bluuebunny/crossref_metadata_2025_split huggingface dataset:
On Overfitting and Asymptotic Bias in Batch Reinforcement Learning with Partial Observability
Authors: Francois-Lavet Vincent , Rabusseau Guillaume , Pineau Joelle , Ernst Damien , Fonteneau Raphael 
Published: May 2019

This paper provides an analysis of the tradeoff between asymptotic bias (suboptimality with unlimited data) and overfitting (additional suboptimality due to limited data) in the context of reinforcement learning with partial observability. Our theoretical analysis formally characterizes that while potentially increasing the asymptotic bias, a smaller state representation decreases the risk of overfitting. This analysis relies on expressing the quality of a state representation by bounding $L_1$ error terms of the associated belief states. Theoretical results are empirically illustrated when the state representation is a truncated history of observations, both on synthetic POMDPs and on a large-scale POMDP in the context of smartgrids, with real-world data. Finally, similarly to known results in the fully observable setting, we also briefly discuss and empirically illustrate how using function approximators and adapting the discount factor may enhance the tradeoff between asymptotic bias and overfitting in the partially observable context.
Comprehensive Clinical Trial Data Summation for BRAF-MEK Inhibition and Checkpoint Immunotherapy in Metastatic Melanoma
Authors: Luke Jason J. 
Published: May 2019

Abstract

Background
Immune checkpoint inhibitors, along with BRAF and MEK inhibitors, have dramatically changed the management of and outlook for patients with metastatic melanoma. Analyses of long-term follow-up data and subanalyses based on disease characteristics may inform clinical decision making.

Methods
Reports of clinical trials in metastatic melanoma published between January 1, 2012, and August 30, 2018, were identified using PubMed (terms: melanoma AND [dabrafenib OR trametinib OR vemurafenib OR cobimetinib OR encorafenib OR ipilimumab OR nivolumab OR pembrolizumab]) and were systematically reviewed. Relevant congress proceedings were also assessed. Efficacy data from key phase III trials were analyzed and trends identified.

Results
Substantial improvements in objective response rates, progression-free survival, and overall survival were documented across 14 identified publications. Subgroup findings supported that patients with lower disease burden derive greater benefit than patients with more advanced disease, limiting the value of disease burden in the clinical decision-making process. However, these agents consistently conferred benefits despite the presence of poor prognostic features. Several clinically relevant questions remain, including how best to sequence immune checkpoint inhibitors and combination targeted therapy.

Conclusion
This research, coupled with ongoing investigations, including those on predictive biomarkers, suggests that the treatment decision-making process is likely to become more nuanced.

Implications for Practice
The management of melanoma has been rapidly advancing with new classes of agents, including immune checkpoint and BRAF inhibitors. With long-term follow-up, their impact on response rates and survival outcomes is well documented. Additional findings from subgroup analyses suggest that patients with lower disease burden derive greater benefit, yet both consistently confer benefit in patients with higher disease burden. Currently, there is a paucity of data to guide first-line treatment selection between immunotherapy and BRAF-targeted therapy in clinical practice or to estimate their impact when sequenced. Gaining these insights will facilitate a more nuanced management approach.
Best Practices and Recommendations for Magnetic Directional Surveying in the Barents Sea
Authors: Edvardsen Inge , Nyrnes Erik , Gullikstad Johnsen Magnar , Naemi Willer Anna 
Published: May 2019

Abstract
In the coming years, several oil and gas fields in the Barents Sea will be developed. The Barents Sea is located between 71-74° latitude and is a part of the Arctic Ocean. At such high latitudes, surveying with magnetic Measurement-while-drilling (MWD) and gyro survey instruments result in almost twice the azimuth uncertainties of the North Sea latitudes.
Magnetic MWD is the most common survey method, mainly due to low cost and time consumption to perform a measurement. However, the main drawback with magnetic MWD survey instruments is the sensitivity to external magnetic fields resulting from magnetic components in the bottom hole assembly (BHA), magnetic particles in drilling fluids, and fluctuations in the Earth's magnetic field. The Barents Sea is in the auroral zone where the largest geomagnetic field disturbances are experienced. Consequently, achieving accurate reference field parameters for MWD surveying is challenging.
Different methods exist to maintain an acceptable quality of magnetic survey data at high latitudes. One approach is to isolate the magnetometer sensors from external magnetic interference and apply uncorrected azimuth calculation. This is advantageous because uncorrected azimuth is less sensitive to external field disturbances than corrected azimuth achieved by drill string interference (DSI) correction or multi-station analysis (MSA). For offshore sites, limitations exist for using geomagnetic reference data from land-based monitoring stations to correct MWD data.
Large azimuth uncertainties result in major lateral wellbore position uncertainties and give less room for blunders and gross survey errors when high accuracy is required. Consequently, it is vital to minimize the effects of external error sources. Several downsides of large position uncertainties exist, such as increased distance between wells to avoid collisions and decreased chance of hitting geological targets. The combined effect of external error sources is complex and in specific cases certain error sources cannot be detected using conventional quality control procedures.
In this paper, recommendations to overcome the above-mentioned challenges will be presented.
Well Integrity – Managing the Risk Using Accurate Design Factors
Authors: Brechan Bjorn , Sangesland Sigbjorn , Dale Stein 
Published: May 2019

