bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Dynamic Shear Force on Fastener Loosening in Assemblies
Authors: Dong Yubo , Hess Daniel P.
Published: February 2021

Placement and orientation of fasteners in assemblies is generally based on convenience or static load and strength considerations. Vibration and other dynamic loads can result in loosening of threaded product, particularly when cyclic shear stresses are present. This paper investigates the placement of a bolt and nut on a compound cantilever beam subjected to dynamic inertial loading. Calculations for an inertial loaded, cantilever, Euler-Bernoulli beam show that the dynamic shear stress is maximum near the dynamic nodal lines, and essentially vanishes near the anti-nodes. Experiments with a compound cantilever beam assembly with one fastener reveal that loosening occurs more readily when the bolt and nut are placed near a nodal line. Data presented include time to loosen, break-away torque, and acceleration level. The data shows that fastener integrity is maintained for longer periods of time and with lower tightening torques, when the bolt and nut are positioned away from nodal lines where shear stresses are lower, even though acceleration levels are higher.
Precision Placement Analysis of a New Multi-DOF Piezoelectric End-Effector via Finite Elements
Authors: Bahrami Hassan , Tzou H. S.
Published: February 2021

Piezoelectric materials are increasingly being applied to various fieldS of research and engineering applications. In recent years for example, much work has been concentrated on active vibration control of structures by incorporating piezoelectric as both sensorS and actuators. In the industry, piezoelectrics are widely being accepted as effective sensors, giving engineers more leverage to add new features to their products. In this paper, piezoelectric composite structure is studied for precision placement of a multiple degrees off freedom (DOF) end–effector per the converse piezoelectric effect. This new design of the multi–DOF cantilever beam, by attaching multiple piezoelectric rectangular rods together, will provide a way to accurately position the end of this beam structure. The computation of this advanced composite structure is done by the finite element method incorporating the piezoelectric effects.
A Global Methodology for the Modal Reduction of Large Nonlinear Systems Containing Quadratic and Cubic Nonlinearities
Authors: Pesheck E. , Pierre C.
Published: February 2021

A methodology is presented for the systematic modal reduction of structural systems which contain quadratic and cubic nonlinearities in displacement. The procedure is based on the center manifold approach for describing individual nonlinear modes, but it has been extended to account for simultaneous motion within several chosen modal coordinates. Motions of the reduced system are constrained to lie on high-dimensional manifolds within the phase space of the original system. Polynomial approximations of these manifolds are obtained through third order for arbitrary system parameters. Algorithms have been developed for automation of this procedure, and they are applied to an example system. Free and forced responses of the reduced system are discussed and compared to responses reduced through simple modal truncation. A more rigorous treatment of harmonic forcing is proposed, which will allow for the production of high-dimensional, time-dependent manifolds through a simple adaptation of the unforced procedure.
Nonlinear Normal Modes of Buckled Beams: Three-to-One and One-to-One Internal Resonances
Authors: Nayfeh Ali H. , Lacarbonara Walter , Chin Char-Ming
Published: February 2021

Nonlinear normal modes of a buckled beam about its first buckling mode shape are investigated. Fixed-fixed boundary conditions are considered. The cases of three-to-one and one-to-one internal resonances are analyzed. Approximate expressions for the nonlinear normal modes are obtained by applying the method of multiple scales to the governing integro-partial-differential equation and boundary conditions. Curves displaying variation of the amplitude with the internal resonance detuning parameter are generated. It is shown that, for a three-to-one internal resonance between the first and third modes, the beam may possess either one stable mode, or three stable normal modes, or two stable and one unstable normal modes. On the other hand, for a one-to-one internal resonance between the first and second modes, two nonlinear normal modes exist. The two nonlinear modes are either neutrally stable or unstable. In the case of one-to-one resonance between the third and fourth modes, two neutrally stable, nonlinear normal modes exist.
Nonlinear Nonplanar Dynamics of Parametrically Excited Cantilever Beams
Authors: Arafat Haider N. , Nayfeh Ali H. , Chin Char-Ming
Published: February 2021

The nonlinear nonplanar response of cantilever inextensional metallic beams to a principal parametric excitation of two of its “exural modes, one in each plane, is investigated. The lowest torsional frequencies of the beams considered are much larger than the frequencies of the excited modes so that the torsional inertia can be neglected. Using this condition as well as the inextensionality condition, we develop a Lagrangian whose variation leads to the two integro-partial-differential equations of Crespo da Silva and Glynn. The method of time-averaged Lagrangian is used to derive four first-order nonlinear ordinary-differential equations governing the modulation of the amplitudes and phases of the two interacting modes. The modulation equations exhibit the symmetry property found by Feng and Leal by analytically manipulating the interaction coefficients in the modulation equations obtained by Nayfeh and Pai by applying the method of multiple scales to the governing integro-partial-differential equations. A pseudo arclength scheme is used to trace the branches of the equilibrium solutions and an investigation of the eigenvalues of the Jacobian matrix is used to assess their stability. The equilibrium solutions experience pitchfork, saddle-node, and Hopf bifurcations. A detailed bifurcation of the dynamic solutions of the modulation equations is presented. Five branches of dynamic (periodic and chaotic) solutions were found. Two of these branches emerge from two Hopf bifurcations and the other three are isolated. The limit cycles undergo symmetry-breaking, cyclic-fold, and period-doubling bifurcations, whereas the chaotic attractors undergo attractor-merging and boundary crises.
PC Based Nonlinear Dynamic Simulation and Animation of the Tilting Pad Guide Bearing in Large Hydro-Unit
Authors: Zhang X. Z. , Ma L. F. , Zhao Y. C.
Published: February 2021

