bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Analysis of Couette-Taylor Flow With Periodic Oscillation of the Inner Cylinder in Different Flow Regimes
Authors: Mahmoudirad Shima , Shirani Ebrahim , Aloui Fethi
Published: October 2021

The structures of flow in laminar Couette-Taylor flow with periodic oscillation of the inner cylinder rotation velocity (which linearly increases from zero to a fixed maximum value and then goes to zero again in each period) for different three regimes; Couette flow, Taylor vortex and wavy vortex, with the effect of the Womersley number, Wo, for different periods and the critical Taylor number are investigated numerically. The Wo varies between. 0.38 ≤ Wo ≤ 8.59. To understand how the flow responds to a given boundary conditions, the critical Taylor number is calculated and the structure of vortices which formed in the flow field is investigated. The results show that if Wo is increased, i.e. when the slope of rotational velocity of inner cylinder is increased, more delay in changing the flow regime compare to the steady state (when the inner cylinder rotates with constant velocity) is observed. Also for large values of Wo, due to the inertia, the flow does not follow the given boundary condition so for the higher value of the Womersley number, Wo = 8.59, there is a time lag and vortices do not appear until the second period of the inner cylinder oscillations. The reason is that the time scale of the dynamics of flow is less than the time scale that is associated with the flow instability, thus the flow regime behaves like a laminar Couette flow at the initial period. Comparing the present results with that of steady state, it is appeared that for a minimum value of Wo used in this paper, i.e. Wo = 0.38, the primary critical Taylor number is 50% higher than that of steady state.
Experimental Investigations on the Effect of a Wavy Surface on Hydrodynamic Instabilities in a Taylor-Couette System
Authors: Gaied Lamia , Lippert Marc , Keirsbulck Laurent , Aloui Fethi , Berrich Emna
Published: October 2021

In this work, we propose an experimental study of the effect of surface roughness of the internal cylinder Couette-Taylor system in order to investigate the hydrodynamic instabilities of the flow. During experiments, the inner cylinder, which presents a rough surface with u cylinder corrugations, rotates at a given angular speed and the outer cylinder, which is smooth, is kept fixed.

The main objective of the study is to demonstrate the effect of geometric parameters on the flow (the shape of the roughness). Experimental results have shown that the shapes of the surface irregularities have an effect on the appearance of the first instabilities, which strongly depend on the size, shape and nature of the roughness. In fact, the nature of surface roughness not only affects the friction on the wall, but also strongly influences the transport of mass and momentum in a given flow regime. The flow therefore evokes more friction when the inner (rotating) cylinder has a rough surface. This friction, which slows the speed of the fluid particles, strongly depends on the surface nature in contact with the fluid. The movement of the particles in these irregularities will therefore, be damped as a function of the shape of the roughness. In addition, the results also showed that once Couette-Taylor vortices are present, surface roughness can promote continued flow disturbance. The resulting flow then becomes less slow in the troughs of surface irregularities; thus, leads to less friction.
Application and Verification of Time-Domain Impedance Boundary Conditions in CAA Simulations
Authors: Li Ang , Chen Jun
Published: October 2021

In computational fluid dynamic (CFD) and computational aeroacoustics (CAA) simulations, the wall surface is normally treated as a purely reflective wall. However, some surface treatments are usually applied in experiments. Thus, the simulation results cannot be validated by experimental results. In aeroacoustics analysis, impedance is a quantity to characterize reflectivity and absorption of an acoustically treated surface. One of the major numerical challenges in CAA simulations is to define acoustically well-posed boundary conditions. The impedance boundary condition is a frequency-domain boundary condition. However, CFD and CAA simulations are time-domain computations, which means the frequency-domain impedance boundary condition cannot be adopted directly. Several methods, including the three-parameter model, the z-transform method and the reflection coefficient model, were developed. In the present study, a coupling method that combines the time-domain impedance boundary condition and Large Eddy Simulations (LES) is proposed. A channel flow with wall impedance is simulated at different acoustic resistance and reactance. The approach is verified by the case with purely reflective wall impedance. For the flow with wall impedance. The effects of acoustic resistance and reactance are investigated. It is found that the wall impedance contributes to the noise reduction in the near-wall region, and with the decrease of the resistance or reactance, the sound pressure level is decreased. The method developed in this study is expected to be applied to a variety of noise-control problems.
Influence of Thermal Plume on Particle Inhalability of a Lying Mannequin in a Room
Authors: Habibi Maryam , Heidary Mohsen , Tavakol Mohammad Mehdi , Ahmadi Goodarz
Published: October 2021

In this study, the dispersion and deposition of particles in the respiratory system attached to a mannequin lying down inside a room were investigated numerically. The respiratory system model was prepared by processing the CT scan images of a volunteer and was attached to a mannequin lying in the middle of a room. The flow field around the mannequin and effects of the thermal plume on the particle aspiration by the mannequin model was simulated using the Ansys-Fluent software. The aspiration efficiency of spherical particles in the airway was studied with the Lagrangian particle trajectory analysis, including the turbulence dispersion effects. For validation of numerical simulations, the aspiration efficiency of the particles obtained from the numerical solution was compared with the case of a standing mannequin. The results are presented for two different modes with upward and downward thermal plumes. For the first mode, due to the strong effect of the thermal plume in the upward direction, the aspiration efficiency of midrange particles increases. However, the aspiration efficiency of large micro-particles decreases for the first mode. For the second mode, with the downward thermal plume, the aspiration efficiency of small micro-particles increases significantly.
3-D Computational Study of a Diffuser Augmented Micro Wind Turbine
Authors: M. S. Kiran , Rajawat Aakash , Ranjan Pritanshu
Published: October 2021

