bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the Influence of Sand Erosion Process on the Wear and Damage of Heat-Treated U75V Rail Steel
Authors: Shu Kang , Wang Wen-Jian , Meli Enrico , Ding Hao-Hao , Han Zhen-Yu , Zou Ming , Liu Qi-Yue
Published: November 2020

Usually, rail materials are exactly affected by the erosion of windblown sand in the desert environment. For this reason, the influence of impact angle, particle velocity, and particle size on the erosion wear behavior of the U75V heat-treated rail steel, a material frequently employed in Chinese railways, were studied in this work. The results showed that, with increasing impact angle, the erosion rate increased between 15 deg and 45 deg, decreased between 45 deg and 75 deg, and then increased again between 75 deg and 90 deg. The highest erosion rate occurred at about 45 deg. When the particle velocity increased, the erosion rate increased approximately in a quadratic way. As the sand particle size increased, the erosion rate presented a decreasing trend. During the initial stage of erosion, shear craters, indentation craters, and ploughing craters were the main surface damage features. The shear craters predominated at the impact angle of 45 deg whereas the indentation craters predominated at 90 deg. During the steady-state of erosion, the rail damage was mainly composed of craters, platelets, and cracks. Both the length and depth of craters increased almost linearly with increasing particle velocity, whereas the increased rate of length was significantly higher than that of depth. The length and depth of craters increased with increasing particle size at 90 deg, whereas only the length increased with increasing particle size at 45 deg. The microstructure evolution and the formation mechanism of platelet at low impact angles were different from those at high impact angles. Platelet formation was the main erosion wear mechanism.
Provision of Industrial Information Resources Through Hypermedia
Authors: Crowder Richard M. , Wills Gary , Hall Wendy
Published: November 2020

As information relating to manufacturing becomes more complex, it is inevitable that information overload will occur. When the information cannot be retrieved with ease, it is human nature to work without it.

This paper discusses the use of an open hypermedia system, to resolve this problem. To be viable the hypermedia resource base must operate factory wide, and not centered on a single piece of plant. However the scale of the problem introduces a wide range of problems. We present a number of methodologies that need to be implemented to ensure that the introduction of hypermedia on the factory floor is successful. By considering two industrial applications, it is shown that in all cases information is retrieved faster and to a higher quality than current practice.
Fast and Smooth NC Milling Animation Using Partial Redrawing Technique
Authors: Inui Masatomo , Takano Makoto
Published: November 2020

Animation display of the NC milling process is helpful for detecting potential problems of a cutter path prior to actual machining. In the milling animation, machined shape of the workpiece is repeatedly computed and displayed after every short motion of the cutter. A single cutter motion usually removes very small portion of the workpiece, therefore most part of two successive pictures in the animation becomes the same. Based on this characteristic of the pictures, the authors develop “partial redrawing technique” for fast and smooth animation of the NC milling process. This method efficiently generates a new picture of the workpiece by properly modifying a limited part of the latest picture in the screen. The picture area to modify is determined based on the removed shape of the workpiece. An experimental system is implemented and some animations of complex milling processes are demonstrated.
Fuzzy Cell Mapping Applied to Autonomous Systems
Authors: Song Y. , Edwards D. , Manoranjan V. S.
Published: November 2020

Nonlinear systems appear in many scientific disciplines such as engineering, physics, chemistry, biology, economics, and demography. Therefore methods of analysis of nonlinear systems, which can provide a good understanding of their behavior have wide applications. Although there are several analytical methods (See Hsu [3] and references therein), determining the global behavior of strongly nonlinear systems is still a substantially difficult task. The direct approach of numerical integration is a viable method. However, such an approach is sometimes prohibitively time consuming even with the powerful present-day computers.
Particle Tracking in Combustion Chamber of Solid Rocket Motor
Authors: Xiao Yumin , Amano R. S. , Cai Timin , Li Jiang , He Guoqiang
Published: November 2020

It has been a challenge to investigate how to trace particles in a solid rocket motor (SRM) using aluminized composite solid propellant and submerged nozzle. In using CFD simulations, the boundary conditions for the ejecting particles constrain their trajectories, hence these affect the two-phase flow calculations, and thus significantly affect the evaluation of the slag accumulation. The RTR (X-ray Real-time Radiography) technique is a new method to detect the particles in a firing SRM. A method was developed to simulate the particle ejection from the propellant surface. The moving trajectories of metal particles in a firing combustion chamber were measured by using the RTR high-speed motion analyzer. Numerical simulations with different propellant-surface boundary conditions were performed to calculate particle trajectories. Through this study an appropriate surface velocity condition on the propellant surface was discovered. The method developed here can be used for the future CRM research.
Design Sensitivity Analysis for the Meshfree Shell Structure
Authors: Choi Kyung K. , Kim Nam H. , Botkin Mark E.
Published: November 2020

