bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical Control-Centric Modeling for Precision Model-Based Sliding Mode Control of a Hydraulic Artificial Muscle Actuator
Authors: Slightam Jonathon E. , Nagurka Mark L.
Published: January 2021

Artificial muscles (AMs) traditionally rely on pneumatic sources of fluid power. The use of hydraulics can increase the power and force to weight and volume ratios of AM actuators. This paper develops a control-centric third-order single-input single-output (SISO) lumped-parameter dynamic model and sliding mode position controller based on Filippov's principle of equivalent dynamics for a braided hydraulic artificial muscle (HAM) actuator. The model predicts the nonlinear behavior of the HAM free contraction and captures the fluid and actuator nonlinear dynamic interactions in addition to the braid deformation. Model simulations are compared to experimental results for quasi-static pressurization, isometric pressurization, and open-loop square wave commands at 0.25, 0.5, and 1 Hz. Experiments of sine wave tracking at 0.25, 0.5, and 1 Hz and continuous square wave tracking at 0.067 Hz are conducted using a sliding mode controller (SMC) derived from the model. The SMC achieves a steady-state error of 6 μm at multiple setpoints within the actuator's 17 mm stroke. Compared to a proportional-integral-derivative (PID) controller, the SMC root-mean-square (RMS) error, mean error, and absolute maximum error are reduced on average by 53%, 61%, and 44%, respectively, demonstrating the benefit of model-based approaches for controlling HAMs.
Influences of Small Jet-to-Wall Spacings on Heat Transfer Characteristics and Flow-Field Entrainment Effects of Microscale Jets
Authors: Subrahmanyam Prabhakar , Gnanavel B. K.
Published: January 2021

Detailed heat transfer distributions of multiple microscaled tapered jets orthogonally impinging on the surface of a high-power density silicon wall is presented. The tapered jets issued from two different impingement setup are studied—(a) single circular nozzle and (b) dual circular nozzles. Jets are issued from the inlet(s) at four different Reynolds numbers {Re = 8000, 12,000, 16,000, 20,000}. The spacing between the tapered nozzle jets and the bare die silicon wall (z/d) is adjusted to be 4, 8, 12, and 16 jet nozzle diameters away from impinging influence. The impact of varying the nozzle to the silicon wall (z/d) standoff spacing up to 16 nozzle jet diameters and its effects on flow fields on the surface of the silicon, specifically the entrainment pattern on the silicon surface, is presented. Heat transfer characteristics of impinging jets on the hot silicon wall is investigated by means of large eddy simulations (LES) at a Reynolds of 20,000 on each of the four z/d spacing and compared against its equivalent Reynolds-averaged Navier–Stokes (RANS) cases. Highest heat transfer coefficients are obtained for the dual inlet system. A demarcation boundary region connecting all the microvortices between impinging jets is prominently visible at smaller z/d spacing—the region where the target silicon wall is within the sphere of influence of the potential core of the jet. This research focuses on the underlying physics of multiple tapered nozzles jet impingement issued from single and dual nozzles and its impact on turbulence, heat transfer distributions, entrainment, and other pertinent flow-field characteristics.
Effect of Stress-Sensitive Permeability and Porosity on Production Performance in Water-Soluble Gas Reservoirs
Authors: Huang Xiaoliang , Qi Zhilin , Zhang Hao , Yan Wende , Yan Chang , Li Sainan , Li Jiqiang
Published: January 2021

Water-soluble gas reservoirs have the characteristics of high temperature and high pressure (HTHP) and experience obvious pressure-sensitive effects during the production process. Therefore, the influences of formation water and dissolved natural gas in formation water on water-soluble gas reservoirs are different from conventional gas reservoirs. In view of this, this work first carried out a stress sensitivity test with irreducible water and variable internal pressure at high temperature for a water-soluble gas reservoir, showing that permeability loss ratio and effective stress have an exponential relationship, a result basically consistent with conventional tests. However, the stress sensitivity test result with irreducible water was greater than the stress sensitivity test result without irreducible water; porosity decreased slightly with increasing confining pressure, and the total decrease ratio was less than 5.2%, with an average of 3.01%. Second, a high-pressure, high-temperature, nuclear magnetic resonance (NMR) online detection system was introduced to detect the pore signal of core samples under different effective stress states, and pore compression and deformation characteristics were evaluated. Results show large pores to have been compressed slightly more than small pores, pores to be significantly compressed in the initial stage, and the greater the increase in effective stress, the more obvious the compression. Third, the occurrence and characteristic changes of irreducible water in the process of rock compression were detected by the NMR online system, indicating irreducible water to be difficult to migrate through compression in water-soluble gas reservoirs under slight compression of rock and pore structure and the occurrence and characteristics of irreducible water to have not changed significantly. Finally, by establishing a theoretical model of water-soluble gas reservoirs to simulate the water breakthrough of gas wells under stress sensitivity conditions, this work shows that when stress sensitivity exists, gas-well water breakthrough time is earlier and production is diminished.
Development and Optimization of a Tribometer for Radial Shaft Seals
Authors: Burkhart Christoph , Weyrich Dominik , Thielen Stefan , Schollmayer Tim , Sauer Bernd
Published: January 2021

