bluuebunny/crossref_metadata_2025 huggingface dataset:
Pneumatic Microextrusion-Based Additive Biofabrication of Polycaprolactone Bone Scaffolds: Part II – Investigation of the Influence of Polymer Flow Parameters
Authors: Yu Mohan , Lawrence Logan , Claudio Pier Paolo , Day James B. , Salary Roozbeh (Ross)
Published: August 2021

Pneumatic micro-extrusion (PME), a direct-write additive manufacturing process, has emerged as a high-resolution method for the fabrication of a broad range of biological tissues and organs. However, the PME process is intrinsically complex, governed by complex physical phenomena. Hence, investigation of the effects of consequential parameters would be an inevitable need. The goal of this research work is to fabricate biocompatible, porous bone tissue scaffolds for the treatment of osseous fractures, defects, and eventually diseases. In pursuit of this goal, the objective of this study is to investigate the influence of material deposition factors — i.e., (i) deposition head temperature, (ii) flow pressure, and (iii) infill pattern — on the mechanical performance of PME-fabricated bone scaffolds.

It was observed that the deposition head temperature as well as the flow pressure significantly affected scaffold diameter (unlike scaffold height). In addition, material deposition rate increased significantly as a result of an increase in the deposition temperature; this phenomenon stems from a reduction in Polycaprolactone (PCL) viscosity. Furthermore, there was a direct correlation between the amount of deposited mass and scaffold stiffness. Overall, the results of this study pave the way for future investigation of PME-deposited PCL scaffolds with optimal functional properties for incorporation of stem cells toward the treatment of osseous fractures and defects.
Characterization of Flow Curves for Ultra-Thin Steel Sheets With the In-Plane Torsion Test
Authors: Stiebert Fabian , Traphöner Heinrich , Meya Rickmer , Tekkaya A. Erman
Published: August 2021

The in-plane torsion test is a shear test that has already been successfully used to determine flow curves up to high strains for thin sheets with thicknesses between 0.5 mm and 3.0 mm. In the same way as with other shear tests, the formation of wrinkles is a major challenge in determining flow curves with the in-plane torsion test, especially when testing ultra-thin sheets with a thickness between 0.1 mm and 0.5 mm. A new method for suppressing wrinkling is introduced, in which the formation of wrinkles is avoided by arranging and gluing single sheets to multi-layered specimens. The influence of the used adhesive on the determination of flow curves is negligible. The proposed method is used to identify flow curves for two materials, the high strength steel TH620 and the soft steel TS230, used in the packaging industry. The Materials are tested in sheet thicknesses between 0.17 mm and 0.6 mm. The determined equivalent plastic strains for the TH620 with a sheet thickness of 0.20 mm, could be increased from 0.38 (bulge-test) to over 0.8 with the new method by using four-layered specimens.
Trajectory-Dependent Compensation Scheme to Reduce Manipulator Execution Errors for Manufacturing Applications
Authors: Bhatt Prahar M. , Malhan Rishi K. , Rajendran Pradeep , Shembekar Aniruddha V. , Gupta Satyandra K.
Published: August 2021

Robotic manipulators are increasingly being used for performing a wide variety of manufacturing processes. Some of the manufacturing processes performed using robotic manipulators require high trajectory execution accuracy. Automatically generated trajectories often exhibit significant execution errors due to robot model inaccuracies and controller behaviors. This suggests that a trajectory compensation scheme can be used to modify trajectory to reduce execution error. Unfortunately, the nature of the trajectory and the end-effector loading affect the trajectory tracking errors. So, the error reduction using a trajectory-independent automated compensation scheme does not always work. Our paper presents a method to sample the input trajectory, generate the training data by measuring the sampled trajectory execution, and learning the compensation scheme based on the physical run. The learned trajectory-dependent compensation scheme is capable of reducing the execution error. To demonstrate the compensation scheme’s effectiveness, we perform experiments on manipulators. After the trajectory compensation, the manipulator has considerably low trajectory execution errors, with the average path error close to the robot’s repeatability.
Deformation Analysis of 3D Printed Metacarpophalangeal and Interphalangeal Joints via Transfer Learning
Authors: Toscano Juan Diego , Hajifar Sahand , Segura Christian Oswaldo , Segura Luis Javier , Sun Hongyue
Published: August 2021

A cast/brace is a tight garment that restricts the movement and provides support to an injured zone. Traditional casts/braces suffer from material wastage, discomfort, patient dissatisfaction, odor, unnecessary weight, and dangerous extraction procedures. These issues can be solved partially by constructing the casts/braces via 3D printing. Toward this end, we print the personalized metacarpal casts/braces (MCB) via fused deposition modeling (FDM), and investigate their mechanical properties to ensure the desired functionality. However, printing the full-size MCB is time-consuming (takes more than 11 hours in our design), making it hard to collect a sufficient data set for the mechanical properties investigation. Here, we explore the utilization of reduced-size MCB to facilitate the analysis of full-size MCB via transfer learning. In particular, three critical process variables (i.e., raster width, layer height, and extrusion temperature) were varied, and a universal testing machine was used to measure the total deformation of the MCB. We then perform the prediction of the deformation in full-size MCB with transfer learning of data from reduced-size MCB and limited data from full-size MCB. From the case study, the transfer learning approach can reduce the needs of data collection in the time-consuming full-size MCB by leveraging the information from reduced-size MCB.
A FPGA-Based Cloud-Edge Collaboration Platform in Cloud Manufacturing
Authors: Xiao Chuan , Zhao Chun , Liu Yue , Zhang Lin
Published: August 2021

