Journal articles on the topic 'Art. 52 c. 3 c.p'
To see the other types of publications on this topic, follow the link: Art. 52 c. 3 c.p.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Art. 52 c. 3 c.p.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Farias, Miguel Angel, Silvia Andrea Medici, Aldo Fabián Squassi, and Gabriel Antonio Sánchez. "Unmet dental treatment need impairs quality of life in Hepatitis C Virus-infected patients." STOMATOLOGY EDU JOURNAL 7, no. 3 (2020): 191–96. http://dx.doi.org/10.25241/stomaeduj.2020.7(3).art.5.
Full textAbstract:
Introduction The hepatitis C virus (HCV) infection is a health condition affecting 3% of the world population, which oral manifestations and associated factors interest both physicians and dentists. The aim of this work was to describe the dental treatment need and the impact of the perception of the oral component of health on the quality of life in HCV+ patients. Methodology Descriptive study on a convenience sample. 45 HCV+ patients (46±5 y.o.) completed the OHIP-14 questionnaire, which consists of 14 questions grouped in 7 domains (D1 functional limitation, D2 physical pain, D3 psychological discomfort, D4 physical disability, D5 psychological disability, D6 social disability and D7 general disability). The participants indicated their responses using a Likert-type frequency scale. The Community Caries Index of Treatment Need (CCITN) was determined for each patient. The proportion and CI95% of the social impact on the quality of life were calculated. The association between CCITN and the quality of life was assessed by Chi2 (p<0.05). Results The CCITN was 11 (8-14). The overall social impact was 38% (24-52%). The increasing order relationship of the impact on each of the domains was D1, D7, D6, D4, D5, D2, D3. A significant association between oral health-related quality of life and CCITN was observed (Chi2 = 7.57, p = 0.006), showing greater impairment of the quality of life as the treatment need increased. Conclusion The association between CCITN and quality of life becomes evident using OHIP-14 during dental appointments. The results suggest the need for comprehensive interventions during the provision of oral health care to HCV+ patients.
2
Yuen, Man-Fung, Danny Ka-Ho Wong, Erwin Sablon, He-Jun Yuan, Siu-Man Sum, Chee-Kin Hui, Annie On-On Chan, Benjamin Chun-Yu Wong, and Ching-Lung Lai. "Hepatitis B Virus Genotypes B and C Do Not Affect the Antiviral Response to Lamivudine." Antiviral Therapy 8, no. 6 (August 1, 2002): 531–34. http://dx.doi.org/10.1177/135965350300800610.
Full textAbstract:
To date, there have been no studies examining the role of hepatitis B virus (HBV) genotypes on the response to lamivudine therapy and the development of YMDD mutations. The present study aimed at determining any differences in the antiviral response and risk of YMDD mutations between lamivudine-treated patients with HBV genotype B and genotype C. Eighty-two patients receiving lamivudine were recruited. HBV genotypes at baseline and YMDD mutations at week 52 were determined by line probe assays (LiPA). HBV DNA levels were determined by the Cobas Amplicor HBV Monitor Test. Seventeen (20.7%) and sixty-four (78%) patients had single genotypes of B and C, respectively. At both week 24 and 52 there were no differences in the median reduction of HBV DNA levels (median 4 logs drop), the median reduction of alanine aminotransferase (ALT) levels, and the proportion with normalization of ALT [8/8 (100%) vs 26/37 (70.3%), P=0.19] between patients with genotypes B and C. The rate of HBeAg seroconversion [3/17 (17.6%) vs 6/64 (9.4%), P=0.39] and the chance of YMDD mutation development [3/17 (17.6%) vs 12/64 (18.8%), P=1.0] at week 52 were also similar between patients with genotype B and C, respectively. In conclusion, there was no difference in the antiviral response and the rate of development of YMDD mutations in Chinese patients with genotype B and C after 1 year of lamivudine. Determination of HBV genotypes before lamivudine therapy was probably not an important pre-treatment investigation to predict antiviral responses in Chinese patients.
3
Karzai, Fatima H., Bamidele Adesunloye, Yangmin M. Ning, Ravi Amrit Madan, James L. Gulley, Andrea Borghese Apolo, Melony A. Beatson, et al. "Use of supportive measures to improve outcome and decrease toxicity in docetaxel-based antiangiogenesis combinations." Journal of Clinical Oncology 31, no. 6_suppl (February 20, 2013): 128. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.128.
Full textAbstract:
128 Background: We have recently completed accrual of 63 patients (pts) to our study combining lenalidomide (L), with bevacizumab (B), docetaxel (D), and prednisone (P) (ART-P). Due to the lack of improved survival and the increased toxicity of anti-angiogenic docetaxel combinations in the MAINSAIL and CALGB 90410 trials we attempted to contrast and compare our studies with the failed phase III trials. Methods: Among the first 52 pts on the ART-P, 3 received L 15 mg daily, 3 had 20 mg daily, and the rest had 25 mg daily for 14 days of every 21−day cycle (C). We later enrolled 11 more pts at L 15 mg. All pts received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and enoxaparin daily throughout each C. Pegfilgrastim was given on day 2. Patients on CALGB 90410 received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and on MAINSAIL received D 75 mg/m2, L 25 mg daily for 14 days of every 21−day cycle with daily P. Patients on CALGB 90410 and MAINSAIL did not receive enoxaparin or pegfilgrastim prophylactically. Results: Median number of Cs in ART-P was 16 (3−38). PFS was 22 months and median OS has not been reached. Pts with measurable disease had 1 CR and 25 PR (86.7% RR). Two patients (3%) had deep vein thromboses. Of 1,219 cycles given, 14 cycles were complicated by febrile neutropenia (FN) (1.1%). There were no treatment related deaths. In comparison, median number of Cs in MAINSAIL L+DP arm was 6, with a PFS of 45 weeks and an OS of 77 weeks. Thirty-four pts (6.5%) developed pulmonary emboli and there were 2 deaths due to toxicity in the experimental arm. Nearly 12% of Cs were complicated by FN. In the experimental arm of CALGB 90410 trial, median OS was 22.6 months with median PFS of 9.9 months. Median number of Cs was 8, and 19 pts developed thromboses/emboli (3.6%). In addition, 7% of patients developed FN and treatment related deaths were reported at 4%. Conclusions: The use of supportive care allows the ART-P combination to be given for more cycles than were given in MAINSAIL and CALGB 90401 potentiating a longer PFS, RR and possibly OS with an improved toxicity profile. This data demonstrates the potential importance of supportive measures and is hypothesis generating for future combination studies. Clinical trial information: NCT00942578.
4
Karzai, Fatima H., Ravi Amrit Madan, Andrea Borghese Apolo, Yangmin M. Ning, Howard L. Parnes, Philip M. Arlen, Melony A. Beatson, et al. "Use of supportive measures to improve outcome and decrease toxicity in docetaxel-based antiangiogenesis combinations in metastatic castrate resistant prostate cancer (mCRPC)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e16017-e16017. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e16017.
Full textAbstract:
e16017 Background: We have completed accrual of 63 patients (pts) to our study combining lenalidomide (L), with bevacizumab (B), docetaxel (D), and prednisone (P) (ART-P) in mCRPC. Due to the lack of improved survival and the increased toxicity of anti-angiogenic docetaxel combinations in the MAINSAIL and CALGB 90401 trials, we attempted to compare and contrast our studies with these failed phase III trials. Methods: Among the first 52 pts on ART-P, 3 received L 15 mg daily, 3 received 20 mg daily, and the others received 25 mg daily for 14 days of every 21−day cycle (C). We then enrolled 11 pts at L 15 mg. All pts received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and enoxaparin daily. Pegfilgrastim was given on day 2. Patients on CALGB 90401 received D 75 mg/m2 and B 15 mg/kg on day 1, with P 10 mg. On MAINSAIL, pts received D 75 mg/m2, L 25 mg daily for 14 days of every 21−day cycle with daily P. Patients on CALGB 90401 and MAINSAIL did not receive enoxaparin or pegfilgrastim prophylactically. Results: The median number of Cs on ART-P is 18 (1-52). Median PFS is 19.1 months. Twenty-seven pts had a PR, and one pt with measurable disease had a CR. Two patients (3%) had deep vein thromboses. Of 1,334 Cs given, 14 cycles were complicated by febrile neutropenia (FN) (1%). There were no treatment related deaths. In comparison, median number of Cs in MAINSAIL L+DP arm was 6, with a PFS of 45 weeks and an OS of 77 weeks. Thirty-four pts (6.5%) developed pulmonary emboli and there were 2 deaths due to toxicity in the experimental arm. Nearly 12% of Cs were complicated by FN. In the experimental arm of CALGB 90401 trial, median OS was 22.6 months with median PFS of 9.9 months. The median number of Cs were 8 and 19 pts developed thrombosis/emboli (3.6%). In addition, 37 patients developed FN and treatment related deaths were reported at 4%. Conclusions: The use of supportive care allowed longer treatment duration with the ART-P combination as compared to D+L (MAINSAIL) and D+B (CALGB 90401), potentiating a longer PFS, RR and possibly OS with an improved safety profile. This data demonstrates the potential importance of supportive measures and is hypothesis generating for future combination studies. Clinical trial information: NCT00942578.
5
Yastrebova, E. B., O. E. Chernova, A. M. Kalyshenko, and G. A. Vertogradova. "Chronic hepatitis C in children with HIV infection: disease phenotype and efficacy of antiviral therapy." Infekcionnye bolezni 19, no. 2 (2021): 52–58. http://dx.doi.org/10.20953/1729-9225-2021-2-52-58.
Full textAbstract:
Objective. To analyze the course of chronic hepatitis C (CHC) and efficacy of its treatment in children with HIV infection. Patients and methods. This study included 29 children aged 12 to 17 years (mean age 15.1 ± 0.2 years) with perinatal HIV infection and CHC. HIV stages were distributed as follows: stage 4A in 24 individuals (82.8%), stage 4B in 4 individuals (13.8%), and stage 4B in 1 individual (3.4%). All 29 patients received antiretroviral therapy. The distribution of children by HCV genotypes was as follows: 1a in one child (3.4%), 1b in 12 children (41.4%), and 3a in 16 children (55.2%). Antiviral therapy for CHC included glecaprevir/pibrentasvir (3 tablets; 100 mg + 40 mg) once a day for 56 days. Data analysis was performed using the Statistica for Windows software (version 10.0). Results. The mean HCV RNA level was 595,666 ± 34,734 IU/mL (range: 1,100–3,863,025 IU/mL). After 4, 8, or 12 weeks of antiviral therapy for HCV, HCV RNA clearance was achieved in all study participants (p = 0.01). Before treatment initiation, mean CD4+ count was 738 ± 34 cells/μL (above 500 cells/μL), which indicated the absence of immunodeficiency in the group analyzed. Successful antiviral therapy for HCV (sustained virologic response at week 12; SVR 12) also resulted in increase of the CD4+ lymphocytes level, which was considered as a positive effect of glecaprevir/pibrentasvir (p = 0.15). We observed significant differences in the level of liver enzymes (ALT and AST) (p = 0.01) between samples collected before antiviral therapy initiation and those collected during treatment, as well as 12 weeks after its completion (SVR12). All children demonstrated good tolerance of glecaprevir/pibrentasvir; none of them had adverse events, complaints, or clinical/laboratory changes. Conclusion. Thus, all children with HIV infection and CHC achieved SVR12 after the 8-week course of antiviral therapy with glecaprevir/pibrentasvir regardless of HCV genotype. Clinical manifestations (hepatosplenomegaly in 62.1%; asthenovegetative syndrome in 31.0%) were eliminated after 8 weeks of therapy. Laboratory manifestations (hepatic cytolysis (AST/ALT)) were normalized after 4 weeks of therapy. Antiviral treatment for HCV resulted in some increase in the level of CD4+ lymphocytes. We observed no adverse events caused by glecaprevir/pibrentasvir (neither clinical symptoms nor changes in complete blood count or liver function tests), which confirms the safety of this treatment regimen. Key words: antiretroviral therapy, HIV infection, children, direct-acting antivirals, chronic hepatitis C
6
Vaubourdolle, M., O. Chazouillères, I. Briaud, C. Legendre, L. Serfaty, R. Poupon, and J. Giboudeau. "Plasma alpha-glutathione S-transferase assessed as a marker of liver damage in patients with chronic hepatitis C." Clinical Chemistry 41, no. 12 (December 1, 1995): 1716–19. http://dx.doi.org/10.1093/clinchem/41.12.1716.
Full textAbstract:
Abstract alpha-Glutathione S-transferase (alpha-GST; EC 2.5.1.18) has been advocated as a better marker of hepatocellular damage than the transaminases in toxic and autoimmune hepatitis. We have assessed the potential interest of plasma alpha-GST determination in 94 anti-hepatitis C virus-positive patients with histologically proven chronic hepatitis C (34 women, 60 men, ages 40.0 +/- 11.9 years). Blood samples were assayed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase, alkaline phosphatase, and alpha-GST on the same day a liver biopsy was performed. alpha-GST concentrations were significantly above reference values in 64% of patients (compared with 58% for AST, 68% for ALT), and this increase was seen in 52% of patients with normal values for transaminases and a Knodell score > 3. Furthermore, there was a significant correlation between alpha-GST and lobular necrosis score (r = 0.31; P < 0.01). Our findings suggest that association of plasma alpha-GST with ALT may improve the biochemical assessment of liver damage in patients with chronic hepatitis C.
7
Schmitz, Sandra, Marc Hamoir, Herve Reychler, Michele Magremanne, Birgit Weynand, Renaud Lhommel, Francois-Xavier Hanin, et al. "Safety, molecular, and imaging responses to cetuximab administered in a window pre-operative study in squamous cell carcinoma of the head and neck (SCCHN)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 5519. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.5519.
Full textAbstract:
5519 Background: Only a minority of SCCHN pts benefits from anti-EGFR mAbs. Trials with pre- and post-therapy tumor biopsies are crucial to better characterize the molecular pathways involved in treatment response or resistance. Targeted agents (TA) are often investigated in unselected end-stage cancer pts, making difficult optimal translational research. One way to resolve this issue is to perform “window” studies where a TA is given during the incompressible period between the diagnosis and surgery. Methods: We conducted a phase I/II study: cetuximab (C) was given pre-operatively to treatment-naïve SCCHN pts selected for primary curative surgery. C (400mg/m2 first wk followed by 250mg/m2/wk) was given during 2 wks (day -15 until day -1, 3 infusions) before surgery (day 0). Tumour biopsies, FDG/PET, and CT were performed at diagnosis and surgery. In the phase I, we investigated the safety of preoperative C by progressively reducing the delay between the last dose of C and surgery (minimum delay : 24 hrs ; 3+3 phase 1 design). The aims of the phase II were (i) safety, (ii) C activity by FDG-PET (Po=0.10, P1=0.35, a=0.05 and b= 0.10). As controls, 5 additional pts were included without C treatment but with the same requirements regarding biopsies and imaging. Results: The phase 1 study (n=18) demonstrated that C infusion given 24 hrs before surgery was safe. Safety was confirmed in the phase II (n=20). 90 % had a FDG-PET partial response (PR) (EORTC guideline) in the C group and 0% in the controls. 52% had a ΔSUVmax decrease of >50%. 2 pts evaluable by CT/MRI had a PR (RECIST). Then, we compared the pre-and post treatment biopsies by immunochemistry. For the whole group, C did not reduce Ki67 (p=0.1) and did not seem to induce apoptosis (caspase). However, for pts with ΔSUVmax decrease > 25% or > 50%, Ki67 was decreased (p=0.04 and 0.006). C induced downregulation of pEGFR (p=0.0004) and pERK (p=0.007) but not pAKT/AKT (Histoscore). Conclusions: Pre-operative study with C is safe. Our findings suggest that the main downstream molecular pathway blocked by C in SCCHN is the RAS/RAF/ERK. Further analyses are ongoing to better characterize molecular response and escape mechanisms.
8
Vergote, Ignace, Florian Heitz, Paul Buderath, Matthew A. Powell, Jalid Sehouli, Christine M. Lee, Anne L. Hamilton, et al. "A randomized, double-blind, placebo-controlled phase Ib/II study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine (G) and carboplatin (C) versus GC for women with recurrent platinum-sensitive ovarian cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 5537. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.5537.
Full textAbstract:
5537 Background: p38 mitogen-activated protein kinase (MAPK) regulates cytokine production in the tumor microenvironment and enables therapeutic resistance of cancer cells. Ralimetinib (R) is a selective small-molecule inhibitor of p38α and p38β MAPKs. Methods: Main inclusion criteria: ≥18 y; recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal, cancer after first-line treatment. Phase (Ph)1b was to determine the recommended Ph2 dose (RP2D) of R administered 12-hourly (Q12H) on Days 1-10 (21-day cycle [Q21D]) in combination with gemcitabine (G: 1000 mg/m2 on Days 3 and 10) and carboplatin (C: AUC 4 on Day 3) for 6 cycles. In Ph2, patients (pts) were randomized double-blind, 1:1 to RP2D R+GC or placebo (P)+GC, for 6 cycles, followed by R 300 mg Q12H or P on Days 1-14, Q28D until disease progression. The stratified log-rank test compared progression-free survival (PFS; primary endpoint) between treatment groups in Ph2, at a 1-sided α level of 0.2. ClinicalTrials.gov, NCT01663857. Results: 118 pts received ≥1 dose of R or P (safety population); 8 in Ph1b and 110 in Ph2 (R+GC N = 58; P+GC N = 52). The RP2D for R in combination with GC was 200 mg Q12H. The study met its primary objective (median PFS: R+GC 10.3 mo vs P+GC 7.9 mo; HR = 0.773, 2-sided p = 0.246). The secondary objectives of median overall survival (R+GC 29.2 mo vs P+GC 25.1 mo; HR = 0.827, p = 0.469) or overall response rate (R+GC 46.6% vs P+GC 46.2%; p = 0.967) were not statistically significant, and 32.4% vs 25.0% of pts had normalized CA125 at the end of cycle 6. Most pts (safety population) experienced ≥1 Grade 3/4 treatment-emergent adverse event (TEAE: R+GC 63/66 [95.5%]; P+GC 48/52 [92.3%]). Decreased neutrophil count (60.6% vs 76.9%), platelet count (43.9% vs 38.5%), and white blood cell count, (30.3% vs 26.9%), anemia (22.7% vs 25.0%), and increased alanine aminotransferase (ALT) (19.7% vs 3.8%) were the Grade 3/4 TEAEs in ≥10% of pts in the R+GC and P+GC arms, respectively. Conclusions: Addition of ralimetinib to GC resulted in modest improvements in PFS. Grade 3/4 elevated ALT was more common in the ralimetinib arm. Clinical trial information: NCT01663857.
9
Arcasoy, Murat O., Paul Hanlon, Ping Fu, Charles Steenbergen, and Elizabeth Murphy. "Mechanisms of Erythropoietin-Mediated Cardioprotection during Ischemia-Reperfusion Injury: Role of Protein Kinase C Signaling." Blood 104, no. 11 (November 16, 2004): 2907. http://dx.doi.org/10.1182/blood.v104.11.2907.2907.
Full textAbstract:
Abstract The biologic effects of erythropoietin (EPO) are mediated by its cellular receptor EPOR, a member of the cytokine receptor superfamily. EPOR expression in non-hematopoietic cells is associated with novel biologic effects for EPO in diverse organ systems. We recently demonstrated functional EPOR expression in adult rat cardiac myocytes and found that recombinant EPO exerts a rapid cardioprotective effect during ischemia-reperfusion injury of the isolated, perfused heart. Here we investigated the mechanisms of the cardioprotective effect of EPO using Langendorff-perfused rat hearts while left-ventricular-developed pressure (LVDP) was measured continuously to assess contractile function. Hearts were treated directly with EPO in the presence or absence of inhibitors of specific signal transduction pathways prior to normothermic global ischemia followed by reperfusion. Post-ischemic recovery of contractile function was determined by measuring LVDP at the end of reperfusion and expressed as a percentage of the baseline pre-treatment measurement. We investigated EPO-mediated activation of signal transduction pathways in the isolated, perfused heart and observed phosphorylation of p44/p42 MAP kinases ERK 1/2 (Thr202/Tyr204) and protein kinase B/Akt (Ser473), a downstream target of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Furthermore, EPO treatment of the isolated, perfused heart was associated with translocation of protein kinase C (PKC) ε and δ isoforms to the membrane fraction. We investigated the role of specific signaling pathways in EPO-mediated cardioprotection by employing inhibitors targeting PI3K, PKC and MAP kinase kinase (MEK1). PI3K inhibitors LY294002 and wortmannin attenuated EPO-induced phosphorylation of Akt but had no effect on EPO-mediated cardioprotection. MEK1 inhibitor U0126 had no effect on EPO-mediated cardioprotection. The PKC catalytic inhibitor chelerythrine (chel) significantly inhibited EPO-mediated improvement in post-ischemic recovery of LVDP (figure 1). Hearts pre-treated with EPO exhibited significantly improved post-ischemic recovery of LVDP compared to control hearts (mean±SE: 72±3 in EPO-treated versus 35±3% in control hearts, P<0.05 by ANOVA and Bonferroni post-hoc test, n=10 experiments each group) and the protective effect of EPO was significantly inhibited in chel-treated hearts (52±4% in EPO+chel versus 72±3% in EPO-treated hearts, P<0.05, n=10). As a control, treatment of the hearts with chelerythrine alone had no significant effect on LVDP (49±4%) compared to control hearts. These data demonstrate that EPO-mediated activation of the PKC signaling pathway is required for the cardioprotective effect of EPO during ischemia-reperfusion injury. Figure Figure
10
Muvarak, Nidal E., Shannon M. Kelley, Mario Tarasco, Maria R. Baer, Kara A. Scheibner, and Feyruz Rassool. "C-MYC and C-MYC-Regulated Micrornas Increase The Activity Of The Error-Prone ALT NHEJ Pathway Through Upregulation Of LIG3 and PARP1 In Tyrosine Kinase-Activated Leukemias." Blood 122, no. 21 (November 15, 2013): 809. http://dx.doi.org/10.1182/blood.v122.21.809.809.
Full textAbstract:
Abstract Constitutively activated tyrosine kinases (TK) BCR-ABL1 and FLT3/ITD not only increase cell survival and proliferation, but also increase levels of endogenous DNA damage and activity of an error-prone DNA double-strand break (DSB) repair pathway. This genomic instability leads to acquisition of genomic alterations that can result in disease progression and/or resistance to therapy. We have previously demonstrated that, in TK-activated leukemias, activity of the classic non homologous end-joining (C-NHEJ) pathway that repairs DSBs is decreased, and, as a consequence, an alternative, highly error-prone form of NHEJ (ALT NHEJ) predominates, evidenced by increased expression of DNA ligase IIIα (LIG3) and PARP1 (components of ALT NHEJ), increased frequency of large DNA deletions, and repair using DNA microhomologies. In this study, we sought to elucidate the role of a key downstream target of TKs, c-MYC, in upregulating LIG3 and PARP1 expression and consequently increasing ALT NHEJ and genomic instability. We demonstrated that MYC increases the expression of LIG3 and PARP1 through two mechanisms: 1) Increased binding to the promoters of LIG3 and PARP1, leading to increased transcription, and 2) Repression of microRNAs (miRs) that putatively regulate LIG3 and PARP1. Chemical and siRNA-mediated knockdown of MYC in MO7e-BCR/ABL and FLT3/ITD(+) MOLM14 cells results in significant reduction (p<0.05) in LIG3 and PARP1 mRNA and protein compared to controls. Chromatin immunoprecipitation assays revealed MYC binding to the promoters of LIG3 and PARP1 in AML (MOLM14) and CML (K562 and MO7e-BCR/ABL) cell lines. Additionally, transfection of PARP1 and LIG3 promoter-luciferase constructs into TK-activated (32D-FLT3/ITD, MO7e-BCR/ABL) cells showed significantly (p<0.01) increased LIG3 and PARP1 promoter activity compared to parental controls (32D, MO7e). Moreover, knockdown of MYC in 32D-FLT3/ITD and MO7e-BCR/ABL cells resulted in a significant reduction of promoter activity in luciferase assays (p<0.05). Conversely, overexpression of c-MYC in 293T cells caused an increase (p<0.05) in LIG3 and PARP1 promoter activity. We next determined whether MYC-repressed miRs that have predicted binding sites in the 3’-UTR and coding regions of LIG3 and PARP1 are involved in regulating expression of LIG3 and PARP1. We found that there was a significant inverse correlation between LIG3 expression and miR-22, miR-23a, and miR-150 (Pearson’s r ≤ -0.3, p<0.05). Similarly, there was a significant inverse correlation between PARP1 expression and miR-22, miR-23a, miR-27a, and miR-150 (Pearson r ≤ -0.3, p<0.05). Over-expression of miR-22 in the CML cell line K562 decreased both LIG3 and PARP1 protein levels by 52% and 63% respectively. Similar results were seen upon over-expression of miR-34a (59% and 45%) and miR-150 (46% and 62%) for LIG3 and PARP1. This indicates that MYC-regulated miRs may function coordinately to regulate NHEJ repair. Importantly, our functional NHEJ assays demonstrate an overall significant (p<0.05) reduction in the average size of deletions at the sites of DSB repair when MYC is knocked down, indicating a reduction in ALT NHEJ activity. To determine whether increased expression of LIG3 and PARP1 correlated with MYC expression in primary leukemia samples, we examined mRNA levels from bone marrow of 21 CML patients (12 chronic phase, 1 accelerated, 7 blast crisis, and 1 unknown). Twelve patients were resistant to Imatinib, 7 were responsive, and 2 undetermined. There was a strong positive correlation between levels of MYC and PARP1 (Pearson’s r= 0.75, p=0.001), as well as MYC and LIG3 (Pearson’s r =0.45, p=0.03). While there was no correlation between levels of gene expression and disease phase, we found that the majority of samples with elevated levels of MYC, LIG3 and PARP1 were from Imatinib-resistant patients (64%), compared to samples from Imatinib-sensitive patients (36%) (p=0.03). Additionally, 2 patient samples with TKI-resistant T315I mutation in BCR-ABL1 exhibited elevated levels of MYC, LIG3 and PARP1. Thus, increased MYC expression, and repression of miRs 22, 150 and 34a augment expression of LIG3 and PARP1, generating DSB repair errors that may lead to resistance to TKI therapy. Altered expression of MYC, LIG3, PARP1 and miRs 22, 150 and 34a may be biomarkers for those patients likely to become resistant to TKI therapy. Disclosures: No relevant conflicts of interest to declare.
11
Hsu, Cheng-Er, Yen-Chun Liu, Ya-Ting Cheng, Wen-Juei Jeng, Rong-Nan Chien, Chun-Yen Lin, Dar-In Tai, and I.-Shyan Sheen. "Hepatitis B Co-Infection Has Limited Impact on Liver Stiffness Regression in Chronic Hepatitis C Patients Treated with Direct-Acting Antivirals." Viruses 14, no. 4 (April 10, 2022): 786. http://dx.doi.org/10.3390/v14040786.
