Anticipating Energy-driven Crises in Process Industry by AI-based Scenario Planning

Power outages and fluctuations represent serious crisis situations in energy-intensive process industry like glass and paper production, where substances such as oil, gas, wood fibers or chemicals are processed. Power disruptions can interrupt chemical reactions and produce tons of waste as well as damage of machine parts. But, despite of the obvious criticality, handling of outages in manufacturing focuses on commissioning of expensive proprietary power plants to protect against power outages and implicit gut feeling in anticipating potential disruptions. With AISOP, we introduce a model for AI-based scenario planning for predicting crisis situations. AISOP uses conceptual, well-defined scenario patterns to capture entities of crisis situations. Data streams are mapped onto these patterns for determining historic crisis scenarios and predicting future crisis scenarios by using inductive knowledge and machine learning. The model was exemplified within a proof of concept for energy-driven disruption prediction. We were able to evaluate the proposed approach by means of a set of data streams on weather and outages in Germany in terms of performance in predicting potential outages for manufacturers of paper industry with promising results

Control of distributed generators and direct harmonic voltage controlled active power filter for accurate current sharing and power quality improvement in islanded microgrid

Harmonics are regarded as one of the main challenges in a microgrid. This issue may even get worse when different distributed generators (DGs) work together to solve the load sharing problems due to mismatched feeder impedances and diversified DG ratings. Even though load sharing can be achieved, the microgrid suffers from voltage unbalance and total harmonic distortion (THD) issues at the output of DG terminals as well as at the point of common coupling (PCC). Thus, in this paper, the power quality improving method is discussed, with a target of load sharing under the hierarchical control of different DG units and an active power filter (APF) in microgrids. To achieve this objective, we propose integrating a direct harmonic voltage controlled APF with DGs to improve their harmonic compensation performance. This proposed control scheme has many advantages over conventional control using a shunt resistive active power filter (R-APF) with voltage controlled DGs. First, based on the existing THD level of the PCC voltage, the proposed scheme provides improved voltage compensation and reduction in THD in the islanded microgrid. Secondly, equal load sharing can be achieved simultaneously. Thus, the proposed scheme provides better performance and a seamless interface as the proposed study mainly contains both the voltage controlled DGs and the local based voltage detection APF

Antimicrobial Susceptibility Pattern among Patients Presenting with Acute Exacerbation of COPD

Background: The irrational use of antibiotics in outpatient as well as indoor patients without studying the culture and sensitivity patterns may have led to resistance in common organisms causing acute exacerbation of chronic obstructive pulmonary disease. The objective of this study was to determine the culture and sensitivity patterns of bacteria in the sputum of patients presenting with acute exacerbation of chronic obstructive pulmonary disease (COPD) in our population.Material and Methods: This cross-sectional study was conducted in the Medicine Department, Jinnah Hospital Lahore from 1st January 2018 to 25th June 2018. A total of 215 patients with acute exacerbation of COPD were collected through non-probability consecutive sampling technique. COPD was diagnosed on the basis of history, examination, chest X-ray and spirometry. Acute exacerbation was taken as an acute rise in one or more of the following; sputum volume and/or purulence, frequency and severity of cough and dyspnea. Two sputum samples were collected from each patient. Antimicrobial susceptibility testing was done as per CLSI guidelines. Data was analyzed by SPSS version 21.0. with p-value ≤ 0.05 considered as statistically significant.Results: Among 215 selected cases, 118 (54.88%) were males and 97 (45.12%) were females. A total of 110 (51.16%) cultures were positive and 105 (48.84%) were negative for bacterial growth. Klebsiella pneumoniae (n=69; 62.72%) was the most frequent microorganism in patient’s sputum followed by Pseudomonas aeruginosa (n=21; 19.1%) and Staphylococcus aureus (n=20; 18.2%). Regarding sensitivity pattern, amikacin was found to be the most sensitive antibiotic against these organisms followed by gentamicin and ciprofloxacin.Conclusions: Klebsiella pneumoniae was the most common microorganism in the sputum of patients presenting with acute exacerbation of COPD, while amikacin was reported to be most sensitive antibiotic against the microorganism.Key words: Acute exacerbation, Antimicrobial susceptibility pattern, COP

