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Background and objectivesCystic fibrosis (CF) is a heterogeneous disease with a diverse genetic spectrum among populations. Few patients with CF of Chinese origin have been reported worldwide. The objective of this study is to characterise the genotypic features of CF in Chinese children.MethodsWe recruited and characterised the genetic manifestations of 103 Chinese children with CF in Beijing Children’s Hospital from 2010 to 2022. Whole-exome sequencing were performed to define the genotypes. Meanwhile, other 99 genetically confirmed patients with Chinese origin described in 45 references were also summarised.Results158 different variants including 23 novel observations were identified after sequencing. The majority ofCFTRvariants (82.3%) in Chinese have been observed only once or twice. 43.7% of the variants were only identified in patients of Chinese origin. The c.2909G>A(p.Gly970Asp), c.1766+5G>T and c.1657C>T(p.Arg553X) were the most frequent variants among Chinese patients, with allele frequency of 12.1%, 5.4% and 3.6%, respectively. The first two variants both showed significant Chinese ethnic tendency, while the latter one most likely came from Europeans for historical reasons. They also demonstrated significant differences in geographical distribution. c.1521_1523delCTT(p.F508del) was rarely observed in patients of pure Chinese origin, with an allele frequency of 1.8%. Two de novo variants (c.960dupA[p.Ser321IlefsX43] and c.2491-2A>G) and two deep-intronic variants (c.3718–2477C>T and c.3874-4522A>G) were identified, which were also quite rare among Chinese.ConclusionsThe genetic spectrum of CF in Chinese is unique and quite different from that observed in Caucasians. The geographical distributions of the most frequent variants were reported for the first time.

Objective: To describe the clinical characteristics of Covid-19 in infants during the Omicron variant outbreak in Henan, 2022. Methods: We retrospectively analyzed the clinical data, epidemiological exposure, and maternal vaccination status of infants infected with Omicron variant admitted to Zhengzhou First People’s Hospital from October 20, 2022 to December 15, 2022. Results: We admitted 21 infants (12 males and 9 females). All had epidemiological exposure in household or nursing institution settings. The most common respiratory manifestations were fever (19 cases), cough (11 cases), and nasal congestion (8 cases). The most frequent gastrointestinal manifestations were anorexia and diarrhea (8 cases each) and vomiting (4 cases). Of the 12 infants who underwent complete blood count, 8 had normal white blood cell counts and 3 had leukopenia. C-reactive protein was normal in 11 cases and mildly elevated in 1 case. Chest CT showed increased lung markings in 7 cases, focal consolidation in 6 cases each, and ground-glass opacities in 5 cases. The mean time to negative conversion was 6.7 days. All 21 infants recovered and were discharged after symptomatic treatment, with a mean length of stay of 11.5 days. Two weeks after discharge, none had recurrence or retested positive for SARS-CoV-2 RNA. We found no correlations between maternal vaccination status and clinical symptoms or SARS-CoV-2 RNA negative conversion time (P>0.05). Conclusion: All Covid-19 infants had epidemiological exposure in household or nursing institution settings. They mostly had mild infection with respiratory and/or gastrointestinal symptoms and a good short-term prognosis.

The ability to analyze drilling data to obtain continuous monitoring statistics of the drilling process and make prompt decisions are two important elements of a successful drilling operation. A mud motor is one of the important components of the downhole assembly, which enables the drill bit to penetrate the rock during drilling a well. Correctly predicting mud motor failure and the remaining useful life of the components are essential for obtaining drilling efficiency, avoiding costly operational expenses, and achieving timely maintenance. The remaining useful life indicator with low uncertainty identifies the life cycle of mud motors by preventing redundant maintenance and costly drilling operation failures.This paper presents an industry-unique prognostics and health-management (PHM) solution for monitoring and maintaining the mud motor condition. This solution combines three algorithms, including a power section PHM algorithm, lower-end critical connections PHM algorithm, and mud motor degradation algorithm. The workflow solution allows for obtaining valuable information about the mud motor condition at the system and component levels.The power section PHM algorithm, based on a remaining useful life prediction for the mud motor's power section, provides information about the elastomer condition inside of the stator as a percentage of the remaining life cycle. The lower-end critical connections PHM algorithm estimates the remaining useful life of the mud motor's lower-end connections. Both algorithms are component level; i. e., they help to improve managing the life cycle of the appropriate components. The mud motor degradation algorithm is a system-level algorithm. This algorithm uses drilling data to compute the severity of mud motor degradation; thus, identifying possible problems with the mud motor as a complete system.The PHM solution helps to prevent expensive mud motor failure. Furthermore, the solution provides the opportunity to perform additional drilling runs before the motor components must be retired or removed for maintenance. The significant advantage of applying the PHM solution is it only makes use of existing drilling measurements and does not require any special downhole equipment.The mud motor PHM solution is currently in use by one of the biggest oil & gas service company worldwide. In addition to presenting the three algorithms, this paper presents field application case studies that demonstrate the commercial value and efficiency gains achieved by their use. Significant sustainability benefits have been achieved by using the power section and mud motor degradation algorithms due to their assistance in drilling applications.

This report describes a case of an 11-year-old Chinese boy with cystic fibrosis (CF) bearing the c.1521_1523delCTT/c.3874-4522AG genotype, an extremely rare CF genotype in the Chinese population. Notably, the deep intron mutation c.3874-4522AG, which has mainly been reported in patients with phenotypically mild CF, is identified here for the first time in a Chinese patient with severe CF. In the case discussed here, the c.3874-4522AG mutation was associated with severe pulmonary disease with early symptoms onset, progressive bronchiectasis, recurrent airway infection with both Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus, rapid decline of lung function and poor weight gain. Despite intensive hospital-based pulmonary care and optimized therapy, the child died of cardiopulmonary failure 3 months after discharge.

We report a small case series of childhood-onset Takayasu arteritis (c-TA) presenting as pyoderma gangrenosum (PG)-like vasculitic ulceration. The cutaneous vasculitic ulcers in systemic vasculitis are rare and severe, sometimes leading to delayed diagnosis and treatment. We summarised the clinical features and highlighted the warning signs of c-TA associated with PG-like vasculitic ulceration.