Full textAbstract:
Introduction: High sustained virological response (SVR) rate (>95%) and liver stiffness regression can be achieved with direct acting antivirals treatment (DAA) in patients with chronic hepatitis C virus (CHC) infection. Reactivation of hepatitis B virus (HBV) was reported during DAA treatment in patients co-infected with HBV, although its impact on liver stiffness remains unknown. This study aims to investigate whether the liver stiffness (LSM) regression is different between HBV/HCV co-infected and mono-HCV-infected patients. Materials and Methods: CHC patients with/without HBV co-infection who received DAA treatment and achieved SVR12 between March 2015 and December 2019 in Chang Gung Memorial Hospital, Linkou branch were prospectively enrolled. LSM was assessed by transient elastography (TE, Fibroscan) at baseline and after SVR. Propensity score matching (PSM) at 3:1 ratio, adjusted for age, gender, pre-DAA alanine aminotransferase (ALT), platelet count, and LSM, between CHC with and without HBV co-infection, was performed before further analysis. Results: Among 906 CHC patients enrolled, 52 (5.7%) patients had HBV/HCV co-infection. Patients with HBV/HCV co-infection were of younger age (61.8 vs. 63.2, p = 0.31), with a higher proportion of males (53.8% vs. 38.9%, p = 0.03), and lower pretreatment LSM level (8.15 vs. 10.2 kPa, p = 0.09), while other features were comparable. After PSM, patients with HBV/HCV co-infection had insignificantly lower LSM regression compared to mono-HCV-infected patients (−0.85 kPa vs. −1.65 kPa, p = 0.250). Conclusions: The co-infection of HBV among CHC patients has limited impact on liver stiffness regression after successful DAA treatment.
12
Delaloge, S., K. L. Tedesco, J. Blum, A. Gonçalves, J. Lubinski, N. Efrat, C. Osborne, C. Lebedinsky, J. C. Tercero, and F. A. Holmes. "Preliminary safety and activity results of trabectedin in a phase II trial dedicated to triple-negative (ER-, PR-, HER2-), HER2+++, or BRCA1/2 germ-line-mutated metastatic breast cancer (MBC) patients (pts)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 1010. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.1010.
Full textAbstract:
1010 Background: Trabectedin ([T]; Yondelis) binds to the minor groove of DNA; its cytotoxicity is determined by the synergistic action of two DNA repair mechanisms, the efficient nucleotide excision repair (NER) and deficient homologous recombination repair (HRR) machinery. T has EMEA authorization in soft tissue sarcoma after failure of standard treatment. Preliminary data have shown activity of T as single agent in MBC. Clinical and preclinical data suggested T may display specific activity among certain NER-intact or HRR-deficient MBC, and prompted this phase II trial dedicated to 3 subgroups: triple-negative (TN), HER-2-overexpressed, and BRCA1/2 germline-mutated MBC. Methods: T was given at 1.3 mg/m2 as a 3- hour iv infusion every 3 weeks to pts with pretreated progressive MBC: Group A: TN; Group B: HER-2+++; Group C: BRCA1/2 mutation carriers. Endpoints were objective response (OR) rate by RECIST, duration of response, progression free survival (PFS), tumor volume changes, safety and exploratory pharmacogenomics (PGx). Results: A total of 95 women (median [med] age 52, ECOG 0/1 48/52%) have been enrolled (A:50, B:24, C:21) with data available for 72 pts. Med number of prior chemotherapy regimens: 4 (1–10). Med number of T cycles administered: 2 (1–12) for all groups. The most commonly reported grade 3/4 AEs are neutropenia (29/21%), ALT (28/2%) and AST (13/0). Alopecia/stomatitis, only G1, was reported in <2% each. Long-lasting disease stabilizations were described in all groups. While OR were rare among TN MBC pts (2PR/43 evaluable), preliminary analysis by investigator shows efficacy in group C (4PR/11 evaluable). Tissue samples from 36 pts were collected for RNA expression analysis (XPG + ERCC1 + BRCA1). Preliminary results show high XPG is associated with longer PFS: 4.1 months (95% CI 2.6-not reached) versus 1.3 months (95% CI 1.2–3.7), p = 0.01. Analyses are ongoing. Conclusions: Trabectedin shows a manageable safety profile in the 3 groups of MBC with promising efficacy in certain DNA-repair machinery sub-categories defined molecularly. TN group was closed due to low response. More mature PGx results will be discussed to help selecting the patients who are at highest chance for response. [Table: see text]
13
Simoen, Eddy, K. Takakura, Brent Hsu, and Cor Claeys. "(Electronics and Photonics Division Award) The Impact of Defects on the Performance of Semiconductor Devices and Materials." ECS Meeting Abstracts MA2022-01, no. 31 (July 7, 2022): 1299. http://dx.doi.org/10.1149/ma2022-01311299mtgabs.
Full textAbstract:
Since the early days of the semiconductor industry, defect control has been key to the successful development of devices and circuits. It requires a thorough understanding of their formation and the impact on the electrical material parameters. This has only been possible by the invention of powerful structural, chemical and electrical characterization tools, with the device itself perhaps as the most sensitive probe. This evolution was paralleled by the development of ab initio calculation methods, based on Density Functional Theory and more recently, also TCAD tools allowing more and more refined modelling of the impact of defects on the electrical characteristics of devices. The implementation of other materials than Si and SiO2 in CMOS through the hetero-epitaxial growth on a silicon substrate for example, has renewed the interest in defect engineering during the last two decades, leading to single-defect analysis methods like Random Telegraph Noise (RTN) [1] or novel growth schemes like Aspect Ratio Trapping (ART) [2] for the removal of extended defects from the device active regions. In this presentation, some state-of-the-art analysis techniques will be highlighted, including Deep Level Transient Spectroscopy (DLTS) [3], Generation-Recombination (GR) noise and RTN spectroscopy [1,4] and p-n diode lifetime analysis [5]. These methods will be applied to several case studies. As shown in Fig. 1, threading extended defects impact the recombination lifetime of lowly-doped n-type In0.47Ga0.53As starting from a density of a few 107 cm-2. Likewise, it will be demonstrated that the GR noise observed in GaN-on-Si MOSHEMTs (Fig. 2) most likely originates from threading dislocations [6]. It is concluded that when hetero-epitaxial layers can be grown with a sufficiently low defect density, their impact will be more on the variability of the electrical parameters rather than on the effective values. In addition, the position of the defect with respect to strategic nodes like a p-n junction or depletion region largely determines its electrical impact, as has been validated by TCAD simulations. References [1] E. Simoen and C. Claeys, “Random Telegraph Signals in Semiconductor Devices”, The Institute of Physics, Bristol, UK (2016). [2] J. Z. Li et al., Appl. Phys. Lett., 91, p. 021114 (2007). [3] E. Simoen, J. Lauwaert and H. Vrielinck, Semiconductors and Semimetals, Eds. L. Romano, V. Privitera and C. Jagadish, 91, pp. 205-250, Elsevier 2015. [4] D. Boudier et al., Solid-St. Electron., 128, pp. 102-108 (2017). [5] Po-Chun (Brent) Hsu et al., J. Phys. D: Appl. Phys., 52, p. 485102 (2019). [6] K. Takakura et al., IEEE Trans. Electron Devices, 67, pp. 3062-3068 (2020). Figure 1
14
Miluski, Piotr, Marcin Kochanowicz, Jacek Zmojda, and Dominik Dorosz. "Multicolor emission of Tb3+/Eu3+ co-doped poly(methyl methacrylate) for optical fibre technology." Photonics Letters of Poland 9, no. 4 (December 31, 2017): 110. http://dx.doi.org/10.4302/plp.v9i4.788.
Full textAbstract:
The article presents multicolor emission observed in poly(methyl methacrylate) specimens co-doped by trivalent terbium and europium ions. The bright luminescence was obtained using organometallic complexes of lanthanides and energy transfer antenna effect. Spectroscopic characterization exhibit wide excitation spectrum according to chelating structure of used complexes and characteristic Tb3+ and Eu3+ emission peaks in luminescence spectra. The calculated CIE 1931 chromaticity coordinates confirm that colorful emission from green to red can be obtained using proposed materials. Full Text: PDF ReferencesJ.-H. Jou, M.-C. Sun, H.-H. Chou, C.-H. Li, "White organic light-emitting devices with a solution-processed and molecular host-employed emission layer", Appl. Phys. Lett. 87, 043508 (2005). CrossRef R. Mac Ciarnain, D. Michaelis, T. Wehlus, A. F. Rausch, N. Danz, A. Brauer, A. Tünnermann, "Emission from outside of the emission layer in state-of-the-art phosphorescent organic light-emitting diodes", Organic Electronics 44, 115 (2017). CrossRef G. Williams, C. Backhouse, H. Aziz, "Integration of Organic Light Emitting Diodes and Organic Photodetectors for Lab-on-a-Chip Bio-Detection Systems", Electronics 3, 43 (2014). CrossRef P. Miluski, D. Dorosz, M. Kochanowicz and J. Żmojda, "Fluorescent polymeric optical fibre illuminator", Electronics Letters, 52, 18 (2016). CrossRef L. Bilro, N. Alberto, J. L.Pinto, R. Nogueira, "Optical Sensors Based on Plastic Fibers", Sensors 12, 12184 (2012). CrossRef P. Miluski, D. Dorosz, J. Żmojda, M. Kochanowicz, J. Dorosz, "Luminescent Polymer Optical Fibre Sensor for Temperature Measurement", Acta Phys. Pol. A 127, 730 (2015) CrossRef C. Lethien, C. Loyez, J. P. Vilcot, N. Rolland, P. A. Rolland, "Exploit the Bandwidth Capacities of the Perfluorinated Graded Index Polymer Optical Fiber for Multi-Services Distribution", Polymers 3, 1006 (2011). CrossRef J. Zubia, J. Arrue, "Plastic Optical Fibers: An Introduction to Their Technological Processes and Applications", Opt. Fiber Technol. 7, 101 (2001). CrossRef N. Sultanovaa, S. Kasarovaa, I. Nikolov, "Dispersion Properties of Optical Polymers", Acta Physica Polonica A 116, 585 (2009). CrossRef J. Arrue, F. Jiménez, I. Ayesta, M. Asunción Illarramendi, J. Zubia, "Polymer-Optical-Fiber Lasers and Amplifiers Doped with Organic Dyes", Polymers 3,1162 (2011). CrossRef P. Miluski, M. Kochanowicz, J. Żmojda, "Spectroscopic investigation of organic co-doped PMMA for optical fiber technology", Journal Of Optoelectronics And Advanced Materials, 19, 379 (2017). DirectLink P. Miluski, M. Kochanowicz, J. Żmojda, and D. Dorosz, "Emission properties and energy transfer in Perylene-Rhodamine 6 G co-doped polymeric fiber", Chinese Optics Letters 14, 12, 121602 (2016). CrossRef H. Liang, Z. Yang, L. Xiao, F. Xie, " Radiative transition probability of a europium (III) chelating polymer", Optoelectronics And Advanced Materials ? Rapid Communications 4, 9, 1396 (2010). CrossRef H. Jiu, J. Ding, Y. Sun, J. Bao, C. Gao, Q. Zhang, "Fluorescence enhancement of europium complex co-doped with terbium complex in a poly(methyl methacrylate) matrix", Journal of Non-Crystalline Solids 352, 197 (2006). CrossRef K. Kuriki, S. Nishihara, Y. Nishizawa, A. Tagaya, Y. Koike, Y. Okamoto, "Spectroscopic properties of lanthanide chelates in perfluorinated plastics for optical applications", Journal of the Optical Society of America B 19, 8, 1844 (2002). CrossRef P. Miluski, M. Kochanowicz, J. Żmojda, D. Dorosz, "Luminescent properties of Tb3+-dopedpoly(methyl methacrylate) fiber" Chinese Optics Letters, 15, 7, 070602 (2017). DirectLink P. Miluski, M. Kochanowicz, J. Żmojda, D. Dorosz, "Properties of Eu3+ doped poly(methyl methacrylate) optical fiber", Optical Engineering, 56, 2, 027106 (2017). CrossRef D. Oh, N. Song and J.-J. Kim, "Plastic optical amplifier using europium complex", Proc. SPIE, 4282, (2001). CrossRef X. Xu, H. Ming, Q. Zhang, "Optical-transition probabilities of Nd3+ ions in polymer optical fibers", Optics Communications 199, 369 (2001). CrossRef Z.-Q. Zheng, H. Liang, H. Ming, Q.-J. Zhang, X.-H. Han, G.-Z. Wang, J.-P. Xie, "Optical Transition Probability of Sm 3+ Ions in a Polymer Optical Fibre", Chin. Phys. Lett. 21, 2, 291 (2004). CrossRef
15
Hapidin, Winda Gunarti, Yuli Pujianti, and Erie Siti Syarah. "STEAM to R-SLAMET Modification: An Integrative Thematic Play Based Learning with R-SLAMETS Content in Early Child-hood Education." JPUD - Jurnal Pendidikan Usia Dini 14, no. 2 (November 30, 2020): 262–74. http://dx.doi.org/10.21009/jpud.142.05.
Full textAbstract:
STEAM-based learning is a global issue in early-childhood education practice. STEAM content becomes an integrative thematic approach as the main pillar of learning in kindergarten. This study aims to develop a conceptual and practical approach in the implementation of children's education by applying a modification from STEAM Learning to R-SLAMET. The research used a qualitative case study method with data collection through focus group discussions (FGD), involving early-childhood educator's research participants (n = 35), interviews, observation, document analysis such as videos, photos and portfolios. The study found several ideal categories through the use of narrative data analysis techniques. The findings show that educators gain an understanding of the change in learning orientation from competency indicators to play-based learning. Developing thematic play activities into continuum playing scenarios. STEAM learning content modification (Science, Technology, Engineering, Art and Math) to R-SLAMETS content (Religion, Science, Literacy, Art, Math, Engineering, Technology and Social study) in daily class activity. Children activities with R-SLAMETS content can be developed based on an integrative learning flow that empowers loose part media with local materials learning resources.
Keyword: STEAM to R-SLAMETS, Early Childhood Education, Integrative Thematic Learning
References
Ali, E., Kaitlyn M, C., Hussain, A., & Akhtar, Z. (2018). the Effects of Play-Based Learning on Early Childhood Education and Development. Journal of Evolution of Medical and Dental Sciences, 7(43), 4682–4685. https://doi.org/10.14260/jemds/2018/1044
Ata Aktürk, A., & Demircan, O. (2017). A Review of Studies on STEM and STEAM Education in Early Childhood. Journal of Kırşehir Education Faculty, 18(2), 757–776.
Azizah, W. A., Sarwi, S., & Ellianawati, E. (2020). Implementation of Project -Based Learning Model (PjBL) Using STREAM-Based Approach in Elementary Schools. Journal of Primary Education, 9(3), 238–247. https://doi.org/10.15294/jpe.v9i3.39950
Badmus, O. (2018). Evolution of STEM, STEAM and STREAM Education in Africa: The Implication of the Knowledge Gap. In Contemporary Issues in Science, Technology, Engineering, Arts and Mathematics Teacher Education in Nigeria.
Björklund, C., & Ahlskog-Björkman, E. (2017). Approaches to teaching in thematic work: early childhood teachers’ integration of mathematics and art. International Journal of Early Years Education, 25(2), 98–111. https://doi.org/10.1080/09669760.2017.1287061
Broadhead, P. (2003). Early Years Play and Learning. In Early Years Play and Learning. https://doi.org/10.4324/9780203465257
Canning, N. (2010). The influence of the outdoor environment: Den-making in three different contexts. European Early Childhood Education Research Journal, 18(4), 555–566. https://doi.org/10.1080/1350293X.2010.525961
Clapp, E. P., Solis, S. L., Ho, C. K. N., & Sachdeva, A. R. (2019). Complicating STEAM: A Critical Look at the Arts in the STEAM Agenda. Encyclopedia of Educational Innovation, 1–4. https://doi.org/10.1007/978-981-13-2262-4_54-1
Colucci, L., Burnard, P., Cooke, C., Davies, R., Gray, D., & Trowsdale, J. (2017). Reviewing the potential and challenges of developing STEAM education through creative pedagogies for 21st learning: how can school curricula be broadened towards a more responsive, dynamic, and inclusive form of education? BERA Research Commission, August, 1–105. https://doi.org/10.13140/RG.2.2.22452.76161
Conradty, C., & Bogner, F. X. (2018). From STEM to STEAM: How to Monitor Creativity. Creativity Research Journal, 30(3), 233–240. https://doi.org/10.1080/10400419.2018.1488195
Conradty, C., & Bogner, F. X. (2019). From STEM to STEAM: Cracking the Code? How Creativity & Motivation Interacts with Inquiry-based Learning. Creativity Research Journal, 31(3), 284–295. https://doi.org/10.1080/10400419.2019.1641678
Cook, K. L., & Bush, S. B. (2018). Design thinking in integrated STEAM learning: Surveying the landscape and exploring exemplars in elementary grades. School Science and Mathematics, 118(3–4), 93–103. https://doi.org/10.1111/ssm.12268
Costantino, T. (2018). STEAM by another name: Transdisciplinary practice in art and design education. Arts Education Policy Review, 119(2), 100–106. https://doi.org/10.1080/10632913.2017.1292973
Danniels, E., & Pyle, A. (2018). Defining Play-based Learning. In Encyclopedia on Early Childhood Development (Play-Based, Issue February, pp. 1–5). OISE University of Toronto.
DeJarnette, N. K. (2018). Implementing STEAM in the Early Childhood Classroom. European Journal of STEM Education, 3(3), 1–9. https://doi.org/10.20897/ejsteme/3878
Dell’Erba, M. (2019). Policy Considerations for STEAM Education. Policy Brief, 1–10.
Doyle, K. (2019). The languages and literacies of the STEAM content areas. Literacy Learning: The Middle Years, 27(1), 38–50. http://proxy.libraries.smu.edu/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=eue&AN=133954204&site=ehost-live&scope=site
Edwards, S. (2017). Play-based learning and intentional teaching: Forever different? Australasian Journal of Early Childhood, 42(2), 4–11. https://doi.org/10.23965/ajec.42.2.01
Faas, S., Wu, S.-C., & Geiger, S. (2017). The Importance of Play in Early Childhood Education: A Critical Perspective on Current Policies and Practices in Germany and Hong Kong. Global Education Review, 4(2), 75–91.
Fesseha, E., & Pyle, A. (2016). Conceptualising play-based learning from kindergarten teachers’ perspectives. International Journal of Early Years Education, 24(3), 361–377. https://doi.org/10.1080/09669760.2016.1174105
Finch, C. R., Frantz, N. R., Mooney, M., & Aneke, N. O. (1997). Designing the Thematic Curriculum: An All Aspects Approach MDS-956. 97.
Gess, A. H. (2019). STEAM Education. STEAM Education, November, 2011–2014. https://doi.org/10.1007/978-3-030-04003-1
Gronlund, G. (n.d.). “ Addressing Standards through Play-Based Learning in Preschool and Kindergarten .”
Gronlund, G. (2015). Planning for Play-Based Curriculum Based on Individualized Goals to Help Each Child Thrive in Preschool and Kindergarten Gaye Gronlund.
Gull, C., Bogunovich, J., Goldstein, S. L., & Rosengarten, T. (2019). Definitions of Loose Parts in Early Childhood Outdoor Classrooms: A Scoping Review. The International Journal of Early Childhood Education, 6(3), 37–52.
Hapidin, Pujianti, Y., Hartati, S., Nurani, Y., & Dhieni, N. (2020). The continuous professional development for early childhood teachers through lesson study in implementing play based curriculum (case study in Jakarta, Indonesia). International Journal of Innovation, Creativity and Change, 12(10), 17–25.
Hennessey, P. (2016). Full – Day Kindergarten Play-Based Learning : Promoting a Common Understanding. Education and Early Childhood Development, April, 1–76. gov.nl.ca/edu
Henriksen, D. (2017). Creating STEAM with Design Thinking: Beyond STEM and Arts Integration. Steam, 3(1), 1–11. https://doi.org/10.5642/steam.20170301.11
Inglese, P., Barbera, G., La Mantia, T., On, P., Presentation, T., Reid, R., Vasa, S. F., Maag, J. W., Wright, G., Irsyadi, F. Y. Al, Nugroho, Y. S., Cutter-Mackenzie, A., Edwards, S., Moore, D., Boyd, W., Miller, E., Almon, J., Cramer, S. C., Wilkes-Gillan, S., … Halperin, J. M. (2014). Young Children’s Play and Environmental Education in Early Childhood Education. PLoS ONE, 2(3), 9–25. https://doi.org/10.1586/ern.12.106
Jacman, H. (2012). Early Education Curriculum. Pedagogical Development Unit, FEBRUARY 2011, 163. https://www.eursc.eu/Syllabuses/2011-01-D-15-en-4.pdf
Jay, J. A., & Knaus, M. (2018). Embedding play-based learning into junior primary (Year 1 and 2) Curriculum in WA. Australian Journal of Teacher Education, 43(1), 112–126. https://doi.org/10.14221/ajte.2018v43n1.7
Kennedy, A., & Barblett, L. (2010). Supporting the Early Years Learning Framework. Research in Practise Series, 17(3), 1–12.
Keung, C. P. C., & Cheung, A. C. K. (2019). Towards Holistic Supporting of Play-Based Learning Implementation in Kindergartens: A Mixed Method Study. Early Childhood Education Journal, 47(5), 627–640. https://doi.org/10.1007/s10643-019-00956-2
Keung, C. P. C., & Fung, C. K. H. (2020). Exploring kindergarten teachers’ pedagogical content knowledge in the development of play-based learning. Journal of Education for Teaching, 46(2), 244–247. https://doi.org/10.1080/02607476.2020.1724656
Krogh, S., & Morehouse, P. (2014). The Early Childhood Curriculum : Inquiry Learning Through Integration.
Liao, C. (2016). From Interdisciplinary to Transdisciplinary: An Arts-Integrated Approach to STEAM Education. Art Education, 69(6), 44–49. https://doi.org/10.1080/00043125.2016.1224873
Lillard, A. S., Lerner, M. D., Hopkins, E. J., Dore, R. A., Smith, E. D., & Palmquist, C. M. (2013). The impact of pretend play on children’s development: A review of the evidence. Psychological Bulletin, 139(1), 1–34. https://doi.org/10.1037/a0029321
Maxwell, L. E., Mitchell, M. R., & Evans, G. W. (2008). Effects of Play Equipment and Loose Parts on Preschool Children’s Outdoor Play Behavior: An Observational Study and Design Intervention. Children, Youth and Environments, 18(2), 37–63.
McLaughlin, T., & Cherrington, S. (2018). Creating a rich curriculum through intentional teaching. Early Childhood Folio, 22(1), 33. https://doi.org/10.18296/ecf.0050
Mengmeng, Z., Xiantong, Y., & Xinghua, W. (2019). Construction of STEAM Curriculum Model and Case Design in Kindergarten. American Journal of Educational Research, 7(7), 485–490. https://doi.org/10.12691/education-7-7-8
Milara, I. S., Pitkänen, K., Laru, J., Iwata, M., Orduña, M. C., & Riekki, J. (2020). STEAM in Oulu: Scaffolding the development of a Community of Practice for local educators around STEAM and digital fabrication. International Journal of Child-Computer Interaction, 26, 100197. https://doi.org/10.1016/j.ijcci.2020.100197
Moomaw, S. (2012). STEM Begins in the Early Years. School Science and Mathematics, 112(2), 57–58. https://doi.org/10.1111/j.1949-8594.2011.00119.x
Peng, Q. (2017). Study on Three Positions Framing Kindergarten Play-Based Curriculum in China: Through Analyses of the Attitudes of Teachers to Early Linguistic Education. Studies in English Language Teaching, 5(3), 543. https://doi.org/10.22158/selt.v5n3p543
Pyle, A., & Bigelow, A. (2015). Play in Kindergarten: An Interview and Observational Study in Three Canadian Classrooms. Early Childhood Education Journal, 43(5), 385–393. https://doi.org/10.1007/s10643-014-0666-1
Pyle, A., & Danniels, E. (2017). A Continuum of Play-Based Learning: The Role of the Teacher in Play-Based Pedagogy and the Fear of Hijacking Play. Early Education and Development, 28(3), 274–289. https://doi.org/10.1080/10409289.2016.1220771
Quigley, C. F., Herro, D., & Jamil, F. M. (2017). Developing a Conceptual Model of STEAM Teaching Practices. School Science and Mathematics, 117(1–2), 1–12. https://doi.org/10.1111/ssm.12201
Ridgers, N. D., Knowles, Z. R., & Sayers, J. (2012). Encouraging play in the natural environment: A child-focused case study of Forest School. Children’s Geographies, 10(1), 49–65. https://doi.org/10.1080/14733285.2011.638176
Ridwan, A., Rahmawati, Y., & Hadinugrahaningsih, T. (2017). Steam Integration in Chemistry Learning for Developing 21st Century Skills. MIER Journail of Educational Studies, Trends & Practices, 7(2), 184–194.
Rolling, J. H. (2016). Reinventing the STEAM Engine for Art + Design Education. Art Education, 69(4), 4–7. https://doi.org/10.1080/00043125.2016.1176848
Sancar-Tokmak, H. (2015). The effect of curriculum-generated play instruction on the mathematics teaching efficacies of early childhood education pre-service teachers. European Early Childhood Education Research Journal, 23(1), 5–20. https://doi.org/10.1080/1350293X.2013.788315
Sawangmek, S. (2019). Trends and Issues on STEM and STEAM Education in Early Childhood. Képzés És Gyakorlat, 17(2019/3-4), 97–106. https://doi.org/10.17165/tp.2019.3-4.8
Science, A. I. (n.d.). STEM Project-Based Learning.
Spencer, R., Joshi, N., Branje, K., Lee McIsaac, J., Cawley, J., Rehman, L., FL Kirk, S., & Stone, M. (2019). Educator perceptions on the benefits and challenges of loose parts play in the outdoor environments of childcare centres. AIMS Public Health, 6(4), 461–476. https://doi.org/10.3934/publichealth.2019.4.461
Taylor, J., Bond, E., & Woods, M. (2018). A Multidisciplinary and Holistic Introduction.
Varun A. (2014). Thematic Approach for Effective Communication in Early Childhood Education Thematic Approach for effective communication in ECCE. International Journal of Education and Psychological Research (IJEPR), 3(3), 49–51. https://www.researchgate.net/publication/289868193
Wang, X., Xu, W., & Guo, L. (2018). The status quo and ways of STEAM education promoting China’s future social sustainable development. Sustainability (Switzerland), 10(12). https://doi.org/10.3390/su10124417
Whitebread, D. D. (2012). The Importance of Play. Toy Industries of Europe, April, 1–55. https://doi.org/10.5455/msm.2015.27.438-441
Wong, S. M., Wang, Z., & Cheng, D. (2011). A play-based curriculum: Hong Kong children’s perception of play and non-play. International Journal of Learning, 17(10), 165–180. https://doi.org/10.18848/1447-9494/cgp/v17i10/47298
Zosh, J. M., Hopkins, E. J., Jensen, H., Liu, C., Neale, D., Hirsh-Pasek, K., Whitebread, Solis, S. L., & David. (2017). Learning through play : a review of the evidence (Issue November). The LEGO Foundation.
16
Birzu, C., A. Hillairet, M. Giry, N. Grandin, P. Verrelle, K. Mokhtari, Y. Marie, et al. "OS9.7 Telomere length, TERTp mutation and ALT status in adult diffuse gliomas." Neuro-Oncology 21, Supplement_3 (August 2019): iii19—iii20. http://dx.doi.org/10.1093/neuonc/noz126.065.
Full textAbstract:
Abstract BACKGROUND The current classification of adult diffuse gliomas integrates two alternative telomere maintenance mechanisms: reactivation of telomerase activity by TERT promoter (TERTp) mutations or ATRX mutations associated with alternative length telomere (ALT). We investigated here the relation between these two mechanisms, telomere length, and outcome in a large series of diffuse gliomas. MATERIAL AND METHODS We performed C-circle assay (CCA) to determine ALT status, determined telomere length in tumor (RTLt) and leukocyte (RTLl) in a cohort of 354 adult diffuse gliomas, and sequenced ATRX gene. We calculated an age-adjusted telomere score considering tumor and leukocyte (blood) telomere length and corrected by age. This score was used in univariate and multivariate survival analyses to evaluate the potential impact of telomere length on the prognosis of gliomas. We used the TCGA LGG-GBM dataset to validate our findings in an independent cohort. RESULTS RTLl and RTLt were associated with ATRX mutation and ALT phenotype, and negatively associated with age and TERTp mutations. ATRX mutations (found in 52% (64/123) of samples) were mostly transitions (C>T or T>C), and were associated with ALT phenotype. None of 1p/19q co-deleted oligodendrogliomas harbored an ALT phenotype. No patients with TERTp mutations had ALT phenotype except for a very small subgroup of patients (3/87, 3.4%) suggesting that multiple ways of telomere maintenance, may co-exist in a single tumor, probably expressed in different clones. Telomere age-adjusted score was independently associated with better outcome (HR= 0.73 [95% CI 0.56–0.97], p-value 0.03 adjusted for age, TERTp mutation, IDH mutation, 1p/19q co-deletion and WHO grade). These results were validated using the LGG-GBM TCGA dataset. CONCLUSION We unravel the relation between RTLl and RTLt, TERTp mutation and ALT phenotype and describe a novel telomere age-adjusted score independently associated with better prognosis in adult diffuse gliomas.
