bluuebunny/crossref_metadata_2025 huggingface dataset:
A Quintic Spline Interpolator for Motion Command Generation of Computer-Controlled Machines
Authors: Yang D. C. H. , Wang Fu-Chung
Published: March 2021

This paper presents a new method of motion command generation for computer controlled multi-axis machines. The method is based on a quintic spline interpolator (QSI) which generates motion commands to trace a set of desired discrete position data via a composite quintic spline (CQS). This CQS is nearly arc length parametrized and has both tangents and curvatures continuous at the data points. Consequently, the generated motion trajectories are continuous in both velocity and acceleration throughout the motion. A quick motion command generation scheme is also developed. Compared to the existing linear interpolator (LI), the proposed method takes comparable execution time, but is superior in many other aspects, including position accuracy, speed smoothness, acceleration continuity, torque requirement and jerk reduction. Compared to the existing cubic spline interpolator (CSI), the proposed method is able to maintain a similarly smooth composite profile, but better speed accuracy. On-line implementation of this interpolator is believed very promising.
Optimization of Mechanism Timing Using Noncircular Gearing
Authors: Bernard Judd
Published: March 2021

A single degree of freedom mechanism whose input link is a crank driven through continuous revolutions will generate output motions dependent upon the inherent mechanism geometry. For example, the slider of a slider-crank mechanism has a linear displacement (the output motion) as a function of the crank rotation (input). Only within the realm of link proportioning can the slider crank output-input function be altered.

In this investigation, the continuously rotating crank of a mechanism is rigidly attached to a gear which is one of a pair of externally meshing noncircular gears. By using noncircular gears, it will be shown that the output motion of the given mechanism can be correlated to the rotation of the mating gear to which the crank is not attached. In this fashion, the output link can then be made to execute its motion according to any prescribed law. The above technique has been implemented for the cases of a crank and rocker mechanism and a slider-crank mechanism.
Synthesis of an RSSR-SS Mechanism Using a Continuation Method
Authors: Subbian Thiagaraj , Flugrad Donald R.
Published: March 2021

Precision position synthesis of an RSSR-SS mechanism is considered. The RSSR-SS mechanism is broken up into two RS and one SS dyads. These components are designed independently using a continuation method. This treatment is possible for a maximum of four precision positions.

A parameter homotopy is implemented for the RS dyads and a 3-homogeneous traditional homotopy is used for the SS dyad design. Two example problems are considered.
Position and Force Control of Multibody Systems by Feedback Linearization
Authors: Woernle Christoph
Published: March 2021

A unified formulation of the feedback linearization method to the hybrid position and force control of constrained multibody systems is developed. Similar to the feedback linearization of unconstrained systems, linear decoupled input-output channels for position and force control variables, which can be controlled separately, and a nonlinear nonobservable internal dynamics are obtained. Technical applications are robotic systems with multiple, interacting arms, multifingered grippers grasping an object, mechanisms with controlled motion, or walking machines.
Formulating Dynamic Equations of Elastic Multibody System via the Method of Typical Substructures
Authors: Hongzhao Liu , Cao Wei-qing
Published: March 2021

In this paper, a method of using multibodies as substructures to establish the dynamic equations of elastic multibody systems involving closed loops is put forward. Plane elastic linkage is divided into four typical substructures, and equations of free two-link dyad — the most general one among the four substructures — are derived. Also some examples of substuctures’ partitioning of mechanisms are given to show the present method’s advantages. By means of the present method, the number of system’s constraint equations can be greatly reduced, and it will facilitate solving dynamic equations on a microcomputer.
The Effects of the Manipulator Type on the Vibrational Excitation During Motion
Authors: Tu Q. , Rastegar Jahangir
Published: March 2021

The relationship between the structural type of a manipulator and its susceptibility to motion induced vibrational excitation is examined. For manipulators of different type, the average potential resonant energy transfer to a robot manipulator system by the higher harmonics of the actuating torques (forces) necessary for tracking trajectories that are uniformly distributed within a representative task space are determined, and used as a measure of the potential for vibrational excitation during motion. The manipulators are kinematically and dynamically equivalent. From the vibration and control points of view, manipulator types that do not demand high frequency actuating torque harmonics are more desirable, since the natural modes of vibration of mechanical systems are most likely to be excited by the higher harmonics of the actuating torques, and because of practical dynamic response limitations of all mechanical systems. As examples, plane two and three degrees-of-freedom manipulators constructed with revolute and prismatic joints are studied. Numerical calculations of the aforementioned and the total expected (average) energy input and the corresponding variances are presented for the two degrees-of-freedom manipulators. A number of points of interest are discussed.
Computer-Based Kinematical Analysis of Spatial Multiloop Mechanisms
Authors: Hiller Manfred , Möller Manfred
Published: March 2021