Background: Despite the growing awareness of Cystic Fibrosis (CF) in China, few cases have been reported in Henan, which is the most populous province in the country. This study aimed to describe the clinical phenotype and genotype of children with CF in Henan. Methods: We recruited 14 Chinese children with CF who presented to Children’s Hospital affiliated to Zhengzhou University from January 2019 to January 2023. The demographic data, imaging examinations, and laboratory tests of the patients were reviewed to clarify the clinical phenotype. Whole exome sequencing was conducted to identify the genotype. Results: Respiratory diseases were the main clinical manifestation, including recurrent/persistent pneumonia (85.7%), sinusitis (71.4%), bronchiectasis (71.4%). CF-related liver disease (CFLD) and pancreatic insufficiency (PI) were less common (21.4% each). Infant cases had high frequency of pseudo-Bartter Syndrome (80.0%). Chest computed tomography showed bronchiectasis in older children and air trapping in infant cases. The most common pathogens in the airway were Pseudomonas aeruginosa and Staphylococcus aureus (71.4% respectively). Twenty-four different CFTR gene variants were detected, including four novel observations (c.869+3A>T, c.1064C>G[p.Pro355Arg], c.1209+1G>C and c.1925C>G [p.Ser642X]). The most common variant was c.2909G>A (p.Gly970Asp), with a detected rate of 16.7%. Conclusion: Children with CF in Henan had varied clinical phenotypes by age, with respiratory disease being predominant. The most frequent CFTR gene variant was c.2909G>A(p.Gly970Asp). This study is the first and most comprehensive one on the clinical phenotype and genotype of children with CF in Henan, China. We also reported the first CF case of M. abscessus infection in China.

SummaryAs drilling sections become deeper and longer, transferring more weight downhole to improve rate of penetration is the primary concern for the operator. Drillstring dynamics and buckling are some primary limiters for drilling efficiency. Aggressive drilling parameters may lead to severe downhole dynamics, which leads to cutter breakage and tool damage. When axial compression exceeds a certain threshold, the drillstring buckles sinusoidally inside the wellbore first, followed by helical buckling. Buckling leads to accelerated joint wear, tool fatigue failures, and lower drilling efficiency. To better manage drillstring dynamics and buckling, we propose a method of simulating drillstring dynamics motion and postbuckling state using an advanced transient dynamics model.An analysis methodology was developed on the basis of the finite element transient dynamics model. The model captures the enriched physics of drillstring dynamics and loading: the large deformation of buckled drillstring, the strong nonlinearity of contact and friction forces, and the dynamically triggered instability caused by drilling rotation. Transient dynamics simulations are conducted for drillstring with the actual well trajectory and rotation speed. The weight on bit (WOB) is ramped up gradually, and the drillstring deformation is monitored to detect the onset of buckling or dynamics instability.To conduct the model validation, the buckling inception loads predicted by the model are compared against the analytical equation of critical buckling loads. A field extended reach drilling (ERD) job was simulated by the model. The downhole weight and torque data from the measurement-while-drilling (MWD) tool was used to validate the weight transfer prediction by the model. Most existing buckling theories use the analytical equations of critical buckling load, which were normally derived on the basis of the idealized assumptions, such as perfect wellbore shape and uniform tubular geometry. The proposed method simulates the drillstring behaviors in the field drilling conditions and aims to capture effects of wellbore friction and string rotation. The transient dynamics model is capable of simulating drillstring dynamics movement (whirling and snaking) and weight lockup under severe helical buckling. An automatic method is proposed to interpret the drillstring behaviors from the simulation results. Using the transient dynamics model, the procedure presented in this article can simulate the dynamics and buckling behaviors of drillstring and help mitigate associated risks in well-planning and execution phases.

This report entails a case of an 11-year-old Chinese boy with cystic fibrosis (CF), who bears the c.1521_1523delCTT/c.3874-4522A>G genotype, which is extremely rare in Chinese population. Notably, the deep intron mutation c.3874-4522A>G was the first time identified among Chinese patients, which was reported mainly associated with mild phenotype. It is generally considered that a mild allele sustains CFTR function in a dominant fashion, even if paired with a severe allele. However, in the present report, the c.3874-4522A>G mutation was found related to severe pulmonary diseases, including early symptom onset, progressive bronchiectasis, recurrent airway P. aeruginosa combined with MRSA, rapid decline of lung function, and poor weight gain, which suggesting severe phenotype. Despite intensive chest care and optimized therapy, the child ultimately died of cardiopulmonary failure 3 months after discharge.

Objective: To investigate the clinical manifestations, diagnosis and treatment processes of two siblings with PCD caused by the same compound heterozygous mutations in DNAAF2. Methods: With clinical diagnosis of PCD, the two siblings were recruited in the study. We collected their clinical histories, laboratory tests, bronchoscopy, otoscope images, and radiographic data. Whole blood of the siblings and their parents were separately harvested for whole-exome sequencing and Sanger sequencing. Results: The 7-year-old girl presented with recurrent respiratory tract infection, sinusitis and otitis media. Auxiliary examinations showed pneumonia, atelectasis, bronchiectasis, low nitric oxide concentration (nNO), and conducting hearing loss. The younger brother, 10-month boy, exhibited pneumonia, sinusitis, otitis media, intestine malrotation and with lower nNO, atelectasis in chest CT, obstructive ventilator dysfunction by pulmonary function and conductive hearing loss. Two compound heterozygous mutations in DNAAF2 were detected in both of the siblings, nonsense mutation c.156C＞A and frameshift mutation c.177_178insA, and the c.177_178insA (p.E60Rfs*3) mutation is a novel mutation. Conclusion: The study enriches our knowledge of clinical manifestations and genetic information of PCD caused by DNAAF2.