Abstract
Wells closed in due to integry issues compose large volumes of recoverable hydrocarbons. In recent years, there has been advances in the understanding of pipe performance. The understanding of these advances is kept with a few specialists, and the industry standard remains unchanged for most engineers working with well intergrity. This paper shed light on these advances and the impact they have to well integrity. A modest estimate for an average well is an upfront saving potential of ~$45,000 USD for tubulars and a reduction of more than 50 metric tons of CO2 saving of the environment. The larger values, however, is with wells closed in due to integrity marginally under the acceptable. This article shows a hidden design margins. On average, pipe resistance to collapse is ~10 to 25% above the industry standard calculations. And for burst design, the real limit is often more than 7% higher than the industry standard calculations.
Well integrity is a discipline ensuring safe hydrocarbon recovery on behalf of an operator. Every well is scrutinized and every signal outside the set boundaires from a well is ensued until the integrity is understood and a decision can be made to safely produce or to suspend the well. Well integrity is based on performance of the equipment in the barrier envelopes. Pipe is an important element in both the primary and secondary envelopes. Following a better understanding of pipe integrity, a new integrity work flow is proposed. Well Integrity is a relatively young discipline, where guidelines and stanards have evolved significantly over the last decade. There are still several important issues to be standardized, such as the minimum integrity information to be defined for a well. Examples are operational parameters such as (assumed) effective hole diameter, cementing parameters (rate, preflush, slurry, etc.) which have an impact to the integrity. Other important information to standardize is the restrictions in pressure testing of casing to avoid damage of the cement sheaths. Finally, this article proposes "information management" as the 4th element in the definition of well intergrity. The digitalization wave washing over the industry is about making optimal use of data, which is essential to make good decision in well integrity as much as any other area in the oil and gas industry.
Real-Time Fluid Mapping Ensures Reserve Development Via Optimized High-Angle Infill Drilling
Authors: Bravo Maria Cecilia , Baig Mirza Hassan , Gueze Nicolas , Kotwicki Artur , Horstmann Mathias , Blanco Yon , Guevara Carlos , El-Khoury Jules , Scott Paul 
Published: May 2019

Abstract
Reservoirs containing complex structures require additional technology to obtain optimum performance from planned production wells. In this scenario, logging-while-drilling (LWD) technologies play an important role in well construction from purely geometric trajectories to the real-time trajectory steering and formation and fluid characteristics measurements.
A North Sea Alvheim field case study is presented in this paper. During the exploration and initial development phase of the field, the oil/water contact (OWC) varied to 7 m due to the presence of mudstone baffles and faults. The field has been on production since 2008 using bottom-aquifer drive, and current fluid contacts have shifted from their initial levels. To enhance field recoverable reserves, an infill development plan was required to place the wells within a thin oil rim between the gas/oil contact (GOC) and the OWC.
Field objectives included achieving optimal well landing, identifying the moveable oil in situ, mapping the hydrocarbon-bearing reservoir, and identifying the hydrocarbon type (oil or gas) along the wellbore trajectory. To address the challenges, an integrated drilling bottomhole assembly (BHA) consisting of a deep-directional resistivity (DDR) tool to refine the reservoir delineation and structural positioning, a downhole fluid analyzer (DFA) using optical spectrometry to identify in-situ fluids, and advanced petrophysical measurements provided a complete quantitative reservoir evaluation during well construction.
This paper presents the design, execution, and interpretation of the acquisition program to achieve the well objectives, including positioning the producer well in the desired moveable fluid zone. The final results demonstrated that integrating LWD measurements in the operation added significant value toward achieving the desired wellbore trajectory by optimally positioning the wellbore in the desired reservoir fluid layer.
Precision Surgery for Well Workover: An Innovation in Well Intervention
Authors: Benguergoura M. C , Bergem J 
Published: May 2019

