bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in Clamp-On Flow Measurement Techniques
Authors: Arsalan Muhammad
Published: November 2020

This paper addresses the need and challenges associated with the clamp-on gas and oil flow and water-cut measurement techniques for efficient and reliable flow allocation and production management. This will be useful for production, as well as, reservoir engineering in both traditional and unconventional multiphase flow environments. Furthermore the paper reviews the advancements in the available clamp-on measurement techniques and evaluate their advantages and shortcomings in different flow conditions.
Improving Well Production Performance By Using Realtime Wash Desalting Planning Tool WDPT in the North Sea
Authors: Octaviano Ryvo , Hornstra Erik , Poort Jonah , Shoeibi Omrani Pejman , Linden Ruud van , Slot Harmen , Dechelette Benoit
Published: November 2020

Due to natural depletion many mature fields are currently suffering from productivity issues due to halite precipitation in the North Sea. Main actions to prevent or solve this type of scaling issues include increasing flowing pressures (topside choking or velocity strings), but often considered easiest and most economical are fresh water washes to dissolve downhole halite deposits. The main objective of this study is to increase production by optimizing washing sequences. Having an accurate washing schedules predicted allows to anticipate on production degradation and its mitigating actions.

To predict production decline due to halite, a virtual flow meter is developed combining a well model (Vertical Lift Performance, known as VLP curve), reservoir model (Inflow Performance Relation, known as IPR curve) and a dynamic model for the extra pressure drops due to deposition. The flow is calculated including the additional pressure drop. The virtual flow meter is calibrated using the last 3-6 months of production data. The Well Desalting Planning Tool (WDPT) makes real-time estimates of short-term pressure drops for each well and finally determines a date to water wash. It shows the schedule in the Planning Dashboard of the web-based WDPT tool. The software can be used to assist the operations department in prioritizing platform visits and optimize production. WDPT is developed as part of company Digital Oil Field (DOF).
Innovation in a New Normal – How Can the Upstream Industry Develop New, Fit-for-Purpose Technology?
Authors: Clegg John
Published: November 2020

The upstream oil and gas industry suffered an unprecedented dual shock in 2020. Suppression of demand caused by the global Covid-19 pandemic combined with oversupply caused by competition for production market share between major suppliers across the globe. Although the world that will emerge in 2021 is hard to predict, it is very likely that it will be different from the past. It is equally likely to change much more quickly, therefore needing new ways of developing and introducing new technology-based products and services. This paper introduces the dichotomies that will emerge. In particular the industry will need to be focused in order to deliver technology on time, at the same time being flexible in response to rapid changes. It can be challenging to meet both of these apparently conflicting requirements. By exploring the principles of innovation theory from a number of perspectives, this paper offers insights and suggestions to help the industry develop the highly efficient technological solutions it will need to thrive in 2021 and beyond in the face of significant restrictions on financial and other resources. It also describes the impact of stakeholder interests, including the pressures arising from environmental, social and governance (ESG) issues, which will not go away despite the shock to the industry that 2020 brought, and suggests how these may be met while developing effective new technology. The paper uses real-world examples, including examples from other industries, to describe strategies for product and service development, and business model adjustment. It concludes with a toolbox of ideas and techniques that should be broadly applicable across the upstream industry.
Physical Performance Testing of a Prototype Gerotor Pump Operating in Liquid and Gas-Liquid Conditions
Authors: Ejim Chidirim , Xiao Jinjiang , Oshinowo Lanre
Published: November 2020

Gerotors are positive displacement pumps and potential artificial lift options in the oil and gas industry. This study presents the performance characteristics from physical testing of a unique one-stage, equal-walled gerotor pump design operating in oil and oil-air mixtures. The pump was tested at various rotational speeds in a flow loop. The performance results were obtained to ascertain potential design optimizations of the pump before embarking on manufacturing and testing of the field prototype pump.

A physical prototype of a one-stage 400 series gerotor pump, suitable for application in a 5.5-inch casing, was designed, manufactured, assembled, and tested. Mineral oil and air were used as the operating media. For given pump outlet valve settings, the pump rotational speeds were set to 200, 250, 300, and 350 revolutions per minute (RPM). Gas volume fractions (GVF) at the pump inlet were varied from 0% to the maximum the current pump design could handle. For each test point, the corresponding pump parameters were measured. Dimensionless performance plots were established for obtaining pump performance at other flow conditions.