Response of Starter Broiler Chickens to Feed Diets Treated with Organic Acids

Background: Organic acids contain one or more carboxylic acid groups which are linked with covalent bond and  have acidic properties that can enhance the reservation of protein and some other nutrients in birds. Antibiotic growth promoters have been banned due to their residues that remain in the meat and effects the human beings. Therefore, the organic acids are used as their alternatives. The present study is aimed to inspect the outcome of organic acids on uptake of feed, feed gain ratio, and live weight gain in broiler chickens.Methods: A total of 150 unsexed broiler chickens were used for this experiment which were having five categories of treatment as T1, T2, T3, T4, and T5. Each category had thirty birds. T1 was treated with a standard diet, T2was treated with acetic acid, T3 with butyric acid, T4 with citric acid and T5 with formic acid.  The duration of this experiment was 28 days. After the specified time of this experiment, the data of uptake of feed and body weight was gathered on weekly basis.  Comparison of all the five treatments was done by using the Duncan's multiple range test.Results: Feed Conversion Ratio (FCR) was found lower in T5 than other treatments. T5 group showed the highest average value of final body weight of broilers in contrast to the T3 group which showed the lowest final body weight.  Feed intake was found significantly different within the treatments. T3 showed significantly lower value as compared to other treatments. The lowest value of average regular uptake of grains was found in T3 treatment group. Broilers fed on formic acid have shown a better protein efficiency ratio than that of butyric acid and citric acid. Broilers treated with citric acid have a significant difference which indicates more water consumption as compared to other treatments.Conclusion: Organic acids have a productive effect on the growth of animals and broiler chickens. Organic acids including butyric acid, acetic, citric, formic, fumaric, and propionic acid vary in their biochemical actions in the system of animals. Organic acid affects the final weight gain, average regular gain in weight, total uptake of feed, and feed to gain ratio, daily intake of protein, protein efficiency ratio, total water uptake, average water intake, and water feed ratio. Based on the present study, further analysis is required to look over the impacts of addition of organic acid on the growth accomplishment of broiler chicks.Keywords: Broiler chicks; Organic acid; Butyric acid; Citric acid; Acetic acid; Formic acid 

P783 Clinical, Humanistic, and Economic Burden in Patients with PNH Receiving C5 Inhibition Treatment across UK, Germany, and France. Insights from the Commodore Burden of Illness Study

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening blood disorder. In the UK, Germany, and France, C5 complement inhibitors, such as eculizumab and ravulizumab, both of which are intravenously (IV) infused, are the standard of care for PNH

Chronic lymphocytic leukemia therapy guided by measurable residual disease

Background:Ibrutinib (I) and venetoclax (V) improve chronic lymphocytic leukemia (CLL) outcomes compared to chemo-immunotherapy. We hypothesized I+V is more effective than fludarabine-cyclophosphamide-rituximab (FCR), and personalizing treatment duration, using measurable residual disease (MRD), would optimize outcomes.Methods:FLAIR, a phase III, multicenter, randomized, controlled, open-label platform trial for untreated CLL, compared I+V and I, to FCR. In I+V, after 2m I, V was added for up to 6y of therapy. The duration of I+V was defined by MRD assessed in peripheral blood (PB) and bone marrow (BM) and was double the time to undetectable MRD (uMRD). The primary endpoint was progression-free survival for I+V vs FCR, reported herein. Key secondary endpoints were overall survival, response, MRD and safety. Results:523 participants were randomized to FCR or I+V. At median 43.7m, there were 87 progressions (75 FCR, 12 I+V). The hazard ratio (HR) for progression-free survival for I+V vs FCR is 0.13 (95% confidence interval [CI], 0.07-0.24; P&lt;0.0001). There were 34 deaths (25 FCR, 9 I+V). The HR for overall survival for I+V vs FCR is 0.31 (95%CI, 0.15-0.67). At 3y, 58.0% I+V participants stopped therapy due to uMRD. After 5y of I+V, 65.9% and 92.7% participants were BM and PB uMRD, respectively. Infection rates were similar. There were more cardiovascular events with I+V (10.7%) vs FCR (0.4%). Conclusion:MRD-directed I+V improved progression-free survival and favored overall survival compared to FCR. (Funded by Cancer Research UK and others; Trial Registration number: ISRCTN01844152 and EudraCT, 2013-001944-76.) <br/

Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial

Background Treatment of chronic lymphocytic leukaemia (CLL) has seen a substantial improvement over the last few years. Combination immunochemotherapy, such as fludarabine, cyclophosphamide and rituximab (FCR), is now standard first-line therapy. However, the majority of patients relapse and require further therapy, and so new, effective, targeted therapies that improve remission rates, reduce relapses, and have fewer side effects, are required. The FLAIR trial will assess whether ibrutinib plus rituximab (IR) is superior to FCR in terms of progression-free survival (PFS). Methods/design FLAIR is a phase III, multicentre, randomised, controlled, open, parallel-group trial in patients with previously untreated CLL. A total of 754 participants will be randomised on a 1:1 basis to receive standard therapy with FCR or IR. Participants randomised to FCR will receive a maximum of six 28-day treatment cycles. Participants randomised to IR will receive six 28-day cycles of rituximab, and ibrutinib taken daily for 6 years until minimal residual disease (MRD) negativity has been recorded for the same amount of time as it took to become MRD negative, or until disease progression. The primary endpoint is PFS according to the International Workshop on CLL (IWCLL) criteria. Secondary endpoints include: overall survival; proportion of participants with undetectable MRD; response to therapy by IWCLL criteria; safety and toxicity; health-related quality of life (QoL); and cost-effectiveness. Discussion The trial aims to provide evidence for the future first-line treatment of CLL patients by assessing whether IR is superior to FCR in terms of PFS, and whether toxicity rates are favourable. Trial registration ISRCTN01844152. Registered on 8 August 2014, EudraCT number 2013-001944-76. Registered on 26 April 2013

Ibrutinib Plus Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: The CLARITY Study.

PURPOSE:The treatment of chronic lymphocytic leukemia (CLL) has been revolutionized by targeted therapies that either inhibit proliferation (ibrutinib) or reactivate apoptosis (venetoclax). Both significantly improve survival in CLL and replace chemoimmunotherapy for many patients. However, individually, they rarely lead to eradication of measurable residual disease (MRD) and usually are taken indefinitely or until progression. We present the CLARITY trial that combined ibrutinib with venetoclax to eradicate detectable CLL with the intention of stopping therapy. PATIENTS AND METHODS:CLARITY is a phase II trial that combined ibrutinib with venetoclax in patients with relapsed or refractory CLL. The primary end point was eradication of MRD after 12 months of combined therapy. Key secondary end points were response by International Workshop on CLL criteria, safety, and progression-free and overall survival. RESULTS:In 53 patients after 12 months of ibrutinib plus venetoclax, MRD negativity (fewer than one CLL cell in 10,000 leukocytes) was achieved in the blood of 28 (53%) and the marrow of 19 (36%). Forty-seven patients (89%) responded, and 27 (51%) achieved a complete remission. After a median follow-up of 21.1 months, one patient progressed, and all patients were alive. A single case of biochemical tumor lysis syndrome was observed. Other adverse effects were mild and/or manageable and most commonly were neutropenia or GI events. CONCLUSION:The combination of ibrutinib plus venetoclax was well tolerated in patients with relapsed or refractory CLL. There was a high rate of MRD eradication that led to the cessation of therapy in some patients. The progression-free and overall survival rates are encouraging for relapsed and refractory CLL

GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In CLL (GALACTIC) trial: study protocol for a phase II/III randomised controlled trial

Background: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Achieving minimal residual disease (MRD) negativity in CLL is an independent predictor of survival even with a variety of different treatment approaches and regardless of the line of therapy. Methods/design: GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In CLL (GALACTIC) is a seamless phase II/III, multi-centre, randomised, controlled, open, parallel-group trial for patients with CLL who have recently responded to chemotherapy. Participants will be randomised to receive either obinutuzumab (GA-101) consolidation or no treatment (as is standard). The phase II trial will assess safety and short-term efficacy in order to advise on continuation to a phase III trial. The primary objective for phase III is to assess the effect of consolidation therapy on progression-free survival (PFS). One hundred eighty-eight participants are planned to be recruited from forty research centres in the United Kingdom. Discussion: There is evidence that achieving MRD eradication with alemtuzumab consolidation is associated with improvements in survival and time to progression. This trial will assess whether obinutuzumab is safe in a consolidation setting and effective at eradicating MRD and improving PFS. Trial registration: ISRCTN, 64035629. Registered on 12 January 2015. EudraCT, 2014-000880-42. Registered on 12 November 2014