To address the issue that many devices are connected to the cloud during the manufacturing process, which causes severe delays in analyzing massive manufacturing data in the cloud, an FPGA-based architecture of cloud edge collaboration is proposed. In this architecture, manufacturing equipment is connected to the cloud through an FPGA-based embedded edge node. The device data obtained by the edge node is processed by the FPGA module and the embedded system module according to the time-sensitivity. Considering the limited computing power of a single edge node, to realize cloud-edge collaborative computing, a communication-oriented task model and a computing model for edge nodes are designed. The task model learns cloud to edge and edge-edge communication, and the task model realizes the function of migrating computing tasks to other nodes. The edge node system’s design is realized based on the communication-oriented task model and the computing model for edge nodes. The cloud edge collaboration method is researched and explored based on this system. A series of comparative experiments, comparing the time delay of the FPGA module and embedded system module processing the same data, the framework’s usability and data processing ability can be verified.
Conduction Heat Assisted Friction Element Welding
Authors: Grimm Tyler J. , Parvathy Gowtham V. , Mears Laine
Published: August 2021

Increasing awareness of global warming and strict government regulations have required the automotive industry to pursue lightweighting as an avenue towards increased vehicle efficiency. Lightweight designs typically rely heavily on multi-material use, which enables selective strengthening of critical areas without additional, unnecessary mass. Joining these materials during manufacturing has proven to be a challenging endeavor.

Friction element welding (FEW) is one process that is capable of joining aluminum to steel. This two-sided joining technique utilizes a fastener to secure the aluminum sheet by creating a friction weld with the steel sheet. While this process is extremely robust for most materials, the FEW process can result in the extrusion of material from underneath the head of the fastener, termed chipping, which leads to corrosion and aesthetic issues. This behavior is typically seen in high strength aluminum alloys, such as 7075. A solution to chipping is implemented herein, which utilizes a modified downholder to conductively heat the aluminum sheet prior to the FEW process. This heating method was explored experimentally and through various numerical analyses. This method was found to be a viable option for relieving chipping. While the process time was only increased by a maximum of 2.5 seconds, faster, more localized heating should be targeted for future work.
Experimental Study on the Effect of Surface Integrity on Fatigue Performance of Aero-Engine Blades
Authors: Huang Yun , Li Shaochuan , Xiao Guijian , Chen Benqiang , He Yi , Wang Wenxi , Zhou Kun
Published: August 2021

As the core component of aero-engine, the service performance of aero-engine blade has an important influence on the engine’s reliability and safety performance. Existing studies have shown that machined surface characteristics affect the fatigue strength of components. However, current studies are all based on regular fatigue samples. The structure of blades different from fatigue samples, and the influence mechanism of structural differences on the service performance of blades is still unclear. In addition, the conventional fatigue test conditions are not representative for the blades’ actual service conditions, so it is difficult to realize the processing process for the service performance optimization. In this study, the aero-engine blades processed by abrasive belt grinding and the vibration fatigue test bench were used to explore the influence of surface roughness, surface texture, and surface residual stress on the fatigue performance of aero-engine blades under actual working conditions. The aero-engine blades were ground with different process parameters to obtain different single-factor surface characteristics. By comparing the vibration fatigue life of blades with different surface features, the influence degree of each surface feature on the fatigue life was explored. Results showed that surface roughness has the greatest influence on fatigue strength, followed by residual stress, and surface texture has the least influence on fatigue strength.
Greenhouse Gas Emission Analysis of Integrated Production-Inventory-Transportation Supply Chain Enabled by Additive Manufacturing
Authors: Di Lei , Shah Gaurav Manish , Yang Yiran , Wei Cuicui
Published: August 2021

The manufacturing industry is a major source of greenhouse gas emissions (GHG). Additive manufacturing, owing to its multiple advantages, plays a critical role in innovating the current manufacturing industry, especially from a supply chain perspective. Currently, the majority of research on GHG emissions in the manufacturing industry is focused on traditional manufacturing, either single processes in the supply chain or specific case studies, indicating the lack of models on GHG emissions in additive manufacturing-enabled supply chain structures. In this work, a mathematical model is established to estimate the GHG emissions in both traditional manufacturing and additive manufacturing-enabled supply chains. To explore the advantages of additive manufacturing in terms of fast production and reduced or even eliminated the need for assembly and labor involvement, a unique integrated production-inventory-transportation structure is investigated in additive manufacturing case studies. The results indicate that a potential reduction of 26.43% of GHG emissions can be achieved by adopting the additive manufacturing technique in the supply chain. Also, the impacts of rush order rate, emission intensity, and vehicle GHG emission constant rate on the overall GHG emissions are investigated in the sensitivity analysis. Results indicate that a 20% variation in GHG emission intensity (the amount of CO2eq emissions caused by generating a unit of electricity) can lead to a 6.26% change in the total GHG emissions in additive manufacturing.
An OSGi-Based Adaptation Access of Machine Tools in the Cloud Manufacturing Environment
Authors: Li Xiaobin , Yin Chao
Published: August 2021