The results showed that pump flow rate decreased with increasing differential pressure, typical of positive displacement pumps. At 200 and 350 RPM, maximum pump delivery is about 190 and 330 barrels per day (BPD) of oil, respectively, at zero differential pressure. The pump can supply flow against a differential pressure of up to about 5.5 psi at 200 RPM and 15 psi at 350 RPM. For the 200-350 RPM speed range, volumetric efficiencies varied from 30% to 73%, whereas the electric power input varied from 145 W to 191 W. When pumping oil-air mixtures, the current gerotor pump design can handle 15% GVF maximum, at 250, 300, and 350 RPM. For certain pump outlet pressures, the total fluid flow rates decreased as the GVF increased to 15%. The volumetric efficiencies at 15% GVF varied from 32% to 53%, for the 300 to 350 RPM speed range, whereas the motor electric power input decreased with increasing GVF up to 15%. In conclusion, increasing the pump rotational speed improves the volumetric efficiency and gas-handling capability of the gerotor pump. These observations will aid in the required design optimization to enhance the performance of the future field prototype gerotor pump.

This study presents the capabilities of gerotors as potential artificial lift alternatives to handle liquid and gas-liquid mixtures for boosting applications in oilfield operations. The technology with additional design optimization can be readily integrated into oilfield equipment architecture. The mechanical simplicity of gerotors and their compactness provides a promising artificial lift substitute that may be implemented for downhole or surface production of liquid or gas-liquid mixtures in the oil and gas industry.
Pipe Strain Effects on Pumps - Case Study
Authors: Abdulelah Abdullah , Abdullah Abdulrahman , Ioannis Ioannis
Published: November 2020

Striving to achieve high level of plant's reliability, and realizing the wide impact of piping misalignment on rotating equipment premature failures, Oil & Gas industry has come up with many standards and best practices aiming to eliminate or minimize to the possible extent the effects of pipe strain on rotating equipment. Pipe strain is considered as one of the most frequent reasons causing rotating equipment to fail. It occurs when there is a misalignment between the piping and the equipment's suction and/or discharge flanges. A case study of a vertical crude charge pump at Saudi Aramco plant, experiencing high vibration and repetitive mechanical seal failures due to piping misalignment and subsequent pipe strain effects will be considered in this paper, highlighting the corrective actions adopted following the relevant investigation and troubleshooting conducted by Operation, Maintenance and Engineering (OME) team. Moreover, a Finite Element Analysis (FEA) model will be presented, demonstrating the significant impact of pipe strain on the pump's shaft behaviour and the potential modes of failure in case pump-to-pipe flanges misalignments are not seriously considered.
Dealing with EPC Project Management Problems and Challenges A Case Study on Petrochemical, Oil and Gas EPC Projects in Middle-East
Authors: Akhtar Mujahid
Published: November 2020

Project schedule delay and cost overrun have become a normal matter to witness and at a certain point, it textures almost likely that it would be an inevitable result. Such result could be avoided if we identify the causes of delay and try to mitigate the challenges early phase in the project. An effective Project Manager manages all aspects of EPC project and he must understand the causes of problems. This case study aims to explore problems faced in EPC projects that lead to cost overrun and schedule delay, and to explore good practices to minimize impact on overall project.

The methodology adopted consists of survey, interviews and case study approach. A survey was used to collect the common causes of EPC Project delays and cost overrun. An interview approach used to find out significant delay and success factors together with effective management practices collected from survey. Later, case study approach is used to validate the information gathered previously and to understand the relation and consequences of each factor. The interviewee were project managers, project controls manager, construction manager, discipline engineers, subject matter experts and client representatives, etc. from several EPC contractors and clients.

There are several causes of EPC projects delay and cost overrun and every project may have its own challenges but many found to be common among projects. Sometimes, it may be a single trigger event that leads to delays or a combination of events. The case study reveals that major factors contributing to schedule delay and cost overrun are mostly related to project complexity, aggressive unrealistic schedule, weak or poor planning and control, inherited bidding inaccuracies and estimation mistakes, ineffective leadership and poor decision-making, absence of project management practices, etc. Also, design changes, delay in placing POs, lack of team competency, late client approvals, late vendor information, delay in PTW issuance, inadequate construction resources, quality issues and reworks, and ignoring previous project's lesson learned. Further most, poor risk management, poor interface management between project stakeholders contributes to cost overrun and delays. This case study findings may be helpful to EPC contractors, clients, project sponsors, project managers, construction managers and other stakeholders to understand the major factors, causes and problems that they may face during EPC project lifecycle and how to overcome such challenges effectively.

