival (OS) was 5.2 months (95% CL, 4.1- 6.6) (Figure 1A). The median OS was even shorter in pts who failed during the first month (1.9 months [95% CL, 1.1- 3.2] vs 6.7 months [95 CL 5.5 : 9.3] p<0.0001) (Figure 1B). 26.9% of the pts in the overall cohort were alive at 6 months, but only 18.9% were alive in the group of pts relapsing during the first month. In multivariate analysis, predictors of OS were high LDH level at time of infusion, time to failure < 1 month after CAR T-cells, no access to immuno-oncology treatment such as TCE or lenalidomide. Conclusion . This study is the first analysis reporting the outcome of patients with R/R aggressive BCL relapsing after anti-CD19 CAR T-cells. These results demonstrate the poor outcome of these pts and identifies the need for further innovative treatment strategies. Figure1. Overall survival from the CAR T-cell infusion in patients with R/R LBCL relapsing after CAR T-cells. (A) overall population. (B) according to the interval between CAR T-infusion and relapse (< 1 month and > 1 month) Figure 1 Figure 1. Disclosures Di Blasi: Novartis: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Le Bras: Takeda: Honoraria, Research Funding; Kite Gilead: Honoraria; Novartis: Honoraria; Celgene BMS: Research Funding. Feugier: Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria. Casasnovas: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Mohty: Amgen: Honoraria; Jazz: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Adaptive Biotechnologies: Honoraria. Sesques: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Chugai: Honoraria. Morschhauser: Servier: Consultancy; Incyte: Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees.
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Murillo, Ilda, Marcio M. Andrade, Anel Montes, Jose M. Grasa, and Pilar Giraldo. "Are IgM Hevylite® Immunoglobulin Heavy Chain/Light Chain Analysis a Useful Tool to Differentiate IgM MGUS From Waldenström Macroglobulinemia?" Blood 120, no. 21 (November 16, 2012): 5097. http://dx.doi.org/10.1182/blood.v120.21.5097.5097.
Full textAbstract:
Abstract Abstract 5097 Background: Monoclonal IgM is the biomarker that characterize to Waldenstrom's macroglobulinemia (WM), a rare low grade B-cell lymphoma derived of the lymphoplasmacytic cell, even serum IgM component also is presented in MGUS. Recently new determinations of heavy chain/light chain immunoglobulins pairs (HLC) have been developed as biomarkers to apply to every day clinical practice. The diagnostic and prognostic potential of these biomarkers is under investigation. The aim of this study is to present our experience in the use of free light chain assay (sFLC) and HLC as biomarkers at diagnostic in order to discriminate between MGUS and WM, and to evaluate their potential prognostic value during disease course. Patients and Methods: A total of 43 patients (pts) were detected as having a serum monoclonal IgM in the Hematology Department of MSUH. Pts were classified as MGUS or WM according to the morphological, immunophenotype characteristics of lymphoplasmacitic bone marrow cells and CT-scan data. Pts were examined every 3–6 months following our clinical protocol in order to detect progression or transformation. Serum samples were collected prior and during treatment and were kept frozen at −70°C since collection and incorporate to our regional Biobank. Analysis of IgM were performed with the sFLC, (Freelite® test, the Binding Site, Birmingham, UK) and the HLC (Hevylite® immunoassay the Binding Site). Freelite® test is a nephelometric measurement of kappa and lambda light chains that circulate not bound to immunoglobulin heavy chain. Hevylite® immunoassay is based on specific polyclonal antibodies that recognize epitopes spanning the junction of the heavy and light chains of the individual immunoglobulin isotypes, it measures specifically IgMkappa and IgMlambda, separately. A normal range of IgM Hevylite assay was produced from normal (blood donor) sera, median (CI 95%) were: IgMkappa, 0. 634 g/L (0. 29–1. 82); IgMlambda, 0. 42g/L (0. 17–0. 94); HLC ratio (HLCR), 1. 6 (0. 95–2. 3). For ease of comparison IgM HLCR was expressed as the involved monoclonal immunoglobulin (iHLC)/uninvolved polyclonal immunoglobulin (uHLC). Results: The study included a series of 25 WM, 18 IgM-MGUS (included 2 IgM-cryoglobulinemia), 36 at diagnosis and 7 at relapse/refractory. The median age was 67. 1 years (13–85); IgM HLCR was 114. 68 (1. 02 – 353) in WM symptomatic, 71. 55 (1. 02 – 286. 43) in WM asymptomatic and 9. 5 (0. 45 – 50. 74) in IgM MGUS (p=0. 003). HLCR was higher in WM patients requiring treatment (n=13) at diagnosis than in pts (n=30) not requiring treatment (113 v 15. 77 p=0. 019) and also HLCR was significantly higher at relapse/refractory (n=9) than in pts (n=34) not relapse (113 v 17. 17 p=0. 012) uHLC was significantly higher in IgM-MGUS than WM to IgMkappa (n=28) and IgMlambda (n=15) iHLC: 0. 37 g/L (0. 11–1. 25) v 0. 1 g/L (0. 02–4. 03), p=0. 022; and 0. 69 g/L (0. 08–4. 09) v 0. 32 g/L (0. 22–0. 63), p=0. 05 respectively. sFLC level was 64 mg/L (10. 88–993) in WM and 31. 7 mg/L (6. 08–141) in IgM MGUS (p=0. 05). sFLC level was higher in WM requiring treatment at diagnosis than in pts not requiring treatment (73. 7 v 36. 85 p=0. 039). sFLC level was not significative in relapse/refractory (p=0. 168), it was not separate between WM asymptomatic and WM symptomatic (p=0. 092). There was a good correlation between HLCR and sFLC ratio (r=0. 3, p=0. 044) but not with sFLC level, HLCR, sFLC level and sFLC ratio did not predict for overall survival (OS) and progression free survival (PFS) in our study. Mean estimated OS was 78. 3 months (95% CI: 53. 67–102. 94) and PFS 69. 7 months (95% CI: 47. 28–92. 13). Conclusion: It seems that HLCR and sFLC could be good biomarkers to differentiate between IgM-MGUS and WM at diagnostic. High levels of HLC and sFLC were also seen in pts requiring treatment. HLCR discriminates WM symptomatic/asymptomatic and progressing pts uHLC levels were significantly higher in IgM-MGUS than WM pts showing that IgM-MGUS have a more robust immune system. Further studies are needed to evaluate their prognostic value. This work has been partially sponsored by a grant from FEHHA Disclosures: No relevant conflicts of interest to declare.
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Karuturi, Meghan S., Gabrielle B. Rocque, Joseph C. Cappelleri, Joanne L. Blum, Steven L. McCune, Bijoy Telivala, Sobha Kurian, et al. "Abstract P1-18-25: Real-world quality of life (QoL) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer (ABC) treated with palbociclib: A patient-reported outcome (PRO) analysis from POLARIS." Cancer Research 82, no. 4_Supplement (February 15, 2022): P1–18–25—P1–18–25. http://dx.doi.org/10.1158/1538-7445.sabcs21-p1-18-25.
Full textAbstract:
Abstract Background: POLARIS is an ongoing, prospective, real-world, noninterventional, multicenter study in patients with HR+/HER2- ABC receiving palbociclib in the United States and Canada. This report describes PRO data from a real-world setting of patients with ABC receiving palbociclib. Methods: POLARIS has a targeted enrollment of 1500 patients from ~110 sites in the United States and Canada. Key inclusion criteria included patients with HR+/HER2- ABC with evidence of metastatic disease. QoL was assessed with the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30). A clinical problem threshold for 5 functioning and 9 symptom scales of the EORTC QLQ-C30 was established with anchor questions assigned for each domain to assess functional health and symptom burden. Results: As of March 16, 2021, 1240 patients were treated with palbociclib and had EORTC QLQ-C30 data collected and analyzed (at baseline, n=1240; after 6 months of palbociclib treatment, n=1076; after 12 months of palbociclib treatment, n=926). At baseline, the median age of patients was 64 years (Table 1). The majority of patients were white (82%) and 98.8% were female. Nearly 95% of patients had stage 4 metastatic disease, 5.1% had locally advanced stage (III), 68% had a recurrent disease from the earlier stage (0-III), and 27.3% had de novo stage IV disease diagnosed at enrollment. In this cohort, 98.3% of patients were estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+), 94% were HER2-, with 99% of patients HER2- also ER+/PR+ at or nearest to the enrollment date. The percentages of patients with functioning scale scores (physical [baseline=54.6%; month 6=50.2%; month 12=50.4%], role [baseline=28.6%; month 6=20.1%; month 12=18.6%], social [baseline=24.2%; month 6=15%; month 12=15%], emotional [baseline=37.1%; month 6=29.6%; month 12=29.4%], and cognitive [baseline=34.2%; month 6=34.5%; month 12=31.7%]) below the clinical problem threshold remained stable over the first 12 months of palbociclib treatment (Table 2). A similar trend across time was observed with the symptom scales with the percentages of patients (fatigue, pain, nausea and vomiting, insomnia, appetite loss, constipation, dyspnea, diarrhea, and financial difficulties) above the clinical problem threshold also remaining stable over the first 12 months (Table 2). Conclusions: In this PRO analysis, palbociclib treatment did not have any significant adverse impact on QoL in patients with HR+/HER2- ABC as assessed by QLQ-C30 functioning and symptom scales. Pfizer (NCT03280303) Table 1.Patient Demographic CharacteristicsCharacteristicTotal. (N=1240)Age at study enrollmentMedian (range), y64 (22-97)Distribution, n (%)<40 y61 (4.9)40 to 50 y144 (11.6)51 to 69 y622 (50.2)70 to 74 y181 (14.6)75 to 84 y198 (16.0)≥85 y34 (2.7)Sex, n (%)Male15 (1.2)Female1225 (98.8)Race, n (%)American Indian or Alaska Nativea8 (0.6)Asian19 (1.5)Black or African Americana138 (11.1)Native Hawaiian or other Pacific Islandera5 (0.4)White1017 (82.0)Not reported due to confidentiality regulations27 (2.2)Other23 (1.9)Not reported3 (0.2)Ethnicity, n (%)Hispanic or Latinob104 (8.4)Not Hispanic or Latino1099 (88.6)Not reported due to confidentiality regulations36 (2.9)Time from ABC/mBC diagnosis date to study enrollment dateMedian (range), y1.35 (0-248)Missing, n7Distribution, n (%)≤1 mo508 (41.0)>1 to 2 mo247 (19.9)>2 to 3 mo71 (5.7)>3 to 4 mo22 (1.8)>4 to 5 mo23 (1.9)>5 to 6 mo12 (1.0)>6 mo350 (28.2)aMinority. bMinority among White. ABC=advanced breast cancer; mBC=metastatic breast cancer. Table 2.Percentages of Symptoms and Functional ImprovementScaleClinical problem (threshold)Baselinea n (%)Month 6a n (%)Month 12a n (%)Functioning ScalesbPhysical functioningc<83629 (54.6)365 (50.2)239 (50.4)Mean (SD)73.3 (24.8)76.9 (22.2)76.7 (21.7)Role functioningc<58330 (28.6)146 (20.1)88 (18.6)Mean (SD)70.4 (32.7)76.0 (27.8)77.2 (26.6)Social functioningd<58278 (24.2)109 (15.0)71 (15.0)Mean (SD)74.4 (29.8)80.7 (25.0)81.0 (25.3)Emotional functioninge<71427 (37.1)215 (29.6)139 (29.4)Mean (SD)74.3 (23.1)79.6 (20.4)80.5 (21.0)Cognitive functioninge<75394 (34.2)251 (34.5)150 (31.7)Mean (SD)78.9 (24.4)80.4 (21.3)80.7 (22.9)Symptom ScalesbFatiguec>39421 (36.5)256 (35.2)144 (30.4)Mean (SD)36.7 (26.9)34.2 (23.0)33.0(24.4)Painc>25614 (53.3)341 (46.9)221 (46.6)Mean (SD)34.8 (31.7)26.7 (26.4)26.6 (27.2)Nausea and vomitingc>8423 (36.7)233 (32.0)153 (32.3)Mean (SD)12.4 (21.2)9.4 (17.4)9.7 (17.3)Insomniaf>50279 (24.2)156 (21.5)89 (18.8)Mean (SD)31.7 (31.1)29.3 (28.9)26.8 (29.0)Appetite lossf>50205 (17.8)72 (9.9)48 (10.1)Mean (SD)23.3 (30.2)16.9 (25.0)15.9 (25.2)Constipationc>50142 (12.3)71 (9.8)46 (9.7)Mean (SD)18.9 (27.6)15.7 (23.7)15.3 (23.8)Dyspneag>17547 (47.6)323 (44.5)207 (43.7)Mean (SD)23.0 (28.8)19.1 (24.8)18.5 (24.5)Diarrheah>17327 (28.5)209 (28.7)120 (25.4)Mean (SD)12.9 (23.5)12.8 (22.6)10.5 (20.1)Financial Impact of Diseasei>17563 (49.0)322 (44.3)198 (42.0)Mean (SD)26.9 (33.2)22.5 (30.3)20.2 (27.9)aThe number of patients eligible at a visit is based on data expected to be available through the latest date of exposure, visit date, or questionnaire date. Baseline, N=1240; Month 6, N=1076; Month 12, N=926. bPercentages for functional and symptom scales were calculated based on “n,” the number of measurements available. Values for Mean (Standard Deviation, SD) were also based on “n”. cn (missing), Baseline=1152 (88); Month 6=727 (349); Month 12=474 (452) dn (missing), Baseline=1151 (89); Month 6=726 (350); Month 12=473 (453) en (missing), Baseline=1151 (89); Month 6=727 (349); Month 12=473 (453) fn (missing), Baseline=1151 (89); Month 6=727 (349); Month 12=474 (452) gn (missing), Baseline=1149 (91); Month 6=726 (350); Month 12=474 (452) hn (missing), Baseline=1149 (91); Month 6=727 (349); Month 12=473 (453) in (missing), Baseline=1149 (91); Month 6=727 (349); Month 12=471 (455) Note: For functioning scales, scoring below the clinical problem threshold indicates a clinically important problem whereas, for the symptom scales, scores above the clinical problem threshold indicate such a problem. Citation Format: Meghan S. Karuturi, Gabrielle B. Rocque, Joseph C. Cappelleri, Joanne L. Blum, Steven L. McCune, Bijoy Telivala, Sobha Kurian, Daniel M. Anderson, Michaela Tsai, Timothy Pluard, John Migas, Yao Wang, Monica Z. Montelongo, Debu Tripathy. Real-world quality of life (QoL) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer (ABC) treated with palbociclib: A patient-reported outcome (PRO) analysis from POLARIS [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-25.
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Popesco, Timothée, Quentin Gardet, Jonathan Bossard, Nicola A. Maffiuletti, and Nicolas Place. "Effects of pulse width and frequency on evoked responses in electrostimulation: comparison between three muscle groups." Current Issues in Sport Science (CISS) 9, no. 2 (February 6, 2024): 022. http://dx.doi.org/10.36950/2024.2ciss022.
Full textAbstract:
Introduction Neuromuscular electrical stimulation (NMES) is an innovative and effective (re)training strategy to improve or restore neuromuscular function (Maffiuletti et al., 2018). Contractions induced by NMES differ in many aspects from voluntary contractions, as motor unit (MU) recruitment is random, synchronous and spatially fixed (mostly superficial; Maffiuletti, 2010). Consequently, several limitations, such as higher fatigability (Vanderthommen et al., 1999) and discomfort (Delitto et al., 1992) might restrain its clinical implementation. The use of specific stimulation parameters may partly overcome these limitations. Indeed, the use of wide pulses (≥ 1 ms) delivered at low stimulation intensity leads to a preferential recruitment of Ia sensory axons (Veale et al., 1973) which may promote MU central (reflexive) recruitment. Furthermore, the high stimulation frequencies (> 80 Hz) would facilitate the temporal summation of post-synaptic excitatory potentials and reflexively activate spinal motoneurons through Ia afferents (Dideriksen et al., 2015), which may increase force production. Another potential advantage of wide pulse high frequency (WPHF) NMES is that low stimulation intensities are required to limit antidromic collision, and these lower intensities are associated with less discomfort (Delitto et al., 1992). Therefore, by stimulating at intensities expected to generate ~10% of the maximal voluntary contraction (MVC) force, WPHF NMES induces, in some individuals, a progressive increase in force during the stimulation, called ‘extra force’. It can reach up to 80% of the MVC force in plantar flexors (Neyroud et al., 2018) but the response to WPHF NMES in other muscle groups is less documented. Extra force is usually accompanied by a prolongation of the surface electromyographic (EMG) activity after cessation of the stimulation, also called ‘sustained EMG activity’ which is interpreted as MU recruited through the central pathway (Neyroud et al, 2018). The main aim of the present study was to explore the effect of varying stimulation parameters on the NMES-evoked force and sustained EMG activity in the plantar flexors, knee extensors and elbow flexors. It was hypothesized that the plantar flexors would show higher centrally-mediated responses to NMES than knee extensors and elbow flexors, especially with large pulse duration. Methods Sixteen volunteers, 2 women and 14 men (29 ± 6 yr, 177 ± 6 cm, 74 ± 11 kg) participated to three experimental sessions - one for each muscle group - in a randomized order. The experimental protocol was similar for the three muscle groups and included twelve 10-s NMES trains separated by at least 2 min of rest and delivered at an intensity set initially to evoke 10% of the maximal voluntary contraction force. Stimulation trains were randomly delivered with a combination of frequencies (20, 50, 100 and 147 Hz) and pulse durations (0.2, 1 and 2 ms). Force was collected using specific isometric ergometers and EMG activity was recorded with bipolar electrodes on the soleus, vastus lateralis and biceps brachii muscles. Extra force was calculated as the relative force difference between the last second and the 2nd second of stimulation. Sustained EMG activity was identified as the visible activity on the EMG after the end of the stimulation and quantified over 500 ms as the root mean square (RMS) of this signal normalized by the RMS of the EMG activity measured during the MVC. Results Stimulation frequency. Extra force was significantly higher for the plantar flexors than for the elbow flexors at 50 Hz (69 ± 68% vs 38 ± 53%, p = 0.025), 100 Hz (84 ± 71% vs 21 ± 72%, p < 0.001) and 147 Hz (75 ± 84% vs 16 ± 82%, p < 0.001), but not at 20 Hz (p = 0.649). For all the tested frequencies, extra force was not significantly different between plantar flexors and knee extensors (p = 0.065 - 0.743). Extra force was significantly higher for the knee extensors than for the elbow flexors at 100 Hz (63 ± 106% vs 21 ± 72%, p = 0.012), but not at the other frequencies (p = 0.156 - 0.388). Sustained EMG activity was significantly higher for the plantar flexors than for the elbow flexors at all frequencies (p < 0.001) as well as compared to the knee extensors at 50 Hz, 100 Hz and 147 Hz (p = 0.010, p = 0.009, p = 0.003 respectively) but not at 20 Hz (p = 0.483). Finally, sustained EMG activity was significantly higher for the knee extensors than for the elbow flexors at for all the tested stimulation frequencies (p < 0.05). Pulse duration. Extra force was significantly higher for the plantar flexors than for the elbow flexors with pulse durations of 1 ms (76 ± 74% vs 23 ± 48%, p < 0.001) and 2 ms (73 ± 70% vs 29 ± 88%, p < 0.001) but not with 0.2 ms (p = 0.064). Extra force was not significantly different between the plantar flexors and the knee extensors, and the knee extensors showed a higher extra force than elbow flexors with 1 ms (56 ± 99% vs 23 ± 48%, p = 0.002). Sustained EMG activity was significantly higher for the plantar flexors than the elbow flexors with all pulse durations (p < 0.001) and than the knee extensors with 1 and 2 ms (p < 0.001). Knee extensors showed a higher sustained EMG activity than elbow flexors with 0.2 ms and 2 ms (p < 0.001) but not with 1 ms. Discussion/Conclusion WPHF NMES is a promising tool for (re)training and the results of the present study suggest that its use to induce centrally-mediated force is more pertinent in lower limb muscles. The difference in responses between muscle groups could be explained by muscle typology and density in neuromuscular spindles. Indeed, muscles involved in precise movements and postural control have a greater number of neuromuscular spindles, which are mainly located in type 1 fibers (Botterman et al., 1978). The greater centrally-mediated responses in the plantar flexors compared with the elbow flexors can be explained by the difference in muscle typology (more type I muscle fibers in the postural lower limb muscles). It may also justify the absence of difference in extra force between plantar flexors and knee extensors as they both contribute to postural maintenance (Jusić et al., 1995). Since the effectiveness of NMES for neuromuscular adaptations depends on the amount of force generated during training (Maffiuletti et al., 2018), these results suggest that the use of WPHF NMES would be efficient on plantar flexors and knee extensors for training and rehabilitation and that wide pulses and high frequencies should be preferentially used when implementing this NMES modality in clinical settings. References Botterman, B. R., Binder, M. D., & Stuart, D. G. (1978). Functional anatomy of the association between motor units and muscle teceptors. American Zoologist, 18(1), 135–152. https://doi.org/10.1093/icb/18.1.135 Delitto, A., Strube, M. J., Shulman, A. D., & Minor, S. D. (1992). A study of discomfort with electrical stimulation. Physical Therapy, 72(6), 410–421. https://doi.org/10.1093/ptj/72.6.410 Dideriksen, J. L., Muceli, S., Dosen, S., Laine, C. M., & Farina, D. (2015). Physiological recruitment of motor units by high-frequency electrical stimulation of afferent pathways. Journal of Applied Physiology, 118(3), 365–376. https://doi.org/10.1152/japplphysiol.00327.2014 Jusić, A., Baraba, R., & Bogunović, A. (1995). H-reflex and F-wave potentials in leg and arm muscles. Electromyography and Clinical Neurophysiology, 35(8), 471–478. Maffiuletti, N. A., Gondin, J., Place, N., Stevens-Lapsley, J., Vivodtzev, I., & Minetto, M. A. (2018). Clinical Use of Neuromuscular Electrical Stimulation for Neuromuscular Rehabilitation: What Are We Overlooking? Archives of Physical Medicine and Rehabilitation, 99(4), 806-812. https://doi.org/10.1016/j.apmr.2017.10.028 Maffiuletti, N. A. (2010). Physiological and methodological considerations for the use of neuromuscular electrical stimulation. European Journal of Applied Physiology, 110(2), 223–234. https://doi.org/10.1007/s00421-010-1502-y Neyroud, D., Grosprêtre, S., Gondin, J., Kayser, B., & Place, N. (2018). Test–retest reliability of wide-pulse high-frequency neuromuscular electrical stimulation evoked force. Muscle & Nerve, 57(1), E70–E77. https://doi.org/10.1002/mus.25747 Vanderthommen, M., Gilles, R., Carlier, P., Ciancabilla, F., Zahlan, O., Sluse, F., & Crielaard, J. M. (1999). Human muscle energetics during voluntary and electrically induced isometric contractions as measured by 31P NMR spectroscopy. International Journal of Sports Medicine, 20(5), 279–283. https://doi.org/10.1055/s-2007-971131 Veale, J. L., Mark, R. F., & Rees, S. (1973). Differential sensitivity of motor and sensory fibres in human ulnar nerve. Journal of Neurology, Neurosurgery & Psychiatry, 36(1), 75–86.