17
Wu, R., L. Wang, X. Zheng, Y. Wang, G. Wang, X. Li, and X. Li. "THU0242 REGULATORY ROLE OF TRANSCRIPTION FACTOR BLIMP-1 IN SJÖGREN’S SYNDROME." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 348. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2618.
Full textAbstract:
Background:The pathogenesis of primary sjögren’s syndrome (pSS) is multifactorial. Self-antigen-driven responses perform a vital function in the development of autoimmune diseases [1]. B cells, only 20-25% of total infiltrating cells in labial glands, are the cellular basis for spontaneous antibody production [2].Genome-wide association studies (GWAS) have identified Blimp-1 as a susceptibility gene for autoimmune diseases and played an important role in the pathogenesis of autoimmune diseases [3].Objectives:To investigate the expression and effect of B lymphocyte induced maturation protein 1 (Blimp-1) in pSS and the correlation of Blimp-1 with B cell subsets and clinical features.Methods:The PRDM1 mRNA expression in B lymphocyte and labial gland were examined by RT-PCR. The levels of B cell subsets were examined by flow cytometry. Hematoxylin-eosin (HE) staining and immunohistochemistry (IHC) were used to examine the invasion degree of lymph cell and Blimp-1 distribution, respectively. The correlation of PRDM1 mRNA with B cell subsets and clinical indicators were also analyzed.Results:The levels of PRDM1 mRNA expression of B cells were significantly higher in SS than in healthy controls (HC) and which were also significantly higher in the high immunoglobulin (Ig) group than that in normal Ig group (P<0.02, Fig. 1a-b). The number of CD19+B cells and CD138+ plasma cells(PC) have increased while the CD27+ cells decreased in SS(P<0.05). The percentage of PC and PC/B is positively correlated with PRDM1 mRNA(r=0.380,P=0.002;r=0.317,P=0.009, Fig. 1c-d). Blimp-1 expression level showed a positive correlation with invasion degree of lymph cell in histology (Fig. 2a-c), Ig levels and ESSDAI score and an inverse correlation with the glucocorticoids usage (Fig. 3c).Fig. 1(a-b) RT-PCR showed that PRDM1 mRNA expression in SS patients and HC. (c-d) Correlation between PRDM1 mRNA expression and PC and PC/B.Fig. 2(a) Expression of Blimp-1 in labial glands of sjögren’s syndrome. (b) PRDM1 mRNA levels in different invasion degree of lymph cell group. (c) Correlation between PRDM1 mRNA expression and invasion degree of lymph cell. *p<0.05, ***p<0.001.Fig. 3(a-b) RT-PCR showed that PRDM1 mRNA expression in different usage of glucocorticoids. (c) Correlation between PRDM1 mRNA expression and different glucocorticoid usage. **p<0.01, ***p<0.001.Conclusion:Blimp-1 displayed high expression in SS, which could affect pSS disease activity. SS activity is suppressed by glucocorticoid which might be through inhibition of Blimp-1.References:[1]Kapsogeorgou EK, Abu-Helu RF, Moutsopoulos HM, Manoussakis MN (2005) Salivary gland epithelial cell exosomes: A source of autoantigenic ribonucleoproteins. Arthritis Rheum 52(5):1517-21.https://doi.org/10.1002/art.21005[2]Arneth BM (2019) Impact of B cells to the pathophysiology of multiple sclerosis. J Neuroinflammation 16(1):128.https://doi.org/10.1186/s12974-019-1517-1[3]Bönelt P, Wöhner M, Minnich M et al (2019) Precocious expression of Blimp-1 in B cells causes autoimmune disease with increased self-reactive plasma cells. EMBO J 38(2). pii:e100010.https://doi.org/10.15252/embj.2018100010Table 1.Clinical characteristics of pSS and HC.HC(n=17)pSS(n=50)Sex (Male/Female)0/170/50Age(x±s)45.24±18.5546.8±11.05Xerostomia(positive/negative)0/1743/7Keratoconjunctivitis sicca0/1735/15Arthralgia0/1732/18Fatigue0/1718/32ESSDAI(x±s)-2.78±1.61 (0~7)ESSPRI(x±s)-3.3±1.39 (1~6)ANA(positive/negative)-49/1SSA-49/1SSB-18/32pSS: primary sjögren ‘s syndrome; HC: Healthy controls; ESSDAI: The European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index; ESSPRI: EULAR Sjögren’s Syndrome Patient Reported Index.** P<0.01,*** P<0.001.Acknowledgments :This study was supported by the grants from the National Natural Science Foundation of China (81871271).Disclosure of Interests: :None declared
18
Burnett, Alan K., William J. Kell, Anthony H. Goldstone, Donald Milligan, Ann Hunter, Archie G. Prentice, Nigel H. Russell, Brenda Gibson, Keith Wheatley, and Robert K. Hills. "The Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy for AML Improves Disease Free Survival without Extra Toxicity: Preliminary Analysis of 1115 Patients in the MRC AML15 Trial." Blood 108, no. 11 (November 16, 2006): 13. http://dx.doi.org/10.1182/blood.v108.11.13.13.
Full textAbstract:
Abstract The MRC AML15 Trial is primarily for patients with any form of AML who are under 60 years. One of the questions addressed was whether the addition of the immunoconjugate, Gemtuzumab Ozogamicin (GO) to induction (course 1) and/or consolidation (course 3) is beneficial. In induction patients are randomised to receive either DA (Daunorubicin/Ara-C) or ADE (Ara-C/Daunorubicin/Etoposide) or FLAG-Ida (Fludarabine/Ara-C/Idarubicin/G-CSF) and in consolidation either MACE (Amsacrine/Etoposide) or HD Ara-C (3.0g/m2 or 1.5g/m2 per dose). Our prior pilot trial had shown that GO 3mgs/m2 could be safely added to day 1 of each of these treatments (Kell et al Blood102, 4277–4283). Here we report the preliminary results of the effect of combining GO with induction chemotherapy. This randomisation achieved its recruitment target and was closed on 30 June 2006. All other comparisons in the trial, including GO in consolidation, remain open. Patients: A total of 1115 patients were randomised between July 2002 and June 2006. The median age was 49 (range 0–71) years: 53% of patients were male: 92% (n=1027) had de novo disease: 95% had WHO performance score of <2: 43% received DA, 43% FLAG-Ida, and 14% ADE. (Recruitment to ADE+GO opened in June 2005). Patients with WBC > 30 x 109/l and LFT’s > normal were initially excluded but admitted from March 2004. APL patients were not eligible for entry. 15% of patients with data had favourable 71% intermediate, and 14% adverse cytogenetics. Over 83% were CD33 positive. Results: The overall remission rate was 85% with no differences between the arms for GO vs no GO in CR (85% vs 85%) induction death (8% vs 7%) or resistant disease (7% vs 8%). There was a modest increase in mucositis on the GO arm in course 1 only (p=0.04) and increased AST and Alt toxicity in C1 (p=.002; p=.03) but no difference in bilirubin grades. GO patients used more platelets (19 vs 14; p<0.0001), but not red cells, and had more days on IV antibiotics (20.6 vs 18.6 p=0.001). The haemopoietic recovery and days in hospital were similar. With a median follow-up of 15 months (range 0–45), there is no significant difference in deaths in CR (GO vs no GO): 36 vs 45 (HR 0.75; CI.49–1.16 p=0.2), but relapse was reduced: 37% vs 52% at 3 years (HR 0.70 (0.52–0.92) p=0.01) resulting in an improved DFS: 51% vs 40% at 3 years (HR 0.72 (0.56–0.91) p=0.008). There is so far no significant difference in OS (53% vs 46% at 3 years; HR 0.91(0.73–1.14) p=0.4). Conclusion: This preliminary analysis of 1115 randomised patients indicates that the addition of GO to induction chemotherapy can reduce the relapse risk without adding significant extra toxicity and this has significantly improved the DFS in the GO arm. Longer follow up is required to determine the impact on survival.
19
Petri, M. A., G. Bertsias, M. Daniels, N. L. Fox, B. H. Hahn, A. Hammer, J. Harris, H. Quasny, C. Tani, and A. Askanase. "POS0183 THE EFFECT OF BELIMUMAB ON SRI-4 RESPONSE IN MULTIPLE SUBGROUPS OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS OF A LARGE INTEGRATED ANALYSIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 323.1–323. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1807.
Full textAbstract:
BackgroundBelimumab (BEL) is approved for the treatment of active autoantibody-positive systemic lupus erythematosus (SLE).1 Four Phase 3 studies have consistently demonstrated greater SLE Responder Index (SRI) response rates with BEL vs placebo (PBO).2-5 This robust dataset allows for additional exploration of the onset of efficacy of BEL and response rates by patient (pt) characteristics.ObjectivesTo perform a post hoc analysis evaluating the effect of BEL on SRI-4 response across a large, pooled population and pt subgroups.MethodsThe Belimumab Summary of Lupus Efficacy (Be-SLE) integrated analysis evaluated data from adults with SLE from 5 double-blind, PBO-controlled BEL trials: BLISS-76, BLISS-52, BLISS-NEA, BLISS-SC, and EMBRACE.2-6 Pts were randomised to BEL (monthly intravenous 10 mg/kg or weekly subcutaneous 200 mg) or PBO, plus standard therapy. Data were collected every 4 weeks (wks) from baseline (BL) to Wk 52. The SRI-4 response rate (a composite measure that includes ≥4-point reduction in Safety of Estrogens in Lupus Erythematosus National Assessment - SLE Disease Activity Index [SELENA-SLEDAI] score, stable Physician Global Assessment [PGA] increase of <0.3, and no new British Isles Lupus Assessment Group [BILAG] 1A/2B organ domain scores) by visit and time to first SRI-4 response maintained through Wk 52 were determined for both treatment groups. SRI-4 response rates at Wk 52 were evaluated by BL characteristic subgroups: SELENA-SLEDAI score; SLE International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score; disease duration; biomarker levels (anti-dsDNA, complement [C]3/C4); glucocorticoid (GC), immunosuppressant (IS), and antimalarial (AM) use.ResultsOverall, 3086 pts were included (BEL, n=1869; PBO, n=1217). Most were female (94.4%); mean (standard deviation [SD]) age was 37.0 (11.6) years. Mean (SD) SLE duration was 6.4 (6.4) years.At Wk 52, in the overall population, significantly more BEL vs PBO pts were SRI-4 responders (Figure 1). A significantly greater proportion of SRI-4 responders was observed with BEL vs PBO as early as Wk 8 (38.4% vs 33.3%; odds ratio, OR [95% confidence interval, CI] 1.25 [1.07, 1.46]; p=0.0060), which continued to increase to Wk 52 (54.8% vs 41.6%; OR [95% CI] 1.70 [1.46, 1.98]; p<0.0001). At Wk 52, more BEL vs PBO pts had a 4-point reduction in SELENA-SLEDAI (56.3% vs 43.1%; OR [95% CI] 1.71 [1.47, 2.00]; p<0.0001), no worsening in PGA (76.6% vs 67.9%; OR [95% CI] 1.52 [1.28, 1.79]; p<0.0001), and no new BILAG 1A/2B organ domain scores (77.1% vs 69.4%; OR [95% CI] 1.47 [1.25, 1.74]; p<0.0001). Pts on BEL were 52% more likely to experience an SRI-4 response that was maintained through Wk 52 (hazard ratio, HR [95% CI] 1.52 [1.36, 1.69]; p<0.0001).Figure 1.SRI-4 response at Wk 52 in the overall population and by BL characteristic subgroups.*OR (95% CI) and p-value are from a logistic regression model for BEL vs PBO comparison with covariates of treatment group, study and BL SELENA-SLEDAI score (≤9 vs ≥10)SRI-4 response rates were significantly higher with BEL vs PBO in most subgroups, with the highest response rates observed in pts with SELENA-SLEDAI score of ≥10, low C3 and/or C4 + anti-dsDNA ≥30 IU/ml, and low C3 and/or C4 at BL (Figure 1).ConclusionSignificantly more pts receiving BEL had SRI-4 response rates that occurred from Wk 8 and were maintained through Wk 52 compared with pts receiving PBO. The efficacy of BEL was consistent across multiple pt subgroups, with higher response rates in pts with SELENA-SLEDAI scores of ≥10, low C3 and/or C4 + anti-dsDNA ≥30 IU/ml and low C3 and/or C4 at BL. These results further substantiate the benefits of BEL in the treatment of adults with SLE.References[1]GlaxoSmithKline. Benlysta US prescribing information. 2021[2]Furie R, et al. Arthritis Rheumatol 2011;63(12):3918–30[3]Navarra SV, et al. Lancet 2011;377(9767):721–31[4]Stohl W, et al. Arthritis Rheum 2017;69(5):1016–27[5]Zhang F, et al. Ann Rheum Dis 2018;77(3):355–63[6] Ginzler E, et al. Arthritis Rheum 2021; doi: 10.1002/art.41900AcknowledgementsThis analysis was funded by GlaxoSmithKline (GSK). Medical writing support was provided by Lulu Hill, MPharmacol, Fishawack Indicia Ltd. UK, part of Fishawack Health, and was funded by GSK.Disclosure of InterestsMichelle A Petri Consultant of: GSK, Grant/research support from: GSK, George Bertsias Speakers bureau: Pfizer, Aenorasis, UCB, Novartis, Lilly, SOBI, Consultant of: Novartis, GSK, AstraZeneca, Grant/research support from: GSK, Pfizer, Mark Daniels Shareholder of: GSK, Employee of: GSK, Norma Lynn Fox Shareholder of: GSK, Employee of: GSK, Bevra H. Hahn Consultant of: UCB, GSK, Anne Hammer Shareholder of: GSK, Employee of: GSK, Julia Harris Shareholder of: GSK, Employee of: GSK, Holly Quasny Shareholder of: GSK, Employee of: GSK, Chiara Tani Speakers bureau: GSK, AstraZeneca, Anca Askanase Consultant of: AstraZeneca, Aurinia Pharmaceuticals Inc., Amgen, AbbVie Inc., BMS, GSK, Grant/research support from: AstraZeneca, Eli Lilly and Company, GSK, Idorsia Pharmaceuticals Ltd, Janssen Pharmaceuticals, Pfizer
20
Merli, Michele, Michele Spina, Stefano Luminari, Claudia Basilico, Clara Targhetta, Carlo Visco, Alessandro Levis, et al. "Prognostic Models to Predict Survival In Indolent and Aggressive Non-Hodgkin's Lymphomas Associated with Hepatitis C Virus Infection: a Multicenter Italian Study on 1,043 Patients." Blood 116, no. 21 (November 19, 2010): 2821. http://dx.doi.org/10.1182/blood.v116.21.2821.2821.
Full textAbstract:
Abstract Abstract 2821 Epidemiological studies demonstrated that HCV is associated with B-cell NHL. A precise prognostication of HCV+ NHL is not available; in particular, the impact of liver toxicity on the outcome of pts treated with (immuno)-chemotherapy is not fully clarified. Aim of the present study was to analyse clinical and virological characteristics, toxicity and prognosis of a large series of indolent and aggressive HCV+ NHL. We studied 1,043 pts with HCV+ NHL diagnosed and treated from January 1993 to December 2009 in 15 italian hematologic institutions; 539 cases were aggressive NHL (522 DLBCL) and 504 indolent NHL (265 MZL). All pts were HIV negative, 3% carried HBsAg and 91% were HCV-RNA+. Thirteen out of 56 HCV-RNA negative pts cleared HCV by means of antiviral therapy before NHL diagnosis. An (immuno)-chemotherapy regimen was administered as first-line treatment in 859 pts: 537 received CHOP-like regimen (+ Rituximab 243), 66 III generation regimen, 174 alkylators, 30 purine analogues, 31 other regimens, 21 R alone. Doses of chemotherapy since first cycle were reduced in 31% of pts. A watch-and-wait policy was adopted in 82 pts, other treatments in 68 pts and anti-HCV antiviral therapy in 34 pts with indolent NHL (12 of whom obtained both a complete virologic and hematologic response). Hepatic toxicity was evaluable in 597 patients: among 347 pts with normal ALT at NHL diagnosis, 52 (15%) developed WHO hepatic toxicity ≥ grade 2; among 250 pts (42%) with abnormal ALT, 26 (11%) experienced ALT increase >3.5 times baseline value. Overall, a significant liver toxicity developed in 78 pts (13%) (15% of aggressive NHL and 10% of indolent NHL). Use of Rituximab was not associated with significant liver toxicity (p=0.4); particularly, in DLBCL, R-CHOP and CHOP showed the same rate of significant hepatic toxicity (15%, p=ns), although maximum grade of liver toxicity was registered earlier in patients treated with R-CHOP than in those treated with CHOP (before 3rd cycle respectively in 57% vs 41%, p=0.006). Planned treatment was not completed in 134 pts (29 for liver toxicity). After a median F-UP of 2.6 years, 321 pts died (24 for liver failure). 5-yrs OS was 76% for indolent NHL and 62% for DLBCL. In indolent NHL, the parameters associated with a shorter OS in univariate analysis were: elevated LDH (p<0.001), ECOG ≥2 (p<0.001), AA stage III-IV (p=0.04), age > 60 yrs (p<0.001), B symptoms (p<0.001), serum albumin <3.5 g/dl (p<0.001), Child score (p=0.003), HCV-RNA >106 UI/ml (p<0.02), no antiviral therapy at any time (p<0.001). According to a forward stepwise multivariate Cox regression analysis on OS the following parameters retained statistical significance: ECOG ≥2 (HR 2.82, p=0.005), age > 60 yrs (HR 2.11, p=0.02), AA stage III-IV (HR 2.0, p=0.04), no antiviral therapy at any time (HR 2.56, p=0.01). In DLBCL, the parameters associated with a shorter OS in univariate analysis were: elevated LDH (p<0.001), ECOG ≥2 (p<0.001), AA stage III-IV (p<0.001), age > 60 yrs (p=0.003), liver involvement by lymphoma (p=0.02), B symptoms (p<0.001), serum albumin <3.5 g/dl (p<0.001), INR >1.7 (p=0.01), Child score (p<0.001), HCV-RNA >106 UI/ml (p<0.001), HBsAg+ (p=0.01), HAI grade >9 and/or fibrosis stage >2 at liver biopsy (p=0.03). Moreover IPI, aaIPI and R-IPI were predictive for OS (p<0.001). According to a forward stepwise multivariate Cox regression analysis on OS the following parameters retained statistical significance: ECOG ≥2 (HR 3.12, p=0.001), HCV-RNA >106 UI/ml (HR 3.59, p=0.001), serum albumin <3.5 g/dl (HR 2.53, p=0.01), while other IPI factors (age, AA stage, LDH, extranodal sites) were excluded from the final model. We combined the 3 factors significantly associated to a worse OS (ECOG, albumin, HCV-RNA load) in a new HCV Prognostic Score (HPS) able to discriminate 3 categories of risk (low=0; intermediate=1; high risk ≥2 factors) (p<0.001) (Fig. 1). After adjusting by IPI in multivariate Cox regression analysis, the HPS retained prognostic effect (p<0.001), while IPI itself did not. In conclusion, a significant proportion of pts with HCV+ NHL, when treated with conventional (immuno)-chemotherapy, develops severe liver toxicity. In indolent NHL, employment of antiviral therapy at any time during lymphoma history ameliorates OS. In HCV+ DLBCL, addition of rituximab to CHOP scheme does not increase hepatic toxicity; moreover, the new score HPS performs better than IPI in discriminating different risk categories. Disclosures: No relevant conflicts of interest to declare.
21
Ataniyazov, Kh, G. Khamidullaeva, G. Abdullaeva, A. Abdullaev, A. Kevorkov, and D. Zakirova. "Clinical and Genetic Features of Uncontrolled, Complicated Arterial Hypertension in Hypertensive Patients of the Aral Sea Region." International Journal of Biomedicine 12, no. 3 (September 5, 2022): 360–66. http://dx.doi.org/10.21103/article12(3)_oa2.
Full textAbstract:
The purpose of this study was to assess the clinical and genetic features of the course of hypertension, complicated by a hypertensive crisis in the inhabitants of the Aral Sea region. Methods and Results: The study included 132 patients (52 men and 80 women) with AH who applied at least 5 times (4.9±2.4) during 1 year to the Nukus Emergency Medical Care Center with a diagnosis of “Uncomplicated hypertensive crisis.” The mean age of the patients was 57.2±11.6 years, the mean duration of AH ‒ 8.85±3.4 years. The control group consisted of 50 healthy people (mean age of 52.7±6.4 years), women and men in equal proportions. A cardio Hypertension Panel of multiplex RT-PCR assay was used to detect 4 SNP [ADD1 rs4961 (G460T), GNB3 rs5443 (C825T), AGT rs4762 (C521T), and AGT rs699 (T704C)]. To assess the strength of the association between a genetic marker and AH, measured by the OR, we used multiplicative and additive models. According to the results of office BP measurement, the average SBP corresponded to AH Grade 3 (200.8±22.6 mmHg), and DBP corresponded to AH Grade 2 (105.4±7.62 mmHg). All AH patients, regardless of gender, were diagnosed with left ventricular hypertrophy and increased carotid intima-media thickness. Microalbuminuria was detected in 89 (67.4%) patients, proteinuria in 39 (29.6%) patients. Among AH patients, 88% had a high salt taste sensitivity threshold (STST) and 12% had a medium STST (χ²=269.455, P=0.0001). Analysis of the multiplicative and additive models for the AGT rs699 (Т704С) SNP showed a significant risk of AH with the carriage of the T allele (OR=3.70, 95% CI: 1.88-7.26, P=0.000) and the homozygous TT genotype and heterozygous CT genotype (OR=12.55, 95% CI: 0.72-218.80, P=0.000, and OR=2.67, 95% CI: 1.24-5.74, P=0.000, respectively). At the same time, the carriage of the C allele and CC genotype may be protective against the development of AH in individuals of the Aral Sea region. Analyzing the additive models, we also found a significant risk of AH with the carriage of the homozygous CC genotype of the AGT rs4762 (C521T) SNP (OR=5.92, 95% CI: 2.78-12.63, P=0.000). For the ADD1 rs4961 (G460Т) SNP and the GNB3 rs5443 (C825T) SNP, we did not find associations with the risk of AH. The presence of ethnic differences in the prevalence and associative links of AH candidate genes with the development of the salt-sensitivity phenotype require further extended searches in this direction, especially in the Aral Sea region.
22
Drewniak, Sabina Elżbieta, and Łukasz Drewniak. "The influence of the type of graphite on the size of reduced graphene oxide." Photonics Letters of Poland 14, no. 2 (July 1, 2022): 34. http://dx.doi.org/10.4302/plp.v14i2.1153.
Full textAbstract:
Reduced graphene oxide is a very attractive material for sensor applications. It exhibits high conductivity at room temperature and high specific surface area. Since it can be produced in many ways, its properties can be influenced by the fabrication method. In this paper, we investigated the influence of graphite precursors (flake, scalar and synthetic) on the size of reduced graphene oxide. We have shown that the size of the precursor determines the size of the obtained rGO. We have noted that the larger graphite size, the larger rGO size. Full Text: PDF ReferencesR. Peng, Y. Li, T. Liu et al., "Reduced graphene oxide/SnO2@Au heterostructure for enhanced ammonia gas sensing", Chem. Phys. Lett., 737, 136829 (2019). CrossRef S. Pei and H. M. Cheng, "The reduction of graphene oxide", Carbon N. Y., 50, 9 (2012). CrossRef N. Sharma, V. Sharma, R. Vyas et al., "A new sustainable green protocol for production of reduced graphene oxide and its gas sensing properties", J. Sci. Adv. Mater. Devices, 4, 3 (2019) CrossRef R. Tarcan, O. Todor-Boer, I. Petrovai, C. Leordean, S. Astilean, I. Botiz, "Reduced graphene oxide today", J. Mater. Chem. C, 8, 4 (2020). CrossRef X. Jiao, Y. Qiu, L. Zhang, and X. Zhang, "Comparison of the characteristic properties of reduced graphene oxides synthesized from natural graphites with different graphitization degrees", RSC Adv., 7, 82 (2017). CrossRef J.A. Quezada-Renteria, C.O. Ania, L.F. Chazaro-Ruiz, J.R. Rangel-Mendez, "Influence of protons on reduction degree and defect formation in electrochemically reduced graphene oxide", Carbon N. Y., 149 (2019). CrossRef H. Gao, Y. Ma, P. Song, J. Leng, Q. Wang, "Characterization and cytocompatibility of 3D porous biomimetic scaffold derived from rabbit nucleus pulposus tissue in vitro", J. Mater. Sci. Mater. Electron., 32, 8 (2021). CrossRef A.T. Lawal, "Graphene-based nano composites and their applications. A review", Biosens. Bioelectron., 141, 111384, (2019). CrossRef E. Aliyev, V. Filiz, M.M. Khan, Y.J. Lee, C. Abetz, V. Abetz, "Structural Characterization of Graphene Oxide: Surface Functional Groups and Fractionated Oxidative Debris", Nanomaterials, 9, 8 (2019). CrossRef S. Sali, H.R. Mackey, A.A. Abdala, "Effect of Graphene Oxide Synthesis Method on Properties and Performance of Polysulfone-Graphene Oxide Mixed Matrix Membranes", Nanomaterials, 9, 5 (2019). CrossRef G. Lu, L.E. Ocola, J. Chen, "Reduced graphene oxide for room-temperature gas sensors", Nanotechnology, 20, 44 (2009). CrossRef C. Botas, P. Alvarez, C. Blanco et al., "Critical temperatures in the synthesis of graphene-like materials by thermal exfoliation–reduction of graphite oxide", Carbon N. Y., 52, 2013. CrossRef
23
Abdul Razzack, A., S. Abdul Razzack, P. Shenasan, N. Shenasan, S. Mishra, R. Zarrar, J. Pablo Sosa, et al. "POS0701 ANIFROLUMAB, AN ANTI-INTERFERON-Α RECEPTOR MONOCLONAL ANTIBODY IN SYSTEMIC LUPUS ERYTHEMATOSUS- A META ANALYSIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 600.1–600. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2782.