Machine tools (MTs) are the core manufacturing resources for discrete manufacturing enterprises. In the cloud manufacturing environment, MTs are massive, heterogeneous, widely dispersed and highly autonomous, which makes it difficult for cloud manufacturing mode to be deeply applied to support the networked collaboration operation among manufacturing enterprises. Realizing universal access and cloud application of various MTs is an essential prerequisite to solve the above problem. In this paper, an OSGi-based adaptation access method of MTs is proposed. First, the MTs information description model in the cloud manufacturing environment is built. Then, an OSGi-based adaptation access framework of MTs is constructed, and key enabling technologies, including machine tool information acquisition and processing, Bundle and Subsystem construction, are studied. Finally, an application case is conducted to verify the effectiveness and feasibility of the proposed method.
A Rheological Study of Bio-Ink: Shear Stress and Cell Viability
Authors: Habib Md Ahasan , Khoda Bashir
Published: August 2021

3D bio-printing is an emerging technology to fabricate tissue scaffold in-vitro through the controlled allocation of biomaterial and cell, which can mimic the in-vivo counterpart of living tissue. Live cells are often encapsulated into the biomaterials (i.e., bio-ink) and extruded by controlling the printing parameters. The functionality of the bioink depends upon three factors: (a) printability, (b) shape fidelity, and (c) bio-compatibility. Increasing viscosity will improve the printability and the shape fidelity; but will require higher applied extrusion pressure, which is detrimental to the living cell dwelling in the bio-ink, which is often ignored in bio-ink optimization process. In this paper, we demonstrate a roadmap to develop and characterize bio-inks ensuring the printability, shape fidelity, and cell survivability, simultaneously. The pressure exerted on the bio-ink during extrusion processes is measured analytically and the information is incorporated in the rheology design of the bio-ink. Cell-laden filament is fabricated with Human Embryonic Kidney (HEK 293) cell and analyzed the cell viability. The overall cell viability of the filament fabricated with 8 psi and 12 psi is 90% and 74% respectively. Additionally, a crossectional live-dead assay of the printed filament with HEK 293 cell is performed which demonstrates the spatial pattern that matches our findings as well.
Experimental Investigation of the Material Removal Rate in Grinding of Calcified Plaque by Rotational Atherectomy
Authors: Li Xinxiao , Chernjavsky Patrick , Angjeli Katerina , Hoffman Sola , Frunzi Sara , Zheng Yihao
Published: August 2021

Rotational atherectomy (RA) utilizes a high-speed, metal-bonded diamond-abrasive grinding wheel to remove the calcified atherosclerotic plaque inside arteries, restore blood flow, and treat cardiovascular diseases. RA operational guidelines have been clinically investigated to improve clinical outcomes and reduce complication rates, but are still in lack of consensus. Particularly, the effect of the grinding wheel rotational speed on plaque material removal rate (MRR) is unclear. This study experimentally investigates the RA MRR over a range of wheel rotational speeds based on a vascular simulator with a calcified plaque surrogate. The MRR, presented as the luminal area gain, with the increase of the number of grinding passes, was measured at the rotational speed of 120,000, 150,000, and 180,000 rpm. The luminal area was characterized via microscopy and image processing. The ground surface morphology and surface roughness at different rotational speeds were investigated. The results showed that a higher rotational speed led to a higher MRR and a smoother ground surface. This observation is significant for RA clinical guideline improvement.
Selective Laser Melting of Stainless Steel 316L for Mechanical Property-Gradation
Authors: Parikh Yash , Kuttolamadom Mathew
Published: August 2021

With an end goal of creating single-alloy functionally-graded additively manufactured (FGAM) parts, this paper investigates the manufacture and properties of stainless steel 316L samples via a pulsed selective laser melting (SLM) process. The focus is on elucidating the underlying causes of property variations (within a functionally-acceptable range) through material characterization and testing. Five samples (made via different volumetric energy density-based process parameter sets) were down-selected from preliminary experimental results and analyzed for their microstructure, mechanical and physical properties (hardness, density/porosity, Young’s modulus). It was observed that property variations resulted from combinations of porosity types/amounts, martensitic phase fractions, and grain sizes. Based on these, various functionally-graded specimens of different sizes were built as per ASTM standards, each having intended property changes along its gauge volumes. The presented findings establish that a methodical control of microstructure and mechanical properties could be obtained in a repeatable and reproducible manner by changing the process parameters. This work lays the foundation for understanding and tuning the global mechanical performance of FGAM bulk structures as well as the role of interfacial zones.
Nonadiabatic localization of H2 in the field of two external positive tip charges
Authors: Schattke W. , Van Hove M. A. , Díez Muiño R.
Published: August 2021

