Barrier chemicals are used for coating a substrate fabric surface when air-proofness or water-proofness is desired in military operations. The properties of the base fabric changes depending upon the barrier chemical employed for coating. In this study, authors selected inherently flame retardant Kevlar as base fabric and coating was done using four chemicals viz: Natural rubber (NR), Polyurethane (PU), Neoprene, and Hypalon. While NR and PU readily burn, Neoprene and Hypalon resist ignition due to the presence of chlorine atom. The resultant flame retardant properties were studied using UL-94 V and NFPA-701 methods. Although Kevlar is flame retardant in nature, it was observed that some coatings burned readily leaving behind charred base fabric.

Concrete is the common extensively utilized man-made material in the world. Concrete plays an important role in our Infrastructure development that shows our status worldwide among the other nations. One of the difficulties that have arisen since the introduction of concrete structures in the building business is how to increase concrete strength while still being efficient and cost-effective. The use of novel materials in concrete will boost the strength of the concrete in a more significant way; one such development is High Strength Concrete.

Barrier chemicals are used for coating a substrate fabric surface when air-proofness or water-proofness is desired in military operations. The properties of the base fabric changes depending upon the barrier chemical employed for coating. In this study, authors selected inherently flame retardant Kevlar as base fabric and coating was done using four chemicals viz: Natural rubber (NR), Polyurethane (PU), Neoprene, and Hypalon. While NR and PU readily burn, Neoprene and Hypalon resist ignition due to the presence of chlorine atom. The resultant flame retardant properties were studied using UL-94 V and NFPA-701 methods. Although Kevlar is flame retardant in nature, it was observed that some coatings burned readily leaving behind charred base fabric.

SJL/J mice exhibit a high incidence of mature B-cell lymphomas that require CD4+ T cells for their development. We found that their spleens and lymph nodes contained increased numbers of germinal centers and T follicular helper (TFH) cells. Microarray analyses revealed high levels of transcripts encoding IL-21 associated with high levels of serum IL-21. We developed IL-21 receptor (IL21R)–deficient Swiss Jim Lambart (SJL) mice to determine the role of IL-21 in disease. These mice had reduced numbers of TFH cells, lower serum levels of IL-21, and few germinal center B cells, and they did not develop B-cell tumors, suggesting IL-21–dependent B-cell lymphomagenesis. We also noted a series of features common to SJL disease and human angioimmunoblastic T-cell lymphoma (AITL), a malignancy of TFH cells. Gene expression analyses of AITL showed that essentially all cases expressed elevated levels of transcripts for IL21, IL21R, and a series of genes associated with TFH cell development and function. These results identify a mouse model with features of AITL and suggest that patients with the disease might benefit from therapeutic interventions that interrupt IL-21 signaling.

The research examines the outcomes of shear and flexure testing on reinforced concrete beams made from steel and polypropylene fibre. As well as assessing the impact of fibre in this structural integrity with shear strengthening ratios, certain elements in the characteristics of the cement that is both new and hardened are presented. 14 square beams being put into practice. Tests were made. There were beams produced from 7 distinct mixing dimensions, depending on the kind and the fibre content. For each composite mix there were two beams: one with and the other without stirrups. The primary changes caused by the introduction of fibres were enhanced shear strength, rigidity (especially after the first breaking stage) and ductility. The characteristics of hard concrete (tensile strength, compressive strength and elasticity modules), longitudinal reinforcement concrete, stresses in stirrups, were other factors utilized for the analysis of performance (at the compression and web zone).

This paper deals with the preparation, characterization, and isothermal study on lead removal from synthetic solution using an algae Liagora viscida. The sorption experiments were performed by batch mode of operation and the parametric conditions studied are pH (2–8), contact time (1–180 min), and initial metal solution concentration (20–200 mg/L). The surface morphology of the Liagora viscida has been described using Scanning electron microscopy (SEM). Isothermal study confirmed that the data is well fitted by Freundlich isotherm. In summary, the inexpensive marine algae Liagora viscida proved as an excellent sorbent for lead removal from synthetic solution.