The paper describes a process with which the nonlinear dynamical simulation and the animation of tilting pad guide bearing in large hydro-unit can be performed on a PC computer. Based on non-stationary Reynolds equation the effects of the nonlinear displacement and velocity of journal center as well as the nonlinear swing angle and velocity of pad on oil film forces are taken into consideration. The animation displays vividly the pictures of the rotation of shaft, the movement of journal center and the swing motion of pad. As an example, the response due to momentarily created unbalance is given.
Dynamic Analysis of a Ramp-Roller Clutch
Authors: Chang Chin-Tzung , Seireg Ali A.
Published: February 2021

This study deals with the design and dynamic analysis of a ramp-roller clutch which can be utilized in developing a mechanical function generator. The dynamic behavior with non-linear torsional spring and damping characteristics is first investigated. Three major design parameters are identified and further optimized for the objective of minimizing the settling time. As a result of underdamping, undesired vibration can occur during the engagement. In order to minimize these unwanted vibrations, coulomb dampers are considered. By adding a properly tuned auxiliary damper, the settling time can be significantly reduced. An example is also given to illustrate the use of one-directional clutches for mechanical function generation where an arbitrary function is synthesized by sequentially triggering 7 clutches. Phase shifting is incorporated in the to reduce the error in the generated function.
Dynamics of a Rotating System With a Nonlinear Eddy-Current Damper
Authors: Kligerman Yuri , Gottlieb Oded
Published: February 2021

The investigation of nonlinear dynamics and stability of a rotating system with an electromagnetic non-contact eddy-current damper is carried out. The damper is modeled by a thin nonmagnetic disk that is translating and rotating with a shaft in an air gap of a direct current electromagnet. The damper dissipates energy of the rotating system lateral vibration through induced eddy-currents. The dynamical system also includes a cubic restoring force representing nonlinear behavior of rubber o-rings supporting the shaft. The equilibrium state of the balanced rotating system with an eddy-current damper becomes unstable via a Hopf bifurcation and exact solutions for the limit cycle radius and frequency of the self-excited oscillation are obtained analytically. Forced vibration induced by the rotating system mass imbalance is also investigated analytically and numerically. System response includes periodic and quasiperiodic solutions. Stability of the periodic solutions obtained from the balanced self-excited motion and the unbalance forced response is analyzed by use of Floquet theory. This analysis enables an explanation of the nonlinear dynamics and stability phenomena documented for rotating systems controlled by electromagnetic eddy-current dampers.
Evaluation of AMB Turbomachinery Auxiliary Bearings
Authors: Kirk R. G.
Published: February 2021

The use of active magnetic bearings (AMB) for turbomachinery has experienced substantial growth during the past two decades. The advantages for many applications make AMB’s a very attractive solution for potentially low loss and efficient support for both radial and thrust loads. New machinery must be shop tested prior to shipment to the field for installation on-line. For AMB turbomachinery, one additional test is the operation of the auxiliary drop or overload bearings. A major concern is ability of the selected auxiliary bearing to withstand the contact forces following an at speed rotor drop. The proper design of AMB machinery requires the calculation of the anticipated loading for the auxiliary bearings. Analytical techniques to predict the rotor transient response are reviewed. Results of transient response evaluation of a full-size compressor rotor are presented to illustrate some of the important parameters in the design for rotor drop.
Vibrations of Ballooning Elastic Strings
Authors: Zhu Fang , Sharma Rajiv , Rahn Christopher D.
Published: February 2021

This paper investigates the nonlinear dynamic response of a linearly elastic string fixed at one boundary and undergoing constant speed circular motion at the other boundary. The response divides into nonlinear, steady state ballooning that is fixed relative to a rotating coordinate system and linearized vibration about the steady state. Single loop balloons have high tension and purely imaginary eigenvalues. The single loop vibration frequencies generally decrease with increasing balloon length. Highly extensible strings whirl in first and higher modes with forward whirling modes having lower frequencies. Axially stiff strings exhibit whirling only in higher modes. If the nondimensional string stiffness is larger than 1000 then the inextensible steady state solutions and the lowest six vibration frequencies match the extensible results to within 3%. One and a half loop balloons are divergently unstable. Long and/or sufficiently extensible strings form low tension double loop balloons. Inextensible double balloons are coupled mode flutter unstable. The steady state balloons, steady state eyelet tension, and balloon stability are experimentally verified.
Parametric Identification of Nonlinear Systems Using Higher-Order Spectra
Authors: Khan Khalil A. , Balachandran B.
Published: February 2021

A novel procedure to parametrically identify the nonlinearities in a system is presented. In this procedure, the relationships among higher-order transfer functions and higher-order spectra are utilized and expressions are derived for coefficients of non-linearities. Two different nonlinear oscillators are considered as examples to illustrate the procedure. Numerical results are also provided for a nonlinear oscillator.
The Dynamics of the Celt With Second Order Averaging and Computer Algebra
Authors: Blackowiak A. D. , Rand R. H. , Kaplan H.
Published: February 2021