A unified design sensitivity analysis method for a meshfree shell structure with respect to sizing, shape, and configuration design variables is presented in this paper. A shear deformable shell formulation is characterized by a CAD connection, thickness degeneration, meshfree discretization, and nodal integration. The design variable is selected from the CAD parameters, and a consistent design velocity field is then computed by perturbing the surface geometric matrix. The material derivative concept is used to obtain a design sensitivity equation in the parametric domain. Numerical examples show the accuracy and efficiency of the proposed design sensitivity analysis method compared to the analytical solution and the finite difference solution.
Design on an International Project
Authors: Pfund Philip A.
Published: November 2020

Three US National Laboratories are cooperating on a project to design and provide hardware for a new particle accelerator in a European laboratory. This paper describes the efforts and tools that are being used to coordinate the design and to control the design requirements and configurations between Europe and the US laboratories. The uses of design reviews, technical specifications, and electronic communications are described.
The Multiple Contributions of Jorgen Lund’s Ph.D. Dissertation, “Self-Excited, Stationary Whirl Orbits of a Journal in Sleeve Bearings,” RPI, 1966, Engineering Mechanics
Authors: Childs Dara W.
Published: November 2020

Lund set out to define the circumstances under which stable limit-cycle orbits could exist for the linearly unstable motion of a rigid rotor. He also undertook to examine the nature of these stable limit cycles when they are demonstrated to exist. He obviously succeeded in meeting both these objectives; however, Lund’s really remarkable and most useful contributions are covered “incidentally” in the course of developing his nonlinear analytical/computational solutions.
Feedback Control of Truss Structures With Distributed Flexibility
Authors: Kevorkian Sandrine , Pascal Madeleine
Published: November 2020

Among other applications, truss structures are used for space applications and several strategies of active control are studied, including recently the use of piezoelectric actuators. However, the standard method for designing active control of structures is to use modal approximation for distributed flexibility. The actual system is infinite-dimensional and the modes describing its flexible behavior depend on the feedback control. Very few attempts to use the continuous elements method for purposes of control were proposed in the past and concern only manipulators composed of one or two flexible arms. In this work, a strategy of active control using the exact transfer matrix of a two-cells planar truss is defined. Both collocated and non collocated control are considered. For both cases, the closed-loop pole locations are compared as a function of feedback controller parameters.
On the Vibrations of a Linear, and a Weakly Nonlinear Damped System
Authors: Yò Darmawijo , van Horssen W. T.
Published: November 2020

In this paper initial-boundary value problems for a linear, and a weakly nonlinear string (or wave) equation are considered. One end of the string is assumed to be fixed and the other end of the string is attached to a spring-mass-dashpot system, where the damping generated by the dashpot is assumed to be small. This problem can be regarded as a simple model describing oscillations of flexible structures such as overhead power transmission lines. For a linear problem a semigroup approach will be used to show the well-posedness of the problem as well as the asymptotic validity of formal approximations of the solution on long time-scales. It is also shown hov a multiple time-scales perturbation method as described in Kevorkian and Cole (Kevorkian and Cole, 1981) can be used effectively to construct asymptotic approximations of the solution on long timescales.
Stochastically Perturbed Rotating Shafts
Authors: Vedula Lalit , Namachchivaya N. Sri
Published: November 2020

The objective of this work is to study the long term effects of small symmetry-breaking, dissipative and noisy perturbations on the dynamics of a rotating shaft. Hamilton’s principle is used to derive the equations of motion and a one mode Galerkin approximation is applied to obtain a two-degree-of-freedom (four dimensional) model. A stochastic averaging method is developed to reduce the dimension of this four dimensional system. Making use of the interaction between the gyroscopic and dissipative forces and the separation of time scales, the original system is reduced to a one dimensional Markov process. Depending on the system parameters, the reduced Markov process takes its values on a line or a graph. For the latter case, the glueing conditions required to complete the description of the problem in the reduced space are derived. This provides a qualitatively accurate and computationally feasible description of the system. Analytical results are obtained for the mean first passage time problem. The stationary probability density is obtained by solving the Fokker Planck Equation (FPE). Finally, the qualitative changes in the stationary density as a result of varying the system parameters are described.
Digital Signal Processor Based Active Vibration Control System Using Adaptive Control Algorithm and Smart Actuators/Sensors
Authors: Shashikala P. , Shankar V. , Nagaraja B. V. , Balasubramaniam R. , Harikrishnan J.
Published: November 2020

Adaptive feed forward control of structure based on ‘filtered -x’ LMS algorithm has been brought out for the active control of vibration in a typical CFRP beam structure. Initially the conventional filtered-x LMS control configuration and offline system identification method using DSP is discussed. Also the on-line system identification and control by additive random noise technique has been brought out. FIR filters are used for both system identification and control.