In this paper a method for the automatical analysis of the kinematics of spatial multiloop mechanisms is presented. The mechanism is regarded as a multibody system. Connecting joints are revolute joints (R), prismatic joints (P), spherical joints (S) and all further joints that can be modelled as combinations of these joints. The concept allows the application for a user without deeper theoretical knowledge of spatial kinematics. Special effort has been taken in the reduction of the number of nonlinear constraint equations that must be solved. This is done by using an approach, yielding a suitable structure of the system of nonlinear constraint equations, where only those with interesting unknown joint coordinates must be solved. An optimized solution of these equations allows in many cases a partly and sometimes even a completely explicit solution of the constraint equations. The described method is also applicable to overconstrained spatial mechanisms.
Assemblability, Circuits, Branches, Locking Positions and Rotatability of Input Link of Mechanisms With Four Closures
Authors: Kohli Dilip , Cheng Jyun-Cheng , Tsai K. Y.
Published: March 2021

A general analytical treatment is provided for determining the conditions for the assemblability, rotatability of input link, locking positions and the number of circuits of mechanisms with four closures and a quartic input-output displacement polynomial. It is shown that the assemblability, rotatability of input crank and the locking positions are branch dependent properties for the mechanisms with four closures and such mechanisms, in genera], can have many branch dependent circuits. Such mechanisms may be assemblable for only two branches instead of all four. It is shown that the input link rotatability is not only branch dependent but also depends on the starting position and the direction of motion of the input link. The input link may be continuously rotatable for one branch while for the other branch it may go through one cycle of rotation (> 2π but less than 4π) and then experience a locking position.

Examples dealing with assemblability, branching, locking positions, and rotatability of the input link is presented for the spatial five-link RRRSR, RPRSR, RRPSR, and RRRSR mechanisms are presented.
Study on the Spatial Linkage With the Property of Constant Pressure Angle
Authors: Wenjun Zhang , Breteler A. J. Klein
Published: March 2021

This paper for the first time detects a new kind of spatial linkage which has the property of constant pressure angle (termed as CPA), that is, the pressure angle of linkage keeps a constant value during the gross motion of the input. The existence and the method to detect out this kind of spatial linkage have been discussed. Two cases with the property of CPA have been found for the spatial linkage RSSR.
Motion Representation: Different Conventional Forms, Duplex Mapping and Conjugation Form
Authors: Chen Chih-Hsin , Chen Hong-Jian
Published: March 2021

Four fundamental forms for representing rigid body motion, i.e. the rotation-of-vector form, the matrix form, the quaternion form and the screw form, all based on the conventional concept that motion is specified by the movement of a reference point together with an orientation change, are expounded. The inter-relationships among these forms are elucidated. The geometric images of these representation-forms, i.e. the motion mappings, are explained, and an innovative duplex-mapping, a powerful tool for mobility analysis of multi-loop mechanisms and robots, is introduced. An exotic motion representation, based on a concept totally different from the conventional concept, is described. This is a purely geometric representation, a representation by a pair of conjugate curves on respective conjugate surfaces, and is called the conjugation form of motion representation. The conversion from the conjugation form to the rotation-of-vector form and the inverse conversion are described. These conversions, which constitute the essential and featured contents of the Theory of Conjugate Surfaces, have great potential applications in motion design for numerically controlled manufacturing and in surface generation by numerically controlled manufacturing. The basis equations for the conversions, i.e. the three relationship-equations, are deduced. The fundamental equation conjugation, the four conjugato-kinematic entities and the five differential formulas for the inverse conversion are derived.
Periodic Response and Stability of Flexible Rod Slider Crank Mechanism
Authors: Lee Shyr Wen , Beale David G.
Published: March 2021

Periodic steady state solutions are generated from the nonlinear differential equation of an Euler-Bernoulli beam rod, constant speed crank, slider crank mechanism. The system is approximated by a single ordinary differential equation. To facilitate Harmonic Balance, the response and difficult nonlinear and linear portions of the ODE are expanded into two separate Fourier Series. Harmonic Balance/Fast Fourier Transform method is utilized to determine the harmonic content of each Fourier Series and generate periodic solutions which compared favorably with Runge-Kutta numerical integration. Stability of periodic solutions was examined using the monodromy matrix method. Nondimensional amplitude versus nondimensional crank speed was plotted to examine the effect on dynamic response of external force, piston mass, and crank length. Jump and period doubling bifurcations and regions of amplified response were found.
The Elastic Slider-Crank Mechanism: A Study of the Intrinsic Configuration-Dependent Modal Properties
Authors: Midha Ashok , Karam D. , Thompson B. S.
Published: March 2021

In recent years, an ever-increasing demand has been placed on manufacturing for increased productivity, requiring machines to run faster, quieter and with greater precision. This has necessitated that the elastodynamic behavior of mechanisms be carefully evaluated if better machinery must be designed. Although numerous works have been presented for computing the response of mechanisms containing elements characterized by distributed mass and elasticity, very little has been revealed about their modal properties. This paper addresses the modeling of planar slider-crank mechanisms, a popular class of mechanisms, for geometrically nonlinear, elastodynamic response. A modal analysis is performed for varying positions of the crank, and configuration-dependent natural frequencies and mode shapes are presented as functions of the crank position. The results, which includes a study of the effects of some design parameters on these modal properties, should provide new and valuable insights to the designer and researcher alike. These intrinsic modal properties will directly affect the parametric vibrational response and stability characteristics of elastic slider-crank mechanisms.
An Analytical Method for Locating Velocity Instantaneous Centers
Authors: Yan Hong-Sen , Hsu Meng-Hui
Published: March 2021