It is often essential that the behavior of certain tools inside of the bottomhole assembly (BHA) be understood, prior to automating the well construction process. The mud motor is one of the most frequently used BHA components worldwide. This paper presents several digital well construction procedures in which a mud motor is located inside of the BHA. Mud motors can be directly used in a steering mode or can be combined with the most advanced rotary steerable system (RSS) tools in power only mode because their downhole power ability is unrivaled, and their usage reduces the power needed from surface, making the well construction more sustainable. When considering the six primary surface measurements of well construction (hookload, block position, torque, rpm, pressure, and flow), the interpretation of four of the measurements is directly affected by the presence or not of a mud motor inside the BHA, whether the mud motor is in steering mode or in power only mode. To understand these measurements, a basic understanding of the mud motor physics is required. This paper will present some of the kinematics of the mud motor power section and how it relates to the monitoring, advising, or controlling of the drilling process. In particular, some key equations will be shown that correlate surface measurements to the downhole drill-bit motion through the motor physics. It will be shown that when a mud motor is present, there is a torque discontinuity between the upper portion (above the motor) of the BHA and drillstring and the lower portion of the BHA (below the motor). In addition, equations to fit mud motor power curves are derived, which enables interpretation of the motor power section performance based on the chosen configuration. The acoustic impedance theory for the mud motor will also be shown, which enables understanding the transient effect of flow fluctuations when different torque demands from the drill-bit exist. All these derivations are included in a new mechanical specific energy (MSE) calculation which will be used to derive an autonomous well construction scheme. A novel approach to understanding the monitoring, advising, and controlling of the drilling process when a mud motor is present within the BHA is presented. This approach, which is based on the careful understanding of the mud motor physics and enables automation of the well construction, would be a forerunner for most artificial intelligence (AI) and machine learning (ML) algorithms used to optimize drilling operations when a hydromechanical power generator is present in the BHA.

This paper presents the design and analysis of a database containing more than 24,000 polycrystalline diamond compact (PDC) cutter scrape tests performed using a pressurized experimental laboratory setup. This unique data set contains high-frequency (2 kHz) measurements of the three-axis forces acting on the cutter in various rocks, cutter types and sizes, cutter orientations, depths-of-cut (DOC), and confining pressures. The database can be accessed, visualized, sorted, classified, and analyzed in detail, offering substantial opportunities to increase the knowledge of the rock-cutting process by PDC cutters. Using this database, the authors initially analyzed the rock type, cutter orientation, and DOC effects on the forces acting on the cutter. By using signal processing techniques, algorithms were developed to extract features from the force data. For example, each test was scored based on the rock chipping that occurred during cutting, which manifests itself as sawtooth patterns in the force data. These data allowed for qualitative evaluation of the effects of confining pressure and DOC on the chipping. In addition, the rock types most prone to chipping were identified. This massive dataset allowed for statistical quantification of the forces acting on the cutters, which resulted in new ways for modeling the rock-cutting process, which is inherently stochastic. Furthermore, it is also possible to quantify the efficiency improvement with different cutter shapes when cutting different rocks, which assists in selecting the correct cutter shape for the targeted application to improve drilling performance. In summary, this extensive database provides novel understandings of the rock-cutting process, which are fundamental to the efficiency of the drilling operations, drilling dynamics modeling, and drilling tool development.

Operators drilling a directional well may suffer the uncertainties from the downhole environment, the equipment, and the human decision-making process. We proposed a method to evaluate steering decisions of multiple reinforcement learning agents by calculating the estimated total future reward (ETR) through a validation agent using a simulator. The final decision would be chosen as the one with the maximum total reward among the multi-agent decisions. The multi-agent approach stabilizes the final decision-making for directional drilling and results in a higher success rate and better overall steering performance. In our previous work (Yu et. al, 2021), a single agent was trained to make decisions for directional drilling through the deep reinforcement learning framework. To improve the stability of the decisions, we extend the single-agent approach to this multi-agent framework including a working environment and a validation environment. The system includes a working environment that includes a pool of working agents. The working environment represents the current physical drilling environment (e.g., rig state, geology, bit location, and planned trajectory). In addition, a validation agent is working in a validation environment using a hole propagation simulator for projecting the ETR. When the system is in action, the working agents receive inputs such as surveys and planned information in the working environment and each of them makes their own decisions. Their decisions, as action proposals, are passed to the validation agent while the validation environment synchronizes the state from the working environment. The validation agent then carries out each action proposal in the virtual environment through the simulator and continues drilling to the target multiple times given a variety of formation priors. An average score of ETRs is then calculated for each action proposal. As a result, the action proposal with the maximum average score wins the competition and goes back to the working environment for execution. The multi-agent framework could optimize and stabilize the sequence of decisions while minimizing uncertainties. Our validation results demonstrate that the total rewards were successfully improved than the single-agent decision-making.

Objectives To characterize the clinical and genotypic features of Cystic fibrosis-associated pseudo-Bartter syndrome (CF-PBS) in Chinese children. Methods We recruited and characterized the clinical manifestations of 12 Chinese children with CF-PBS. Sweat test, blood and urinary analysis, sputum culture, chest and sinus computed tomography, and abdominal ultrasonography were obtained. Whole-exome sequencing, bioinformatics analysis, and sanger sequencing validation were performed to define the genotypes. Results CF-PBS was accompanied by recurrent and/or persistent pneumonia (91.7%), pancreatitis (83.3%), vomiting and/or diarrhea (66.7%), failure to thrive and liver disease (58.3% respectively) among our patients. The predominant organisms found in the airways were Pseudomonas aeruginosa (83.3%) and Staphylococcus aureus (75.0%). The mean concentrations of blood gas and electrolytes were: pH 7.58, bicarbonate 40.8 mmol/L, sodium 125.9 mmol/L, chloride 77.5 mmol/L, and potassium 2.6 mmol/L. A high recurrence rate (50.0%) of CF-PBS was observed despite continued electrolyte supplementation during follow up. 19 different variants of CFTR gene were identified, and 10 of these were found to be novel observations (c.262_266delTTATA[p.L88FfsX21], c.579+2insACAT, c.1210-3C>G, c.1733T>C[p.L578P], c.2236_2246delGAGGCGATACTinsAAAAATC[p.E746KfsX8], c.3068T>G [p.I1023R], c.3635delT[p.V1212AfsX16], c.3859delG[p.G1287EfsX2], c.3964-7A>G and ΔE23 [c.3718-?_3873+?del]). The c.2909G>A[p.G970D] was the most common variant, with an allele frequency of 16.6%. A homozygous genotype of c.1521_1523delCTT[p.F508del] was discovered for the first time in patients of Chinese origin. Conclusions In China, CF-PBS usually presents early and recurs frequently in infancy, accompanied by multiple comorbidities. Recurrence of CF-PBS in school-going patients does occur but is rare. The p.G970D is the most frequent variant, with a significant ethnic tendency of Chinese origin. This article is protected by copyright. All rights reserved.