Recent advances in electronics, high-speed digital signal processors have made active systems realizable, effective and inexpensive. Hence the active control method has been used to investigate a typical composite CFRP beam structure bonded externally with PZT actuators/sensors. At present vibration reduction of the order of 3db has been achieved.
Analysis of Axial Vibration of Compound Bars by Several Different Methods
Authors: Bert Charles W. , Zeng Huan
Published: November 2020

Although solutions for the free vibration of dynamically slender prismatic or tapered bars in axial vibration are well known, apparently there have been only a few published analyses for the case of compound bars, i.e., bars of different cross section connected in mechanical series. The primary objective here is to analyze this problem by several exact methods: (1) classical solution of the set of governing differential equations, and (2) application of a relatively new technique originated in 1986 and known as the differential transformation (DT) method. The secondary objective is to present some simple approximate algebraic formulas for the fundamental frequency of an n-segment, axially vibrating bar for preliminary design use.
Magneto-Elastic Compliant Mechanisms
Authors: Venkataraghavan Janarthanan , Srinivasa Arun R.
Published: November 2020

The motivation for this work has been a variety of motions like navigation of pipelines, insertion operations in assembly, and gripping actions, which require the adaptation of the mechanism to the external constraints, rather than avoid them. To this effect, efforts have been made towards building mechanisms that obtain the required degrees of freedom through deformations rather than explicit joints in them. Although the use of many joints provides the required number of degrees of freedom, it does so at the cost of making the system very bulky and complex. With the advent of new polymers, the possibility of building such mechanisms without joints, that fulfil the requirements of adaptation, have increased. Based on this approach, a Magneto Active Polymer (MAP) material has been developed in-house at the Texas A&M University, in which the actuation is performed by the conversion of electromagnetic energy into mechanical energy. The initial experimentation has proved the vast potential of the use of such a material, and a few mechanisms, like a magneto active peristaltic pump, have already been developed and tested, using this material. In this mechanism the pumping action is obtained when a moving magnetic field produces peristaltic waves in the magneto active material shaped as a tube. These waves help in pushing the fluid forward, in the tube. The advantage of this mechanism is that there is not physical contact of the actuating mechanism an the MAP tube, thereby reducing the wear. In developing the design for the peristaltic pump and other conceptual models described in this paper, ideas have been drawn from the different modes of locomotion and actuators used, in lower organisms and these have been good sources of inspiration for the work detailed in this paper.
Comparative study on the molecular beam epitaxial growth and characterization of AlGaN nanowire structures on AlN buffer layer and on Si
Authors: Lu Jiaying , Zhong Yun , Zhao Songrui
Published: November 2020

AlGaN in the form of nanowires is an important platform for semiconductor ultraviolet light sources on Si. In the past, significant efforts have been devoted to improving the quality of AlGaN nanowires. In this context, we present a comparative study on the molecular beam epitaxial growth and characterization of AlGaN nanowire structures on the AlN buffer layer on Si and on Si directly. It is found that AlGaN nanowires grown on the AlN buffer layer shows an improved internal quantum efficiency, compared with the nanowires grown on Si directly. This improvement is attributed to the reduced nanowire coalescence due to the improved vertical alignment of the nanowires grown on the AlN buffer layer.
The Anthropometric, Physiological, and Strength-Related Determinants of Handcycling 15-km Time-Trial Performance
Authors: Nevin Jonpaul , Smith Paul M.
Published: November 2020

Purpose: The aim of this study was to investigate the relationship between selected anthropometric, physiological, and upper-body strength measures and 15-km handcycling time-trial (TT) performance. Methods: Thirteen trained H3/H4 male handcyclists performed a 15-km TT, graded exercise test, 15-second all-out sprint, and 1-repetition-maximum assessment of bench press and prone bench pull strength. Relationship between all variables was assessed using a Pearson correlation coefficient matrix with mean TT velocity representing the principal performance outcome. Results: Power at a fixed blood lactate concentration of 4 mmol·L−1 (r = .927; P < .01) showed an extremely large correlation with TT performance, whereas relative (peak oxygen uptake) (r = .879; P < .01), power-to-mass ratio (r = .879; P < .01), peak aerobic power (r = .851; P < .01), gross mechanical efficiency (r = 733; P < .01), relative prone bench pull strength (r = .770; P = .03) relative bench press strength (r = .703; P = .11), and maximum anaerobic power (r = .678; P = .15) all demonstrated a very large correlation with performance outcomes. Conclusion: Findings of this study indicate that power at a fixed blood lactate concentration of 4 mmol·L−1, relative , power-to-mass ratio, peak aerobic power, gross mechanical efficiency, relative upper-body strength, and maximum anaerobic power are all significant determinants of 15-km TT performance in H3/H4 handcyclists.
Blinding practices during acute point-of-care ultrasound research: the BLIND-US meta-research study
Authors: Prager Ross , Wu Kay , Bachar Roudi , Unni Rudy R , Bowdridge Joshua , McGrath Trevor A , Thavanathan Rajiv , Woo Michael Y , McInnes Matthew D F
Published: November 2020

Objectives

Point-of-care ultrasound (POCUS) diagnostic accuracy research has significant variation in blinding practices. This study characterises the blinding practices during acute POCUS research to determine whether research methodology adequately reflects POCUS use in routine clinical practice.

Design, settings and participants

A search for POCUS diagnostic accuracy studies published inEmergency Medicine,AnaesthesiaandCritical Carejournals from January 2016 to January 2020 was performed. Studies were included if they were primary diagnostic accuracy studies. The study year, journal impact factor, population, hospital area, body region, study design, blinding of the POCUS interpreter to clinical information, whether the person performing the POCUS scan was the same person interpreting the scan, and whether the study reported incremental diagnostic yield were extracted in duplicate by two authors. Descriptive statistics were provided and prespecified subgroup analysis was performed.