This case study can be viewed as a lesson learned approach. This study will guide them in developing and adopting necessary effective and efficient project management practice to complete the EPC projects within budget, on schedule with good quality, and safety. Stakeholders’ awareness about causes of delay give them more options and improve capability in problem-solving throughout the project life-cycle.
Decision Tree Regressions for Estimating Liquid Holdup in Two-Phase Gas-Liquid Flows
Authors: Almashan Meshal , Narusue Yoshiaki , Morikawa Hiroyuki
Published: November 2020

In producing oil and gas wells, two-phase flow of gas and liquid is inevitable. Gas density is lighter than liquid density, as a result, gas travels faster than liquid, leaving the liquid phase to build up in pipe segments. The amount of liquid occupying each pipe segment varies. This phenomenon is called liquid holdup, which is defined as the ratio of the liquid volume in a pipe element to the volume of the pipe element. Liquid holdup presents challenges in calculating mixture physical properties and two-phase flow pressure drop. Estimating liquid holdup is the first step to investigate production wells problems. Early detection and identification of liquid holdup (HL) in oil and gas wells is needed to reduce the maintenance downtime and thus increase production. This is significantly crucial in designing oil and gas facilities. Consequently, many studies on predicting liquid holdup have been carried out in the past, considering different flow conditions, resulting in a large number of empirical correlations with various degrees of accuracy.

Machine learning approaches in predicting liquid holdup in multiphase flows have been recently studied to improve the prediction accuracy compared to the existing empirical correlations. However, these approaches ignored the heuristic feature importance of the input parameters to the predicted HL values. In our study, a machine learning predictive model, boosted decision tree regression (BDTR), is trained, tested and evaluated in predicating HL in multiphase flows in oil and gas wells. Decision trees are considered as non-parametric machine learning models. The datasets used in training and testing the predictive model are experimental and they were collected from literature (111 data-points). Air-kerosene and air-water mixtures were used in obtaining the 111 experimental data-points.

Results show that, the proposed BDTR model outperforms the best empirical correlations and the fuzzy logic model used in estimating HL in gas-liquid multiphase flows. For the built model, the most important input feature in estimating HL is the superficial gas velocity (Vsg). The empirical correlations developed in the past for identifying HL in the multiphase flow phenomenon can only be applied under certain flow conditions by which they were originally developed but this machine learning model does not suffer from this limitation.

To the best of our knowledge, the present study is the first work that shows how the decision forest regression predictive models can accurately predict HL. Using the BDTR model with its interpretable representation, one can clearly determine the heuristic feature importance of the input features used in building the model. Heuristic feature importance can help in having a better insight of the issues associated with the HL studies, such as the liquid loading phenomenon.
Well Portfolio Optimization: Rapid Screening of Production Enhancement Opportunities
Authors: Sinha Rajeev Ranjan , Songchitruksa Praprut , Holy Ralf , Vadivel Karthick , Ramachandran Sreekrishnan , Martinez Henry
Published: November 2020

Objectives/Scope

A system providing a standardized and automated approach to rapidly screen and rank large well count assets (hundreds or thousands of wells) in a fraction of the time and repeatably, is proposed. The solution enables the proactive management of existing wells by keeping the production enhancement opportunity pipeline full and expediting potential candidates through the Opportunity maturation process (OMP) in an integrated and collaborative framework.

Methods, Procedures, Process

The solution is based on a hybrid and automated decision-support system anchored in a knowledge-based framework. Hybrid refers to the integration of (1) petroleum engineering analysis methods and best practices with (2) advanced machine learning algorithms for autonomous well performance signature identification, and (3) the operator's business logic driving the economics of the field. Automated alludes to a continuous running workflow requiring minimal interaction, utilizing machine learning approaches such as neural networks, bayesian belief network models, logistic regressions, advanced optimization, etc.

Results, Observations, Conclusions

The application of the proposed solution led to workover and intervention candidate evaluations now routinely performed on a weekly basis (compared to the previous bi-yearly approval review and approval process across almost 200 well completions, with engineers confirming and validating the system-generated opportunities before escalating them for approval. Moreover, in its early evaluation, the new system has provided 89% in time savings in both the identification and review of intervention candidates and 88% in cost savings resulting from the elimination of manually tedious and routine work.

Novel/Additive Information

Asset teams are entrusted with proposing enough well production opportunities on a regular basis. The identification of potential workover candidates remains a manual, tedious and repetitive process consuming several weeks of engineers’ time in every iteration. With the addition of the proposed solution in the existing body of literature, asset teams can proactively manage opportunities in their fields.
Geomechanical Laboratory Studies to Mitigate the Wellbore Instability Problems in Nahr Umr Shale Formation in Offshore Abu Dhabi
Authors: Shaver M. A. , Yudhia D. P. , Al Ameri S. M. , Couzigou E.. , Al Marzouqi A.. , Mahgoub F.. , Vican K.. , Koronfol S.. , Martin J. W. , Muniz E..
Published: November 2020

Wellbore instability challenges encountered while drilling the Nahr Umr Shale include, but are not limited to, hole collapse leading to hole enlargement. Wellbore instability leads to huge cost increases in the drilling process and in rare cases well abandonment. Observations from drilling data suggest that wellbore stability varies with different wellbore deviations and azimuths, especially in areas of highly laminated formations and anisotropic in-situ field stresses. Accurate information on the rock strength and rock failure behavior in shale has a major impact on the improvement of drilling efficiency. Knowledge of the mechanical properties of shale is essential to implement any 3D shale anisotropy borehole instability model (Crook AJL, et. al., 2002).