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Sibagariang, Pradita Permatasari, and Weny Savitry S. Pandia. "Teaching Approach and Teacher Self-Efficacy during Early Childhood Distance Learning." JPUD - Jurnal Pendidikan Usia Dini 15, no. 1 (April 30, 2021): 41–59. http://dx.doi.org/10.21009/jpud.151.03.
Full textAbstract:
Child Distance Learning (CDL) during the pandemic has led to an optimal development of children and effective teaching and learning processes in kindergartens. To overcome this, teachers need to apply a teaching approach in accordance with the principles of kindergarten education. In addition, teachers' self-efficacy of their ability to teach is also important for developing children's skills. This study aims to describe the teaching approach and the efficacy of kindergarten teachers during the CDL process and to identify the relationship between the two. The research method used is quantitative through document analysis as a source of data findings. A total of 116 Public Kindergarten (PK) teachers in DKI Jakarta participated in filling out the Classroom Management Scale and Teachers' Sense of Efficacy Scale online. All data were processed using descriptive statistics and correlation. Furthermore, there is a document analysis carried out on the Daily / Weekly Learning Program Design in PK Jakarta. The findings identified that the teaching approach of kindergarten teachers during CDL included only two principles of kindergarten education, namely thematic teaching and developing life skills. Furthermore, PK teachers in the Jakarta area showed low self-efficacy during CDL. The teaching approach and self-efficacy were caused by teachers' unpreparedness in facing challenges during CDL. In addition, other findings indicate that there is a relationship between teaching approaches and teacher self-efficacy. Another CDL model Interventions to increase teacher self-efficacy and the extent to which the relationship between the two variables can be studied further in future studies.
Keywords: Early Childhood, Distance Learning, Teaching Approach, Teacher Self-Efficacy
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Novi Sekar Sari, Ririn Tri Ratnasari, Ismah Osman, and Ega Rusanti. "Materialism and Environmental Knowledge as a Mediator for Relationships between Religiosity and Ethical Consumption." Jurnal Ekonomi Syariah Teori dan Terapan 10, no. 5 (September 30, 2023): 467–81. http://dx.doi.org/10.20473/vol10iss20235pp467-481.
Full textAbstract:
ABSTRACTOn a global and regional scale, Indonesia has one of the least environmentally sustainable economies in the Asia-Pacific region. Consumption is one of the key factors contributing to environmental degradation. By using materialism and environmental knowledge as mediators, this study aimed to understand how religiosity affects ethical consumption. This research used quantitative methods with structural equation modeling (SEM) analysis techniques based on partial least squares (PLS). The data came from a questionnaire distributed online. 153 valid questionnaires were selected for analysis. All respondents came from Indonesia, were adults (from 18 years old), and were Muslims. Findings show that religiosity influences ethical consumption, materialism, and environmental knowledge. This research also reveals that materialism and environmental knowledge influence ethical consumption, as well as the mediating effect of materialism and environmental knowledge on the influence between religiosity and ethical consumption. So, all hypotheses from this research can be accepted. These findings contribute theoretically to explaining the relationship between religiosity, materialism, environmental knowledge, and ethical consumption. Thus, this findings contribute to the field of Islamic economics. Practically, the findings of this research can help marketers formulate communication strategies that take into account the level of religiosity of consumers in Indonesia. Marketers must avoid unethical practices to encourage ethical consumption.Keywords: Religiosity, ethical consumption, materialism, environmental knowledge ABSTRAKPada skala global dan regional, Indonesia merupakan salah satu negara dengan perekonomian paling tidak ramah lingkungan di kawasan Asia-Pasifik. Konsumsi merupakan salah satu faktor utama yang berkontribusi terhadap degradasi lingkungan. Dengan menggunakan materialisme dan enviromental knowledge sebagai mediator, penelitian ini berupaya memahami bagaimana religiosity mempengaruhi ethical consumption. Penelitian ini menggunakan metode kuantitatif dengan teknik analisis Structural Equation Model (SEM) berbasis Partial Least Square (PLS). Data berasal dari kuesioner yang disebarkan online. 153 kuesioner yang valid dipilih untuk analisis. Seluruh responden berasal dari Indonesia, dewasa (mulai 18 tahun) dan beragama Islam. Temuan menunjukkan bahwa religiosity berpengaruh terhadap ethical consumption, materialism, dan environmental knowledge. Selain itu juga diketahui bahwa materialism dan environmental knowledge berpengaruh ethical consumption, serta adanya efek mediasi dari materialism dan environmental knowledge pada pengaruh antara religiosity dan ethical consumption. Sehingga, semua hipotesis penelitian ini dapat diterima. Secara praktis, temuan penelitian ini dapat membantu pemasar untuk merumuskan strategi komunikasi yang mempertimbangkan tingkat religiosity konsumen di Indonesia. Pemasar harus menghindari praktik tidak etis untuk mempromosikan ethical consumption.Kata Kunci: Religiosity, ethical consumption, materialism, environmental knowledge REFERENCES Adib, H., & El-Bassiouny, N. (2012). Materialism in young consumers: An investigation of family communication patterns and parental mediation practices in Egypt. Journal of Islamic Marketing, 3(3), 255–282. doi:10.1108/17590831211259745 Adil, M. (2022). Influence of religiosity on ethical consumption: The mediating role of materialism and guilt. Journal of Islamic Marketing, 13(10), 2173–2192. doi:10.1108/JIMA-01-2020-0035 Al-Aidaros, A., Shamsudin, F. M., & Idris, K. M. (2013). Ethics and ethical theories from an Islamic perspective. International Journal of Islamic Thought, 4(1), 1–13. doi:10.24035/ijit.04.2013.001 Al Glenid, M. A., Al Sabbagh, A. 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Smolen, J. S., P. Emery, W. Rigby, Y. Tanaka, J. Ignacio Vargas, N. Damjanov, M. Jain, et al. "POS0847 UPADACITINIB AS MONOTHERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS AND PRIOR INADEQUATE RESPONSE TO METHOTREXATE: RESULTS AT 260 WEEKS FROM THE SELECT-MONOTHERAPY STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 723–24. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2423.
Full textAbstract:
BackgroundUpadacitinib (UPA), an oral JAK inhibitor, was shown to be safe and effective in improving the signs and symptoms of moderate-to-severe RA through 84 weeks (wks) when administered as monotherapy in patients (pts) with a prior inadequate response to MTX in the phase 3 SELECT-MONOTHERAPY trial (NCT02706951).[1]ObjectivesTo evaluate the efficacy and safety of UPA monotherapy up to wk 260 from the long-term extension (LTE) of SELECT-MONOTHERAPY.MethodsPts with active RA on stable MTX were randomly assigned to either continue MTX (cMTX) or switch to UPA monotherapy at 15 mg (UPA15) or 30 mg (UPA30) once daily (QD) during the 14-wk randomized, double-blind treatment period. From wk 14, the start of the LTE, pts receiving cMTX were switched to UPA15 or 30 per pre-specified assignment at baseline; pts randomly assigned to UPA15 or 30 continued their initial treatment assignment. After the study protocol was amended (13 December 2019), all pts treated with UPA30 were eventually switched to UPA15 (approved dose). Efficacy outcomes through wk 260 are presented by randomized treatment group and reported as observed and using non-responder imputation. Safety results are presented based on actual treatment received with treatment-emergent adverse events (TEAEs) summarized per 100 pt years (PY) of exposure through a cut-off date of 10 August 2022, when all pts completed wk 260.ResultsOf 648 pts randomized, 299 (46%) discontinued the study drug by wk 260 primarily due to AEs (16%), consent withdrawal (12%), or other reasons (11%). At wk 260, pts on UPA maintained or further demonstrated clinical improvement across various endpoints; similar efficacy outcomes were also observed among pts who switched from cMTX to UPA15 or 30 (Table 1). As observed, over three-quarters of pts achieved low disease activity based on CDAI and DAS28(CRP) at wk 260. Total PY of exposure were 1111.0 for UPA15, 812.5 for UPA30, and 300.2 for UPA15 switched from UPA30. The most frequently reported TEAEs were urinary tract infection, creatine phosphokinase (CPK) elevation, upper respiratory tract infection, nasopharyngitis, bronchitis, and RA worsening/flare. COVID-19 pneumonia was the most common serious AE. Pts on UPA30 had higher rates of herpes zoster (HZ), hepatic disorder, neutropenia, lymphopenia, and CPK elevation than pts on UPA15; rates of serious infection and malignancy excluding non-melanoma skin cancer (NMSC) were similar between UPA doses (Figure 1). Most HZ events affected 1–2 dermatomes with 2 ophthalmic (UPA15; 0.2 E/100 PY) and 1 disseminated (UPA30; 0.1 E/100 PY) cases reported. Eleven adjudicated MACE (UPA15: 0.5 E/100 PY; UPA30: 0.7 E/100 PY) and 10 adjudicated VTE (UPA15: 0.6 E/100 PY; UPA30: 0.4 E/100 PY; UPA15 switched from UPA30: 0.3 E/100 PY) all occurred in pts with ≥ 1 cardiovascular risk factor. Through wk 260, 16 deaths were reported (10 treatment-emergent) with 5 related to COVID-19 infection.ConclusionUPA monotherapy continued to be effective in treating RA signs and symptoms through wk 260. No new safety signals were identified with longer-term exposure to UPA, consistent with prior findings[1–3]and the established safety profile of UPA across indications.References[1]Smolen JS, et al.ARD. 2020;79:331–2.[2]Smolen JS, et al.Lancet. 2019;393:2303–11.[3]Smolen JS, et al.Arthritis Rheumatol. 2019;71(suppl 10).Table 1.Efficacy Endpoints at Week 260 (AO and NRI)Response, %cMTX -> UPA 15 mgcMTX ->UPA 30 mgUPA 15 mgUPA 30 mgAOaN = 57 – 65NRI N = 108AOaN = 54 – 56NRI N = 108AOaN = 107 – 114NRI N = 217AOaN = 117 – 123NRI N = 215ACR20/50/7089/82/6148/43/3286/75/5743/39/3090/76/5950/42/3293/80/6350/44/34DAS28(CRP)≤ 3.2/< 2.686/7243/3684/6741/3389/7142/3484/7644/40CDAI≤ 10/≤ 2.888/4948/2882/4040/2086/4243/2179/5442/29BooleanRemission3921321732164223AO, as observed; cMTX, continue MTX; NRI, non-responder imputation; UPA, upadacitinib.aAO response rate was calculated from patients with observed records only.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsJosef S. Smolen Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, BMS, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, Roche, Samsung, and UCB, Consultant of: AbbVie, Amgen, AstraZeneca, Astro, BMS, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, Roche, Samsung, and UCB, Grant/research support from: AbbVie, Amgen, AstraZeneca, Astro, BMS, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, Roche, Samsung, and UCB, Paul Emery Consultant of: AbbVie, BMS, Eli Lilly, Gilead, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung, Grant/research support from: AbbVie, BMS, Eli Lilly, Gilead, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung, William Rigby Consultant of: AbbVie, BMS, Genentech, and Pfizer, Yoshiya Tanaka Speakers bureau: AbbVie, Amgen, Asahi-Kasei, Astellas, AstraZeneca, Boehringer-Ingelheim, BMS, Chugai, Corrona, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Kowa, Mitsubishi-Tanabe, Takeda, YL Biologics, and Takeda, Consultant of: AbbVie, Amgen, Asahi-Kasei, Astellas, AstraZeneca, Boehringer-Ingelheim, BMS, Chugai, Corrona, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Kowa, Mitsubishi-Tanabe, Takeda, YL Biologics, and Takeda, Grant/research support from: AbbVie, Amgen, Asahi-Kasei, Astellas, AstraZeneca, Boehringer-Ingelheim, BMS, Chugai, Corrona, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Kowa, Mitsubishi-Tanabe, Takeda, YL Biologics, and Takeda, Juan Ignacio Vargas Consultant of: AbbVie, Nemanja Damjanov Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche., Grant/research support from: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche., Manish Jain Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Medac, Novartis, Pfizer, and Takeda, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Medac, Novartis, Pfizer, and Takeda, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Medac, Novartis, Pfizer, and Takeda, Koji Kato Shareholder of: Employee of AbbVie and may own stock or options, Employee of: AbbVie, Kyle Carter Shareholder of: Employee of AbbVie and may own stock or options, Employee of: AbbVie, Nasser Khan Shareholder of: Employee of AbbVie and may own stock or options, Employee of: AbbVie, Heidi Camp Shareholder of: Employee of AbbVie and may own stock or options, Employee of: AbbVie, Stanley B. Cohen Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Gilead, Pfizer, Roche, and Sandoz, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Gilead, Pfizer, Roche, and Sandoz.
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Aliev, Amil R., Isa R. Akhmedov, Murad G. Kakagasanov, and Zakir A. Aliev. "ПРЕДПЕРЕХОДНЫЕ ЯВЛЕНИЯ В ОБЛАСТИ СТРУКТУРНОГО ФАЗОВОГО ПЕРЕХОДА В СУЛЬФАТЕ КАЛИЯ." Kondensirovannye sredy i mezhfaznye granitsy = Condensed Matter and Interphases 21, no. 3 (September 26, 2019): 350–57. http://dx.doi.org/10.17308/kcmf.2019.21/1148.
Full textAbstract:
Методами спектроскопии комбинационного рассеяния света исследованы структурно-динамические свойства и процессы молекулярной релаксации в кристаллическом сульфате калия K2SO4 в интервале температур от 293 до 900 К. Проанализированы температурные зависимости положения максимума v (частоты), ширины w и интенсивности I спектральной полосы, отвечающей полносимметричному колебанию v1(A) сульфат-иона SO4 2–, в спектральном интервале от 963 до 976 см–1. С ростом температуры частота колебания уменьшается. Примерно при 650 K имеют место определённые особенности температурной зависимости v(T). При дальнейшем увеличении температуры частота продолжает уменьшаться. В точке структурного фазового перехода первого рода (Ts = 854 K)уменьшение частоты приостанавливается. С ростом температуры ширина возрастает, а интенсивность уменьшается. Примерно при 650 K имеют место определённые особенности температурных зависимостей w(T) и I(T). Уменьшение интенсивности приостанавливается, и в интервале температур 650–850 K интенсивность остаётся почти постоянной. При структурном фазовом переходе первого рода (Ts = 854 K) интенсивность уменьшается. Рост ширины при температуре T ≈ 650 K приостанавливается, а затем снова ширина начинает увеличиваться. Ближе к структурному фазовому переходу первого рода (Ts = 854 K) рост ширины замедляется и в точке структурного фазового перехода первого рода (Ts = 854 K) имеет место уменьшение ширины. Установлено, что в кристаллическом сульфате калия K2SO4 структурный фазовый переход первого рода носит растянутый характер. При температуре фазового перехода (Ts = 854 К) ширина резко возрастает, а частота резко уменьшается, уменьшаясь и при дальнейшем увеличении температуры. Обнаружено существование предпереходной области в исследованном кристаллическом сульфате калия K2SO4. Эта предпереходная область имеет место в интервале температур от 650 К до Ts = 854 К.
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Agredo Orozco, Andres Felipe, Diego Andres Acosta Maya, Carlos Arturo Rodriguez Arroyave, and Luis Fernando Sierra Zuluaga. "Wax and bentonite blends for prototyping industrial clay development: preliminary results." Universidad Ciencia y Tecnología 25, no. 111 (December 10, 2021): 134–44. http://dx.doi.org/10.47460/uct.v25i111.524.
Full textAbstract:
The automotive design process and the materials in the automotive industry in recent years has caused great interest to the industrial and academic sector. In this study was to evaluate the effect of the amount of bentonite on the thermal and rheological properties of the compound bentonite / paraffin wax. Two bentonite ratios were used: paraffin wax (40:60 and 30:70). The paraffin was characterized by Fourier transform infrared spectroscopy (FTIR), the bentonite was characterized by means of x-ray diffraction (XRD), thermogravimetric analysis (TGA), X-ray fluorescence (XRF). The bentonite/paraffine wax composite was characterized by differential-scanning calorimetry (DSC) and rheology. The sample that contains a higher amount of bentonite shows a lower latent heat, and this could cause a greater heat transfer. Finally, the sample that has a lower amount of bentonite evidenced a lower viscosity, and it could be related to a lower interaction between the particles. The sample S1 due to its lower latent heat compared to S2 could represent an interesting alternative to develop prototypingclays. since these materials are characterized by their low working temperatures and easy malleability.
Keywords: automotive, prototyping, latent heat, bentonite, paraffin.