Importance: Surfactant protein C (SP-C) dysfunction is a rare disease associated with interstitial lung disease. Early therapies may improve outcomes but the diagnosis is often delayed owing to variability of manifestations. Objective: To investigate the manifestations and outcomes of SP-C dysfunction. Methods: We retrospectively analyzed the records of five pediatric patients who were diagnosed with SP-C dysfunction between February 2014 and April 2017 at Beijing Children’s Hospital. Results: The five patients included two boys and three girls with a median age at diagnosis of 1.3 years. All patients presented with interstitial lung disease and had a heterozygous SFTPC mutation, including an I73T mutation in three patients, a V39L mutation in one patient, and a Y104H mutation in one patient. In addition to common respiratory manifestations, hemoptysis and anemia were observed in one patient with the I73T mutation. Elevated levels of autoantibodies and a large number of hemosiderin-laden macrophages in bronchoalveolar lavage fluid were found in two patients with the I73T mutation, suggesting the presence of diffuse alveolar hemorrage and autoimmunity. Chest high-resolution computed tomography features included ground-glass opacities, reticular opacities, cysts, and pleural thickening. Transbronchial lung biopsy was performed in one patient with the I73T mutation, which revealed the presence of some hemosiderin-laden macrophages in alveolar spaces. All patients received treatment with corticosteroids; two received combined treatment with hydroxychloroquine. During follow-up, the two patients who received hydroxychloroquine showed improved symptoms; of the remaining three patients, two died after their families refused further treatment, while the final patient was lost to follow-up. Interpretation: This is the first report to describe a new phenotype of diffuse alveolar hemorrhage with autoimmunity in patients with I73T SFTPC mutation. Treatment with hydroxychloroquine should be considered for patients with SP-C dysfunction. Key words: Autoimmunity; Diffuse alveolar hemorrhage; Interstitial lung disease; Rheumatoid arthritis; Surfactant protein C

It is common to have measured depth exceeding 20,000 ft for unconventional oil and gas wells. To ensure the pressure pulse can be detected on the surface, many MWD tools have been designed to generate mud pressure pulse with very large amplitude. While the large pressure pulse solved the problem of sending the measured information up to the surface, it creates significant impact on drilling system energy variation and downhole drilling dynamics. This paper focuses on understanding the effects using big data and drilling system modeling. When a commonly used MWD tool generates mud pulse sequence, it chokes the flow path at designed patterns. This creates mud flow variation in the mud motor below the MWD tool. It also generates axial force variations due to pressure changes, which affect WOB. These changes cause the motor and the bit to experience significant rpm variations. The combined rpm variation and WOB variation often excite more severe axial and lateral shock and vibration. These effects are quantified by thousands of high-frequency downhole datasets and advanced numerical modeling. In the high-frequency downhole datasets, some of them are obtained from BHAs with MWD tools generating large mud pressure pulse, and some of them are obtained from BHAs with MWD tools generating smaller mud pressure pulse or transmitting the measurements using electromagnetic signal. Statistics of rpm variation and axial and lateral shock and vibrations are compared. It clearly shows that the BHAs utilizing large mud pressure pulse experience more severe torsional, axial, and lateral vibrations. When looking into specific datasets, it showed that mud pressure pulse could cause the motor to lose more than half of its rpm during the flow choking phase. Typical datasets indicate that mud pressure pulse correlates to severe high-frequency torsional oscillation (HFTO) in motorized rotary steerable BHA. An advanced transient drilling dynamics model was built to simulate the whole drilling system subjecting to mud pressure pulse incurred loading conditions. It was found that large-magnitude mud pressure pulse induced more stick/slip and axial and lateral vibrations as recorded in downhole high-frequency data. The increased rotational, axial, and lateral vibrations correspond to more loading variations in the mud motor components and PDC cutters on the drill bit. These variations could cause accelerated damage to the drill bit and downhole tools. In summary, large mud pressure pulse utilized by some MWD tools introduces significant rpm variation and shock and vibration, which is quantified by big data and further demonstrated by drilling system modeling. The information could help make decisions on BHA design and tool selection to achieve improved drilling performance and reduce the risk of premature tool failure.

Motivated by the emergence of dominant retail platforms operating using a store-within-a-store strategy, we study the interaction of such a retailer's decision on the selling format and a manufactu...

This paper studies how a manufacturer should engage with a platform retailer and a traditional reseller. Our work is motivated by the emergence of increasingly powerful retail platforms in China’s consumer electronics and appliances markets. The manufacturer pays a slotting fee and a portion of its sales revenue to the platform retailer in exchange for the opportunity to manage its own space within the retailer’s store. The manufacturer can also sell its product to a traditional reseller thereby earning its wholesale price. We first formulate a Stackelberg game where the platform retailer leads by setting the revenue‐sharing rate while the manufacturer follows by choosing to sell through one or both channels. We derive the equilibrium channel and characterize each party’s associated sales quantities, prices, and profits. After confirming, it is always beneficial for the platform retailer to determine the slotting fee and revenue‐sharing rate simultaneously, we then formulate two bargaining models between the manufacturer and the platform retailer. In the first model, they can negotiate just the revenue‐sharing rate and in the second they negotiate both the revenue‐sharing rate and the slotting fee. In the second model, a win‐win result for the manufacturer and platform retailer is possible. We find that the slotting fee is neither always beneficial to the platform retailer nor always harmful to the manufacturer; it depends on the demand substitution effect between the two retail channels.