Starting with a no-slip, dissipation-free model of the celt developed by Kane and Levinson in 1982, we obtain a three-dimensional slow flow using second order averaging. The coefficients of the slow flow are obtained in symbolic form through the use of computer algebra, thus permitting a bifurcation analysis to be performed. It is shown that for all physically relevant parameters the celt is predicted to exhibit an infinite number of spin reversals. The analysis assumes small energy and small inertial asymmetry.
Canonical Perturbation of a Fast Time-Periodic Hamiltonian via Liapunov-Floquet Transformation
Authors: Butcher Eric A. , Sinha S. C.
Published: February 2021

In this study a possible application of time-dependent canonical perturbation theory to a fast nonlinear time-periodic Hamiltonian with strong internal excitation is considered. It is shown that if the time-periodic unperturbed part is quadratic, the Hamiltonian may be canonically transformed to an equivalent form in which the new unperturbed part is time-invariant so that the time-dependent canonical perturbation theory may be successfully applied. For this purpose, the Liapunov-Floquet (L-F) transformation and its inverse associated with the unperturbed time-periodic quadratic Hamiltonian are computed using a recently developed technique. Action-angle variables and time-dependent canonical perturbation theory are then utilized to find the solution in the original coordinates. The results are compared for accuracy with solutions obtained by both numerical integration and by the classical method of directly applying the time-dependent perturbation theory in which the time-periodic quadratic part is treated as another perturbation term. A strongly excited Mathieu-Hill quadratic Hamiltonian with a cubic perturbation and a nonlinear time-periodic Hamiltonian without a constant quadratic part serve as illustrative examples. It is shown that, unlike the classical method in which the internal excitation must be weak, the proposed formulation provides accurate solutions for an arbitrarily large internal excitation.
Interrelation of Self-Excited Friction Vibrations With Thermal Processes in Brakes
Authors: Gekker Feodor R. , Chichinadze Avtandil V. , Khairaliev Serik I. , Suvorov Aleksey V.
Published: February 2021

The method results of the self-excited friction vibrations calculation in brake systems is presented. The problem of obtain some parameters necessary for calculation has received special attention.
Lateral Vibration of a Consistent Continuous Beam With a Crack
Authors: Chondros Thomas G. , Dimarogonas Andrew D. , Yao Jonathan
Published: February 2021

A continuous cracked beam vibration theory is developed for the lateral vibration of cracked Euler-Bernoulli beams with single-edge or double-edge cracks. The Hu-Washizu-Barr variational formulation was used to develop the differential equation and the boundary conditions of the cracked beam as an one-dimensional continuum. The displacement field about the crack was used to modify the stress and displacement field throughout the bar. The crack was modelled as a continuous flexibility using the displacement field in the vicinity of the crack, found with fracture mechanics methods.

The results of three independent evaluations of the lowest natural frequency of lateral vibrations for beams with a single-edge crack are presented: the continuous cracked beam vibration theory developed here, the lumped crack beam vibration analysis, and an asymptotic solution. Experimental results from aluminum beams with fatigue cracks are very close to the values predicted. A steel beam with a double-edge crack was also investigated with the above mentioned methods, and results compared well with experimental data.
Effect of the Gravity Force on the Propagation of a Rotating Flexible Rod After Impact
Authors: Gau Wei-Hsin
Published: February 2021

The aim of this paper is to analyze the effect of the gravity force on the impact-induced elastic waves which propagate on a radially rotating rod. The equations of motion of the system are developed using the principle of virtual work in dynamics. The impact load is included by the use of the generalized impulse momentum equations, involving the coefficient of restitution. The system is solved using the Fourier method. The deformation of the rod is supposed to be at any instant a linear combination of a set of shape functions. These shape functions are, in this investigation, the modes of a cantilever beam. The weight of the rod is modeled as a concentrated force applied at any instant at the center of the rod.
Autonomous Modal Identification of the Space Shuttle Tail Rudder
Authors: Pappa Richard S. , James George H. , Zimmerman David C.
Published: February 2021

Autonomous modal identification automates the calculation of natural vibration frequencies, damping, and mode shapes of a structure from experimental data. This technology complements damage detection techniques that use continuous or periodic monitoring of vibration characteristics. The approach shown in the paper incorporates the Eigensystem Realization Algorithm (ERA) as a data analysis engine and an autonomous supervisor to condense multiple estimates of modal parameters using ERA’s Consistent-Mode Indicator and correlation of mode shapes. The procedure was applied to free-decay responses of a Space Shuttle tail rudder and successfully identified the seven modes of the structure below 250 Hz. The final modal parameters are a condensed set of results for 87 individual ERA cases requiring approximately five minutes of CPU time on a DEC Alpha computer.
Experimental Validation and Modal Analysis for a Highway Bridge
Authors: Sun Jinghui , Pang Jian , Song Gang , Patten William N.
Published: February 2021

This paper presents preliminary results of an experimental investigation of the modal characteristics of a 400′ continuous composite girder highway bridge on U.S. Interstate 35. The test data is compared to an analytical model based on the finite element (FE) method. An impact hammer was used as an exciter, and the bridge acceleration response was measured at 36 points. The results indicate that the analytical model can faithfully predict the modal response of the bridge.
Development of Structural Identification Accuracy Indicators Using Fuzzy Logic
Authors: Woodard Stanley E. , Pappa Richard S.
Published: February 2021