For two external spherical tips with equal positive charges, the ground state of a hydrogen molecule is variationally determined within the quantum Monte Carlo scheme. For finiteness, the system is enclosed in a spherical container with randomly reflecting unstructured walls. The 12-dimensional system of two protons and two electrons is investigated ab initio without any adiabatic restrictions. We focus on the hydrogen center of mass (COM) distribution in continuation of previous work on ground state and vibration modes at a COM that was fixed in space. Our general purpose is to control the molecule’s position and orientation by external means, such as by two charged tips. To this end, knowledge is needed in order to find specific COM regions with a desired molecular orientation in the container at significant probability density of the molecule.
Comments on “Influences of low-frequency energy and testing environment on annoyance responses to supersonic aircraft noise when heard indoors” [J. Acoust. Soc. Am. 148(1), 414–429 (2020)]
Authors: Vos Joos
Published: August 2021

Carr, Davies, Loubeau, Rathsam, and Klos [J. Acoust. Soc. Am. 148, 414–429 (2020)] found that indoor annoyance caused by sonic booms may be predicted from the A-weighted sound exposure level and the heaviness of the booms. Moreover, they suggest that, irrespective of the outdoor-to-indoor sound reduction, indoor annoyance may be predicted from outdoor sound levels. The present paper shows that their data to some extent also support a model in which the contribution of heaviness is level-dependent and that data reported in the literature point out that it is unlikely that indoor annoyance is independent of the degree of façade attenuation.
Spherical harmonic decomposition of a sound field based on observations along the equator of a rigid spherical scatterer
Authors: Ahrens Jens , Helmholz Hannes , Alon David Lou , Amengual Garí Sebastià V.
Published: August 2021

We present a method for computing a spherical harmonic representation of a sound field based on observations of the sound pressure along the equator of a rigid spherical scatterer. Our proposed solution assumes that the captured sound field is height invariant so that it can be represented by a two-dimensional (2D) plane wave decomposition (PWD). The 2D PWD is embedded in a three-dimensional representation of the sound field, which allows for perfectly undoing the effect of the spherical scattering object. If the assumption of height invariance is fulfilled, then the proposed solution is at least as accurate as a conventional spherical microphone array of the same spherical harmonic order, which requires a multiple of the number of sensors. Our targeted application is binaural rendering of the captured sound field. We demonstrate by analyzing the binaural output signals that violations of the assumptions that the solution is based on—particularly height invariance and consequently also horizontal propagation—lead to errors of moderate magnitude.
Diffuse energy transport and coda-wave interferometry for resonant transmission between reverberant structures
Authors: Weaver Richard L. , Lee SangMin
Published: August 2021

Approximate analytic and numerical theories are developed with which to model, and compare with laboratory measurements, the diffuse ultrasonic field transmitted from one elastic body to another through a resonant coupling. Particular focus is on the sensitivity of the transmitted field to perturbations in the natural frequency of the coupling and the manifestation of such perturbations as time delays in the second body. The immediate application is to measurements of slow dynamic elastic nonlinearity. It is found that the developed approximate theories do a good job of predicting the time dependence of the mean square transmitted signal and signal spectra. They also predict the time delays, both their erratic character and means. Analytic dependence of these time shifts on the fractional frequency perturbation df/f is derived.
Effect of acoustically-induced elastic softening on sound absorption coefficient of hollow glass beads with inner closed cavities
Authors: Tsuruha Takumasa , Otani Makoto , Takano Yasushi
Published: August 2021

This study investigated the effects of sound wave magnitude on the sound absorption characteristics of granular materials. The normal incidence sound absorption coefficients of the hollow glass bead packings were measured with different incident sound pressure levels. The measurement results exhibited spectral peaks of sound absorption coefficients at several frequencies, implying that the first peak was caused by the resonance of the hollow glass beads as a layer. Although the first peak in the sound absorption coefficients did not vary when an incident sound pressure was low, the first peak shifted to a lower frequency when the sound pressure exceeded a certain magnitude. These results indicate that the hollow glass beads are softened at high incident sound pressures. Furthermore, by modelling the velocity-dependent elasticity of the hollow glass beads, the velocity and elasticity in the hollow glass beads were simulated in the direction of the sound propagation. The simulation results indicate that the velocity and elasticity profiles depend on the sound wave magnitude. Finally, the velocities of the hollow glass beads under acoustic excitation were measured by inserting an accelerometer into the beads. The measurement results demonstrated that the velocity profile depends on the sound wave magnitude, which parallels the simulation results.
Unfolded protein response inhibitors cure group A streptococcal necrotizing fasciitis by modulating host asparagine
Authors: Anand Aparna , Sharma Abhinay , Ravins Miriam , Biswas Debabrata , Ambalavanan Poornima , Lim Kimberly Xuan Zhen , Tan Rachel Ying Min , Johri Atul Kumar , Tirosh Boaz , Hanski Emanuel
Published: August 2021

Inhibiting the formation and release of host asparagine cures invasive group A streptococcal infections in mice.
Dual targeting of CTLA-4 and CD47 on T
reg
cells promotes immunity against solid tumors
Authors: Zhang Anli , Ren Zhenhua , Tseng Kuo-Fu , Liu Xiaojuan , Li Huiyu , Lu Changzheng , Cai Yueqi , Minna John D. , Fu Yang-Xin
Published: August 2021