Main outcome measures

The primary outcome was the number of studies that blinded the POCUS interpreter to at least some part of the clinical information. Secondary outcomes included whether the person performing the POCUS scan was the same person interpreting it and whether the study reported incremental diagnostic yield.

Results

520 abstracts were screened with 97 studies included. The POCUS interpreter was blinded to clinical information in 37 studies (38.1%), not blinded in 34 studies (35.1%) and not reported in 26 studies (26.8%). The POCUS interpreter was the same person obtaining the images in 72 studies (74.2%), different in 14 studies (14.4%) and not reported in 11 studies (11.3%). Only four studies (4.1%) reported incremental diagnostic yield for POCUS. Inter-rater reliability was moderate (k=0.64). Subgroup analysis based on impact factor, body region, hospital area, patient population and study design did not show significant differences after completing pairwise comparisons.

Conclusions

Although blinding the POCUS interpreter to clinical information may be done in a perceived attempt to limit bias, this may result in accuracy estimates that do not reflect routine clinical practice. Similarly, having a different clinician perform and interpret the POCUS scan significantly limits generalisability to practice as it does not truly reflect ‘point-of-care’ ultrasound at all. Reporting incremental diagnostic yield from implementing POCUS into a diagnostic pathway better reflects the value of POCUS; however, this methodology was infrequently used.

Trial registration number

The study protocol was registered on Open Science Framework (https://osf.io/h5fe7/).
High incidence of glucocorticoid-induced hyperglycaemia in inflammatory bowel disease: metabolic and clinical predictors identified by machine learning
Authors: McDonnell Martin , Harris Richard J , Borca Florina , Mills Tilly , Downey Louise , Dharmasiri Suranga , Patel Mayank , Zare Benjamin , Stammers Matt , Smith Trevor R , Felwick Richard , Cummings J R Fraser , Phan Hang T T , Gwiggner Markus
Published: November 2020

Background

Glucocorticosteroids (GC) are long-established, widely used agents for induction of remission in inflammatory bowel disease (IBD). Hyperglycaemia is a known complication of GC treatment with implications for morbidity and mortality. Published data on prevalence and risk factors for GC-induced hyperglycaemia in the IBD population are limited. We prospectively characterise this complication in our cohort, employing machine-learning methods to identify key predictors of risk.

Methods

We conducted a prospective observational study of IBD patients receiving intravenous hydrocortisone (IVH). Electronically triggered three times daily capillary blood glucose (CBG) monitoring was recorded alongside diabetes mellitus (DM) history, IBD biomarkers, nutritional and IBD clinical activity scores. Hyperglycaemia was defined as CBG ≥11.1 mmol/L and undiagnosed DM as glycated haemoglobin ≥48 mmol/mol. Random forest (RF) regression models were used to extract predictor-patterns present within the dataset.

Results

94 consecutive IBD patients treated with IVH were included. 60% (56/94) of the cohort recorded an episode of hyperglycaemia, including 57% (50/88) of those with no history of DM, of which 19% (17/88) and 5% (4/88) recorded a CBG ≥14 mmol/L and ≥20 mmol/L, respectively. The RF models identified increased C-reactive protein (CRP) followed by a longer IBD duration as leading risk predictors for significant hyperglycaemia.

Conclusion

Hyperglycaemia is common in IBD patients treated with intravenous GC. Therefore, CBG monitoring should be included in routine clinical practice. Machine learning methods can identify key risk factors for clinical complications. Steroid-sparing treatment strategies may be considered for those IBD patients with higher admission CRP and greater disease duration, who appear to be at the greatest risk of hyperglycaemia.
Cohort profile: The Forzani & MacPhail Colon Cancer Screening Centre biorepository, Calgary, Alberta
Authors: Hilsden Robert J , Heitman Steven J , Lamidi Mubasiru , Diallo Mamadou Dian , English Janine , Town Susanna , Cartwright Shane , Maxwell Courtney , McGillivray Mary-Elizabeth , McGregor Elizabeth , Barberio Amanda , Pader Joy , Brenner Darren , Rabeneck Linda
Published: November 2020

Purpose

The Colon Cancer Screening Centre (CCSC) biorepository (Calgary, Canada) supports a wide range of research topics related to colorectal cancer (CRC) by collecting, and storing biospecimens (blood, urine, normal colon tissue) from consenting patient participants. Housing unique biospecimens along with detailed participant lifestyle and health history questionnaire data, the CCSC biorepository can support a variety of research related to CRC risk factors, biomarkers, genetic causes and more.

Participants

Currently, 2292 average risk CRC patients have consented to participate in the CCSC cohort and have provided stored biospecimens. The collected samples and data provide important high-quality materials for research, discovery and evaluation related to CRC screening and carcinogenesis and is available for access by outside researchers. In addition to biological samples, the CCSC collects detailed patient information on their lifestyle, physical activity and dietary patterns through questionnaires at the time of their enrolment.

