ALBERT

Description: In this research study, a multiterminal voltage source converter (VSC) medium voltage DC (MVDC) distribution network hierarchical control scheme is proposed for renewable energy (RE) integration in a co-simulation environment of MATLAB and PSCAD/EMTDC. A DC optimal power flow (DC OPF) secondary controller is created in MATLAB. In PSCAD/EMTDC, the main circuit containing the adaptive DC voltage droop with a dead band and virtual synchronous generator (VSG) based primary controller for the VSCs is implemented. The simulation of the MVDC network under the proposed hierarchical control scheme is investigated considering variations in wind and solar photovoltaic (PV) power. The network is also connected to the standard IEEE-39 bus system and the hierarchical scheme tested by assessing the effect of tripping as well as restoration of the REs. The results show that during random variations in active power such as increasing wind and PV power generation, a sudden reduction or tripping of wind and PV power, the primary controller ensures accurate active power sharing amongst the droop-based VSCs as well as regulates DC voltage deviations within the set range of 0.98–1.02 pu with an enhanced dynamic response. The DC OPF secondary control optimizes the system’s losses by 38% regularly giving optimal droop settings to the primary controllers to ensure proper active power balance and DC voltage stability. This study demonstrates that the hierarchical control strategy is effective for RE integration in the MVDC distribution network.

Description: Electric vehicles (EVs) have been receiving greater attention as a tool for frequency control due to their fast regulation capability. The proliferation of EVs for primary frequency regulation is hampered by the need to simultaneously maintain industrial microgrids dispatch and EV state of charge levels. The current research aims to examine the operative and dominating role of the charging station operator, along with a vehicle to grid strategy; where, indeterminate tasks are executed in the microgrid without the EVs charging/discharging statistics. The role of the charging station operator in regulation is the assignment of the job inside the primary frequency control capacity of electric vehicles. Real-time rectification of programmed vehicle to grid (V2G) power ensures electric vehicles’ state of charge at the desired levels. The proposed V2G strategy for primary frequency control is validated through the application of a two-area interconnected industrial micro-grid and another microgrids with renewable resources. Regulation specifications are communicated to electric vehicles and charging station operators through an electric vehicle aggregator in the proposed strategy. At the charging station operator, V2G power at the present time is utilized for frequency regulation capacity calculation. Subsequently, the V2G power is dispatched in light of the charging demand and the frequency regulation. Furthermore, V2G control strategies for distribution of regulation requirement to individual EVs are also developed. In summary, the article presents a novel primary frequency control through V2G strategy in an industrial microgrid, involving effective coordination of the charging station operator, EV aggregator, and EV operator.

Description: The advent of renewable energy resources and distributed energy systems herald a new set of challenges of power quality, efficient distribution, and stability in the power system. Furthermore, the power electronic converters integration has been increased in interfacing alternate energy systems and industries with the transmission and distribution grids. Owing to the intermittency of renewable energy resources and the application of power electronic converters the power distribution faces peculiar challenges. The dead-time effects are among the main challenges, which leads to the distortion of third harmonics, phase angle, torque pulsation, and induction motor current, causing severe quality problems for power delivery. To tackle these problems, this paper proposes a novel dead time compensation technique for improving the power quality parameters and improving the efficiency of power converters. The proposed model is simulated in MATLAB and the parametric equations are plotted against the corresponding parametric values. Furthermore, by implementing the proposed strategy, significant improvements are attained in the torque pulsation, speed, and total harmonic distortion of the induction motor. The comparisons are drawn between with and without dead time compensation technique, the former shows significant improvements in all aspects of the power quality parameters and power converters efficiency.