Publishers, advertisers, and users are the three players in online display advertising, where the traded object is an impression (i.e., a user's visit). The publisher usually sells impressions months in advance of their physical appearance by signing contracts on prices and quantities with advertisers. With the introduction of ad exchanges, the publisher can also sell impressions that are unsold in the contracting market in a spot market. We build a bi-objective optimization problem to maximize the publisher's expected revenue and the advertisers’ fairness of impression allocation in the presence of a spot market and impression supply uncertainty. Here, the publisher decides on the contract prices and creates a plan for impression allocations. The problem is a non-convex program, solved by integrating local and global heuristic methods. We also set a lower bound and an upper bound to facilitate and justify the solutions. Numerical examples indicate that ignoring supply uncertainty may over-estimate the expected revenue, and that fairness may be achieved by sacrificing a small portion of revenue. However, too much fairness may reduce the revenue. It is also shown that the heuristic algorithms are computationally effective.

Background Mediastinal teratoma is uncommon in children. It can be very difficult to diagnose especially in early stage. Rarely, teratoma may rupture into adjacent structures and lead to lung lesions or pleuritis. The main rarity of our reported cases was the dynamic imaging findings very similar to the developmental process of tuberculosis in patients 1 and 2, the pachypleuritis in patients 2 and 3, the extremely elevated inflammatory markers very similar to empyema in patient 3, and the extremely atypical tumor shape in all patients. Case presentation We present three pediatric patients presenting predominantly with recurrent hemoptysis and/or chest pain who were ultimately diagnosed with mediastinal teratoma containing pancreatic tissue. All three patients were initially suspected to have tuberculosis or empyema, and underwent relevant treatment, but without improvement. Patient 1 had left hilar enlargement, and subsequently an enlarging calcified cavity within high-density consolidation was identified. Patient 2 initially presented with right-sided pulmonary consolidation and pleuritis, and subsequently developed right lower lobe calcification, pleural thickening, and irregular soft tissue in the right inferior mediastinum. Patient 3 was initially found to have right lobe consolidation accompanied by a massive right-sided pleural effusion with extremely elevated inflammatory markers in serum and pleural effusion. The effusion later acquired heterogeneous density and appeared to become encapsulated. In patients 2 and 3, pleural biopsy identified fibrous tissue (with and without granuloma). Thoracotomy/thoracoscopy revealed mediastinal teratoma in each case, all of which were completely excised and the patients made uneventful recoveries. Histopathologic analysis revealed mature cystic-solid teratoma containing pancreatic tissue in all patients, and calcification in patients 1 and 2. Conclusions Clinicians should be mindful that mediastinal teratoma is a potential cause of hemoptysis, lung lesions and pleuritis. Calcification and pachypleuritis on chest imaging especially in patients without fever should be highly suspected of mediastinal teratoma. Pleural biopsy sometimes fails to assist in making a definitive diagnosis.

Hereditary hemorrhagic telangiectasia (HHT) can be clinically diagnosed, but children often lack characteristic features. We report a family with homozygous growth differentiation factor 2 (GDF2)–related HHT diagnosed by genetic testing. A boy aged 5 years and 2 months presented with isolated hypoxemia. He was the product of a consanguineous marriage; his parents were second cousins. Physical examination revealed cyanosis of nail beds and clubbed fingers. Pulse oxygen saturation was 84% to 89%. Lung function, contrast-enhanced lung computed tomography, and noncontrast echocardiography were normal. A pulmonary perfusion scan revealed radioactivity in the brain and bilateral kidney, suggesting the existence of a intrapulmonary shunt. Whole-exome sequencing revealed a homozygous variant [c.1060_1062delinsAG (p.Tyr354ArgfsTer15)] in GDF2, which was found to be inherited from his heterozygous parents. At the age of 8 years, he developed epistaxis, and an angiogram revealed diffuse pulmonary arteriovenous malformations. At the age of 9 years, he was treated with sirolimus, and his condition improved significantly. However, his now 7-year-old sister with the same homozygous variant currently has no symptoms. Physical examinations revealed 1 pinpoint-sized telangiectasia on the chest of his mother and a vascular lesion on the forehead of his sister. Additionally, the patient’s father and great-uncle had a history of mild to moderate epistaxis. Mutation in GDF2 is a rare cause of HHT. Ours is the first report of homozygous GDF2-related HHT; in addition, this variant has not been reported previously. In our report, we also confirm variable expressivity, even with the same pathogenic variant in GDF2-related HHT.

As the drilling sections become deeper and longer, transferring more weight downhole to improve ROP is the primary concern to the operator. Drillstring buckling is a primary concern when using very aggressive drilling parameters. Buckling is a phenomenon where the drillstring suddenly loses stability as axial compression exceeds a certain threshold. The drillstring first buckles sinusoidally inside the wellbore which is then followed by helical buckling. Buckling leads to accelerated joint wear, tool fatigue failures, and lower drilling efficiency. To better manage the buckling risk, this paper proposes a method of simulating drillstring buckling inception and post-buckling state using an advanced transient dynamics model. A buckling and post-buckling analysis methodology was developed based on the finite element transient dynamics model. The model captures the enriched physics involved in the buckling phenomenon: the large deformation of buckled drillstring, the strong non-linearity of contact and friction forces, and the dynamically triggered buckling due to drilling rotation. Transient dynamics simulations are conducted for drillstring with the actual well trajectory and rotation speed. Weight on bit (WOB) is ramped up gradually, and the drillstring deformation is monitored to detect the onset of buckling. The post-buckling state is examined to evaluate drilling efficiency and string reliability. To conduct the model validation, an extended reach drilling (ERD) job was analyzed by the model. A measurement while drilling (MWD) tool was deployed in BHA to measure the downhole weight and torque. The simulation implies the helical buckling occurs in drill-pipe and captures the drilling weight and torque loss due to buckled string. Most existing buckling theories use the analytical equations of critical buckling load, which were normally derived based on the idealized assumptions, such as perfect wellbore shape and uniform tubular geometry, but neglect friction and string rotation. The proposed method simulates the drillstring buckling in the actual field drilling conditions. It gives more realistic predictions of buckling inception load and post-buckling configuration. The transient dynamics model is capable of simulating drillstring whirl and weight lockup under the severe helical buckling. Based on the simulated the post buckling configuration of the string, an automatic interpretation method was proposed to detect the buckling mode and location along the drillstring. Using the transient dynamics model, the simulation procedure presented in this paper can significantly improve drillstring buckling and post-buckling predictions and help mitigate buckling risk in well planning and execution phases.