Selective CD47 blockade on CTLA-4
high
tumor-infiltrating T
reg
cells reduces systemic toxicity and enhances antitumor immunity.
Microbial Metal Resistance within Structured Environments Is Inversely Related to Environmental Pore Size
Authors: Harvey Harry J. , Mitzakoff Anna M. T. , Wildman Ricky D. , Mooney Sacha J. , Avery Simon V.
Published: August 2021

Interactions between cells and their structured environments are poorly understood but have significant implications for organismal success in both natural and nonnatural settings. This work used a multidisciplinary approach to develop laboratory models with which the influence of a key parameter of environmental structure—pore size—on cell activities can be dissected.
Competition between Ammonia-Oxidizing Archaea and Bacteria from Freshwater Environments
Authors: French Elizabeth , Kozlowski Jessica A. , Bollmann Annette
Published: August 2021

Nitrification is an important process in the global nitrogen cycle. The first step, ammonia oxidation to nitrite, can be carried out by ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB).
The Monod Model Is Insufficient To Explain Biomass Growth in Nitrogen-Limited Yeast Fermentation
Authors: Henriques David , Balsa-Canto Eva
Published: August 2021

Problematic fermentations still occur in the winemaking industrial practice. Problems include low rates of fermentation, which have been linked to insufficient levels of assimilable nitrogen.
Direct Evidence for Deterministic Assembly of Bacterial Communities in Full-Scale Municipal Wastewater Treatment Facilities
Authors: Kim Taegyu , Behrens Sebastian , LaPara Timothy M.
Published: August 2021

Understanding the mechanisms of bacterial community assembly is one of the grand challenges of microbial ecology. In environmental systems, this challenge is exacerbated because replicate experiments are typically impossible; that is, microbial ecologists cannot fabricate multiple field-scale experiments of identical, natural ecosystems.
Periphytic Microbial Response to Environmental Phosphate (P) Bioavailability and Its Relevance to P Management in Paddy Fields
Authors: Zhang Jianchao , Su Jing , Ma Chao , Hu Xiangyu , Teng Henry H.
Published: August 2021

The ability of periphyton to buffer environmental P in shallow aquatic ecosystems may be a natural lesson on P utilization and retention in paddy fields. This work revealed the routes and tools through which periphytic organisms adapt to and regulate ambient P fluctuation.
A Real-World Comparison of SARS-CoV-2 Rapid Antigen Testing versus PCR Testing in Florida
Authors: Allan-Blitz Lao-Tzu , Klausner Jeffrey D.
Published: August 2021

The reported sensitivity of rapid, antigen-based diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection varies. Few studies have evaluated rapid antigen tests in real-world settings or among large populations.
Marburg and Ebola Virus mRNA 3′ Untranslated Regions Contain Negative Regulators of Translation That Are Modulated by ADAR1 Editing
Authors: Khadka Sudip , Williams Caroline G. , Sweeney-Gibbons Joyce , Basler Christopher F.
Published: August 2021

UTRs comprise a large percentage of filovirus genomes and are apparent targets of editing by ADAR1, an enzyme with pro- and antiviral activities. However, the functional significance of the UTRs and ADAR1 editing has been uncertain.
Progression of SARS-CoV-2 Seroprevalence in St. Louis, Missouri, through January 2021
Authors: Smith Brittany K. , Janowski Andrew B. , Fremont Arim C. , Adams Lucas J. , Dai Ya-Nan , Farnsworth Christopher W. , Gronowski Ann M. , Roper Stephen M. , Wang David , Fremont Daved H.
Published: August 2021

This study determined the percentage of children and adult samples from the St. Louis metropolitan area in Missouri with SARS-CoV-2 antibodies during three collection periods spanning April 2020 to January 2021. By January 2021, 20.68% of the tested individuals had antibodies. These results show the evolution of the SARS-CoV-2 pandemic in St. Louis, Missouri, and provide a snapshot of the extent of infection just prior to the start of mass vaccination.
Recovery and Its Dynamics of Filamentous Fungi from Clinical Specimen Cultures: An Extensive Study
Authors: Bao Jian R. , Master Ronald N. , Jones Robert S. , Clark Richard B. , Moore Elizabeth C. , Shier Kileen L.
Published: August 2021

Fungal culture is the gold standard method of diagnosing fungal infections, but important information, such as the impact of media and incubation times on fungal recovery, is not well documented. This study addressed these gaps using extensive data-based evaluation focused on molds.
Predicting hospital admissions from individual patient data (IPD): an applied example to explore key elements driving external validity
Authors: Meid Andreas Daniel , Gonzalez-Gonzalez Ana Isabel , Dinh Truc Sophia , Blom Jeanet , van den Akker Marjan , Elders Petra , Thiem Ulrich , Küllenberg de Gaudry Daniela , Swart Karin M A , Rudolf Henrik , Bosch-Lenders Donna , Trampisch Hans J , Meerpohl Joerg J , Gerlach Ferdinand M , Flaig Benno , Kom Ghainsom , Snell Kym I E , Perera Rafael , Haefeli Walter Emil , Glasziou Paul , Muth Christiane
Published: August 2021

Objective

To explore factors that potentially impact external validation performance while developing and validating a prognostic model for hospital admissions (HAs) in complex older general practice patients.