Full textAbstract:
Background:Type I interferons such as Anifrolumab have been implicated in Systemic lupus erythematosus (SLE) pathogenesis on the basis of increased interferon-stimulated gene expression and genetic susceptibility. Little is known regarding its efficacy and safety profile.Objectives:To assess the efficacy and safety of Anifrolumab in patients with SLE.Methods:Electronic databases (PubMed, Embase, Scopus, Cochrane) were searched from inception until December 15th, 2020. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p<0.05. The primary outcome of interest was British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). Secondary outcomes included the proportion of patients who achieved an SLE responder index of 4 (SRI-4) reduction of 50% or more in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), reductions in the glucocorticoid dose and adverse effects.Results:A total of three studies1,2,3 with 839 participants (Anifrolumab=372, Placebo=467) were included in our analysis. Follow-up duration was at week 52. A statistically significant different was observed in the Anifrolumab arm in terms of BICLA response (OR 0.44 95%CI 0.34-0.59;p < 0.00001, I2=4), ≥50% reduction in CLASI activity score (OR 0.36 95%CI 0.21-0.60;p=0.0001, I2=0), glucocorticoid reduction (OR 0.41 95%CI 0.28-0.59;p<0.00001; I2=0) and SRI-4 response (OR 0.52 95% CI 0.30-0.90; p=0.02, I2=75). However, Adverse events were less likely in the placebo arm as compared to Anifrolumab (OR 1.54 95%CI 1.05-2.25; p=0.03; I2=0).Conclusion:Anifrolumab was found to be more effective than placebo for the management of SLE, but may also cause more severe adverse effects.References:[1]Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, Bae SC, Brohawn PZ, Pineda L, Berglind A, Tummala R; TULIP-2 Trial Investigators. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020 Jan 16;382(3):211-221. doi: 10.1056/NEJMoa1912196. Epub 2019 Dec 18. PMID: 31851795.[2]Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, Illei GG, Drappa J, Wang L, Yoo S; CD1013 Study Investigators. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017 Feb;69(2):376-386. doi: 10.1002/art.39962. PMID: 28130918; PMCID: PMC5299497.[3]Furie RA, Morand EF, Bruce IN, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol 2019; 1(4):e208-e219.Disclosure of Interests:None declared
24
Day, Nancy, Janet Ayello, Ian Waxman, Evan Shereck, Catherine McGuinn, Carmella van de Ven, Megan S. Lim, Sherrie L. Perkins, and Mitchell S. Cairo. "Inhibition of DLEU1 Following siRNA Transfection in Burkett’s Lymphoma (BL): Implication for Tumor Repressor Role of DLEU1 in C-Myc-Activated BL Lymphomagenesis." Blood 112, no. 11 (November 16, 2008): 5335. http://dx.doi.org/10.1182/blood.v112.11.5335.5335.
Full textAbstract:
Abstract Background: The progress of childhood BL and DLBCL has improved dramatically in the past three decades; however, patients with a 13q-deletion have a significantly poorer outcome (Cairo/Patte et al Blood, 2007 and Patte/Cairo et al Blood, 2007; Poirel/Cairo et al Leukemia 2008). DLEU1, a potential tumor suppressor gene, is located within the 13q-deletion. DLEU1 was reported to be a key gene in the Burkitt classifier genes (Dave/Staudt et al NEJM, 2006) and c-myc binds to the promoter region of DLEU1. DLEU1-network proteins include, among others, E3 ubiquitin-protein ligase (UBR1), Tubulin beta-2C (TUBB2C) and RASSF1A. We previously demonstrated that UBR1, TUBB2C, and RASSF1A, were differentially expressed in BL vs DLBCL patients and cell lines by global gene profiles and real time RT-PCR studies (Day/Cairo et al AACR 2008; Day/Cairo et al ICML 2008). We further demonstrated decreased expression of UBR1 (33.2±4.5% reduction compared to control (p<0.02)) and TUBB2C (30.0±3.5% reduction compared to control (p<0.001)) by DLEU1 gene siRNA knock down, while expression of RASSF1A was not changed (Day/Cairo, et al SIOP 2008). Taken together, these data suggest the hypothesis that DLEU1 interacting with UBR1 may interfere with microtubule function, and therefore act as a tumor repressor in c-myc-activated BL lymphomagenesis, by arrest of the cell cycle at G2/M and subsequent inducion of apoptosis. Objective: In this study, we investigated the role of DLEU1 in regulation of apoptosis in BL by inhibition of DLEU1 gene expression by a DLEU1 siRNA and evaluated it effects on the apoptotic rate in a BL cell line. Methods: The Ramos BL cell line was transiently transfected with a 25-nucleotide modified DLEU1 siRNA (5′-AUACUUGGCAUGAAUGAACUUAUGU-3′ and 3′-UAUGAACCGUACUUACUUGAAUACA-5′). Stealth RNAi whose GC content is similar to that of this DLEU1 siRNA was used as negative control. The transient transfection of DLEU1 siRNA (10 – 20 nM) was achieved using Lipofectamine RNAiMAX. The transfection efficiency of siRNA was evaluated using Alexa Fluor Red Fluorescent Oligo. DLEU1 contents were measured by qRT-PCR with ddCt relative quantitative determination. GAPDH was used as endogenous control. Statistical analysis was conducted by one-way analysis of variance (ANOVA) followed by Tukey-Kramer multiple comparisons test. To determine the early and late stages of apoptosis, we transfected Ramos BL cells with DLEU1 siRNA, and then incubated cells with Annexin V-FITC and Propidium Iodide for 15 minutes, respectively (BD Pharmingen), followed by FACS using BD LSRII with FACSDiva. Results: The DLEU1 siRNA decreased the expression of DLEU1 RNA (52±13%; p<0.0006). The transfection efficiency of siRNA was 85 – 90%. Comparing to untreated cells, DLEU1 siRNA treatment significantly reduced early apoptosis (16.90±0.37%; p<0.001) and late stage apoptosis (14.70±0.27%; p<0.0001). Conclusion: These results suggest that when DLEU1 gene expression is decreased in BL cells, there is a significant reduction in both early and late apoptosis. The results strongly support a relationship between DLEU1 gene and regulation of BL apoptotic mechanisms. In concert with previous investigations, this data suggests that DLEU1 may function as a tumor growth repressor via UBR1 and TUBB2C-regulated mechanism in the cellular apoptotic process. Since c-myc binds promoter region of DLEU1 and these two genes are a part of the c-myc signaling network, this further underscores the importance of DLEU1 and its network proteins may play in c-myc-activated BL lymphomagenesis.
25
Holle, Julia U., Christin Dubrau, Karen Herlyn, Martin Heller, Petra Ambrosch, Bernhard Noelle, Eva Reinhold-Keller, and Wolfgang L. Gross. "Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations." Annals of the Rheumatic Diseases 71, no. 3 (October 21, 2011): 327–33. http://dx.doi.org/10.1136/ard.2011.153601.
Full textAbstract:
ObjectiveFirst, to investigate the overall efficacy and safety of rituximab (RTX) in refractory granulomatosis with polyangiitis (GPA) in a tertiary referral centre. Second, to compare the efficacy of RTX in granulomatous and vasculitic manifestations in GPA.Patients and methodsThis study comprised a retrospective, standardised data collection from all patients who received RTX for refractory Wegener's granulomatosis from 2002 to 2010. Patients were assessed by a standardised interdisciplinary diagnostic procedure (including ear, nose and throat and ophthalmology assessment, MRI, immunodiagnostics, B-cell levels and Birmingham Vasculitis Activity Score) and were treated by standardised therapeutic regimens according to available evidence.Results59 patients received 75 cycles of RTX. 9.3% achieved complete remission. A response was documented in 61.3% (improvement in 52%, unchanged disease activity in 9.3%), 26.7% had refractory disease. Birmingham Vasculitis Activity Score, disease extent index, erythrocyte sedimentation rate, C-reactive protein and prednisolone demand decreased significantly. All patients achieved B-cell depletion. Granulomatous manifestations such as orbital granuloma and pachymeningitis were more frequently refractory to RTX than vasculitis or other granulomatous manifestations. Thus, for example, complete remission/improvement was found in 89.2% of patients with renal disease and in only 44.4% of those with orbital masses (p=0.003). The relapse rate was 44.4% after a median period of 13.5 months. Adverse events occurred in 29%, pneumonia in 15% and death in 3%.ConclusionThe overall response rate of refractory GPA to RTX was high (61.3% complete remission or improvement). Response rates of vasculitic manifestations were excellent; failure of response/progress was mostly due to granulomatous manifestations, especially orbital masses. Relapse rates were high (40%) despite maintenance treatment.
26
Yin, Changhong, Tae-Hoon Chung, Janet Ayello, Tae-Hyun Park, Carmella van de Ven, Mitchell S. Cairo, and Sanghoon Lee. "Overexpression Of Deleted In Lymphocytic Leukemia 1 (DLEU1) Significantly Induces Programmed Cell Death and Inhibits Cell Proliferation In Primary Mediastinal B-Cell Lymphoma (PMBL): DLEU1 May Be a Tumor Suppressor Gene In a Subset Of Patients With PMBL." Blood 122, no. 21 (November 15, 2013): 3852. http://dx.doi.org/10.1182/blood.v122.21.3852.3852.
Full textAbstract:
Abstract Background Primary Mediastinal large B-cell lymphoma (PMBL) is a rare form of Non Hodgkin Lymphoma (NHL) representing 2% of mature B-cell non-Hodgkin lymphoma in patients less than 18 years of age (Lones/Cairo et al., JCO, 2000; Burkhardt et al., BJH, 2005). PMBL has similar histo-pathological features along the biologic spectrum between Diffuse Large B-Cell Lymphoma (DLBCL) and classical HL (cHL) (Abramson et al., Blood, 2005). We have recently reported that a significantly decrease in EFS among children and adolescent PMBL patients compared with other stage III non-PMBL pediatric DLBCL patients following FAB/LMB96 therapy, suggesting that children and adolescent PMBL may be an inherently different B-NHL (Gerrard/Cairo et al., Blood, 2013). Nevertheless, the genetic mechanisms underlying the pathogenesis of PMBL remain unknown. Using high-resolution, microarray-based genomic techniques chromosomal losses at 13q14 was identified in 5 of the 37 (13%) PMBL tumor samples indicating localization of potential tumor suppressor genes at 13q that may be involved in the etiology of PMBL (Wessondorf, et al, Leuk., 2007). DLEU1 (Deleted in lymphocytic Leukemia 1) is a Burkitt lymphoma (BL) classifier gene (Dave et al., NEJM, 2006) and is located in the chromosome 13q14.3 region. DLEU1 interacts with 19 proteins including of c-Myc, RASSF1, TUBB2C and UBR1. DLEU1 has been implicated as a tumor suppressor in BL (Lee/Yin/Cairo et al., ASH, 2012) and in chronic lymphocytic leukemia (Garding et al., Plos Genet., 2013). Objectives We hypothesize that DLEU1 may act as a tumor suppressor gene through induction of caspase-3/7 activity thereby inhibiting cell proliferation and down-regulation of constitutively activated signaling pathways in PMBL. Methods The full length of cDNA encoding DLEU1 was fused into pEGFP-N3 vector and pEGFP-DLEU1fusion construct (Lee/Yin/Cairo et al., ASH, 2012) was transfected into Karpas-1106P cells using Amaxa Nucleofector kit, followed by the manufacturer’s instruction. Forty-eight hours post transient transfection, total RNA was extracted and 1ug of total RNA was used for cDNA synthesized as above. For comparison of mRNA expression of network genes, quantitative RT-PCR was performed by CFX96 Real-time (Bio-rad). The expression of DLEU1 protein in DLEU1 transient transfected Karpas-1106P cells was confirmed both by western blotting analysis and under fluorescent microscope. In brief, the total lysates was prepared from DELU1 transfected cells at 48hours post-transfection, and membrane was hybridized with Rabbit polyclonal DLEU1 antibody (ProteinTech) on immune blotting. MTS (Promega) and Caspase 3/7 assay (Promega) were employed to examine the effects on cell proliferation and apoptosis. Statistical significance was determined by one tailed paired Student t-test. Results The expression of DLEU1 mRNA in DLEU1 transiently transfected Karpas-1106P (DLEU1-Karpas) cells was significantly higher than empty vector alone transfected cell as mock control (78-fold increase, p<0.01). Comparing mRNA expression of DLEU1 network genes in DLEU1-Karpas cells to mock control cells, we observed a significant decrease in mRNA expression of the anti-apoptotic gene, Bcl-xL (73% reduction, p<0.01) and suppressors of cell signaling genes, SOCS1 and SOCS3 (52% reduction, p<0.05 and 44% reduction, p<0.01, respectively). There was a significant reduction in the mRNA expression of oncogenes, Pim-1 and c-Myc (72% reduction, p<0.04 and 54% reduction, p<0.03) respectively, in DLEU1-Karpas cells compared to mock control cells. Cell proliferation was significantly inhibited 18% (p<0.03) whereas Caspase 3/7 activity was significantly increased 1.5-fold (p<0.03) in DLEU1-Karpas cells at 48hours post transfection. Lastly, we found significant decreases of protein expression in phoshpho-Akt (67% reduction, p<0.01), phoshpho-ikBa (48% reduction, p<0.02), phoshpho-STAT3 (15% reduction, p<0.02) and c-Myc (25% reduction, p<0.01), respectively in DLEU1-Karpas cells. Conclusions We demonstrated that transient overexpression of DLEU1 1) significantly inhibits cell proliferation and induces programmed cell death, and 2) downregulates constitutively activated signaling pathways in PMBL, and therefore, DLEU1 may in part act as a tumor suppressor gene in a subset of patients with PMBL. Disclosures: No relevant conflicts of interest to declare.
27
Lal, Ashutosh, Nancy Sweeters, Matt Herz, Dru Foote, Lynne Neumayr, Greg Kurio, Paul R. Harmatz, and Elliott P. Vichinsky. "Safety of Combined Chelation Therapy with Deferasirox and Deferoxamine in Transfusion-Dependent Thalassemia." Blood 114, no. 22 (November 20, 2009): 2021. http://dx.doi.org/10.1182/blood.v114.22.2021.2021.
Full textAbstract:
Abstract Abstract 2021 Poster Board I-1043 Therapeutic regimens that combine two chelators have the potential to improve iron excretion while avoiding toxicities associated with high doses of single agents. This pilot study was designed to explore the safety of the combined treatment with deferasirox (DFX) and deferoxamine (DFO) in individuals with transfusion-dependent thalassemia and iron overload who had failed standard therapy. Subjects underwent baseline evaluation of liver iron, cardiac iron, cardiac function and target organ damage, and were enrolled in 3 groups (n=5 in each group) - Group B: adults with liver iron concentration (LIC) >15 mg/g dry weight, group A: adults with LIC >5 and <15 mg/g plus iron-related organ dysfunction, and Group C: children between 8-18 years with LIC >5 mg/g dry weight plus iron related organ dysfunction. The duration of therapy was 52 weeks, with DFX (20-30 mg/Kg) given daily and (DFO 35-50 mg/Kg/infusion) given for 3-5 days/week (groups A and C), or 5-7 days/week (group B). Subjects were monitored for hepatic and renal toxicity, visual or auditory changes, and development of new symptoms. Changes in serum ferritin, LIC (ferritometer), cardiac function (MRI) and myocardial iron (MRI T2*) were monitored. We have enrolled 14 subjects (target 15 subjects) with a median follow up of 29 weeks (range 18-52). The mean daily dose of DFO was 16, 33, and 17 mg/Kg/day for groups A, B and C, respectively, at the start of the study. The corresponding mean DFX dose was 21, 25 and 22 mg/Kg/day. At the end of 26 weeks, the mean LIC (mg/g dry wt) in evaluable patients declined from 13.0 (3.9-21.7) to 10.6 (0.60-18.3, p=0.015), and the mean ferritin (ng/mL) fell from 2631 (1000-5230) to 2158 (319-5845, p=n.s.). Cardiac evaluation revealed that mean MRI T2* (msec) improved from 22.7 (6.7-32.6) to 25.5 (10.7-38.1) and the mean LVEF (%) from 63.4 (47.5-68.5) to 64.3 (53.4-72.2), but these changes were not statistically significant. No subject developed evidence of significant myocardial iron (T2* <20 msec) loading during the trial. Elevation of serum creatinine or ALT was not observed in any subject. One subject from group B died 9 weeks after start of therapy from sepsis. One subject interrupted DFX therapy because of abdominal pain. In all other cases the treatment was well tolerated and no dose adjustment or suspension of therapy was required owing to toxicity. Protocol mandated modification of treatment (temporary cessation of DFX) occurred in two subjects resulting from a marked fall in serum ferritin and LIC. This suggests that simultaneous administration DFX and DFO at these doses is well tolerated and has low potential for toxicity. From these preliminary data, this combination seems to be effective in lowering body iron in high-risk patients. A larger clinical trial will be needed to assess the benefits of long-term combined chelation therapy on iron balance and end-organ damage in chronically transfused patients with thalassemia. Disclosures: Lal: Novartis: Research Funding. Harmatz:Novartis: Research Funding. Vichinsky:Novartis: Consultancy, Research Funding.
28
Yesilipek, M. Akif, Gulsun Karasu, Zuhre Kaya, Baris B. Kuskonmaz, Vedat Uygun, Ilkiz Dag, Asli Birkent, and Mehmet Ertem. "Interim Results from a Phase 2, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with Beta-Thalassemia Major." Blood 126, no. 23 (December 3, 2015): 959. http://dx.doi.org/10.1182/blood.v126.23.959.959.
Full textAbstract:
Abstract Introduction: Hematopoietic stem cell transplantation (HSCT) is being increasingly used as curative therapy for severe disorders of the hematopoietic system and transfusional iron overload (TIO) contributes considerably to treatment-related morbidity and mortality after HSCT. Management of iron overload in the post-HSCT setting may be complicated since the use of therapeutic phlebotomies is often not feasible due to ongoing anemia and compliance to deferoxamine is low. Studies that evaluate the safety dose of deferasirox (DFX), which is the most commonly used chelation therapy, in this setting are limited. Purpose & Methods: This is a prospective, phase 2, multicenter, single-arm study to evaluate the efficacy and safety of iron chelation with oral DFX in beta-thalassemia major (TM) patients who have undergone HSCT. The study was conducted in 7 centers from Turkey. The primary objective was to evaluate if DFX could provide clinically safe chelation in a target pool of 26 pediatric patients with TIO within a minimum of 6 months and maximum of 2 years after related/unrelated HSCT. Patients had to be transfusion-independent and have iron overload at screening defined by serum ferritin (SF) of >1000 μg/L or cardiac MRI T2* <20 ms or liver iron concentration (LIC, by MRI R2) of ≥5 mg/g. The study included male and female TM patients ≥2 to <18 years old who had undergone HSCT with a washout period from immunosuppressive therapy of at least 3 months. Patients received DFX at an initial dose of 10 mg/kg/day with up titration every 3 months by 5 mg/kg/day per investigator judgment to a maximum of 20 mg/kg/day. Therapy continued for 52 weeks or until SF reached below 500 μg/L. Aside from AE monitoring, assessments were undertaken at baseline and every 28 days (unless closer assessments were need for dose initiation and adjustment) and included complete blood counts, biochemistry and urinalysis, and SF. MRI assessment of liver (R2) and cardiac (T2*) iron were also conducted at baseline and 52 weeks. Results: Interim data from the first 18 of 26 patients (mean age 8.3 years, 66.7% males) who completed 12 months follow up are presented in this analysis. A total of 97 AEs were recorded in the 18 patients. The majority of AEs were of Grade I (n=57) or II (n=34) severity. Five (5.2%) were suspected to be related to study drug and 6 AEs (6.2%) were considered serious. Five (5.2%) AEs resulted in study drug temporary interruption or dose adjustment, 2 (2.1%) required hospitalization, 54 (55.7%) required concomitant medication, while 36 (37.1%) had no action taken. Three patients had dose decrease due to AEs. The dose was re-escalated up to 20 mg/kg/day after the AEs resolved. In total, 11 (61.1%) patients achieved 20 mg/kg/day. Only one patient dropped out due to progressive ALT increase. Median ALT level decreased from 26 IU/L (range: 10-117) at baseline to 18 IU/L (range: 9-101) at week 52. The median SCr was similar at baseline 0.4 mg/dL (range: 0.2-0.6) and week 52 0.4 mg/dL (range: 0.2-0.8). Median cystatin C was similar at baseline 0.7 mg/mL (range: 0.6-0.9) and week 52 0.7 mg/mL (range: 0.5-1.1) (Figure 1A-B). Five patients had proteinuria at baseline and increased proteinuria compared to previous visit by dipstick analysis was described in 7 (38.9%) patients, irrespective of DFX dose by 52 weeks. No patient with proteinuria required any dose adjustments by 52 weeks. SF significantly and consistently decreased throughout the 52 weeks from a median of 1752.3 μg/L (range: 873.7-2716) to 915.2 μg/L (range: 250.1-2740), p<0.001 (Figure 2). At week 52, 6 (33.3%) patients had reached SF <500 μg/L. LIC also significantly decreased from a median of 9.9 mg/g (range: 4.8-43) to 4.1 mg/g (range 0.9-8.5), p<0.001. Cardiac T2* increased from a median of 26.1 ms (range: 18.7-41) to 28.8 ms (18.5-44), p=0.605. Conclusions: Our preliminary results showed that DFX up to 20 mg/kg/day is safe and effective in reducing iron burden for TM patients following HSCT. This was evident through significant reductions of systemic, hepatic and cardiac iron overload. Final data from the completed study should confirm these findings and establish the role for DFX in this patient population. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Dag: Novartis: Employment. Birkent:Novartis: Employment.
29
Gozalbes-Cravioto, Enrique, and Helena Gozalbes García. "Hallazgos de monedas greco-massaliotas en la provincia de Cuenca (España)." Vínculos de Historia Revista del Departamento de Historia de la Universidad de Castilla-La Mancha, no. 11 (June 22, 2022): 280–95. http://dx.doi.org/10.18239/vdh_2022.11.12.
Full textAbstract:
Publicamos una pequeña serie de monedas, relacionadas con las piezas conocidas inicialmente como de ejemplares “tipo Auriol”. Se trata de varias imitaciones greco-massaliotas, relacionadas con el ciclo numismático griego del Occidente mediterráneo. La importante novedad de las mismas se fundamenta en el lugar de hallazgo, pues este se ha producido en una zona interior de la Península Ibérica, donde hasta el momento no se había documentado el descubrimiento de numismas de este tipo. Palabras clave: moneda, imitaciones, edetanosTopónimos: Massalia, Emporion, AuriolPeriodo: Edetanos ABSTRACTThe text presents a small series of coins, similar to those initially known as "Auriol type". These are various Greek-Massalian imitations, related to the Greek numismatic cycle of the Western Mediterranean. What makes these coins particularly interesting is their place of discovery, since they were found in an inland area of the Iberian Peninsula, where the appearance of specimens of this type had not previously been documented. Keywords: coin, imitations, AuriolPlace names: Massalia, Emporion,Period: edetans REFERENCIASAmorós, J. V. (1934), Les monedes emporitanes anteriors a les dracmes, Barcelona, Gabinet Numismàtic de Catalunya.Arévalo González, A. (2002), “La moneda griega foránea en la Península Ibérica”, en Actas del X Congreso Nacional de Numismática, Madrid, Museo Casa de la Moneda, pp. 1-15.Babelon, E. C. F. (1901), Traité des monnaies grecques et romaine, vol. 1, Paris, Ernest Leroux Editeur.Benezet, J., Delhoeste, J. Lentillon, J.-P. (2003), “Une monnaie du “type d´Auriol” dans la plaine roussillonnaise”, Cahiers Numismatiques, 158, pp. 5-8.Blancard, M. (1870-1871), “Iconographie des monnaies du trésor d´Auriol acquises par le cabinet des médailles de Marseille”, en Mémoires del´Académie des Sciences, Belles-Lettre et Arts de Maseille, Marseille, Barlatier-Feissat Pére et fils, pp. 17-33.Blanchet, A. (1905), Traité des monnaies gauloises, vol. 1, Paris, Ernest Leroux Editeur.Campo Díaz, M. (1987), “Circulación de monedas massaliotas en la Península Ibérica (s. V-IV a. C.)”, en Mélanges offerts au docteur J. B. Colbert de Beaulieu, Paris, Leópard d`or, pp. 175-187.— (1997), “La moneda griega y su influencia en el contexto indígena”, en Historia monetaria de Hispania antigua, Madrid, Jesús Vico, pp. 19-49.— (2002), “Las emisiones de Emporion y su difusión en el entorno ibérico”, La monetazione dei Focei in Occidente, Atti dell´XI Convegno del Centro Internazionale di studi Numismatici, Roma, Istituto italiano di Numismatica, pp. 139-165.— (2003), “Les primeres imatges gregues: l´inici de les fraccionàries d´Emporion”, en VII Curs d´Història Monetaria d´Hispània. Les imatges monètaries: llenguatge i significat, Barcelona, Museu Nacional d´Art de Catalunya, pp. 25-45. Campo Díaz, M. y Sanmartí, E. (1994), “Nuevos datos para ña cronología de las monedas fraccionarias de Emporion: revisión del tesoro Neapolis-1926”, Huelva Arqueológica, 13, pp. 153-172.Chevillon, J. A. (2002), “Les monnaies archaïques d´Emporion dans le trésor d´Auriol”, Bulletin de la Société Française de Numismatique, 57, pp. 30-33.Chevillon, J. A., Bertaud, O. y Guernier, R. (2008), “Nouvelles données relatives au monnayage archaïque massaliète”, Revue Numismatique, 164, pp. 209-244.Chevillon, J. A. Ripollès, P. P. (2014), “The Greeck Far West: un exceptional adaptation of a design from Asia Menor with bull und lion foreparts”, Journal of the Numismatic Association of Australia, 25, pp. 44-46.Chevillon, J. A., Ripollès, P. P. y López, C. (2013), “Les têtes de taureau dans le mnnayage postarchaïque empuritain du V siècle av. J. C.”, OMNI. Revue Numismatique, 6, pp. 10-14. De Saucy, F., De Berthélemy, A. y Hucher, E. (1875), “Examen détaillée du trésor d´Auriol (Bouches-du-Rhone)”, en Mélanges de Numismatique 1, Paris, Le Mans, pp. 12-44.Furtwängler, A. E. (1971), “Remarques sur les plus anciennes monnaies frapées en Espagne”, Schweizer Münzblätter, 81, pp. 13-21.— (1978), Monnaies grecques en Gaule. Le trésor d´Auriol et le monnayage de Massalia 525/520-460 av. J. C., Fribourg.— (2002), “Monnaies grecques en Gaule: nouvelles trouvalles (6ème-5 ème s. av. J.-C.)”, en La monetazione dei Focei in Occidente. Atti dell`XI Convegno del Centro Internazionale di Studi Numismatici, Rome, Istituto italiano di Numismatica, pp. 93-11.García-Bellido, M. P. (1993), Las cecas libio-fenicias, Ibiza, Museu Arqueologic d´Eivissa e Formentera.— (1998), “La moneda griega de Iberia”, en Los griegos en España, Madrid, Ministerio de Cultura, pp. 158-178. — (2017), “Las copias de la moneda Tipo Auriol en el Golfo de León: foceos y nativos”, Gaceta Numismática, 194, pp. 3-14.Gozalbes Cravioto, E. (2014), “La economía monetaria en la provincia de Cuenca en la antigüedad”, E. Gozalbes Cravioto, J. A. Hernández Rubio y J. A. Almonacid Clavería (coords.), Cuenca: historia en sus monedas, Cuenca, Universidad de Castilla-La Mancha, pp. 55-84.— (2017a), “La ceca de Ikalesken y el problema de su localización”, Gaceta Numismática, 193, pp. 3-19.— (2017b), “Una pieza de Urkesken y la localización de la ceca”, Gaceta Numismática, 193, pp. 21-30.Gozalbes Fernández de Palencia, M. y Ripollès, P. P. (2002), “Nuevos hallazgos de monedas foráneas en el territorio de Arse-Saguntum”, en P. P. Ripollès y M. M. Llorens, Arse-Saguntum. Historia monetaria de la ciudad y su territorio, Sagunto, Fundación Bancaja, pp. 528-533.Gozalbes García, H. y Gozalbes Cravioto, E. (2017), “Une obole massaliote datant du Ve siècle av. J. C. sur le territoire de Cuenca (Espagne)”, Bulletin de la Société Française de Numismatique, 72.2, pp. 52-56.Guadán, A. M. (1968), Las monedas de plata de Emporion y Rhode vol. I, Barcelona, Ayuntamiento de Barcelona.— (1970), Las monedas de plata de Emporion y Rhode, vol. II, Barcelona, Ayuntamiento de Barcelona.Lambert, E. (1864), Essai sur la numismatique gauloise du Nord-Ouest de la France, Paris, Derache.Maurel, G. (2013), Corpus des monnaies de Marseille et Provence, Languedoc oriental et vallée du Rhone (520-20 av. notre ère), Montpellier, Omni, 2013.Omos, R. (1995), “Usos de la moneda en la Hispania prerromana y problemas de lectura iconográfica”, en M. P. García-Bellido y R. M. Centeno (eds.), La moneda hispánica. Ciudad y territorio, Madrid, Consejo Superior de Investigaciones Científicas, pp. 41-52.Planas Palau, A. y Martí Mañanes, A. (1991), Las monedas de otras cecas encontradas en Ibiza, Ibiza, Puig Castellar. Ripollès, P. P. (1982), La circulación monetaria en la Tarraconense mediterránea, Valencia, Federico Domenech. — (1985), “Las monedas del tesoro de Morella, conservadas en la B. N de París”, Acta Numismàtica, 19, (1985), pp. 47-64.— (1989), “Fracciones ampuritanas. Estado de la investigación”, Archivo de Prehistoria Levantina, 19,pp. 303-317.— (2005), “Las acuñaciones antiguas de la península Ibérica: dependencias e innovaciones”, en C. Alfaro, C. Marcos y P. Otero (coords.), Actas del XIII Congreso Internacional de Numismática, vol. 1, Madrid, Ministerio de Cultura, pp. 187-208.— (2011), “Cuando la plata se convierte en moneda: Iberia oriental”, en Barter, Money and Coinage in the Ancienr Mediterranean (10th-1st Centuries B.C.). Actas del IV Encuentro Peninsular de Numismátic Antigua, Madrid, Consejo Superior de Investigaciones Científicas, pp. 213-226.— (2013), “Ancient Iberian Coinage”, Documentos Digitales de Arqueología, 2, pp. 1-55.— (2015), “Los divisores ampuritanos con cabeza de carnero y puntos en el campo”, OMNI. Revue Numismatique, 9, pp. 13-16.Ripollès, P. P. Chevillon, J. A. (2013), “The Archaic coinage of Emporion”, The Numismatic Chronicle, 173, pp. 1-21.Ripollès, P. P. y Llorens, M. M. (2002), Arse-Saguntum. Historia monetaria de la ciudad y su territorio, Sagunto, Fundación Bancaja.Rodríguez Casanova, I. (2014), “El tesoro de Valeria: nuevas aportaciones sesenta años después”, en E. Gozalbes, J. A. Hernández Rubio y J. A. Almonacid (coords.), Cuenca: la Historia en sus monedas, Cuenca, Universidad de Castilla-La Mancha, pp. 85-106.Savès, G. (1976), Les monnaies gauloises à la croix, Toulouse, Privat, 1976.Villaronga, L. (1987), “Les oboles massaliotes à la roue et leurs imitations dans la Péninsule Ibérique”, en Mélanges offerts au docteur J. B. Colbert de Beaulieu, Paris, Leópard d`or, 1987, pp. 769-777.— (1995), “L´emissió emporitana amb cap de be i revers de creu puntejada de la segona meitat del segle V a.C.”, Acta Numismática, 25, (1995), pp. 17-33.— (1997), Monedes de plata emporitanes dels secles V-VI a. C., Barcelona, Leandre, 1997.— (2003), “La troballa de l´Emporà”, Acta Numismàtica, 33, pp. 15-46.Villaronga, L. Benages, J. (2011), Ancient Coinage of the Iberian Peninsula. Greek, Punic, Iberian, Roman, Barcelona, Societat Catalana d´Estudis Numismàtics, 2011 (citado como ACIP).