An analytical method is presented for locating all velocity instantaneous centers of linkage mechanisms with single or multiple degrees of freedom. The method is based on the fact that the coefficient matrix of the derived velocity equations for vector loops, independent inputs, and instantaneous centers is singular. This approach also works for special cases with kinematic indeterminacy or singular configurations.
Kinematic Analysis and Design of Two-Input, Five-Bar Mechanisms Driven by Relatively Small Cranks
Authors: Basu Partha Sarathi , Farhang Kambiz
Published: March 2021

Single input mechanisms driven by relatively small cranks have been shown to have output link motions which may be approximately described as simple harmonic functions of the input crank angular displacement. This paper presents a mathematical formulation for the approximate analysis and design of two-input, small-crank five-bar mechanisms for function generation. A perturbation technique is employed for the derivation of the approximate equations. Coefficients of the harmonic terms in the output motion equations are obtained from the mechanism geometry and application of the perturbation technique. The output link motions are shown to be approximately described by a linear combination of two simple harmonic functions, in terms of the two input crank angles. The utility of the equations are demonstrated through several mechanism synthesis examples.
An Efficient Algorithm for Finding Optimum Code Under the Condition of Incident Degree
Authors: Jongsma T. J. , Zhang W.
Published: March 2021

This paper deals with the identification of kinematic chains. A kinematic chain can be represented by a weighed graph. The identification of kinematic chains is thereby transformed into the isomorphism problem of graph. When a computer program has to detect isomorphism between two graphs, the first step is to set up the corresponding connectivity matrices for each graph, which are adjacency matrices when considering adjacent vertices and the weighed edges between them. Because these adjacency matrices are dependent of the initial labelling, one can not conclude that the graphs differ when these matrices differ. The isomorphism problem needs an algorithm which is independent of the initial labelling. This paper provides such an algorithm.
Dynamics of Single-Loop Mechanisms With Flexible Links
Authors: Darcovich John , Angeles Jorge , Misra Arun K.
Published: March 2021

A formulation of the dynamical equations of a general, spatial, single-loop mechanism with any combination of rigid and flexible links is developed. This formulation resorts to the natural orthogonal complement (NOC) to eliminate non-working constraint forces from the equations of motion, an approach which offers several advantages. First, the equations of motion are formulated disregarding the non-working constraint forces, since they are eventually eliminated and need not be computed. Secondly, the final equations of motion are described in terms of a minimum number of generalized coordinates, this number being the degree of freedom of the system at hand. Finally, the problems associated with solving a system of differential and algebraic equations, which usually occurs when Lagrange multipliers are introduced, are avoided, since the constraints are incorporated naturally into the differential equations of motion. The above formulation is used to perform dynamic simulations of flexible-link mechanisms with a kinematic loop.
On the Limitations of Predictions of the Dynamic Response of Machines With Clearance Connections
Authors: Deck Joseph F. , Dubowsky Steven
Published: March 2021

The results of experimental and analytical studies of the dynamic response of machines with flexible links and connection clearances are presented. These results suggest that the actual dynamic response of such systems inherently exhibits both a large amount of variability and high sensitivity to small parameter changes and operating conditions. This work suggests that the accuracy of the dynamic force predictions given by computer simulations for such systems is fundamentally limited, and therefore such simulations should be used in system design with care.
Virtual Wedging in Three Dimensional Peg Insertion Tasks
Authors: Sturges Robert H. , Laowattana Schitt
Published: March 2021

Quasi-static wedging of three-point contacts is investigated, wherein the concepts of virtual and redundant wedging due to a resultant force falling into a friction cone are proposed. We consider the fully-started case of a square peg and hole consisting of two point-surface contacts and one line-line contact. An analysis of the wedging diagram for this highly constrained configuration is carried out and compared to the two dimensional case. An approximate wedging diagram is constructed which shows that wedging of square pegs into square holes is more likely than cylindrical pegs and holes of similar sizes.
Selective Robotic Assembly
Authors: Berzak Nir
Published: March 2021

A new approach to robotic high precision selective assembly is presented. The basis for this selective assembly is a gripper which both grips the part to be assembled along its mating planes and inspects its dimensions while gripping. One hundred percent interchangeability of spare parts is achieved by selecting the appropriate parts for inventory, during assembly. Cost reduction and the increase in product quality are shown by example.
Collision-Free Path Generation for Autonomous Manipulators Using Non-Uniform Rational B-Spline (NURBS) via Artificial Transformation
Authors: Soni N. , Shirkhodaie A. , Soni A. H.
Published: March 2021