Findings to date

The majority of participants (75%) are between 50 and 64 years of age. Women make up 46% (1055) of the cohort. Additional characteristics of the cohort included 44% reporting a body mass index of 25–30 kg/m2 (overweight), 53% having never smoked tobacco and 13% having a family member with CRC.

Future plans

The CCSC cohort plans to include the recruitment of high risk CRC cohorts. High-risk participants would comprise patients with a positive faecal immunochemical test and family history of CRC.
Development and validity testing of the Adolescent Health Literacy Questionnaire (AHLQ): Protocol for a mixed methods study within the Irish school setting
Authors: Spillane Ailbhe , Belton Sarahjane , McDermott Clare , Issartel Johann , Osborne Richard H , Elmer Shandell , Murrin Celine
Published: November 2020

Introduction

Health literacy research has focused predominantly on the adult population, and much less is understood about this concept from an adolescent perspective. The tools currently available to measure adolescent health literacy have been adapted from adult versions. This limits their applicability to young people because of the developmental characteristics that impact on adolescents’ behaviour, including impulse control and judgement skills. This protocol describes the intended development and validity testing of a questionnaire to measure health literacy in adolescents.

Methods and analysis

This protocol describes this mixed methods study that has three phases: the first phase will involve grounded research with adolescents using qualitative group interviews, co-design and concept mapping workshops to understand what health and healthy behaviours mean to adolescents and to explore their health literacy needs and the potential domains for the questionnaire. The draft health literacy domains identified will be presented to the youth advisory panel, and the questionnaire will be altered based on their feedback. Cognitive pretesting of the questionnaire items will also be conducted. Phase 2 will involve piloting the questionnaire to a two-stage random sample of young people in five urban and rural schools in Ireland. Test–retest reliability will be conducted using Pearson correlation coefficient. Confirmatory factor analysis will also be conducted to analyse the psychometric properties of the questionnaire. Phase 3 will involve the questionnaire being rolled out to a nationally representative sample of adolescents (n=6052) in Ireland to assess their levels of health literacy.

Ethics and dissemination

Ethical approval to conduct this study has been granted from the University College Dublin Human Research Ethics Committee – Sciences (LS-20–08). Informed assent from adolescents and informed consent from parents/guardians will be sought. The findings of this research will be disseminated at national and international conferences, as well as through publication in peer-reviewed journals.
Factors associated with attitudes towards HIV cure research among transgender women and travestis: a cross-sectional survey in São Paulo, Brazil
Authors: Wozniak Robert J , Cerqueira Natalia B , Dantas Maria Candida S , Mahafe Bianca , Barros Daniel A C , Alves de Medeiros Edmilson , Soares de Oliveira Ana Carolina , Sabino Thiago , Roggenbuck Albert , Avelino-Silva Vivian Iida , Johnston Carrie D , Marston Jez L , Bidegain Sebastian C , Magnus Manya , Kallas Esper G , Nixon Douglas F , Donini Camila S
Published: November 2020

Objective

Characterising the perceptions of groups most affected by HIV is fundamental in establishing guidelines for biomedical advancement. Although Brazil has successfully fought HIV/AIDS through several measures, transgender women still have a likelihood of HIV infection 55 times higher than the general population. This study aimed to better understand the perception and awareness of HIV cure research among the trans-identifying population in São Paulo, Brazil, and to determine factors that motivate or discourage participation in HIV cure studies.

Setting

This cross-sectional study analysed data collected from a questionnaire administered to 118 transgender women and travestis at 5 sites within the city of São Paulo. It uses quantitative methodology to describe the perspectives of transgender and travesti people in relation to HIV cure research and the context in which such perspectives are produced.

Results

Of 118 participants, most participants (73%) had some knowledge of HIV cure research and were most willing to participate in online surveys (52%), interviews (52%), focus groups (52%) and studies involving blood draws (57%). Those with a higher education or employment status were more likely to agree that someone had been cured of HIV, people living with HIV are discriminated against, and more information about HIV cure research is needed before the community embraces it. Only 55% of participants completely trusted their physician. The biggest motivational factors included gaining additional knowledge about HIV infection (77%) and the potential for a longer, healthier life for all (73%).

Conclusions

As a primary analysis of HIV cure attitudes among the transgender and travesti population as well as the social context in which they are formed, this study identifies opportunities to strengthen the dialogue and develop more educational collaborations between scientific investigators, community educators and the trans-identifying population to ensure that HIV cure research is inclusive of diverse perspectives.
Fidelity of human ovarian cancer patient-derived xenografts in a partially humanized mouse model for preclinical testing of immunotherapies
Authors: Odunsi Adekunle , McGray A J Robert , Miliotto Anthony , Zhang Yali , Wang Jianming , Abiola Adebukola , Eppolito Cheryl , Huang Ruea-Yea
Published: November 2020

Background

Immune checkpoint blockers (ICBs) have been approved by the Food and Drug Administration to be used alone in front-line therapies or in combination with other regimens for certain advanced cancers. Since ICB only works in a subset of patients and has limited efficacy in treating ovarian cancer (OVC), developing preclinical models that help to understand which patients may derive benefit from ICB would be of tremendous benefit in OVC.