In order to systematically investigate the tribological behavior of machine elements, several different tribometers based on simplifications of the contact situation have been developed and used successfully in the past. Many of these tribometers have become a standard testing equipment for tribologists. For the contact of radial shaft seals (RSSs), currently no such tribometer exists that can be used to characterize their behavior in a satisfying manner. In this paper, a tribologically equivalent system for RSSs is presented. The contact between the sealing lip and shaft is reproduced using a ring-shaped sample prepared from elastomer test slabs of the respective application material in contact with a conical shaft. The cone angle is chosen to properly represent the contact angles of the RSS under investigation by means of finite element (FE)-simulation of the contact pressure. The test rig allows for the on-line determination of friction, contact temperature, and wear progress. Results show good agreement of friction coefficient and wear behavior for the pairing of two typical elastomers with synthetic and mineral-based lubricants.
Effect of Differential Hardness on Static Load Capacity of AISI 52100 Bearing Steel
Authors: Shareef Iqbal , Brandes Joshua A. , Zaretsky Erwin V.
Published: January 2021

Static Load Capacity as defined by Palmgren is the load (stress) applied to a bearing that results in an indentation greater than 0.0001 times the diameter of the rolling element. The effect of hardness on the Static Load Capacity of AISI 52100 bearing steel heat treated to six different hardnesses was investigated. Indentation, depth, diameter, volume, and surface area were measured by the white light interferometer. A total of 468 hardness ball–plate combination tests were conducted. For a given plate (race) hardness, the Static Load Capacity was dependent on plate (race) hardness and independent of mating ball hardness from Rockwell C 56 to 66. For plate (race) hardness between Rockwell C 56 and 60, the Static Load Capacity was relatively constant. At Rockwell C hardness between 60 and 61, the Static Load Capacity increased and then rapidly decreased at a plate hardness of Rockwell C 66, below that value obtained at Rockwell C 56. Experimental results obtained for Static Load Capacity using the Palmgren criteria correlated with the finite element analysis for ball-on-plate indentation but not with Hertz theory. The Static Load Capacity based on Yhland for ball bearings was equal to a maximum Hertz stress of 3.71 GPa (538 ksi) at a ball-race conformity of 52%. This value is 12% lower than that specified in the ISO and ANSI/ABMA Bearing Standards. The manufacturers’ Static Load Rating can be reduced from 4% to 7% for ball bearings and from 8% to 25% for roller bearings.
Nanosilica-Based Loss Circulation Composition to Cure Moderate to Severe Losses
Authors: Wagle Vikrant , Kalgaonkar Rajendra , AlYami Abdullah , AlKhalaf Sara
Published: January 2021

The loss circulation composition comprising a combination of a nanoparticle-based dispersion and a chemical activator has been designed to treat moderate to severe losses. The nanomaterial used is an environmentally friendly nanosilica-based dispersion. The composition is designed to give delayed gelling of the nanoparticle-based dispersion. A major advantage of this technology is its ability to place the composition into the target loss circulation zone before the nanoparticle-based dispersion gels up. Premature gelling of the nanoparticle-based dispersion would avoid premature setting of the treatment fluid before it reaches the target zone. The newly developed system can be used effectively up to 300 °F. In this paper, experiments have been performed with three different types of nanoparticles differing in their surface charges and particle sizes. Two negatively charged nanoparticle-based dispersions with a particle size of 5 nm and 17 nm, respectively, and one positively charged nanoparticle-based dispersion with a particle size greater than 17 nm have been evaluated as loss circulation materials. Two different types of chemical activators, one organic and the other inorganic, have been used in this study, and their effect on the gelling time has been evaluated. The gelling time experiments have been done at four different temperatures viz. 150 °F, 200 °F, 250 °F, and 300 °F. The effect of activator concentration and different shear rates on the gelling time of the three nanoparticle-based dispersions has been studied. Permeability plugging tests have been performed using 2 mm slotted disks to evaluate the effectiveness in controlling moderate to severe losses.
Mass Transfer Performance of a Marine Zooplankton Olfactometer
Authors: Alkhafaji Ahmed A. , Selim Osama M. , Amano Ryoichi S. , Strickler J. R. , Hinow P. , Jiang Houshuo , Sikkel Paul C. , Kohls N.
Published: January 2021

By adopting different methods to the inlet of a zooplankton olfactometer, the current study investigates the effect of the energy of chemical flow on the Gnathiid isopod crustaceans predicted behavior. These are mobile external parasites of fishes that have a significant impact on the health of their hosts. They rely at least in part on olfactory cues to find the host fish. To better understand host-finding dynamics in these parasites, a study was conducted with the simulations as a blueprint for developing a 3-dimensional test apparatus similar to what has been used for studying olfactory orientation in insects. The simulated olfactometer has four legs, each leg forming an inlet where fluids are introduced into the flow domain. There is one outlet at the center of the device. A mixture of water and chemicals is presented by applying a multi-component system. The shear and chemical concentration distribution were conducted to see how fluid physics plays a role in creating a chemical landscape. Computational results show distinct regions separated by high chemical concentration gradients when introducing chemicals from one leg. Changing the fluid inflow from one common inlet to three inlets shows that the chemical distribution exhibits steeper gradients than the typical inlet case, depicting that the gradual chemical concentrations can drive the animal toward the target faster. The best behavior that gives higher chemical gradients is obtained through the study when using three sub-inlets and Schmidt number between 3 and 10.
Investigation of the Factors Influencing the Flowback Ratio in Shale Gas Reservoirs: A Study Based on Experimental Observations and Numerical Simulations
Authors: Hun Lin , Xiang Zhou , Yulong Chen , Bing Yang , Xixiang Song , Xinyi Sun , Lifei Dong
Published: January 2021