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Alqahtani, Sarra, and Rose Gamble. "Volume 2, Issue 3, Special issue on Recent Advances in Engineering Systems (Published Papers) Articles Transmit / Received Beamforming for Frequency Diverse Array with Symmetrical frequency offsets Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 1-6 (2017); View Description Detailed Analysis of Amplitude and Slope Diffraction Coefficients for knife-edge structure in S-UTD-CH Model Eray Arik, Mehmet Baris Tabakcioglu Adv. Sci. Technol. Eng. Syst. J. 2(3), 7-11 (2017); View Description Applications of Case Based Organizational Memory Supported by the PAbMM Architecture Martín, María de los Ángeles, Diván, Mario José Adv. Sci. Technol. Eng. Syst. J. 2(3), 12-23 (2017); View Description Low Probability of Interception Beampattern Using Frequency Diverse Array Antenna Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 24-29 (2017); View Description Zero Trust Cloud Networks using Transport Access Control and High Availability Optical Bypass Switching Casimer DeCusatis, Piradon Liengtiraphan, Anthony Sager Adv. Sci. Technol. Eng. Syst. J. 2(3), 30-35 (2017); View Description A Derived Metrics as a Measurement to Support Efficient Requirements Analysis and Release Management Indranil Nath Adv. Sci. Technol. Eng. Syst. J. 2(3), 36-40 (2017); View Description Feedback device of temperature sensation for a myoelectric prosthetic hand Yuki Ueda, Chiharu Ishii Adv. Sci. Technol. Eng. Syst. J. 2(3), 41-40 (2017); View Description Deep venous thrombus characterization: ultrasonography, elastography and scattering operator Thibaud Berthomier, Ali Mansour, Luc Bressollette, Frédéric Le Roy, Dominique Mottier Adv. Sci. Technol. Eng. Syst. J. 2(3), 48-59 (2017); View Description Improving customs’ border control by creating a reference database of cargo inspection X-ray images Selina Kolokytha, Alexander Flisch, Thomas Lüthi, Mathieu Plamondon, Adrian Schwaninger, Wicher Vasser, Diana Hardmeier, Marius Costin, Caroline Vienne, Frank Sukowski, Ulf Hassler, Irène Dorion, Najib Gadi, Serge Maitrejean, Abraham Marciano, Andrea Canonica, Eric Rochat, Ger Koomen, Micha Slegt Adv. Sci. Technol. Eng. Syst. J. 2(3), 60-66 (2017); View Description Aviation Navigation with Use of Polarimetric Technologies Arsen Klochan, Ali Al-Ammouri, Viktor Romanenko, Vladimir Tronko Adv. Sci. Technol. Eng. Syst. J. 2(3), 67-72 (2017); View Description Optimization of Multi-standard Transmitter Architecture Using Single-Double Conversion Technique Used for Rescue Operations Riadh Essaadali, Said Aliouane, Chokri Jebali and Ammar Kouki Adv. Sci. Technol. Eng. Syst. J. 2(3), 73-81 (2017); View Description Singular Integral Equations in Electromagnetic Waves Reflection Modeling A. S. Ilinskiy, T. N. Galishnikova Adv. Sci. Technol. Eng. Syst. J. 2(3), 82-87 (2017); View Description Methodology for Management of Information Security in Industrial Control Systems: A Proof of Concept aligned with Enterprise Objectives. Fabian Bustamante, Walter Fuertes, Paul Diaz, Theofilos Toulqueridis Adv. Sci. Technol. Eng. Syst. J. 2(3), 88-99 (2017); View Description Dependence-Based Segmentation Approach for Detecting Morpheme Boundaries Ahmed Khorsi, Abeer Alsheddi Adv. Sci. Technol. Eng. Syst. J. 2(3), 100-110 (2017); View Description Paper Improving Rule Based Stemmers to Solve Some Special Cases of Arabic Language Soufiane Farrah, Hanane El Manssouri, Ziyati Elhoussaine, Mohamed Ouzzif Adv. Sci. Technol. Eng. Syst. J. 2(3), 111-115 (2017); View Description Medical imbalanced data classification Sara Belarouci, Mohammed Amine Chikh Adv. Sci. Technol. Eng. Syst. J. 2(3), 116-124 (2017); View Description ADOxx Modelling Method Conceptualization Environment Nesat Efendioglu, Robert Woitsch, Wilfrid Utz, Damiano Falcioni Adv. Sci. Technol. Eng. Syst. J. 2(3), 125-136 (2017); View Description GPSR+Predict: An Enhancement for GPSR to Make Smart Routing Decision by Anticipating Movement of Vehicles in VANETs Zineb Squalli Houssaini, Imane Zaimi, Mohammed Oumsis, Saïd El Alaoui Ouatik Adv. Sci. Technol. Eng. Syst. J. 2(3), 137-146 (2017); View Description Optimal Synthesis of Universal Space Vector Digital Algorithm for Matrix Converters Adrian Popovici, Mircea Băbăiţă, Petru Papazian Adv. Sci. Technol. Eng. Syst. J. 2(3), 147-152 (2017); View Description Control design for axial flux permanent magnet synchronous motor which operates above the nominal speed Xuan Minh Tran, Nhu Hien Nguyen, Quoc Tuan Duong Adv. Sci. Technol. Eng. Syst. J. 2(3), 153-159 (2017); View Description A synchronizing second order sliding mode control applied to decentralized time delayed multi−agent robotic systems: Stability Proof Marwa Fathallah, Fatma Abdelhedi, Nabil Derbel Adv. Sci. Technol. Eng. Syst. J. 2(3), 160-170 (2017); View Description Fault Diagnosis and Tolerant Control Using Observer Banks Applied to Continuous Stirred Tank Reactor Martin F. Pico, Eduardo J. Adam Adv. Sci. Technol. Eng. Syst. J. 2(3), 171-181 (2017); View Description Development and Validation of a Heat Pump System Model Using Artificial Neural Network Nabil Nassif, Jordan Gooden Adv. Sci. Technol. Eng. Syst. J. 2(3), 182-185 (2017); View Description Assessment of the usefulness and appeal of stigma-stop by psychology students: a serious game designed to reduce the stigma of mental illness Adolfo J. Cangas, Noelia Navarro, Juan J. Ojeda, Diego Cangas, Jose A. Piedra, José Gallego Adv. Sci. Technol. Eng. Syst. J. 2(3), 186-190 (2017); View Description Kinect-Based Moving Human Tracking System with Obstacle Avoidance Abdel Mehsen Ahmad, Zouhair Bazzal, Hiba Al Youssef Adv. Sci. Technol. Eng. Syst. J. 2(3), 191-197 (2017); View Description A security approach based on honeypots: Protecting Online Social network from malicious profiles Fatna Elmendili, Nisrine Maqran, Younes El Bouzekri El Idrissi, Habiba Chaoui Adv. Sci. Technol. Eng. Syst. J. 2(3), 198-204 (2017); View Description Pulse Generator for Ultrasonic Piezoelectric Transducer Arrays Based on a Programmable System-on-Chip (PSoC) Pedro Acevedo, Martín Fuentes, Joel Durán, Mónica Vázquez, Carlos Díaz Adv. Sci. Technol. Eng. Syst. J. 2(3), 205-209 (2017); View Description Enabling Toy Vehicles Interaction With Visible Light Communication (VLC) M. A. Ilyas, M. B. Othman, S. M. Shah, Mas Fawzi Adv. Sci. Technol. Eng. Syst. J. 2(3), 210-216 (2017); View Description Analysis of Fractional-Order 2xn RLC Networks by Transmission Matrices Mahmut Ün, Manolya Ün Adv. Sci. Technol. Eng. Syst. J. 2(3), 217-220 (2017); View Description Fire extinguishing system in large underground garages Ivan Antonov, Rositsa Velichkova, Svetlin Antonov, Kamen Grozdanov, Milka Uzunova, Ikram El Abbassi Adv. Sci. Technol. Eng. Syst. J. 2(3), 221-226 (2017); View Description Directional Antenna Modulation Technique using A Two-Element Frequency Diverse Array Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 227-232 (2017); View Description Classifying region of interests from mammograms with breast cancer into BIRADS using Artificial Neural Networks Estefanía D. Avalos-Rivera, Alberto de J. Pastrana-Palma Adv. Sci. Technol. Eng. Syst. J. 2(3), 233-240 (2017); View Description Magnetically Levitated and Guided Systems Florian Puci, Miroslav Husak Adv. Sci. Technol. Eng. Syst. J. 2(3), 241-244 (2017); View Description Energy-Efficient Mobile Sensing in Distributed Multi-Agent Sensor Networks Minh T. Nguyen Adv. Sci. Technol. Eng. Syst. J. 2(3), 245-253 (2017); View Description Validity and efficiency of conformal anomaly detection on big distributed data Ilia Nouretdinov Adv. Sci. Technol. Eng. Syst. J. 2(3), 254-267 (2017); View Description S-Parameters Optimization in both Segmented and Unsegmented Insulated TSV upto 40GHz Frequency Juma Mary Atieno, Xuliang Zhang, HE Song Bai Adv. Sci. Technol. Eng. Syst. J. 2(3), 268-276 (2017); View Description Synthesis of Important Design Criteria for Future Vehicle Electric System Lisa Braun, Eric Sax Adv. Sci. Technol. Eng. Syst. J. 2(3), 277-283 (2017); View Description Gestural Interaction for Virtual Reality Environments through Data Gloves G. Rodriguez, N. Jofre, Y. Alvarado, J. Fernández, R. Guerrero Adv. Sci. Technol. Eng. Syst. J. 2(3), 284-290 (2017); View Description Solving the Capacitated Network Design Problem in Two Steps Meriem Khelifi, Mohand Yazid Saidi, Saadi Boudjit Adv. Sci. Technol. Eng. Syst. J. 2(3), 291-301 (2017); View Description A Computationally Intelligent Approach to the Detection of Wormhole Attacks in Wireless Sensor Networks Mohammad Nurul Afsar Shaon, Ken Ferens Adv. Sci. Technol. Eng. Syst. J. 2(3), 302-320 (2017); View Description Real Time Advanced Clustering System Giuseppe Spampinato, Arcangelo Ranieri Bruna, Salvatore Curti, Viviana D’Alto Adv. Sci. Technol. Eng. Syst. J. 2(3), 321-326 (2017); View Description Indoor Mobile Robot Navigation in Unknown Environment Using Fuzzy Logic Based Behaviors Khalid Al-Mutib, Foudil Abdessemed Adv. Sci. Technol. Eng. Syst. J. 2(3), 327-337 (2017); View Description Validity of Mind Monitoring System as a Mental Health Indicator using Voice Naoki Hagiwara, Yasuhiro Omiya, Shuji Shinohara, Mitsuteru Nakamura, Masakazu Higuchi, Shunji Mitsuyoshi, Hideo Yasunaga, Shinichi Tokuno Adv. Sci. Technol. Eng. Syst. J. 2(3), 338-344 (2017); View Description The Model of Adaptive Learning Objects for virtual environments instanced by the competencies Carlos Guevara, Jose Aguilar, Alexandra González-Eras Adv. Sci. Technol. Eng. Syst. J. 2(3), 345-355 (2017); View Description An Overview of Traceability: Towards a general multi-domain model Kamal Souali, Othmane Rahmaoui, Mohammed Ouzzif Adv. Sci. Technol. Eng. Syst. J. 2(3), 356-361 (2017); View Description L-Band SiGe HBT Active Differential Equalizers with Variable, Positive or Negative Gain Slopes Using Dual-Resonant RLC Circuits Yasushi Itoh, Hiroaki Takagi Adv. Sci. Technol. Eng. Syst. J. 2(3), 362-368 (2017); View Description Moving Towards Reliability-Centred Management of Energy, Power and Transportation Assets Kang Seng Seow, Loc K. Nguyen, Kelvin Tan, Kees-Jan Van Oeveren Adv. Sci. Technol. Eng. Syst. J. 2(3), 369-375 (2017); View Description Secure Path Selection under Random Fading Furqan Jameel, Faisal, M Asif Ali Haider, Amir Aziz Butt Adv. Sci. Technol. Eng. Syst. J. 2(3), 376-383 (2017); View Description Security in SWIPT with Power Splitting Eavesdropper Furqan Jameel, Faisal, M Asif Ali Haider, Amir Aziz Butt Adv. Sci. Technol. Eng. Syst. J. 2(3), 384-388 (2017); View Description Performance Analysis of Phased Array and Frequency Diverse Array Radar Ambiguity Functions Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 389-394 (2017); View Description Adaptive Discrete-time Fuzzy Sliding Mode Control For a Class of Chaotic Systems Hanene Medhaffar, Moez Feki, Nabil Derbel Adv. Sci. Technol. Eng. Syst. J. 2(3), 395-400 (2017); View Description Fault Tolerant Inverter Topology for the Sustainable Drive of an Electrical Helicopter Igor Bolvashenkov, Jörg Kammermann, Taha Lahlou, Hans-Georg Herzog Adv. Sci. Technol. Eng. Syst. J. 2(3), 401-411 (2017); View Description Computational Intelligence Methods for Identifying Voltage Sag in Smart Grid Turgay Yalcin, Muammer Ozdemir Adv. Sci. Technol. Eng. Syst. J. 2(3), 412-419 (2017); View Description A Highly-Secured Arithmetic Hiding cum Look-Up Table (AHLUT) based S-Box for AES-128 Implementation Ali Akbar Pammu, Kwen-Siong Chong, Bah-Hwee Gwee Adv. Sci. Technol. Eng. Syst. J. 2(3), 420-426 (2017); View Description Service Productivity and Complexity in Medical Rescue Services Markus Harlacher, Andreas Petz, Philipp Przybysz, Olivia Chaillié, Susanne Mütze-Niewöhner Adv. Sci. Technol. Eng. Syst. J. 2(3), 427-434 (2017); View Description Principal Component Analysis Application on Flavonoids Characterization Che Hafizah Che Noh, Nor Fadhillah Mohamed Azmin, Azura Amid Adv. Sci. Technol. Eng. Syst. J. 2(3), 435-440 (2017); View Description A Reconfigurable Metal-Plasma Yagi-Yuda Antenna for Microwave Applications Giulia Mansutti, Davide Melazzi, Antonio-Daniele Capobianco Adv. Sci. Technol. Eng. Syst. J. 2(3), 441-448 (2017); View Description Verifying the Detection Results of Impersonation Attacks in Service Clouds." Advances in Science, Technology and Engineering Systems Journal 2, no. 3 (May 2017): 449–59. http://dx.doi.org/10.25046/aj020358.
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Abdelhedi, Fatma, and Nabil Derbel. "Volume 2, Issue 3, Special issue on Recent Advances in Engineering Systems (Published Papers) Articles Transmit / Received Beamforming for Frequency Diverse Array with Symmetrical frequency offsets Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 1-6 (2017); View Description Detailed Analysis of Amplitude and Slope Diffraction Coefficients for knife-edge structure in S-UTD-CH Model Eray Arik, Mehmet Baris Tabakcioglu Adv. Sci. Technol. Eng. Syst. J. 2(3), 7-11 (2017); View Description Applications of Case Based Organizational Memory Supported by the PAbMM Architecture Martín, María de los Ángeles, Diván, Mario José Adv. Sci. Technol. Eng. Syst. J. 2(3), 12-23 (2017); View Description Low Probability of Interception Beampattern Using Frequency Diverse Array Antenna Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 24-29 (2017); View Description Zero Trust Cloud Networks using Transport Access Control and High Availability Optical Bypass Switching Casimer DeCusatis, Piradon Liengtiraphan, Anthony Sager Adv. Sci. Technol. Eng. Syst. J. 2(3), 30-35 (2017); View Description A Derived Metrics as a Measurement to Support Efficient Requirements Analysis and Release Management Indranil Nath Adv. Sci. Technol. Eng. Syst. J. 2(3), 36-40 (2017); View Description Feedback device of temperature sensation for a myoelectric prosthetic hand Yuki Ueda, Chiharu Ishii Adv. Sci. Technol. Eng. Syst. J. 2(3), 41-40 (2017); View Description Deep venous thrombus characterization: ultrasonography, elastography and scattering operator Thibaud Berthomier, Ali Mansour, Luc Bressollette, Frédéric Le Roy, Dominique Mottier Adv. Sci. Technol. Eng. Syst. J. 2(3), 48-59 (2017); View Description Improving customs’ border control by creating a reference database of cargo inspection X-ray images Selina Kolokytha, Alexander Flisch, Thomas Lüthi, Mathieu Plamondon, Adrian Schwaninger, Wicher Vasser, Diana Hardmeier, Marius Costin, Caroline Vienne, Frank Sukowski, Ulf Hassler, Irène Dorion, Najib Gadi, Serge Maitrejean, Abraham Marciano, Andrea Canonica, Eric Rochat, Ger Koomen, Micha Slegt Adv. Sci. Technol. Eng. Syst. J. 2(3), 60-66 (2017); View Description Aviation Navigation with Use of Polarimetric Technologies Arsen Klochan, Ali Al-Ammouri, Viktor Romanenko, Vladimir Tronko Adv. Sci. Technol. Eng. Syst. J. 2(3), 67-72 (2017); View Description Optimization of Multi-standard Transmitter Architecture Using Single-Double Conversion Technique Used for Rescue Operations Riadh Essaadali, Said Aliouane, Chokri Jebali and Ammar Kouki Adv. Sci. Technol. Eng. Syst. J. 2(3), 73-81 (2017); View Description Singular Integral Equations in Electromagnetic Waves Reflection Modeling A. S. Ilinskiy, T. N. Galishnikova Adv. Sci. Technol. Eng. Syst. J. 2(3), 82-87 (2017); View Description Methodology for Management of Information Security in Industrial Control Systems: A Proof of Concept aligned with Enterprise Objectives. Fabian Bustamante, Walter Fuertes, Paul Diaz, Theofilos Toulqueridis Adv. Sci. Technol. Eng. Syst. J. 2(3), 88-99 (2017); View Description Dependence-Based Segmentation Approach for Detecting Morpheme Boundaries Ahmed Khorsi, Abeer Alsheddi Adv. Sci. Technol. Eng. Syst. J. 2(3), 100-110 (2017); View Description Paper Improving Rule Based Stemmers to Solve Some Special Cases of Arabic Language Soufiane Farrah, Hanane El Manssouri, Ziyati Elhoussaine, Mohamed Ouzzif Adv. Sci. Technol. Eng. Syst. J. 2(3), 111-115 (2017); View Description Medical imbalanced data classification Sara Belarouci, Mohammed Amine Chikh Adv. Sci. Technol. Eng. Syst. J. 2(3), 116-124 (2017); View Description ADOxx Modelling Method Conceptualization Environment Nesat Efendioglu, Robert Woitsch, Wilfrid Utz, Damiano Falcioni Adv. Sci. Technol. Eng. Syst. J. 2(3), 125-136 (2017); View Description GPSR+Predict: An Enhancement for GPSR to Make Smart Routing Decision by Anticipating Movement of Vehicles in VANETs Zineb Squalli Houssaini, Imane Zaimi, Mohammed Oumsis, Saïd El Alaoui Ouatik Adv. Sci. Technol. Eng. Syst. J. 2(3), 137-146 (2017); View Description Optimal Synthesis of Universal Space Vector Digital Algorithm for Matrix Converters Adrian Popovici, Mircea Băbăiţă, Petru Papazian Adv. Sci. Technol. Eng. Syst. J. 2(3), 147-152 (2017); View Description Control design for axial flux permanent magnet synchronous motor which operates above the nominal speed Xuan Minh Tran, Nhu Hien Nguyen, Quoc Tuan Duong Adv. Sci. Technol. Eng. Syst. J. 2(3), 153-159 (2017); View Description A synchronizing second order sliding mode control applied to decentralized time delayed multi−agent robotic systems: Stability Proof Marwa Fathallah, Fatma Abdelhedi, Nabil Derbel Adv. Sci. Technol. Eng. Syst. J. 2(3), 160-170 (2017); View Description Fault Diagnosis and Tolerant Control Using Observer Banks Applied to Continuous Stirred Tank Reactor Martin F. Pico, Eduardo J. Adam Adv. Sci. Technol. Eng. Syst. J. 2(3), 171-181 (2017); View Description Development and Validation of a Heat Pump System Model Using Artificial Neural Network Nabil Nassif, Jordan Gooden Adv. Sci. Technol. Eng. Syst. J. 2(3), 182-185 (2017); View Description Assessment of the usefulness and appeal of stigma-stop by psychology students: a serious game designed to reduce the stigma of mental illness Adolfo J. Cangas, Noelia Navarro, Juan J. Ojeda, Diego Cangas, Jose A. Piedra, José Gallego Adv. Sci. Technol. Eng. Syst. J. 2(3), 186-190 (2017); View Description Kinect-Based Moving Human Tracking System with Obstacle Avoidance Abdel Mehsen Ahmad, Zouhair Bazzal, Hiba Al Youssef Adv. Sci. Technol. Eng. Syst. J. 2(3), 191-197 (2017); View Description A security approach based on honeypots: Protecting Online Social network from malicious profiles Fatna Elmendili, Nisrine Maqran, Younes El Bouzekri El Idrissi, Habiba Chaoui Adv. Sci. Technol. Eng. Syst. J. 2(3), 198-204 (2017); View Description Pulse Generator for Ultrasonic Piezoelectric Transducer Arrays Based on a Programmable System-on-Chip (PSoC) Pedro Acevedo, Martín Fuentes, Joel Durán, Mónica Vázquez, Carlos Díaz Adv. Sci. Technol. Eng. Syst. J. 2(3), 205-209 (2017); View Description Enabling Toy Vehicles Interaction With Visible Light Communication (VLC) M. A. Ilyas, M. B. Othman, S. M. Shah, Mas Fawzi Adv. Sci. Technol. Eng. Syst. J. 2(3), 210-216 (2017); View Description Analysis of Fractional-Order 2xn RLC Networks by Transmission Matrices Mahmut Ün, Manolya Ün Adv. Sci. Technol. Eng. Syst. J. 2(3), 217-220 (2017); View Description Fire extinguishing system in large underground garages Ivan Antonov, Rositsa Velichkova, Svetlin Antonov, Kamen Grozdanov, Milka Uzunova, Ikram El Abbassi