Methods

Here, we generated preclinical human OVC models from freshly resected tumors, which include six patient-derived xenografts (PDXs) from six different patient tumors, three transplantable OVC PD spheroid lines (PD-sphs), and 3 cell lines (PD-CLs). We tested the therapeutic combination of anti-PD1/CTLA4 antibodies with (1) autologous tumor-associated leukocytes (TALs) on the growth of PD-sphs in a coculture system in vitro, (2) with adoptively transferred autologous peripheral blood mononuclear cells or TALs in patient-derived OVC models using partially humanized mice, NSG-HHDxSGM3 (N-HSGM3).

Results

We show that PD-1 and CTLA-4 dual blockade when combined with autologous TALs effectively reduced PD-sph number in a co-culture system and led to regression of established PD-CLs and PDXs in the N-HSGM3 mice. Combinatorial PD-1 and CTLA-4 blockade increased the frequency and function of tumor-specific CD8 T cells. These CD8 T cells persisted in the tumor microenvironment, exhibited memory phenotype and protected animals from tumor growth on tumor rechallenge. Gene expression analysis of tumors resistant to dual PD1/CTLA4 blockade treatment identified upregulation of antigen processing and presentation pathways and downregulation of extracellular matrix organization genes.

Conclusions

These findings describe a novel platform for developing patient-derived preclinical tumor models suitable for rationally testing combinatorial ICB in the context of autologous tumor-reactive T cells. This platform can be further developed for testing additional targeted therapies relevant to OVC.
Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial
Authors: Chen Xiaofeng , Wu Xiaofeng , Wu Hao , Gu Yanhong , Shao Yang , Shao Qianwen , Zhu Feipeng , Li Xiao , Qian Xiaofeng , Hu Jun , Zhao Fengjiao , Mao Weidong , Sun Jing , Wang Jian , Han Gaohua , Li Changxian , Xia Yongxiang , Seesaha Poshita Kumari , Zhu Dongqin , Li Huajun , Zhang Junling , Wang Guoqiang , Wang Xuehao , Li Xiangcheng , Shu Yongqian
Published: November 2020

Background

Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response.

Methods

In this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m2) and oxaliplatin (85 mg/m2). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment.

Results

54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28).

Conclusion

Camrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX.

Trial registration number

NCT03486678.
Plasma-based microsatellite instability detection strategy to guide immune checkpoint blockade treatment
Authors: Wang Zhenghang , Zhao Xiaochen , Gao Chan , Gong Jifang , Wang Xicheng , Gao Jing , Li Zhongwu , Wang Jie , Yang Bo , Wang Lei , Zhang Bei , Zhou Yifan , Wang Dalei , Li Xiaofang , Bai Yuezong , Li Jian , Shen Lin
Published: November 2020

Background

Microsatellite instability (MSI) represents the first pan-cancer biomarker approved to guide immune checkpoint blockade (ICB) treatment. However its widespread testing, especially outside of gastrointestinal cancer, is hampered by tissue availability.

Methods

An algorithm for detecting MSI from peripheral blood was established and validated using clinical plasma samples. Its value for predicting ICB efficacy was evaluated among 60 patients with advanced gastrointestinal cancer. The landscape of MSI in blood was also explored among 5138 advanced solid tumors.

Results

The algorithm included 100 microsatellite markers with high capture efficiency, sensitivity, and specificity. In comparison with orthogonal tissue PCR results, the method displayed a sensitivity of 82.5% (33/40) and a specificity of 96.2% (201/209), for an overall accuracy of 94.0% (234/249). When the clinical validation cohort was dichotomized by pretreatment blood MSI (bMSI), bMSI-high (bMSI-H) predicted both improved progression-free survival and overall survival than the blood microsatellite stable (bMSS) patients (HRs: 0.431 and 0.489, p=0.005 and 0.034, respectively). Four patients with bMSS were identified to have high blood tumor mutational burden (bTMB-H) and trended towards a better survival than the bMSS-bTMB-low (bTMB-L) subset (HR 0.026, 95% CI 0 to 2.635, p=0.011). These four patients with bMSS-bTMB-H plus the bMSI-H group collectively displayed significantly improved survival over the bMSS-bTMB-L patients (HR 0.317, 95% CI 0.157 to 0.640, p<0.001). Pan-cancer prevalence of bMSI-H was largely consistent with that shown for tissue except for much lower rates in endometrial and gastrointestinal cancers, and a remarkably higher prevalence in prostate cancer relative to other cancer types.