Description: Background and Objective: Disease relapse remains the primary cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Oral azacitidine (5-aza) was associated with clinical benefit as maintenance therapy in transplant ineligible patients. However, contradicting data have been reported regarding the role of 5-aza as a maintenance therapy to reduce relapse rate -post-allo-HSCT. We conducted this systematic review to describe the efficacy and safety of 5-aza in this context. Materials and Methods: We systematically searched multiple databases, including PubMed, Embase, Cochrane, and Clinicaltrials.gov. We also searched major conferences for oral or poster presentations. We used MeSH terms and keywords for MDS, AML, Allo-HSCT, and 5-aza. We included all retrospective and prospective studies of 5-aza (all formulations) published until March 2020. The primary database search yielded 1209 articles. We excluded irrelevant, duplicate, and review articles. The final search revealed 20 articles that we explored in detail for various efficacy and safety outcomes. Results: A total of 1211 patients were enrolled in 14 prospective and 6 retrospective studies. Of those, 1169 patients were evaluable. Prospective studies CALGB 100801 trial by Vij et al. (2015) reported overall survival (OS) of 45.7% and progression-free survival (PFS) of 41.2% at 24 months following reduced intensity conditioning (RIC) in a phase 2 trial of 41 patients. In a randomized control trial, Oran et al. (2018) evaluated relapse-free survival (RFS) as the primary outcome after 12 cycles of 5-aza at 32 mg/m2/day (n=187). Only 30% of the patients in the azacitidine arm completed the targeted number of cycles. The study showed a median RFS of 24.8 months in the treatment arm vs 15.3 months in the control arm (p=0.43). In a phase 2 trial conducted by Guillaume, T et al. (2019) the cumulative incidence of relapse was 27.6% in patients who received 5-aza, compared with 41.9% in 58 matched patients control group (p=0.21). Platzbecker et al. (2018-2019) studied a higher dose of azacitidine (75mg/m2/day) in a phase 2 trial as a pre-emptive strategy for patients who develop minimal residual disease (MRD) within 24 months. The 12-month OS and PFS were 94% and 44%, respectively. De Lima et al. (2018) studied the role of maintenance Oral 5-aza in Phase I/II trial (n=30). A dose-escalation design was used with a dosage ranging from 150 mg to 400 mg, received in a 7- or 14-day cycles. The 12-month PFS was 54% and 72% and estimated survival was 86% and 81% among 7-days and 14-days cycles, respectively. (Table 1) Retrospective studies: Mishra et al. (2017) reported a better OS in 14 patients who received 5-aza maintenance compared with a control arm (p-value 0.026). Cheikh et al. reported a 12-month OS of 70%. Ali, N et al. (2020) (n=107) compared 5-aza group vs. control group retrospectively. EFS was 53.1% vs. 49.5% (p=0.02) while OS was 56.8 and 53.4 months (p=0.01) in the treatment arm vs the control arm respectively. Safety: The most common grade 3 or 4 hematological adverse effect was neutropenia, while some patients also experienced grade 3 or 4 anemia, thrombocytopenia, or lymphopenia. The main non-hematological adverse effects were infections, fatigue, and gastrointestinal distress. The incidence of acute graft versus host disease varied from 13% to 50%. The most common reason for treatment discontinuation was disease relapse. A minority of patients discontinued treatment due to side effects. Conclusion: To our knowledge, this is the first comprehensive systematic review for the role of 5-aza maintenance -post-Allo-HSCT in patients with MDS or AML. The heterogeneity of the studies, in terms of dosing regimens, variable duration of treatment and patient selection, precludes definitive conclusions. Despite that, 5-aza seems to improve relapse rates and OS at least numerically but also significantly in some studies, as illustrated in this review. Low number of patients involved in most of these studies contributed to non-significant p-values. Azacitidine remains a valid and safe option, especially in patients with high risk of relapse. Further studies aiming at those high risk patients, such as AML with myelodysplasia related changes (AML-MRC) and high-risk MDS following RIC, are of utmost need. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Takeda: Consultancy, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Janssen: Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Karyopharm: Speakers Bureau; Jazz: Consultancy, Speakers Bureau.