30
Hering, B. J., C. C. Browatzki, A. Schultz, R. G. Bretzel, and K. F. Federlin. "Clinical Islet Transplantation — Registry Report, Accomplishments in the past and Future Research Needs." Cell Transplantation 2, no. 4 (July 1993): 269–82. http://dx.doi.org/10.1177/096368979300200403.
Full textAbstract:
This review provides the results of a recent analysis of the Islet Transplant Registry on clinical adult islet transplants performed worldwide through June 30, 1992. Between December 12, 1893 and June 30, 1992, 167 adult islet transplants were performed at 25 institutions worldwide, including 104 at 9 institutions in North America, 62 at 15 institutions in Europe, and 1 elsewhere. The total number of diabetic patients reported to be insulin independent after adult islet allotransplantation through June 30,1992, was 19. In an analysis by era, the percentage of patients that showed positive basal C-peptide levels (i.e. ≥ 1 ng/mL at ≥ 1 mo) posttransplant, and that became insulin independent (>1 wk) in the 1985-1989 era (n = 35 cases) were 20% and 6%, and in the 1990-1992 era (n = 69 cases) were 64% and 20%, respectively, and thus have improved significantly (p < 0.001 and p < 0.05). For the 1990-1992 period, the percentage of patients who showed positive basal C-peptide levels post-transplant, and who became insulin independent in the single donor pancreas group (n = 31 cases) were 52% and 13%, and in the multiple donor pancreata group (n = 36 cases) were 75% and 28%, respectively. Islet graft function rates were nearly identical for grafts prepared from pancreata stored ≤6 h (n = 27) and >6 ≤ 12 h (n = 29), so that 67% and 72% showed positive basal C-peptide levels, and 30% and 21% of the recipients became insulin independent, respectively. No single patient showed islet graft function sufficient to allow withdrawal from insulin, if the pancreata have been stored for more than 12 h. In regard to recipient category for the six groups, namely IAK (islet after kidney), SIK (simultaneous islet kidney transplantation), SIL (simultaneous islet liver transplantation), SIL(C) (simultaneous islet liver transplantation after cluster operation), SIKL (simultaneous islet kidney liver transplantation), and SIH-L (simultaneous islet heart-lung transplantation), the number of patients who showed positive basal C-peptide levels post-transplant was 11 (58%), 17 (57%), 5 (83%), 8 (80%), 1 (50%), and 0 (0%), and the number of insulin independent patients was 4 (21%), 4 (13%), 0 (0%), 6 (60%), 0 (0%), and 0 (0%), respectively. Comparing the two largest recipient categories, namely IAK and SIK, no difference in the outcome of these transplants was apparent. The only sites of transplantation in the period between 1990-1992 were the liver, epiploic flap, and spleen, with the total number of recipients being 60 (90%), 4 (6%), and 3 (4%), respectively. For these three groups, the number of patients who showed positive basal C-peptide levels was 38 (63%), 2 (50%), and 1 (33%), and the number of insulin independent patients was 13 (22%), 0 (0%) and 0 (0%), respectively. In the overwhelming majority of cases, recipient selection was not based on prospective HLA donor/recipient matching. In different categories of HLA mismatching (i.e., AB-, DR-, BDR-, and ABDR-mismatch) no obvious tendency or difference in outcome could be demonstrated. In the 1990-1992 period, 16 patients (24%) received OKT3, 26 patients (39%) received ALS, ALG, or ATG, and 25 patients (37%) received neither monoclonal nor polyclonal T-cell antibodies for induction immunosuppression. For the three groups mentioned, the number of patients who showed positive basal C-peptide levels was 12 (86%), 16 (62%), and 15 (60%), and the number of insulin independent patients was 2 (14%), 6 (23%), and 6 (24%), respectively. A synopsis of all pretransplant C-peptide-negative Type I diabetic patients who succeeded in insulin independence revealed certain common characteristics, such as transplantations of ≥8000 islet equivalents per kilogram body weight, a purity of transplanted islets ≥ 50% (in all but one case), the liver as implantation site, and OKT3 or ALG/ ALS/ATG for induction immunosuppression (“state of the art” cases). Because it has been unequivocally proven that islet transplantation can be performed successfully in association with other organ transplants, more attention should be drawn to the nonuremic, nonkidney Type I diabetic patients, who have not been reported in a single case since 1990. This is the real target group, that could benefit most from islet replacement. However, islet transplantation in this recipient category will only have an undisputable indication, if low-risk, but effective methods other than life-long immunosuppression to protect the islet graft from rejection can be developed.
31
Wadhva, Rajesh Kumar, Muhammad Manzoorul Haque, Nasir Hassan Luck, Abbas Ali Tasneem, Zaigham Abbas, and Muhammad Mubarak. "Diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis 4 scores in predicting advanced liver fibrosis in patients with end-stage renal disease and chronic viral hepatitis: Experience from Pakistan." Journal of Translational Internal Medicine 6, no. 1 (March 28, 2018): 38–42. http://dx.doi.org/10.2478/jtim-2018-0008.
Full textAbstract:
Abstract Objectives The aim was to assess the diagnostic accuracy of APRI and FIB-4 in assessing the stage of liver fibrosis in end stage renal disease (ESRD) patients with chronic viral hepatitis and to compare the two tests with standard tru-cut liver biopsy. Material and Methods The study was conducted at Sindh Institute of Urology and Transplantation Karachi (SIUT) from May 2010 to May 2014. All ESRD patients, being considered as candidates for renal transplantation and in whom liver biopsy was performed were included. Fibrosis stage was assessed on liver biopsy using Ishak scoring system. The serum transaminases and platelet counts were used to calculate APRI and FIB-4 scores. Results Out of 109 patients, hepatitis C and B virus infections were present in 104 (95.4%) and 3(2.8%), respectively, while 2 (1.8%) patients had both infections. The mean Ishak fibrosis score was 1.95 ± 2. Advanced fibrosis was noted in 37 (34%) patients. Univariate analysis showed that advanced liver fibrosis was associated with lower platelets counts (P=0.001) and higher aspartate aminotransferase (AST) (P=0.001), alanine aminotransferase (ALT) (P=0.022), APRI score (P=0.001) and FIB-4 score (P=0.001). On logistic regression analysis, only APRI score (P < 0.001) was found to be the independent variable associated with advanced liver fibrosis. APRI score cutoff ≥1 indicating advanced fibrosis showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 91.9%, 90.3%, 82.9%, 95.6%, respectively with area under the curve (AUC) of 0.97. Similarly, a FIB-4 score cutoff ≥1.1 had sensitivity, specificity, PPV and NPV of 70.27%, 66.67%, 52% and 81.36%, respectively with AUC of 0.74. Conclusion APRI is more accurate noninvasive test for assessing advanced liver fibrosis in ESRD patients as compared to FIB-4. It can be used to obviate the need for liver biopsy in this high risk population.
32
Čelakovská, Jarmila, Josef Bukač, Eva Cermákova, Radka Vaňková, Hana Skalská, Jan Krejsek, and Ctirad Andrýs. "Analysis of Results of Specific IgE in 100 Atopic Dermatitis Patients with the Use of Multiplex Examination ALEX2—Allergy Explorer." International Journal of Molecular Sciences 22, no. 10 (May 17, 2021): 5286. http://dx.doi.org/10.3390/ijms22105286.
Full textAbstract:
Background and aim: Progress in laboratory diagnostics of IgE-mediated allergy is the use of component-resolved diagnosis. Our study analyses the results of specific IgE to 295 allergen reagents (117 allergenic extracts and 178 molecular components) in patients suffering from atopic dermatitis (AD) with the use of ALEX2 Allergy Explorer. Method: The complete dermatological and allergological examination, including the examination of the sensitization to molecular components with ALEX2 Allergy Explorer testing, was performed. The statistical analysis of results was performed with these methods: TURF (total unduplicated reach and frequency), best reach and frequency by group size, two-sided tests, Fisher’s exact test, and chi-square test (at an expected minimum frequency of at least 5). Results: Altogether, 100 atopic dermatitis patients were examined: 48 men, 52 women, the average age 40.9 years, min. age 14 years, max. age 67 years. The high and very high level of specific IgE was reached in 75.0% of patients to 18 molecular components: from PR-10 proteins (Aln g 1, Bet v 1, Cor a1.0103, Cor a1.0401, Fag s 1), lipocalin (Can f 1), NPC2 family (Der f 2, Der p 2), uteroglobin (Fel d 1), from Alternaria alternata (Alt a 1), Beta expansin (Lol p 1, Phl p 1), molecular components from Timothy, cultivated rye (Secc pollen) and peritrophin-like protein domain Der p 23. The high and very high level of specific IgE to other lipocalins (Fel d 7, Can f 4), to arginine kinase (Bla g 9, German cockroach), and to allergen extracts Art v (mugwort), and Cyn d (Bermuda grass) reached 52.0% of patients. The severity of AD is in significant relation to the sensitization to molecular components of storage mites (Gly d 2, Lep d 2—NPC2 family), lipocalins (Can f 1, Can f 2, Can f 4, and Can f 6), arginine kinase (Asp f 6, Bla g 9, Der p 20, Pen m 2), uteroglobin (Fel d 1, Ory c 3), Mn superoxide dismutase (Mala s 11), PR-10 proteins (Fag s 1, Mal d 1, Cor a 1.0401, Cor a 1.0103), molecular components of the peritrophin-like domain (Der p 21, Der p 23), and to Secc pollen. In the subgroup of patients suffering from bronchial asthma, the significant role play molecular components from house dust mites and storage mites (Lep d 2, Der p 2, Der f 2—NPC2 family), cysteine protease (Der p 1), peritrophin-like protein domain (Der p 21, Der p 23), enolase from Alternaria alternata (Alt a 6), and Beta expansin Phl p 1. Conclusion: The results of our study demonstrate the detailed profile of sensitization to allergens reagents (allergen extract and molecular components) in patients with atopic dermatitis. We show the significance of disturbed epidermal barrier, resulting in increased penetration of allergens. We confirmed the significant relationship between the severity of AD, the occurrence of bronchial asthma and allergic rhinitis, and high levels of specific IgE to allergen reagents. Our results may be important for regime measures and immunotherapy; Der p 23 shall be considered as an essential component for the diagnosis and specific immunotherapy of house dust mite allergy.
33
Hapidin, Erie Siti Syarah, Yuli Pujianti, and Winda Gunarti. "Instilling Children's Ocean Literacy Through Comic Media: STEAM to R-SLAMET Learning Design for ECE educators." JPUD - Jurnal Pendidikan Usia Dini 16, no. 1 (April 30, 2022): 01–16. http://dx.doi.org/10.21009/jpud.161.01.
Full textAbstract:
Ocean literacy is currently at the forefront of the development of the notion of marine environmental sustainability. It is critical to compare ocean literacy ideas in curriculum standards. Comics Convey various messages of maritime insight content on integrated, contextual, and meaningful learning. This study aims to design STEAM (to R-SLAMET; Religion, Science, Literacy, Art, Math, Engineer, and Technology) learning that contains ocean literacy messages in a comic media. Through the qualitative research method with study case type, researchers seek to aid early childhood education (ECE) educators in designing R-SLAMET learning through the media to overcome maritime cultural literacy problems. The participants of this study consisted of three educators and 43 children. The findings show that the natural play experience of early childhood can be a source of inspiration to find ocean literacy through R-SLAMET learning activities. Contextual play by children becomes a reference for designing comic-based R-SLAMET learning. Comic media can integrate R-SLAMET learning in improving children's ocean literacy.
Keywords: children ocean literacy, comic media, STEAM to R-SLAMET learning design
References:
Arthur, J. (1990). Cultural Literacy. College English, 52(3), 281–281. JSTOR. https://doi.org/10.2307/377758
Campbell, D. T., & Stanley, J. C. (2015). Experimental and Quasi-Experimental Designs for Research. Ravenio Books. https://books.google.co.id/books?id=KCTrCgAAQBAJ
Castek, E. J., Hagerman, M. S., Woodard, R., Bonine, K., Coiro, J., Graville, C., Jordan, M., Mencher, R., Olivares, M., Smith, B. E., Stornaiuolo, A., Sult, L., Tan, E., Tucker-raymond, E., & Wen, W. (2019). Principles for Equity-centered Design of STEAM Learning-through-Making. 34–35.
Chang, C.-C., Hirenkumar, T. C., & Wu, C.-K. (2021). The Concept of Ocean Sustainability in Formal Education—Comparative Ocean Literacy Coverage Analysis of the Educational Standards of India and the USA. Sustainability, 13(8), 4314. https://doi.org/10.3390/su13084314
Chujan, W., Kilenthong, W. T., Patricia, A., Robert, J., Richard, C., Charles, D., John, D., Jere, E., Leslie, A., Jerome, S., Robert, C., Bancroft, K., Lee, J., Carol, S., Lees, N., Mills, R., Haley, S., Eleanor, E., Robert, P., … Erden, F. T. (2019). An early evaluation of a HighScope-based curriculum intervention in rural Thailand. International Journal of Innovation, Creativity and Change, 12(103), 17–25. https://doi.org/10.7822/omuefd.604939
Creswell, J. W. (2015). Educational research: Planning, conducting, and evaluating quantitative and qualitative research (Fifth edition). Pearson.
Fortner, R. W., & Mayer, V. J. (1989). Marine and aquatic education – a challenge for science educators. Science Education, 73(2), 135–154. https://doi.org/10.1002/sce.3730730203
Hapidin, Gunarti, W., Pujianti, Y., & Siti Syarah, E. (2020). STEAM to R-SLAMET Modification: An Integrative Thematic Play Based Learning with R-SLAMETS Content in Early Child-hood Education. JPUD - Jurnal Pendidikan Usia Dini, 14(2), 262–274. https://doi.org/10.21009/jpud.142.05
Hapidin, Nurjannah, S. H. (Universitas N. J. (2018). Pengembangan Model Pembelajaran Tematik Seribu. Pendidikan Usia Dini, 12(Marine Education), 51–65. https://doi.org/10.21009/JPUD.121
Hartley, B. L., Thompson, R. C., & Pahl, S. (2015). Marine litter education boosts children’s understanding and self-reported actions. Marine Pollution Bulletin, 90(1), 209–217. https://doi.org/10.1016/j.marpolbul.2014.10.049
Hawthorne, M., & Alabaster, T. (1999). Citizen 2000: Development of a model of environmental citizenship. Global Environmental Change, 9(1), 25–43. https://doi.org/10.1016/S0959-3780(98)00022-3
Hermawanti, O., & Susilaningsih, S. (2020). Development of Educational Comic Media Based on PowerPoint Class III Indonesian Language Content. Elementary School Teacher, 4(2), 5. https://doi.org/10.15294/est.v4i2.29027
Hidayat, S., & Ridwan. (2017). Kebijakan poros maritim dan keamanan nasional indonesia: Tantangan dan harapan. Pertahanan & Bela Negara, 7(3), 107–121.
Koutníková, M. (2018). The Application of Comics in Science Education. Acta Educationis Generalis, 7(3), 88–98. https://doi.org/10.1515/atd-2017-0026
Melliou, K., Moutafidou, A., & Bratitsis, T. (2014). Digital Comics Use to Develop Thinking Dispositions in Early Childhood Education. 2014 IEEE 14th International Conference on Advanced Learning Technologies, 502–504. https://doi.org/10.1109/ICALT.2014.148
Mogias, A., Boubonari, T., Realdon, G., Previati, M., Mokos, M., Koulouri, P., & Cheimonopoulou, M. Th. (2019). Evaluating Ocean Literacy of Elementary School Students: Preliminary Results of a Cross-Cultural Study in the Mediterranean Region. Frontiers in Marine Science, 6, 396. https://doi.org/10.3389/fmars.2019.00396
Mokos, M., Realdon, G., & Zubak Čižmek, I. (2020). How to Increase Ocean Literacy for Future Ocean Sustainability? The Influence of Non-Formal Marine Science Education. Sustainability, 12(24). https://doi.org/10.3390/su122410647
Ntobuo, N. E., Arbie, A., & Amali, L. N. (2018). The Development of Gravity Comic Learning Media Based on Gorontalo Culture. Jurnal Pendidikan IPA Indonesia, 7(2), 246–251. https://doi.org/10.15294/jpii.v7i2.14344
Oliver, K. L. (1998). A Journey into Narrative Analysis: A Methodology for Discovering Meanings. Journal of Teaching in Physical Education, 17(2), 244–259. https://doi.org/10.1123/jtpe.17.2.244
Pramitasari, M., Yetti, E., & Hapidin, H. (2018). Pengembangan Media Sliding Book Untuk Pengenalan Sains Kehidupan (Life Science) Kelautan Untuk Anak Usia 6-7 Tahun. JPUD - Jurnal Pendidikan Usia Dini, 12(2), 281–290. https://doi.org/10.21009/jpud.122.09
Puspitorini, R., Prodjosantoso, A. K., Subali, B., & Jumadi, J. (2017). Penggunaan Media Komik Dalam Pembelajaran Ipa Untuk Meningkatkan Motivasi Dan Hasil Belajar Kognitif Dan Afektif. Jurnal Cakrawala Pendidikan, 3(3). https://doi.org/10.21831/cp.v3i3.2385
Rahmatullah, R., Inanna, I., Rakib, M., Mustari, M., & Rabania, R. (2020). Developing Tematic Economic Comic with Characters for Early Childhood. Journal of Educational Science and Technology (EST), 293–300. https://doi.org/10.26858/est.v6i3.14949
Rina, N., Suminar, J. R., Damayani, N. A., & Hafiar, H. (2020). Character education based on digital comic media. International Journal of Interactive Mobile Technologies, 14(3), 107–127. https://doi.org/10.3991/ijim.v14i03.12111
Santoro, F., Santin, S., Gail, S., Fauville, G., & Tuddenham, P. (2017). Ocean Literacy for All; A toolkit. UNESCO United Nations Educational.
Steel, B. S., Smith, C., Opsommer, L., Curiel, S., & Warner-Steel, R. (2005). Public ocean literacy in the United States. Ocean & Coastal Management, 48(2), 97–114. https://doi.org/10.1016/j.ocecoaman.2005.01.002
Syarah, E. S., Yetti, E., Fridani, L., Yufiarti, Hapidin, & Pupala, B. (2019). Electronic comics in elementary school science learning for marine conservation. Jurnal Pendidikan IPA Indonesia, 8(4), 500–511. https://doi.org/10.15294/jpii.v8i4.19377
Tatalovic, M. (2009). Science comics as tools for science education and communication: A brief, exploratory study. Journal of Science Communication, 8(4).
Tuddenham, P., Schoedinger, S., Cava, F., & Strang, C. (2005). Science Content and Standards for Ocean Literacy: A Report on Ocean Literacy. https://doi.org/10.13140/RG.2.2.12126.84804
Visbeck, M. (2018). Ocean science research is key for a sustainable future. Nature Communications, 9(1), 690. https://doi.org/10.1038/s41467-018-03158-3
Yulianti, D., Khanafiyah, S., & Sulistyorini, S. (2016). Inquiry-Based Science Comic Physics Series Integrated with Character Education. 7.
Yunandar, Y. (2018). Budaya Bahari Dam Tradisi Nelayan di Indonesia. Sabda: Jurnal Kajian Kebudayaan, 1(1), 22. https://doi.org/10.14710/sabda.v1i1.13243
34
Carradice, Duncan, Peter Shuttleworth, Jeffrey Szer, Andrew Roberts, and Andrew Grigg. "Tissue Iron Overload Is Common Post Transplantation (Allo BMT) and Is Associated with Red Cell Transfusion Load and HFE Genotype." Blood 104, no. 11 (November 16, 2004): 2262. http://dx.doi.org/10.1182/blood.v104.11.2262.2262.
Full textAbstract:
Abstract In order to analyse the incidence of iron overload after allo BMT and assess the role of venesection in preventing complications, we retrospectively analysed 168 consecutive patients undergoing allo BMT at our institution from 1998–2003 surviving at least one year. Iron studies were performed routinely pre-BMT, at D100, one & two years post BMT. Iron overload was defined by at least one of the following criteria i)liver biopsy (n=24), one of : a) dry weight iron concentration >80μmol/g; b) iron index >1.9; c) Perl’s stain grade 3 or 4, ii) CT liver iron >1.0mg/ml (n=13) iii) raised ferritin >1000 μg/L and transferrin saturation >55% on 2 occasions, persisting >6/12 post BMT (n=11), iv) venesection >5g iron (n=1). Using these criteria, iron overload occurred in 49/168 (29%) pts. 12/119 in the non-overloaded group had further investigation but did not meet the criteria; liver biopsy (n=10) or CT (n=2). Elevated ferritin, particularly early post-transplant, did not reliably predict for iron overload, with 55/91 evaluable patients having values >1000μg/L at D100 not fulfilling the criteria for iron overload. There was no difference between overloaded and non-overloaded patients with respect to age or sex. Acute (15/49 vs. 26/113) or chronic liver GVHD (25/46 vs. 47/105) was not different between the two groups (both p>0.05). Only 3 patients were hepatitis B sAg+ or hepatitis C Ab+. The iron overloaded group was more likely to i) have been transplanted for acute leukaemia (29/49 vs. 33/119; p 0.0002) ii) be C282Y heterozygotes (11/46 vs. 10/110, p 0.02) (iii) been transfused more units of red cells (mean 42 vs. 19; p<0.0001) and iv) have persistently abnormal liver function post-transplant, ALT (IU/ml; normal <55) at 1 year 77 vs. 52 and at 2 years 67 vs. 37 (all p<0.05). There was no effect of hetero- or homozygosity for H63D. 63 patients were analysed for the S65C, V59M and Q283P mutations. One patient was heterozygous for the S65C mutation (non-overloaded group). A mean of 12.3 units were venesected in 22 patients (range 2–46), all of whom had received >25 units of red cells. ALT fell significantly (mean pre venesection 189 IU/ml, post 36, p<0.05), as did transferrin saturation (mean pre venesection 68%, post 29%, p<0.05). We conclude that tissue iron overload is common after BMT, that biochemical measures of iron stores (ferritin and transferrin saturation) may be unreliable in this context, particularly in the early post BMT period and that radiological or histological assessment to distinguish hyperferritinaemia due to inflammation from true tissue iron overload may be required. Patients at risk of iron overload (transfusions >25 units, C282Y heterozygotes) should be closely monitored and early venesection therapy instituted to minimise organ damage.
35
Sydorova, A., and O. Iaremenko. "POS1248 URIC ACID AND COVID-19: PATTERN OF CHANGES AND ASSOCIATION WITH PROGNOSIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 958–59. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3479.
Full textAbstract:
BackgroundCoronavirus disease causes a proximal tubule dysfunction of kidneys, inducing uric acid loss [1]. It has been established that several changes in laboratory markers (C-reactive protein (CRP), ferritin, interleukin-6 (IL-6)) can predict the severity of Covid-19 [2]. The purpose of this retrospective study was to analyze whether uric acid could act as another predictor of severe Covid-19.ObjectivesTo evaluate the relationship between the severity of Covid-19 and uric acid levels on admission to the hospital.MethodsThis retrospective study included 150 hospitalized patients with confirmed Covid-19 (mean age 60.3±14.6 years; 52% were men), the severity of which was determined by the presence and type of oxygen support: (1) without O2, (2) O2 by mask or nasal cannula, (3) continuous positive airway pressure, (4) positive bi-pressure in the airways or high-flow oxygen, (5) invasive ventilation. Among them, 90 subjects required oxygen support, and 60 people didn’t. The mortality rate in our study was 9.3%. The average uric acid level was compared with patients without Covid-19 (40 subjects). The study included patients who didn’t receive urate-lowering therapy. Levels of CRP, ferritin, IL-6, D-dimer were also determined on admission. The Spearman’s rank coefficient was used for measuring correlation.ResultsThe mean uric acid level in patients with coronavirus disease was 251.5±104.1 µmol/L; without Covid-19 it was significantly higher — 328.6±96.9 µmol/L (p<0.001). Approximately one in four (24.6%) Covid-19 patients had uric acid levels below the lower limit of normal (208 µmol/L for men, 155 µmol/L for women). A decrease in serum uric acid levels was also observed in patients suffering from asymptomatic hyperuricemia or gout. However, there was no correlation between uric acid levels and disease severity (r=0.01, p=0.88). Also, uric acid levels did not correlate with other laboratory markers of severe Covid-19 (CRP: r=0.07, p=0.73; ferritin: r=0.15, p=0,07; IL-6: r=0.11, p=0,22; D-dimer: r=0.02, p=0,79).ConclusionLow uric acid levels are common in patients with Covid-19, but are not predictive of a more severe course of this disease. A correlation between uric acid and the level of other laboratory markers of severe Covid-19 was not found.References[1]Dufour, I., Werion, A., Belkhir, L. et al. (2021). Serum uric acid, disease severity and outcomes in COVID-19. Crit Care 25, 212 https://doi.org/10.1186/s13054-021-03616-3[2]Huang, I., Pranata, R., Lim, M. A., et al. (2020). C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis. Therapeutic advances in respiratory disease, 14, 1753466620937175. https://doi.org/10.1177/1753466620937175Disclosure of InterestsNone declared
36
Gagnon, B., R. R. Simard, R. Lalande, and J. Lafond. "Improvement of soil properties and fruit yield of native lowbush blueberry by papermill sludge addition." Canadian Journal of Soil Science 83, no. 1 (February 1, 2003): 1–9. http://dx.doi.org/10.4141/s02-011.