The present study focuses on the design optimization of a 3D DAMWT (Diffuser Augmented Micro Wind Turbine geometry). DAMWTS are compact devices with a swept area of only few square meters and energy production capacity of a few kilowatts. Their small size makes it convenient for domestic power generation. The box-shaped shroud makes it possible to stack multiple DAMWTS in an array configuration, thereby multiplying power output. 3-D CFD simulations were carried out using the k-ω SST turbulence model to compare the performance characteristics of different turbine geometries with a square inlet. With a constant shroud diffuser angle of 12 degrees as obtained in a previous study, the shroud nozzle angle and curvature were varied to obtain the maximum velocity factor and minimize flow stagnation at the inlet. Best performance was obtained with a nozzle angle of approximately 27 degrees and semi-concave curvature, with a velocity factor of 1.2. Further increase in nozzle angle resulted in a decline in performance and an increased flow stagnation. To analyze the influence of stacking on flow characteristics, a computational study of two DAMWTS placed horizontally next to each other was carried out. An investigation of the effectiveness of Vortex Generators in inhibiting flow stagnation at the inlet was also conducted.
Influence of Rectangular Strips’ Size on Aerodynamic Performance of a High-Speed Train Subjected to Crosswind
Authors: Wang Mengying , Sun Zhenxu , Ju Shengjun , Yang Guowei
Published: October 2021

Conventional studies usually assume that the train surface is smooth, so as to simplify the numerical calculation. In fact, the surface of the train is irregular, which will change the flow characteristics in the boundary layer and further affect the aerodynamic performance of a train. In this work, roughness is applied to the roof of a 1:25 scaled train model in the form of longitudinal strips. Firstly, the improved delayed detached eddy simulation (IDDES) method is adopted to simulate the aerodynamic performance of the train model with both smooth and rough surface, which are subjected to crosswind. Results show that the side force coefficient and the roll moment coefficient subjected to rough model decreased by 3.71% and 10.56% compared with the smooth model. Then, the width, height and length of the strips are selected as variables to design different numerical simulation schemes based on the orthogonal experimental design method. Through variance analysis, it can be found that four design parameters have no significant effect on the side force coefficient. Meanwhile, for the roll moment coefficient, the length of the strips in the straight region of the train has a significant effect and the width of the strips has a highly significant effect on it. These conclusions can provide a theoretical basis to improve the aerodynamic performance of the high-speed train subjected to crosswind.
Computational Study of Viscoelastic Flows in Microchannels
Authors: Xue Guanyang , Cheng Xuanhong , Oztekin Alparslan
Published: October 2021

Computational Fluid Dynamics (CFD) simulations have been performed in a 2D cross-section of the microchannel to characterize the viscoelastic flow field using OpenFOAM with customized stabilizing methods. The continuity and momentum equations coupled with the Giesekus constitutive model are solved. The computational domain consists of a straight main channel that is 100 μm in width and a 1:4 square-shaped cavity in the middle of the channel. The mesh convergence study is performed with both structured and unstructured cells. Flow and stress fields are compared with different cell densities. The numerical study is carried out on various Deborah numbers (De). The first normal stress difference is computed to examine the elastic lift force for future studies for nanoparticle separations. The vortex on the expansion side shrinks while the contraction side expands as De is increased. A banded zone of stronger N1 in the bulk region of the cavity, observed at higher De, could be favorable in particle separation applications. As the simulation process being validated, this study can help with future improvements to achieve higher flow rates.
Numerical Investigation of Cloud Cavitation and Its Induced Shock Waves
Authors: Ushioku Takahiro , Yoshimura Hiroaki
Published: October 2021

This paper numerically investigates unsteady behavior of cloud cavitation, in particular, to elucidate the induced shock wave emission. To do this, we consider a submerged water-jet injection into still water through a nozzle and make some numerical analysis of two-dimensional multiphase flows by Navier-Stokes equations. In our previous study [7], we have shown that twin vortices symmetrically appear in the injected water, which plays an essential role in performing the unsteady behavior of a cloud of bubbles. In this paper, we further illustrate the elementary process of the emission of the shock waves. First, we set up the mixture model of liquid and gas in Lagrangian description by the SPH method, together with the details on the treatment of boundary conditions. Second, we show the velocity fields of the multiphase flow to illustrate the inception, growth as well as the collapse of the cloud. In particular, we explain the mechanism of the collapse of the cloud in view of the motion of the twin vortices. Further, we investigate the pressure fields of the multiphase flow in order to demonstrate how the shock wave is emitted associated with the collapse of the cloud. Finally, we show that a small shock wave may be released prior to the main shock wave emission.
Three-Dimensional Two-Phase Flow Simulations of Water Braking Phenomena for High-Speed Test Track Sled
Authors: Terrazas Jose , Rodriguez Arturo , Kumar Vinod , Adansi Richard , Kotteda V. M. Krushnarao
Published: October 2021