This paper presents an algorithm for collision free path planning of autonomous manipulators among obstacles. The algorithm uses powerful features of Non-Uniform Rational B-splines (NURBS) to determine the path of the manipulator in the complimentary space of the obstacles. Initially the algorithm artificially transforms the obstacles to point size. It then uses these point obstacles and start & target position of the manipulator as control points to determine a NURBS path which is the initial collision-free path. Obstacles are then iteratively increased in size by small increments. After each increment the new collision control points with obstacles are determined and a new collision-free NURBS path is generated to guide the manipulator through crowded obstacles. This procedure is continued till all the obstacles attain their full size and resulting path is maintained free of collision. The developed algorithm is most suited for manipulators facilitated with range sensors for remote detection of obstacles. The paper details the technique for obtaining a smooth collision-free path of a manipulator moving around a crowded environment with static obstacles.
A Robotic Tool Transformation Teacher
Authors: Hunt Scott E. , Derby Stephen J.
Published: March 2021

The objective of this project was to design and build a system for teaching robot tool transformations. A PUMA and an Adept One robot were used for testing the feasibility of the system. The Tool Transformation Teacher provides for both the manual and programmed control of a robotic manipulator with respect to a tool coordinate system, thus increasing robot flexibility.
Robotic Assembly of Welded Truss Structures in Space
Authors: Jones Clyde S. , Thomas Frank , Brewer William V.
Published: March 2021

A capability for welding in-space as a method of making permanent joints for vehicles and structures assembled on-orbit is under development. This project is part of an in-space assembly and construction program to develop the requirements and technology needed to build elements in space. This paper describes an approach to the welding of tubular truss strut joints for a range of diameters. The conceptual design of a mechanism to position the strut in the truss and weld it in place is also outlined. Considerations for the use of welding as a tool for in-space construction are discussed.
Testing CALS Standards for Engineering and Manufacturing Applications
Authors: Craig J. I. , Fulton Robert E. , Stephen E. R. , Jarnagin A. B.
Published: March 2021

Standards verification in a CALS environment can be a complex and demanding process requiring not only a complete understanding of the standard but also the planned application and software implementation. An area of particular concern is the adequacy of vector or geometry based standards such as IGES to represent engineering and manufacturing applications. In such cases the visual similarity of geometry can be an inadequate test of the validity of a data exchange. Analytically oriented use of the geometry representation of some design and manufacturing applications may require very precise exchange of geometric entities.

This paper will focus on testing strategies to provide comprehensive evaluations of vector based geometry standards such as IGES for engineering analysis, design and manufacturing use. The tests will show effective ways to measure whether vendor translators adequately capture key behavior needed in such applications. Results will be illustrated through tests at the Georgia Tech CALS Research Center which includes several different workstations and associated CAD software systems. CALS Class II test suites taken from representative aerospace applications are used to illustrate these concepts. The results show the importance of such testing in the verification of future CALS standards built around the PDES/STEP efforts. Finally the paper will outline the role and importance of an analytic testing facility in a comprehensive academic research program on information technology for engineering and how it influences current and future engineering education.
Implementing the CAM-I Application Interface Specification With UNIX Interprocess Communication
Authors: Richardson David C. , Magleby Spencer P.
Published: March 2021

The CAM-I Application Interface Specification (AIS) allows applications to access a geometric modeler for model analysis using a standardized interface. This is accomplished by linking the source or object codes of the application and modeler together at compile time along with the AIS implementation for the modeler. This methodology requires at least the object code of both programs and results in a single, large executable program dedicated to the use of the specific application and modeler only. By using interprocess communication (IPC) with the AIS, the two programs can remain separate and be used with other modelers and applications rather than only with each other. The approach used in defining the AIS/IPC adaptation issues and developing and testing concepts to address those issues resulted in successfully implementing AIS using the messaging routines of IPC. This allowed an independent application to invoke and interface with an independent geometric modeler and perform analyses on representative models. The implications of the approach used and the implementation of AIS with IPC in engineering are broad. Using a modified form of the AIS/IPC, an application could theoretically interface with a modeler on a remote system far from the host.
Critical Success Factors for Implementing a Configuration Management System
Authors: Novy David R.
Published: March 2021

Companies must deliver quality products to market in the shortest possible time in order to remain competitive in today’s business environment. One technology tool which is emerging as a key to reducing time to market is configuration management. This paper discusses why configuration management is important and the the critical success factors for the effective implementation of a configuration management system.
A Product Data Model for Design Support Using Functional Skeletons
Authors: Stadlbauer Harald
Published: March 2021

This paper presents a new method called Functional Skeletons and its usage for a product data model for the design process. The Functional Skeletons represent the main functional flows in a product and allow the efficient storage of designs as well as the generation of verified (in respect to their specification) products. The Functional Skeletons can be used as the basis of a new type of product data models.
IFNAR1 signaling in NK cells promotes persistent virus infection
Authors: Huang Zhe , Kang Seung Goo , Li Yunqiao , Zak Jaroslav , Shaabani Namir , Deng Kaiyuan , Shepherd Jovan , Bhargava Raag , Teijaro John R. , Xiao Changchun
Published: March 2021

IFNAR1 signaling in NK cells compromises cellular and humoral immune responses to hamper virus control.
Atomic–layer–confined multiple quantum wells enabled by monolithic bandgap engineering of transition metal dichalcogenides
Authors: Kim Yoon Seok , Kang Sojung , So Jae-Pil , Kim Jong Chan , Kim Kangwon , Yang Seunghoon , Jung Yeonjoon , Shin Yongjun , Lee Seongwon , Lee Donghun , Park Jin-Woo , Cheong Hyeonsik , Jeong Hu Young , Park Hong-Gyu , Lee Gwan-Hyoung , Lee Chul-Ho
Published: March 2021