Abstract
Conventional well interventions using drill pipes, coiled tubing, and slickline suffer much from inaccuracy, absence of downhole control, and lack of surface monitoring. The oil and gas industry has been pushing for a better, lighter, and more innovative approach. During the last 25 years, emerging downhole electric and electrohydraulic tools deployed on electric line (e-line) have gradually replaced some conventional methods, enabling more efficient and precise operational execution with the help of surface read-out data and real-time monitoring while controlling the downhole tools via commands sent through the e-line, adjusting to the needs transmitted by sensors integrated in the tools themselves. The results have been well received, and precision has become a necessity in certain well interventions, especially where the life of a well is expected to extend and the recovery to become more sustainable. Consequently, precision interventions save considerable time and cost to the operators while offering safer alternatives to other methods.
In this case, we show how two cutting-edge, e-line technologies have solved two important challenges for an operator: (1) Orienting an e-line puncher tool sideways to secure circulation when punching tubing at high deviation, and (2) cutting tubing in compression without damaging the outer casing, leaving a clean, beveled edge for subsequent runs.
Both solutions were made available and executed flawlessly for the operator. Surface read-out data from both tools helped real-time monitoring and successful execution. This case demonstrates, once again, what a combination of e-line intervention and disruptive innovation can currently achieve for operators.
On a subsequent well, both solutions described above were combined in one run, saving further rig time and cost, and resulting in safer operations than alternative, conventional methods.
Efficient Optimization of Well Drilling Sequence with Learned Heuristics
Authors: Wang Lingya , Oliver Dean S. 
Published: May 2019

Abstract
When preparing a field development plan, the forecast value of the development can be sensitive to the order in which the wells are drilled. Determining the optimal drilling sequence generally requires many simulation runs. In this paper, we formulate the sequential decision problem of drilling schedule as one of finding a path in a decision tree that is most likely to generate the highest net-present-value (NPV). A non-parametric online learning methodology is developed to efficiently compute the sequence of drilling wells that is optimal or near optimal. The main ideas behind the approach are that heuristics from relaxed problems can be used to estimate the maximum value of complete drilling sequences constrained to previous wells, and that multiple online learning techniques can be used to improve the accuracy of the estimated values. The performance of various heuristic methods is studied in a model for which uncertainty in properties is neglected. The initial heuristic utilized in this work generates a higher estimated NPV than the actual maximum NPV. Although such a heuristic is guaranteed to find the true optimal drilling order when used in A* search, the cost of the search can be prohibitive unless the initial heuristic is highly accurate. For the variants of heuristic search methods with weighting parameters, the results show that it may not be possible to identify parameters that can be used to find a solution quickly without sacrificing the accuracy of the estimated NPV in this drilling sequence problem. In contrast, the online learned heuristics based on the observations from previous drilling steps are demonstrated to outperform the other variants of heuristic methods in terms of running time, accuracy of the estimated value and solution quality. Multi-learned heuristic search with space reduction is an efficient and fast method to find a solution with high value. Continuing the search with space restoration is guaranteed to improve the solution quality or find the same solution as the multi-learned heuristic search without any space reduction.
Flow Loop Trial of an Autonomous Downhole Choke for Compensation of Rig Heave-Induced Surge & Swab
Authors: Gorski Dmitri , Kvernland Martin , Borgen Harald , Godhavn John-Morten , Aamo Ole Morten , Sangesland Sigbjørn 
Published: May 2019

Abstract
Harsh weather conditions result in severe heave motion on floating drilling rigs. The drill string is heave-compensated during drilling ahead, however, when slips are set during drill pipe connections, the topside heave compensation system is disabled, and the drill string is then moving up and down together with the rig. Pressure oscillations below and around the drill bit, induced by such movement, are known as "surge & swab". These oscillations can be in the order of 20 bar or more during drill pipe connections in the North Sea and pose a serious challenge to drilling of wells with narrow pressure margins from floating rigs in harsh weather environment. A managed pressure drilling (MPD) choke at the surface cannot be used to control rig heave-induced surge & swab due to the fast nature of the pressure oscillations in question, stochastic character of the sea waves that cause them and long time-delay between topside choking and bottomhole response. Continuous Circulation System (CCS) might be able to reduce the pressure oscillations somewhat by maintaining constant mud flow during connections.
Computer simulations and laboratory experiments were previously used to investigate a novel method for attenuating surge & swab by utilizing an autonomous choke to be installed in the bottom-hole assembly (BHA). The bottomhole pressure oscillations can be effectively reduced through dynamic in-situ control of the mud flow through BHA by a downhole choke. This paper presents the downhole choke system and the results from the first pilot trial conducted in a mud flow loop at Ullrigg test rig in Stavanger utilizing a full-scale version of the choke. The prototype was subjected to drilling mud with flow rates up to 2500 lpm and differential pressure up to 250 bar to investigate its ability to accurately control the flow while at the same time withstanding the demanding conditions.
Satisfactory choke valve characteristics were obtained, indicating ability to control the flow with sufficient precision. Flow testing resulted in severe erosion of carbon steel components while wolfram carbide components were able to withstand the erosive nature of the flow. The test also uncovered challenges related to operation of the choke with high differential pressure and flow rates which could later be related to the motor, used to control the downhole choke assembly.
The next phase of the project is to design a downhole prototype and test it in an onshore test well to achieve Technology Readyness Level (TRL) 4 qualification ("ready for first use offshore"). The final goal is to qualify the downhole choke together with MPD and a Continuous Circulation System (CCS) for use on floating drilling rigs in harsh weather environment.
CASSETTE - clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation: study protocol for a randomised controlled trial
Authors: Dotel Ravindra , Tong Steven YC , Bowen Asha , Nelson Jane N , O'Sullivan Matthew VN , Campbell Anita J , McMullan Brendan J , Britton Philip N , Francis Joshua R , Eisen Damon P , Robinson Owen , Manning Laurens , Davis Joshua S 
Published: May 2019