Specializing in high-speed testing, Holloman High-Speed Test Track (HHSTT) uses a process called ‘water braking’ as a method to bring vehicles at the test track to a stop. This method takes advantage of the higher density of water, compared to air, to increase braking capability through momentum exchange. By studying water braking using Computational Fluid Dynamics (CFD), forces acting on track vehicles can be approximated and prepared for prior to actual test. In this study, focus will be made on the brake component of the track sled that is responsible for interacting with the water for braking. By discretizing a volume space around our brake, we accelerate water and air to relatively simulate the brake engaging. The model is a multi-phase flow that uses the governing equations of gas and liquid phases with the finite volume method, to perform 3D simulations. By adjusting the inflow velocity of air and water, it is possible to simulate HHSTT sled tests at various operational speeds. In the development of the 3D predictive model, convergence issues associated with the numerical mesh, initial/boundary conditions, and compressibility of the fluids were encountered. Once resolved, the effect of inflow velocities of water and air on the braking of the sled are studied.
Assessment of Predictive Capability of Hybrid RANS/LES Turbulence Models for Thermofluid Applications
Authors: Zope Anup , Schemmel Avery , Wang Xiao , Bhushan Shanti , Singh Prashant , Luke Edward
Published: October 2021

In this study, we have assessed performance of URANS model, various hybrid RANS/LES turbulence models such as detached eddy simulation, Nichols-Nelson HRLES model, dynamic HRLES (DHRL) model, as well as LES for two classes of problems: (a) heat transfer due to subsonic swirling flow subjected to a sudden expansion leading to cylindrical chamber, and (b) flow separation due to oblique shock wave-turbulent boundary layer interaction (STBLI). The results are assessed using the heat transfer characteristics, separation and reattachment characteristics, and capability to predict flow unsteadiness. The study indicates that URANS can predict large scale flow features reasonably well. However, it fails to resolve turbulence. PANS improves TKE prediction, hence, improves heat transfer prediction. Among the hybrid RANS/LES models, DHRL coupled with ILES is capable of providing accurate prediction of flow separation/reattachment characteristics for boundary layer flows. For free-shear dominated flows, implicit LES performs better compared to the explicit LES models.
A Gas-Particle Analogue to the Richtmyer-Meshkov Instability: Comparing Multiphase Simulations to Shock Tube Experiments
Authors: Ouellet Frederick , Rollin Bertrand , Durant Bradford , Koneru Rahul Babu , Balachandar S.
Published: October 2021

A research area emerging in the multiphase flow community is the study of Shock-Driven Multi-phase Instability (SDMI), a gas-particle analog of the traditional fluid-fluid Richtmyer-Meshkov instability (RMI). In this work, we study the interaction of planar air shocks with corrugated glass particle curtains through the use of numerical simulations with an Eulerian-Lagrangian approach. This approach has simulations track computational particle trajectories in a Lagrangian framework while evolving the surrounding fluid flow on a fixed Eulerian mesh. In addition to observing the evolution of the perturbed particle curtain in the simulations, we also observe the evolution of the curtain of gas which is initially trapped inside of the particle curtain as the simulation progresses. The objective of this study is to compare the evolving simulation curtains (both particle and gas) to a comparable set of shock tube experiments performed to analyze traditional fluid RMI evolution. The simulations are set to match the experimental shock Mach numbers and perturbation wavelengths (3.6 and 7.2 mm) while matching the Atwood number of the experiments to the multiphase Atwood number of the simulations. However, multiple particle diameters are tested in the simulations to get a view into the impact of the particle diameter on the evolution of the particle curtain. This simulation setup allows for a one-to-one comparison between RMI and SDMI under comparable conditions while also allowing for a separate study into the validity of the use of both the multiphase Atwood number and the fluid-only Atwood number to compare the single-phase and multiphase instabilities. In particular, we show that this validity is at least partly dependent on the diameters of the particles in the curtain (thus, dependent on the Stokes number of the flow). We also analyze the effect of the multiphase terms of the vorticity evolution equation on the vorticity deposition in SDMI. Also discussed is the effect of the particle diameter on the multiphase generation terms as well as in the baroclinic vorticity generation term in SDMI as the shock passes over the curtain.
Application of Scale-Resolving Simulations and Hybrid Models for Contraction-Expansion Pipe Flows
Authors: Darihaki Farzin , Zhang Jun , Shirazi Siamack A.
Published: October 2021