Multiple quantum wells based on 2D semiconductors are realized by monolithic bandgap engineering and van der Waals stacking.
Multimerization variants as potential drivers of neofunctionalization
Authors: Lee Youngwoo , Szymanski Daniel B.
Published: March 2021

A high-throughput analysis of protein complex variants among orthologs provides a mechanistic model for neofunctionalization.
Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability
Authors: Nagayoshi Y. , Chujo T. , Hirata S. , Nakatsuka H. , Chen C.-W. , Takakura M. , Miyauchi K. , Ikeuchi Y. , Carlyle B. C. , Kitchen R. R. , Suzuki T. , Katsuoka F. , Yamamoto M. , Goto Y. , Tanaka M. , Natsume K. , Nairn A. C. , Suzuki T. , Tomizawa K. , Wei F.-Y.
Published: March 2021

Defective tRNA 2′-
O
-modification impairs translation efficiency at Phe codon in the brain and induces a neurological dysfunction.
Structural tuning of heterogeneous molecular catalysts for electrochemical energy conversion
Authors: Wang Jiong , Dou Shuo , Wang Xin
Published: March 2021

The structural tuning of first and second coordination spheres of heterogeneous molecular catalysts is reviewed.
Oxidation of trimethylamine to trimethylamine
N
-oxide facilitates high hydrostatic pressure tolerance in a generalist bacterial lineage
Authors: Qin Qi-Long , Wang Zhi-Bin , Su Hai-Nan , Chen Xiu-Lan , Miao Jie , Wang Xiu-Juan , Li Chun-Yang , Zhang Xi-Ying , Li Ping-Yi , Wang Min , Fang Jiasong , Lidbury Ian , Zhang Weipeng , Zhang Xiao-Hua , Yang Gui-Peng , Chen Yin , Zhang Yu-Zhong
Published: March 2021

Accumulation of trimethylamine
N
-oxide improves both growth and survival of deep-sea bacteria under high hydrostatic pressure.
A cross-talk between CAR T cell subsets and the tumor microenvironment is essential for sustained cytotoxic activity
Authors: Boulch Morgane , Cazaux Marine , Loe-Mie Yann , Thibaut Ronan , Corre Béatrice , Lemaître Fabrice , Grandjean Capucine L. , Garcia Zacarias , Bousso Philippe
Published: March 2021

A cross-talk involving CAR T cell–derived IFN-γ and host-derived IL-12 is essential to maintain CAR T cell killing potential in vivo.
Decoupling of Au and As during rapid pyrite crystallization
Authors: Wu Ya-Fei , Evans Katy , Hu Si-Yu , Fougerouse Denis , Zhou Mei-Fu , Fisher Louise A. , Guagliardo Paul , Li Jian-Wei
Published: March 2021

Gold (Au) is largely hosted by pyrite in a variety of hydrothermal systems, but the incorporation of Au into pyrite under disequilibrium conditions remains poorly understood. We integrate synchrotron X-ray fluorescence microscopy, electron backscatter diffraction, nanoscale secondary ion mass spectrometry, and laser ablation–multicollector–inductively coupled plasma–mass spectrometry to constrain the processes that sequester Au into zoned pyrite in the hydrothermal cement of breccia ores from the world-class Daqiao orogenic Au deposit, central China. Euhedral pyrite cores with oscillatory and sector zoning, variable δ34S values, and lower Au-As contents than the mantles are attributed to crystallization during oxidation of metal-depleted ore fluids with local variation in fluid conditions. The isotopically uniform colloform mantles are formed by pyrite crystallites separated by low-angle boundaries and are characterized by unusual decoupling of Au and As. Mantle formation is attributed to rapid disequilibrium precipitation from a metal-rich FeS2-supersaturated fluid. Incorporation of Au into the pyrite mantles was facilitated by abundant lattice defects produced by rapid nucleation. Gold-As–poor pyrite rims were deposited from an evolved ore fluid or other metal-depleted fluids. These results show that chemical variations recorded by fine layering within minerals can provide valuable insights into disequilibrium mass transfer and ore formation. The decoupling between Au and As in pyrite mantles indicates that As is not always a reliable proxy for Au enrichment in rapidly crystallized porous pyrite.
Granulomatosis with polyangiitis manifesting as fever of unknown origin
Authors: Mahfooz Faisal , Duffee Douglas , Chavda Rupal
Published: March 2021