Shale mechanical properties were evaluated from laboratory tests. Well-preserved core samples retrieved from the Nahr Umr Shale were put through several tests to describe the mechanical characteristics related to rock strength and in-situ stresses with the aim to determine the effect of the anisotropy and plane of weakness in drilling high-sailing angle trajectories. Strength anisotropy was assessed using the plane of weakness model (Jaeger, J.C., & Cook, N.G.W., 1979) which assumes that the heterogeneous media is composed of a matrix rock and a plane of weakness (e.g., bedding/laminations, interface between lithotypes or laminations). Shear failure occurs once the shear stress acting on the plane of weakness exceeds its shear strength. Laboratory tests include both extremely slow triaxial tests and multistress path testing performed on three orientations. Failure envelopes were created to develop the plane of weakness model to predict the orientation of the weakest plane and determine the magnitude of the strength reduction. Elastic anisotropy data from plugs is combined with advanced sonic logs, enabling a more robust evaluation of the formation anisotropy to improve both stress predictions and the allowable mud-weight windows during wellbore stability assessment.
Impact of WAX on Asphaltene Deposition under Jet Pump Operation as Revealed by Asphaltene Inhibitor Field Test
Authors: Yoshimoto Tatsuya , Kurosawa Masaharu , Fukuda Jun , Yonebayashi Hideharu , Murakami Yuji
Published: November 2020

In a Japanese oil field, which applying jet pump (coiled tubing running, standard flow type, produced oil as power fluid containing asphaltenes and waxes) since 2014, unstable power fluid injection pressure has been observed since 2016 due to asphaltene deposition on jet pump nozzle area, which limited power fluid rate and therefore production rate. The objective of this study was to achieve high oil production rate by overcoming the pressure fluctuation due to asphaltene deposition problems.

Asphaltene inhibitors (AI) from various suppliers were tested to measure asphaltene deposition amount as a laboratory screening. The best AI candidate was implemented in a field trial test during which, asphaltene deposition amount in strainers were measured, production oil was collected to measure asphaltene deposition rate under stock tank condition, and operation data was monitored and analyzed. To confirm the new AI efficiency, these data were compared with the ones during the original AI before starting the field test.

This paper presents specific features which were found in the field test. Selected AI was efficient at dispersing asphaltenes. It achieved stable injection pressure and reduced asphaltene deposition amount in production oil sample. However, it became worse again within one month. The main reason was that the new AI worked as dispersant to delay asphaltene deposition so that asphaltenes finally accumulated under jet pump production system which is semi-closed loop. Asphaltene deposition amount on strainers increased during winter, especially shut down periods, because process temperature was close to ambient condition. This temperature-dependent observation means asphaltene deposition was highly influenced by wax deposition. A follow-up laboratory test revealed the asphaltene deposition amount decreased by adding paraffin inhibitor (PI). This field test result revealed the asphaltene and paraffin interaction in field scale.
Design of Thermoresponsive Polymers to Selective Permeability Reduction in Porous Media
Authors: Maddinelli Giuseppe , Bartosek Martin , Carminati Stefano , Moghadasi Leili , Manfredini Nicolò , Moscatelli Davide
Published: November 2020

A critical issue in waterflooding operations is determined by reservoir heterogeneity, which generates preferential flow through high permeable paths limiting contact with oil bearing zones. The use of Thermoresponsive Polymers, a novel type of chemicals, has been evaluated as a method to improve the oil displacement by better addressing water flow through un-swept regions. The placement of chemicals able to impair the high permeable layers, blocking water and diverting flow to richest oil zones could improve the final oil recovery. We describe a method based on novel, water soluble polymeric materials characterized by thermoresponsive properties, inducing reversible viscosity variation. This type of temperature stimulated co-polymers are molecules subjected to a reversible transition in correspondence to a certain "lower critical solution temperature" (LCST). Below such critical temperature, the molecules are completely soluble in water (low viscosity), while in the range over the LCST, a phase transition occurs, creating a gel-like structure with a consistent increase of the solution viscosity. This phase transition could be exploited to decrease consistently the permeability of the area occupied by the fluids. These products have the potential, by proper tailoring of the chemical structure, to design the range of working temperature to match the reservoir peculiar conditions.