The flowback behavior of hydraulic fractured horizontal well in shale gas reservoir is relatively different from that of conventional reservoirs. Therefore, it is necessary to investigate the relationship between the potential influencing factors and the flowback behavior in shale gas reservoirs. This study is based on experimental observations and numerical simulations. In the experiments, the flowback process was simulated through a gas displacement experiment, and the cores were scanned simultaneously to obtain the water distribution. Then, the water migration and retention mechanisms were investigated to determine the flowback behavior. For the numerical simulations, a multi-porosity model was established. The mathematical model accounted for the capillary pressure term. By matching the fluid saturation-front curves of the experimental and simulation results, a fitted capillary pressure curve, which reflects the multiple mechanisms controlling flowback, was obtained. Based on the established model and fitted capillary pressure, the flowback behavior and relevant influencing factors of the shale gas were investigated. The results show that the flowback ratio is inversely proportional to the clay content of the shale. A high salinity fracturing fluid or a surfactant solution can increase the flowback ratio. In addition, the injection pressure is proportional to the flowback ratio, while the matrix permeability and the flowback ratio have an inverse relationship. The adsorption–desorption process of gas has no significant effect on the flowback ratio. This study aims to provide a new method for analyzing the flowback performance of shale gas using a combination of experimental and numerical simulation methods.
Finite Element Analysis of Flow Field in Drill Bit Design for Gas-Lift Drilling
Authors: Luo Yi , Guo Boyun , Zhang Liehui , Xiao Dong
Published: January 2021

The hole cleaning issue in gas-lift drilling has been a concern and has not been previously investigated due to the difficulties of experimental studies and analytical modeling. The objective of this study is to deliver an assessment of hole cleaning capacity of drilling fluid in reverse circulation conditions for different bit designs. We use the finite element method (FEM) to target this issue and address a critical question in gas-lift drilling. The result of the theoretical investigation indicates that clean bottom hole can be achieved in gas-lift drilling through optimization of drill bit design to balance fluid energy (cleaning power) between tooth blades. Three drill bit designs were investigated in this study. The flow power balance between blades can be achieved with a 3-orifice bit design and a 2-orifice bit design, but there exist flow stagnation zones between these orifices, which are not desirable for bit tooth and borehole cleaning. The 1-orifice bit design with four cutter blades can eliminate flow stagnation zone and improve flow field to achieve a much better flow power balance between blades and thus bit tooth and borehole cleaning. Therefore, drill bits with one orifice are desirable for reverse circulation gas-drilling. This paper presents a novel technique of using FEM to evaluate bit hydraulics for hole cleaning in reverse drilling conditions. Future laboratory tests are desirable to obtain real data for further validating the model result.
Analysis of Influencing Factors of Modification Potential of Abandoned Coal Mine Into Pumped Storage Power Station
Authors: Shang Dacheng , Pei Peng
Published: January 2021

By modifying underground spaces of abandoned coal mines into underground pumped storage power stations, it can realize the efficient and reasonable utilization of underground space and, at the same time, meet the increasing demand for energy storage facilities of the grid, bringing social, economic, and environmental benefits. Previous research in this area has been limited to the stage of conceptual discussion, and there is no scientific evaluation method for the modification and utilization potential of abandoned coal mine spaces. Establishing a scientific evaluation indicator system forms the basis for evaluating the underground space development and utilization capacity of abandoned mines. Based on the principle of pumped energy storage and the characteristics of coal mine roadway conditions, this paper utilized an analytical hierarchy process (AHP) to evaluate the main influencing factors, including elevation difference between the upper and lower reservoirs, reservoir capacity, roadway surrounding rock stability, and roadway permeability. It analyzed the modification potential of underground spaces and then verified the development potential of the underground spaces of abandoned mines by a statistic model. The study found that the elevation difference between the upper and lower reservoirs is the most influential indicator; second, the capacity of the upper and lower reservoirs is also an important evaluation indicator. The research methods and conclusions will provide useful tools and decision-making basis for analyzing the feasibility and techno-economic benefit of modifying the underground spaces of abandoned coal mines into pumped storage power stations.
Tart Cherry Supplementation and Recovery From Strenuous Exercise: A Systematic Review and Meta-Analysis
Authors: Hill Jessica Amie , Keane Karen Mary , Quinlan Rebecca , Howatson Glyn
Published: January 2021