Fever of unknown origin (FUO) has a broad differential diagnosis, including infectious, inflammatory and malignant aetiologies. Granulomatosis with polyangiitis (GPA) can present with non-specific symptoms, including fever, lethargy and flu-like illness. While systemic vasculitis causing FUO has been well-documented, GPA as an underlying cause for FUO poses a diagnostic and therapeutic challenge for clinicians. We present the case of a 65-year-old man who presented to the emergency department with a report of fever, myalgia and night sweats for greater than 3 weeks. After an extensive workup, the patient was diagnosed with GPA and he eventually responded to corticosteroids and immunosuppressive therapy. This case aims to raise awareness of FUO secondary to GPA and serves as a reminder to clinicians that early recognition and prompt treatment of this syndrome improves patient outcomes.
Lack of effect ofLactobacillus rhamnosusGG andBifidobacterium lactisBb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomised controlled trial
Authors: Groele Lidia , Szajewska Hania , Szalecki Mieczysław , Świderska Jolanta , Wysocka-Mincewicz Marta , Ochocińska Agnieszka , Stelmaszczyk-Emmel Anna , Demkow Urszula , Szypowska Agnieszka
Published: March 2021

Introduction

The gut microbiota may be relevant in the development of type 1 diabetes (T1D). We examined the effects ofLactobacillus rhamnosusGG andBifidobacterium lactisBb12 on beta-cell function in children with newly diagnosed T1D.

Research design and methods

Children aged 8–17 years with newly (within 60 days) diagnosed T1D were enrolled in a double-blind, randomised controlled trial in which they receivedL. rhamnosusGG andB. lactisBb12 at a dose of 109colony-forming units or placebo, orally, once daily, for 6 months. The follow-up was for 12 months. The primary outcome measure was the area under the curve (AUC) of the C-peptide level during 2-hour responses to a mixed meal.

Results

Ninety-six children were randomised (probiotics, n=48; placebo n=48; median age 12.3 years). Eighty-eight (92%) completed the 6-month intervention, and 87 (91%) completed the follow-up at 12 months. There was no significant difference between the study groups for the AUC of the C-peptide level. For the secondary outcomes at 6 months, there were no differences between the study groups. At 12 months, with one exception, there also were no significant differences between the groups. Compared with the placebo group, there was a significantly increased number of subjects with thyroid autoimmunity in the probiotic group. However, at baseline, there was also a higher frequency of thyroid autoimmunity in the probiotic group. There were no cases of severe hypoglycemia or ketoacidosis in any of the groups. No adverse events related to the study products were reported.

Conclusions

L. rhamnosusGG andB. lactisBb12, as administered in this study, had no significant effect in maintaining the residual pancreatic beta-cell function in children with newly diagnosed T1D. It remains unclear which probiotics, if any, alone or in combination, are potentially the most useful for management of T1D.

Trial registration number

NCT03032354.
Incidence and pathophysiology of diabetes in South Asian adults living in India and Pakistan compared with US blacks and whites
Authors: Narayan K M Venkat , Kondal Dimple , Daya Natalie , Gujral Unjali P , Mohan Deepa , Patel Shivani A , Shivashankar Roopa , Anjana Ranjit Mohan , Staimez Lisa R , Ali Mohammed K , Chang Howard H , Kadir Masood , Prabhakaran Dorairaj , Selvin Elizabeth , Mohan Viswanathan , Tandon Nikhil
Published: March 2021

Introduction

We compared diabetes incidence in South Asians aged ≥45 years in urban India (Chennai and Delhi) and Pakistan (Karachi), two low-income and middle-income countries undergoing rapid transition, with blacks and whites in the US, a high-income country.

Research design and methods

We computed age-specific, sex-specific and body mass index (BMI)-specific diabetes incidence from the prospective Center for Cardiometabolic Risk Reduction in South Asia Study (n=3136) and the Atherosclerosis Risk in Communities Study (blacks, n=3059; whites, n=9924). We assessed factors associated with incident diabetes using Cox proportional hazards regression.

Results

South Asians have lower BMI and waist circumference than blacks and whites (median BMI, kg/m2: 24.9 vs 28.2 vs 26.0; median waist circumference, cm 87.5 vs 96.0 vs 95.0). South Asians were less insulin resistant than blacks and whites (age-BMI-adjusted homeostatic model assessment of insulin resistance, µIU/mL/mmol/L: 2.30 vs 3.45 vs 2.59), and more insulin deficient than blacks but not whites (age-BMI-adjusted homeostasis model assessment of β-cell dysfunction, µIU/mL/mmol/L: 103.7 vs 140.6 vs 103.9). Age-standardized diabetes incidence (cases/1000 person-years (95% CI)) in South Asian men was similar to black men and 1.6 times higher (1.37 to 1.92) than white men (26.0 (22.2 to 29.8) vs 26.2 (22.7 to 29.7) vs 16.1 (14.8 to 17.4)). In South Asian women, incidence was slightly higher than black women and 3 times (2.61 to 3.66) the rate in white women (31.9 (27.5 to 36.2) vs 28.6 (25.7 to 31.6) vs 11.3 (10.2 to 12.3)). In normal weight (BMI <25 kg/m2), diabetes incidence adjusted for age was 2.9 times higher (2.09 to 4.28) in South Asian men, and 5.3 times (3.64 to 7.54) in South Asian women than in white women.