After a first screening of different polymer properties by bulk tests, the final performance evaluation was done by core-flooding experiments. Clashach sandstone was selected as reservoir rock analog. The injectivity performance of the polymer solution (2% w/w), was measured by differential pressure monitoring. The permeability reduction, due to transition over the critical temperature (typically, 70°C in our experiments), was evaluated by permeability to brine measurements before and after the polymer treatment. The results obtained in terms of injectivity and permeability reduction are positive and promising for a field application. The polymers studied represent a novel class of products, sensitive to temperature, suitable for conformance control application. It allows a precise tailoring of their features, i.e. the transition temperature from low to high viscosity, adjusted to the temperature and permeability of the reservoir. These parameters need to be carefully estimated, before running the treatment, through a tracer campaign and reservoir simulation.
The relationship between survival gastric cancer patients and neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio diagnosed before surgery
Authors: Mohammadi Sareh , Veisi Zeinab , Moazeni Mohammad , Kheiri Soleiman , Lorigooini Zahra , masomi Rohollah
Published: November 2020

Aim: This study aims to investigate the relationship of two prognostic factors NLR and PLR to patient survival in gastric cancer patients diagnosed before surgery.Background: Due to the high prevalence of gastric cancer and the lack of appropriate prognostic factors, most patients are diagnosed at advanced stages of the disease. Therefore, this study aimed to determine the appropriate prognostic factor investigated investigate the relationship of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in gastric cancer patients.Methods: This retrospective study was performed on all gastric cancer patients referred to Kashani Hospital of Shahrekord (Chaharmahal and Bakhtiari province) in 2011-2016. Demographic and biological variables such as NLR and PLR were evaluated. Patient survival was calculated by subtracting the date at disease diagnosis (using endoscopy) from the date at death and expressed in month. Data was analyzed by SPSS software.Results: The mean age of patients was 63.79 ± 15.03 (range: 10-92) years. 76% of patients were male and the rest were female. Only NLR had significant effect on survival (P < 0.05) and PLR had no significant effect on survival (P > 0.05).Conclusion: With the increase in NLR by one point, the risk of death in gastric cancer patients increased by 18%. In other words, with increase in NLR, survival rate of gastric cancer after surgery significantly decreased. It is suggested that further studies be conducted with a more statistical population to ensure the reproducibility of the results of the present study.
U-IMD: The First Unified European Registry for Inherited Metabolic Diseases
Authors: Opladen Thomas , Gleich Florian , Kozich Viktor , Scarpa Maurizio , Martinelli Diego , Schaefer Franz , Jeltsch Kathrin , Palacios Natalia Julia , Cazorla Angels Garcia , Vici Carlo Dionisi , Kölker Stefan
Published: November 2020

Background: Following the broad application of new analytical methods, more and more pathophysiological processes in previously unknown diseases have been elucidated. The spectrum of clinical presentation of rare inherited metabolic diseases (IMDs) is broad and ranges from single organ involvement to multisystemic diseases. With the aim of overcoming the limited knowledge about the natural course, current diagnostic and therapeutic approaches, the project has established the first unified patient registry for IMDs that fully meets the requirements of the European Infrastructure for Rare Diseases (ERDRI). Results: In collaboration with the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN), the Unified European registry for Inherited Metabolic Diseases (U-IMD) was established to collect patient data as an observational, non-interventional natural history study. Following the recommendations of the ERDRI the U-IMD registry uses common data elements to define the IMDs, report the clinical phenotype, describe the biochemical markers and to capture the drug treatment. Until today, more than 1100 IMD patients have been registered.Conclusion: The U-IMD registry is the first observational, non-interventional patient registry that encompasses all known IMDs. Full semantic interoperability for other registries has been achieved, as demonstrated by the use of a minimum common core data set for equivalent description of metabolic patients in U-IMD and in the patient registry of the European Rare Kidney Disease Reference Network (ERKNet). In conclusion, the U-IMD registry will contribute to a better understanding of the long-term course of IMDs and improved patients care by understanding the natural disease course and by enabling an optimization of diagnostic and therapeutic strategies.
Exome Sequencing in Paediatric Patients with Movement Disorders with Treatment Possibilities
Authors: Kwong Anna Ka-Yee , Tsang Mandy Ho-Yin , Fung Jasmine Lee-Fong , Mak Christopher Chun-Yu , Chan Kate Lok-San , Rodenburg Richard J.T. , Lek Monkol , Huang Shushu , Pajusalu Sander , Yau Man-Mut , Tsoi Cheung , Fung Sharon , Liu Kam-Tim , Ma Che-Kwan , Wong Sheila , Yau Eric Kin-Cheong , Tai Shuk-Mui , Fung Eva Lai-Wah , Wu Nick Shun-Ping , Tsung Li-Yan , Smeitink Jan , Chung Brian Hon-Yin , Fung Cheuk-Wing
Published: November 2020

Background: Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis. Results: We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential targeted treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation. Conclusion: A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management using targeted therapies. The study highlights the potential of implementing precision medicine in the patients.
A Novel Two-phase Cycle Algorithm for Effective Cyber Intrusion Detection in Edge Computing
Authors: Gong Yiguang , Liu Yunping , Yin Chuanyang
Published: November 2020