Contractions and expansions are commonly found in various piping systems including flow control in the oil and gas industry. They impose complex flow characteristics such as flow recirculation, boundary layer separation and unsteady re-attachment. Computational Fluid Dynamics (CFD) using RANS simulations can offer general information about the time-averaged flow properties in expansion and contraction geometries including the pressure drop across the fitting. However, they generally fail to provide details of turbulent flow such as shedding of vortices and high turbulent intensities which are observed in experimental data at the expansion and contraction regions. Large Eddy Simulations (LES) can resolve a turbulence spectrum by filtering Navir-Stokes equations over the computational cells. In this study, LES is utilized to examine a sudden-contraction and expansion pipe flow. Furthermore, Stress-Blended Eddy Simulations (SBES) as a hybrid LES-RANS model is employed for comparison. All of these Scale-Resolving Simulations (SRS) are examined against the experimental data and compared to commonly used RANS simulations. Various flow parameters are examined at different locations for a 50.8 mm pipe which is suddenly reduced to a 25.4 mm pipe and then suddenly expands to the original size, and highlights of each model are presented. The details of the turbulent flow in these geometries are critical to many applications such as particle-laden flows and this investigation would provide insight into the appropriate flow modeling in the expansion and contraction geometries.
Computational Analysis of Non-Premixed Combustion in a Scramjet Combustor With a Wedge Shaped Strut Injector
Authors: Katare Sajal , Yadav Nagendra P.
Published: October 2021

This paper focuses the computational study of non-premixed combustion in a scramjet combustor. The wedge shaped strut injector was used in the combustion process. In order to investigate the flame holding mechanism of the wedge shaped strut in supersonic flow, the two-dimensional coupled implicit RANS equations, the standard k-ε turbulence model and the finite-rate/eddy-dissipation reaction model are introduced to simulate the flow field of the hydrogen fueled scramjet combustor with a strut flame holder under different conditions. The static pressure of the case under the engine ignition condition is much higher than that of the case under the cold flow condition. The reflection of shock waves improves the mixing of hydrogen with the stream of inlet air and thus increases combustion efficiency. The mass flow rate of air is optimized for the best performance of engine.
Liutex Core Line for Vortex Structure in Turbulence
Authors: Alvarez Oscar , Yu Yifei , Liu Chaoqun
Published: October 2021

Liutex is a vortex identification method that provides a vector interpretation of local fluid rotation. Liutex produces a vector quantity which can be used to determine the absolute and relative strength of a vortex, the local rotation axis of a vortex, the vortex core center, the size of the vortex core, and the vortex boundary. Vortex identification and visualization is essential in computational fluid turbulence analysis and fluid mechanics in general. Until Liutex, there has not been a way to identify the core of a vortex structure or even the center of rotation of a vortex structure. Since Liutex, tools have been created to assist in the identification and analysis of vortical structures. The Liutex Core Line has been developed to better understand turbulent fluid structures. A Liutex core is defined as a concentration of Liutex vectors and defined to be unique and the Liutex core line is the center of rotation of that Liutex core. Currently, iso-surfaces are the most popular way to visualize the structure of turbulent flow but there is no reason to believe that it is the best way to represent a vortex’s structure. Previous methods that use iso-surface are strongly threshold dependent and since the Liutex core line is unique, it is independent of threshold and can show the real vortex structure. In this paper we show the benefits and promises of the Liutex Core Line as a better way of representing vortex structures.
Investigation of the Effect of Cross Section on the Convective Heat Transfer Performance of Nanoemulsion in Microchannel Heat Exchanger
Authors: Gameda Takele , Kabir M. Mehdi , Xu Jiajun
Published: October 2021

The present study aims to numerically investigate the effect of cross section on the heat transfer performance of single-phase flow of Ethanol/Polyalphaolefin nanoemulsion fluid with ethanol concentrations of 8 wt.% in a microchannel heat exchanger. While the exterior geometry of the microchannels’ solid structure remains the same, four different cross sections of channels including: circular, upward semi-circular, rectangular, and trapezoidal, are designed with keeping the channels’ wetted perimeters, mass flow rate, and Reynolds number constant for comparison purposes. In the present study, the hydrodynamic and heat transfer characteristics, including local Nusselt number, heat transfer coefficient, and velocity profile, were investigated under a uniform wall heat flux boundary conditions within the laminar flow regime. The channel models of different cross sections were developed by the COMSOL-Multiphysics for numerical analysis. The heat transfer characteristics were then compared for different cross sections under the same operating conditions, and the effect of aspect ratio for rectangular and trapezoidal cross sections were also studied.
Experimental and Computational Studies on Flow Characteristics of Single Expansion Nozzle
Authors: Inturi Dakshina Murthy , Pinnam Lovaraju , Vegesna Ramachandra Raju
Published: October 2021

The present investigation aims to study the flow field characteristics of a single expansion nozzle (SEN). The flow field characteristics of conventional convergent-divergent (C-D) nozzle are also investigated for comparison. The experimental and computational studies were carried out for nozzle pressure ratios of 1.45, 1.55, 1.75, 2, 3, 4 and 5. The studies reveal that, for the single expansion nozzle the oblique shock moves towards the solid boundary with the increase of nozzle pressure ratio, which makes the flow to accelerate continuously in the majority of the divergent portion. The single expansion nozzle delivers the flow with higher Mach number than the C-D nozzle at the exit of the nozzle.
Toward a quantum future for South Africa
Authors: Forbes Andrew , Petruccione Francesco , Roux Filippus S.
Published: October 2021