Full textAbstract:
Combined primary and secondary papermill sludge (PS) is a good potential source of C and other nutrients to restore low organic matter sandy soils supporting native lowbush blueberry (Vaccinium angustifolium Ait.). A 3-yr field study was conducted to compare the effect of PS with mineral fertilizers (MF) on the blueberry yield and soil chemical properties and enzyme activities of a l’Afrique sand (Humo-Ferric Podzol) in the Saguenay-Lac Saint-Jean area (Quebec, Canada). The PS was applied in the spring of the sprout year at 0, 8.5, 17 and 34 Mg ha-1 and MF was applied at 0, 13, 26 and 52 kg N ha-1. The highest fresh fruit yields were obtained at 8.5 and 17 Mg PS ha-1. The 34 Mg PS ha-1 treatment produced berry yield comparable to the control. This PS rate reduced pH, but increased inorganic N, Mehlich-3 extractable P and Mn in the 0- to 15-cm soil layer. The NO3−-N content of the 15- to 30-cm and 30- to 60-cm soil layers was also increased by PS, suggesting leaching. The MF significantly affected soil inorganic N content only at 3 wk after its application in the first year. The PS rate linearly increased the soil acid phosphatase activity in the first year. The arylsulfatase activity was also higher in PS than in MF treatment, but was severely depressed by 34 Mg PS ha-1 in the last 2 yr. This study indicated that PS, when used at low rates, improves lowbush blueberry yield and the soil enzyme activity on this low fertility sand. Key words: Papermill sludge, lowbush blueberry, soil composition, soil enzyme
37
Merli, Michele, Alessandro Re, Michele Bibas, Davide Dalu, Emanuele Ravano, Guido Gini, Carlo Visco, et al. "Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases." Blood 138, Supplement 1 (November 5, 2021): 1434. http://dx.doi.org/10.1182/blood-2021-151174.
Full textAbstract:
Abstract Background: Hepatitis C virus (HCV) chronic infection has been associated with increased risk of non-Hodgkin lymphoma (NHL) in people living with human immunodeficiency virus (HIV) as well as with a trend of inferior overall survival (OS) in HIV-associated NHL in the modern antiretroviral therapy (ART) era (Besson 2020). The recent introduction of interferon (IFN)-free direct-acting antivirals (DAAs) led to the achievement of sustained virologic response (SVR) in nearly all treated patients (pts) with negligible toxicity in all settings, including HIV/HCV coinfected pts, in which, however, careful attention to interactions with ART is required. We recently showed that DAAs' administration after immuno-chemotherapy (I-CT) may improve long-term outcome in HIV-negative HCV-associated diffuse large B-cell lymphomas (DLBCL) pts (Merli 2019), however, only scant data have been reported so far about the use of DAAs in HIV/HCV coinfected NHL pts. METHODS: We retrospectively collected clinical and virological features, treatments and outcome data of all consecutive pts with NHL and HIV/HCV co-infection, diagnosed and treated at 13 Italian centers between 2005 and 2021, with a special focus on pts affected by DLBCL and treated with DAAs. Only pts who received ART were included. The primary endpoints were SVR rate after DAAs and 2-year OS in HIV/HCV-positive NHL pts. RESULTS: Overall, we collected data of 74 HIV/HCV coinfected pts with NHL (69 males, 93%), including 52 DLBCL, 13 Burkitt lymphoma (BL), 5 plasmablastic lymphoma (PL), 1 anaplastic large-cell ALK negative, 1 T lymphoblastic, 1 gastric MALT and 1 lymphoplasmacytic lymphoma (Table 1). Median age was 51 years (22-57). Previous AIDS defining event was recorded in 16 cases (22%). The main HIV transmission group was represented by intravenous drug users (69%). Stage was III-IV in 63 pts (85%) and aaIPI was ≥2 in 57 pts (77%). At NHL diagnosis 38% of pts had CD4+ <200/mmc and 31% ≥400 HIV-RNA copies/ml. ARL-IPI score was intermediate or high in 49 pts (64%). HCV genotype was 1 in 26 pts (58%), 3 in 12 (27%) and 4 in 7 (15%). Cirrhosis was present in 39% of pts (Child-Pugh B or C in 25%). Overall, 70 pts underwent curative first line therapy alongside ART, including (R-)CHOP-like in 50 (71%), (R-)EPOCH in 9 (13%), (R-)CODOX-M/IVAC in 8 (11%). Rituximab was used in 53% of cases (60% in DLBCL). 46 pts (66%) achieved a complete response (CR), 7 (10%) a partial response (PR), while 17 (24%) did not respond or progressed. At a median follow-up of 1.8 years (95%CI 0.1-12.3), 33 pts (45%) progressed, with a 2-year PFS of 53.5% (95%CI 40.7-64.8), and 38 (51%) died (30 due to NHL, 7 to infections and 1 to hepatocellular carcinoma), with a 2-year OS of 58.2% (95%CI 45.7-78.9). Two-year OS for DLBCL was 61.4% (95%CI 46.3-73.4), significantly higher than BL (39%, 95%CI 14.1-62.8; p=.0.47, Fig. 1). Considering anti-HCV therapy, 13 pts received IFN-based regimens, 5 of whom achieved SVR (38%). After 2016, 21 pts (14 DLBCL, 3 BL, 2 indolent and 2 T-cell lymphoma), including 4 who previously failed IFN, received various DAAs regimens after I-CT (sofosbuvir-based in 20). Toxicity of DAAs was minimal, with only 2 grade (G) ≥2 adverse events (1 G2 peripheral neuropathy and 1 G2 insomnia). SVR was achieved in 20/21 pts (95%): notably, the only non-responder had discontinued DAAs autonomously. DAAs use was associated with improved OS in all pts (p=0.01) and in DLBCL (p=0.04) and with better PFS (p=0.01) in all pts. Similarly, the achievement of SVR after either DAAs or IFN predicted a better OS (Fig.2) and PFS in all pts (p=0.005 and p=0.008, respectively) and in DLBCL (p=0.018 and p=0.047, respectively). The impact of DAAs and SVR on OS remained significant also if considering only pts who achieved CR or PR after I-CT (p<0.05). At univariate analysis, age >60 years (p=0.02), ARL-IPI (p=0.013), PS ECOG ≥2 (p=0.018) were associated with inferior OS. By applying multivariate Cox regression analysis, age >60 years (HR 67.9, 95% CI 7.2- 643.3, p<0.001), ARL-IPI (HR 2.87, 95%CI 1.03-8.06, p=0.044) and SVR after IFN or DAAs (HR 0.30, 95%CI 0.12-0.75, p=0.01) retained independent prognostic influence on OS. CONCLUSIONS: In this very high risk series of HIV/HCV coinfected pts with NHL, mainly represented by DLBCL, the administration of DAAs after I-CT resulted feasible and effective (SVR 95%), and displayed an independent favourable influence on OS. These results strongly support DAAs' use in this hard to treat population. Figure 1 Figure 1. Disclosures Tisi: Incyte: Membership on an entity's Board of Directors or advisory committees; BWS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zilioli: Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Takeda: Other: travel expenses, accommodation; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau. Passamonti: AbbVie: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Arcaini: Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Gilead Sciences: Research Funding; Celgene: Speakers Bureau.
38
Jia, ZhuXia, Min Zhou, Xuzhang Lu, Lingdi Ma, Rong Xiao, Ri Zhang, and HongYing Chao. "Cooperating Mutations of IDH1,IDH2, JAK2V617F, NPM1, FLT3-ITD,C-KIT Genes in Chinese Patients with De Novo Acute Myeloid Leukemias." Blood 118, no. 21 (November 18, 2011): 4638. http://dx.doi.org/10.1182/blood.v118.21.4638.4638.
Full textAbstract:
Abstract Abstract 4638 Introduction: Acute myeloid leukemia (AML) is a heterogeneous group of aggressive disease with complex process,gene mutations play an important role in AML pathogenesis. Several genes have been identified in AML,such as FLT3, c-KIT, NPM1 and JAK2. Indeed, some mutations have revealed prognosis subgroups and modified the therapeutic management of these leukemias. Recently,novel mutations in IDH1(amino acid R132)and IDH2 (R140 and R172)have been found in patients with AMLs,but the frequency and impact on biological and prognostic features in Chinese patients with AMLs remain unknown. We aimed at studying the potential significance of IDH1 and IDH2 mutations in AML and analyzed their interaction with other mutations in Chinese patients with de novo AMLs. Methods: We searched 163 Chinese patients with de novo AML for mutations in the IDH1,IDH2, JAK2, NPM1, FLT3-ITD,C-KIT genes.Female/male ratio was 98/65 and age ranged from 17.0–74.0years (median, 41.0years).Genomic DNA was extracted from diagnostic marrow specimens,FLT3 internaltandem duplication(FLT3 –ITD) and JAK2V617F mutations were screened using polymerase chain reaction (PCR),c-KIT, NPM1 and IDH genes were assessed by PCR followed by direct sequencing, according to previously described protocols. Results: Overall, IDH mutations were found in 25 patients (15.3%) —IDH1 in 7 patients (4.29%) and IDH2 in 18 patients (11.04%). A total of 4 types of IDH1 mutations were identified(c.395G>A, p.R132H,n=4 Gc.394C>A, p.R132S,n=1 Gc.394C>G, p.R132G,n=1 Gc.315C>T, n=1),six out of the seven patients with the missense mutations and the overall frequency of missense mutations in IDH1 was 3.68% (6/163). Both synonymous substitution (c.315C>T; rs11554137) in IDH1 and IDH2R140 mutation occurred in one patient. No mutated cases had both IDH1 and IDH2 missense mutations, suggesting that the mutations are mutually exclusive. IDH2 mutations caused changes of R140 (c.419G>A,p.R140Q,n=18), R172 mutation was not found in our study. The NPM1 mutation in exon 12 was present in 18.35% (n=29 29/158), 25 cases had FLT3-ITD(15.8% 25/158),One case had frame insertion/deletions of c-KIT in exon 8,7 cases had the substitution of a single amino acid in exon 17(4.57%,7/153),none of them had JAK2V617F mutation. IDH- mutated cases showed a higher frequency of concurrent NPM1 mutation compared with wildtype cases (48.3% 14/29 vs 10.8% 11/129), IDH mutations were also more frequent in FLT3-ITD mutation vs FLT3-ITD wildtype (44.0% 11/25 vs 10.5%14/133).10 patients had both FLT3-ITD and NPM1 mutations, concurrent mutations in NPM1, FLT-ITD were detected in 5 cases with the IDH mutation. None of all cases had both IDH and C-KIT mutations. IDH mutations were more often in cytogenetically normal AML cases(20.5% 15/73 vs5.8% 3/52. Patients with IDH mutations were older (51:40 P=0.003), whereas, there were no differences in sex,WBC and platelet count for IDHmut and IDHwt. Conclusion: Our results show that IDH mutations, especially IDHR140 were frequent genetic alterations in Chinese patients with de novo AMLs, and associated with older age, normal karyotype at diagnosis.There was strong association of IDH mutations with NPM1 and FLT3-ITD mutations, suggesting that IDH mutations may act cooperatively in leukemogenesis. Disclosures: No relevant conflicts of interest to declare.
39
Chi, Kim N., Neeraj Agarwal, Anders Bjartell, Byung Ha Chung, Andrea Juliana Pereira de Santana Gomes, Robert W. Given, Álvaro Juárez Soto, et al. "First results from TITAN: A phase III double-blind, randomized study of apalutamide (APA) versus placebo (PBO) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) receiving androgen deprivation therapy (ADT)." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 5006. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.5006.
Full textAbstract:
5006 Background: TITAN was designed to determine whether APA, a selective next-generation androgen receptor inhibitor, plus ADT improves radiographic progression-free survival (rPFS) and overall survival (OS) compared with PBO plus ADT in pts with mCSPC. Methods: In this randomized, double-blind phase 3 study, pts with mCSPC regardless of extent of disease were randomized (1:1) to APA (240 mg/d) or PBO, added to ADT, in 28-day cycles. Pts with prior treatment (tx) for localized disease or prior docetaxel for mCSPC were allowed. All pts received continuous ADT. Dual primary end points were rPFS and OS. Secondary end points were time to a) initiation of cytotoxic chemotherapy, b) pain progression, c) chronic opioid use, d) skeletal-related event. Time-to-event end points were estimated by Kaplan-Meier and Cox proportional hazards methods. This first planned OS interim analysis took place after ~50% of expected events. Results: 525 pts were randomized to APA and 527 to PBO. Median age was 68 y; 8% had prior tx for localized disease; 11% had prior docetaxel. 63% and 37% had high- or low-volume disease, respectively. At median 22.6 mo follow-up, 66% APA and 46% PBO pts remained on tx. APA significantly improved rPFS (HR, 0.48; 95% CI, 0.39-0.60; p < 0.0001), with a 52% reduction in risk of death or radiographic progression; benefit was observed across all subgroups analyzed. Median rPFS was not reached in the APA group and 22.1 mos in the PBO group. APA also significantly improved OS (HR, 0.67; 95% CI, 0.51-0.89; p = 0.0053), with a 33% reduction in risk of death. Median OS was not reached in the APA or PBO group. Time to initiation of cytotoxic chemotherapy was significantly improved with APA (HR, 0.39; 95% CI, 0.27-0.56; p < 0.0001). Based on these results, the independent data monitoring committee recommended unblinding to allow crossover of PBO pts to receive APA. Rates of grade 3/4 adverse events (AEs) (42% APA, 41% PBO) were similar, and discontinuations due to AEs (8% APA, 5% PBO) were low. Conclusions: In the TITAN study in pts with mCSPC, including pts with high- and low-volume disease and prior docetaxel, addition of APA to ADT significantly improved rPFS and OS, and the safety profile was tolerable. These results support the addition of APA to ADT for tx of pts with mCSPC. Clinical trial information: NCT02489318.
40
Gomez Garcia, Antonio Ramon, Pamela Merino Salazar, and Michael Silva Pena-Herrera. "Mortality due to road traffic injuries in older adults in the Republic of Ecuador between 1990 and 2018: a descriptive study." Universidad Ciencia y Tecnología 26, no. 112 (March 8, 2022): 17–25. http://dx.doi.org/10.47460/uct.v26i112.541.
Full textAbstract:
The present study aimed to estimate the trend in road traffic injury mortality in older adults (60 years of age or older) and comparison with those <60 years of age in Ecuador (1990-2018). Official death records and population projections were used to calculate mortality rates per 100,000 population, rate ratios, years of potential life lost (YPLL), and trends. Those under 60 years of age had mortality rates of 16.7 (per 100,000) compared to 36.2 (per 100,000) for older adults, with an increasing trend in YPLL. Older adults recorded fewer deaths than the younger population. However, it is necessary to develop road safety strategies oriented to the progressive aging of the Ecuadorian population.
Keywords: older adults, traffic accidents, mortality, trends, Ecuador.
References
[1]World Health Organization (2018, May 17). Global Status Report on Road Safety 2018 [Online]. Available: https://www.who.int/violence_injury_prevention/road_safety_status/2018/en/
[2]A. F. Algora-Buenafé, M. Russo-Puga, P. R. Suasnavas-Bermúdez, P. Merino-Salazar and A. R. Gómez-García,"Tendencias de los accidentes de tránsito en Ecuador: 2000-2015", Gerencia y Políticas de Salud, vol. 16, n.º 33, pp. 52–58, noviembre de 2017. [Online]. Available: https://doi.org/10.11144/javeriana.rgps16-33.tate. [Last Access: September 2nd, 2021 ].
[3]Pan American Health Organization (2019, June 22). Status of Road Safety in the Region of the Americas [Online]. Available: http://iris.paho.org/xmlui/handle/123456789/51088.
[4]S. J. Eun, "Trends in mortality from road traffic injuries in South Korea, 1983–2017: Joinpoint regression and age-period-cohort analyses", Accident Analysis &Prevention, vol. 134, p. 105325, January 2020. [Online]. Available: https://doi.org/10.1016/j.aap.2019.105325. [Last Access: September 2nd, 2021 ].
[5]S. Azami-Aghdash, M. H. Aghaei, and H. Sadeghi-Bazarghani, "Epidemiology of Road Traffic Injuries among Elderly People; A Systematic Review and Meta-Analysis", Bulletin of Emergency and Trauma, vol. 6, n.º 4, pp. 279–291, October 2018. [Online]. Available: https://doi.org/10.29252/beat-060403. [Last Access: September 7th, 2021 ].
[6]Y. Abolfathi Momtaz, R. Kargar, R. Hosseiny, and R. Sahaf, "Rate and pattern of road traffic accidents among older and younger drivers", Healthy Aging Research, vol. 7, n.º 2, June 2018, art. n.º e18. [Online]. Available: https://doi.org/10.1097/hxr.0000000000000018. [Last Access: October 13th, 2021 ].
[7]P. Martínez, D. Contreras and M. Moreno, "Safe mobility, socioeconomic inequalities, and aging: A 12-year multilevel interrupted time-series analysis of road traffic death rates in a Latin American country", PLOS ONE, vol. 15, n.º 1, enero de 2020, art. n.º e0224545. [Online]. Available: https://doi.org/10.1371/journal.pone.0224545. [Last Access: October 10th, 2021 ].
[8]G. Bergen et al., "How do older adult drivers self-regulate? Characteristics of self-regulation classes defined by latent class analysis", Journal of Safety Research, vol. 61, pp. 205–210, June 2017. [Online]. Available: https://doi.org/10.1016/j.jsr.2017.01.002. [Last Access: October 9th, 2021 ]
[9]Instituto Nacional de Estadística y Censos (2018, February 2). Registros Estadísticos de Nacidos Vivos, Defunciones Fetales y Defunciones Generales [Online]. Available: https://www.ecuadorencifras.gob.ec/nacimientos_y_defunciones.
[10]Instituto Nacional de Estadística y Censos (2017, August 2). Proyecciones Demográficas, 2010 – 2020. [Online]. Available: https://sni.gob.ec/proyecciones-y-estudios-demograficos.
[11]W. Y. Yee, "Road traffic injuries in the elderly", Emergency Medicine Journal, vol. 23, n.º 1, pp. 42–46, January 2006. [Online]. Available: https://doi.org/10.1136/emj.2005.023754. [Last Access: October 21st, 2021]
[12]L. McElroy, J. Juern, A. Bertleson, Q. Xiang, A. Szabo and J. Weigelt, "A single urban center experience with adult pedestrians struck by motor vehicles", WMJ:official publication of the State Medical Society of Wisconsin, vol. 112(3), pp. 117-122, 2013.
[13]K. Bhalla, M. Naghavi, S. Shahraz, D. Bartels and C. J. L. Murray, "Building national estimates of the burden of road traffic injuries in developing countries from all available data sources: Iran", Injury Prevention, vol. 15, n.º 3, pp. 150–156, June 2009. [Online]. Available: https://doi.org/10.1136/ip.2008.020826. [Last Access: October 1st, 2021].
[14]D. Bartels, K. Bhalla, S. Shahraz, J. Abraham, R. Lozano and C. J. L. Murray, "Incidence of road injuries in Mexico: country report", International Journal of Injury Control and Safety Promotion, vol. 17, n.º 3, pp. 169–176, September 2010. [Online]. Available: https://doi.org/10.1080/17457300903564553. [Last Access: November 16th, 2021].
[15]W. R. Boot, C. Stothart and N. Charness, "Improving the Safety of Aging Road Users: A Mini-Review", Gerontology, vol. 60, n.º 1, pp. 90–96, 2014. [Online]. Available: https://doi.org/10.1159/000354212. [Last Access: November 6th, 2021]
[16]Y. L. Michael, E. P. Whitlock, J. S. Lin, R. Fu, E. A. O'Connor and R. Gold, "Primary Care–Relevant Interventions to Prevent Falling in Older Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force", Annals of Internal Medicine, vol. 153, n.º 12, p. 815, December 2010. [Online]. Available: https://doi.org/10.7326/0003-4819-153-12-201012210-00008.[Last Access: November 29th, 2021]
[17]H. Etehad, S. Yousefzadeh-Chabok, A. Davoudi-Kiakalaye, D. A. Moghadam, H. Hemati and Z. Mohtasham-Amiri, "Impact of road traffic accidents on the elderly", Archives of Gerontology and Geriatrics, vol. 61, n.º 3, pp. 489–493, November de 2015. [Online]. Available: https://doi.org/10.1016/j.archger.2015.08.008. [Last Access: November 3th, 2021].
[18]B. H. Ang, W. S. Chen and S. W. H. Lee, "Global burden of road traffic accidents in older adults: A systematic review and meta-regression analysis", Archives of Gerontology and Geriatrics, vol. 72, pp. 32–38, September 2017. [Online]. Available: https://doi.org/10.1016/j.archger.2017.05.004. [Last Access: December 19th, 2021]
[19]J. P. Thompson, M. R. J. Baldock and J. K. Dutschke, "Trends in the crash involvement of older drivers in Australia", Accident Analysis & Prevention, vol. 117, pp. 262–269, August 2018. [Online]. Available: https://doi.org/10.1016/j.aap.2018.04.027. [Last Access: December 16th, 2021].
41
Antonczak, Laurent, Marion Neukam, and Sophie Bollinger. "When industry meets academia." Pacific Journal of Technology Enhanced Learning 4, no. 1 (February 1, 2022): 14–16. http://dx.doi.org/10.24135/pjtel.v4i1.134.
Full textAbstract:
This presentation focuses on a transdisciplinary approach to innovative and collaborative learning practices driven by technology. It highlights two salient elements associated with industry practices and processes in relation to learning and educational contexts: empowerment of individuals and communities of practice through technology, and a broader consideration of industrial approaches to the concept of learning and teaching enhanced within a digital environment.
More precisely, this presentation will feature some of the key theoretical frameworks used in three different settings of learning and teaching in France with regards to the life-long learning approach thanks to Social and Emotional Learning (SEL) (WEF, 2016). It will also discuss the positive effect of the Internet and its affordances (Southerton & Taylor, 2020) on reducing the differences between theoretical and applied knowledge via professional-focused communities (Danvers, 2003). Thus, it will briefly explain that spatial and cognitive learning proximities (Lave & Wenger 1991; Fruchter, 2001) can be reduced by virtue of technology (Anders, 2016; Antonczak, 2019; Glazewski & Hmelo-Silver, 2019) and that ‘computer-supported collaborative learning’ methods can facilitate social and shared problem-solving (Sawyer, 2005; Levallet & Chan, 2018; Presicce et al., 2020) without the ‘restriction of time and place’ (Cheng et al., 2019, 489). Additionally, it will point out some aspects of problem-solving through ‘emancipatory learning and social action’ (Merriam, 2001, 9) through the use of ‘actual’ content and ‘actionable feedback’ (Woods & Hennessy, 2019) enhanced by digital tools and tactics.
Next, it will focus on three case studies by concisely presenting key specifics for each of the courses, including the various digital tools used and followed by some quick interim reflections.
Then it will summarise the challenges and the barriers encountered across the different practices such as virtual delivery, the size of the students' groups and some connectivity considerations. It will be followed by the principal advantages and opportunities, like the professionalisation dimension through interactive and authentic learning enhanced by affordances. And it will conclude with some managerial recommendations as experiential and practical methods (knowledge codification) thanks to industry-based teaching supported by digital technologies.
The presentation will close with the overall conclusion in relation to digital technology and some of the key 21st-century career skills. In general, the findings will be of interest to academics, practitioners and policymakers. The added value of this transdisciplinary investigation is that it improves research on collaborative innovation and collective knowledge by creating a bridge between the fields of Education and Business.
Bibliography
Anders, A. (2016). Team communication platforms and emergent social collaboration practices. International Journal of Business Communication, 53(2), pp. 224-261.
Ananiadou, K. & M. Claro (2009). 21st Century Skills and Competences for New Millennium Learners in OECD Countries, OECD Education Working Papers, No. 41, OECD Publishing.
Antonczak, L. (2019). Scaling-up collaborative practices through mobile technology. The 25th International Conference on Engineering/International Technology Management Conference (ICE/ITMC), June 17-19, Nice.
Askay, D. A. & Spivack, A. J. (2010). The multidimensional role of trust in enabling creativity within virtual communities of practice: A theoretical model integrating swift, knowledge-based, institution-based, and organizational trust. In 43rd Hawaii International Conference on System Sciences, Hawaii, pp. 1-10.
Cairns, L. (2000). The process/outcome approach to becoming a capable organization. In Australian Capability Network Conference, Sydney, 1-14.
Cheng, E. W., Chu, S. K., & Ma, C. S. (2019). Students’ intentions to use PBWorks: a factor-based PLS-SEM approach. Information and Learning Sciences, 120(7/8), 489-504.
Cochrane, T., Antonczak, L., Guinibert, M., Mulrennan, D., Rive, V., & Withell, A. (2017). A framework for designing transformative mobile learning. In Mobile Learning in Higher Education in the Asia-Pacific Region ( 25-43). Springer, Singapore.
Danvers, J. (2003). Towards a radical pedagogy: Provisional notes on learning and teaching in art & design. International Journal of Art & Design Education, 22(1), 47-57.
Dewey, J. (1991). Logic: The theory of inquiry. In J. A. Boydston (Ed.), John Dewey: The Later Works, 1925–1953, Vol. 12 (1-5). Carbondale, IL: SIU Press. [Originally published in 1938]
Dziuban, C., Graham, C. R., Moskal, P. D., Norberg, A., & Sicilia, N. (2018). Blended learning: the new normal and emerging technologies. International Journal of Educational Technology in Higher Education, 15(1), 1-16.
Fruchter, R. (2001). Dimensions of teamwork education. International Journal of Engineering Education, 17(4/5), 426-430.
Glazewski, K. D., & Hmelo-Silver, C. E. (2019). Scaffolding and supporting the use of information for ambitious learning practices. Information and Learning Sciences, 120(1/2), 39-58.
Hase, S. & Kenyon, C. (2007). Heutagogy: A child of complexity theory. Complicity: An International Journal of Complexity and Education, 4(1), 111-119.
Lave, J. & Wenger, E. (1991). Situated Learning: Legitimate Peripheral Participation. Cambridge: Cambridge University Press.
Levallet, N., & Chan, Y. E. (2018). Role of Digital Capabilities in Unleashing the Power of Managerial Improvisation. MIS Quarterly Executive, 17(1), 1-21.
Lewin, K. (1947). Group decision and social change. Readings in Social Psychology, 3(1), 197-211.
McKenney, S., & Reeves, T. C. (2013). Systematic review of design-based research progress: Is a little knowledge a dangerous thing?. Educational Researcher, 42(2), 97-100.
Makri, S., Ravem, M., & McKay, D. (2017). After serendipity strikes: Creating value from encountered information. Proceedings of the Association for Information Science and Technology, 54(1), 279-288.