Edge computing extends traditional cloud services to the edge of the network, closer to users, and is suitable for network services with low latency requirements. With the rise of edge computing, its security issues have also received more and more attention. In this paper, a novel two-phase cycle algorithm is proposed for effective cyber intrusion detection in edge computing based on multi-objective genetic algorithm (MOGA) and modified back propagation neural network (MBPNN), namely TPC-MOGA-MBPNN. In the first phase, the MOGA is employed to build multi-objective optimization model that tries to find Pareto optimal parameter set for MBPNN. The Pareto optimal parameter set is applied for simultaneous minimization of average false positive rate (Avg FPR), mean squared error (MSE), and negative average true positive rate (Avg TPR) in the dataset. In the second phase some MBPNNs are created based on the parameter set obtained by MOGA and are trained to search for more optimal parameter set locally. The parameter set obtained in the second phase is used as the input of the first phase, and the training process is repeated until the termination criteria are reached. Benchmark dataset namely KDD cup 1999 is used to demonstrate and validate the performance of the proposed approach for intrusion detection. The proposed approach can discover a pool of MBPNN based solutions. Combining these MBPNN can significantly improve prediction performance, and a GA is used to find the optimal MBPNN combination. The result shows that the proposed approach could reach an accuracy of 98.81% and a detection rate of 98.23%, which outperform most systems of previous works found in the literature. In addition, the proposed approach is a generalized classification approach that is applicable to the problem of any field having multiple conflicting objectives.
Chimeric Antigen Receptor T Cells Engineered to Secrete CD40 Agonist Antibodies Enhance Antitumor Efficacy
Authors: Zhang Yajun , Wang Pei , wang tengjiao , Fang Yuan , Ding Yongmei , Qian Qijun
Published: November 2020

BackgroundAlthough chimeric antigen receptor (CAR) T-cell therapy has made remarkable achievements against hematological malignancies, the efficacy of it against solid tumors has been limited. By being combined with immune checkpoint inhibitors, such as PD-1, PD-L1, or CTLA-4 antibodies, this therapy has been shown to be a promising strategy to enhance the antitumor efficacy of CAR-T cells. However, due to the fact that acquired resistance to checkpoint inhibitors will occur in most patients, it is vital to investigate other strategies to further improve the antitumor efficacy of CAR-T cell therapy in solid tumors. Recently, CD40 agonist antibodies have been shown to possess potential antitumor efficacy by activating the CD40 pathway.ResultsBased on the piggyBac transposon system, rather than the widely used viral vector, we constructed a meso3-CD40 CAR-T targeting region III of mesothelin (MSLN) that possesses the ability to secrete anti-CD40 antibodies. The results show that compared with meso3 CAR-T, which does not secrete the anti-CD40 antibody, meso3-CD40 CAR-T secreted more cytokines and had a relatively higher proportion of central memory T (TCM) cells after being stimulated by the target antigen. In addition, compared with meso3 CAR-T, we found that meso3-CD40 CAR-T had a more powerful cytotoxicity effect on target cells at a relatively low effector to target ratio. More importantly, we demonstrated that meso3-CD40 CAR-T also had enhanced antitumor activity in a human ovarian cancer xenograft in vivo.ConclusionsIn conclusion, these results showed that anti-CD40-secreting CAR-T cells generated by non-viral vectors could be a potential clinical strategy for improving the efficacy of CAR-T cell therapies.
Higher-Order Kinematics Modeling of 3-RRS Parallel Mechanism Based on CGA
Authors: Wang Chang , Zhao Tieshi , Li Erwei , Zhao Yanzhi , Bian Hui , Geng Mingchao
Published: November 2020

Higher-order kinematics of mechanisms has been applied in servo motor control, human-robot interaction and machinery life design fields, etc. The representations of acceleration and jerk by screws have been fully developed by researchers with the methods of the differential of the matrix representation of SE(3) group. Clifford algebra, which is tighter and with higher computational efficiency than the matrix method, is another representation of the motions of rigid bodies. It has been used in position kinematics, grub task motion planning, and robot vision for its convenience of geometric representations and calculations. As far as we know, the work of higher-order kinematics of mechanisms based on Clifford algebra is rare. First, after recalling the based theory of motion representation in conformal geometric algebra (CGA), the mathematical relationships between flag and motor are built. Second, a method for the higher-order kinematics modeling of serial chain mechanisms is proposed. Finally, the higher-order kinematics of the 3-RRS parallel mechanism is built to prove the correctness of the algorithm. This work further enriches the application of CGA for the higher-order kinematics modeling of parallel mechanisms.
The Efficacy and Safety of Niraparib for Advanced Ovarian Cancer: A Single-center Observational Study From China
Authors: Ni Jing , Cheng Xianzhong , Zhao Qian , Dai Zhiqin , Xu Xia , Guo Wenwen , Gu Hongyuan , Zhou Rui , chen xiaoxiang
Published: November 2020

BackgroundNiraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD) positive. We present real-world experience from China. MethodsPatients with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx®) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity. ResultsTwenty-two patients all received niraparib at an bolus of 200mg/d. 50% of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI=0.060-0.759) and DCR of 50% (95%CI=0.140-0.861) in the exploratory multi-line monotherapy group. Commonly AEs were nausea, thrombocytopenia, and anemia. Grade 3-4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event. Conclusion﻿It is feasible for patients received a bolus of 200mg/d in Chinese population with promising efficacy and well tolerated. This is first real world data about niraparib in ovarian cancer patients with HRD status from China.
DegSampler: Gibbs sampling strategy for predicting E3-binding sites with position-specific prior information
Authors: Maruyama Osamu , Matsuzaki Fumiko
Published: November 2020

Background: The ubiquitin-proteasome system is a pathway in eukaryotic cells for degrading polyubiquitin-tagged proteins through the proteasomal machinery to control various cellular processes and maintain intracellular homeostasis. In this system, the E3 ubiquitin ligase (hereinafter E3) plays an important role in selectively recognizing and binding to specific regions of its substrate proteins. The relationship between a substrate protein and its sites bound by E3s is not well understood. Thus, it is challenging to computationally identify such sites in substrate proteins. Results: In this study, we proposed a collapsed Gibbs sampling algorithm called DegSampler (Degron Sampler) to identify the binding sites of E3s. DegSampler employs a position-specific prior probability distribution, based on the estimated information of the disorder-to-order region bound by any protein. Conclusions: Our computational experiments show that DegSampler achieved 5 and 3.5 times higher the F-measure values of MEME and GLAM2, respectively. Thus DegSampler is the first model demonstrating an effective way of using estimated information on disorder-to-order binding regions in motif discovery. We expect our results to improve further as higher quality proteome-wide disorder-to-order binding region data become available.
The Impact of Childhood Psychological Maltreatment on Mental Health Outcomes in Adulthood: A Protocol for a Systematic Review and Meta-Analysis
Authors: Xiao Zhuoni , Baldwin Mina Murat , Meinck Franziska , Obsuth Ingrid , Murray Aja Louise
Published: November 2020

Background: Research suggests that childhood psychological maltreatment (i.e., emotional abuse and emotional neglect) is associated with mental and physical health problems that persist into adulthood, for example anxiety, depression, post-traumatic stress disorder (PTSD), suicidal ideation, and aggression; however, a systematic review and meta-analysis of the existing literature would help clarify the magnitude and moderators of these associations, and the extent to which they may be affected by publication bias, as well as the methodological strengths and weakness of studies in this area.Method: Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline will be employed to structure the review. Several searches will be carried out via databases including Web of Science, Medline, PubMed, PsycINFO, Applied Social Science Index and Abstract, ERIC and EMBASE. Empirical peer reviewed research articles that fit pre-specified eligibility criteria will be included in the review. This review will include literature written in either English or Chinese. Two independent reviewers will screen and assess studies for inclusion in the review as well as extract the data, with consensus reached through discussion in cases of discrepancy. A third reviewer will be consulted to resolve any discrepancies that cannot be resolved through discussion between the original reviewers. The relevant Newcastle-Ottawa scales will be used for assessing the quality of studies. If a sufficient number of comparable studies are retrieved, a meta-analysis will be conducted using a random effects model. Discussion: This systematic review will provide an understanding of the long-term effects of childhood psychological maltreatment on adult mental health, which adds to previous reviews focusing primarily on the effects of physical and sexual abuse. The results of the review will help inform clinical practice in approaches to treating those with a history of psychological maltreatment in childhood. The gaps and weaknesses in the evidence identified will also inform recommendations for future research.
Circulating Tumor Cells and TWIST Expression in Patients with Metastatic Gastric Cancer
Authors: Jhi Joon Hyung , Kim Gwang Ha , Park Su Jin , Kim Dong Uk , Lee Moon Won , Lee Bong Eun , Kwon Chae Hwa , Cho Yoon-Kyoung
Published: November 2020