South Africa has a long history in quantum research with an explosion of activity in the recent decade. Bolstered by this momentum, in March 2021, the South African Quantum Technologies Initiative (SA QuTI) was formally launched by the South African Department of Science and Innovation with the first seed funding released in September 2021. SA QuTI puts quantum technology firmly on the national agenda with ambitious aims for a quantum industry in South Africa. Here, the authors report this to the international quantum community and share their perspectives on what this means for South Africa's quantum future.
Pseudogene-mediated DNA demethylation leads to oncogene activation
Authors: Kwon Junsu , Liu Yanjing V. , Gao Chong , Bassal Mahmoud A. , Jones Adrianna I. , Yang Junyu , Chen Zhiyuan , Li Ying , Yang Henry , Chen Leilei , Di Ruscio Annalisa , Tay Yvonne , Chai Li , Tenen Daniel G.
Published: October 2021

A pseudogene epigenetically regulates an oncogene by interacting with DNMT1 and affecting its methylation in a specific region.
Single-molecule photocatalytic dynamics at individual defects in two-dimensional layered materials
Authors: Huang Teng-Xiang , Dong Bin , Filbrun Seth L. , Okmi Aisha Ahmad , Cheng Xiaodong , Yang Meek , Mansour Nourhan , Lei Sidong , Fang Ning
Published: October 2021

Single-molecule photocatalysis at defects in 2D layered materials display distinct dynamic features.
Immune checkpoint blockade sensitivity and progression-free survival associates with baseline CD8
+
T cell clone size and cytotoxicity
Authors: Watson Robert A. , Tong Orion , Cooper Rosalin , Taylor Chelsea A. , Sharma Piyush K. , de los Aires Alba Verge , Mahé Elise A. , Ruffieux Hélène , Nassiri Isar , Middleton Mark R. , Fairfax Benjamin P.
Published: October 2021

The cytotoxicity and clone size of CD8
+
T cell pretreatment are prognostic for immune checkpoint blockade.
Necrotising Sweet’s syndrome: a rare presentation of Sweet’s syndrome with unilateral painful swelling of the neck
Authors: Husted Andreas , Udholm Sebastian , Udholm Nichlas
Published: October 2021

This case describes the first documented clinical presentation of Sweet’s syndrome with unilateral swelling of the neck, severe pain and fever. The clinical and radiological manifestation resembled necrotising fasciitis and the patient underwent acute neck dissection. The patient was ultimately diagnosed with a new subtype of Sweet’s syndrome called necrotising Sweet’s syndrome, and quickly recovered after treatment with intravenous administration of prednisolone.
Doxycycline-induced acquired haemophilia A
Authors: Shah Ejaz , Abro Calvin , Zaidi Fawwad , Goel Ruchika
Published: October 2021

An 80-year-old man with no personal or family history of bleeding, presented to hospital with extensive haematomas and skin bruising after using doxycycline. His basic lab workup was concerning for a coagulopathy with an elevated activated partial thromboplastin time and significant anaemia. Mixing studies and other factor levels were tested that led to the diagnosis of acquired haemophilia A with low factor VIII levels and high factor VIII antibodies. He was started on steroids, but his haemoglobin level continued to drop. Later, during his treatment, he was given multiple therapeutic agents, including cyclophosphamide, rituximab and recombinant factor VII (NovoSeven-R). Gradually factor VIII levels increased and haemoglobin stabilised. The hospital course was complicated by COVID-19 pneumonia leading to acute respiratory distress syndrome; the patient eventually expired due to respiratory failure.
Dynamic right-to-left interatrial shunt may complicate severe COVID-19
Authors: Rajendram Rajkumar , Hussain Arif , Mahmood Naveed , Via Gabriele
Published: October 2021

Right-to-left (RTL) interatrial shunt (IAS) may complicate select cases of COVID-19 pneumonia. We describe the use of serial imaging to monitor shunt in critically ill patients. A 52-year-old man presented with COVID-19 pneumonia. Hypoxia worsened despite maximal medical therapy and non-invasive ventilation. On day 8, saline microbubble contrast-enhanced transthoracic echocardiography revealed a patent foramen ovale (PFO) with RTLIAS. Invasive ventilation was initiated the next day. The course was complicated by intermittent severe desaturation without worsening aeration or haemodynamic instability, so PFO closure was considered. However, on day 12, saline microbubble contrast-enhanced transoesophageal echocardiography excluded RTLIAS. The patient was extubated on day 27 and discharged home 12 days later. Thus, RTLIAS may be dynamic and changes can be detected and monitored by serial imaging. Bedside echocardiography with saline microbubble contrast, a simple, minimally invasive bedside test, may be useful in the management of patients with severe hypoxia.
Pulmonary arteriovenous malformation as a cause of ischaemic stroke in the elderly
Authors: Luís Helena , Machado Bela , Barros Carolina , Gomes Mariana
Published: October 2021

Pulmonary arteriovenous malformation (PAVM) is well recognised as a cause of paradoxical brain embolism. The authors report the case of an older woman with a medical history of arterial hypertension who was found unconscious and was discovered to have pulmonary thromboembolism and ischaemic stroke related to a PAVM.
Platypnoea-orthodeoxia syndrome due to a right-to-left interatrial shunt following pneumonectomy
Authors: Steward Matthew , Hall Anthony , Sayers Ross , Dickson Christopher
Published: October 2021