The aim of this study was to determine the efficacy of tart cherry (TC) supplementation on recovery following strenuous exercise. A systematic review and meta-analysis were conducted using studies investigating TC supplementation on measures of muscle soreness, muscular strength, muscular power, creatine kinase, C-reactive protein, Interleukin-6, and tumor necrosis factor alpha. A literature search ending in July 2020 was conducted in three databases (SPORTDiscus, Web of Science, and PubMed). Data from 14 studies were extracted and pooled for analysis. Tart cherry supplementation had a small beneficial effect in reducing muscle soreness (effect size [ES] = −0.44, 95% confidence interval [CI] [−0.87, −0.02]). A moderate beneficial effect was observed for recovery of muscular strength (ES = −0.78, 95% CI [−1.11, −0.46]). A moderate effect was observed for muscular power (ES = −0.53, 95% CI [−0.77, −0.29]); a further subgroup analysis on this variable indicated a large effect of TC supplementation on recovery of jump height (ES = −0.82, 95% CI [−1.18, −0.45]) and a small significant effect of supplementation on sprint time (ES = −0.32, 95% CI [−0.60, −0.04]). A small effect was observed for both C-reactive protein (ES = −0.46, 95% CI [−0.93, −0.00]) and Interleukin-6 (ES = −0.35, 95% CI [−0.68, −0.02]. No significant effects were observed for creatine kinase and tumor necrosis factor alpha. These results indicate that the consumption of a TC supplement can aid aspects of recovery from strenuous exercise.
Single and Combined Effect of Acute Sleep Restriction and Mental Fatigue on Basketball Free-Throw Performance
Authors: Filipas Luca , Ferioli Davide , Banfi Giuseppe , La Torre Antonio , Vitale Jacopo Antonino
Published: January 2021

Purpose: This study aimed to investigate the single and combined effects of sleep restriction (SR) and mental fatigue (MF) on free-throw (FT) performance among adult male basketball players. Methods: A total of 19 amateur male basketball players performed, in a randomized, counterbalanced, and crossover order, 2 identical experimental sessions separated by an interval of 1 week. The difference between the 2 sessions was in the quantity of sleep the night before the sessions, as follows: in one case, the participants followed their habitual sleep–wake routines; in the other session, they were forced to sleep not more than 5 hours. During the experimental sessions, the participants performed 60 basketball FTs on 2 occasions, separated by watching a basketball tactical video for 30 minutes designed to induce MF. As such, the FT test was completed in 4 different conditions: control, MF, SR, and SR and MF combined. Results: The participants registered a significantly lower total sleep time in acute SR (P < .001). The subjective rating of MF was lower in the control than in MF, SR, and SR and MF combined (P < .001). There were no differences between conditions for the subjective ratings of motivation. FT accuracy was higher in the control than in MF, SR, and SR and MF combined (P = .010), while no differences were observed between the 3 experimental conditions (all P > .05). Conclusion: The results indicate that a combined effect of MF and SR induces a small reduction in basketball FT performance, similar to MF or SR alone.
Upper-Body Resistance Training Following Soccer Match Play: Compatible, Complementary, or Contraindicated?
Authors: Sabag Angelo , Lovell Ric , Walsh Neil P. , Grantham Nick , Lacome Mathieu , Buchheit Martin
Published: January 2021

Purpose:During heavily congested schedules, professional soccer players can experience exacerbated fatigue responses, which are thought to contribute to an increased risk of injury. Given that match-induced residual fatigue can last up to 72 hours, many coaches naturally prioritize recovery in the days immediately following match day. While it is intuitive for coaches and training staff to decrease the amount of auxiliary training practices to focus on recovery, prescribing upper-body resistance training on the day after match play has recently emerged as a specific training modality in this context. While these sessions may be implemented to increase training stimulus, there are limited data available regarding the efficacy of such a practice to improve recovery kinetics.Methods:In this narrative review, the authors look at the theoretical implications of performing upper-body resistance training on the day after match play on the status of various physiological and psychological systems, including neuromuscular, metabolic, hormonal, perceptual, and immunological recovery.Results:The available evidence suggests that in most cases this practice, as currently implemented (ie, low volume, low intensity), is unlikely to be complementary (ie, does not accelerate recovery) but is potentially compatible (ie, does not impair recovery).Conclusion:Overall, because the perception of such sessions may be player dependent, their programming requires an individualized approach and should take into account match dynamics (eg, fixture scheduling, playing time, travel).
Nonresonant powering of injectable nanoelectrodes enables wireless deep brain stimulation in freely moving mice
Authors: Kozielski K. L. , Jahanshahi A. , Gilbert H. B. , Yu Y. , Erin Ö. , Francisco D. , Alosaimi F. , Temel Y. , Sitti M.
Published: January 2021

Wireless powering of magnetoelectric nanoelectrodes is used for deep brain stimulation in freely moving and transgene-free mice.
CGG repeat RNA G-quadruplexes interact with FMRpolyG to cause neuronal dysfunction in fragile X-related tremor/ataxia syndrome
Authors: Asamitsu Sefan , Yabuki Yasushi , Ikenoshita Susumu , Kawakubo Kosuke , Kawasaki Moe , Usuki Shingo , Nakayama Yuji , Adachi Kaori , Kugoh Hiroyuki , Ishii Kazuhiro , Matsuura Tohru , Nanba Eiji , Sugiyama Hiroshi , Fukunaga Kohji , Shioda Norifumi
Published: January 2021

CGG repeat–derived RNA G-quadruplexes accelerate liquid-to-solid transition of FMRpolyG.
Optical selection and sorting of nanoparticles according to quantum mechanical properties
Authors: Fujiwara Hideki , Yamauchi Kyosuke , Wada Takudo , Ishihara Hajime , Sasaki Keiji
Published: January 2021

Selective manipulation and spectroscopy of single nanoparticles are realized by measuring and controlling quantum resonant forces.
Targeting cartilage EGFR pathway for osteoarthritis treatment
Authors: Wei Yulong , Luo Lijun , Gui Tao , Yu Feifan , Yan Lesan , Yao Lutian , Zhong Leilei , Yu Wei , Han Biao , Patel Jay M. , Liu Jessica F. , Beier Frank , Levin Lawrence Scott , Nelson Charles , Shao Zengwu , Han Lin , Mauck Robert L. , Tsourkas Andrew , Ahn Jaimo , Cheng Zhiliang , Qin Ling
Published: January 2021