Conclusions

South Asian adults have lower BMI and are less insulin resistant than US blacks and whites, but have higher diabetes incidence than US whites, especially in subgroups without obesity. Factors other than insulin resistance (ie, insulin secretion) may play an important role in the natural history of diabetes in South Asians.
Leaving no one behind in prison: improving the health of people in prison as a key contributor to meeting the Sustainable Development Goals 2030
Authors: Ismail Nasrul , Lazaris Audrey , O'Moore Éamonn , Plugge Emma , Stürup-Toft Sunita
Published: March 2021

Worldwide, approximately 11 million people are currently being held in prison, a number that has steadily grown since the turn of the 21st century. The prison population is more likely to suffer from physical and mental ailments both during and prior to their imprisonment due to poverty, social exclusion and chaotic lifestyles. Recognition of people in prison is noticeably absent from the Sustainable Development Goals (SDGs), despite the goals’ ethos of ‘leaving no one behind’.

We present the first analysis of how improving the health of people in prison can contribute to achieving 15 SDGs. Relevant indicators are proposed to fulfil these goals while meeting the existing international prison health standards. We also assess the political, economic and social challenges, alongside the unparalleled COVID-19 pandemic that can thwart the realisation of the SDGs. To reach the ‘furthest behind first’, prison health must be at the forefront of the SDGs.
Providing food to patients in primary care to induce weight loss: a systematic literature review
Authors: Ball Lauren , Somerville Mari , Crowley Jennifer , Calleja Zoe , Barnes Katelyn
Published: March 2021

Purpose

Primary care is the ideal setting to promote weight management, warranting innovative ways to support patients. This systematic review aimed to determine whether providing food to patients in primary care can help to reduce body weight.

Methods

Four databases were searched for studies that aimed to elicit weight loss by directly providing foodstuffs and/or supplements to patients in primary care settings. Interventions with adults of any gender or race were included. Interventions that involved other components such as exercise classes or education sessions were excluded. The methodological quality of each study was appraised using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies.

Results

Four heterogeneous studies met the eligibility criteria, representing 476 adults. Two studies used meal-replacement products but differed in length and intensity, another study provided green tea and vitamin E supplementation, and the final study provided vouchers for use at a farmers’ market hosted at a primary care clinic. Interventions ranged in length from 4 to 13 weeks. Three of the four studies observed weight loss in some form and all studies observed at least one other improvement in a health outcome such as waist circumference, blood pressure or fasting insulin levels.

Conclusions

A small yet notable body of literature supports the concept of providing food to patients in primary care settings to support weight loss. Further, high-quality research is needed on the efficacy and cost-effectiveness of this approach to ultimately inform policy initiatives for primary care.
Parenteral nutrition complications in palliative medicine
Authors: Smith Zoe , Sills Emily
Published: March 2021

Parenteral nutrition in palliative care is contentious, and decisions on starting or continuing its treatment in palliative patients centre on an individual’s preference, balanced with quality of life. This case report describes the unusual onset of pain and agitation secondary to fluid retention, in a patient with metastatic pseudomyxoma peritonei, established on 2.5 L/day of parenteral nutrition. Immediate volume reduction of the parenteral nutrition to 1 L/day successfully reversed the patient’s symptoms. To our knowledge, this is the first case of parenteral nutrition inducing pain and agitation in a palliative care patient. There is no specific internationally acclaimed guidance concerning parenteral nutrition content and volume in palliative patients, due to a lack of high quality studies. This case study highlights the need for further research into parenteral nutrition content and volume in palliative care, to prevent harmful effects from fluid retention, impacting on quality of life.
Insulin Doses Requirements in Patients with Type 1 Diabetes Using Glargine U300 or Degludec in Routine Clinical Practice
Authors: Carral San Laureano Florentino , Tomé Fernández-Ladreda Mariana , Jiménez Millán Ana Isabel , García Calzado Concepción , del Carmen Ayala Ortega María
Published: March 2021

There are not many real-world studies evaluating daily insulin doses requirements (DIDR) in patients with type 1 diabetes (T1D) using second-generation basal insulin analogs, and such comparison is necessary. The aim of this study was to compare DIDR in individuals with T1D using glargine 300 UI/mL (IGlar-300) or degludec (IDeg) in real clinical practice. An observational, retrospective study was designed in 412 patients with T1D (males: 52%; median age 37.0±13.4 years, diabetes duration: 18.7±12.3 years) using IDeg and IGla-300 ≥6 months to compare DIDR between groups. Patients using IGla-300 (n=187) were more frequently males (59% vs 45.8%; p=0.004) and had lower glycosylated hemoglobin (HbA1c) (7.6±1.2 vs 8.1%±1.5%; p<0.001) than patients using IDeg (n=225). Total (0.77±0.36 unit/kg/day), basal (0.43±0.20 unit/kg/day) and prandial (0.33±0.23 unit/kg/day) DIDR were similar in IGla-300 and IDeg groups. Patients with HbA1c ≤7% (n=113) used significantly lower basal (p=0.045) and total (p=0.024) DIDR, but not prandial insulin (p=0.241), than patients with HbA1c between 7.1% and 8% and >8%. Patients using IGla-300 and IDeg used similar basal, prandial and total DIDR regardless of metabolic control subgroup. No difference in basal, prandial and total DIDR was observed between patients with T1D using IGla-300 or IDeg during at least 6 months in routine clinical practice.
Early plasma circulating tumor DNA (ctDNA) changes predict response to first-line pembrolizumab-based therapy in non-small cell lung cancer (NSCLC)
Authors: Ricciuti Biagio , Jones Greg , Severgnini Mariano , Alessi Joao V , Recondo Gonzalo , Lawrence Marissa , Forshew Tim , Lydon Christine , Nishino Mizuki , Cheng Michael , Awad Mark
Published: March 2021