Adv. Sci. Technol. Eng. Syst. J. 2(3), 221-226 (2017); View Description Directional Antenna Modulation Technique using A Two-Element Frequency Diverse Array Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 227-232 (2017); View Description Classifying region of interests from mammograms with breast cancer into BIRADS using Artificial Neural Networks Estefanía D. Avalos-Rivera, Alberto de J. Pastrana-Palma Adv. Sci. Technol. Eng. Syst. J. 2(3), 233-240 (2017); View Description Magnetically Levitated and Guided Systems Florian Puci, Miroslav Husak Adv. Sci. Technol. Eng. Syst. J. 2(3), 241-244 (2017); View Description Energy-Efficient Mobile Sensing in Distributed Multi-Agent Sensor Networks Minh T. Nguyen Adv. Sci. Technol. Eng. Syst. J. 2(3), 245-253 (2017); View Description Validity and efficiency of conformal anomaly detection on big distributed data Ilia Nouretdinov Adv. Sci. Technol. Eng. Syst. J. 2(3), 254-267 (2017); View Description S-Parameters Optimization in both Segmented and Unsegmented Insulated TSV upto 40GHz Frequency Juma Mary Atieno, Xuliang Zhang, HE Song Bai Adv. Sci. Technol. Eng. Syst. J. 2(3), 268-276 (2017); View Description Synthesis of Important Design Criteria for Future Vehicle Electric System Lisa Braun, Eric Sax Adv. Sci. Technol. Eng. Syst. J. 2(3), 277-283 (2017); View Description Gestural Interaction for Virtual Reality Environments through Data Gloves G. Rodriguez, N. Jofre, Y. Alvarado, J. Fernández, R. Guerrero Adv. Sci. Technol. Eng. Syst. J. 2(3), 284-290 (2017); View Description Solving the Capacitated Network Design Problem in Two Steps Meriem Khelifi, Mohand Yazid Saidi, Saadi Boudjit Adv. Sci. Technol. Eng. Syst. J. 2(3), 291-301 (2017); View Description A Computationally Intelligent Approach to the Detection of Wormhole Attacks in Wireless Sensor Networks Mohammad Nurul Afsar Shaon, Ken Ferens Adv. Sci. Technol. Eng. Syst. J. 2(3), 302-320 (2017); View Description Real Time Advanced Clustering System Giuseppe Spampinato, Arcangelo Ranieri Bruna, Salvatore Curti, Viviana D’Alto Adv. Sci. Technol. Eng. Syst. J. 2(3), 321-326 (2017); View Description Indoor Mobile Robot Navigation in Unknown Environment Using Fuzzy Logic Based Behaviors Khalid Al-Mutib, Foudil Abdessemed Adv. Sci. Technol. Eng. Syst. J. 2(3), 327-337 (2017); View Description Validity of Mind Monitoring System as a Mental Health Indicator using Voice Naoki Hagiwara, Yasuhiro Omiya, Shuji Shinohara, Mitsuteru Nakamura, Masakazu Higuchi, Shunji Mitsuyoshi, Hideo Yasunaga, Shinichi Tokuno Adv. Sci. Technol. Eng. Syst. J. 2(3), 338-344 (2017); View Description The Model of Adaptive Learning Objects for virtual environments instanced by the competencies Carlos Guevara, Jose Aguilar, Alexandra González-Eras Adv. Sci. Technol. Eng. Syst. J. 2(3), 345-355 (2017); View Description An Overview of Traceability: Towards a general multi-domain model Kamal Souali, Othmane Rahmaoui, Mohammed Ouzzif Adv. Sci. Technol. Eng. Syst. J. 2(3), 356-361 (2017); View Description L-Band SiGe HBT Active Differential Equalizers with Variable, Positive or Negative Gain Slopes Using Dual-Resonant RLC Circuits Yasushi Itoh, Hiroaki Takagi Adv. Sci. Technol. Eng. Syst. J. 2(3), 362-368 (2017); View Description Moving Towards Reliability-Centred Management of Energy, Power and Transportation Assets Kang Seng Seow, Loc K. Nguyen, Kelvin Tan, Kees-Jan Van Oeveren Adv. Sci. Technol. Eng. Syst. J. 2(3), 369-375 (2017); View Description Secure Path Selection under Random Fading Furqan Jameel, Faisal, M Asif Ali Haider, Amir Aziz Butt Adv. Sci. Technol. Eng. Syst. J. 2(3), 376-383 (2017); View Description Security in SWIPT with Power Splitting Eavesdropper Furqan Jameel, Faisal, M Asif Ali Haider, Amir Aziz Butt Adv. Sci. Technol. Eng. Syst. J. 2(3), 384-388 (2017); View Description Performance Analysis of Phased Array and Frequency Diverse Array Radar Ambiguity Functions Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 389-394 (2017); View Description Adaptive Discrete-time Fuzzy Sliding Mode Control For a Class of Chaotic Systems Hanene Medhaffar, Moez Feki, Nabil Derbel Adv. Sci. Technol. Eng. Syst. J. 2(3), 395-400 (2017); View Description Fault Tolerant Inverter Topology for the Sustainable Drive of an Electrical Helicopter Igor Bolvashenkov, Jörg Kammermann, Taha Lahlou, Hans-Georg Herzog Adv. Sci. Technol. Eng. Syst. J. 2(3), 401-411 (2017); View Description Computational Intelligence Methods for Identifying Voltage Sag in Smart Grid Turgay Yalcin, Muammer Ozdemir Adv. Sci. Technol. Eng. Syst. J. 2(3), 412-419 (2017); View Description A Highly-Secured Arithmetic Hiding cum Look-Up Table (AHLUT) based S-Box for AES-128 Implementation Ali Akbar Pammu, Kwen-Siong Chong, Bah-Hwee Gwee Adv. Sci. Technol. Eng. Syst. J. 2(3), 420-426 (2017); View Description Service Productivity and Complexity in Medical Rescue Services Markus Harlacher, Andreas Petz, Philipp Przybysz, Olivia Chaillié, Susanne Mütze-Niewöhner Adv. Sci. Technol. Eng. Syst. J. 2(3), 427-434 (2017); View Description Principal Component Analysis Application on Flavonoids Characterization Che Hafizah Che Noh, Nor Fadhillah Mohamed Azmin, Azura Amid Adv. Sci. Technol. Eng. Syst. J. 2(3), 435-440 (2017); View Description A Reconfigurable Metal-Plasma Yagi-Yuda Antenna for Microwave Applications Giulia Mansutti, Davide Melazzi, Antonio-Daniele Capobianco Adv. Sci. Technol. Eng. Syst. J. 2(3), 441-448 (2017); View Description Verifying the Detection Results of Impersonation Attacks in Service Clouds Sarra Alqahtani, Rose Gamble Adv. Sci. Technol. Eng. Syst. J. 2(3), 449-459 (2017); View Description Image Segmentation Using Fuzzy Inference System on YCbCr Color Model Alvaro Anzueto-Rios, Jose Antonio Moreno-Cadenas, Felipe Gómez-Castañeda, Sergio Garduza-Gonzalez Adv. Sci. Technol. Eng. Syst. J. 2(3), 460-468 (2017); View Description Segmented and Detailed Visualization of Anatomical Structures based on Augmented Reality for Health Education and Knowledge Discovery Isabel Cristina Siqueira da Silva, Gerson Klein, Denise Munchen Brandão Adv. Sci. Technol. Eng. Syst. J. 2(3), 469-478 (2017); View Description Intrusion detection in cloud computing based attack patterns and risk assessment Ben Charhi Youssef, Mannane Nada, Bendriss Elmehdi, Regragui Boubker Adv. Sci. Technol. Eng. Syst. J. 2(3), 479-484 (2017); View Description Optimal Sizing and Control Strategy of renewable hybrid systems PV-Diesel Generator-Battery: application to the case of Djanet city of Algeria Adel Yahiaoui, Khelifa Benmansour, Mohamed Tadjine Adv. Sci. Technol. Eng. Syst. J. 2(3), 485-491 (2017); View Description RFID Antenna Near-field Characterization Using a New 3D Magnetic Field Probe Kassem Jomaa, Fabien Ndagijimana, Hussam Ayad, Majida Fadlallah, Jalal Jomaah Adv. Sci. Technol. Eng. Syst. J. 2(3), 492-497 (2017); View Description Design, Fabrication and Testing of a Dual-Range XY Micro-Motion Stage Driven by Voice Coil Actuators Xavier Herpe, Matthew Dunnigan, Xianwen Kong Adv. Sci. Technol. Eng. Syst. J. 2(3), 498-504 (2017); View Description Self-Organizing Map based Feature Learning in Bio-Signal Processing Marwa Farouk Ibrahim Ibrahim, Adel Ali Al-Jumaily Adv. Sci. Technol. Eng. Syst. J. 2(3), 505-512 (2017); View Description A delay-dependent distributed SMC for stabilization of a networked robotic system exposed to external disturbances." Advances in Science, Technology and Engineering Systems Journal 2, no. 3 (June 2016): 513–19. http://dx.doi.org/10.25046/aj020366.
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Biran, Yahav, George Collins, Borky John M, and Joel Dubow. "Volume 2, Issue 3, Special issue on Recent Advances in Engineering Systems (Published Papers) Articles Transmit / Received Beamforming for Frequency Diverse Array with Symmetrical frequency offsets Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 1-6 (2017); View Description Detailed Analysis of Amplitude and Slope Diffraction Coefficients for knife-edge structure in S-UTD-CH Model Eray Arik, Mehmet Baris Tabakcioglu Adv. Sci. Technol. Eng. Syst. J. 2(3), 7-11 (2017); View Description Applications of Case Based Organizational Memory Supported by the PAbMM Architecture Martín, María de los Ángeles, Diván, Mario José Adv. Sci. Technol. Eng. Syst. J. 2(3), 12-23 (2017); View Description Low Probability of Interception Beampattern Using Frequency Diverse Array Antenna Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 24-29 (2017); View Description Zero Trust Cloud Networks using Transport Access Control and High Availability Optical Bypass Switching Casimer DeCusatis, Piradon Liengtiraphan, Anthony Sager Adv. Sci. Technol. Eng. Syst. J. 2(3), 30-35 (2017); View Description A Derived Metrics as a Measurement to Support Efficient Requirements Analysis and Release Management Indranil Nath Adv. Sci. Technol. Eng. Syst. J. 2(3), 36-40 (2017); View Description Feedback device of temperature sensation for a myoelectric prosthetic hand Yuki Ueda, Chiharu Ishii Adv. Sci. Technol. Eng. Syst. J. 2(3), 41-40 (2017); View Description Deep venous thrombus characterization: ultrasonography, elastography and scattering operator Thibaud Berthomier, Ali Mansour, Luc Bressollette, Frédéric Le Roy, Dominique Mottier Adv. Sci. Technol. Eng. Syst. 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Syst. J. 2(3), 116-124 (2017); View Description ADOxx Modelling Method Conceptualization Environment Nesat Efendioglu, Robert Woitsch, Wilfrid Utz, Damiano Falcioni Adv. Sci. Technol. Eng. Syst. J. 2(3), 125-136 (2017); View Description GPSR+Predict: An Enhancement for GPSR to Make Smart Routing Decision by Anticipating Movement of Vehicles in VANETs Zineb Squalli Houssaini, Imane Zaimi, Mohammed Oumsis, Saïd El Alaoui Ouatik Adv. Sci. Technol. Eng. Syst. J. 2(3), 137-146 (2017); View Description Optimal Synthesis of Universal Space Vector Digital Algorithm for Matrix Converters Adrian Popovici, Mircea Băbăiţă, Petru Papazian Adv. Sci. Technol. Eng. Syst. J. 2(3), 147-152 (2017); View Description Control design for axial flux permanent magnet synchronous motor which operates above the nominal speed Xuan Minh Tran, Nhu Hien Nguyen, Quoc Tuan Duong Adv. Sci. Technol. Eng. Syst. 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J. 2(3), 210-216 (2017); View Description Analysis of Fractional-Order 2xn RLC Networks by Transmission Matrices Mahmut Ün, Manolya Ün Adv. Sci. Technol. Eng. Syst. J. 2(3), 217-220 (2017); View Description Fire extinguishing system in large underground garages Ivan Antonov, Rositsa Velichkova, Svetlin Antonov, Kamen Grozdanov, Milka Uzunova, Ikram El Abbassi Adv. Sci. Technol. Eng. Syst. J. 2(3), 221-226 (2017); View Description Directional Antenna Modulation Technique using A Two-Element Frequency Diverse Array Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 227-232 (2017); View Description Classifying region of interests from mammograms with breast cancer into BIRADS using Artificial Neural Networks Estefanía D. Avalos-Rivera, Alberto de J. Pastrana-Palma Adv. Sci. Technol. Eng. Syst. J. 2(3), 233-240 (2017); View Description Magnetically Levitated and Guided Systems Florian Puci, Miroslav Husak Adv. Sci. Technol. Eng. Syst. J. 2(3), 241-244 (2017); View Description Energy-Efficient Mobile Sensing in Distributed Multi-Agent Sensor Networks Minh T. Nguyen Adv. Sci. Technol. Eng. Syst. J. 2(3), 245-253 (2017); View Description Validity and efficiency of conformal anomaly detection on big distributed data Ilia Nouretdinov Adv. Sci. Technol. Eng. Syst. J. 2(3), 254-267 (2017); View Description S-Parameters Optimization in both Segmented and Unsegmented Insulated TSV upto 40GHz Frequency Juma Mary Atieno, Xuliang Zhang, HE Song Bai Adv. Sci. Technol. Eng. Syst. J. 2(3), 268-276 (2017); View Description Synthesis of Important Design Criteria for Future Vehicle Electric System Lisa Braun, Eric Sax Adv. Sci. Technol. Eng. Syst. J. 2(3), 277-283 (2017); View Description Gestural Interaction for Virtual Reality Environments through Data Gloves G. Rodriguez, N. Jofre, Y. Alvarado, J. Fernández, R. Guerrero Adv. Sci. Technol. Eng. Syst. J. 2(3), 284-290 (2017); View Description Solving the Capacitated Network Design Problem in Two Steps Meriem Khelifi, Mohand Yazid Saidi, Saadi Boudjit Adv. Sci. Technol. Eng. Syst. J. 2(3), 291-301 (2017); View Description A Computationally Intelligent Approach to the Detection of Wormhole Attacks in Wireless Sensor Networks Mohammad Nurul Afsar Shaon, Ken Ferens Adv. Sci. Technol. Eng. Syst. J. 2(3), 302-320 (2017); View Description Real Time Advanced Clustering System Giuseppe Spampinato, Arcangelo Ranieri Bruna, Salvatore Curti, Viviana D’Alto Adv. Sci. Technol. Eng. Syst. J. 2(3), 321-326 (2017); View Description Indoor Mobile Robot Navigation in Unknown Environment Using Fuzzy Logic Based Behaviors Khalid Al-Mutib, Foudil Abdessemed Adv. Sci. Technol. Eng. Syst. J. 2(3), 327-337 (2017); View Description Validity of Mind Monitoring System as a Mental Health Indicator using Voice Naoki Hagiwara, Yasuhiro Omiya, Shuji Shinohara, Mitsuteru Nakamura, Masakazu Higuchi, Shunji Mitsuyoshi, Hideo Yasunaga, Shinichi Tokuno Adv. Sci. Technol. Eng. Syst. J. 2(3), 338-344 (2017); View Description The Model of Adaptive Learning Objects for virtual environments instanced by the competencies Carlos Guevara, Jose Aguilar, Alexandra González-Eras Adv. Sci. Technol. Eng. Syst. J. 2(3), 345-355 (2017); View Description An Overview of Traceability: Towards a general multi-domain model Kamal Souali, Othmane Rahmaoui, Mohammed Ouzzif Adv. Sci. Technol. Eng. Syst. J. 2(3), 356-361 (2017); View Description L-Band SiGe HBT Active Differential Equalizers with Variable, Positive or Negative Gain Slopes Using Dual-Resonant RLC Circuits Yasushi Itoh, Hiroaki Takagi Adv. Sci. Technol. Eng. Syst. J. 2(3), 362-368 (2017); View Description Moving Towards Reliability-Centred Management of Energy, Power and Transportation Assets Kang Seng Seow, Loc K. Nguyen, Kelvin Tan, Kees-Jan Van Oeveren Adv. Sci. Technol. Eng. Syst. J. 2(3), 369-375 (2017); View Description Secure Path Selection under Random Fading Furqan Jameel, Faisal, M Asif Ali Haider, Amir Aziz Butt Adv. Sci. Technol. Eng. Syst. J. 2(3), 376-383 (2017); View Description Security in SWIPT with Power Splitting Eavesdropper Furqan Jameel, Faisal, M Asif Ali Haider, Amir Aziz Butt Adv. Sci. Technol. Eng. Syst. J. 2(3), 384-388 (2017); View Description Performance Analysis of Phased Array and Frequency Diverse Array Radar Ambiguity Functions Shaddrack Yaw Nusenu Adv. Sci. Technol. Eng. Syst. J. 2(3), 389-394 (2017); View Description Adaptive Discrete-time Fuzzy Sliding Mode Control For a Class of Chaotic Systems Hanene Medhaffar, Moez Feki, Nabil Derbel Adv. Sci. Technol. Eng. Syst. J. 2(3), 395-400 (2017); View Description Fault Tolerant Inverter Topology for the Sustainable Drive of an Electrical Helicopter Igor Bolvashenkov, Jörg Kammermann, Taha Lahlou, Hans-Georg Herzog Adv. Sci. Technol. Eng. Syst. J. 2(3), 401-411 (2017); View Description Computational Intelligence Methods for Identifying Voltage Sag in Smart Grid Turgay Yalcin, Muammer Ozdemir Adv. Sci. Technol. Eng. Syst. J. 2(3), 412-419 (2017); View Description A Highly-Secured Arithmetic Hiding cum Look-Up Table (AHLUT) based S-Box for AES-128 Implementation Ali Akbar Pammu, Kwen-Siong Chong, Bah-Hwee Gwee Adv. Sci. Technol. Eng. Syst. J. 2(3), 420-426 (2017); View Description Service Productivity and Complexity in Medical Rescue Services Markus Harlacher, Andreas Petz, Philipp Przybysz, Olivia Chaillié, Susanne Mütze-Niewöhner Adv. Sci. Technol. Eng. Syst. J. 2(3), 427-434 (2017); View Description Principal Component Analysis Application on Flavonoids Characterization Che Hafizah Che Noh, Nor Fadhillah Mohamed Azmin, Azura Amid Adv. Sci. Technol. Eng. Syst. J. 2(3), 435-440 (2017); View Description A Reconfigurable Metal-Plasma Yagi-Yuda Antenna for Microwave Applications Giulia Mansutti, Davide Melazzi, Antonio-Daniele Capobianco Adv. Sci. Technol. Eng. Syst. J. 2(3), 441-448 (2017); View Description Verifying the Detection Results of Impersonation Attacks in Service Clouds Sarra Alqahtani, Rose Gamble Adv. Sci. Technol. Eng. Syst. J. 2(3), 449-459 (2017); View Description Image Segmentation Using Fuzzy Inference System on YCbCr Color Model Alvaro Anzueto-Rios, Jose Antonio Moreno-Cadenas, Felipe Gómez-Castañeda, Sergio Garduza-Gonzalez Adv. Sci. Technol. Eng. Syst. J. 2(3), 460-468 (2017); View Description Segmented and Detailed Visualization of Anatomical Structures based on Augmented Reality for Health Education and Knowledge Discovery Isabel Cristina Siqueira da Silva, Gerson Klein, Denise Munchen Brandão Adv. Sci. Technol. Eng. Syst. J. 2(3), 469-478 (2017); View Description Intrusion detection in cloud computing based attack patterns and risk assessment Ben Charhi Youssef, Mannane Nada, Bendriss Elmehdi, Regragui Boubker Adv. Sci. Technol. Eng. Syst. J. 2(3), 479-484 (2017); View Description Optimal Sizing and Control Strategy of renewable hybrid systems PV-Diesel Generator-Battery: application to the case of Djanet city of Algeria Adel Yahiaoui, Khelifa Benmansour, Mohamed Tadjine Adv. Sci. Technol. Eng. Syst. J. 2(3), 485-491 (2017); View Description RFID Antenna Near-field Characterization Using a New 3D Magnetic Field Probe Kassem Jomaa, Fabien Ndagijimana, Hussam Ayad, Majida Fadlallah, Jalal Jomaah Adv. Sci. Technol. Eng. Syst. J. 2(3), 492-497 (2017); View Description Design, Fabrication and Testing of a Dual-Range XY Micro-Motion Stage Driven by Voice Coil Actuators Xavier Herpe, Matthew Dunnigan, Xianwen Kong Adv. Sci. Technol. Eng. Syst. J. 2(3), 498-504 (2017); View Description Self-Organizing Map based Feature Learning in Bio-Signal Processing Marwa Farouk Ibrahim Ibrahim, Adel Ali Al-Jumaily Adv. Sci. Technol. Eng. Syst. J. 2(3), 505-512 (2017); View Description A delay-dependent distributed SMC for stabilization of a networked robotic system exposed to external disturbances Fatma Abdelhedi, Nabil Derbel Adv. Sci. Technol. Eng. Syst. J. 2(3), 513-519 (2017); View Description Modelization of cognition, activity and motivation as indicators for Interactive Learning Environment Asmaa Darouich, Faddoul Khoukhi, Khadija Douzi Adv. Sci. Technol. Eng. Syst. J. 2(3), 520-531 (2017); View Description Homemade array of surface coils implementation for small animal magnetic resonance imaging Fernando Yepes-Calderon, Olivier Beuf Adv. Sci. Technol. Eng. Syst. J. 2(3), 532-539 (2017); View Description An Encryption Key for Secure Authentication: The Dynamic Solution Zubayr Khalid, Pritam Paul, Khabbab Zakaria, Himadri Nath Saha Adv. Sci. Technol. Eng. Syst. J. 2(3), 540-544 (2017); View Description Multi-Domain Virtual Network Embedding with Coordinated Link Mapping Shuopeng Li, Mohand Yazid Saidi, Ken Chen Adv. Sci. Technol. Eng. Syst. J. 2(3), 545-552 (2017); View Description Semantic-less Breach Detection of Polymorphic Malware in Federated Cloud." Advances in Science, Technology and Engineering Systems Journal 2, no. 3 (June 2017): 553–61. http://dx.doi.org/10.25046/aj020371.