EGFR activation by overexpressing HBEGF in cartilage or intra-articular delivery of TGFα nanoparticles attenuates osteoarthritis development in mice.
Enhanced drug delivery to the reproductive tract using nanomedicine reveals therapeutic options for prevention of preterm birth
Authors: Zierden Hannah C. , Ortiz Jairo I. , DeLong Kevin , Yu Jingqi , Li Gaoshan , Dimitrion Peter , Bensouda Sabrine , Laney Victoria , Bailey Anna , Anders Nicole M. , Scardina Morgan , Mahendroo Mala , Mesiano Sam , Burd Irina , Wagner Gunter , Hanes Justin , Ensign Laura M.
Published: January 2021

Vaginally delivered nanoformulations of progesterone and histone deacetylase inhibitors prevent inflammation-induced preterm birth in mice.
Heightened resistance to host type 1 interferons characterizes HIV-1 at transmission and after antiretroviral therapy interruption
Authors: Gondim Marcos V. P. , Sherrill-Mix Scott , Bibollet-Ruche Frederic , Russell Ronnie M. , Trimboli Stephanie , Smith Andrew G. , Li Yingying , Liu Weimin , Avitto Alexa N. , DeVoto Julia C. , Connell Jesse , Fenton-May Angharad E. , Pellegrino Pierre , Williams Ian , Papasavvas Emmanouil , Lorenzi Julio C. C. , Salantes D. Brenda , Mampe Felicity , Monroy M. Alexandra , Cohen Yehuda Z. , Heath Sonya , Saag Michael S. , Montaner Luis J. , Collman Ronald G. , Siliciano Janet M. , Siliciano Robert F. , Plenderleith Lindsey J. , Sharp Paul M. , Caskey Marina , Nussenzweig Michel C. , Shaw George M. , Borrow Persephone , Bar Katharine J. , Hahn Beatrice H.
Published: January 2021

Interferon-mediated pressures vary throughout HIV-1 infection but are the highest during viral rebound after treatment interruption.
In aged hosts, T cells turn traitorous
Authors: Billi Allison C.
Published: January 2021

Multimodal profiling of the aging immune system has identified highly abundant age–associated CD8
+
T cells that home to organs and drive inflammation.
Evaluation of the Xpert Xpress SARS-CoV-2/Flu/RSV Assay for Simultaneous Detection of SARS-CoV-2, Influenza A and B Viruses, and Respiratory Syncytial Virus in Nasopharyngeal Specimens
Authors: Leung Eddie Chi-man , Chow Viola Chi-ying , Lee May Kin-ping , Tang Kevin Pui-san , Li Daniel Kwok-cheung , Lai Raymond Wai-man
Published: January 2021

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A (flu A), influenza B (flu B), and respiratory syncytial virus (RSV) have overlapping clinical presentations, but the approaches to treatment and management of infections caused by these viruses are different. Therefore, rapid diagnosis in conjunction with infection prevention measures is important to prevent transmission of the diseases.
Draft Genome Sequence of
Cytophagales
sp. Strain WSM2-2, Isolated from Garden Soil
Authors: Aoki Masataka , Oshiki Mamoru , Iwagaki Mizuki , Hatamoto Masashi , Yamaguchi Takashi , Araki Nobuo
Published: January 2021

We report the draft genome sequence of the
Cytophagales
sp. strain WSM2-2, isolated from garden soil. A 5.5-Mb genome sequence comprising four contigs was successfully obtained using Illumina NovaSeq and MinION sequencers. This draft genome sequence will contribute to the genomic knowledge of the bacterial order
Cytophagales.
Stroke masquerading as cardiac arrest: the artery of Percheron
Authors: Quetsch Megan , Nagiah Sureshkumar , Hedger Stephen
Published: January 2021

The artery of Percheron (AOP) is a rare arterial variant of the thalamic blood supply. Due to the densely packed collection of nuclei it supplies, an infarction of the AOP can be devastating. Here we highlight a patient who had an AOP stroke in the community, which was initially managed as cardiac arrest. AOP strokes most often present with vague symptoms such as reduced conscious level, cognitive changes and confusion without obvious focal neurology, and therefore are often missed at the initial clinical assessment. This case highlights the importance of recognising an AOP stroke as a cause of otherwise unexplained altered consciousness level and the use of MRI early in the diagnostic work-up.
D-MannosE to prevent Recurrent urinary tract InfecTions (MERIT): protocol for a randomised controlled trial
Authors: Franssen Marloes , Cook Johanna , Robinson Jared , Williams Nicola , Glogowska Margaret , Yang Yaling , Allen Julie , Butler Christopher C , Thomas Nick , Hay Alastair , Moore Michael , Hayward Gail
Published: January 2021

Introduction

Recurrent urinary tract infections (RUTIs) have a significant negative impact on quality of life and healthcare costs. To date, daily prophylactic antibiotics are the only treatment which have been shown to help prevent RUTIs. D-mannose is a type of sugar which is believed to inhibit bacterial adherence to uroepithelial cells, and is already being used by some women in an attempt to prevent RUTIs. There is currently insufficient rigorous evidence on which to base decisions about its use. The D-mannose to prevent recurrent urinary tract infections (MERIT) study will evaluate whether D-mannose is clinically and cost-effective in reducing frequency of infection and symptom burden for women presenting to UK primary care with RUTI.