A 62-year-old man presents with breathlessness 6 months following right pneumonectomy for lung adenocarcinoma. Previous investigations had not yielded a diagnosis and his symptoms were progressing. The patient described worsened symptoms when stood up (platypnoea), with profound hypoxia until laid supine (orthodeoxia). Platypnoea-orthodeoxia syndrome due to a right-to-left interatrial shunt was diagnosed on contrast-enhanced transoesophageal echocardiography with the patient undergoing successful percutaneous patent foramen ovale closure. Patent foramen ovale is often asymptomatic with a population prevalence of around 20%–30%. Anatomical shifts postpneumonectomy can open, or worsen a previously closed interatrial communication leading to right-to-left shunting of blood. Platypnoea-orthodeoxia is under-recognised, impairing quality of life and patient outcome. Investigations can be falsely reassuring, or poorly sensitive for the causative pathology. Percutaneous closure is safe with high success rates and this case highlights the need for a high index of suspicion for shunts, particularly in postpneumonectomy patients.
Normative data on cardiovascular autonomic function in Greenlandic Inuit
Authors: Christensen Marie Mathilde Bjerg , Hansen Christian Stevns , Fleischer Jesper , Vistisen Dorte , Byberg Stine , Larsen Trine , Laursen Jens Christian , Jørgensen Marit Eika
Published: October 2021

Introduction

Diabetes is increasing among Greenlandic Inuit; however, the prevalence of cardiovascular autonomic neuropathy (CAN) is yet unknown. The assessment of CAN requires an ability to differentiate between normal and abnormal. The aim was to establish normative reference data of cardiovascular autonomic function in Greenlandic Inuit.

Research design and methods

In this cross-sectional study, cardiovascular autonomic function was evaluated in participants without diabetes during theGreenlandic Population Study 2018and in the town Qasigiannguit in 2020. Assessment included cardiovascular autonomic reflex tests (CARTs) and power spectral analysis of heart rate variability (HRV). Normative reference limits were estimated by applying quantile regression models at the lowest fifth percentile, with age as the exposure variable and adjusted for sex. HRV models were additionally adjusted for resting heart rate.

Results

Based on examinations of 383 participants (60.6% females), normative reference data was established for all outcomes. Mean age was 52 years (SD 12.9). Higher age was inversely associated with all outcomes of CARTs and HRV. A linear fall in cardiovascular autonomic function tended to level off beyond age of 60 years for supine-to-upright position ratio. However, the number of observations in subjects older than 60 years was limited, which may have caused a flattening of the curve around that age. No other associations were found.

Conclusions

The general level of the CARTs and HRV for all age groups is notably lower than in previous studies from other nationalities. We speculate that sociodemographic and cultural aspects of the Greenlandic Inuit population including body mass index, smoking, physical activity and alcohol consumption may have affected the cardiovascular autonomic function.
Overview of attacks against civilian infrastructure during the Syrian civil war, 2012–2018
Authors: Muzzall Evan , Perlman Brian , Rubenstein Leonard S , Haar Rohini J
Published: October 2021

Background

Hundreds of thousands of people have been killed during the Syrian civil war and millions more displaced along with an unconscionable amount of destroyed civilian infrastructure.

Methods

We aggregate attack data from Airwars, Physicians for Human Rights and the Safeguarding Health in Conflict Coalition/Insecurity Insight to provide a summary of attacks against civilian infrastructure during the years 2012–2018. Specifically, we explore relationships between date of attack, governorate, perpetrator and weapon for 2689 attacks against five civilian infrastructure classes: healthcare, private, public, school and unknown. Multiple correspondence analysis (MCA) via squared cosine distance, k-means clustering of the MCA row coordinates, binomial lasso classification and Cramer’s V coefficients are used to produce and investigate these correlations.

Results

Frequencies and proportions of attacks against the civilian infrastructure classes by year, governorate, perpetrator and weapon are presented. MCA results identify variation along the first two dimensions for the variables year, governorate, perpetrator and healthcare infrastructure in four topics of interest: (1) Syrian government attacks against healthcare infrastructure, (2) US-led Coalition offensives in Raqqa in 2017, (3) Russian violence in Aleppo in 2016 and (4) airstrikes on non-healthcare infrastructure. These topics of interest are supported by results of the k-means clustering, binomial lasso classification and Cramer’s V coefficients.

Discussion

Findings suggest that violence against healthcare infrastructure correlates strongly with specific perpetrators. We hope that the results of this study provide researchers with valuable data and insights that can be used in future analyses to better understand the Syrian conflict.
Impact of stimulation among non-crying neonates with intact cord versus clamped cord on birth outcomes: observation study
Authors: KC Ashish , Budhathoki Shyam Sundar , Thapa Jeevan , Niermeyer Susan , Gurung Rejina , Singhal Nalini
Published: October 2021

Background

Stimulation of non-crying neonates after birth can help transition to spontaneous breathing. In this study, we aim to assess the impact of intact versus clamped umbilical cord on spontaneous breathing after stimulation of non-crying neonates.

Methods

This is an observational study among non-crying neonates (n=3073) born in hospitals of Nepal. Non-crying neonates born vaginally at gestational age ≥34 weeks were observed for their response to stimulation with the cord intact or clamped. Obstetric characteristics of the neonates were analysed. Association of spontaneous breathing with cord management was assessed using logistic regression.