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Daranas Peláez, Mariano. "Constitución del Reino de Marruecos." Revista de las Cortes Generales, April 1, 2011, 481–561. http://dx.doi.org/10.33426/rcg/2011/82/362.
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SUMARIO: Nota-resumen sobre la reforma constitucional de 1° de julio de 2011. I.- Introducción: Antecedentes inmediatos. Método de la exposición. A) Antecedentes inmediatos. B) Método expositivo. II.- Objeto y contenido de la reforma. A) Datos generales. B) Descripción de los elementos esenciales. 1) Definición del Estado. 2) El Rey como clave de bóveda del sistema constitucional. 3) Límites a la prerrogativa regia en la formación de gobierno. 4) Reconocimiento oficial de la oposición. 5) Refuerzo del poder de los partidos políticos en el Parlamento. 6) Notable ampliación de la lista de derechos, libertades y garantías. III.- Conclusiones. Constitución del Reino de Marruecos.
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Du, Mengxi, and Fang Fang Zhang. "Dietary Supplement Use Among Adult Cancer Survivors in the United States." FASEB Journal 31, S1 (April 2017). http://dx.doi.org/10.1096/fasebj.31.1_supplement.168.6.
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BackgroundMany cancer patients initiated supplement use after cancer diagnosis and yet the effect of supplement use on survival has not been established. The trend of and factors associated with dietary supplement use in cancer survivors warrant further investigation.MethodsWe examined the trend of dietary supplemental use in 1,902 adult cancer survivors who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2012, and compared the frequency of supplement use in cancer survivors to that of 3,804 individuals with no history of cancer who were matched to the cancer survivors by age, sex, and race/ethnicity. The use of any supplements and individual supplements in the past 30 days was assessed based on self‐report. We further evaluated factors associated with supplement use in cancer survivors.ResultsAdult cancer survivors reported a significantly higher frequency of using any supplements (58% vs. 54%, p=0.0009) and individual supplements such as folic acid (26% vs. 23%, p=0.01), vitamin D (21% vs. 17%, p=0.0002), vitamin C (19% vs. 16%, p=0.01), and magnesium (12% vs. 10%, p=0.03) than non‐cancer individuals. Cancer survivors also reported an increasing trend of using vitamin D (11% in 1999–2000 vs. 41% in 2011–2012, p for trend<0.0001) and fish oil (1% in 1999–2000 vs. 15% in 2011–2012, p for trend<0.0001) but a decreasing trend of using calcium (18% in 1999–2000 vs. 10% in 2011–2012, p for trend=0.002). Compared to survivors who reported no supplement use, those who reported any supplement use were older (60 vs. 56 years of age, p<0.0001) and more likely to be non‐Hispanic Whites (86% vs. 76%, p<0.0001), college graduates (62% vs. 46%, p<0.0001), nonsmokers (42% vs. 38%, p<0.0001), and moderate alcohol drinkers defined as <=1 drink/d for women and <=2 drinks/d for men (41% vs. 31%, p=0.004), having a diagnosis of breast cancer (22% vs.14%, p=0.004), and being diagnosed with cancer at an older (49 vs. 45 years of age, p<0.0001). Gender, weight status, and years since diagnosis were not associated with supplement use in cancer survivors.ConclusionsIn a national sample of US adults, cancer survivors reported a higher frequency of supplement use than non‐cancer individuals. Supplement use in cancer survivors has been increasing for vitamin D and fish oil but decreasing for calcium.Support or Funding InformationNIH/NCI 1R03CA199516 Supplement Use in Adult Cancer Survivors and Individuals without Cancer in NHANES 1999–2012 Supplement Use Cancer Survivors (n=1,902) Individuals without Cancer (n=3,804) P value N (%) N (%) Any supplement use1 1,111 (58.4) 2046 (53.8) 0.0009 Multivitamin and mineral (MVM) supplement use2 Multivitamin with mineral 182 (9.6) 336 (8.8) 0.36 Multivitamin without mineral 75 (3.9) 111(2.9) 0.04 Single supplement use 444 (23.3) 877 (23.1) 0.81 Vitamins Folic Acid 492 (25.9) 862 (22.7) 0.01 Vitamin D 393 (20.7) 631 (16.6) 0.0002 Vitamin C 362 (19.0) 622 (16.4) 0.01 Vitamin E 331 (17.4) 609 (16.0) 0.18 Vitamin B12 212 (11.2} 385 (10.1) 0.23 Vitamin B6 181 (9.5) 327 (8.6) 0.25 Vitamin A 177 (9.3) 364 (9.6) 0.75 Vitamin B3 161 (8.5) 303 (8.0) 0.52 Vitamin K 54 (2.8) 118 (3.1) 0.58 Minerals Calcium 274 (14.4) 551 (14.5) 0.94 Magnesium 225 (11.8) 377 (9.9) 0.03 Zinc 153 (8.0) 311 (8.2) 0.86 Iron 130 (6.8) 242 (6.4) 0.49 Selenium 118 (6.2) 214 (5.6) 0.38 Potassium 114 (6.0) 212 (5.6) 0.52 Copper 93 (4.9) 201 (5.3) 0.53 Phosphorus 56 (2.9) 109 (2.9) 0.87 Others Fish Oil 116 (6.1) 218 (5.7) 0.58 Glucosamine 43 (2.3) 88 (2.3) 0.90 Garlic 40 (2.1) 82 (2.2) 0.90 Fiber 27 (1.4) 60 (1.6) 0.65 Glutamine 4 (0.2) 7 (0.2) 0.83 Echinacea 8 (0.4) 22 (0.6) 0.44 Any supplement use was defined as the use of the selected vitamins, minerals, non‐vitamin non‐mineral supplements. Multivitamin/mineral (MVM) supplemental use was defined as containing 3 or more vitamins with or without minerals. B‐complex vitamin is considered as a multivitamin supplement. Factors Associated with Supplemental Use in Adult Cancer Survivors1 Characteristics Survivors who reported supplemental use (N=1,111) Survivors who did not report supplemental use (N=791) P value OR (95% CI) Age, years, mean (SEM) 59.8 (0.5) 55.6 (0.6) <.000l Gender, N (%) Men 450 (34.9) 348 (37.0) 0.50 1.0 (ref.) Women 661 (65.1) 443 (63.0) 1.1 (0.8–1.4) Race/ethnicity, N (%) Non‐Hispanic White 747 (86.4) 410 (76.1) < 0001 1.0 (ref.) Non‐Hispanic Black 179 (6.0) 209 (12.2) 0.4 (0.3–0.6) Other 185 (7.6) 172 (11.7) 0.6 (0.4–0.8) Education, N (%) Grades 0–12 242 (14.3) 289 (25.1) <.000l 1.0 (ref.) Some post high school 265 (23.3) 206 (29.2) 1.4 (1.0–1.9) College graduate 602 (62.4) 296 (45.7) 2.4 (1.8–3.2) Smoking, N (%) Nonsmokers 481 (42.2) 308 (38.0) <.0001 1.0 (ref.) Former smokers 472 (42.7) 272 (31.9) 1.2 (0.9–1.6) Current smokers 157 (15.1) 210 (30.1) 0.5 (0.3–0.6) Alcohol, drink/week, N (%) Nondrinkers 414 (33.3) 345 (40.6) 0.004 1.0 (ref.) Moderate drinkers 421 (41.4) 215 (30.8) 1.6 (1.2–2.2) Heavy Drinkers 219 (25.4) 164 (28.6) 1.1 (0.8–1.5) Body mass index (BMI), kg/m2, mean (SEM) 28.9 (0.2) 29.4 (0.3) 0.13 Weight status, N (%) Normal weight (BMI=18.5–24.9) 308 (31.1) 186 (28.1) 0.60 1.0 (ref.) Overweight (BMI=25–29.9) 374 (31.8) 276 (33.2) 0.9 (0.6–1.2) Obese (BMI≥30) 429 (37.1) 329 (38.7) 0.9 (0.6–1.2) Primary diagnosis, N (%) Breast cancer 233 (22.0) 114 (14.3) 0.004 1.7 (1.2–2.4) Prostate cancer 184 (11.6) 162 (12.9) 0.45 0.9 (0.7–1.2) Colon cancer 94 (6.7) 77 (7.5) 0.54 0.9 (0.6–1.3) Lung cancer 33 (3.0) 20 (2.4) 0.40 1.3 (0.7–2.1) Other 500 (50.0) 381 (57.0) 0.02 0.8 (0.6–0.9) Multiple 67 (6.7) 37 (5.8) 0.60 1.2 (0.7–2.1) Age at diagnosis, years, mean (SEM) 49.0 (0.6) 44.6 (0.7) <.0001 Time from diagnosis, years, mean (SEM) 10.8 (0.5) 11.0 (0.4) 0.76 Time from diagnosis, N (%) >10 453 (42.0) 324 (43.0) 0.98 1.0 (ref) 5–9 279 (24.4) 196 (24.4) 1.1 (0.6–1.9) 1–4 331 (28.6) 230 (27.9) 1.1 (0.8–1.4) <1 48 (5.0) 41 (4.7) 1.0 (0.8–1.3) Frequencies, odds ratio, and 95% confidence intervals presented were weighted. Trend of Supplemental Use in Adult Cancer Survivors and Individuals without Cancer1 Supplement Use Cancer Survivors (n=1,902) p trend Individuals Without Cancer (n=3,804) p trend 99–00 01–02 03–04 05–06 07–08 09–10 11–12 99–00 01–02 03–04 05–06 07–08 09–10 11–12 Any supplement use2 125 (62.1) 133 (62.9) 156 (64.2) 131 (63.3) 192 (60.0) 197 (62.6) 177 (67.3) 0.95 239 (55.0) 286 (56.9) 313 (61.0) 260 (59.8) 352 (59.1) 332 (54.7) 264 (57.2) 0.44 Folic Acid 39 (20.7) 69 (31.5) 78 (33.0) 66 (31.3) 95 (30.4) 75 (27.9) 70 (24.5) 0.26 85 (19.3) 124 (23.9) 129 (25.3) 130 (28.2) 155 (26.7) 139 (24.6) 100 (22.0) 0.49 Vitamin D 21 (11.3) 30 (15.3) 44 (18.7) 38 (19.9) 68 (21.7) 96 (33.7) 96 (41.3) <.0001 38 (10.2) 53 (11.1) 78 (15.8) 71 (16.1) 125 (21.8) 134 (24.9) 132 (27.4) <.0001 Vitamin C 45 (22.2) 43 (26.3) 68 (29.9) 43 (21.8) 59 (18.0) 58 (19.3) 46 (16.5) 0.08 71 (17.4) 103 (22.1) 92 (16.9) 86 (20.6) 105 (19.0) 85 (15.9) 80 (19.0) 0.48 Calcium 34 (17.6) 41 (22.4) 46 (20.3) 37 (19.1) 40 (12.6) 43 (14.5) 33 (10.3) 0.002 65 (16.4) 79 (15.5) 86 (16.3) 89 (21.2) 87 (15.0) 70 (12.8) 75 (17.9) 0.02 Magnesium 28 (14.0) 23 (12.1) 36 (13.1) 26 (13.9) 36 (12.0) 41 (14.0) 35 (16.5) 0.89 45 (13.3) 55 (10.2) 50 (9.8) 53 (13.7) 67 (11.4) 59 (10.7) 48 (14.1) 0.45 Zinc 13 (6.5) 15 (7.9) 18 (7.0) 23 (12.7) 28 (7.8) 30 (11.8) 26 (11.8) 0.34 25 (6.6) 54 (10.6) 42 (7.9) 48 (9.8) 57 (9.9) 42 (8.0) 43 (10.8) 0.54 Fish Oil 1 (0.7) 4 (1.6) 6 (2.8) 13 (7.6) 26 (6.6) 32 (8.8) 34 (15.8) <.0001 3 (1.4) 10 (2.7) 19 (4.3) 59 (9.7) 66 (13.1) 66 (13.1) 44 (6.6) <.0001 Frequencies presented were weighted frequencies. Any supplement use was defined as the use of the selected vitamins, minerals, non‐vitamin non‐mineral supplements.
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Osinibi, Elizabeth, Hong Doan, Alejandro Mercado-Campero, Jayasimha Abbaraju, Shikohe Masood, and Sanjeev Madaan. "The implications when offering percutaneous nephrostomy for the management of malignant obstructive uropathy secondary to urological malignancy: can we be more selective?" Therapeutic Advances in Urology 15 (January 2023). http://dx.doi.org/10.1177/17562872231207729.
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Background & Objectives: Percutaneous nephrostomy (PN) for malignant ureteric obstruction (MUO) is increasingly accessible with high success rates. However, it is not without associated risks and morbidity, impacting quality of life, while not improving overall survival. In two UK hospitals, we investigated the outcomes of undergoing PN for MUO, to inform future patient counselling and selection for this intervention. Methods: A retrospective audit of electronic records identified patients that received PN for bladder, and prostate cancer (PCa) between January 2015 and December 2018. Hospital 1 had a 24-h nephrostomy service, while Hospital 2 had a limited service; Group A: recurrent or treatment-resistant PCa, Group B: primary PCa, Group C: Bladder cancer. Results: A total of 261 patients (Hospital 1 = 186, Hospital 2 = 75), had PN insertion. Seventy-eight had prostate or bladder cancer. Group A n = 30, Group B n = 12, Group C n = 36. Median age = 79 [interquartile range (IQR) = 72–86]. Following PN insertion, 12-month mortality was significantly greater in Hospital 1 at 82%, versus 52% in Hospital 2 ( p = 0.015). Median survival: Group A: 177 days (IQR = 80–266), Group B: 209 days (IQR = 77–352), Group C: 145 days (IQR = 97–362). There was no significant difference in same-admission mortality, although group A had the greatest same-admission mortality at 17%. A total of 69% of all patients received bilateral nephrostomies. Patients with bilateral versus unilateral PN had no difference in mortality or nadir creatinine. Conclusion: Most patients with malignant obstruction secondary to prostate or bladder cancer lived less than 12 months after PN insertion. When offering PN, careful consideration of disease prognosis should be made, and frank discussion of the implications of a life-long nephrostomy with patients and relatives.
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Benghanem, Sarah, Lee S. Nguyen, Martine Gavaret, Jean-Paul Mira, Frédéric Pène, Julien Charpentier, Angela Marchi, and Alain Cariou. "SSEP N20 and P25 amplitudes predict poor and good neurologic outcomes after cardiac arrest." Annals of Intensive Care 12, no. 1 (March 15, 2022). http://dx.doi.org/10.1186/s13613-022-00999-6.
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Abstract Background To assess in comatose patients after cardiac arrest (CA) if amplitudes of two somatosensory evoked potentials (SSEP) responses, namely, N20-baseline (N20-b) and N20–P25, are predictive of neurological outcome. Methods Monocentric prospective study in a tertiary cardiac center between Nov 2019 and July-2021. All patients comatose at 72 h after CA with at least one SSEP recorded were included. The N20-b and N20–P25 amplitudes were automatically measured in microvolts (µV), along with other recommended prognostic markers (status myoclonus, neuron-specific enolase levels at 2 and 3 days, and EEG pattern). We assessed the predictive value of SSEP for neurologic outcome using the best Cerebral Performance Categories (CPC1 or 2 as good outcome) at 3 months (main endpoint) and 6 months (secondary endpoint). Specificity and sensitivity of different thresholds of SSEP amplitudes, alone or in combination with other prognostic markers, were calculated. Results Among 82 patients, a poor outcome (CPC 3–5) was observed in 78% of patients at 3 months. The median time to SSEP recording was 3(2–4) days after CA, with a pattern “bilaterally absent” in 19 patients, “unilaterally present” in 4, and “bilaterally present” in 59 patients. The median N20-b amplitudes were different between patients with poor and good outcomes, i.e., 0.93 [0–2.05]µV vs. 1.56 [1.24–2.75]µV, respectively (p < 0.0001), as the median N20–P25 amplitudes (0.57 [0–1.43]µV in poor outcome vs. 2.64 [1.39–3.80]µV in good outcome patients p < 0.0001). An N20-b > 2 µV predicted good outcome with a specificity of 73% and a moderate sensitivity of 39%, although an N20–P25 > 3.2 µV was 93% specific and only 30% sensitive. A low voltage N20-b < 0.88 µV and N20–P25 < 1 µV predicted poor outcome with a high specificity (sp = 94% and 93%, respectively) and a moderate sensitivity (se = 50% and 66%). Association of “bilaterally absent or low voltage SSEP” patterns increased the sensitivity significantly as compared to “bilaterally absent” SSEP alone (se = 58 vs. 30%, p = 0.002) for prediction of poor outcome. Conclusion In comatose patient after CA, both N20-b and N20–P25 amplitudes could predict both good and poor outcomes with high specificity but low to moderate sensitivity. Our results suggest that caution is needed regarding SSEP amplitudes in clinical routine, and that these indicators should be used in a multimodal approach for prognostication after cardiac arrest.