A fuzzy expert system was developed for autonomous in-space identification of spacecraft modal parameters. The in-space identification can be used to validate analytical predictions, detect structural damage, or tune automatic control systems as required. A fuzzy expert system determines accuracy of vibration data analysis performed autonomously using the Eigensystem Realization Algorithm. Evaluation of the data analysis output is imprecise and somewhat subjective. The expert system was developed using the knowledge provided the co-developer of the Eigensystem Realization Algorithm. The accuracy indicator represents the analyst’s degree of confidence in the analysis results. The fuzzy membership functions of the expert system were parameterized and tuned using numerical optimization.
Physically significant phase shifts in matter-wave interferometry
Authors: Overstreet Chris , Asenbaum Peter , Kasevich Mark A.
Published: February 2021

Many different formalisms exist for computing the phase of a matter-wave interferometer. However, it can be challenging to develop physical intuition about what a particular interferometer is actually measuring or about whether a given classical measurement provides equivalent information. Here, we investigate the physical content of the interferometer phase through a series of thought experiments. In low-order potentials, a matter-wave interferometer with a single internal state provides the same information as a sum of position measurements of a classical test object. In high-order potentials, the interferometer phase becomes decoupled from the motion of the interferometer arms, and the phase contains information that cannot be obtained by any set of position measurements on the interferometer trajectory. This phase shift in a high-order potential fundamentally distinguishes matter-wave interferometers from classical measuring devices.
Cardiorespiratory Responses to Constant and Varied-Load Interval Training Sessions
Authors: Beltrami Fernando G. , Roos Elena , von Ow Marco , Spengler Christina M.
Published: February 2021

Purpose: To compare the cardiorespiratory responses of a traditional session of high-intensity interval training session with that of a session of similar duration and average load, but with decreasing workload within each bout in cyclists and runners. Methods: A total of 15 cyclists (maximal oxygen uptake [] 62 [6] mL·kg−1·min−1) and 15 runners ( 58 [4] mL·kg−1·min−1) performed both sessions at the maximal common tolerable load on different days. The sessions consisted of four 4-minute intervals interspersed with 3 minutes of active recovery. Power output was held constant for each bout within the traditional day, whereas power started 40 W (2 km·h−1) higher and finished 40 W (2 km·h−1) lower than average within each bout of the decremental session. Results: Average oxygen uptake during the high-intensity intervals was higher in the decremental session in cycling (89 [4]% vs 86 [5]% of , P = .002) but not in running (91 [4]% vs 90 [4]% of , P = .38), as was the time spent >90% of and the time spent >90% of peak heart rate. Average heart rate (P < .001), pulmonary ventilation (P < .001), and blood lactate concentration (P < .001) were higher during the decremental sessions in both cycling and running. Conclusions: Higher levels of physiological perturbations were achieved during decremental sessions in both cycling and running. These differences were, however, more prominent in cycling, thus making cycling a more attractive modality for testing the effects of a training intervention.
A distinct population of heterogeneously color-tuned neurons in macaque visual cortex
Authors: Nigam Sunny , Pojoga Sorin , Dragoi Valentin
Published: February 2021

Diverse color tuning in V4 receptive fields points to its possible role in encoding complex color stimuli in natural environment.
An autophagy-related protein Becn2 regulates cocaine reward behaviors in the dopaminergic system
Authors: Kim Yoon-Jin , Kong Qingyao , Yamamoto Soh , Kuramoto Kenta , Huang Mei , Wang Nan , Hong Jung Hwa , Xiao Tong , Levine Beth , Qiu Xianxiu , Zhao Yanxiang , Miller Richard J. , Dong Hongxin , Meltzer Herbert Y. , Xu Ming , He Congcong
Published: February 2021

The addictive effects of cocaine are regulated by an autophagy protein and can be prevented by autophagy inhibitors.
Offshore pelagic subsidies dominate carbon inputs to coral reef predators
Authors: Skinner C. , Mill A. C. , Fox M. D. , Newman S. P. , Zhu Y. , Kuhl A. , Polunin N. V. C.
Published: February 2021

Coral reef predators are overwhelmingly sustained by offshore pelagic plankton sources rather than by reef-based sources.
Probing the genetic future of humanity
CRISPR People: The Science and Ethics of Editing Humans
Henry T. Greely
MIT Press, 2021. 400 pp.
Authors: Goldman Michael A.
Published: February 2021

A bioethicist breaks down the first human germline genome editing experiment
Opioid prescribing for chronic musculoskeletal pain in UK primary care: results from a cohort analysis of the COPERS trial
Authors: Ashaye Tomi , Hounsome Natalia , Carnes Dawn , Taylor Stephanie J C , Homer Kate , Eldridge Sandra , Spencer Anne , Rahman Anisur , Foell Jens , Underwood Martin R
Published: February 2021

Objective

To establish the level of opioid prescribing for patients with chronic musculoskeletal pain in a sample of patients from primary care and to estimate prescription costs.

Design

Secondary data analyses from a two-arm pragmatic randomised controlled trial (COPERS) testing the effectiveness of group self-management course and usual care against relaxation and usual care for patients with chronic musculoskeletal pain (ISRCTN24426731).

Setting

25 general practices and two community musculoskeletal services in the UK (London and Midlands).

Participants

703 chronic pain participants; 81% white, 67% female, enrolled in the COPERS trial.

Main outcome measures

Anonymised prescribing data over 12 months extracted from GP electronic records.