Background

Currently available biomarkers are imperfect in their ability to predict responses to the multiple first-line treatment options available for patients with advanced non-small cell lung cancer (NSCLC). Having an early pharmacodynamic marker of treatment resistance may help redirect patients onto more effective alternative therapies. We sought to determine if changes in circulating tumor DNA (ctDNA) levels after initiation of first-line pembrolizumab±chemotherapy in NSCLC would enable early prediction of response prior to radiological assessment.

Methods

Plasma collected from patients with advanced NSCLC prior to and serially after starting first-line pembrolizumab±platinum doublet chemotherapy was analyzed by next-generation sequencing using enhanced tagged-amplicon sequencing of hotspots and coding regions from 36 genes. Early change in ctDNA allele fraction (AF) was correlated with radiographic responses and long-term clinical outcomes.

Results

Among 62 patients who received first-line pembrolizumab±platinum/pemetrexed and underwent ctDNA assessment, 45 had detectable ctDNA alterations at baseline. The median change in AF at the first follow-up (at a median of 21 days after treatment initiation) was −90.1% (range −100% to +65%) among patients who subsequently had a radiologic response (n=18), –19.9% (range: −100% to +1884%) among stable disease cases (n=15), and +28.8% (range: −100% to +410%) among progressive disease cases (n=12); p=0.003. In addition, there was a significant correlation between the percent change in ctDNA at the first follow-up and the percent change in tumor target lesions from baseline (R=0.66, p<0.001). AF decrease between the pretreatment and first on-treatment blood draw was associated with significantly higher response rate (60.7% vs 5.8%, p=0.0003), and significantly longer median progression-free survival (8.3 vs 3.4 months, HR: 0.29 (95% CI: 0.14 to 0.60), p=0.0007) and median overall survival (26.2 vs 13.2 months, HR: 0.34 (95% CI: 0.15 to 0.75), p=0.008) compared with cases with an AF increase.

Conclusion

In patients with advanced NSCLC, rapid decreases in ctDNA prior to radiological assessment correlated with clinical benefit. These results suggest a potential role for ctDNA as an early pharmacodynamic biomarker of response or resistance to immunotherapies.
Advocating for equity during the pandemic
Authors: Eke Onyinyechi F , Martin Alister , Khidir Hazar , Otugo Onyeka , Marshall Andrew , Suarez Joanne C. , Macias-Konstantopoulos Wendy L.
Published: March 2021

In response to an imminent surge in COVID-19 cases, the state of Massachusetts (MA) released its Crisis Standards of Care (CSC) guidelines in April 2020. A small group of Boston healthcare providers, community members, lawyers, ethicists and disability advocates brought to bear our collective strengths to forge a formidable coalition now known as the Massachusetts Coalition for Health Equity, to champion the rights of marginalised groups that would be adversely affected by the implementation of the original MA CSC guidelines. In this coalition, members of marginalised communities were adequately represented, led discussions on the implications of implementing inequitable elements of the CSC guidelines and actively involved in creating an alternative framework. In this article, we discuss the process of building a coalition whose concerted advocacy efforts led to the revision of the MA CSC guidelines.
Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis
Authors: Catrina Anca , Krishnamurthy Akilan , Rethi Bence
Published: March 2021

Epidemiological findings suggest a potential role for anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) pathogenesis. ACPA-positive RA is associated with unique genetical and environmental risk factors, in contrast to seronegative RA. ACPA-positive healthy individuals are at risk of developing RA and can develop joint pain and bone loss already before disease onset. ACPA injection triggered bone loss and pain-like behaviour in mice and, in the presence of additional arthritis inducers, exacerbated joint inflammation. In cell culture experiments, ACPAs could bind to and modulate a variety of cellular targets, such as macrophages, osteoclasts, synovial fibroblasts, neutrophil granulocytes, mast cells, dendritic cells and platelets, further underlying a potential role for these autoantibodies in triggering pathogenic pathways and providing clues for their mechanisms of action. Patient-derived ACPA clones have been characterised by unique cellular effects and multiple ways to act on the target cells. ACPAs might directly induce stimulatory signals by ligating key citrullinated cell surface molecules or, alternatively, act as immune complexes on Fc receptors and potentially other molecules that recognise carbohydrate moieties. On the contrary to experimentally manufactured ACPA clones, patient-derived ACPAs are highly promiscuous and cross-reactive, suggesting a simultaneous binding to a range of functionally relevant and irrelevant targets. Moreover, several ACPA clones recognise carbamylated or acetylated targets as well. These features complicate the identification and description of ACPA-induced pathogenic mechanisms. In the current review, we summarise recent data on the functional properties of patient-derived ACPAs and present mechanistic models on how these antibodies might contribute to RA pathogenesis.