Results

Among non-crying neonates, 2563 received stimulation. Of these, a higher proportion of the neonates were breathing in the group with cord intact as compared with the group cord clamped (81.1% vs 68.9%, p<0.0001). The use of bag-and-mask ventilation was lower among those who were stimulated with the cord intact than those who were stimulated with cord clamped (18.0% vs 32.4%, p<0.0001). The proportion of neonates with Apgar Score ≤3 at 1 min was lower with the cord intact than with cord clamped (7.6% vs 11.5%, p=0.001). In multivariate analysis, neonates with intact cord had 84% increased odds of spontaneous breathing (adjusted OR, 1.84; 95% CI: 1.48 to 2.29) compared with those with cord clamped.

Conclusions

Stimulation of non-crying neonates with intact cord was associated with more spontaneous breathing than among infants who were stimulated with cord clamped. Intact cord stimulation may help establish spontaneous breathing in apnoeic neonates, but residual confounding variables may be contributing to the findings. This study provides evidence for further controlled research to evaluate the effect of initial steps of resuscitation with cord intact.
Comparative efficacy and acceptability of psychotherapies for post-traumatic stress disorder in children and adolescents: a systematic review and network meta-analysis
Authors: Xiang Yajie , Cipriani Andrea , Teng Teng , Del Giovane Cinzia , Zhang Yuqing , Weisz John R. , Li Xuemei , Cuijpers Pim , Liu Xueer , Barth Jürgen , Jiang Yuanliang , Cohen David , Fan Li , Gillies Donna , Du Kang , Ravindran Arun V. , Zhou Xinyu , Xie Peng
Published: October 2021

Background

Available evidence on the comparative efficacy and acceptability of psychotherapies for post-traumatic stress disorder (PTSD) in children and adolescents remains uncertain.

Objective

We aimed to compare and rank the different types and formats of psychotherapies for PTSD in children and adolescents.

Methods

We searched eight databases and other international registers up to 31 December 2020. The pairwise meta-analyses and frequentist network meta-analyses estimated pooled standardised mean differences (SMDs) and ORs with random-effects model. Efficacy at post-treatment and follow-up, acceptability, depressive and anxiety symptoms were measured.

Findings

We included 56 randomised controlled trials with 5327 patients comparing 14 different types of psychotherapies and 3 control conditions. For efficacy, cognitive processing therapy (CPT), behavioural therapy (BT), individual trauma-focused cognitive–behavioural therapy (TF-CBT), eye movement desensitisation and reprocessing, and group TF-CBT were significantly superior to all control conditions at post-treatment and follow-up (SMDs between −2.42 and −0.25). Moreover, CPT, BT and individual TF-CBT were more effective than supportive therapy (SMDs between −1.92 and −0.49). Results for depressive and anxiety symptoms were similar to the findings for the primary outcome. Most of the results were rated as ‘moderate’ to ‘very low’ in terms of confidence of evidence.

Conclusions

CPT, BT and individual TF-CBT appear to be the best choices of psychotherapy for PTSD in young patients. Other types and different ways of delivering psychological treatment can be alternative options. Clinicians should consider the importance of each outcome and the patients’ preferences in real clinical practice.
Nivolumab-associated DRESS in a genetic susceptible individual
Authors: Ai Luoyan , Gao Jie , Zhao Shihai , Li Qian , Cui Yue-Hong , Liu Qing , Wu Duojiao , Wang Yimei , Jin Xiaoshi , Ji Yuan , Li Jingjie , Yu Yiyi , Liu Tianshu
Published: October 2021

The use of immune checkpoint inhibitors (ICIs) is rising exponentially in numerous cancers, but immune-related adverse events can occur. We report a rare case of high-grade drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome developed stepwise in a patient with gastric cancer after nivolumab treatment. Subclinical myocarditis was sensitively detected by cardiovascular magnetic resonance 3 weeks after initiating nivolumab. Eruption, eosinophilia, and interstitial pneumonitis occurred 1 week later. Corticosteroids were started and his condition improved. Four months later, when he was still on steroids tapering off, acute kidney injury and sequential herpes zoster virus activation developed. Severe acute tubulointerstitial nephritis (ATN) with an intense infiltration of lymphocytes was observed on renal biopsy. In blood, a substantial shift to Th2 response, an increase of Th17 cells, and strikingly enriched granzyme B+ and perforin+ CD8+ T cells were detected at ATN onset. Serum interleukin (IL)-5, IL-17, interferon gamma, and IL-6 levels were consistently elevated. Further molecular profiling identified a DRESS risk allele human leukocyte antigen (HLA)-A*31:01 in this patient. His ATN responded favorably to a high dose of corticosteroids. In parallel, complete antitumor response was observed during the clinical course of DRESS. This is the first ever case report of nivolumab-associated DRESS syndrome with exploration of the mechanisms from the histopathological, cellular and molecular aspects. Nivolumab-induced DRESS may result from type IV hypersensitivity-related ‘off-target effect’ and PD-1 block-mediated ‘on-target effect’. HLA risk alleles may constitute the genetic susceptible basis. HLA typing assay has the potential to screen susceptible individuals to avoid ICI-induced DRESS.
Bispecific antibody-mediated redirection of NKG2D-CAR natural killer cells facilitates dual targeting and enhances antitumor activity
Authors: Zhang Congcong , Röder Jasmin , Scherer Anne , Bodden Malena , Pfeifer Serrahima Jordi , Bhatti Anita , Waldmann Anja , Müller Nina , Oberoi Pranav , Wels Winfried S
Published: October 2021