Description: Background: Philadelphia negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF). MPNs can progress to accelerated and blast phase (MPN-AP/BP), defined by blast percentage of 10-19% and ≥20%, respectively, based on IWG-MRT. The therapeutic options, aside from allogeneic hematopoietic stem cell transplantation (Allo-HSCT), are limited. Hypomethylating agents (HMAs), including azacitidine (5-aza) and decitabine, are an effective treatment option for myelodysplastic syndrome and acute myeloid leukemia (AML). They have been used for older adults who are ineligible for intensive chemotherapy. Herein, we did a systematic review to evaluate the efficacy and toxicity of HMAs in MPN-AP/BP. Methods We comprehensively searched multiple databases (PubMed, google scholar, EMBASE, and clinicaltrials.gov), from the inception of the database until April 2020. We used MeSH terms and keywords related to azacitidine, decitabine, and MPN-AP/BP. We included studies that used HMAs as monotherapy on in combination to treat Philadelphia negative MPNs AP/BP and were published in the English language. The initial search yielded 2439 articles. After screening by two reviewers and excluding irrelevant articles, 16 studies were explored in detail. Results Of those studies, nine articles looked at HMAs as monotherapy (five articles for 5-aza and four articles for decitabine). The remaining articles looked at different combinations, including decitabine and ruxolitinib in four studies, 5-aza and ruxolitinib in one study, and ruxolitinib with either decitabine or 5-aza in one study. The combined overall response rate of the 5-aza monotherapy trials was 52/91 (57%), complete response rate (CR) was 26/118 (22.0%), partial response (PR) was 15/118 (12.7%), and hematological improvement (HI) was 18/118 (15.2%). The median overall survival (OS) ranged from 8.4-13.5 months. The combination of 5-aza and ruxolitinib was reported by Drummond et al. with ORR, CR, and PR of 33%, 16.6%, and 16.6%, respectively. Hobbs et al. reported that 1/8 patients receiving HMA (unspecified) achieved CR or CR with incomplete platelet recovery. Four studies reported the use of decitabine alone for the treatment of MPN-AP/BP. Three out of the four studies reported the response rate, and the combined ORR based on these studies was 14/29 (48.3%), CR was 6/42 (14.3%), and PR was 6/41 (14.6%), while the median OS ranged from 6.9 to 9.7 months. The fourth study published by Mascarenhas et al. reported outcomes of decitabine in 6 patients with MF-BP. Three out of six patients treated with decitabine died at 5, 7, and 10 months. The combined ORR of the four studies of the combination decitabine and ruxolitinib was 22/46 (47.8%), CR was 8/67 (11.9%), and PR was 6/46 (13.0%), while median OS ranged from 6.9 months to 21 months. Lancman et al. reported a CR rate of 15% with the use of ruxolitinib with either decitabine (n=26) or 5-aza (n=1). The most common hematological adverse effects reported were thrombocytopenia, neutropenia, anemia, and lymphopenia. The significant non-hematological adverse events were gastrointestinal intolerance (nausea, vomiting, and diarrhea), hypokalemia, and injection site reaction, in addition to infections and bleeding. Conclusion All evidence available for the use of HMAs in Philadelphia negative MPNs-AP/BP is from small series and retrospective analysis. Although they are well tolerated as monotherapy and in combination with other agents like ruxolitinib, they have low CR rates (up to 22% only). The tolerability profile along with familiarity with the drug makes them an attractive option. More effective treatment options with reasonable toxicity profile remain an unmet need in the elderly or frail and unfit patients, who are ineligible for induction chemotherapy and Allo-HSCT. Prospective larger-scale studies are warranted to evaluate the efficacy of HMAs, preferably in combination with novel agents, to achieve higher remission rates with minimal toxicity. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Celgene: Speakers Bureau; Karyopham: Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Jansen: Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Description: Background: The JAK-STAT pathway is a vital signaling pathway for various cytokines and growth factors. An abnormal upregulation of this pathway is seen in myeloproliferative disorders, especially the classic BCR-ABL negative myelofibrosis (MF). Janus kinase inhibitors (JAKi) have been evaluated in various clinical trials regarding their efficacy in improving the outcomes for MF patients. In this review, we looked at the reduction of splenomegaly and symptom improvement as markers for efficacy of JAKi. Methods: We did a comprehensive literature search, following PRISMA guidelines, on PubMed, Cochrane, clinicaltrials.gov and Embase databases. We used MeSH terms and related keywords for MF and JAKi, including generic and trade names. We screened 3261 articles and selected 23 trials for our study. Case reports, case series, meta-analysis, review articles, observational studies, phase I trials and studies not reporting spleen response were excluded. Spleen and symptom responses were used to determine the efficacy of JAK inhibitors. Spleen volume reduction (SVR) by 〉35%, spleen length reduction (SLR) by 〉50% and total symptom score (TSS) improvement by 〉50% were set as benchmarks for a positive response. Results: We included 23 trials (n= 4739) in our review. There were 15 phase II trials (n=964) and 8 phase III trials (n=3775). Of these 23 trials, 7 trials (n=598) included patients with median age below 65 years, while 16 trials (n=4141) included patients of median age more than 65 years. Of the 9 of trials of ruxolitinib, 4 were phase III trials (n= 2809) and 5 were phase II trials (n= 416). The dose of ruxolitinib used in these trials ranged from 5 mg twice daily to 20 mg twice daily. The percentage of patients who achieved spleen response ranged from 15.6% to 71.7%. There were 5 trials (n= 861) that evaluated efficacy of momelotinib. Three were phase II trials (n= 221), while 2 were phase III trials (n=326). The doses ranged from 150mg to 300mg. The splenic response in patients ranged from 7% to 48%. In one phase 3 randomized control trial, efficacy of momelotinib (N=215)and roxulotinib (N=217) were compared, and were found to be equally efficacious in terms of spleen response (26.5% in the momelotinib group while 29% in the ruxolitinib group) and symptom response (28.4% in the momelotinib group and 42.2% in the ruxolitinib group). In 4 trials (n= 453) of fedratinib, there were 2 phase II trials (n= 127) and 2 phase III trials (n=326). The splenic response ranged from 31% to 73% of the patient population. In phase II JAKARTA2 study, patients who were resistant or intolerant to ruxolitinib showed SVR of 31%. Lestaurtunib, Ilgitanib, pacritinib and itacitinib were studied in 2,1,1, and 1 phase II trials, respectively. The splenic response was 75%, 31%, 31%, and 68.8% respectively. Symptom response was reported in 12 studies (N=1477). The percentage of patients who achieved symptom response receiving roxulotinib were 20.8-49%, momelotinib (28.4-30.7%), ictatinib (51.1-59.4%), practinib (48%), and fedratinib (27-36%). In terms of safety, the most common hematological side effects seen were anemia (15% - 65%), thrombocytopenia (1.3% - 64%) and neutropenia (1% - 28%). These side effects were seen equally with different medications. The most common non hematological adverse effects included diarrhea (4% - 32%), abdominal pain (2.6% - 27.1%) and fatigue (1.3% - 10%). Conclusion Splenomegaly and associated symptoms are major source of morbidity in MF patients. The rapid advancement in novel agents in the last decade changed the treatment paradigm in this disorder. Our systematic review summarizes the effect of JAKi on spleen and symptom responses. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Karyopharm: Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Janssen: Speakers Bureau.