Study design and setting

Using individual participant data from four cluster-randomised trials conducted in the Netherlands and Germany, we used logistic regression to develop a prognostic model to predict all-cause HAs within a 6-month follow-up period. A stratified intercept was used to account for heterogeneity in baseline risk between the studies. The model was validated both internally and by using internal-external cross-validation (IECV).

Results

Prior HAs, physical components of the health-related quality of life comorbidity index, and medication-related variables were used in the final model. While achieving moderate discriminatory performance, internal bootstrap validation revealed a pronounced risk of overfitting. The results of the IECV, in which calibration was highly variable even after accounting for between-study heterogeneity, agreed with this finding. Heterogeneity was equally reflected in differing baseline risk, predictor effects and absolute risk predictions.

Conclusions

Predictor effect heterogeneity and differing baseline risk can explain the limited external performance of HA prediction models. With such drivers known, model adjustments in external validation settings (eg, intercept recalibration, complete updating) can be applied more purposefully.

Trial registration number

PROSPERO id: CRD42018088129.
Root causes and preventability of emergency department presentations of older patients: a prospective observational study
Authors: Driesen Babiche , Merten Hanneke , Barendregt Rosalie , Bonjer H Jaap , Wagner Cordula , Nanayakkara Prabath W B
Published: August 2021

Objective

More older patients are presenting to the emergency department (ED). It is important to know why these patients present and if the ED is the best place for them to receive the care they need. The primary aim of this study was to identify organisational-related, technical-related, healthcare worker-related and patient-related factors leading to ED presentations of older patients. The secondary aim was to determine patients’ and caregivers’ perspectives on what kinds of ED presentations are potentially preventable.

Design

This is a prospective observational study. A root cause analysis was performed by the Prevention and Recovery Information System for Monitoring and Analysis method. It used basic administrative data collected from patient records and interviews of patients, general practitioners (GPs) and physicians at the ED.

Setting

The ED of an academic hospital in the Netherlands.

Participants

100 older patients (aged ≥70 years) who attended the ED between November 2017 and March 2018.

Results

In 100 patients presenting to the ED, 159 factors that contributed to presentation were identified; most of these factors were related to underlying diseases (59%) and patient-related factors (18%). These presentations were considered potentially preventable by 23% of the physicians at the ED and 21% of the GPs, but only 10% of the patients. In only four cases was there overall agreement between the patients and the healthcare workers.

Conclusion

The most frequent underlying factors contributing to an ED presentation in older patients are disease-related and patient-related. The low percentage of ED presentations considered potentially preventable shows that a ‘preventable ED presentation’ is difficult to define and therefore interventions to reduce them are unlikely to be simple. Novel solutions within the acute care pathway are required in order to deliver care of optimal quality and safety to older patients.
Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications
Authors: Saracino Dario , Dorgham Karim , Camuzat Agnès , Rinaldi Daisy , Rametti-Lacroux Armelle , Houot Marion , Clot Fabienne , Martin-Hardy Philippe , Jornea Ludmila , Azuar Carole , Migliaccio Raffaella , Pasquier Florence , Couratier Philippe , Auriacombe Sophie , Sauvée Mathilde , Boutoleau-Bretonnière Claire , Pariente Jérémie , Didic Mira , Hannequin Didier , Wallon David ,   the French Research Network on FTD/FTD-ALS,   the PREV-DEMALS and Predict-PGRN study groups, Colliot Olivier , Dubois Bruno , Brice Alexis , Levy Richard , Forlani Sylvie , Le Ber Isabelle
Published: August 2021

Objective

Neurofilament light chain (NfL) is a promising biomarker in genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated plasma neurofilament light chain (pNfL) levels in controls, and their longitudinal trajectories in C9orf72 and GRN cohorts from presymptomatic to clinical stages.

Methods

We analysed pNfL using Single Molecule Array (SiMoA) in 668 samples (352 baseline and 316 follow-up) of C9orf72 and GRN patients, presymptomatic carriers (PS) and controls aged between 21 and 83. They were longitudinally evaluated over a period of >2 years, during which four PS became prodromal/symptomatic. Associations between pNfL and clinical–genetic variables, and longitudinal NfL changes, were investigated using generalised and linear mixed-effects models. Optimal cut-offs were determined using the Youden Index.

Results

pNfL levels increased with age in controls, from ~5 to~18 pg/mL (p<0.0001), progressing over time (mean annualised rate of change (ARC): +3.9%/year, p<0.0001). Patients displayed higher levels and greater longitudinal progression (ARC: +26.7%, p<0.0001), with gene-specific trajectories. GRN patients had higher levels than C9orf72 (86.21 vs 39.49 pg/mL, p=0.014), and greater progression rates (ARC:+29.3% vs +24.7%; p=0.016). In C9orf72 patients, levels were associated with the phenotype (ALS: 71.76 pg/mL, FTD: 37.16, psychiatric: 15.3; p=0.003) and remarkably lower in slowly progressive patients (24.11, ARC: +2.5%; p=0.05). Mean ARC was +3.2% in PS and +7.3% in prodromal carriers. We proposed gene-specific cut-offs differentiating patients from controls by decades.