Background

Natural killer group 2D (NKG2D) is an activating receptor of natural killer (NK) cells and other lymphocytes that mediates lysis of malignant cells through recognition of stress-induced ligands such as MICA and MICB. Such ligands are broadly expressed by cancer cells of various origins and serve as targets for adoptive immunotherapy with effector cells endogenously expressing NKG2D or carrying an NKG2D-based chimeric antigen receptor (CAR). However, shedding or downregulation of NKG2D ligands (NKG2DL) can prevent NKG2D activation, resulting in escape of cancer cells from NKG2D-dependent immune surveillance.

Methods

To enable tumor-specific targeting of NKG2D-expressing effector cells independent of membrane-anchored NKG2DLs, we generated a homodimeric recombinant antibody which harbors an N-terminal single-chain fragment variable (scFv) antibody domain for binding to NKG2D, linked via a human IgG4Fc region to a second C-terminal scFv antibody domain for recognition of the tumor-associated antigen ErbB2 (HER2). The ability of this molecule, termed NKAB-ErbB2, to redirect NKG2D-expressing effector cells to ErbB2-positive tumor cells of different origins was investigated using peripheral blood mononuclear cells, ex vivo expanded NK cells, and NK and T cells engineered with an NKG2D-based chimeric receptor.

Results

On its own, bispecific NKAB-ErbB2 increased lysis of ErbB2-positive breast carcinoma cells by peripheral blood-derived NK cells endogenously expressing NKG2D more effectively than an ErbB2-specific IgG1mini-antibody able to induce antibody-dependent cell-mediated cytotoxicity via activation of CD16. Furthermore, NKAB-ErbB2 synergized with NK-92 cells or primary T cells engineered to express an NKG2D-CD3ζ chimeric antigen receptor (NKAR), leading to targeted cell killing and greatly enhanced antitumor activity, which remained unaffected by soluble MICA known as an inhibitor of NKG2D-mediated natural cytotoxicity. In an immunocompetent mouse glioblastoma model mimicking low or absent NKG2DL expression, the combination of NKAR-NK-92 cells and NKAB-ErbB2 effectively suppressed outgrowth of ErbB2-positive tumors, resulting in treatment-induced endogenous antitumor immunity and cures in the majority of animals.

Conclusions

Our results demonstrate that combining an NKAB antibody with effector cells expressing an activating NKAR receptor represents a powerful and versatile approach to simultaneously enhance tumor antigen-specific as well as NKG2D-CAR and natural NKG2D-mediated cytotoxicity, which may be particularly useful to target tumors with heterogeneous target antigen expression.
Novel phosphatidylserine-binding molecule enhances antitumor T-cell responses by targeting immunosuppressive exosomes in human tumor microenvironments
Authors: Bhatta Maulasri , Shenoy Gautam N , Loyall Jenni L , Gray Brian D , Bapardekar Meghana , Conway Alexis , Minderman Hans , Kelleher Jr Raymond J , Carreno Beatriz M , Linette Gerald , Shultz Leonard D , Odunsi Kunle , Balu-Iyer Sathy V , Pak Koon Yan , Bankert Richard B
Published: October 2021

Background

The human tumor microenvironment (TME) is a complex and dynamic milieu of diverse acellular and cellular components, creating an immunosuppressive environment, which contributes to tumor progression. We have previously shown that phosphatidylserine (PS) expressed on the surface of exosomes isolated from human TMEs is causally linked to T-cell immunosuppression, representing a potential immunotherapeutic target. In this study, we investigated the effect of ExoBlock, a novel PS-binding molecule, on T-cell responses in the TME.

Methods

We designed and synthesized a new compound, (ZnDPA)6-DP-15K, a multivalent PS binder named ExoBlock. The PS-binding avidity of ExoBlock was tested using an in vitro competition assay. The ability of this molecule to reverse exosome-mediated immunosuppression in vitro was tested using human T-cell activation assays. The in vivo therapeutic efficacy of ExoBlock was then tested in two different human tumor xenograft models, the melanoma-based xenomimetic (X-)mouse model, and the ovarian tumor-based omental tumor xenograft (OTX) model.

Results

ExoBlock was able to bind PS with high avidity and was found to consistently and significantly block the immunosuppressive activity of human ovarian tumor and melanoma-associated exosomes in vitro. ExoBlock was also able to significantly enhance T cell-mediated tumor suppression in vivo in both the X-mouse and the OTX model. In the X-mouse model, ExoBlock suppressed tumor recurrence in a T cell-dependent manner. In the OTX model, ExoBlock treatment resulted in an increase in the number as well as function of CD4 and CD8 T cells in the TME, which was associated with a reduction in tumor burden and metastasis, as well as in the number of circulating PS+ exosomes in tumor-bearing mice.

Conclusion

Our results establish that targeting exosomal PS in TMEs with ExoBlock represents a promising strategy to enhance antitumor T-cell responses.