Description: Background: Clonal plasma cells in multiple myeloma (MM) over express b-cell lymphoma-2 protein (BCL2). Which is the target for venetoclax (VEN). VEN has a promising efficacy and a favorable safety profile in MM patients. This review highlights the efficacy of VEN for the treatment of relapsed refractory (RR) MM. Methodology: We performed a comprehensive database search on four major databases(PubMed, Embase, Cochrane, and Clinical trials.gov). Our search strategy included MeSH terms and keywords for multiple myeloma and VEN, including trade names and generic names, from the date of inception of the database to April 2020.The initial search revealed 782 articles. After excluding review articles, duplicates, and non-relevant articles,we included six studies(four clinical trials and two retrospective studies), which reported an overall response rate (ORR) in RRMM patients. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.0.2) to report the efficacy of VEN. We pooled the results of the experimental arms of included trials using the inverse variance method and logit transformation. Between studies,the variance was calculated using Der Simonian-Laird Estimator. Results: We identified 568 patients from four clinical trials [Moreau et al.2019, the BELLINI trial, (n=291, venetoclax arm= 194, placebo arm= 97)], Costa et al. 2018 (n=42), Kumar et al. 2017(n=66), and Moreau et al. 2017 (n=66)] and two retrospective studies (Kambhampati et al. 2020 (n= 47) and Sidiqi et al.2019 (n=56)). Among which 563 patients were evaluable for the treatment outcomes. One hundred and forty two patients (25%) had t(11:14)mutation. The median age of the patients ranged from 64-66 years, and the median number of prior therapies was ≥2. The median dose of venetoclax ranged from 50 mg/day to 1200 mg/day in dose-escalation cohorts of clinical trials while in the retrospective study by Kambhampati, S et al., the median dose of venetoclax was 800 mg/day. The pooled overall response rate (ORR) for all patients who received venetoclax (n=466) was 57% (95% confidence interval (CI) 0.34-0.77, p

Description: Background Data handling in clinical bioinformatics is often inadequate. No freely available tools provide straightforward approaches for consistent, flexible metadata collection and linkage of related experimental data generated locally by vendor software. Results To address this problem, we created LabPipe, a flexible toolkit which is driven through a local client that runs alongside vendor software and connects to a light-weight server. The toolkit allows re-usable configurations to be defined for experiment metadata and local data collection, and handles metadata entry and linkage of data. LabPipe was piloted in a multi-site clinical breathomics study. Conclusions LabPipe provided a consistent, controlled approach for handling metadata and experimental data collection, collation and linkage in the exemplar study and was flexible enough to deal effectively with different data handling challenges.