Results

Of the 703 trial participants with chronic musculoskeletal pain, 413 (59%) patients were prescribed opioids. Among those prescribed an opioid, the number of opioid prescriptions varied from 1 to 52 per year. A total of 3319 opioid prescriptions were issued over the study period, of which 53% (1768/3319) were for strong opioids (tramadol, buprenorphine, morphine, oxycodone, fentanyl and tapentadol). The mean number of opioid prescriptions per patient prescribed any opioid was 8.0 (SD=7.9). A third of patients on opioids were prescribed more than one type of opioid; the most frequent combinations were: codeine plus tramadol and codeine plus morphine. The cost of opioid prescriptions per patient per year varied from £3 to £4844. The average annual prescription cost was £24 (SD=29) for patients prescribed weak opioids and £174 (SD=421) for patients prescribed strong opioids. Approximately 40% of patients received >3 prescriptions of strong opioids per year, with an annual cost of £236 per person.

Conclusions

Long-term prescribing of opioids for chronic musculoskeletal pain is common in primary care. For over a quarter of patients receiving strong opioids, these drugs may have been overprescribed according to national guidelines.

Trial registration number

ISRCTN24426731; Post-results.
Re-evaluation of potential predictors of calretinin and mesothelin in a population-based cohort study using assays for the routine application in clinical medicine
Authors: Casjens Swaantje , Johnen Georg , Raiko Irina , Pesch Beate , Taeger Dirk , Töpfer Carmen , Schonefeld Sandra , Moebus Susanne , Jöckel Karl-Heinz , Brüning Thomas , Weber Daniel
Published: February 2021

Objectives

Calretinin and mesothelin are molecular markers for the detection of malignant mesothelioma at early stages. Our objective was the re-evaluation of factors influencing calretinin and mesothelin concentrations in plasma of cancer-free men in order to minimise false-positive tests when using commercial assays approved for clinical diagnostics.

Setting

This re-evaluation used data and archived blood samples of the population-based Heinz Nixdorf Recall Study (HNRS) collected from 2011 to 2014.

Participants

The present analysis comprised of 569 cancer-free men at the time of blood sampling (median age 70 years) from HNRS.

Primary and secondary outcomes

Mesothelin plasma concentration was determined using ELISA and CLEIA (chemiluminescent enzyme immunoassay). Calretinin plasma concentration was assessed using ELISA.

Results

Compared with the previous determination of concentrations, we detected less false-positive tests using the commercial assays. In this analysis, we found nine false-positive calretinin tests using the ELISA (specificity 98.4%, 95% CI 97.0% to 99.2%) and 24 false-positive mesothelin tests using both ELISA and CLEIA (specificity 95.8%, 95% CI 93.8% to 97.2%). We confirmed renal dysfunction as major predictor of elevated marker concentrations. Mesothelin was additionally affected by bronchitis. Furthermore, elevated inflammation values and hypertension only affected the mesothelin concentration determined by ELISA.

Conclusions

The newly available assays of calretinin and mesothelin approved for clinical diagnostics showed high specificities in the population-based cohort of elderly men without a malignant disease. The current evaluation provides a basis to consider influencing factors in order to further improve the diagnostic procedure.
Population impact of different hypertension management guidelines based on the prospective population-based Heinz Nixdorf Recall study
Authors: Gronewold Janine , Kropp Rene , Lehmann Nils , Stang Andreas , Mahabadi Amir A , Weimar Christian , Dichgans Martin , Moebus Susanne , Kröger Knut , Hoffmann Barbara , Jöckel Karl-Heinz , Erbel Raimund , Hermann Dirk M
Published: February 2021

Objective

Hypertension guidelines strongly differ between societies. The current American College of Cardiology/American Heart Association (ACC/AHA) guideline recommends higher proportions of the general population for antihypertensive medication than the previous American and European guidelines. How cardiovascular risk differs between persons with and without antihypertensive medication recommendation has not been examined. Additionally, the population impact of American, European and international guidelines has not been compared systematically within the same study population.

Methods

We compared the prevalence of antihypertensive medication recommendation according to the American (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 (JNC7), ACC/AHA 2017), European (European Society of Hypertension (ESH)/European Society of Cardiology (ESC) 2013/2018), and international (WHO/International Society of Hypertension (ISH) 2003, ISH 2020) guidelines in 3092 participants of the population-based Heinz Nixdorf Recall study not taking antihypertensive medication at the baseline examination (58.1±7.5 years, 48.7% males). We furthermore compared incident cardiovascular events during the 5-year follow-up between participants with and without antihypertensive medication recommendation.

Results

The ACC/AHA 2017 guideline recommended the highest percentage of participants for antihypertensive medication (45.8%) compared with the JNC7 (37.2%), ESH/ESC 2013 (17.8%), ESC/ESH 2018 (26.7%), WHO/ISH 2003 (20.3%) or ISH 2020 (25.0%) guidelines. Participants with antihypertensive medication recommendation according to the ACC/AHA 2017 guideline had a significantly higher incidence of cardiovascular events during the 5-year follow-up compared with participants without this recommendation (2.5% vs 1.1%, p=0.003).