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Sinzinger, Helmut, Simona Marchesi, and Graziana Lupattelli. "Abstract 531: Is Earlier Hepatitis A Associated with Abnormal Hepatic Response to Statin Therapy?" Circulation 116, suppl_16 (October 16, 2007). http://dx.doi.org/10.1161/circ.116.suppl_16.ii_94.
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Hepatic enzyme elevation is low (< 3%) in large statin trials. Elevations are reversible after dose reduction or statin withdrawal. Very rare cases of hepatitis have been reported. No data are available how predisposing risk factors /diseases might influence hepatic statin response. Among the patients suffering from hepatic side effects during statin therapy 896 (477 m, 419 f; aged 31–76 years) admitted with (one or more) elevated hepatic enzyme, anamnestic data on hepatitis A, B, C, hepatic steatosis, alcohol abuse, hepatobiliary problems, abnormal enzymes (GOT, GPT, γGT) were assessed. The prevalence (% vs. % statin use in Austria) was for lovastatin n= 4; 0,2 (0,7), fluvastatin n = 111; 12,4 (14,0), simvastatin n = 297; 33,1 (34,8), pravastatin n = 82; 9,2 (11,8), rosuvastatin n = 69; 7,9 (1,5), atorvastatin n = 333; 37,2 (37,2). Only 41 patients (4,27%) had concomitant muscle complaints (21 cramps, 16 aches, 3 stiffness, 1 weakness), 12 (1,33%) CK elevation, 261 (29,13%) elevated isoprostane 8epiPGF 2α . Those with muscle complaints had normal CK levels and vice versa. Pretherapeutic findings (more than one possible) were hepatitis A 326 (36,4% !!), hepatitis B 7 (0,8%), hepatitis C 3 (0,3%), hepatic steatosis 141 (15,7%), alcohol abuse 104 (11,6%) and /or hepatobiliary problems 17 (1,9%). Abnormal enzymes GOT 116 (12,9%), GPT 113 (12,6%), γGT 147 (16,4%) persisted for < 1 week. Patients after hepatitis A had significantly (p < 0,001) higher transaminases as compared to the other patients. Withdrawal of the respective statin normalized transaminases within 4 weeks in 129 patients (14,4%), in only 7 elevation persisted for a longer period (up to 7 months). After 1 year all were in the normal range. Transaminase levels due to steatosis hepatis even sometimes showed improvement after statin therapy (mean: −12,7% GOT; −14,1 GPT; −16,0 γGT). Reexposure to another statin compound after a 4 weeks drug free interval caused recurrence of side effects in 87 patients (49 with earlier hepatitis A = 56,3%). Hepatitis A seems to represent a high risk for abnormal liver function response on statin therapy and reexposure to other compounds of this family. The combination of abnormal hepatic response with muscle complaints is very rare.
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Zagatina, A., D. Shmatov, G. Kim, Q. Ciampi, R. Citro, and E. Picano. "Stress echocardiography and outcomes after cardiac surgery in patients with ischemic mitral regurgitation." European Heart Journal 42, Supplement_1 (October 1, 2021). http://dx.doi.org/10.1093/eurheartj/ehab724.048.
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Abstract Background Ischaemic mitral regurgitation (IMR) is a frequent complication of coronary artery disease. This is generally associated with double mortality rates. Poor prognosis could be observed despite successful cardiac surgery. There is a gap about predictors of further negative outcomes after surgical treatment. Owing to the dynamic nature of IMR, we hypothesize that multiparametric stress echocardiography (SE) would be helpful in assessing risk stratification. Aim: To evaluate the relationship between multiparametric SE parameters and outcomes after cardiac surgery in patients with IMR. Methods We prospectively enrolled 30 patients (62.7±8.5 yrs, 18 men), who have severe IMR by ESC classification, referred for coronary artery bypass grafting (CABG) with or without mitral surgery. Before cardiac surgery, the patients performed semi-supine bicycle multiparametric SE. Wall motion abnormalities, systolic and diastolic volumes of left ventricle, B-lines (lung congestion feature), left atrium volume, pulmonary pressure, mitral regurgitation volume, and effective regurgitation orifice area (EROA) were assessed before and during exercise. Ejection fraction (EF) and left contractile reserve were calculated. All-cause death was an endpoint. Results All patients had indications for CABG due to severe three-vessel disease. Before exercising, EF was 42±12%, end-diastolic volume was 167±49 ml, systolic volume of left ventricle was 86±39 ml, left atrium was 103±37 ml, global longitudinal strain was 12±4%, index of wall motion abnormality was 1.83±0.48, EROA was 0.39±0.22 cm2, regurgitation volume was 58±27 ml, systolic pulmonary pressure was 43±16 mmHg, and B-lines were 2.4±2. During exercise, EF was 44±17%, end-diastolic volume was 148±54 ml, systolic volume of left ventricle was 98±44 ml, index of wall motion abnormality was 2.30±0.49, EROA was 0.45±0.2 cm2, regurgitation volume was 70±32 ml, systolic pulmonary pressure was 51±14 mmHg, and B-lines were 5.4±3.3. A median follow-up time was 332 days (224–335). ROC analysis demonstrated that left ventricle end-diastolic volume during exercise (the cut-off value 192 ml, area under the ROC curve 0.77, p<0.03), EROA during exercise (the cut-off value 0.37 cm2, the area 0.86, p<0.0003), regurgitant volume during stress (the cut-off value 82 ml, the area 0.79, p<0.02), the difference between stress and rest B-lines (the cut-off value 6 lines, the area 0.83, p<0.0001), the difference between stress and rest EROA (the cut-off value 0.15 cm2, the area 0.77, p=0.05) were associated with death. Conclusion The stress echocardiographic parameters were associated with increased mortality after cardiac surgery in patients with IMR over the 1-year follow-up. B-lines (objective evidence of severe congestive heart failure), EROA, regurgitation volume (severity of mitral regurgitation during exercise) were all associated with worse outcome. These preliminary results should be confirmed in the larger studies. Funding Acknowledgement Type of funding sources: None.
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Moore, Cecilia L., Anna Turkova, Hilda Mujuru, Adeodata Kekitiinwa, Abbas Lugemwa, Cissy M. Kityo, Linda N. Barlow-Mosha, et al. "ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing." BMC Infectious Diseases 21, no. 1 (January 4, 2021). http://dx.doi.org/10.1186/s12879-020-05672-6.
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Abstract Background Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children < 14 kg while dosing was in development. Methods ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children < 18 years starting first-line ART (ODYSSEY A) or switching to second-line ART (ODYSSEY B). The primary endpoint is clinical or virological failure by 96 weeks. Results Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ART-naïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9–18.0]. 82 (12%) children weighed 14 to < 20 kg, 135 (19%) 20 to < 25 kg, 206 (29%) 25 to < 35 kg, 284 (40%) ≥35 kg. 128 (18%) had WHO stage 3 and 60 (8%) WHO stage 4 disease. Challenges encountered include: (i) running the trial across high- to low-income countries with differing frequencies of standard-of-care viral load monitoring; (ii) evaluating pragmatic DTG dosing in PK sub-studies alongside FDA- and EMA-approved dosing and subsequently transitioning participants to new recommended doses; (iii) delays in dosing information for children weighing 3 to < 14 kg and rapid recruitment of ART-naïve older/heavier children, which led to capping recruitment of participants weighing ≥35 kg in ODYSSEY A and extending recruitment (above 700) to allow for ≥60 additional children weighing between 3 to < 14 kg with associated PK; (iv) a safety alert associated with DTG use during pregnancy, which required a review of the safety plan for adolescent girls. Conclusions By employing a basket design, to include ART-naïve and -experienced children, and nested PK sub-studies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children. Trial registration NCT, NCT02259127, registered 7th October 2014; EUDRACT, 2014–002632-14, registered 18th June 2014 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002632-14/ES); ISRCTN, ISRCTN91737921, registered 4th October 2014.
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Moustafa, Muhamad. "A Comprehensive Review of Monoclonal Antibodies for the Treatment of Follicular Lymphoma Including Both Approved and Investigational Options." Medical Research Archives 11, no. 11 (2023). http://dx.doi.org/10.18103/mra.v11i11.4745.
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Follicular lymphoma (FL) is the most common type of indolent lymphoma in the Western world, accounting for approximately 30% of lymphoma cases. FL is known for its recurrent nature, necessitating diverse treatment options. The introduction of rituximab, an anti-CD20 antibody, has greatly improved FL outcomes and paved the way for targeted therapies. In this review, we thoroughly explore the structure, mechanism of action, clinical outcomes, and side effects of currently approved monoclonal antibodies (mAb) for FL. Furthermore, we provide insights into ongoing clinical trials and emerging monoclonal antibodies that hold promise for the future of FL treatment. A comprehensive literature search was conducted using various medical databases, including ASH and ASCO publications, as well as PubMed. The clinicaltrials.gov website was used to compile a list of investigational monoclonal antibodies from ongoing clinical trials. The future of antibody-based therapy for follicular lymphoma shows great promise, with a focus on enhancing antibody efficacy, prioritizing optimized combination therapies to address treatment resistance, and evaluating bispecific antibodies as first-line therapies, all while carefully balancing risks and benefits and sequencing treatments appropriately for better disease management. These directions have the potential to establish antibodies as a central component of follicular lymphoma treatment. Article Details How to Cite MOUSTAFA, Muhamad Alhaj. A Comprehensive Review of Monoclonal Antibodies for the Treatment of Follicular Lymphoma Including Both Approved and Investigational Options. Medical Research Archives, [S.l.], v. 11, n. 11, nov. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4745>. Date accessed: 02 dec. 2023. doi: https://doi.org/10.18103/mra.v11i11.4745. 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D'Cruz, Glenn. "Darkly Dreaming (in) Authenticity: The Self/Persona Opposition in Dexter." M/C Journal 17, no. 3 (June 10, 2014). http://dx.doi.org/10.5204/mcj.804.
Full textAbstract:
This paper will use the popular television character, Dexter Morgan, to interrogate the relationship between self and persona, and unsettle the distinction between the two terms. This operation will enable me to raise a series of questions about the critical vocabulary and scholarly agenda of the nascent discipline of persona studies, which, I argue, needs to develop a critical genealogy of the term “persona.” This paper makes a modest contribution to such a project by drawing attention to some key questions regarding the discourse of authenticity in persona studies. For those not familiar with the show, Dexter portrays the life of a serial killer who only kills other serial killers. This is because Dexter, under the tutelage of his deceased father, develops a code that enables him to find a “socially useful” purpose for his homicidal impulses—by exclusively targeting other killers he rationalises his own deadly acts. Dexter necessarily leads a double life, which entails performing a series of normative social roles that conceal his true identity, and the murderous activities of his “dark passenger.” This apparent split between “true” self and “false” persona says a lot about popular conceptions of the performative nature of the self in contemporary culture, and provides a useful framework for unpacking some of the aporias generated by the concept of persona.My aim in the present context is to substantiate the argument that persona studies needs to engage with the philosophical discourse of “self” and “authenticity” if it is to provide a convincing account of the status and function of persona today. The term “persona” derives from the classical Latin word for mask, and has its roots in the theatre of ancient Greece. The Oxford English Dictionary defines the term thus:1. An Assumed character or role, especially one adopted by an author in his or her writing, or by a performer.2.a. as the aspect of a person’s character that is displayed to or perceived by others.b. Psychol. In Jungian psychology: the outer or assumed aspect of character; a set of attitudes adopted by an individual to fit his or her perceived social role. Contrasted with anima.For Jung the persona is “a complicated system of relations between individual consciousness and society, fittingly enough a kind of mask, designed on the one hand to make a definite impression upon others, and, on the other, to conceal the true nature of the individual” (305). We can see that all these usages share a theatrical or actorly dimension. Persona is something we adopt, display, or assume. Further, it is an external quality, which masks, presumably, that which is not assumed or displayed—the private self. Thus, persona is predicated on an opposition between inside and outside. Moreover, it is not a value neutral concept, but one, I will argue, that connotes a sense of “inauthenticity” through suggesting a division between self and role. The “self” is a complicated word with a wide range of usages and connotations. The OED notes that when used with reference to a person the word refers to an essential entity.3. Chiefly Philos. That which in a person is really and intrinsically he (in contradistinction to what is adventitious); the ego (often identified with the soul or mind as opposed to the body); a permanent subject of successive and varying states of consciousness.Of course both terms are further complicated by the way they function within specific specialised discourses. Jung’s use of the term “persona” is part of a complex psychological theory of personality, and the term “self” appears in a multitude of forms in a plethora of scholarly disciplines. The “self” is obviously a key concept in psychology and philosophy, where it is sometimes conflated with something called the subject, or discussed with reference to questions of personal identity. Michel Foucault’s project to track “the constitution of the subject across history which has led us up to the modern concept of the self” (202) is perhaps the most complex and rich body of work with which persona studies must reckon if it is to produce a distinctive account of the relationship between persona and self. In broad terms, this paper advocates a loosely Foucauldian approach to understanding the relationship between self and persona, but defers a detailed encounter with Foucault’s work on the subject (which requires a much larger canvas).For the moment I want to focus on the status of authenticity in the self/persona relationship with specific reference to world of Dexter, which provides an accessible forum for examining a contemporary manifestation of the self/persona relationship with specific reference to the question of authenticity. Dexter conveys the division between authentic inner self and persona through the use of a first person narrative voice that provides a running commentary on the character’s thoughts, and exposes the gap between Dexter’s various social roles and his real sociopathic self. Dexter Morgan is, of course, an unreliable narrator, yet he is acutely aware of how others perceive him, and his narrative voice-over functions as a device to bind the viewer to the character’s first-person perspective. This is important because Dexter is devoid of empathy—he lacks the ability to feel genuine emotion, and conform to the social conventions that govern everyday activities, yet he is focus of audience identification. This means the voice-over must perform the work of making Dexter sympathetic.The voice-over narration in Dexter is characterised by an obsession with the presentation of self, and the disparity between self and persona. In an early episode, Dexter’s narrative voice proclaims a love of Halloween because it is “the one time of year when everyone wears a mask—not just me. People think it's fun to pretend you're a monster. Me, I spend my life pretending I'm not. Brother, friend, boyfriend—all part of my costume collection” (Dexter “Let’s Give the Boy a Hand”).Dexter develops a series of social masks and routines to disguise his “real” self. He is compelled to develop a series of elaborate ruses to appear like a regular guy—a “normal” person who needs to perform a series of social roles. He thus becomes a studious observer of everyday life, and much of the show’s appeal lies in the way he dissects the minutiae of human behavior in order to learn how be normal. Indeed, because he does not comprehend emotion he must learn how to read the external signs that convey care, love, interest, concern and so on—“I just don't understand all that emotion, which makes it tough to fake,” he declares (Dexter, “Popping Cherry”). Each social role requires a considerable degree of actorly preparation, and Dexter demonstrates what we might call, with Erving Goffman, a dramaturgical approach to everyday life (2).For example, Dexter enters into a relationship with Rita, an ostensibly naïve, doe-eyed single mother of two children and a victim of domestic violence—he chooses her because he believes that she is as damaged as he is, and unlikely to challenge him too strongly—“Rita's ex-hubby, the crack addict, repeatedly raped her, knocked her around. Ever since then she's been completely uninterested in sex. That works for me!” (Dexter “Dexter”). Rita provides the perfect cover because she facilitates Dexter’s construction of himself as a normal, heterosexual family man. However, in order to play this most paradigmatic normative role, he must learn how to play with children, and feign affection and intimacy. J. M. Tyree observes that Dexter “employs a fake-it-till-you-make-it strategy for imitating normal life” (82). Of course, he cannot maintain the role too long before Rita becomes suspicious, and aware of Dexter’s repeated lies and evasions.In short, Dexter dramatises what Goffman calls impression management—the character of Dexter Morgan must consistently “give off” signs of normativity (80). Goffman argues that we are all compelled to perform social roles in the manner of Dexter, and this perhaps accounts for why the show appealed to such a wide audience. In many ways, Dexter exposes normative behavior as an “act” that nobody can sustain no matter how hard they try. Dexter’s struggle to decode the conventions that govern everyday life make him a sympathetic character despite his obviously sociopathic tendencies. In other words we are all a little bit like Dexter insofar we must all perform social roles we may not find comfortable. Of course, the whole question of impression management in Dexter becomes even more complex if one considers Michael C. Hall’s celebrity persona and his performance as the titular character, but I do not have the space to pursue this line of inquiry in the present context.So, Dexter is a consummate actor within his “everyday” world, and neatly, perhaps too neatly, confirms Goffman’s “dramaturgical” theory of the “self.” In his essay, “Letter to a Poor Actor” David E. R. George provides a fascinating critique of Goffman from the perspective of a theatre studies scholar. George provocatively claims that Goffman was attracted to theatrical metaphors because of the “anti-theatrical prejudice” embedded within the western tradition. George cites Jonash Barish’s authoritative tome on this topic, which argues “that with infrequent exceptions, terms borrowed from the theatre—theatrical, operatic, melodramatic, stagey, etc.—tend to be hostile or belittling” (1).Barish cites instances of this prejudice from Plato through to St Augustine and beyond, and George situates Goffman within this powerful tradition. He writes,the theatrum mundi metaphor has always been a recipe for paranoia, and in this respect Goffman appears merely to be continuing a long philosophical tradition: the actor-as-paranoiac puts on the maximum number of masks to protect a threatened and fragile self against the daily threat of intimacy, disrespect, deception. (353)It is hardly surprising, then, that Dexter, a paranoid sociopath, stands as an exemplary instance of Goffman’s dramaturgical conception of the self, for Dexter is a show that consistently presents narratives about the relationship between the need to protect the “fragile” self through the construction of various personae. George also argues, with Lyman and Scott, that a “dramatistic” approach to understanding the world produces a cynical perspective because drama is predicated on the split between appearance and reality, nothing is what it appears to be, and nobody is what they appear to be (7). The actor, traditionally, has always worn a mask in some form or another. From the literal masks worn by the actors in ancient Greece to the sophisticated make-up and prosthetic devices worn by today’s thespians, actors, even when they are supposedly playing themselves, expose the gap between self and persona. Arguably, the most challenging and provocative aspect of George’s theory of the actor for persona studies lies in his thesis about how the reviled art of the theatre, which has been pilloried for so many centuries, can function as a paradigm for authenticity. He cites Artaud and Grotowski as examples of two iconic figures that view the theatre as a sacred space that facilitates ‘close encounters of the authentic kind (George 361).George attempts to rescue an authentic core identity, which he perceives to be under siege from the likes of Goffman, who proffers an “onion” model of the self. In George’s reading, Goffman produces a self without an essential, authentic core. This is hardly surprising given Goffman’s background. As an advocate of symbolic interactionism, a school of sociology that proposes that the self is produced as a result of various acts of socialisation, Goffman’s dramaturgical account of the self reinforces George Herbert Mead’s belief that “when a self does appear it always involves an experience of another; there could not be an experience of the self simply by itself” (195).Dexter not only dramatises this self/other dynamic, but also underscores the extent to which we, to use the terminology of Benita Luckmann, inhabit a series of “small life-worlds.” In other words, we lead a series of part-time lives in part-time worlds—modern life, for Luckmann writing in 1970, unfolds on multiple stages that are not necessarily connected or operate according to the same regulatory principles. She writes,The multi-world existence of modern man requires frequent ‘gear-shifting.’ As he moves from one small world into the next, he is faced with at least marginally different expectations, requiring different role performances in concert with different sets of people. (590)Dexter must negotiate a variety of different social roles, each with different requirements and demands. He must, therefore, cultivate a professional persona as a blood-splatter analyst, and perform the personal roles of brother, lover, husband, and so on. Each of these roles occurs in a different “life world” and requires a different presentation of self. Luckmann’s analysis of modern life remains compelling despite being written more than 40 years ago, and she raises one of the most crucial questions for persona studies: what “self,” if any, functions as the executive “gear-shifter?” In Dexter, the narrative voice, the voice behind the masks implies such an essential entity—the true, authentic self, which is consistent with Jung’s account of the relationship between self and persona.Despite a welter of critical theory that debunks the possibility of an essential, self-identical, authentic self (from Adorno’s anti-Heideggerean argument in The Jargon of Authenticity to various post-structuralist theories of subjectivity, especially Judith Butler’s conception of performativity) the idea of sovereign self stubbornly persists in everyday discourse. One of the tasks of persona studies must be to examine these common notions of self and authenticity. On one level, most people experience the “self” as something that refers to what we might call a singular sense of being, and speak about when the feel “most like themselves.” For some, the self emerges within the private realm, the “backstage” areas to use Goffman’s terminology (3). Others speak of feeling most like themselves in executing a social role or some kind of professional occupation. For example, take this extract from a contemporary self-growth web site:Are you feeling like you don’t know who you are anymore? Or maybe you feel like you never really knew yourself. Perhaps you’ve gone through most of your life living by other people’s agendas or ideas of who you should be, and are just now realizing that you really don’t know yourself, your dreams, or your purpose. (Ewing 2013)From the Platonic exhortation to “know thyself” through to the advice dispensed by self-help gurus, the self emerges as a persistent, if elusive, trope in scholarly and everyday discourse. Persona studies needs to reckon with the scope and breadth of the deployment of the self. Indeed it is the very ubiquity of terms like self, authenticity, and persona that require genealogical analysis in the Foucauldian sense of the term. This task entails looking for and uncovering the conditions of possibility for talking about the self across a wide range of contexts.In summary, then, I contend that persona studies needs to carefully examine the relationship between various theories of self and the discourse of authenticity, and establish the extent to which Goffman’s apparently cynical account for the self challenges the assumed authenticity of the self in the Jungian paradigm. Of course, there are many other approaches one could take to this question. For example, Sartrean existentialism problematises any simple opposition between self and persona in its insistence that the self is the product of the others’ perceptions of the subject. This position is captured in his famous maxim that “hell is other people.” This is not because other people are inherently antagonistic or hostile, but that one’s sense of self is in the hands of others. Sartre dramatises this conundrum elegantly in his 1944 play, No Exit.Sartre’s philosophy also engages with the discourse of authenticity, which it borrows from Heidegger’s Being and Time. Existentialism, in its many guises, dominated continental philosophy up until the 1960s and popularised the idea of “authenticity” as an ideal, which enables one to avoid the tyranny of the “They” and avoid the pitfalls of living in bad faith. There is a possibility that the nascent discipline of Persona Studies, as articulated by P. David Marshall and others, risks ignoring the crucial relationship between the discourse of authenticity and the presentation of self by concentrating on the “presentational self” as a set of pragmatic, tactical techniques designed to maximise the impact of impression management within a variety of social and professional contexts (Marshall “Persona”; Barbour and Marshall “Academic”). A more detailed and direct engagement with Foucault’s account of the emergence and constitution of the modern subject, as well as with theories of performativity and authenticity that challenge the arguments and verities of Goffman, and Jung, can provide a richer account of how the concept of persona operates today with reference to, say, “the networked self” (Papacharissi; Barbour and Marshall).So, I would like to conclude by returning to Dexter and the question of authenticity. Dexter can never really manage to identify his authentic self—his “gear-changing” core.It’s there always, this Dark Passenger. And when he’s driving, I feel alive, half sick with the thrill of complete wrongness [...] lately there are these moments when I feel connected to something else... someone. It’s like the mask is slipping and things... people... who never mattered before are suddenly starting to matter. (Dexter, “An Inconvenient Lie”)In this speech, he paradoxically identifies his “dark passenger” as the driver (Luckmann’s “gear-changer”) but then feels “the mask” slipping. There is something beyond what he assumed to be his dark core—the innermost aspect of being that makes executive decisions. Moreover, the status of Dexter’s “dark passenger” is unclear in this speech—is he ‘”he self” or some external agent impelling Dexter to commit murder. Either way Dexter questions the motives and authenticity of this “dark passenger” and those of us with a stake in the nascent discipline of persona studies would do well to be equally skeptical about the status of our key terms.References Adorno, Theodor. The Jargon of Authenticity. Trans. Tarnowski, Knut and Will, Fredric. London and New York: Routledge, 2009.“An Inconvenient Lie.” Dexter. Season 2, Episode 3. DVD Showtime, 2007.Barbour K and Marshall P. D. “The Academic Online: Constructing Persona through the World Wide Web.” First Monday 17.9 (2012). 16 May 2014 http://firstmonday.org/ojs/index.php/fm/article/view/3969/3292.Barish, Jonas. The Anti-Theatrical Prejudice. University of California Press, 1981.Butler, Judith. Gender Trouble. London and New York: Routledge, 1990.“Dexter.” Dexter. Season 1, Episode 1. DVD Showtime, 2006.Ewing, Catherine. ‘Do You Feel Like a Stranger to Yourself?’ 17 April 2014 ‹ http://reawakenyourdreamer.com/2013/09/feel-like-stranger/ ›.Foucault, Michel. “About the Beginnings of the Hermeneutics of the Self: Two Lectures at Dartmouth.” Political Theory (1993): 198-227.George, David E.R. “Letter to a Poor Actor.” New Theatre Quarterly 2.8 (1986): 352-362.Goffman, Erving. The Presentation of Self in Everyday Life. New York: Doubleday, 1959.Heidegger, Martin. Being and Time. Trans. John Macquarie and Edward Robinson. London: Blackwell, 2006.Jung, Carl. Collected Works 7: Two Essays on Analytical Psychology. Princeton: Princeton University Press, 1972.“Let’s Give the Boy a Hand.” Dexter. Season 1, Episode 4. DVD Showtime, 2006.Luckmann, Benita. “The Small Life-Worlds of Modern Man.” Social Research 37.4 (1970): 580-596.Lyman, S. M., and Scott, M. B. The Drama of Social Reality. Oxford: Oxford University Presss, 1975.Marshall, P. David. “Persona Studies: Mapping the Proliferation of the Public Self.” Journalism 15 (2014): 153-170.Mead, George Herbert. Mind, Self and Society. Chicago: University of Chicago Press, 1934.Papacharissi, Zizi (ed.). A Networked Self: Identity, Community, and Culture on Social Network Sites. London and New York: Routledge, 2011.“persona, n.” OED Online. Oxford University Press, March 2014. 12 April 2014.“Popping Cherry.” Dexter. Season 1, Episode 3. DVD Showtime, 2006.Sartre, Jean-Paul. No Exit and Three Other Plays. Trans. Stuart Gilbert. New York: Vintage, 1989.“self, pron., adj., and n.” OED Online. Oxford University Press, March 2014. 13 April 2014.Tyree, J.M. “Spatter Pattern.” Film Quarterly 62.1 (2008): 82-85.
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Knopp-Schwyn, Collin, and Michael Fracentese. "Ayo, Bisexual Check." M/C Journal 26, no. 1 (March 14, 2023). http://dx.doi.org/10.5204/mcj.2967.
Full textAbstract:
Introduction A 2021 listicle pronouncing “10 Things That Are Bisexual Culture” concludes that “claiming that random things are ‘bi culture’ is the most bi-culture thing of all” (Wilber n.p.). While posed as tongue-in-cheek, the assignment of status as a signifier of bisexuality to seemingly arbitrary actions and items reinforces the notion that bi people seek a distinct visual and cultural identity and struggle to make one. We consider how creators on the algorithmically driven social media platform TikTok responded to an open-ended 2019 prompt (“ayo, bisexual check”) to show off styles and accessories that project a bisexual display, and how these videos, understood collectively, contribute to the cohesion of a prototype for a bisexual social uniform. By social uniform, we refer to informally standardised clothing that identifies members of a group but lacks the bureaucratic regulation of an institutional uniform (Joseph). This lens is productive for interpreting subcultural dress norms, including those of queer identities at various scopes (e.g. Nelson, “Here”; Stines). The development of these social uniforms can allow for stronger group coherence and provide individuals with “self-esteem through conformity” with one’s group and “self-regard by conflict” with other groups (Joseph 74). There is added utility to this signalling for queer people as a means to seek community and partnership against a societal backdrop of stigmatisation (Brennan). Being able to identify who is like oneself at a glance lets one know when and where one is safe to outwardly present an authentic version of oneself (Huxley and Hayfield; Rostosky et al.; Wang and Feinstein). Bisexual communities notably lack such a uniform (Hayfield, Bisexual; Hayfield, “Invisibility”; Hayfield, “Never”; Hayfield and Wood; Huxley et al.). While bi people have expressed interest in having a distinct, coherent aesthetic or set of visual markers to express their bisexuality and recognise others as specifically bisexual, they have encountered obstacles towards the establishment of such a bi uniform (Madison, “Representing”; Nelson, “What”). The conception of homosexuality and heterosexuality as a binary leaves little room for the notion of bisexuality at all (Nelson, “Here”). In instances when people do attempt to stake a claim to a specifically bisexual visual identity, the result tends to be read binaristically nonetheless (Daly et al.; Hartman; Hayfield, Bisexual; Morgan and Davis-Delano; Nelson, “What”). Attempts to visually “split the middle” of established gay and straight styles have thus historically failed, with onlookers (even bisexual onlookers) either assuming the bi person in question is gay or straight (Hartman). Rosie Nelson goes so far as to contend that “the body of the bisexual is incapable of declaring itself outwardly bisexual to a monosexist society” (“Here” 87). In other words, Nelson argues that a distinctly bi visual identity—a bi social uniform—may be impossible so long as bisexuality remains invisible in broader discourses of sexual orientation and that only improved or increased representations of bisexuality in media, law, research, and culture can foment the conditions for bisexual visibility in the most literal sense (“Here”). TikTok’s Bisexual Displays Within this context of binary assumptions of gender and sexual orientation, Julie Hartman-Linck conceived the “bisexual display” (Hartman 39). By analogy with gender display as theorised by Lorber and building on Goffman’s construction of identity performance, the bisexual display refers to attempts to project a bisexual identity “using the accoutrements of gender, as well as more direct visual and verbal cues” (Hartman 43). Bisexuality is discursively erased, and even seemingly straightforward attempts to make bi identities known are often misconstrued by observers, either through ignorance (e.g., unfamiliarity with the significance of the bi pride flag) or through willful disbelief (e.g., doubt in the authenticity of bisexuality / the bisexual; see Alarie and Gaudet). Therefore, analysis of bisexual display focusses on the intended effect of the performer rather than on the actual understandings of their audiences: bisexual display offers a productive theoretical lens through which to consider how a bisexual identity is intentionally fashioned, even if attempts to fashion the bisexual identity may be misunderstood or ignored. Emiel Maliepaard, in his research on bisexual geographies, argues that bisexual spaces are “temporal, local and (often) unplanned” (47). We identified one such space on TikTok, an algorithmically driven video-centric social media platform. TikTok affords creators a great deal of power to respond to and remix other creators’ content, most prominently with the “use this sound” function which lets creators incorporate audio either originating from or used in another video (colloquially a TikTok) into their own (Abidin and Kaye). The memetic process of (re)using a sound with some amount of variation generates a constituency of creators and other users whose participation in the video creation and engagement process aligns with what Zulli and Zulli theorised as TikTok’s imitation publics: “a collection of people whose digital connectivity is constituted through the shared ritual of content imitation and replication” (1882). These imitation publics in turn may spawn these temporal, local, and unplanned spaces, including virtual bisexual spaces. Here, we conducted a content analysis of 50 short videos posted in 2019 with over 1,000 likes using the “ayo, bisexual check” (“ABC”) sound, which was first uploaded in late March 2019. The originator of the sound posted a video of themselves saying “ayo, bisexual check” and then showing off certain elements of clothing and reifying or countering certain stereotypes about bi identity. When other creators subsequently began to use the sound and associated format to do the same, they constituted the “ABC” sound’s imitation public. While there are multiple possible ways creators might have understood the prompt of a “bisexual check” (e.g., as encouraging them to dress in a way that projects their own bisexuality; to dress in a way that projects bisexuality most legibly to other bisexual or nonbisexual people; to dress in a way that feels most comfortable to them, as a bisexual; etc.), the intention behind these videos can be understood broadly to display some bisexual identity. The simple and direct nature of the prompt (“bisexual check”) generates the virtual “bisexual space”, both “highly temporal and specific” (Maliepaard 59). This space both offers an open-ended venue for creators to engage with a culture of visual identity, and maximises the potential for audiences to read what transpires in the videos as demonstrative (if not constitutive) of bisexual identity. By creating these TikToks, users are not waiting for more or better bisexual representation on TikTok but instead are actively embodying it, responding to the need identified by Nelson. Elements of the Bisexual Check At the broadest level, creators in the 50 sampled videos primarily showcased discrete fashion elements or accessories, rather than entire outfits. The structure of “ABC” TikToks allowed creators to draw attention to specific pieces of clothing, jewelry, haircuts and styles, makeup looks, and ways of fashioning clothes (see fig. 1 for an example). This mode of engaging with the “bisexual check” challenge differs from the mode of engagement we saw in videos using the “ABC” sound posted after 2019; while onscreen text, closed captions, and video descriptions in TikToks posted in 2019 were primarily in English, text in videos posted in 2020 and later was mostly in Tagalog. This suggested that 2019 and post-2019 TikToks emerged from distinct and separate cultural contexts; despite using the same “ABC” sound, they represented different imitation publics. The post-2019 videos tended to show their creators posing for one or several shots without focussing on particular elements of their outfits, instead displaying their looks as a whole. The later videos offer a useful variation in memetic content and stance (Shifman), a contrast which permits us to understand the 2019 “ABC” videos as attempts to display bisexuality chiefly through discrete visual markers (e.g., fashion elements). Fig. 1: A screencap from the authors’ mocked-up “ABC” TikTok in which the creator uses a fingergun to showcase their cuffed jeans. Studies of bi people in the past two decades (almost all of which have been about bi women; see Clarke et al., though see Rogers for a recent exception) have identified several ways bi subjects attempt to make their bisexuality known in the face of overwhelming invisibility. Hayfield summarised research about bi women’s fashion, documenting styles that are “funky, flamboyant, or associated with alternative looks and looking (e.g., hippie, Goth, punk, and so on) including through piercings and tattoos” (“Invisibility” 180). Hartman-Linck recorded bi women using bumper stickers, pride flags and pride flag iconography, pins, and jewelry using the pink-purple-blue bi pride flag design, as well as a general playfulness with specific gendered markers (Hartman). Madison likewise found bi people using the bi pride flag design and colours on clothes and jewelry, as well as bi-specific iconography like the biangles (overlapping pink and blue triangles that generate a smaller purple triangle between them), interlocking Mars and Venus signs (⚤), and pun-based symbols like the “bisexuwhale” (“Representing” 151–3). More recently, the Internet has been a fruitful venue for discussions among bisexuals about a visual culture (Madison, “Bisexual”); discourse among bisexual people on social media sites like Twitter and Tumblr has generated some seemingly novel styles and fashions that have been highlighted as specifically bi looks. A 2017 tweet about jeans cuffed at the ankles (see fig. 1) and baggy shirts tucked in at the waist being “bisexual culture” has been mentioned in numerous popular news articles and blogs (e.g., Cao; Wilber). A Tumblr post from around the same time with images of three fictional characters sporting neck-length hairstyles cut straight at the bottoms appears to have been the genesis of the “bisexual bob”, a bob haircut worn by a bi person (usually a woman) that received similar coverage and discussion to the cuffed jeans and tucked-in shirts tweet (e.g., Locke; Vandervalk; Wilber). Other items identified in listicles as constituting “bi culture” include: being unable to sit in chairs “correctly”, dyed pink hair, puns, Converse brand shoes, plaid shirts, outer space, (excessive) use of the bi pride flag and colours, and anxiety disorders. Within our sample, we identified an uptake of these nascent bi fashions, with 62% of videos featuring clothing being cuffed (most frequently jeans), 36% of videos highlighting shirts tucked into pants, and 20% of videos demonstrating bi bobs. More explicit iconography like bi pride flags and colours (what Hartman-Linck referred to as “sign equipment” in her conceptualisation of bisexual display) appeared in 16% of videos, compared to more general rainbow iconography, which showed up in 20% of them (Hartman). Button-down shirts appeared in 34% of videos, and both floral print shirts and Converse shoes appeared in 18% of the total corpus. Nose piercings actively contributed to the “bisexual check” in 12% of sampled TikToks, while a full-body dress appeared in just one video (2%). We identified no instances of biangles, interlocking Mars and Venus signs, or punny sign equipment. Display Becoming Prototype, Prototype Becoming Uniform Interpreting “ABC” videos as bisexual displays on the individual level and conceptualising the community of “ABC” creators and engagers as an imitation public allows us to understand the process taking place as social identity work, “the construction of identities for groups of people” (Eschler and Menking 2). Eschler and Menking (drawing upon Donath as well as Schwalbe and Mason-Schrock) argued that for social identities (like bisexuality), certain memes can offer prototypes: “a set of minimal social cues that a person can use to infer other information about an individual’s social world” (9). Similarly, Joseph argued that for any complex of sartorial meaning, there is a minimal symbol: “the least symbol necessary to suggest a uniform” (24). By their nature, prototypes (or minimal symbols) will be limited to the fewest key elements required to demarcate a social identity. TikTok creators have the capacity to share their own “bisexual checks” with the “use this sound” feature or duet other creators’ videos to mirror or counter elements of the original creators’ checks in their own lives. Further, even if not posting their own “ABC” content, users have the ability to share, comment on, and like TikToks to engage with a creator’s bisexual display. Each new “ABC” video accomplishes what Rogers identified in his research on images of bi men on Instagram: they “add to a discourse and visual culture of bisexuality that both describes and prescribes the visual forms in which bisexuality appears” (366). Each contribution introduces a new, or more likely reifies an existing (if nascent) indicator of a bisexual identity. It is no surprise, then, that visual indicators that had already garnered some popular support within online bisexual spaces (bi bobs, cuffed jeans, tucked-in shirts) were among the most common in our sample. Still, a fashion choice having already entered the bisexual public consciousness does not solely explain why it recurred in our sample while other choices and items mentioned in listicles did not. The userbase of creators who tend to achieve virality on TikTok skews young, white, wealthy, and female (Boffone; Kennedy), so styles favoured by bi people who share at least some of these identities (e.g., white teen or twentysomething girls and women with personal or familial wealth) are likely to recur more frequently and receive increased engagement from the broader TikTok userbase, which also skews young and female (Cyca). Anecdotally, this demographic picture of TikTok mirrored our sample, suggesting that markers posited by creators and received by users were most likely to reflect the tastes and norms of young, white, and female creators. Indeed, one of the few nonwhite “ABC” creators was the only person in our sample to use the sound to argue against the core premise of the videos, contending that all one needed to be bisexual was attraction to people of multiple genders rather than any of the specific visual markers posed by others in the sample. While a universal “bisexual check” is suggested by the sparse wording of the challenge, the resulting videos nonetheless demonstrate a specific racially, temporally, and culturally positioned understanding of bi identity. Just because anyone has the capacity to contribute their own vision of the “bisexual check” does not mean that all “ABC” videos will land with equal frequency on users’ For You Page feeds (TikTok’s “homepage” where videos are algorithmically delivered to users; see Simpson and Semaan), nor enjoy the same volume of attention from TikTok’s userbase. Eschler and Menking consider the prototype to be “the least common denominator” (9), meaning that users will take the few most common elements shared amongst the “ABC” videos as symbols of a bisexual style. That the top “ABC” videos (those we sampled) heavily skew young, white, and female means that a bi uniform emerges from elements favoured by users sharing those demographics. Our mode of investigating this sound’s videos (moving systematically through all the videos using the “ABC” sound from most liked to less liked) does not contravene the affordances of TikTok’s platform but is somewhat outside of the app’s environment of expected use (Light et al.), which we understand to be either scrolling through the user’s For You Page or receiving and viewing TikToks messaged privately by friends. Still, users in these settings served two or more “ABC” videos are likely to consciously or unconsciously begin to identify the prototypical elements of a bisexual look as being those shared across multiple videos: the most frequently recurring markers creators choose to share as part of their bisexual displays reify existing styles already identified as “bi looks” or introduce new ones to the viewer. Through the continuous and repeated proposal of bisexual looks, the prototype emerges for a bisexual uniform. These accoutrements (cuffed sleeves and pantlegs, especially on jeans, bi bob haircuts, tucked-in shirts) point towards a bi uniform that is put-together and favours clothes like jeans and button-down shirts that are commonly worn across genders. That a bisexual uniform that may be comfortably worn by members of any gender follows logically from the necessity for a bi look that is both shaped by and liable to be worn by bisexuals, who may be of any gender. Further, this bi uniform emphasises alterations that may be undertaken on items commonly already held rather than distinct new pieces that must first be acquired. This may be one reason that creators favoured these styles, rather than more blatant sign equipment like pins or shirts with bi iconography on them: they were simply more likely to have jeans in their closet than a biangles T-shirt. The creators in our sample, regardless of the specific accoutrements displayed, answered Nelson’s call for increased and better bisexual representation, building one of many possible images for how bi people can fashion themselves (“Here”). The “ABC” imitation public’s collagic vision of a bisexual uniform may, in the future, be adapted, rejected, or serve as inspiration for others in the endlessly cyclical process of identity formation and reinforcement. Conclusion We have sought to understand what TikTok users have accomplished through the creation of and engagement with “ABC” videos, both specifically (i.e., what are the predominant visual indicators across the most popular videos) and generally (i.e., what processes are taking place and how they contribute towards the establishment of a bisexual social uniform). Creators are unlikely to have set out with a larger project of developing a bi uniform in mind when posting their 15-second “ayo, bisexual check” videos, but as part of one of TikTok’s innumerable imitation publics, their personal bisexual displays nonetheless offer prototypes for what a bisexual uniform could be. Any single “ABC” video is an example of a creator using TikTok’s affordances to respond individually to an open-ended prompt, but taken collectively, a consensus about the least common denominators for a bisexual uniform begins to emerge. Whether this online effort to cohere bisexual style results in bi people being able to identify one another (and/or be identified by nonbisexuals) remains to be seen, but we hope this article provides both a useful record of styles favoured by bisexuals on TikTok in 2019 and a productive explanation of the way individual posts in TikTok’s ecosystem of imitation publics may begin to constitute a social uniform for a community whose members have historically lacked one. Acknowledgments Thanks to Elizabeth Fetterolf, Amy Giacomucci, Trevor Harty, and the editors and reviewers for helpful comments on earlier drafts of this article. All online sources have been archived via Archive.org. References Abidin, Crystal, and D. Bondy Valdovinos Kaye. “Audio Memes, Earworms, and Templatability: The ‘Aural Turn’ of Memes on TikTok.” Critical Meme Reader: Global Mutations of the Viral Image. Eds. Chloë Arkenbout, Jack Wilson, and Daniel de Zeeuw. 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Duncan, Pansy Kathleen. "The Uses of Hate: On Hate as a Political Category." M/C Journal 20, no. 1 (March 15, 2017). http://dx.doi.org/10.5204/mcj.1194.