Conclusions

We have developed a reliable and robust next generation sequencing-based bMSI detection strategy which, in combination with a panel enabling concurrent profiling of bTMB from a single blood draw, may better inform ICB treatment.
Prognostic significance and immune correlates of CD73 expression in renal cell carcinoma
Authors: Tripathi Abhishek , Lin Edwin , Xie Wanling , Flaifel Abdallah , Steinharter John A , Stern Gatof Emily N , Bouchard Gabrielle , Fleischer Justin H , Martinez-Chanza Nieves , Gray Connor , Mantia Charlene , Thompson Linda , Wei Xiao X , Giannakis Marios , McGregor Bradley A , Choueiri Toni K , Agarwal Neeraj , McDermott David F , Signoretti Sabina , Harshman Lauren C
Published: November 2020

Background

CD73–adenosine signaling in the tumor microenvironment is immunosuppressive and may be associated with aggressive renal cell carcinoma (RCC). We investigated the prognostic significance of CD73 protein expression in RCC leveraging nephrectomy samples. We also performed a complementary analysis using The Cancer Genome Atlas (TCGA) dataset to evaluate the correlation of CD73 (ecto-5′-nucleotidase (NT5E), CD39 (ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)) and A2 adenosine receptor (A2AR;ADORA2A) transcript levels with markers of angiogenesis and antitumor immune response.

Methods

Patients with RCC with available archived nephrectomy samples were eligible for inclusion. Tumor CD73 protein expression was assessed by immunohistochemistry and quantified using a combined score (CS: % positive cells×intensity). Samples were categorized as CD73negative(CS=0), CD73lowor CD73high(< and ≥median CS, respectively). Multivariable Cox regression analysis compared disease-free survival (DFS) and overall survival (OS) between CD73 expression groups. In the TCGA dataset, samples were categorized as low, intermediate and highNT5E,ENTPD1andADORA2Agene expression groups. Gene expression signatures for infiltrating immune cells, angiogenesis, myeloid inflammation, and effector T-cell response were compared betweenNT5E,ENTPD1andADORA2Aexpression groups.

Results

Among the 138 patients eligible for inclusion, ‘any’ CD73 expression was observed in 30% of primary tumor samples. High CD73 expression was more frequent in patients with M1 RCC (29% vs 12% M0), grade 4 tumors (27% vs 13% grade 3 vs 15% grades 1 and 2), advanced T-stage (≥T3: 22% vs T2: 19% vs T1: 12%) and tumors with sarcomatoid histology (50% vs 12%). In the M0 cohort (n=107), patients with CD73hightumor expression had significantly worse 5-year DFS (42%) and 10-year OS (22%) compared with those in the CD73negativegroup (DFS: 75%, adjusted HR: 2.7, 95% CI 1.3 to 5.9, p=0.01; OS: 64%, adjusted HR: 2.6, 95% CI 1.2 to 5.8, p=0.02) independent of tumor stage and grade. In the TCGA analysis, highNT5Eexpression was associated with significantly worse 5-year OS (p=0.008).NT5EandENTPD1expression correlated with higher regulatory T cell (Treg) signature, whileADORA2Aexpression was associated with increased Treg and angiogenesis signatures.

Conclusions

High CD73 expression portends significantly worse survival outcomes independent of stage and grade. Our findings provide compelling support for targeting the immunosuppressive and proangiogenic CD73–adenosine pathway in RCC.
New non-invasive device to promote primary closure of the fascia and prevent loss of domain in the open abdomen: a pilot study
Authors: Rezende-Neto Joao Baptista , Camilotti Bruna Gewehr
Published: November 2020

Background

Primary closure of the fascia at the conclusion of a stage laparotomy can be a challenging task. Current techniques to medialize the fascial edges in open abdomens entail several trips to the operating room and could result in fascial damage. We conducted a pilot study to investigate a novel non-invasive device for gradual reapproximation of the abdominal wall fascia in the open abdomen.

Methods

Mechanically ventilated patients ≥16 years of age with the abdominal fascia deliberately left open after a midline laparotomy for trauma and acute care surgery were randomized into two groups. Control group patients underwent standard care with negative pressure therapy only. Device group patients were treated with negative pressure therapy in conjunction with the new device for fascial reapproximation. Exclusion criteria: pregnancy, traumatic hernias, pre-existing ventral hernias, burns, and body mass index ≥40 kg/m2. The primary outcome was successful fascial closure by direct suture of the fascia without mesh or component separation. Secondary outcomes were abdominal wall complications.

Results

Thirty-eight patients were investigated, 20 in the device group and 18 in the control group. Primary closure of the fascia by direct suture without mesh or component separation was achieved in 17 patients (85%) in the device group and only 10 patients (55.6%) in the control group (p=0.0457). Device group patients were 53% more likely to experience primary fascial closure by direct suture than control group patients. Device group showed gradual reduction (p<0.005) in the size of the fascial defects; not seen in control group. There were no complications related to the device.

Conclusions

The new device applied externally on the abdominal wall promoted reapproximation of the fascia in the midline, preserved the integrity of the fascia, and improved primary fascial closure rate compared with negative pressure therapy system only.