Methods and analysis

MERIT will be a two-arm, individually randomised, double blind placebo controlled, pragmatic trial. Participants will be randomised to take D-mannose powder or placebo powder daily for 6 months. The primary outcome will be the number of medical attendances attributable to symptoms of RUTI. With 508 participants we will have 90% power to detect a 50% reduction in the chance of a further clinically suspected UTI, assuming 20% lost to follow-up. Secondary outcomes will include: number of days of moderately bad symptoms of UTI; time to next consultation; number of clinically suspected UTIs; number of microbiologically proven UTIs; number of antibiotic courses for UTI; quality of life and healthcare utilisation related to UTI. A within trial economic evaluation will be conducted to examine cost-effectiveness of D-mannose in comparison with placebo. A nested qualitative study will explore participants’ experiences and perceptions of recruitment to, and participation in a study requiring a daily treatment.

Ethics and dissemination

Ethical approval has been obtained from South West-Central Bristol Research Ethics Committee. Publication of the MERIT study is anticipated to occur in 2021.

Trial registration number

ISRCTN 13283516.
Evaluation of an automated feedback intervention to improve antimicrobial prescribing among primary care physicians (OPEN Stewardship): protocol for an interrupted time-series and usability analysis in Ontario, Canada and Southern Israel
Authors: Soucy Jean-Paul R , Low Marcelo , Acharya Kamal Raj , Ellen Moriah , Hulth Anette , Löfmark Sonja , Garber Gary E , Watson William , Moran-Gilad Jacob , Fisman David N , MacFadden Derek R
Published: January 2021

Introduction

Antimicrobial resistance undermines our ability to treat bacterial infections, leading to longer hospital stays, increased morbidity and mortality, and a mounting burden to the healthcare system. Antimicrobial stewardship is increasingly important to safeguard the efficacy of existing drugs, as few new drugs are in the developmental pipeline. While significant progress has been made with respect to stewardship in hospitals, relatively little progress has been made in the primary care setting, where the majority of antimicrobials are prescribed. OPEN Stewardship is an international collaboration to develop an automated feedback platform to improve responsible antimicrobial prescribing among primary care physicians and capable of being deployed across heterogeneous healthcare settings. We describe the protocol for an evaluation of this automated feedback intervention with two main objectives: assessing changes in antimicrobial prescribing among participating physicians and determining the usability and usefulness of the reports.

Methods and analysis

A non-randomised evaluation of the automated feedback intervention (OPEN Stewardship) will be conducted among approximately 150 primary care physicians recruited from Ontario, Canada and Southern Israel, based on a series of targeted stewardship messages sent using the platform. Using a controlled interrupted time-series analysis and multilevel negative binomial modelling, we will compare the antimicrobial prescribing rates of participants before and after the intervention, and also to the prescribing rates of non-participants (from the same healthcare network) during the same period. We will examine outcomes targeted by the stewardship messages, including prescribing for antimicrobials with duration longer than 7 days and prescribing for indications where antimicrobials are typically unnecessary. Participants will also complete a series of surveys to determine the usability and usefulness of the stewardship reports.

Ethics and dissemination

All sites have obtained ethics committee approval to recruit providers and access anonymised prescribing data. Dissemination will occur through open-access publication, stakeholder networks and national/international meetings.
Symptom heterogeneity and patient subgroup classification among US patients with post-treatment Lyme disease: an observational study
Authors: Rebman Alison W , Yang Ting , Aucott John N
Published: January 2021

Objectives

To identify underlying subgroups with distinct symptom profiles, and to characterise and compare these subgroups across a range of demographic, clinical and psychosocial factors, within a heterogeneous group of patients with well-defined post-treatment Lyme disease (PTLD).

Design

A clinical case series of patents.

Setting

Participants were recruited from a single-site, Lyme disease referral clinic patient population and were evaluated by physical exam, clinical laboratory testing and standardised questionnaires.

Participants

Two hundred and twelve participants met study criteria for PTLD, with medical record-confirmed prior Lyme disease as well as current symptoms and functional impact.

Results

Exploratory factor analysis classified 30 self-reported symptoms into 6 factors: ‘Fatigue Cognitive’, ‘Ocular Disequilibrium’, ‘Infection-Type’, ‘Mood-Related’, ‘Musculoskeletal Pain’ and ‘Neurologic’. A final latent profile analysis was conducted using ‘Fatigue Cognitive’, ‘Musculoskeletal Pain’ and ‘Mood-Related’ factor-based scores, which produced three emergent symptom profiles, and participants were classified into corresponding subgroups with 59.0%, 18.9% and 22.2% of the sample, respectively. Compared with the other two groups, subgroup 1 had similarly low levels across all factors relative to the sample as a whole, and reported lower rates of disability (1.6% vs 10.0%, 12.8%; q=0.126, 0.035) and higher self-efficacy (median: 7.5 vs 6.0, 5.3; q=0.068,<0.001). Subgroup 2 had the highest ‘Musculoskeletal Pain’ factor-based scores (q≤0.001). Subgroup 3 was characterised overall by higher symptom factor-based scores, and reported higher depression (q≤0.001).