Conclusions

Our results call for randomised controlled trials to investigate whether applying the stricter ACC/AHA 2017 recommendation leads to a reduction in cardiovascular disease.
Community-based non-pharmacological interventions for improving pain, disability and quality of life in pregnant women with musculoskeletal conditions: protocol for a systematic review with meta-analyses
Authors: Igwesi-Chidobe Chinonso N , Emmanuel Grace Nneoma , Okezue Obinna Chinedu
Published: February 2021

Introduction

Twenty five per cent of pregnant women with musculoskeletal pain have disabling symptoms that negatively influence quality of life. Studies have reported varying effects of non-pharmacological interventions including exercise, manipulation and pelvic belts for pregnant women with musculoskeletal problems. The overall effectiveness and acceptability of these interventions is uncertain due to lack of synthesised evidence. This protocol is for the first systematic review of community-based non-pharmacological interventions for improving pain, disability and quality of life in pregnant women with musculoskeletal conditions from studies published until August 2020.

Methods and analysis

A detailed search of PubMed, CINAHL, CENTRAL, Global Index Medicus, African Index Medicus, African Journal Online, Western Pacific Region Index Medicus, Latin American and Caribbean Centre on Health Science Information, Index Medicus for South-East Asia Region, IRIS (WHO digital publications), British Library for Development Studies and Google Scholar. Additional studies will be located from the reference list of identified studies and relevant systematic reviews. The databases will be searched from inception to August 2020. Appraisal of study quality will be performed with the Mixed Methods Appraisal Tool. Data will be synthesised using a mixed-studies synthesis design—the convergent synthesis. The description of interventions in all study designs will be summarised narratively. Meta-analyses will be used to statistically summarise the effectiveness of interventions in randomised controlled trials and the factors that influence these. Other quantitative studies will be summarised narratively to answer the objectives. Thematic synthesis will be used to summarise results of qualitative studies. The outcomes of interest include pain, disability and quality of life. This paper is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols 2015 guidelines.

Ethics and dissemination

Ethical clearance is not required. Findings will be presented at conferences and published in peer-reviewed journals.

PROSPERO registration number

CRD42020189535.
Population-based otoscopic and audiometric assessment of a birth cohort recruited for a pneumococcal vaccine trial 15–18 years earlier: a protocol
Authors: Chan Kenny H , Carosone-Link Phyllis , Bautista Mary Thatcher G , Sanvictores Diozele , Uhler Kristin , Tallo Veronica , Lucero Marilla G , De Jesus Joanne , Simões Eric A F
Published: February 2021

Introduction

A cohort of 12 000 children in the Philippines who had enrolled in a 2000–2004 (current ages 16 to 20 years) Phase 3 11-valent pneumococcal conjugate vaccine for the prevention of radiographically confirmed pneumonia are now being asked to participate in a separate study (expected completion date September 2021) to assess the cohort’s current long-term audiometric and otologic status. This new study would allow assessments of the utility of the pneumococcal vaccine in conferring its protective effects on the long-term sequelae of otitis media (OM), if any. Lack of trained local healthcare providers in otolaryngology/audiology and testing equipment in Bohol, Philippines, necessitates the development of a distinct methodology that would lead to meaningful data analysis.

Methods and analysis

Reliable data collection and transfer are achieved by a US otolaryngologist/audiologist team training local nurses on all procedures in a didactic and hands-on process. An assortment of portable otolaryngologic and audiologic equipment suitable for field testing has been acquired, including an operating otoscope (Welch-Allyn), a video-otoscope (JedMed), a tympanometer with distortion product otoacoustic emission measurements (Path Sentiero) and a screening audiometer (HearScreen). Data will then be uploaded to a Research Electronic Data Capture database in the USA.

Tympanometric and audiologic data will be codified through separate conventional algorithms. A team of paediatric otolaryngology advanced practice providers (APPs) have been trained and validated in interpreting video otoscopy. The protocol for classification of diagnostic outcome variables based on video otoscopy and tympanometry has been developed and is being used by APPs to evaluate all otoscopy data.

Ethics and dissemination

The study was approved by the Research Institute of Tropical Medicine, Alabang, Manila, Philippines, and the institutional review board and the Colorado Multiple Institutional Review Board of the University of Colorado School of Medicine, Aurora, Colorado, USA.

Research results will be made available to children and their caregivers with abnormal audiologic outcomes, the funders and other researchers.

Trial registration number

ISRCTN 62323832; Post-results.
Risk factors for COVID-19 infection, disease severity and related deaths in Africa: a systematic review
Authors: Gesesew Hailay Abrha , Koye Digsu Negese , Fetene Dagnachew Muluye , Woldegiorgis Mulu , Kinfu Yohannes , Geleto Ayele Bali , Melaku Yohannes Adama , Mohammed Hassen , Alene Kefyalew Addis , Awoke Mamaru Ayenew , Birhanu Mulugeta Molla , Gebremedhin Amanuel Tesfay , Gelaw Yalemzewod Assefa , Shifti Desalegn Markos , Muluneh Muluken Dessalegn , Tegegne Teketo Kassaw , Abrha Solomon , Aregay Atsede Fantahun , Ayalew Mohammed Biset , Gebre Abadi Kahsu , Gebremariam Kidane Tadesse , Gebremedhin Tesfaye , Gebremichael Lemlem , Leshargie Cheru Tesema , Kibret Getiye Dejenu , Meazaw Maereg Wagnew , Mekonnen Alemayehu Berhane , Tekle Dejen Yemane , Tesema Azeb Gebresilassie , Tesfay Fisaha Haile , Tesfaye Wubshet , Wubishet Befikadu Legesse , Dachew Berihun Assefa , Adane Akilew Awoke
Published: February 2021

Objective

The aim of this study was to provide a comprehensive evidence on risk factors for transmission, disease severity and COVID-19 related deaths in Africa.