Mascheroni, G., & Vincent, J. (2016). Perpetual contact as a communicative affordance: Opportunities, constraints, and emotions. Mobile Media & Communication, 4(3), 310-326.
Merriam, S. B. (2001). Andragogy and self-directed learning: Pillars of adult learning theory. New Directions for Adult and Continuing Education, 89, 3-13.
Pont, B. (2013). Learning Standards, Teaching Standards and Standards for School Principals: A Comparative Study. Rapport no. EDU/WKP(2013)14. Centre of Study for Policies and Practices in Education (CEPPE). Retrieved from: http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=EDU/WKP(2013)14&docLanguage=En (accessed December 31, 2020).
Presicce, C., Jain, R., Rodeghiero, C., Gabaree, L. E., & Rusk, N. (2020). WeScratch: an inclusive, playful and collaborative approach to creative learning online. Information and Learning Sciences, 121(7/8), 695-704.
Reeves, T. C. (2005). Design-based research in educational technology: Progress made, challenges remain. Educational Technology, 45(1), 48-52.
Southerton, C., & Taylor, E. (2020). Habitual disclosure: Routine, affordance, and the ethics of young peoples social media data surveillance. Social Media+ Society, 6(2), https://doi.org/10.1177/2056305120915612
42
Dimogiannis, Konstantinos, Andrzej Sankowski, Conrad Holc, Graham Newton, Darren Anthony Walsh, James O'Shea, Andrei Khlobystov, and Andrzej Sankowski. "Understanding the Mg Cycling Mechanism on a MgTFSI-Glyme Electrolyte." ECS Meeting Abstracts MA2022-01, no. 4 (July 7, 2022): 574. http://dx.doi.org/10.1149/ma2022-014574mtgabs.
Full textAbstract:
The Magnesium battery is considered a potential a high energy, sustainable successor to the lithium-ion battery, due to an almost two-fold increase in the volumetric capacity of magnesium compared to lithium (Li), decreased probability of dendritic growth, cheaper raw material costs, and high natural abundance.[1]–[3] Current electrolytes have been found to be insufficiently stable towards the Mg electrode, leading to reduction of the electrolyte and formation of a solid electrolyte interphase (SEI), which is believed to be detrimental to performance.[4]–[6] Our previous study [7] indicated a cycling mechanism at Mg surface in a Mg(TFSI)2-based electrolyte occurring through Mg deposits and an evolution of interphase chemistry during conditioning that is critical for stable cycling in the Mg(TFSI)2-glyme electrolyte. However, unlike Li metal batteries,[8], [9] where the Li plating and nucleation mechanism has been studied in depth, this is not the case for Mg batteries. In this study, we have combined electrochemical analysis with state-of-the-art cryo-focus ion beam scanning electron microscopy (FIB-SEM) and energy-dispersive X-ray spectroscopy (EDX), aiming to give insight into the Mg nucleation & growth mechanism. In doing so, we are able to reveal the detailed chemical and structural composition of the Mg deposits for the first time. Our studies are performed in Mg(TFSI)2-tetraglyme electrolyte as the leading base electrolyte for the battery. By linking the structure of Mg deposits to their state of charge and cycling performance, we can conclusively demonstrate the origin of the high overpotential in the battery. In addition, we show how Mg is reversibly plated and stripped within the deposit and demonstrate how the structure and size of the Mg deposit fluctuates to accommodate this process. Image caption: Electron microscopy images of the cross -section of a Mg particle after discharge etched using cryo-FIB-SEM, showing. a) secondary electron images of the exposed cross-section and b) In lens secondary electron images highlighting the distinct regions of the particle: Mg-rich inner core, MgO-rich outer core and interphase. References: [1] G. N. Newton, L. R. Johnson, D. A. Walsh, B. J. Hwang, and H. Han, ACS Sustain. Chem. Eng., vol. 9, no. 19, pp. 6507–6509, May 2021 [2] M. Fichtner, Magnesium Batteries: Research and Applications, vol. 2020, no. 23. Royal Society of Chemistry, 2019 [3] J. W. Choi and D. Aurbach, Nat. Rev. Mater., vol. 1, no. 4, p. 16013, 2016 [4] J. Muldoon, C. B. Bucur, and T. Gregory, Chem. Rev., vol. 114, no. 23, pp. 11683–11720, Dec. 2014 [5] A. Ponrouch, J. Bitenc, R. Dominko, N. Lindahl, P. Johansson, and M. R. Palacin, Energy Storage Mater., vol. 20, no. pp. 253–262, Feb. 2019 [6] R. Attias, M. Salama, B. Hirsch, Y. Goffer, and D. Aurbach, Joule, vol. 3, no. 1, pp. 27–52, 2019 [7] C. Holc, K. Dimogiannis, E. Hopkinson, and L. R. Johnson, ACS Appl. Mater. Interfaces, vol. 13, no. 25, pp. 29708–29713, Jun. 2021 [8] Z. Yu et al. Nat Energy, vol 5, pp.526–533 Jun. 2020 [9] B. Liu, J. G. Zhang and W. Xu, Joule, vol 2, no. 16, pp. 833-845, May 2018 Figure 1
43
Dreo, B., D. R. Pietsch, R. Husic, A. Lackner, J. Fessler, J. Rupp, A. S. Muralikrishnan, J. Thiel, M. Stradner, and P. Bosch. "POS1063 STAT PHOSPHORYLATION AS A MARKER FOR DISEASE ACTIVITY IN PATIENTS WITH PSORIATIC ARTHRITIS: AN EXPLORATIVE ANALYSIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 854.1–854. http://dx.doi.org/10.1136/annrheumdis-2022-eular.767.
Full textAbstract:
BackgroundNumerous cytokines that influence disease activity in psoriatic arthritis (PsA) are modulators of the Janus Kinases/Signal Transducers and Activators of Transcription (JAK/STAT) pathway. The JAK1/STAT1/STAT3/STAT5 network can drive the expansion of Th17 and regulatory T cells via proinflammatory cytokines in PsA joints,[1], [2] while hyperphosphorylation of STAT3 in immune cells has previously been shown to promote PsA pathogenesis through the Interleukin (IL)-23/IL-17/IL-22 axis.[3] Therefore, the phosphorylation status of STAT molecules in leucocytes of PsA patients may indicate active disease and could potentially guide treatment with JAK inhibitors.ObjectivesTo analyse phosphorylated STAT (pSTAT) levels of circulating leucocyte subsets in PsA patients with active and inactive diseaseMethodsWhole blood was drawn on consecutive PsA patients fulfilling the CASPAR criteria[4] to perform flow cytometry analysis using the BD FACSLyric platform. Disease activity was assessed using the Disease activity for psoriasis arthritis (DAPSA) score.[5] All steps from storage of drawn blood to cell fixation were performed at 4°C to prevent auto-activation of leucocytes. The geometric mean fluorescence intensities (gMFI) of pSTATs in granulocytes, monocytes, B cells and CD4+/- naïve/memory T cells were compared between patients with moderate to high (MoDA/HDA) and remission to low disease activity (REM/LDA). Correlation analysis between gMFIs and DAPSA scores were performed.ResultsForty-two patients (female ratio: 0.48) with established PsA (median ± standard deviation, age: 56 ± 12.54 years, disease duration: 8.50 ± 7.10 years) were included in this study. Twenty-one percent of patients were in MoDA/HDA, while the remaining 79% were in REM/LDA. Patients in MoDA/HDA showed significantly higher pSTAT3 levels in CD4+ naïve (gMFI median ± standard deviation: 284.5 ± 79.9 vs 238 ± 92.9, p = 0.011), CD4- naïve (297 ± 107.5 vs 238 ± 98.4, p = 0.04), CD4+ memory (227 ± 62.9 vs 190.5 ± 72.2, p = 0.009) and CD4- memory T cells (209 ± 66.8 vs 167.0 ± 64.9, p = 0.036). On the other hand, PsA patients in remission or low disease activity displayed higher pSTAT1 levels in granulocytes (2509 ± 1887 vs 1330.5 ± 784.1, p = 0.040) and monocytes (255 ± 230 vs 144 ± 62.5, p = 0.049). Positive correlations were found between DAPSA scores and pSTAT3 in CD4+ naïve and memory T cells (Spearman’s correlation coefficient rho (ρ) = 0.5, p = 0.0012 and ρ = 0.47, p = 0.0025 resp.) whereas pSTAT1 in granulocytes and monocytes were negatively correlated with the DAPSA scores (ρ = -0.45, p = 0.0074 and ρ = -0.34, p = 0.05).ConclusionDifferential phosphorylation of STAT3 and STAT1 molecules in circulating leucocyte subsets indicates PsA disease activity. Further studies to examine the value of STAT phosphorylation patterns guiding JAK inhibitor therapy are underway.References[1]U. Fiocco et al., “Ex vivo signaling protein mapping in T lymphocytes in the psoriatic arthritis joints,” J. Rheumatol., vol. 93, pp. 48–52, 2015, doi: 10.3899/jrheum.150636.[2]S. K. Raychaudhuri, C. Abria, and S. P. Raychaudhuri, “Regulatory role of the JAK STAT kinase signalling system on the IL-23/IL-17 cytokine axis in psoriatic arthritis,” Ann. Rheum. Dis., vol. 76, no. 10, pp. e36–e36, 2017.[3]E. Calautti, L. Avalle, and V. Poli, “Psoriasis: A STAT3-centric view,” International Journal of Molecular Sciences, vol. 19, no. 1. MDPI AG, Jan. 06, 2018, doi: 10.3390/ijms19010171.[4]W. Taylor, D. Gladman, P. Helliwell, A. Marchesoni, P. Mease, and H. Mielants, “Classification criteria for psoriatic arthritis: Development of new criteria from a large international study,” Arthritis Rheum., vol. 54, no. 8, pp. 2665–2673, 2006, doi: 10.1002/art.21972.[5]M. M. Schoels, D. Aletaha, F. Alasti, and J. S. Smolen, “Disease activity in psoriatic arthritis (PsA): Defining remission and treatment success using the DAPSA score,” Ann. Rheum. Dis., vol. 75, no. 5, pp. 811–818, 2016, doi: 10.1136/annrheumdis-2015-207507.Disclosure of InterestsBarbara Dreo: None declared, Daniel Ruben Pietsch: None declared, Rusmir Husic Speakers bureau: MSD, Lilly und Abbvie, Angelika Lackner: None declared, Johannes Fessler: None declared, Janine Rupp: None declared, Anirudh Subramanian Muralikrishnan: None declared, Jens Thiel Speakers bureau: GSK, BMS, AbbVie, Novartis, Consultant of: GSK, Novartis, Grant/research support from: BMS, Martin Stradner Speakers bureau: Eli Lilly, Pfizer, MSD, BMS, AbbVie, Janssen, Consultant of: Eli Lilly, AbbVie, Janssen, Philipp Bosch Grant/research support from: Pfizer
44
Sitti Rahmaniar Abubakar, Aprillianti, Ahid Hidayat, Muamal Gadafi, and Nanang Sahriana. "Using Mind Mapping Learning Methods for Children’s Language Skills." JPUD - Jurnal Pendidikan Usia Dini 15, no. 1 (April 30, 2021): 141–61. http://dx.doi.org/10.21009/jpud.151.08.
Full textAbstract:
Language skills are significant predictors of early academic and social-emotional outcomes of children and are important predictors of school readiness. This study aims to improve children's language skills through the application of mind mapping learning methods. This classroom action research used Kemmis and Taggart's cycle model. The research subjects were 12 children in group B consisting of eight boys and four girls. The data was collected through observation, interviews, and documentation with the validity of the data using source triangulation and method triangulation. This research uses data analysis techniques in the form of data condensation, data presentation, and drawing conclusions. The results showed that the children's language skills through the application of the mind mapping method in the first cycle were 75%, and in the second cycle had increased to 92%. Based on the results of teacher observations in the implementation of cycle I, the children's language skills obtained a percentage value of 61.5%, and in cycle II increased to 92.3%. While the results of observations of children's activities in the implementation of the first cycle obtained a percentage of 54%, and in the second cycle, it increased to 85%. This study found that the teacher's assessment of this mind mapping method was an easy method to understand so that it was easy to apply in classroom learning. The implication of this research is that it is necessary to carry out further research on the application of the mind mapping method for other aspects of development.
Keywords: Early Childhood, language Skills, Mind Mapping Learning Methods
References:
Abi-El-Mona, I., & Adb-El-Khalick, F. (2008). The influence of mind mapping on eighth graders’ science achievement. School Science and Mathematics, 108(7), 298–312. https://doi.org/10.1111/j.1949-8594.2008.tb17843.x
Alamsyah, M. (2019). Kiat jitu meningkatkan prestasi dengan mind mapping (A. Safa, Ed.; 2nd ed.). Mitra Pelajar.
Arimbi, Y. D., Saparahayuningsih, S., & Ardina, M. (2018). Meningkatkan Perkembangan Kognitif Melalui Kegiatan Mind Mapping. Jurnal Ilmiah Potensia, 3(2), 64–71.
Aykac, V. (2014). An application regarding the availability of mind maps in visual art education based on active learning method. Procedia - Social and Behavioral Sciences, 174, 1859–1866. https://doi.org/10.1016/ j.sbspro.2015.01.848.
Balim, A. G. (2013). The effect of mind-mapping applications on upper primary students success and inquiry-learning skills in science and environment education. International Research in Geographical and Environmental Education, 22(4), 337–352. https://doi.org/10.1080/10382046.2013.826543
Batdi, V. (2015). A Meta-analysis Study of Mind Mapping Techniques and Traditional Learning Methods. The Anthropologist, 20(1–2), 62–68. https://doi.org/10.1080/09720073.2015.11891724
Berman, R. A. (2007). Developing Linguistic Knowledge and Language Use Across Adolescence. In E. Hoff & M. Shatz (Eds.), Blackwell Handbook of Language Development (pp. 347–367). Blackwell Publishing Ltd. https://doi.org/10.1002/9780470757833.ch17
Bishop, D. V. M., Snowling, M. J., Thompson, P. A., Greenhalgh, T., & and the CATALISE-2 consortium. (2017). Phase 2 of CATALISE: A multinational and multidisciplinary Delphi consensus study of problems with language development: Terminology. Journal of Child Psychology and Psychiatry, 58(10), 1068–1080. https://doi.org/10.1111/jcpp.12721
Botting, N., & Conti-Ramsden, G. (2000). Social and behavioural difficulties in children with language impairment. Child Language Teaching and Therapy, 16(2), 105–120. https://doi.org/10.1177/026565900001600201
Budd, J. W. (2004). Mind maps as classroom exercises. Journal of Economic Education, 35(1), 35–46. https://doi.org/10.3200/JECE.35.1.35-46
Budyawati, L. P. I. (2016). Implementasi Metode Mind Mapping untuk Meningkatkan Kemampuan Bercerita Anak kelas B di PAUD Sarin Rare Mas Ubud. Pancaran, 5(3), 1–16.
Buzan, T. (2005). Mind map: The ultimate thinking tool. Thorston.
Buzan, Tony. (2005). Buku Pintar Mind Map. Gramedia Pustaka Utama.
Buzan, Tony. (2007). Buku Pintar Mind Map untuk Anak. Gramedia Pustaka Utama.
Chang, Y. H., Chang, C. Y., & Tseng, Y. H. (2010). Trends of science education research: An automatic content analysis. Journal of Science Education and Technology, 19(4), 315–331. https://doi.org/10.1007/s10956-009-9202-2
Chiou, C. C. (2008). The effect of concept mapping on students’ learning achievements and interests. Innovations in Education and Teaching International, 45(4), 375–387.
Chow, J. C., & Jacobs, M. (2016). The role of language in fraction performance: A synthesis of literature. Learning and Individual Differences, 47, 252–257. https://doi.org/10.1016/j.lindif.2015.12.017
Chularut, P., & DeBacker, T. K. (2004). The influence of concept mapping on achievement, self-regulation, and self-efficacy in students of English as a second language. Contemporary Educational Psychology, 29(3), 248–263. https://doi.org/10.1016/j.cedpsych.2003.09.001
Clegg, J., Law, J., Rush, R., Peters, T. J., & Roulstone, S. (2015). The contribution of early language development to children’s emotional and behavioural functioning at 6 years: An analysis of data from the Children in Focus sample from the ALSPAC birth cohort. Journal of Child Psychology and Psychiatry, 56(1), 67–75. https://doi.org/10.1111/jcpp.12281
Davies, M. (2011). Concept mapping, mind mapping and argument mapping: What are the differences and do they matter? Higher Education, 62, 279–301. https://doi.org/10.1007/s10734-010-9387-6.
DePorter, B., & Hernacki, M. (2015). Quantum Learning: Membiasakan Belajar Nyaman dan Menyenangkan. Kaifa.
Dhieni, N. (2008). Metode Pengembangan Bahasa. Universitas Terbuka.
Dhindsa, HS., M., K., & Anderson, OR. (2011). Constructivist-visual mind map teaching approach and the quality of students’ cognitive structures. Science Education Technology, 20, 186–200. https://doi.org/10.1007/s10956-010- 9245-4.
Duff, F. J., Reen, G., Plunkett, K., & Nation, K. (2015). Do infant vocabulary skills predict school‐age language and literacy outcomes? Journal of Child Psychology and Psychiatry, 56(8), 848–856. https://doi.org/10.1111/jcpp.12378
Farrand, P., Fearzana, H., & Hennessy, E. (2002). The efficacy of the mind map study technique. Medical Education, 36, 426–431.
Hapidin, H., Pujianti, Y., & Juniasih, I. (2019). The The Effectiveness of Using Mind Mapping Method to Improve Child Development Assessment. JPUD - Jurnal Pendidikan Usia Dini, 13(1), 172–186. https://doi.org/10.21009/10.21009/jpud.131.13
Hendarwati, E. (2015). Peningkatan Kemampuan Bahasa Melalui Mind Mapping pada Anak TK Aisyah 29 Surabaya. Jurnal Didaktis, 12(1).
Hoff, E. (2013). Interpreting the early language trajectories of children from low-SES and language minority homes: Implications for closing achievement gaps. Developmental Psychology, 49(1), 4–14. https://doi.org/10.1037/a0027238
Holley, C. D., Dansereau, D. F., McDonald, B. A., Garland, J. C., & Collins, K. W. (1979). Evaluation of a hierarchical mapping technique as an aid to prose processing. Contemporary Educational Psychology, 4(3), 227–237. https://doi.org/10.1016/0361-476X(79)90043-2
Horton, P. B., McConney, A. A., Gallo, M., Woods, A. L., Senn. G. J., & Hamelin, D. (1993). An investigation of the effectiveness of concept mapping as an instructional tool. Science Education, 77, 95–111.
Hulme, C., Nash, H. M., Gooch, D., Lervåg, A., & Snowling, M. J. (2015). The Foundations of Literacy Development in Children at Familial Risk of Dyslexia. Psychological Science, 26(12), 1877–1886. https://doi.org/10.1177/0956797615603702
Indriyani, M. P., Wirya, I. N., & Parmiti, D. P. (2013). Penerapan metoda mind mapping berbantuan media. Jurnal Pendidikan Anak Usia Dini Undiksha, 1(1), 1–10.
Jalongo, M. R. (2014). E arly Childhood Language Arts (6th ed.). Pearson Education, Inc.
Jones, B. D., Ruff, C., Tech, V., Snyder, J. D., Tech, V., Petrich, B., Tech, V., & Koonce, C. (2012). The Effects of Mind Mapping Activities on Students ’ Motivation. International Journal for the Scholarship of Teaching and Learning, 6(1).
Karpicke, J. D., & Blunt, J. R. (2011). Retrieval practice produces more learning than elaborative studying with concept mapping. Science, 331(6018), 772–775. https://doi.org/10.1126/science.1199327
Keles, O. (2012). Elementary teachers’ views on mind mapping. International Journal of Education, 4(1), 93–100.
Kemmis, S., McTaggart, R., & Nixon, R. (2014). The Action Research Planner. Springer Singapore. https://doi.org/10.1007/978-981-4560-67-2
Law, J., Rush, R., Schoon, I., & Parsons, S. (2009). Modeling developmental language difficulties from school entry into adulthood: Literacy, mental health, and employment outcomes. Journal of Speech, Language, and Hearing Research : JSLHR, 52 6, 1401–1416.
Lestari, N. G. A. M. Y. (2020). Penerapan Metode Mind Map Dalam Pengembangan Kreativitas Anak Usia Dini. Pratama Widya: Jurnal Pendidikan Anak Usia DIni, 5(1), 35–42.
Locke, A., Ginsborg, J., & Peers, I. (2002). Development and disadvantage: Implications for the early years and beyond. International Journal of Language & Communication Disorders, 37(1), 3–15. https://doi.org/10.1080/13682820110089911
Madu, BC., & Metu, IC. (2010). Effect of mind map as a notetaking approach on students’ achievements’ in economics. Journal of Emerging Trends in Economics and Management Sciences (JETEMS), 3(3), 247–251.
McGillion, M., Pine, J. M., Herbert, J. S., & Matthews, D. (2017). A randomised controlled trial to test the effect of promoting caregiver contingent talk on language development in infants from diverse socioeconomic status backgrounds. Journal of Child Psychology and Psychiatry, 58(10), 1122–1131. https://doi.org/10.1111/jcpp.12725
Meier, PS. (2007). Mind-mapping. Social Research, 52, 1–4.
Merchie, E., & Van Keer, H. (2016). Mind mapping as a meta-learning strategy: Stimulating pre-adolescents’ textlearning strategies and performance? Contemporary Educational Psychology, 46, 128–147. https://doi.org/10. 1016/j.cedpsych.2016.05.005
Mona, IA., & Khlaick, FA. (2008). The influence of mind mapping on eighth graders’ science achievement. School Science and Mathematics, 108(7), 298–312. https://doi.org/10.1111/j.1949-8594.2008.tb17843.x
Nesbit, J. C., & Adesope, O. O. (2006). Learning with concept and knjowledge maps: A meta-analysis. Review of Educational Research, 76(3), 413–448.
Novak, J. D., & Gowin, D. B. (1984). Learning how to learn. Cambridge University Press.
O‟Donnell, A. M., Dansereau, D. F., & Hall, R. H. (2002). Knowledge maps as scaffolds for cognitive processing. Educational Psychology Review, 14, 71–86.
Olivia, F. (2013). 5—7 Menit Asyik Mind Mapping Kreatif. Elex Media Computindo.
Pace, A., Alper, R., Burchinal, M. R., Golinkoff, R. M., & Hirsh-Pasek, K. (2019). Measuring success: Within and cross-domain predictors of academic and social trajectories in elementary school. Early Childhood Research Quarterly,46, 112–125. https://doi.org/10.1016/j.ecresq.2018.04.001
Padang, J. S. M., & Gurning, B. (2014). Improving Students’ Achievement in Writing Descriptive Text through Mind Mapping Strategy. Register Journal of English Language Teaching of FBS-Unimed, 3, 1–11.
Patmonodewo, S. (2000). Pendidikan Anak Pra Sekolah. Rineka Cipta.
Paxman, CG. (2011). Map your way to speech success! Employing mind mapping as a speech preparation technique. Communication Teacher, 25(1), 7–11. https://doi.org/10.1080/17404622.2010.513994
Riswanto, & Putra, P. P. (2012). The Use of Mind Mapping Strategy in the Teaching of Writing at SMAN 3 Bengkulu , Indonesia. International Journal of Humanities and Social Science, 2(21), 60–68.
Saed, H. A., & AL-Omari, H. A. (2014). The Effectiveness of a Proposed Program Based on a Mind Mapping Strategy in Developing the Writing Achievement of Eleventh Grade EFL Students in Jordan and Their Attitudes Towards Writing. Journal of Education and Practice, 5, 88–109.
San Risqiya, R. (2013). The Use of Mind Mapping in Teaching Reading Comprehension. ELTIN Journal, 1, 32–43.
Serig, D. (2011). Beyond brainstorming: The mind map as art. Teaching Artist Journal, 9(4), 249–257.
Somers, MJ., Passerini, K., Parhankangas, A., & Casal, J. (2014). Using mind maps to study how business school students and faculty organize and apply general business knowledge. The International Journal of Management Education, 12, 1–13.
Warsidi, Burhanuddin, A., & Mustafa, M. (2014). A Collaboration Of Mind Mapping And Organizational Pattern To Improve Students ’ Essay Writing Ability. Jurnal Pasca Unhas, 11, 1–12.
Whitehurst, G. J., & Fischel, J. E. (1994). Practitioner Review: Early Developmental language Delay: What. If Anything. Should the Clinician Do About It? Journal of Child Psychology and Psychiatry, 35(4), 613–648. https://doi.org/10.1111/j.1469-7610.1994.tb01210.x
Williams, M. H. (2012). Physical webbing: Collaborative kinesthetic three-dimensional mind maps. Active Learning in Higher Education, 13(1), 35–49. https://doi.org/10.1177/1469787411429185
Willis, C. L., & Miertschin, S. L. (2006). Mind maps as active learning tools. Journal of Computing Sciences in Colleges, 21(4), 266–272.
Yunus, M. M., & Chien, C. H. (2016). The Use of Mind Mapping Strategy in Malaysian University English Test (MUET) Writing. Creative Education, 07(04), 619–626. https://doi.org/10.4236/ce.2016.74064
45
Cortes, Jorge, Hagop M. Kantarjian, Dong Wook Kim, H. Jean Khoury, Anna G. Turkina, Zhi-Xiang Shen, Tim H. Brummendorf, Mammen Chandy, Steven Arkin, and Carlo Gambacorti-Passerini. "Efficacy and Safety of Bosutinib (SKI-606) in Patients with Chronic Phase (CP) Ph+ Chronic Myelogenous Leukemia (CML) with Resistance or Intolerance to Imatinib." Blood 112, no. 11 (November 16, 2008): 1098. http://dx.doi.org/10.1182/blood.v112.11.1098.1098.
Full textAbstract:
Abstract Bosutinib (SKI-606) is an orally bioavailable dual Src/Abl inhibitor demonstrating inhibitory activity against BCR-Abl phosphorylation, and is 200 times more potent than imatinib but with minimal inhibition of platelet-derived growth factor receptor (PDGFR) or c-kit. The phase I portion of this study identified a treatment dose of 500 mg daily and showed evidence of clinical efficacy. The phase II portion of the study to investigate the efficacy and safety of bosutinib in patients (pts) with CP Ph+ CML who have failed imatinib therapy is ongoing. Preliminary data for 283 treated pts, median age 54 yrs (range 18 – 91 yrs) and 52% male are reported. A subset of pts received treatment in addition to imatinib, including interferon (91 pts), dasatinib (71 pts), nilotinib (7 pts) and stem cell transplant (13 pts). Among pts who failed imatinib (and received no other tyrosine kinase inhibitor treatment), 137 were imatinib-resistant (all received imatinib ≥600mg) and 64 pts were imatinib-intolerant; median duration of bosutinib treatment to date is 7.7 mos (range 0.2 – 28.2 mos) and 4.5 mos (range 0.5 – 21.5 mos), respectively. Among 67 imatinibresistant pts evaluable for hematological response, 53 (79%) had complete hematological response (CHR). Of 84 imatinib-resistant pts evaluable for cytogenetic response, 34 (40%), achieved a major cytogenetic response (MCyR), including 24 (29%) with a complete cytogenetic response (CCyR). Of 34 pts with MCyR, 31 have maintained their response to date. Of 60 evaluable imatinib-resistant pts, 20 (33%) achieved major molecular response, 10 (17%) of which were complete. Among imatinib-intolerant pts, 22 of 29 evaluable (76%) achieved CHR, and 13 of 22 evaluable (59%) achieved MCyR, including 11 (50%) with CCyR. Of 25 evaluable imatinib-intolerant pts, 7 (28%) achieved major molecular response, 5 (20%) of which were complete. Of 105 pts with baseline samples tested for mutations, 17 different mutations were found in 45 pts (43%). CHR occurred in 5/6 pts (83%) with P-loop mutations and 13/17 (76%) with non-P-loop mutations; MCyR occurred in 3/6 pts (50%) and 11/24 pts (46%), with P-loop and non-P-loop mutations, respectively. Treatment was generally well tolerated. The most common adverse events among treated pts (n=283) were gastrointestinal (nausea, vomiting, diarrhea), these were usually grade 1 – 2, manageable and transient, diminishing in frequency and severity after the first 3 – 4 weeks of treatment. Grade 3 – 4 non-hematologic toxicity occurring in ≥5% of pts were diarrhea (8%), rash (8%) and increased ALT (5%). 27 pts (10%) reported grade 1/2 fluid retention adverse events, including 21 pts with edema, and 6 pts with effusions: 4 pleural, 1 pericardial, and 1 pleural and pericardial. A single patient experienced grade 3 pleural effusion possibly related to bosutinib with concomitant pneumonia and a pre-treatment history of recurrent pleural effusions. Grade 3 – 4 hematologic laboratory abnormalities included thrombocytopenia in 65 pts (23%), neutropenia in 37 pts (13%) and anemia in 17 pts (6%). 124 pts (44%) had at least 1 temporary treatment interruption and 85 pts (30%) had at least 1 dose reduction due to toxicity. 37 pts (13%) have permanently discontinued treatment due to adverse event. Bosutinib is effective in pts with CP CML with resistance or intolerance to imatinib across a range of mutations. Unlike other tyrosine kinase inhibitors, bosutinib does not significantly inhibit PDGFR or c-kit, and this may be responsible for the relatively favorable toxicity profile with few pts experiencing hematologic toxicity or fluid retention.