Conclusions

This analysis identified six symptom factors and three potentially clinically relevant subgroups among patients with well-characterised PTLD. We found that these subgroups were differentiated not only by symptom phenotype, but also by a range of other factors. This may serve as an initial step towards engaging with the symptom heterogeneity that has long been observed among patients with this condition.
Government’s subsidisation policy and utilisation of smoking cessation treatments: a population-based cross-sectional study in Taiwan
Authors: Wang Sheng-Kuang , Kao Chi-Wen , Chuang Hui-Wan , Tseng Yi-Kai , Chen Wan-Chun , Yeh Chien-Chih , Lai Chung-Yu , Yen Li-Chen , Chiu Yu-Lung
Published: January 2021

Objectives

This study examined the associations between the Second-Generation Cessation Payment Scheme (SCPS) and the use of smoking cessation treatments. Furthermore, these associations were compared between light and heavy smokers in Taiwan.

Design

This study had a cross-sectional design.

Setting

Data were obtained from the Taiwan Adult Smoking Behaviour Surveillance System 2010–2011 and 2013–2014; data for each year consisted of a nationally representative sample of adults aged 18 years and older.

Participants

Current smokers who had either quit or made a serious attempt to quit smoking were selected for the analysis.

Primary outcome measure

The primary outcome measure was the use of a smoking cessation clinic or pharmacy in a twice daily to quit smoking.

Results

According to multivariate analysis, the SCPS was positively associated with the combined use of a smoking cessation clinic and a pharmacy (OR=3.947; 95% CI: 1.359 to 11.463) when individual-level predictors (gender, age, education level, marital status, monthly household income, daily cigarette consumption, smoking status and self-reported health) were controlled. Heavy smokers showed a signiﬁcant increase in the sole use of a pharmacy (OR=1.676; 95% CI: 1.094 to 2.569) and combined use of a smoking cessation clinic and pharmacy (OR=8.984; 95% CI: 1.914 to 42.173) after the SCPS was introduced. In addition, when related factors were controlled, the use of smoking cessation services was more frequent among heavy smokers than light smokers, including any treatment (OR=1.594; 95% CI: 1.308 to 1.942), a smoking cessation clinic (OR=1.539; 95% CI: 1.232 to 1.922), a pharmacy (OR=1.632; 95% CI: 1.157 to 2.302) and the combination of a smoking cessation clinic and pharmacy (OR=4.608; 95% CI: 1.331 to 15.949) .

Conclusions

The SCPS subsidisation policy increased the use of smoking cessation treatments, particularly among heavy smokers.
Study protocol for COVID-RV: a multicentre prospective observational cohort study of right ventricular dysfunction in ventilated patients with COVID-19
Authors: Willder Jennifer Mary , McCall Philip , Messow Claudia-Martina , Gillies Mike , Berry Colin , Shelley Benjamin
Published: January 2021

Introduction

COVID-19 can cause severe acute respiratory failure requiring management in intensive care unit with invasive ventilation and a 40% mortality rate. Cardiovascular manifestations are common and studies have shown an increase in right ventricular (RV) dysfunction associated with mortality. These studies, however, comprise heterogeneous patient groups with few requiring invasive ventilation. This study will investigate the prevalence and prognostic significance of RV dysfunction in ventilated patients with COVID-19 which may lead to targeted interventions to improve patient outcomes.

Methods and analysis

This prospective multicentre observational cohort study will perform transthoracic echocardiography (TTE) in 150 patients with COVID-19 requiring invasive ventilation for more than 48 hours. RV dysfunction will be defined as TTE evidence of RV dilatation along with the presence of septal flattening. Baseline demographics, disease severity data and clinical information relating to proposed aetiological mechanisms of RV dysfunction (acute respiratory distress syndrome (ARDS), disordered coagulation, direct myocardial injury and ventilation) will be collected and analysed.

Primary outcome measures include the prevalence of RV dysfunction and its association with 30-day mortality. Exploratory outcome measures will investigate the association of the proposed aetiological mechanisms of RV dysfunction to the primary outcomes.

Prevalence of RV dysfunction will be determined along with 95% Clopper-Pearson CIs and 30-day survival will be analysed using logistic regression adjusting for patient demographics, phase of disease and baseline severity of illness. The role of potential aetiological factors (ARDS, disordered coagulation, direct myocardial injury and ventilation) in relation to the primary outcomes will be analysed using logistic regression.

Ethics and dissemination

Approval was gained from Scotland A Research Ethics Committee (REC reference 20/SS/0059). Findings will be disseminated by various methods including webinars, international presentations and publication in peer-reviewed journals.
Protocol for the process evaluation of a complex intervention delivered in schools to prevent adolescent depression: the Future Proofing Study
Authors: Beames Joanne R , Lingam Raghu , Boydell Katherine , Calear Alison L , Torok Michelle , Maston Kate , Zbukvic Isabel , Huckvale Kit , Batterham Philip J , Christensen Helen , Werner-Seidler Aliza
Published: January 2021

Introduction

Process evaluations provide insight into how interventions are delivered across varying contexts and why interventions work in some contexts and not in others. This manuscript outlines the protocol for a process evaluation embedded in a cluster randomised trial of a digital depression prevention intervention delivered to secondary school students (the Future Proofing Study). The purpose is to describe the methods that will be used to capture process evaluation data within this trial.