Conclusions

This study highlights the importance of gene-specific and age-specific references for clinical and therapeutic trials in genetic FTD/ALS. It supports the usefulness of repeating pNfL measurements and considering ARC as a prognostic marker of disease progression.

Trial registration numbers

NCT02590276 and NCT04014673.
Social determinants of health and slippery slopes in assisted dying debates: lessons from Canada
Authors: Downie Jocelyn , Schuklenk Udo
Published: August 2021

The question of whether problems with the social determinants of health that might impact decision-making justify denying eligibility for assisted dying has recently come to the fore in debates about the legalisation of assisted dying. For example, it was central to critiques of the 2021 amendments made to Canada’s assisted dying law. The question of whether changes to a country’s assisted dying legislation lead to descents down slippery slopes has also come to the fore—as it does any time a jurisdiction changes its laws. We explore these two questions through the lens of Canada’s experience both to inform Canada’s ongoing discussions and because other countries will confront the same questions if they contemplate changing their assisted dying law. Canada’s Medical Assistance in Dying (MAiD) law has evolved through a journey from the courts to Parliament, back to the courts, and then back to Parliament. Along this journey the eligibility criteria, the procedural safeguards, and the monitoring regime have changed. In this article, we focus on the eligibility criteria. First, we explain the evolution of the law and what the eligibility criteria were at the various stops along the way. We then explore the ethical justifications for Canada’s new criteria by looking at two elements of the often-corrosive debate. First, we ask whether problems with the social determinants of health that might impact decision-making justify denying eligibility for assisted dying of decisionally capable people with mental illnesses and people with disabilities as their sole underlying medical conditions. Second, we ask whether Canada’s journey supports slippery slope arguments against permitting assisted dying.
Claimed by culture: circumcision, cochlear implants and the ‘intact’ body
Authors: Söderfeldt Ylva
Published: August 2021

This review essay discusses the debates on infant male circumcision and on paediatric cochlear implants, two instances of surgical interventions done on small children without there being any pressing life-threatening indication. Reviewing these two issues together—something that has not previously been done, although there is a vast scholarly debate on both issues separately—helps frame the medical humanities and the current turn in the field towards abandoning the nature/culture and science/humanities divides. The debates on these procedures are fraught with a distinction between medicine and culture which constructs a certain kind of body as ‘natural’ and seeks to defend that body against ‘cultural’ interventions while welcoming supposedly acultural ‘medical’ interventions on other bodies. In the scholarship in medical humanities and medical ethics on these topics, this implicit nature/culture divide and view on medicine as separate from culture is also evident. My contention is that the medical humanities have important work to do here, in particular regarding a critique of the notion of the ‘whole’ or ‘intact’ body.
Classification of the mechanisms by which cardiotoxic plant poisons exert their effects
Authors: Huntington George
Published: August 2021

Episodes of poisoning due to plant-based toxins are an unusual presentation to the emergency department. Plant poisons may be ingested if the source plant is misidentified as benign (eg, Lily of the Valley being mistaken for wild garlic and water hemlock being mistaken for wild celery), or taken as part of a complementary medicine regime or otherwise for psychotropic effect. Numerous plant poisons demonstrate cardiotoxic effects resulting from action against cardiac myocyte ion channels, or other cardiac receptor targets. These mechanisms will produce stereotyped symptoms and including electrocardiogram (ECG) changes dependent on which ion channels or receptors are targeted. These mechanisms are stereotyped and may be grouped by toxidromic effect. This article proposes a novel classification of cardiotoxic plant poisons based on these actions. Given that these mechanisms mirror the Vaughan Williams classification used to categorise therapeutic antiarrhythmic agents, it is felt that this will serve as a mnemonic and diagnostic aid in clinical situations of cardiotoxic plant ingestion.
Sympathetic vasoconstriction in skeletal muscle: modulatory effects of aging, exercise training, and sex
Authors: DeLorey Darren S.
Published: August 2021

The sympathetic nervous system (SNS) is a critically important regulator of the cardiovascular system. The SNS controls cardiac output and its distribution, as well as peripheral vascular resistance and blood pressure at rest and during exercise. Aging is associated with increased blood pressure and decreased skeletal muscle blood flow at rest and in response to exercise. The mechanisms responsible for the blunted skeletal muscle blood flow response to dynamic exercise with aging have not been fully elucidated; however, increased muscle sympathetic nerve activity (MSNA), elevated vascular resistance, and a decline in endothelium-dependent vasodilation are commonly reported in older adults. In contrast to aging, exercise training has been shown to reduce blood pressure and enhance skeletal muscle vascular function. Exercise training has been shown to enhance nitric oxide-dependent vascular function and may improve the vasodilatory capacity of the skeletal muscle vasculature; however, surprisingly little is known about the effect of exercise training on the neural control of circulation. The control of blood pressure and skeletal muscle blood flow also differs between men and women. Blood pressure and MSNA appear to be lower in young women than in men. However, females experience a larger increase in MSNA with aging compared with males. The mechanism(s) underlying the altered SNS control of vascular function in females remains to be determined.