Design

A systematic review has been conducted to synthesise existing evidence on risk factors affecting COVID-19 outcomes across Africa.

Data sources

Data were systematically searched from MEDLINE, Scopus, MedRxiv and BioRxiv.

Eligibility criteria

Studies for review were included if they were published in English and reported at least one risk factor and/or one health outcome. We included all relevant literature published up until 11 August 2020.

Data extraction and synthesis

We performed a systematic narrative synthesis to describe the available studies for each outcome. Data were extracted using a standardised Joanna Briggs Institute data extraction form.

Results

Fifteen articles met the inclusion criteria of which four were exclusively on Africa and the remaining 11 papers had a global focus with some data from Africa. Higher rates of infection in Africa are associated with high population density, urbanisation, transport connectivity, high volume of tourism and international trade, and high level of economic and political openness. Limited or poor access to healthcare are also associated with higher COVID-19 infection rates. Older people and individuals with chronic conditions such as HIV, tuberculosis and anaemia experience severe forms COVID-19 leading to hospitalisation and death. Similarly, high burden of chronic obstructive pulmonary disease, high prevalence of tobacco consumption and low levels of expenditure on health and low levels of global health security score contribute to COVID-19 related deaths.

Conclusions

Demographic, institutional, ecological, health system and politico-economic factors influenced the spectrum of COVID-19 infection, severity and death. We recommend multidisciplinary and integrated approaches to mitigate the identified factors and strengthen effective prevention strategies.
Fentanyl transdermal patches induced chemical leucoderma
Authors: Wattanapisit Sanhapan , Wattanapisit Apichai , Laksanapiya Pornnapat , Petmali Paisit
Published: February 2021

Chemical leucoderma is defined as hypopigmentation or vitiligo-like hypomelanosis caused by repeated chemical exposure, and the diagnosis can be made clinically. Chemical leucoderma induced by fentanyl transdermal patches is rare. This case report involves a 53-year-old man with chronic back pain caused by herniated nucleus pulposus at the L4–L5 level. The patient had used fentanyl transdermal patches for about 2 years. Depigmented lesions were observed in the areas where fentanyl transdermal patches had been applied. Chemical leucoderma was the most likely diagnosis. There remains a debate regarding whether there is a fentanyl dose–response relationship and whether the duration of exposure is relevant. Spontaneous repigmentation may occur after discontinuing the chemical exposure, and follow-ups are recommended to monitor whether spontaneous repigmentation occurs. Additionally, several treatment options have been proposed as specific treatments for chemical leucoderma, including psoralens, corticosteroids, calcineurin inhibitors, immunosuppressive agents and phototherapy.
Phase I study of ABBV-428, a mesothelin-CD40 bispecific, in patients with advanced solid tumors
Authors: Luke Jason J , Barlesi Fabrice , Chung Ki , Tolcher Anthony W , Kelly Karen , Hollebecque Antoine , Le Tourneau Christophe , Subbiah Vivek , Tsai Frank , Kao Steven , Cassier Philippe A , Khasraw Mustafa , Kindler Hedy L , Fang Hua , Fan Frances , Allaire Kathryn , Patel Maulik , Ye Shiming , Chao Debra T , Henner William R , Hayflick Joel S , McDevitt Michael A , Fong Lawrence
Published: February 2021

Background

CD40 agonist immunotherapy can potentially license antigen-presenting cells to promote antitumor T-cell activation and re-educate macrophages to destroy tumor stroma. Systemic administration of CD40 agonists has historically been associated with considerable toxicity, providing the rationale for development of tumor-targeted immunomodulators to improve clinical safety and efficacy. This phase I study assessed the safety, tolerability, preliminary antitumor activity, and preliminary biomarkers of ABBV-428, a first-in-class, mesothelin-targeted, bispecific antibody designed for tumor microenvironment-dependent CD40 activation with limited systemic toxicity.

Methods

ABBV-428 was administered intravenously every 2 weeks to patients with advanced solid tumors. An accelerated titration (starting at a 0.01 mg/kg dose) and a 3+3 dose escalation scheme were used, followed by recommended phase II dose cohort expansions in ovarian cancer and mesothelioma, tumor types associated with high mesothelin expression.

Results

Fifty-nine patients were treated at doses between 0.01 and 3.6 mg/kg. The maximum tolerated dose was not reached, and 3.6 mg/kg was selected as the recommended phase II dose. Seven patients (12%) reported infusion-related reactions. Treatment-related grade ≥3 treatment-emergent adverse events were pericardial effusion, colitis, infusion-related reaction, and pleural effusion (n=1 each, 2%), with no cytokine release syndrome reported. The pharmacokinetic profile demonstrated roughly dose-proportional increases in exposure from 0.4 to 3.6 mg/kg. Best response was stable disease in 9/25 patients (36%) treated at the recommended phase II dose. CD40 receptor occupancy >90% was observed on peripheral B-cells starting from 0.8 mg/kg; however, no consistent changes from baseline in intratumoral CD8+ T-cells, programmed death ligand-1 (PD-L1+) cells, or immune-related gene expression were detected post-ABBV-428 treatment (cycle 2, day 1). Mesothelin membrane staining showed greater correlation with progression-free survival in ovarian cancer and mesothelioma than in the broader dose escalation population.