Background: The clinical significance of circulating tumor cells (CTCs) and TWIST expression in CTCs remains unelucidated in patients with gastric cancer (GC). Here, we evaluated CTCs and TWIST expression in CTCs and explored their correlation with prognosis in patients with metastatic GC. Methods: Peripheral blood samples were prospectively obtained from 31 patients with metastatic GC between September 2017 and December 2018, prior to treatment. CTCs were detected using a centrifugal microfluidic system and CTCs positive for TWIST immunostaining were defined as TWIST (+) CTCs. CTCs and TWIST (+) Results: CTCs were detected in 25 (80.6%) of the 31 patients. CTC count in patients with first diagnosis of metastatic cancer tended to be higher than that in those with recurrent metastatic cancer, but TWIST (+) CTC count was not different between the two groups. There was no difference in CTC and TWIST (+) CTC counts according to histopathologic type, peritoneal dissemination, hematogenous metastasis, serum tumor makers, or response to first-line chemotherapy. Patients with CTCs >7.5/7.5 mL of blood showed shorter overall survival (OS) than those with CTCs ≤7.5/7.5 mL of blood (P = 0.049). Additionally, patients with TWIST (+) CTCs >2.5/7.5 mL of blood showed shorter OS than those with TWIST (+) CTCs ≤2.5/7.5 mL of blood (P = 0.105). Conclusions: Our study demonstrated that high levels of CTCs and TWIST (+) CTCs were associated with worse OS.
Size, Composition and Distribution of Health Workforce in India: Why, and Where to Invest?
Authors: Karan Anup , Negandhi Himanshu , Hussain Suhaib , Zapata Tomas , Mairembam Dilip , De Graeve Hilde , Buchan James , Zodpey Sanjay
Published: November 2020

BACKGROUND: Investment in human resources for health not only strengthen the health system but also generates employment and contributes to economic growth. India can gain from enhanced investment in health workforce in multiple ways. This study in addition to presenting updated estimates on size and composition of health workforce, identifies areas of investment in health workforce in India. METHODS: We analyzed two sources of data: i) National Health Workforce Account (NHWA) 2018 and ii) Periodic Labour Force Survey 2017-18 of the National Sample Survey Office (NSSO). Using the two sources we collated comparable estimates of different categories of health workers in India, density of health workforce and skill-mix at the all India and state levels. RESULTS: The study estimated (from NHWA 2018) a total stock of 5.76 million health workers which included allopathic doctors (1.16 million), nurses/midwives (2.34 million), pharmacist (1.20 million), dentists (0.27 million), and traditional medical practitioner (AYUSH 0.79 million). However, the active health workforce size estimated (from NSSO2017-18) is much lower (3.12 million) with allopathic doctors and nurses/midwives estimated as 0.80 million and 1.40 million respectively. Stock density of doctor and nurses/mid-wives are 8.8 and 17.7 respectively per 10,000 persons as per NHWA. However, active health workers’ density (estimated from NSSO) of doctor and nurses/mid-wives are estimated to be 6.1 and 10.6 respectively. The numbers further drop to 5.0 and 6.0 respectively after accounting for the adequate qualifications. All these estimates are well below the WHO threshold of 44.5 doctor, nurses and midwives per 10,000 population. The results reflected highly skewed distribution of health workforce across states, rural-urban and public-private sectors. A substantial proportion of active health worker were found not adequately qualified on the one hand and on the other more than 20% of qualified health professionals are not active in labour markets. CONCLUSION: India needs to invest in HRH for increasing the number of active health workers and also improve the skill-mix which requires investment in professional colleges and technical education. India also needs encouraging qualified health professionals to join the labour markets and additional trainings and skill building for already working but inadequately qualified health workers.
Influence of 200 Years of Water Resource Management on a Typical Central European River 
Authors: Wolf Stefanie Sabine , Esser Verena , Schüttrumpf Holger , Lehmkuhl Frank
Published: November 2020

Background Over the last 200 years, most European river courses experienced significant irreversible changes. These changes were connected with different kinds of anthropogenic river use and exploitation, which varied from running water mills and rafting to large-scale hydroelectric power plants, industrial water withdrawal and measures for flood protection. Today, in most of the developed countries water quality and ecological river development are stakeholders in water management. The aim of the following study is to evaluate the specific impact of different time periods during the last 200 years on river courses, and its effects on the current river management using the example of the 165 km long German Rur River (North Rhine-Westphalia). The Rur River is a representative central European upland to lowland river, whose catchment has been affected by various phases of industrial development.MethodsIn this study, large-scale morphological changes over the last 200 years are determined based on historic maps and up-to-date orthophotos. The indicators river length, sinuosity, oxbow structures, sidearms and the number of islands are used to investigate human impact. The results are correlated with historic time periods.ResultsThis analysis shows that river straightening does increase especially during the industrial revolution, even without direct hydraulic channelization, which applies not only to the study area but also to further examples worldwide. The period and grade of river straightening has a direct morphodynamic impact on today’s river restorations. Since the Rur River is a typical upland to lowland river, the results show additional impact of geo-factors, like landform configurations.ConclusionsThe morphodynamic development is correlated with five historic periods between 1801 and 2019 of industrial development up to the introduction of the EU - Water Framework Directive (EU-WFD). Each period shows different influence on the watercourse which is connected with human intervention. Even if worldwide comparisons show that the five historical phases differ slightly in time between regions, they are applicable to other study areas.