In recent years, the phenomenon of drill string torsional oscillation at frequencies over 50 Hz has been well documented. This high frequency torsional oscillation (HFTO) creates cyclic fatigue loading on bits and drilling tools within the bottom hole assembly (BHA) and thus limits tool life and drilling performance. However, few models exist which can predict occurrence of HFTO and its severity. To our knowledge; none of these models consider the entire drilling system including the bit-rock interaction, downhole drive(s), BHA design, and surface drilling parameters, and hence there is a need to develop a system model for HFTO mitigation. A 3D transient drilling dynamics model has been extended to study the severity of HFTO and cyclical loading to drilling tools. The accuracy of the model was validated by theoretical calculation, and high frequency downhole data. An example analysis was conducted to evaluate drilling system design performance in terms of HFTO risks. Good correlation was found between the analysis and field data collected from the Permian Basin. Advanced models were developed for mud motors and rotary steerable system (RSS) tools. After conducting a full drilling simulation, the drilling system behavior under HFTO can be fully described. Cyclical torque loading of differing magnitudes and frequencies were observed for different BHA components depending on HFTO vibration mode, HFTO severity and BHA design. PDC cutters were subjected to different cyclical loading depending on bit design, formation and HFTO conditions. The mud motor power section was found to undergo high frequency cyclical loading which could accelerate its rubber degradation. Since the failure of PDC cutters and the degradation of mud motor power sections have a critical effect on drilling performance, the importance of mitigating HFTO cannot be underestimated. By evaluating the loading conditions, an optimized drilling system can be selected. Field data has proved the validity of this approach. The methodology presented in this paper offers a new way for the industry to systematically mitigate HFTO by considering the rock drilled, bit design, mud motor utilized, the mechanics of RSS and other tools in the BHA, as well as drilling parameters. The usage of this approach can reduce premature drilling component failure and improve drilling performance, especially in the high energy drilling applications found in North America Land and other areas.

A common issue encountered when drilling in the Permian Basin involves the twist-off of a bottomhole assembly (BHA) component. A twist-off incident can result in significant costs incurred due to nonproductive time (NPT) as well as lost-in-hole (LIH) charges if retrieval of the fish is unsuccessful. The paper will present several case studies to illustrate the primary cause of the failures. An innovative thread connection for BHA components was designed in 2016 to reduce risk of twist-off. The paper will demonstrate its effect on reducing twist-off risk as well as the enablement of improved drilling performance in 2019. The paper will illustrate statistical analysis of data gathered from 2016 through 2019 comparing the performance of the conventional thread connection versus the new thread design. The goal of the analysis is to evaluate whether the thread design is effective in reducing the frequency of twist-off incidents. The bending moment of each connection within the BHA will be analyzed using modeling software to understand the stress-loading profile. Memory data from the rotary steerable system (RSS), including near-bit attitude measurements and downhole drilling dynamics, will be analyzed in conjunction with data acquired from the rig's surface sensors to identify if any abnormal drilling events are observed prior to the twist off. The BHA bending moment study concludes that connections between the measurements-while-drilling (MWD) tool and the RSS suffer higher stress loading compared to other connections in the BHA. Empirically, field statistics confirm that the connections between RSS and MWD exhibit the highest frequency of twist-off incidents. However, further analysis is required to understand the root cause of the connection failure. The memory data retrieved from the RSS enables the visualization of hole curvature and vibration at the time of the incident. Investigation into several field cases concluded that, immediately prior to connection twist off, there is sudden change in borehole curvature and/or emergence of shock and vibration (S&V) which can dramatically reduce the expected fatigue life of the connection. Based on the statistical analysis, it can be concluded that the new connection design is effective in reducing the twist-off failure rate of the BHA. Consequently, the implementation of the new thread design enabled a step-change in drilling performance through use of a more powerful positive displacement motor (PDM) to drive the RSS system.

This paper investigates a type of platform retailing, where the retailer builds up large facilities, inside which a supplier (manufacturer) rents a mini-store and sells goods directly. The retailer demands a slotting allowance and a portion of the sales revenue from the supplier; however, this fee structure may cause a channel conflict and supplier exclusion. To understand these phenomena, we build a two-supplier–one-retailer Stackelberg model with the retailer acting as the leader and the suppliers acting as the followers. We solve the model analytically and numerically, assuming competitive and non-competitive suppliers, identical and nonidentical slotting allowance, and possibly different revenue-sharing rates for the two suppliers. It is found that supplier exclusion may happen if the slotting allowance is identical across the suppliers, whereby the market size difference and product substitution are the underlying driving forces. We also provide rationales for the existence of a slotting fee.