The proposed Lumped Parameter Thermal Model (LPTM) is complex enough to predict temperatures in most parts of the 3ɸ- Squirrel Cage Induction Motor (3ɸ-SCIM), including the end winding and rotor surface temperatures. It is easily adaptable to a variety of frame sizes because it is formulated using dimensional information and constant thermal coefficients. The solution of linear differential equations adequately describes the thermal behavior of the 3ɸ-SCIM. The application of the thermal model on 15 kW 3ɸ-SCIM is discussed. The rise in temperature at different parts of motor is estimated considering copper loss, constant and variable core loss. The maximum flux density derived from Finite Element Method (FEM) analysis, used to calculate core loss at various loads of a 3ɸ-SCIM. Variable core loss causes deviation in temperature rise, from the results, it is observed that, the relative percentage error considering variable core loss to constant core loss is about 19 %.

Background: One third of patients with myelodysplastic syndrome (MDS) relapse after allogeneic stem cell transplantation (HCT). Early detection of impending relapse would enable pre-emptive treatment and potentially reduce relapse risk but is limited by the lack of sensitive markers for measurable residual disease (MRD). We developed a pipeline where patient-specific mutations, as determined by a myeloid next generation sequencing (NGS) panel are tracked using digital droplet PCR (ddPCR). Aims: To evaluate if personalized MRD detection by ddPCR can predict clinical relapse earlier than conventional methods. Methods: The prospective study (NCT02872662) enrolled patients with MDS, MDS/MPN or MDS-AML with < 30% marrow blasts undergoing HCT. Patients were included before HCT, and serial bone marrow (BM) samples were collected every third month post-HCT for 2 years. Peripheral blood (PB) samples were collected monthly. MRD results were not available for the treating physician. Results: We screened 286 pts between 2016 and 2020, whereof 20 were excluded mainly due to lack of genetic aberration or no HCT performed. 266 pts were included from 12 HCT centers. Median age was 64 (18-78) years and 59% were male. Myeloid panel NGS screening identified a median of 2 (0-9) mutations. The most common mutations were TET2 (n=85), ASXL1 (n=73) and SRSF2 (n=59). Median time of follow up was 886 (4-1934) days. Sixty pts relapsed after a median of 189 (53-1281) days and 46 died due to non-relapse mortality after a median of 121 (4-1036) days. Remaining pts (n=160) were in continuous complete remission (CCR) after a median follow-up of 1053 (479-1934) days. Estimated 1 and 2y overall survival was 79%, and 71%, respectively, while estimated 1 and 2y relapse-free survival (RFS) was 75% and 66%, respectively. MRD data was missing in 46 pts; no post-HCT samples available (n=15), no mutation detected (n=14) and difficulties to design ddPCR primers (n=11). 221 pts were available for MRD analysis with a median number of 4 (0-13) and 5 (0-23) samples from BM and PB, respectively. Of 53 clinical relapses with MRD results available, 42 were preceded by pos MRD (>0.1%) with a median of 70 (range 20-425) days between first pos MRD and clinical relapse. For the 11 remaining pts, 8 were inadequately sampled with a median time of 189 (82-397) days between last sampling and clinical relapse. One patient had an extramedullary relapse only. Of 31 pts who died without relapse, 19 were consistently MRD neg, while 5 were borderline positive (MRD > 0.1% and <0.5%) during the first 100 days but negative thereafter. Four MRD+ patients died without clinical relapse. Three pts were initially MRD+ but turned negative, all of which had chronic GVHD (cGVHD). Of 136 CCR patients, 94 were consistently MRD neg; 26 were borderline pos (MRD > 0.1% and <0.5%) during the first 100 days followed by neg samples; 16 were MRD positive (either > 0.5% during the first 100d or > 0.1% after 100d) of which 10 had a transition from pos to neg samples (all had cGVHD); one patient was treated for a molecular relapse detected by clinical routine method (FISH) and five patients were MRD positive at time of last follow-up. MRD used as a time-dependent co-variate was negatively associated with RFS (HR 7.1, p<0.01). Estimated cumulative incidence of relapse and non-relapse mortality 2y after pos MRD was 60% and 7% respectively (see figure). Image:Summary/Conclusion: We report the development of a highly functional personalized MRD pipeline based on patient-specific mutations showing a high sensitivity to predict relapse and relapse-free survival.