Novelty: This review summarizes our current understanding of the effects of aging, exercise training, and sex on sympathetic vasoconstriction at rest and during exercise. Areas where additional research is needed are also identified.
Differences between predicted outer membrane proteins of Pasteurella multocida, Histophilus somni, and genotype 1 and 2 Mannheimia haemolytica strains isolated from cattle
Authors: Wynn Emily L. , Clawson Michael L.
Published: August 2021

Common bacterial causes of bovine respiratory disease (BRD) include Histophilus somni, Mannheimia haemolytica, and Pasteurella multocida. Within M. haemolytica, two major genotypes are commonly found in cattle (1 and 2); however, genotype 2 strains are isolated from diseased lungs much more frequently than genotype 1 strains. Outer membrane proteins (OMPs) of H. somni, P. multocida, and genotype 2 M. haemolytica may be important factors for acquired host immunity. The predicted OMP differences between genotypes 1 and 2 M. haemolytica have been previously identified. In this study, we expanded the focus to include bovine-isolated strain genomes representing all three species and the two M. haemolytica genotypes. Reported here are the core genomes unique to each of them, core genomes shared between some or all combinations of the three species and two M. haemolytica genotypes, and predicted OMPs within these core genomes. The OMPs identified in this study are potential candidates for further studies and the development of interventions against BRD.
Charting closed-loop collective cultural decisions: from book best sellers and music downloads to Twitter hashtags and Reddit comments
Authors: Schneider Lukas , Scholten Johannes , Sándor Bulcsú , Gros Claudius
Published: August 2021

Charts are used to measure relative success for a large variety of cultural items. Traditional music charts have been shown to follow self-organizing principles with regard to the distribution of item lifetimes, the on-chart residence times. Here we examine if this observation holds also for (a) music streaming charts (b) book best-seller lists and (c) for social network activity charts, such as Twitter hashtags and the number of comments Reddit postings receive. We find that charts based on the active production of items, like commenting, are more likely to be influenced by external factors, in particular by the 24 h day–night cycle. External factors are less important for consumption-based charts (sales, downloads), which can be explained by a generic theory of decision-making. In this view, humans aim to optimize the information content of the internal representation of the outside world, which is logarithmically compressed. Further support for information maximization is argued to arise from the comparison of hourly, daily and weekly charts, which allow to gauge the importance of decision times with respect to the chart compilation period.
Constraining the anisotropy of the Universe with the X-ray and UV fluxes of quasars
Authors: Zhao Dong , Xia Jun-Qing
Published: August 2021

We test the anisotropy in the Finslerian cosmological model with the X-ray and ultraviolet (UV) fluxes of quasars. The 2015 and 2020 compilations of quasars are used in the cosmological constraints. We find that the dipole direction given by the 2015 quasar compilation is not far away from the one provided by the Pantheon sample and the angular differences are around $$30^{\circ }$$

30
∘

. The Pantheon sample is combined with quasars as the “standardized candles” to test the cosmic anisotropy. The results from two combined datasets are consistent. They show that the dipole anisotropy is weak in the Finslerian cosmological model. We investigate the Hubble constant $$H_0$$

H
0

in the Finslerian cosmological model. Though the central value of $$H_0$$

H
0

from the combination of six gravitationally lensed quasars, Pantheon sample, and 2020 quasar compilation decreases a little bit, it is consistent with the result from six gravitationally lensed quasars within statistical uncertainties.
Study the $$B^{0}_{(s)}$$ decays into $$\phi $$ and a scalar or vector meson
Authors: Ahmed Hiwa A. , Wang Zhong-Yu , Sun Zhi-Feng , Xiao C. W.
Published: August 2021

In the present work, we investigate the decays of $$B^{0}_{(s)} \rightarrow \phi \pi ^{+}\pi ^{-}$$

B

(
s
)

0

→
ϕ

π
+

π
-

with the final state interaction based on the chiral unitary approach. In the final state interaction of the $$\pi ^+\pi ^-$$

π
+

π
-

with its coupled channels, we study the effects of the $$\eta \eta $$

η
η

channel in the two-body interaction for the reproduction of the $$f_{0}(980)$$

f
0

(
980
)

state, where its contribution to the $$f_{0}(980)$$

f
0

(
980
)

state can be ignored. Our results for the $$\pi ^+\pi ^-$$

π
+

π
-

invariant mass distributions of the decay $$B^{0}_{s} \rightarrow \phi \pi ^{+}\pi ^{-}$$

B
s
0

→
ϕ

π
+

π
-

describe the experimental data up to 1 GeV well, with the resonance contributions from the $$f_{0}(980)$$

f
0

(
980
)

and $$\rho $$
ρ
. For the predicted invariant mass distributions of the $$B^{0} \rightarrow \phi \pi ^{+}\pi ^{-}$$

B
0

→
ϕ

π
+

π
-

decay, we find that the contributions from the $$f_{0}(500)$$

f
0

(
500
)

are significant, but not from the $$f_{0}(980)$$

f
0

(
980
)

state. With some experimental branching ratios to determine the production vertex factors, we make predictions for the branching ratios of the other decay channels, including the vector mesons, in the $$B^0_{(s)}$$

B

(
s
)

0

decays, some of which are consistent with the experimental measurements within the uncertainties.