Background Bronchopulmonary disease caused by flagellated protozoa infection (BPFP) is thought to be rare in children but may be an emerging or underestimated disease, especially in developing countries. Methods In this study, we retrospectively reviewed records of 15 patients who were presented with a cough, wheezing or bronchopulmonary disease of unknown causes during admission, and patients who were finally diagnosed with BPFP from January 2014 to January 2015 were enrolled. Protozoa were observed in bronchoalveolar lavage fluid by light microscopy. Results A total of 15 pediatric cases (11 male and 4 female individuals, from 1 year 8 months to 12 years 1 month of age) with flagellated protozoa infection diagnosed by light microscopy were recruited. The course of the disease at the time of diagnosis was from 10 days to 11 months. Patients presented with a fever (N = 9), cough (N = 11), wheezing (N = 5) and chest pain (N = 5). Laboratory data showed elevated peripheral blood leucocytes (N = 6), eosinophilic granulocytes (N = 3), C-reactive protein (N = 5) and immunoglobulin E (N = 3). Bronchoscopy revealed a mucus plug (N = 3) and bronchiectasis (N = 1). Lung computed tomography results indicated ground-glass opacification (N = 2), atelectasis (N = 3), bronchiectasis (N = 1), bronchial wall thickening (N = 3) or nodular opacity (N = 6, including 1 case of pulmonary embolism). All children responded to metronidazole for a 2- to 5-week treatment period. Conclusions Patients with BPFP often have a chronic or recurrent course and present with recurrent fever, cough, wheezing and chest pain. Chest imaging may reveal ground-glass opacification, atelectasis, bronchiectasis or nodular opacity (including pulmonary embolism). BPFP responds favorably to metronidazole treatment.

Directional drilling enables reaching farther and more difficult targets and improves well production through increased reservoir contact. Drilling and steering a well with a 3D trajectory path has become very common to achieve multiple objectives such as surface versus target location, well anti-collision on a crowded platform, completion and artificial lift needs, landing the reservoir section in a favorable direction, and maximizing the length of the lateral for optimum production. Those objectives will be a challenge for the bottomhole assembly (BHA) design, including the bit and steering tool selection. The planned BHA must be able to drill the actual wellbore as per the planned trajectory path. It is important to avoid the failure that result from an inability to follow the planned trajectory because it will cause the nonproductive time to change the BHA; introduce additional tortuosity in the well, which can cause other problems; and risk not reaching the target hence requiring a sidetrack and redrilling. Therefore, BHA design and modeling the directional tendency capability become an important aspect in the planning phase. Advances in digital technology and modeling allow us to provide a better tool to design the BHA. Many tendency modeling applications today still use the three-point contact theory. In actual conditions, well propagation is a complex transient process, affected by the bit, BHA, formation drilled, and drilling parameters used, and therefore three-point contact theory does not always give satisfactory prediction due to oversimplification. A new directional tendency prediction workflow was developed based on the finite element method. Finite element modeling allows us to calculate BHA deformation and forces. During drilling, the BHA is subjected to axial loading, torsional loading, wellbore contact force, gravity force, etc. All these forces will affect the BHA tendency. Simulating this in drill-ahead/propagation mode will give us a better prediction of BHA tendency and capture the transient well propagation behavior. This new method has been implemented as an automatic analysis agent in a drilling engineering software platform where every time the BHA design is created or changed, the tendency is automatically calculated, and the results are displayed as traffic lights based on comparison with the planned trajectory. The modeling relies on detailed models of various downhole equipment including steering tools and bit cutting interaction with the rock. The modeling results were validated with extensive field data and there was a good match between prediction and the actual results. The computation was optimized by smart selection of well sections to conduct tendency analysis to evaluate if the BHA can deliver the designed trajectory with good confidence. Computation performance becomes important because the analysis workflow is implemented in an automated planning system where any change of the BHA or other well design aspects will trigger the calculation automatically. This new modeling provides a better tendency prediction which is critical to the well success.

Mechanical specific energy (MSE) has been widely used in the industry to monitor drilling efficiency. However, it does not give detailed information about energy flow in the drilling system and lacks the resolution to identify the root cause of energy loss. The drilling operation is a dynamic process. Energy input may be from a surface-drive system (top drive or rotary table) or a mud motor placed downhole. In a perfect world, all of the energy is used to drill the rock. However, some of the input energy may reside in the drillstring as strain and kinetic energy due to the deformation and motion of the drillstring. Drilling energy is dissipated due to shock, vibration, fluid damping, and frictional contact between the drillstring and wellbore. A novel method has been developed to calculate the drilling energy flow in the drillstring and to enable better drilling energy management by maximizing useful energy consumption and reducing energy waste. The method provides a new way to understand and improve drilling efficiency. The method is based on an advanced transient drilling dynamics model which simulates the full drilling system from surface to bit. The entire drillstring is meshed using 3D beam elements, and its dynamic response history is solved by the finite element method (FEM). The energy input can be calculated from surface drilling parameters, such as torque, rotation speed, flow rate, and motor differential pressure. With the simulated history of forces and dynamics of the drillstring, the corresponding strain energy and kinetic energy of the drillstring can be evaluated. The detailed cutting structure model can provide insight on the energy amount consumed by the rock cutting action of the bit and reamer. Putting all the components together leads to a holistic calculation workflow of drilling energy. Field case studies were conducted to examine the effectiveness of this method. The studies showed the drillstring strain energy and kinetic energy are good performance indicators for drillstring reliability and stability because these energy variables reflect the severity of loading and vibration in the drillstring. The energy variables possess clear signatures for interpretation of different downhole vibration modes. Currently, the drilling efficiency is normally evaluated by MSE, which represents the amount of energy needed to remove a unit volume of rock using the surface drilling data. In this study, the energy loss is calculated to understand the percentage of input energy dissipated due to the interaction of the drillstring with the environment. In contrast to MSE, the calculation provides a more direct and detailed measurement of drilling efficiency. It gives a methodology for understanding detailed energy flow in the drilling system under different drilling vibration modes. It can be applied to bit selection, bottomhole assembly (BHA) design, and drilling parameter optimization to achieve better drilling energy management and improve drilling efficiency. The novel approach calculates drilling energy based on the transient dynamics simulation of the full drilling system. It provides a detailed and holistic view of drilling energy input, propagation, and consumption. This method could help identify the inefficient drilling conditions and optimize drilling operation through evaluating and comparing different options.