Level of evidence

I, randomized controlled trial.
Intraoperative vasopressor use during emergency surgery on injured meth users
Authors: Edwards Alexandra Marie , Johnson Eric Gregory , Bernard Andrew C.
Published: November 2020

Background

Methamphetamine is a growing drug of abuse in America. Patients with recent methamphetamine use pose potential complications to general anesthesia due to changes in hemodynamics and arrhythmias. Limited data exists on the incidence of intraoperative complications on methamphetamine-intoxicated patients requiring urgent or emergent trauma surgery. This study aims to describe intraoperative complications observed in methamphetamine and amphetamine-intoxicated patients requiring emergent surgery.

Methods

Using the Trauma Registry at our ACS-verified level I trauma center, we completed a single-center, descriptive, retrospective cohort review between July 1, 2012 and June 30, 2016, of adult patients requiring emergent surgery with a positive urine-drug screen for methamphetamines or amphetamines. The objective was to evaluate vasopressor utilization during surgical operation.

Results

A total of 92 patients were identified with a positive UDS for amphetamine and/or methamphetamine who went to the operating room within 24 hours of admission. Thirty-two (34%) patients received one or more (≥1) doses of vasopressor, while 60 patients (66%) received no vasopressor. Changes in mean arterial pressure (MAP) were noted in 64%, while only 3% experienced an EKG change. A binomial logistic regression showed age, base deficit and change in MAP to be predictive of vasopressor use (p<0.002). No intraoperative cardiac events or anesthetic complications were seen.

Discussion

Hemodynamic instability in the amphetamine and methamphetamine-intoxicated population may be more directly related to degree of resuscitation required, than the presence of a positive UDS.

Level of evidence

IV
Acute Care Surgery Billing, Coding and Documentation Series Part 2: Postoperative Documentation and Coding; Documentation and Coding in Conjunction with Trainees and Advanced Practitioners; Coding Select Procedures
Authors: Esposito Thomas , Reed Robert , Adams Raeanna C , Fakhry Samir , Carey Dolores , Crandall Marie L
Published: November 2020

This series of reviews has been produced to assist both the experienced surgeon and coder, as well as those just starting practice that may have little formal training in this area. Understanding this complex system will allow the provider to work “smarter, not harder” and garner the maximum compensation for their work. We hope we have been successful in achieving that goal and that this series will provide useful information and be worth the time invested in reading it by bringing tangible benefits to the efficiency of practice and its reimbursement. This second section deals with postoperative documentation and coding, documentation and coding in conjunction with trainees and advanced practitioners, and coding of select procedures.
Potassium and micronutrient fertilizer addition in a mock aquaponic system for drug-type Cannabis sativa L. cultivation
Authors: Yep Brandon , Zheng Youbin
Published: November 2020

Cultivating drug-type Cannabis sativa L. with aquaponics could reduce mineral fertilizer use; however, its nutrient solution is often unbalanced and low in K+ and micronutrients. It is unknown if a K+ fertilizer, a micronutrient fertilizer, or both, would improve C. sativa production in aquaponic solution, as optimal K+ and micronutrient concentrations in the root zone for C. sativa during the flowering stage have not been investigated. To determine the effects of adding a K+ fertilizer and a micronutrient fertilizer to aquaponic solution for C. sativa production, we grew drug-type C. sativa in five aquaponic based solutions: aquaponic solution (control plants) (15 mg·L−1 K+); aquaponic solution with added micronutrients (Fe3+, Cu2+, Mn2+, B3+, Mo3+, and Zn2+); and aquaponic solution with added micronutrients and three K+ concentrations (75, 113, and 150 mg·L−1) during the flowering stage. To evaluate the impact of additional K+ and micronutrients on C. sativa production, we measured growth (vegetative parameters and weight), physiology (leaf gas exchange), leaf nutrition content, and yield (inflorescence weight). Adding the K+ fertilizer at 75 and 113 mg·L−1 with micronutrients to aquaponic solution increased harvest index (marketable inflorescence to shoot weight) by 16% and 22% compared with the control, respectively. Cannabis sativa dry apical inflorescence and total inflorescence yield also increased linearly with increasing K+ concentration. Alternatively, plants grown in the control (suboptimal K+ and micronutrient conditions) had no difference in growth or measured physiological parameters compared with plants with supplemented nutrients. Our study suggests that aquaponic solution mitigates low K+ concentrations from causing deficiency.
The genetics ofCannabis—genomic variations of key synthases and their effect on cannabinoid content
Authors: Singh Aparna , Bilichak Andriy , Kovalchuk Igor
Published: November 2020

Despite being a controversial crop, Cannabis sativa L. has a long history of cultivation throughout the world. Following recent legalization in Canada, Cannabis is emerging as an important plant for both medicinal and recreational purposes. Recent progress in genome sequencing of both cannabis and hemp varieties allow for systematic analysis of genes coding for enzymes involved in the cannabinoid biosynthesis pathway. Single-nucleotide polymorphisms in the coding regions of cannabinoid synthases play an important role in determining plant chemotype. Deep understanding of how these variants affect enzyme activity and accumulation of cannabinoids will allow breeding of novel cultivars with desirable cannabinoid profiles. Here we present a short overview of the major cannabinoid synthases and present the data on the analysis of their genetic variants and their effect on cannabinoid content using several in-house sequenced Cannabis cultivars.