Methods and analysis

Using a hybrid type 1 design, a mixed-methods approach will be used with data collected in the intervention arm of the Future Proofing Study. Data collection methods will include semistructured interviews with school staff and study facilitators, automatically collected intervention usage data and participant questionnaires (completed by school staff, school counsellors, study facilitators and students). Information will be collected about: (1) how the intervention was implemented in schools, including fidelity; (2) school contextual factors and their association with intervention reach, uptake and acceptability; (3) how school staff, study facilitators and students responded to delivering or completing the intervention. How these factors relate to trial effectiveness outcomes will also be assessed. Overall synthesis of the data will provide school cluster-level and individual-level process outcomes.

Ethics and dissemination

Ethics approval was obtained from the University of New South Wales (NSW) Human Research Ethics Committee (HC180836; 21st January 2019) and the NSW Government State Education Research Applications Process (SERAP 2019201; 19th August 2019). Results will be submitted for publication in peer-reviewed journals and discussed at conferences. Our process evaluation will contextualise the trial findings with respect to how the intervention may have worked in some schools but not in others. This evaluation will inform the development of a model for rolling out digital interventions for the prevention of mental illness in schools.

Trial registration number

ANZCTRN12619000855123;https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377664&isReview=true.
Efficacy, safety and response predictors of adjuvant astragalus for diabetic kidney disease (READY): study protocol of an add-on, assessor-blind, parallel, pragmatic randomised controlled trial
Authors: Chan Kam Wa , Kwong Alfred Siu Kei , Tsui Pun Nang , Cheung Simon Chi Yuen , Chan Gary Chi Wang , Choi Wing Fai , Yiu Wai Han , Zhang Yanbo , Wong Michelle Man-Ying , Zhang Zhang-Jin , Tan Kathryn Choon Beng , Lao Lixing , Tang Sydney Chi Wai
Published: January 2021

Introduction

Diabetic kidney disease (DKD) is a prevalent and costly complication of diabetes with limited therapeutic options, being the leading cause of end-stage kidney disease in most developed regions. Recent big data studies showed that add-on Chinese medicine (CM) led to a reduced risk of end-stage kidney disease and mortality among patients with chronic kidney disease (CKD) and diabetes. Astragalus, commonly known as huang-qi, is the most prescribed CM or used dietary herb in China for diabetes and DKD.In vivoandin vitrostudies showed that astragalus ameliorated podocyte apoptosis, foot process effacement, mesangial expansion, glomerulosclerosis and interstitial fibrosis. Nevertheless, the clinical effect of astragalus remains uncharacterised. This pragmatic clinical trial aims to evaluate the effectiveness of add-on astragalus in patients with type 2 diabetes, stage 2–3 CKD and macroalbuminuria, and to identify related response predictors.

Methods and analysis

This is an add-on, assessor-blind, parallel, pragmatic randomised controlled clinical trial. 118 patients diagnosed with DKD will be recruited and randomised 1:1 to receive 48 weeks of add-on astragalus or standard medical care. Primary endpoints are the changes in estimated glomerular filtration rate and urine albumin-to-creatinine ratio between baseline and treatment endpoint. Secondary endpoints include adverse events, fasting blood glucose, glycated haemoglobin, lipids and other biomarkers. Adverse events are monitored through self-complete questionnaire and clinical visits. Outcomes will be analysed by regression models. Subgroup and sensitivity analyses will be conducted for different epidemiological subgroups and statistical analyses. Enrolment started in July 2018.

Ethics and dissemination

This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West/East/Kowloon Central clusters (UW 16-553/HKEC-2019-026/REC (KC/KE)-19-0049/ER-4). We will report the findings in medical journals and conferences. The dataset will be available on reasonable request.

Trial registration number

NCT03535935
Study protocol: randomised controlled trial evaluating exercise therapy as a supplemental treatment strategy in early multiple sclerosis: the Early Multiple Sclerosis Exercise Study (EMSES)
Authors: Riemenschneider Morten , Hvid Lars G , Ringgaard Steffen , Nygaard Mikkel K E , Eskildsen Simon F , Petersen Thor , Stenager Egon , Dalgas Ulrik
Published: January 2021

Introduction

In the relapsing remitting type of multiple sclerosis (MS) reducing relapses and neurodegeneration is crucial in halting the long-term impact of the disease. Medical disease-modifying treatments have proven effective, especially when introduced early in the disease course. However, patients still experience disease activity and disability progression, and therefore, supplemental early treatment strategies are warranted. Exercise appear to be one of the most promising supplemental treatment strategies, but a somewhat overlooked ‘window of opportunity’ exist early in the disease course. The objective of this study is to investigate exercise as a supplementary treatment strategy early in the disease course of MS.

Methods and analysis

The presented Early Multiple Sclerosis Exercise Study is a 48-week (plus 1-year follow-up) national multicentre single-blinded parallel group randomised controlled trial comparing two groups receiving usual care plus supervised high-intense exercise or plus health education (active control). Additionally, data will be compared with a population-based control group receiving usual care only obtained from the Danish MS Registry. The primary outcomes are annual relapse rate and MRI derived global brain atrophy. The secondary outcomes are disability progression, physical and cognitive function, MS-related symptoms, and exploratory MRI outcomes. All analyses will be performed as intention to treat.

Ethics and dissemination

The study is approved by The Central Denmark Region Committees on Health Research Ethics (1-10-72-388-17) and registered at the Danish Data Protection Agency (2016-051-000001 (706)). All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.

Trial registration number

NCT03322761.