Background: The EUMDS Registry started in 2008 as a prospective, non-interventional longitudinal study, enrolling newly diagnosed patients with IPSS low or intermediate-1 MDS from 16 European countries and Israel. Aims: The aim of the present analysis was to see how treatment with or without Erythropoietin Stimulating Agents (ESAs) and/or red blood cell transfusions (RBCT) impact overall survival (OS) and quality of life (QoL). Methods: Patient management was recorded electronically every 6 months (“visit”) in a central database, including treatment, transfusions, blood values, and health related quality of life (HRQoL) using the EQ-5D 3-Level index and Visual Analog Scale (VAS). Patients were eligible to be included in the analyses if their hemoglobin was recorded as less than <10 g/dl at a visit. To overcome potential confounding by non-random allocation of ESA treatment, propensity score matching was performed to ensure that treated and untreated patients had similar characteristics. Only patients with comparable propensity scores were included in the analyses to estimate the effects of ESA treatment on outcomes using standard time to event analyses; OS was estimated from the first visit a Hb value of <10g/dl was recorded. OS was examined for patients treated with ESA stratified by their transfusion status prior to commencing ESA treatment (no RBCT, <4 units, ≥4 units). Patients were separated into 4 groups at each clinical visit, depending on the treatment received in the interval leading up to that visit; no ESA nor RBCT, ESA only, ESA and RBCT and RBCT only. HRQoL at each visit according to the treatment status was summarized for patients who had completed a questionnaire at visit 1 and 2; mean values were examined by treatment group. Results: Of 2562 patients registered by November 2021, 2448 were diagnosed before July 2019 and included in the analysis; these patients were divided into two groups: ESA untreated (n=1265) and ESA treated (n=1183). Patients whose Hb remained above 10g/dl were excluded leaving 529 untreated patients and 749 ESA treated; after propensity score matching was applied two comparable groups were produced: ESA untreated (n= 426) and ESA treated (n= 742). Median OS from reaching the eligibility criteria in the ESA treated vs untreated groups were 44.9 and 34.8 months respectively (Fig 1a), giving a clear survival advantage to the ESA-treated group. (p<0.003). In the ESA-treated group, OS was poorer in those who had been transfused prior to commencing ESA (Fig 1b, p<0.001). Fig 1c shows the number of patients at each visit who had been treated with transfusions or ESA; 647/1278 had received neither at visit 1, the figure shows the “flow” of patients by treatment for the first 6 visits. HRQoL was examined for the 695 patients who had completed a questionnaire at both visit 1 and 2 up to visit 6; differences were seen by treatment (Fig 1d). Patients who had received no treatment reported, on average, the highest mean HRQoL, in contrast, patients who had RBCT had the lowest (p<0.001). Image:Summary/Conclusion: This unique large prospective registry study clearly shows a significant survival advantage for lower-risk MDS patients exposed to ESA treatment at onset of anemia (Hb <10g/dL) but before onset of transfusion therapy, strongly supporting recommendations to start ESA treatment early. The effect on patients with an early transfusion need warrants further studies. Moreover, ESA exposure is associated with maintained QoL, while RBCT development with or without ESA exposure is associated with significantly deterioration in QoL.

Azacitidine is a mainstay of therapy for high-risk MDS and other myeloid neoplasms. A significant correlation between azacitidine response and clinical outcome suggests a potential role of mutational profiling based on next-generation sequencing (NGS) before and after therapy in evaluating response and predicting overall survival (OS), which however has not fully elucidated. Here through NGS-based mutational profiling of large cohorts (n=451) of azacitidine-treated patients with high-risk MDS and other myeloid neoplasms, we show significant roles of multi-hit TP53 and germline DDX41 mutations in pre-treatment samples and post-treatment clone size in the evaluation/prediction of azacitidine response and OS after azacitidine therapy, which outperformed the prediction based only on clinical response and IPSS-R score. Post-treatment clone size strongly correlated with clinical response with exception of large persistent mutations frequently affecting TET2 after achieving complete remission and those with DDX41 mutations, which poorly correlated with clinical response. Our results highlight the importance of evaluating mutations in both pre- and post-treatment samples in the assessment of response and the prediction of OS after azacitidine therapy.