Severe drilling dynamics of a bottomhole assembly (BHA) causes energy to dissipate into vibrations which undermines drilling efficiency. Dangerous dynamics modes, such as backward whirling and high frequency torsional oscillation, could cause downhole drilling tools to fail prematurely. To mitigate the risk of failure due to these dangerous conditions, it is critical to identify the damaging dynamics modes by interpreting the drilling data. Based on a deep learning approach, a novel method was proposed to automatically identify severe drilling dynamics modes directly from the time-series data. The drilling dynamics data can be obtained from either a downhole sensor measurement or transient dynamics simulation. First, a deep neural network, which is composed of convolutional and fully connected layers, is employed to explore patterns in the data by generating a feature map of drilling dynamics. Knowledge of drilling dynamics physics can be used to facilitate data clustering in the feature map. Each data cluster can be tagged with the corresponding drilling dynamics mode. Using the tagged dataset, a machine learning classification model can be trained to automatically identify the dynamics modes based on the input of time-series drilling data. The deep learning approach can be implemented to recognize a collection of dynamics modes of BHA, such as various whirling patterns and high frequency torsional resonance. The most commonly available drilling dynamics data channels, accelerations and collar RPM, were used as the model inputs. The deep neural network was trained to predict the next data sample based on the previous time-series data. One of the hidden layers of the neural network was employed to generate the feature map, in which the dataset forms several clusters. The orbits of BHA movement were plotted on top of the clusters for pattern visualization. After this practice, the simple polygon boundary was drawn between whirling and stable cases, and the dataset was tagged automatically. With the tagged dataset, the classification model was trained to identify various whirling patterns and the stable drilling state. Similar processes can be readily applied to interpret other dynamics modes. Interpreting the drilling dynamics modes provided a high-level description of the data, which offered clues on how to optimize BHA design and drilling practices to improve efficiency. The automatic interpretation of drilling dynamics data can significantly improve the consistency and efficiency of the existing manual interpretation workflow. The generated feature map enables the exploration of new motion patterns and new vibration modes. This approach eliminates the need to manually tag the data. With minimum human interactions, the dataset can be automatically tagged. The model employs only the raw time series data of basic dynamics channels as inputs, which makes the algorithm universally applicable for various data sources.

The drilling process can be broken down into various activities from top-level activities (e.g., drilling and tripping) to lower-level activities (e.g., in-slip, out-of-slip, making connection, and circulation). The detection of the fundamental drilling unit, a stand, is necessary and essential for recognizing and inferring drilling activities. A new method is proposed to detect slip status, pipe change, and drilling/tripping stands based on real-time streaming data. The slip status is a critical element because it indicates a connection is made before drilling or tripping a stand. The proposed method is designed to infer the slip status with hookload, standpipe pressure (SPPA), and surface torque (STOR) sensor data. Specifically, the logic using hookload includes two criteria, a hookload standard deviation criterion and a dynamic hookload threshold criterion. This allows addressing the limitations of prior methods at shallow depth and using a manual threshold, which prevents the full automation of slip detection. In addition, the slip status can be confirmed or corrected with a logic using a combination of SPPA and STOR data. Then, a check is performed on whether a stand is added or removed during in-slip period. If needed, the stand detection can also be run to detect where a stand begins and ends. The method has been extensively tested and validated on many land and deepwater wells with drilling/tripping operations. Without human intervention, the dynamic hookload threshold can be determined automatically and adaptively after one or two drilling or tripping stands. Moreover, the hookload standard deviation criterion works well to detect the change of slip status at shallow depth. It is shown that high accuracy of detection can be achieved when the streaming data have a proper range of sampling rate. The new method addresses two limitations of the existing methods: (1) it automatically determines the dynamic hookload thresholds and eliminates the need of setting up the hookload threshold manually, and (2) it improves the accuracy of slip status and stand detection at shallow depth. This innovative work enables the automation of the slip status and stand detection process in batch runs or in real time without operator input.

A drill bit is subjected to rotational speed variation during drilling, ranging from minor rotational speed oscillations to severe speed variation, including stuck phase. The severe speed variation, referred to as stick-slip, is known to be a major source of problems, such as fatigue failures, bit wear, and poor drilling rates. This paper will provide new insight into the mechanisms that drive severe stick-slip based on continuous high-frequency downhole measurements and 3D transient dynamic drilling simulation. To understand the mechanism of severe stick-slip, a series of drilling tests were conducted at a full-scale drilling test facility. An advanced downhole measurement tool was placed in the bottom hole assembly (BHA) to record three-axis shock and vibration, RPM, bending moment, downhole weight on bit (DWOB), downhole torque (DTOR) and internal and annular pressure at high frequency. The drilling system was then modeled on a 3D transient drilling simulation platform, including detailed bit-rock interaction based on single-cutter tests, the exact BHA, and the wellbore geometry. The downhole recorded data showed clear coupling of severe stick-slip, axial load, and bending moment conditions. Interesting patterns observed between RPM, DWOB, DTOR, and bending moment will be presented in detail. The recorded severe stick-slip condition was successfully reproduced by 3D transient dynamic simulation, and the torque, axial load, and bending moment variations along the BHA revealed coupling between torsional, axial, and lateral motions of the drilling system from simulation. Bit-rock interaction and drillstring-wellbore contact are the drivers supporting the coupling. It was found that the coupling of three motions of the drilling system is the most reasonable explanation to the self-sustained severe stick-slip condition. This mechanism can explain the field observed stick-slip trend (i.e., the higher WOB and lower RPM tend to increase the risk of severe stick-slip tendency). Downhole measurements and transient 3D dynamic simulation of the entire drilling system are essential to fully understand this mechanism. Understanding the stick-slip process opens additional opportunities for controlling severe stick-slip. Because the stick-slip mechanism is driven by the coupling of three motions, it is possible to mitigate this condition by breaking the coupling mechanism. For example, a shock sub possibly will reduce the severity of axial coupling due to added axial compliance. Simulation shows breaking the mechanism could reduce the severity of stick-slip. The study being reported in this paper also proved the validity of applying advanced 3D transient dynamic model to obtain a better understanding of drilling system behavior. Drilling simulation might well be an effective way to plan a drilling system and drilling parameters.