Full textAbstract:
I. First Brexit, then Trump: Has the past year or so ushered in a “wave” (Weisberg), a “barrage” (Desmond-Harris) or a “deluge” (Sidahmed) of that notoriously noxious affect, hate? It certainly feels that way to those of us identified with progressive social and political causes—those of us troubled, not just by Trump’s recent electoral victory, but by the far-right forces to which that victory has given voice. And yet the questions still hanging over efforts to quantify emotional or affective states leaves the claim that there has been a clear spike in hate moot (Ngai 26; Massumi 136-7; Ahmed, Promise 3-8). So let’s try asking a different question. Has this same period seen a rise, across liberal media platforms, in the rhetorical work of “hate-attribution”? Here, at least, an answer seems in readier reach. For no one given to scrolling distractedly through liberal Anglophone media outlets, from The New York Times, to The Guardian, to Slate, will be unfamiliar with a species of journalism that, in reporting the appalling activities associated with what has become known as the “alt-right” (Main; Wallace-Wells; Gourarie), articulates those activities in the rubric of a calculable uptick in hate itself.Before the U.S. Presidential election, this fledgling journalistic genre was already testing its wings, its first shudderings felt everywhere from Univision anchor Jorge Ramos’s widely publicized documentary, Hate Rising (2016), which explores the rise of white supremacist movements across the South-West U.S, to an edition of Slate’s Trumpcast entitled “The Alt-Right and a Deluge of Hate,” which broached the torment-by-Twitter of left-wing journalist David French. In the wake of the election, and the appalling acts of harassment and intimidation it seemed to authorize, the genre gained further momentum—leading to the New Yorker’s “Hate Is on the Rise After Trump’s Election,” to The Guardian’s “Trump’s Election led to Barrage of Hate,” and to Vox’s “The Wave of Post-Election Hate Reportedly Sweeping the Nation, Explained.” And it still has traction today, judging not just by James King’s recent year-in-review column, “The Year in Hate: From Donald Trump to the Rise of the Alt-Right,” but by Salon’s “A Short History of Hate” which tracks the alt-right’s meteoric 2016 rise to prominence, and the New York Times’ recently launched hate-speech aggregator, “This Week in Hate.”As should already be clear from these brisk, thumbnail accounts of the texts in question, the phenomena alluded to by the titular term “hate” are not instances of hate per se, but rather instances of “hate-speech.” The word “hate,” in other words, is being deployed here not literally, to refer to an emotional state, but metonymically, as a shorthand for “hate-speech”—a by-now widely conventionalized and legally codified parlance originating with the U.N. Declaration to describe “violent or violence-inciting speech or acts that “aim or intend to inflict injury, or incite prejudice or hatred, against persons of groups” because of their ethnic, religious, sexual or social affiliation. And there is no doubt that, beyond the headlines, these articles do incredibly important work, drawing connections between, and drawing attention to, a host of harmful activities associated with the so-called “alt-right”—from a pair of mangled, pretzel-shaped swastikas graffiti-ed in a children’s playground, to acts of harassment, intimidation and violence against women, African-Americans, Latinos, Muslims, Jews, and LGBTQ people, to Trump’s own racist, xenophobic and misogynistic tweets. Yet the fact that an emotion-term like hate is being mobilized across these texts as a metonym for the “alt-right” is no oratorical curio. Rather, it perpetuates a pervasive way of thinking about the relationship between the alt-right (a political phenomenon) and hate (an emotional phenomenon) that should give pause to those of us committed to mining that vein of cultural symptomatology now consigned, across the social sciences and critical humanities, to affect theory. Specifically, these headlines inscribe, in miniature, a kind of micro-assessment, a micro-geography and micro-theory of hate. First, they suggest that, even prior to its incarnation in specific, and dangerous, forms of speech or action, hate is in and of itself anathema, a phenomenon so unquestioningly dangerous that a putative “rise” or “spike” in its net presence provides ample pretext for a news headline. Second, they propose that hate may be localized to a particular social or political group—a group subsisting, unsurprisingly, on that peculiarly contested frontier between the ideological alt-right and the American Midwest. And third, they imply that hate is so indubitably the single most significant source of the xenophobic, racist and sexist activities they go on to describe that it may be casually used as these activities’ lexical proxy. What is crystallizing here, I suggest, is what scholars of rhetoric dub a rhetorical “constellation” (Campbell and Jamieson 332)—a constellation from which hate emerges as, a) inherently problematic, b) localizable to the “alt-right,” and, c) the primary engine of the various activities and expressions we associate with them. This constellation of conventions for thinking about hate and its relationship to the activities of right-wing extremist movement has coalesced into a “genre” we might dub the genre of “hate-attribution.” Yet while it’s far from clear that the genre is an effective one in a political landscape that’s fast becoming a political battleground, it hasn’t appeared by chance. Treating “hate,” then, less as a descriptive “grid of analysis” (Sedgwick 152), than as a rhetorical projectile, this essay opens by interrogating the “hate-attribution” genre’s logic and querying its efficacy. Having done so, it approaches the concept of “alternatives” by asking: how might calling time on the genre help us think differently about both hate itself and about the forces catalyzing, and catalyzed by, Trump’s presidential campaign? II.The rhetorical power of the genre of hate-attribution, of course, isn’t too difficult to pin down. An emotion so thoroughly discredited that its assignment is now in and of itself a term of abuse (see, for example, the O.E.D’s freshly-expanded definition of the noun “hater”), hate is an emotion the Judeo-Christian tradition deems not just responsible for but practically akin to murder (John 3:1). In part as a result of this tradition, hate has proven thoroughly resistant to efforts to elevate it from the status of an expression of a subject’s pestiferous inner life to the status of a polemical response to an object in the world. Indeed, while a great deal of the critical energy amassing under the rubric of “affect theory” has recently been put into recuperating the strategic or diagnostic value of emotions long scorned as irrelevant to oppositional struggle—from irritation and envy, to depression, anger and shame (Ngai; Cvetkovich; Gould; Love)—hate has notably not been among them. In fact, those rare scholarly accounts of affect that do address “hate,” notably Ahmed’s excellent work on right-wing extremist groups in the United Kingdom, display an understandable reluctance to rehabilitate it for progressive thought (Cultural Politics). It should come as no surprise, then, that the genre of “hate-attribution” has a rare rhetorical power. In identifying “hate” as the source of a particular position, gesture or speech-act, we effectively drain said position, gesture or speech-act of political agency or representational power—reducing it from an at-least-potentially polemical action in or response to the world, to the histrionic expression of a reprehensible personhood. Yet because hate’s near-taboo status holds across the ideological and political spectrum, what is less clear is why the genre of hate-attribution has achieved such cachet in the liberal media in particular. The answer, I would argue, lies in the fact that the work of hate-attribution dovetails all too neatly with liberal political theory’s longstanding tendency to laminate its social and civic ideals to affective ideals like “love,” “sympathy,” “compassion,” and, when in a less demonstrative humor, “tolerance”. As Martha Nussbaum’s Political Emotions has recently shown, this tradition has an impressive philosophical pedigree, running from Aristotle’s philia (16), John Locke’s “toleration” and David Hume’s “sympathy” (69-75), to the twentieth century’s Universal Declaration of Human Rights, with its promotion of “tolerance and friendship among all nations, racial or religious groups.” And while the labour of what Lauren Berlant calls “liberal sentimentality” (“Poor Eliza”, 636) has never quite died away, it does seem to have found new strength with the emergence of the “intimate public sphere” (Berlant, Queen)—from its recent popular apotheosis in the Clinton campaign’s notorious “Love Trumps Hate” (a slogan in which “love,” unfortunately, came to look a lot like resigned technocratic quietism in the face of ongoing economic and environmental crisis [Zizek]), to its revival as a philosophical project among progressive scholars, many of them under the sway of the so-called “affective turn” (Nussbaum; Hardt; Sandoval; hooks). No surprise, then, that liberalism’s struggle to yoke itself to “love” should have as its eerie double a struggle to locate among its ideological and political enemies an increasingly reified “hate”. And while the examples of this project we’ve touched on so far have hailed from popular media, this set of protocols for thinking about hate and its relationship to the activities of right-wing extremist movements is not unique to media circles. It’s there in political discourse, as in ex-DNC chair Debbie Wasserman Schultz’s announcement, on MSNBC, that “Americans will unite against [Trump’s] hatred.” And it’s there, too, in academic media studies, from FLOW journal’s November 2016 call for papers inviting respondents to comment, among other things, on “the violence and hatred epitomized by Trump and his supporters,” to the SCMS conference’s invitation to members to participate in a pop-up panel entitled “Responding to Hate, Disenfranchisement and the Loss of the Commons.” Yet while the labor of hate-attribution to which many progressive forces have become attached carries an indisputable rhetorical force, it also has some profound rhetorical flaws. The very same stigma, after all, that makes “hate” such a powerful explanatory grenade to throw also makes it an incredibly tough one to land. As Ahmed’s analysis of the online rhetoric of white supremacist organizations should remind us (Cultural Politics), most groups structured around inciting and promoting violence against women and minorities identify, perversely, not as hate groups, but as movements propelled by the love of race and nation. And while left-wing pundits pronounce “hate” the signature emotion of a racist, misogynist Trump-voting right, supporters of Trump ascribe it, just as routinely, to the so-called “liberal elite,” a group whose mythical avatars—from the so-called “Social Justice Warrior” or “SJW,” to the supercilious Washington politico—are said to brand “ordinary [white, male] Americans” indiscriminately as racist, misogynistic, homophobic buffoons. Thus, for example, The Washington Post’s uncanny, far-right journalistic alter-ego, The Washington Times, dubs the SPLC a “liberal hate group”; the Wikipedia mirror-site, Conservapedia, recasts liberal objections to gun violence as “liberal hate speech” driven by an “irrational aversion to weapons”; while one blood-curdling sub-genre of reportage on Steve Bannon’s crypto-fascist soapbox, Breitbart News, is devoted to denouncing what it calls “ ‘anti-White Racism.’” It’s easy enough, of course, to defend the hate-attribution genre’s liberal incarnations while dismissing its right-wing variants as cynical, opportunistic shams, as Ahmed does (Cultural Politics)—thereby re-establishing the wellspring of hate where we are most comfortable locating it: among our political others. Yet to do so seems, in some sense, to perpetuate a familiar volley of hate-attribution. And to the extent that, as many media scholars have shown (Philips; Reed; Tett; Turow), our digital, networked political landscape is in danger of being reduced to a silo-ed discursive battleground, the ritual exchange of terminological grenades that everyone seems eager to propel across ideological lines, but that no one, understandably, seems willing to pick up, seems counter-productive to say the least.Even beyond the genre’s ultimate ineffectiveness, what should strike anyone used to reflecting on affect is how little justice it does to the ubiquity and intricacy of “hate” as an affective phenomenon. Hate is not and cannot be the exclusive property or preserve of one side of the political spectrum. One doesn’t have to stretch one’s critical faculties too far to see the extent to which the genre of hate-attribution participates in the emotional ballistics it condemns or seeks to redress. While trafficking in a relatively simple hate-paradigm (as a subjective emotional state that may be isolated to a particular person or group), the genre itself incarnates a more complex, socially dynamic model of hate in which the emotion operates through logics of projection perhaps best outlined by Freud. In the “hate-attribution” genre, that is, hate—like those equally abjected categories “sentimentality,” “worldliness” or “knowingness” broached by Sedgwick in her bravura analyses of “scapegoating attribution” (150-158)—finds its clearest expression in and through the labor of its own adscription. And it should come as no surprise that an emotion so widely devalued, where it is not openly prohibited, might also find expression in less overt form.Yet to say as much is by no means to discredit the genre. As legal scholar Jeremy Waldron has recently pointed out, there’s no particular reason why “the passions and emotions that lie behind a particular speech act” (34)—even up to and including hate—should devalue the speech acts they rouse. On the contrary, to pin the despicable and damaging activities of the so-called “alt right” on “hate” is, if anything, to do an injustice to a rich and complex emotion that can be as generative as it can be destructive. As Freud suggests in “Group Psychology and the Analysis of the Ego,” for example, hate may be the very seed of love, since the forms of “social feeling” (121) celebrated under the liberal rubric of “tolerance,” “love,” and “compassion,” are grounded in “the reversal of what was first a hostile feeling into a positively-toned tie in the nature of an identification” (121; italics mine). Indeed, Freud projects this same argument across a larger, historical canvas in Civilization and its Discontents, which contends that it is in our very struggle to combat our “aggressive instincts” that human communities have developed “methods intended to incite people into identifications and aim-inhibited relationships of love” (31). For Freud, that is, the practice of love is a function of ongoing efforts to see hate harnessed, commuted and transformed. III.What might it mean, then, to call time on this round of hate-attribution? What sort of “alternatives” might emerge when we abandon the assumption that political engagement entails a “struggle over who has the right to declare themselves as acting out of love” (Ahmed, Cultural Politics 131), and thus, by that same token, a struggle over the exact location and source of hate? One boon, I suggest, is the license it gives those of us on the progressive left to simply own our own hate. There’s little doubt that reframing the dangerous and destructive forms of speech fomented by Trump’s campaign, not as eruptions of hate, or even as “hate-speech,” but as speech we hate would be more consistent with what once seemed affect theory’s first commandment: to take our own affective temperature before launching headlong into critical analysis. After all, when Lauren Berlant (“Trump”) takes a stab at economist Paul Krugman’s cautions against “the Danger of Political Emotions” with the timely reminder that “all the messages are emotional,” the “messages” she’s pointing to aren’t just those of our political others, they’re ours; and the “emotions” she’s pointing to aren’t just the evacuated, insouciant versions of love championed by the Clinton campaign, they’re of the messier, or as Ngai might put it, “uglier” (2) variety—from shame, depression and anger, to, yes, I want to insist, hate.By way of jump-starting this program of hate-avowal, then, let me just say it: this essay was animated, in part, by a certain kind of hate. The social critic in me hates the breathtaking simplification of the complex social, economic and emotional forces animating Trump voters that seem to actuate some liberal commentary; the psychologist in me hates the self-mystification palpable in the left’s insistence on projecting and thus disowning its own (often very well justified) aggressions; and the human being in me, hating the kind of toxic speech to which Trump’s campaign has given rise, wishes to be able to openly declare that hatred. Among its other effects, hate is characterized by hypervigilance for lapses or failings in an object it deems problematic, a hypervigilance that—sometimes—animates analysis (Zeki and Romoya). In this sense, “hate” seems entitled to a comfortable place in the ranks of what Nick Salvato has recently dubbed criticism’s creative “obstructions”—phenomena that, while “routinely identified as detriments” to critical inquiry, may also “form the basis for … critical thinking” (1).Yet while one boon associated with this disclosure might be a welcome intellectual honesty, a more significant boon, I’d argue, is what getting this disclosure out of the way might leave room for. Opting out of the game of hurling “hate” back and forth across a super-charged political arena, that is, we might devote our column inches and Facebook posts to the less sensational but more productive task of systematically challenging the specious claims, and documenting the damaging effects, of a species of utterance (Butler; Matsuda; Waldron) we’ve grown used to simply descrying as pure, distilled “hate”. And we also might do something else. Relieved of the confident conviction that we can track “Trumpism” to a spontaneous outbreak of a single, localizable emotion, we might be able to offer a fuller account of the economic, social, political and affective forces that energize it. Certainly, hate plays a part here—although the process by which, as Isabelle Stengers puts it, affect “make[s] present, vivid and mattering … a worldly world” (371) demands that we scrutinize that hate as a syndrome, rather than simply moralize it as a sin, addressing its mainsprings in a moment marked by the nerve-fraying and life-fraying effects of what has become known across the social sciences and critical humanities as conditions of social and economic “precarity” (Muehlebach; Neil and Rossiter; Stewart).But perhaps hate’s not the only emotion tucked away under the hood. Here’s something affect theory knows today: affect moves not, as more traditional theorists of political emotion have it, “unambiguously and predictably from one’s cognitive processing,” but in ways that are messy, muddled and indirect (Gould 24). That form of speech is speech we hate. But it may not be “hate speech.” That crime is a crime we hate. But it may not be a “hate-crime.” One of the critical tactics we might crib from Berlant’s work in Cruel Optimism is that of decoding and decrypting, in even the most hateful acts, an instance of what Berlant, herself optimistically, calls “optimism.” For Berlant, after all, optimism is very often cruel, attaching itself, as it seems to have done in 2016, to scenes, objects and people that, while ultimately destined to “imped[e] the aim that brought [it to them] initially,” nevertheless came to seem, to a good portion of the electorate, the only available exponent of that classic good-life genre, “the change that’s gonna come” (“Trump” 1-2) at a moment when the Democratic party’s primary campaign promise was more of the free-market same. 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