The 2016 revision of the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues is characterized by a closer integration of morphology and molecular genetics. Notwithstanding, the myelodysplastic syndrome (MDS) with isolated del(5q) remains so far the only MDS subtype defined by a genetic abnormality. About half of MDS patients carry somatic mutations in spliceosome genes, with SF3B1 being the most commonly mutated one. SF3B1 mutation identifies a condition characterized by ring sideroblasts, ineffective erythropoiesis, and indolent clinical course. A large body of evidence supports recognition of SF3B1-mutant MDS as a distinct nosologic entity. To further validate this notion, we interrogated the dataset of the International Working Group for the Prognosis of MDS (IWG-PM). Based on the findings of our analyses, we propose the following diagnostic criteria for SF3B1-mutant MDS: (i) cytopenia as defined by standard hematologic values; (ii) somatic SF3B1 mutation; (iii) morphologic dysplasia (with or without ring sideroblasts); (iv) bone marrow blasts <5% and peripheral blood blasts <1%. Selected concomitant genetic lesions represent exclusion criteria for the proposed entity. In patients with clonal cytopenia of undetermined significance, SF3B1 mutation is almost invariably associated with subsequent development of overt MDS with ring sideroblasts, suggesting that this genetic lesion provides presumptive evidence of MDS in the setting of persistent unexplained cytopenia. Diagnosis of SF3B1-mutant MDS has considerable clinical implications in terms of risk stratification and therapeutic decision making. In fact, this condition has a relatively good prognosis and may respond to luspatercept with abolishment of transfusion requirement.

Background: There are limited treatment options for red blood cell (RBC) transfusion dependent (TD) LR (IPSS Low/Int-1) MDS patients who are relapsed/refractory to ESAs. Imetelstat is a first-in-class telomerase inhibitor that targets cells with short telomeres and active telomerase, characteristics observed in some MDS patients across all disease stages. Preliminary results show that imetelstat is effective treatment in LR-MDS patients inducing durable TI (Steensma et al ASH 2018 Abstr463). Aims: We report updated efficacy data with a median follow-up of 12.1 months in 38 LR non-del(5q) MDS patients, R/R to ESA and LEN/HMA naive from the open-label, single-arm Part 1 of IMerge, an ongoing phase 2/3 study (NCT02598661). Methods: Part 1 of the IMerge study included patients with LR MDS, who were heavily transfused (≥4U/8wks), were R/R to ESA or had sEPO >500 mU/mL. Imetelstat 7.5 mg/kg was administered IV every 4 weeks. The primary endpoint was 8-week TI rate; key secondary endpoints included 24-week TI rate, safety, duration of TI, and hematologic improvement (HI) rate. Among the initially enrolled patients, higher 8-week TI rate was observed in the non-del5q, LEN/HMA naive patients. Therefore, the study was amended to subsequently enroll only these patients. From a total of 57 patients enrolled in Part 1, 38 were non-del(5q), LEN/HMA naïve patients (13 in the initial and 25 in the expansion cohort). Here we report long-term efficacy, safety and biomarker data from these 38 patients. Results: Median baseline RBC transfusion burden was 8U/8weeks (range 4–14), 37% of the patients had IPSS Int-1; 71% had WHO 2001 RARS or RCMD-RS subtype and 32% with evaluable sEPO levels had baseline level >500 mU/mL. As of 23 January 2019, median follow-up was 12.1 months for the 38 patients, representing 30.4 and 11.6 months for the initial 13 and additional 25 patients, respectively. The 8-week TI rate was 45% (17/38) and median TI duration was 8.5 months (range 1.8–32.4). Of the 17 responding patients, 10 (59%) remained transfusion free for over 24 weeks. The 8-week TI rate did not differ based on the presence of ring sideroblasts or baseline sEPO levels. The 24-week TI rate was 26% (10/38). Erythroid HI, defined as transfusion reduction by at least 4 units /8 weeks (IWG2006), was achieved in 68% (26/38) of the patients. The most frequently reported adverse events were manageable and reversible grade ≥3 cytopenias. 6/38 patients had IPSS-R intermediate/poor cytogenetic risk. All 6 patents achieved 8-week TI; 2/6 patients achieved partial cytogenetic response. Post treatment decrease in telomerase hTERT RNA level was observed in 25/34 (73.5%) patients with available sample. Among 7 patients with pre- and post-treatment mutation analyses, six had SF3B1 mutations at baseline, and a decrease in the mutation VAF was observed in 2 patients that had longest TI duration on study. Summary/Conclusion: In high RBC transfusion burden patients with non-del(5q) LR-MDS R/R to ESA and naive to LEN/HMA, single-agent imetelstat yielded 8-week TI rate of 45%, with a median duration of 8.5 months (range 1.8–32.4). The 24-week TI rate was 26%. HI-E rate was 68%. All patients with IPSS-R intermediate and poor cytogenetic risk responded. Biomarker analyses of telomerase activity and mutation allele burden indicate an effect on the malignant mutant clone. These data support Part 2 of IMerge, Phase 3 placebo-controlled, randomized portion of the study, expected to open mid-2019.