Abstract
Background Exotoxins are an important virulence factors in Staphylococcus aureus. Clindamycin, a protein synthesis inhibitor antibiotic, is thought to limit exotoxin production and improve outcomes in severe S. aureus infections. However, randomised prospective data to support this is lacking. Methods An open label, multicenter, randomised controlled trial (RCT) will compare outcome differences in severe S. aureus infection between a standard treatment (flucloxacillin/cefazolin in methicillin-susceptible S. aureus; and vancomycin/daptomycin in methicillin-resistance S. aureus) and a standard treatment plus an additional clindamycin given for 7 days. We will include a minimum of 60 participants (both adult and children) in the pilot study. Participants will be enrolled within 72 hours of an index culture. Severe infections will include septic shock, necrotising pneumonia, or multifocal and non-contiguous skin and soft tissue/osteoarticular infections. Immunosuppressed, moribund, current severe diarrhea or C. difficile infection, pregnant, and those with anaphylaxis to beta-lactams or lincosamides will be excluded. Primary outcomes measure is number of days alive and free (1 or none) of SIRS (Systemic Inflammatory Response Syndrome) within the first 14 days post randomization. Secondary outcomes measure will include all-cause mortality at 14, 42 and 90 days, time to resolution of SIRS, proportion with microbiological treatment failure, and rate of change of C-reactive protein over time. Impacts of inducible clindamycin resistance, strains types, methicillin-susceptibility, and presence of various exotoxins will also be analysed. Discussion This study will assess the effect of adjunctive clindamycin on patient-centered outcomes in severe, toxin mediated S. aureus infections. The Pilot study will provide feasibility for a much larger RCT. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12617001416381p. Registered 06 October 2017
OCT Angiography of Persistent Hyaloid Artery: A case report
Authors: Jeon Hansol , Kim Jinsoo , Kwon Soonil 
Published: May 2019

Abstract
Background

A persistent hyaloid artery is a rare fetal remnant. Several complications such as amblyopia, vitreous hemorrhage, and retinal detachment have been reported. Here, we present a case of vitreous hemorrhage with a persistent hyaloid artery.

Case presentation

A healthy 16-year-old male presented with blurred vision in his left eye. Vitreous hemorrhage occurred and absorbed spontaneously. Slit-lamp examination demonstrated a Mittendorf’s dot and fundus examination revealed a persistent hyaloid artery. Optical coherence tomography showed a Bergmeister’s papilla. The blood flow of the persistent hyaloid artery via the Bergmeister’s papilla was found by OCT angiography.

Conclusion

The persistent hyaloid artery should be considered as a cause of spontaneous vitreous hemorrhage of young healthy patient. The OCT angiography will be a useful noninvasive approach to confirm the patency of the persistent hyaloid artery.
Integrative Analysis of shared Genetic Pathogenesis by Autism Spectrum Disorder and Obsessive-Compulsive Disorder
Authors: Liu Dongbai , Cao Hongbao , Kural Kamil Can , Fang Qi , Zhang Fuquan 
Published: May 2019

Abstract
Background

Many common pathological features have been observed for both autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). However, no systematic analysis of the common gene markers associated both ASD and OCD has been conducted so far.

Results

Here, two batches of large-scale literature based disease-gene relation data (updated in 2017 and 2019, respectively) and gene expression data were integrated to study the possible association between OCD and ASD at the genetic level. Genes linked to OCD and ASD present significant overlap (p-value<2.64e-39). A genetic network of over 20 genes was constructed, through which OCD and ASD may exert influence on each other. The 2017-based analysis suggested six potential common risk genes for OCD and ASD (CDH2, ADCY8, APOE, TSPO, TOR1A, and OLIG2), and the 2019-based study identified two more genes (DISP1 and SETD1A). Notably, the gene APOE identified by the 2017-based analysis has been implicated to have an association with ASD in a recently study (2018) with DNA methylation analysis.

Conclusions

Our results support the possible complex genetic associations between OCD and ASD. Genes linked to one disease is worthy of further investigation as potential risk factors for the other.