46
Diana Putri Amalia. M, Elindra Yetti, and Tjipto Sumadi. "Motions and Songs to Improve Basic Literacy through Animation Videos." JPUD - Jurnal Pendidikan Usia Dini 16, no. 2 (November 30, 2022): 224–39. http://dx.doi.org/10.21009/jpud.162.03.
Full textAbstract:
The government incurs huge costs because of low literacy rates, which are associated with higher crime rates, poor health, and higher welfare costs, therefore the stimulation of basic literacy from an early age is important. This study aims to examine the effectiveness of animated motion learning media and songs that are interesting, innovative, and effective for improving basic literacy aspects of early childhood. This mixed-method design with the research and development stages of the ADDIE model was tested for the effectiveness of the media through a paired sample test. The research was divided into three stages, starting from needs analysis, product development, and product evaluation, involving 11 respondents in the effectiveness test. The data collection technique was carried out using a basic literacy instrument grid questionnaire, for child development, while for the feasibility of the media or products being developed it was also through a questionnaire from experts. Data were analyzed qualitatively and quantitatively. The results of the study show that there is a significant increase in basic literacy values through learning media. The findings of the integration of quantitative and qualitative data form the basis for preparing the final product to revise and complement the deficiencies of movement and song-learning media.
Keywords: basic literacy, animation media, motion, and song, early childhood
References:
Abidin, Y. (2015). Multiliteracy Learning An Answer to the Challenges of 21st Century Education in the Indonesian Context [Pembelajaran Multiliterasi Sebuah Jawaban atas Tantangan Pendidikan Abad Ke -21 dalam Konteks Keindonesiaan (D. Sumayyah, Ed.)]. PT Refika Aditama.
Bedard, C., Bremer, E., & Cairney, J. (2020). Evaluation of the Move 2 Learn program, a community-based movement and pre-literacy intervention for young children. Physical Education and Sport Pedagogy, 25(1), 101–117. https://doi.org/10.1080/17408989.2019.1690645
Bers, M. U. (2018). Coding, playgrounds, and literacy in early childhood education: The development of KIBO robotics and ScratchJr. 2018 IEEE Global Engineering Education Conference (EDUCON), 2094–2102.
Bhadra, A., Brown, J., Ke, H., Liu, C., Shin, E., Wang, X., & Kobsa, A. (2016). ABC3D - Using an Augmented Reality Mobile Game to Enhance Literacy in Early Childhood. 0–3.
Dodge, D. T., Colker, L. J., & Heroman, C. (2002). Creative Curriculum for Presschool (Fourth Edi). Cataloging in Publication.
Edwards, L. C. (2013). Music and Movement A way of Life for the Young Child (Seventh Ed). Pearson Education, Inc.
Fadillah, M., Filasofa, L. M. K., Wantini, Akbar, E., & Fauziyah, S. (2014). Early Childhood Education Edutainment (Creating Interesting, Creative, and Fun Learning) [Edutaintment Pendidikan Anak Usia Dini (Menciptakan Pembelajaran Menarik, Kreatif, dan Menyenangkan)]. Kencana Prenadamedia Group.
Fajriyah, L. (2018). Development of Emergent Literacy in Early Childhood [Pengembangan Literasi Emergen Pada Anak Usia Dini]. Proceedings of the ICECRS, 1(3). https://doi.org/10.21070/picecrs.v1i3.1394
Fox, J. E., & Schirrmacher, R. (2015). Art & Creative Development for Young Children (Eighth Edi). Cengage Learning.
Graber, K. C., & Woods, A. M. (2013). Physical Education & Activity for Elementary Classroom Teachers. Mc Graw Hill.
Heydon, R., McKee, L., & O’Neill, S. (2018). Singing our song: The affordances of singing in an intergenerational, multimodal literacy programme. Literacy, 52(3), 128–136. https://doi.org/10.1111/lit.12135
Jamaris, M. (2017). Multiple Intelligences Measurement [Pengukuran Kecerdasan Jamak]. Ghalia Indonesia.
Juniasih, I. (2015). Increasing Movement Creativity Through Story-Based Educational Dance Activities (Tarita) PAUD PPs Jakarta State University [Peningkatan Kreativitas Gerak Melalui Kegiatan Tari Pendikan Berbasis Cerita ( Tarita ) PAUD PPs Universitas Negeri Jakarta]. Jurnal Pendidikan Usia Dini, 9(2), 319–342.
Karaca, N. H. (2017). Implementation Of Thinking Creatively in Action And Movement Test For Turkish Children Eylem Ve Harekette Yaratıcı Düşünme Testi’nin Türk Çocuklarına Uyarlanması. Mehmet Akif Ersoy Üniversitesi Eğitim Fakültesi Dergisi, 0(42), 240. https://doi.org/10.21764/efd.26968
Lastari, A. A. I. I. A., Gading, I. K., & Antara, P. A. (2016). Audiovisual to Improve Kinesthetic Intelligence in Group B Children [Audiovisual Untuk Meningkatkan Kecerdasan Kinestetik Pada Anak Kelompok B]. Journal Pendidikan Anak Usia Dini Universitas Pendidikan Ganesha, 4(2).
Mariati, P., & Asmara, B. (2017). Development of Innovative Learning Models of Motion and Thematic Songs for Integrated Early Childhood Post Teachers (Ppt) in the City of Surabaya [Pengembangan Model Pembelajaran Inovatif Gerak Dan Lagu Tematik Bagi Guru Pos Paud Terpadu ( Ppt ) Di Kota Surabaya]. Jurnal Anak Usia Dini Dan Pendidikan Anak Usia Dini, 3, 9–20.
Mayesky, M. (2002). Creative activities for Young Children (7 Th Editi). Delmar Thomson Learning.
Nash, K., Howard, J., Miller, E., Boutte, G., Johnson, G., & Reid, L. (2018). Critical racial literacy in homes, schools, and communities: Propositions for early childhood contexts. Contemporary Issues in Early Childhood, 19(3), 256–273. https://doi.org/10.1177/1463949117717293
Pogue, B. J. (2018). Using Music and Movement to Enhance Cognitive Development Using Music and Movement to Enhance Cognitive Development. Education.
Priansa, D. J. (2017). Development of Innovative, Creative, and Achievement Learning Strategies & Models in Understanding Students [Pengembangan Strategi & Model Pembelajaran Inovatif, Kreatif, dan Prestatif dalam Memahami Peserta Didik]. Pustaka Setia.
Rakhmawati, N. I. S. (2016). The Use of Playing Strategy through Movements and Songs in Dealing Hypersensitivity Problems for Early Childhood. Proceedings of International Research Clinic & Scientific Publications of Educational Technology, 2013, 6–29.
Rasi, P., Vuojärvi, H., & Ruokamo, H. (2019). Media Literacy for All Ages. Journal of Media Literacy Education, 11(2), 1–19. https://doi.org/10.23860/jmle-2019-11-2-1
Respati, R., Nur, L., & Rahman, T. (2018). Motion and Song as a Model for Stimulating the Development of Kinesthetic Intelligence in Early Children [Gerak Dan Lagu Sebagai Model Stimulasi Pengembangan Kecerdasan Kinestetik Anak Usia Dini]. Jurnal Pendidikan Usia Dini, Vol.12(No.2), 321–330. https://doi.org/10.21009/JPUD.122.13
Rowe, M. L., Kirby, A. L., Dahbi, M., & Luk, G. (2022). Promoting Language and Literacy Skills through Music in Early Childhood Classrooms. The Reading Teacher, n/a(n/a). https://doi.org/10.1002/trtr.2155
Ruhaena, L. (2015). Multisensory Models: Solutions to Stimulate Literacy in Preschool Children [Model Multisensori: Solusi Stimulasi Literasi Anak Prasekolah]. Jurnal Psikologi, 42(1), 47–60.
Safitri, N., & Agustinus. (2017). Stimulation Dance Creations Art on Gross Motor Development Children Aged. Indonesian Journal of Early Childhood Education Studies, 6(1). https://doi.org/10.15294/ijeces.v6i1.15785
Tomblin, J. B., Oleson, J., Ambrose, S. E., Walker, E. A., & Moeller, M. P. (2018). Early Literacy Predictors and Second-Grade Outcomes in Children Who Are Hard of Hearing. Child Development, 91(1), e179–e197. https://doi.org/10.1111/cdev.13158
Tomblin, J. B., Oleson, J., Ambrose, S. E., Walker, E. A., & Moeller, M. P. (2020). Early Literacy Predictors and Second-Grade Outcomes in Children Who Are Hard of Hearing. Child Development, 91(1), e179–e197. https://doi.org/10.1111/cdev.13158
Trost, W. J., Labbé, C., & Grandjean, D. (2017). Rhythmic entrainment as a musical affect induction mechanism. Neuropsychologia, 96, 96–110. https://doi.org/10.1016/j.neuropsychologia.2017.01.004
Widhianawati, N. (2011). The Effect of Movement and Song Learning in Improving Musical Intelligence and Kinesthetic Intelligence in Early Children [Pengaruh Pembelajaran Gerak dan Lagu dalam Meningkatkan Kecerdasan Musikal dan Kecerdasan Kinestetik Anak Usia Dini]. Jurnal Upi Edu, 2, 220–228.
Yetti, E., & Muanivah, H. (2017). Improved Intelligence Kinesthetic Children Ages 5-6 Years through Activities of Motion and Song. 1, 16–20.
Yetti, E., Syafnita, T., & Siti Syarah, E. (2019). The Effect of Motion and Song on Children`s Speaking Ability. 178(ICoIE 2018), 429–433. https://doi.org/10.2991/icoie-18.2019.92
47
Blanco, Gonzalo, Anna Puiggros, María Rodríguez-Rivera, Carme Melero, María Dolores García-Malo, Rosa Collado, Margarita Ortega, et al. "Chromosome 8 Abnormalities (8p Losses and 8q Gains) in Patients with Chronic Lymphocytic Leukemia (CLL) and Del(17p)." Blood 124, no. 21 (December 6, 2014): 5638. http://dx.doi.org/10.1182/blood.v124.21.5638.5638.
Full textAbstract:
Abstract Basis. Abnormalities in chromosome 8 (8p-/8q+) are observed in 2-5% of CLL patients. Microarray studies have revealed up to 30-40% of 8 alterations in del(17p) patients and an independent association with poor outcome. Large series assessing CLL patients with 8p-/8q+ are scarce. Aims. 1. To describe the frequency of 8q gains (8q+) and 8p losses (8p-) in CLL patients with del(17p); 2. To compare cytogenetic and clinical characteristics between patients with 8p-/8q+ (Alt-chr8) and those with normal chromosome 8 (N-chr8); 3. To assess their prognostic value. Patients and methods. From 2,249 patients included in the Spanish CLL database, 75 del(17p) cases were selected. Gains of MYC (8q24) and losses of LPL (8p22) were studied by FISH. Clinical and cytogenetic data of Alt-chr8 and N-chr8 were compared. Results. 8p- and/or 8q+ were found in 21/75 patients (28%). In the Alt-chr8 group, 8q+ was more frequent than 8p- (71% vs. 52%) and 29% showed concomitance of both abnormalities, suggesting the presence of i(8q). Six different FISH patterns were identified, some of them coexisting in the same patient (Table 1). Conventional cytogenetics data were available in 47 cases (15 Alt-chr8 and 32 N-chr8). Alt-chr8 group showed a higher median number of alterations and frequency of complex karyotypes (P=0.048 and P=0.013). In the Alt-chr8 group, the karyotype revealed 8p-/8q+ in 3 patients and in 9 cases with abnormal karyotype, the presence of marker chromosomes, added material and/or cryptic alterations would explain the FISH results (Table 1). From 66 cases, routine FISH data (13q, 12 and 11q) were available and no significant differences were detected among Alt-chr8 and N-chr8, as with other clinical and analytical parameters at diagnosis. Of note, shorter Overall Survival (OS) was observed for Alt-chr8, although differences were only significant for patients with 8p- (P=0.012, Figure 1). Interestingly, for 3 patients of Alt-chr8 group, previous non-del(17p) samples already presented 8p-/8q+. Conclusions. 1. In CLL patients with del(17p), detection of 8p- and/or 8q+ is associated with an increased karyotypic complexity and a worse outcome; 2. 8p-/8q+ could act as a primary event that trigger del(17p). More cases are required to confirm this hypothesis. Acknowledgments.PI11/01621; RD12/0036/0044, RD12/0036/0069; 2014/SGR585; Fundació La Caixa. Table 1. Karyotypes and FISH results of patients with del(17p) and Alt-chr8. Conventional Cytogenetics FISH ID Karyotype % del(17p) Chromosome 8 alteration % Pattern* 1 46,XX,del(8)(p21),add(10)(q26),add(17)(p13),+2ac[5]/47,XX,+12,add(17)(p13),del(18)(q21),add(22)(q13)[3] 80 20 1O2G 8p- 2 - 95 75 3 46,XX,add(6)(q24),add(14)(q32,3),i(17)(q10)[6]/46,XX[8] 95 75 4 - 76 50 5 45,XY,-5,-9,-15,add(17)(p13),+18,-21,+2mar[13]/46,XY[37] 70 17 6 46,X,der(X),add(8)(p23),del(13)(q12q22),add(17)(p13)[11]/46,XX[13] 10 32 1O3G 8p- and 8q+ 7 - 95 64 8 45,XY,add(3)(q29),del(4)(q26q35),der(7)(1p36-1p32::7p22-7q32::15q22-15q26), -8,der(9),del(13)(q21q34),-15,-17,-18,+19,add(19)(p13),+2mar,+ac[17]/46,XY[3] 78 34/21 1O3G/2O3G 9 44,X,-X,-6,der(13;15)(q10;q10),add(17)(p13),-20,+mar[13]/46,XX[7] 95 10/23 1O3G/1O2G 10 - 95 66/31 11 45,XY,add(6)(q22),del(11)(q11q22),-17[15]/44,XY,add(6)(q22),del(11)(q11q22),-17,-20,-22,+mar[2] 87 40/24 12 46,XX,del(13)(q14q21)[2]/45,X,-X,del(13)(q14q21)[3]/45,XX,add(3)(q27), t(9;10)(q21;q22),+12,der(12)t(12;17)(q11;p11),del(13)(q14q21),-14,-17[7]/46,XX[8] 70 62 2O3G 8q+ 13 46,XY[30] 14 88 14 46,XY[13] 80 82 15 47,XY,+12[8]/46,XY,add(1)(p34),add(2)(q34),t(11;22)(p14;q11),+12,-22[15]/46,XY[11] 75 18 16 43,X,-X,del(2)(p15),+4,-7,add(11)(q21),-12,-13,add(14)(q32),add(17)(p11)[6]/46,XX[9] 19 14 17 45,XY,del(6)(q?),-9,add(14)(q32),-22,+mar[9]/ 46,XY,del(6)(q?),add(17)(p13),add(19)(q13)[21] 55 23 18 45,XY,add(6)(p11),-22[13]/46,XY,i(17)(q10)[5]/46,XY[16] 16 57 19 - 70 66 2O4G 20 - 90 81 2OnG 21 46,XY[11] 43 60 4O4G Tetraploid *O: LPL signal in orange, G: MYC signal in green. Figure 1. Kaplan Meier plots for OS and (A) 8p- and/or 8q+, (B) 8p- or (C) 8q+. Figure 1. Kaplan Meier plots for OS and (A) 8p- and/or 8q+, (B) 8p- or (C) 8q+. Disclosures No relevant conflicts of interest to declare.
48
Kim, S. H., T. N. Olson, N. W. Schaad, and G. W. Moorman. "Ralstonia solanacearum Race 3, Biovar 2, the Causal Agent of Brown Rot of Potato, Identified in Geraniums in Pennsylvania, Delaware, and Connecticut." Plant Disease 87, no. 4 (April 2003): 450. http://dx.doi.org/10.1094/pdis.2003.87.4.450c.
Full textAbstract:
The Plant Disease Diagnostic Laboratory of the Pennsylvania Department of Agriculture received diseased geranium (Pelargonium × hortorum) samples from several Pennsylvania (PA) greenhouses in 1999 and 2000 and from one Delaware (DE) greenhouse in 1999. Originating from Guatemala, plants exhibited yellowing, wilting, stunting, and bacterial oozing from the vascular tissues. Isolations on yeast dextrose-CaCO3 (YDC) and triphenyl-tetrazolium-chloride (TTC) agars resulted in off-white mucoid colonies and white, fluidal colonies with pink centers, respectively. Such colonies are typical of Ralstonia solanacearum (1). The disease was similar to a bacterial wilt of geranium caused by an unidentified biovar of R. solanacearum (3). Preliminary tests using Biolog MicroLog 3 (Hayward, Ca; 4.01A) and enzyme-linked immunosorbent assay (ELISA) (Agdia Inc., Elkhart, IN; BRA 33900/0500) identified the organism as R. solanacearum. For pathogenicity tests, a 10-μl droplet of water suspension containing 1 × 106 CFU of each of five geranium strains (PDA 22056-99, 81849-99, 81862-99, 51032-00, and 64054-00) per milliliter was placed on a stem wound made by cutting off the terminal growth of each of 4 6-leaf stage plants of geranium ‘Orbit Scarlet’, tomato ‘Rutgers’, potato ‘Russet Norkotah’, and eggplant ‘Black Beauty’ in a growth chamber at 28°C, 86% relative humidity, and 12 h light/dark cycle. Water was included as a control. The five strains caused severe yellowing and wilting within 10 days. Colonies typical of R. solanacearum were reisolated from symptomatic tissue on YDC and TTC. To determine the specific biovar, 20 pathogenic geranium strains from PA and DE plus a strain of R. solanacearum originally isolated from a geranium plant of Guatemalan origin received from Connecticut in 1995 were grown up to 28 days on Ayers mineral medium supplemented with a 1% final concentration of D-cellobiose, dextrose, meso-inositol, lactose, maltose, D-ribose, trehalose, mannitol, sorbitol, or dulcitol (1). Acid was produced by 21 test strains from the first five carbohydrates only. Such carbohydrate utilization is typical of bv 2 (1). Bv 2 identification was confirmed by real-time polymerase chain reaction using bv 2-specific primers and probes (N. Schaad, unpublished) designed from a bv 2-specific DNA fragment (2). All tested strains were positive using ELISA. In contrast, strains of bv 2 from geraniums in Wisconsin and South Dakota were reported to be negative using ELISA (4). From our results, it appears that bv 2 was introduced into the United States on geraniums from Guatemala in 1995 and 1999. This cool climate bv 2, a regulated agent by the Agricultural Bioterrorism Protection Act of 2002, has caused extensive crop loss in potatoes in Europe, but has not been found in potatoes in the United States. References: (1) T. P. Denny and A. C. Hayward. Ralstonia solanacearum. Pages 151–174 in: Lab Guide for Identification of Plant Pathogenic Bacteria. N. W. Schaad et al. eds. 3rd ed. The American Phytopathological Society, St. Paul, MN, 2001. (2) M. Fagen et al. Development of a diagnostic test based on the polymerase chain reaction (PCR) to identify strains of R. solanacearum exhibiting the Biovar 2 genotype. Pages 34–43 in: Bacterial Wilt Disease: Molecular and Ecological Aspects. P. H. Prior et al. eds. Springer-Verlag, Berlin, 1998. (3) D. L. Strider et al. Plant Dis. 65:52, 1981. (4) L. Williamson et al. (Abstr.) Phytopathology 91 (Suppl.):S95, 2001.
49
Hearn, Jason W. D., Christopher Sweeney, Nima Almassi, Chad A. Reichard, Chandana A. Reddy, Brian Hobbs, David Frazier Jarrard, et al. "HSD3B1 and overall survival (OS) in men with low-volume (LV) metastatic prostate cancer (PCa) treated with androgen deprivation therapy (ADT) or chemohormonal therapy in the CHAARTED Randomized trial." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 5020. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.5020.
Full textAbstract:
5020 Background: The HSD3B1(1245A > C) variant allele, whose frequency varies by race, encodes a missense sequence that stabilizes the rate-limiting enzyme responsible for extragonadal androgen synthesis, thus enhancing intratumoral dihydrotestosterone (DHT) synthesis. Multiple retrospective studies have found that men inheriting the HSD3B1(1245C) variant allele exhibit early resistance to ADT. We sought to validate these findings with prospective data from the Chemohormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED). Methods: Men with newly metastatic PCa were randomized to receive either ADT plus docetaxel at a dose of 75 mg/m2 every 3 weeks for 6 cycles (arm A) or ADT alone (arm B). We determined germline HSD3B1 genotype in the subset of men with LV disease ( < 4 bone metastases, no visceral metastases). We analyzed freedom from castration-resistant prostate cancer (CRPC) and OS according to HSD3B1 genotype using Cox and Kaplan-Meier methods. Results: 197 patients with LV disease had blood samples available and were genotyped, including 97 in arm A and 100 in arm B. Docetaxel did not improve OS of LV men. Of the 197 men, 47% were homozygous wild-type (WT), 43% were heterozygous, and 10% were homozygous variant. When all 197 men were analyzed as one goup, the median time to CRPC was 39.7 mos. in homozygous WT men vs. 25.0 mos. in men with one or more copies of the variant allele (HR 1.27, 95% CI 0.89 to 1.82; p = 0.187). Although OS data are still maturing, at 52 months OS was 83% (95% CI 75% to 91%) in homozygous WT men vs. 64% (95% CI 55% to 74%) in men with one or more variant alleles. There was a suggestion that docetaxel delayed development of CRPC among men with at least 1 variant allele (20.3 vs. 40.7 mos.; HR 0.66, 95% CI 0.40 to 1.04; p = 0.08). Benefit for men with high-volume disease was not evident. Conclusions: Inheritance of the HSD3B1(1245C) allele that augments DHT synthesis may be associated with lower OS in men treated with ADT with or without docetaxel for LV newly metastatic PCa. Additional study is warranted in patients with LV disease. Clinical trial information: NCT00309985.
50
Lal, Ashutosh, Nancy Sweeters, Vivian Ng, Drucilla Foote, Patricia Evans, Lynne Neumayr, Gregory Kurio, Paul Harmatz, John B. Porter, and Elliott Vichinsky. "Combined Chelation Therapy with Deferasirox and Deferoxamine In Transfusion-Dependent Thalassemia." Blood 116, no. 21 (November 19, 2010): 4269. http://dx.doi.org/10.1182/blood.v116.21.4269.4269.
Full textAbstract:
Abstract Abstract 4269 Therapeutic regimens that combine two iron chelators may enhance chelation efficiency by improving access to different tissue iron stores and control of the toxic labile iron pool. The combination of two chelators can reduce toxicity through averting the need for high doses of a single drug, but it is essential to establish the safety such regimens. We therefore explored the combined use of deferasirox (DSX) and deferoxamine (DFO) in patients with transfusion-dependent thalassemia who had failed standard chelation therapy with single drug. Patients were eligible if the liver iron concentration (LIC) >15 mg/g dry liver-weight or if iron-induced end organ injury was present. Subjects were monitored for hepatic and renal toxicity, visual or auditory changes, and the development of new complications from iron overload. The ability of the combined therapy to control systemic iron burden (serum ferritin and LIC) and myocardial iron overload (MRI T2*) was evaluated. We also measured changes in plasma levels of non-transferrin bound iron (NTBI) and labile plasma iron (LPI). Fifteen subjects were enrolled in 3 groups: adults with LIC <15 mg/g dry liver-weight (group A), adults with LIC >15 mg/g (group B), and children 8–18 years with LIC >5 mg/g (group C). The duration of therapy was 52 weeks. DSX (20-30 mg/Kg) was administered daily and DFO (35-50 mg/Kg/infusion) was infused on 3–7 days/week (as 8–12 hour infusion) based upon the degree of iron overload present at baseline. At the initiation of the study, the mean daily dose of DFO was 16, 33, and 17 mg/Kg/day and mean DSX dose was 21, 25 and 22 mg/Kg/day for groups A, B and C, respectively. At the conclusion of the trial, the median LIC declined by 48% from 10.8 mg/g (3.9-34.8 mg/g) to 5.7 mg/g (1.0-24.0 mg/g, p=0.003). The median ferritin fell by 43% from 2030 ng/mL (1000-5230 ng/mL) to 1150 ng/mL (421-5260 ng/mL, p=0.008). Myocardial iron in the 3 subjects who had T2* <20 msec at study entry (range 6.5–19.5 msec at week 0) showed an average improvement of +2.43 msec following treatment (range 8.8–21.3 msec at week 52, p=0.027). All 3 subjects with left ventricular ejection fraction below 60% at baseline (47.5-58.1%) showed improvement at end of study (60.6-64.4%). There was progressive decline in median plasma NTBI level during the study from 3.26 μM (1.79-5.79 μM) at baseline to 2.38 μM (1.59-3.08 μM) at 12 months (p=0.008). DSX produced immediate and significant decline in plasma NTBI when administered during infusion of DFO. The median plasma NTBI measured on DFO alone was 2.46 μM (0.92-5.90 μM), which decreased to 1.96 μM (0-3.50 μM) following administration of the dose of DSX (p<0.001). A sustained control of the LPI fraction was also demonstrated throughout the study period. At baseline the median LPI was 0.87 μM (0-2.43 μM) which decreased to 0.05 μM (0-1.20 μM) during the study period (p=0.004). No significant toxicity or unusual adverse events were observed with combined chelation therapy in this group of high-risk patients with thalassemia. Elevation of serum creatinine or ALT was not observed in any subject. One subject from group B died at 9 weeks from start of trial from sepsis. One subject interrupted DSX therapy because of abdominal pain. In all other cases the treatment was well tolerated and no dose adjustment or suspension of therapy was required on account of toxicity. Protocol-mandated modification of treatment (temporary cessation of DSX or DFO) occurred in three subjects owing to a marked fall in serum ferritin and LIC. These results suggest that simultaneous administration DSX and DFO is well tolerated and has low potential for toxicity. Combined chelation therapy appears to be effective in rapidly reducing systemic iron burden, lowering myocardial iron, and controlling plasma NTBI and LPI in patients at risk of developing end-organ damage. Disclosures: Harmatz: Ferrokin: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Vichinsky:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.