Conclusions

ABBV-428 monotherapy exhibited dose-proportional pharmacokinetics and an acceptable safety profile, particularly for toxicities characteristic of CD40 agonism, illustrating that utilization of a tumor-targeted, bispecific antibody can improve the safety of CD40 agonism as a therapeutic approach. ABBV-428 monotherapy had minimal clinical activity in dose escalation and in a small expansion cohort of patients with advanced mesothelioma or ovarian cancer.

Trial registration number

NCT02955251.
Use of pembrolizumab with or without pomalidomide in HIV-associated non-Hodgkin’s lymphoma
Authors: Lurain Kathryn , Ramaswami Ramya , Mangusan Ralph , Widell Anaida , Ekwede Irene , George Jomy , Ambinder Richard , Cheever Martin , Gulley James L , Goncalves Priscila H , Wang Hao-Wei , Uldrick Thomas S , Yarchoan Robert
Published: February 2021

Background

Non-Hodgkin’s lymphoma (NHL) is currently the most common malignancy among people living with HIV (PLWH) in the USA. NHL in PLWH is more frequently associated with oncogenic viruses than NHL in immunocompetent individuals and is generally associated with increased PD-1 expression and T cell exhaustion. An effective immune-based second-line approach that is less immunosuppressive than chemotherapy may decrease infection risk, improve immune control of oncogenic viruses, and ultimately allow for better lymphoma control.

Methods

We conducted a retrospective study of patients with HIV-associated lymphomas treated with pembrolizumab±pomalidomide in the HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute.

Results

We identified 10 patients with stage IV relapsed and/or primary refractory HIV-associated NHL who were treated with pembrolizumab, an immune checkpoint inihibitor, with or without pomalidomide. Five patients had primary effusion lymphoma (PEL): one had germinal center B cell-like (GCB) diffuse large B cell lymphoma (DLBCL); two had non-GCB DLBCL; one had aggressive B cell lymphoma, not otherwise specified; and one had plasmablastic lymphoma. Six patients received pembrolizumab alone at 200 mg intravenously every 3 weeks, three received pembrolizumab 200 mg intravenously every 4 weeks plus pomalidomide 4 mg orally every day for days 1–21 of a 28-day cycle; and one sequentially received pembrolizumab alone and then pomalidomide alone. The response rate was 50% with particular benefit in gammaherpesvirus-associated tumors. The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95% CI: 2.96 to not reached). Three patients with PEL had leptomeningeal disease: one had a complete response and the other two had long-term disease control. There were four immune-related adverse events (irAEs), all CTCAEv5 grade 2–3; three of the four patients were able to continue receiving pembrolizumab. No irAEs occurred in patients receiving the combination of pembrolizumab and pomalidomide.

Conclusions

Treatment of HIV-associated NHL with pembrolizumab with or without pomalidomide elicited responses in several subtypes of HIV-associated NHL. This approach is worth further study in PLWH and NHL.
Cosmic inflation in minimal $$U(1)_{B-L}$$ model: implications for (non) thermal dark matter and leptogenesis
Authors: Borah Debasish , Das Suruj Jyoti , Saha Abhijit Kumar
Published: February 2021

We study the possibility of realising cosmic inflation, dark matter (DM), baryon asymmetry of the universe (BAU) and light neutrino masses in non-supersymmetric minimal gauged $$B-L$$

B
-
L

extension of the standard model with three right handed neutrinos. The singlet scalar field responsible for spontaneous breaking of $$B-L$$

B
-
L

gauge symmetry also plays the role of inflaton by virtue of its non-minimal coupling to gravity. While the lightest right handed neutrino is the DM candidate, being stabilised by an additional $$Z_2$$

Z
2

symmetry, we show by performing a detailed renormalisation group evolution (RGE) improved study of inflationary dynamics that thermal DM is generally overproduced due to insufficient annihilations through gauge and scalar portals. This happens due to strict upper limits obtained on gauge and other dimensionless couplings responsible for DM annihilation while assuming the non-minimal coupling to gravity to be at most of order unity. The non-thermal DM scenario is viable, with or without $$Z_2$$

Z
2

symmetry, although in such a case the $$B-L$$

B
-
L

gauge sector remains decoupled from the inflationary dynamics due to tiny couplings. We also show that the reheat temperature predicted by the model prefers non-thermal leptogenesis with hierarchical right handed neutrinos while being consistent with other requirements.
Bounce cosmology in $$f({\mathcal {R}})$$ gravity
Authors: Ilyas M. , Rahman W. U.
Published: February 2021

In this paper, we analyze the modified $$f({\mathcal {R}})$$

f
(
R
)

gravity models in Friedmann–Lemaître–Robertson–Walker (FLRW) background. The actions of bouncing cosmology are studied under consideration of different viable models in $$f({\mathcal {R}})$$

f
(
R
)

gravity theory that can resolve the difficulty of singularity in standard Big-Bang cosmology. Under different viable models in $$f({\mathcal {R}})$$

f
(
R
)

gravity theory, the cosmological constraints are plotted in provisions of cosmic-time, then investigated the bounce circumstance. In addition, the red-shift parameter is used to reconstruct the modified gravity, and compile the cosmological parameters that infer accelerated universe expansion. Finally, the situation stability is evaluated with a sound speed feature, which illustrates late-time stability.