bluuebunny/crossref_metadata_2025 huggingface dataset:
Process Operators and Their Roles in Integrated Assembly Process Planning
Authors: Ling Zhi-Kui , Zhou XiangYu , Mclean Chuck
Published: February 2021

An environment to facilitate assembly process planning is proposed in this study. It includes a design support system with two agents supporting the assembly process. One is assembly design agent, and the other is a geometric design agent. The assembly design agent consists of three modules: the assembly sequence planning module, the assembly resource planning module, and the assembly simulation module. The assembly sequence-planning module takes the design information and generates an assembly sequence. This sequence is structured in a tree form, called the Constructive Assembly Tree (CAT). The leaf nodes of the tree correspond to the components of the product. The intermediate nodes are the assembly process operators, each of which characterizes a particular assembly operation, and their associated subassemblies. The resource module assigns the necessary tools, fixtures, supply bins and other resources to each of the process operators. The assembly simulation module traverses a CAT, extracts the necessary assembly information, and drives external physical simulation/animation system to perform virtual assembly simulation/animation process.
A Heuristic Method to Identify Modules From a Functional Description of a Product
Authors: Stone Robert B. , Wood Kristin L. , Crawford Richard H.
Published: February 2021

Developing product architectures is a key phase in design and development processes. It encompasses the transformation of product function to alternative product layouts. In this paper, we describe a new approach for identifying modules for product architectures. We begin by reviewing the terminology and motivation for modular products. Following that discussion, three heuristic methods for identifying modules from a formal functional decomposition are presented. To aid in this process, a concept known as functional dependency is introduced to further arrange functional models with respect to time. Through this concept and the heuristic methods, modular design can be executed earlier in the product development process, as illustrated by the running example of a power-tool product. A database of 70 consumer products is used to verify and confirm the overall modular design approach.
Artefacting in a Cross-Discipline Design Team
Authors: Logan Gilbert D. , Radcliffe David F.
Published: February 2021

Several empirical studies of design have highlighted the importance of physical objects as aids to the design process. In the main these studies discuss design objects in terms of how they were handled or manipulated by designers. This paper presents a detailed analysis of the relationship between the use of artifacts, gestures and actions in design conversations and the words that accompany their use. We describe this combination of purposeful physical interactions and accompanying talk in design work as artefacting. Empirical data is drawn form an extensive empirical study of a cross discipline, rehabilitation engineering team working carrying out their everyday work.
A Comparative Study of Engineering Change Management in Three Swedish Engineering Companies
Authors: Pikosz Peter , Malmqvist Johan
Published: February 2021

This paper analyses the engineering change management (EC) process in three engineering companies in Sweden. In the paper, the influence of various company specific factors, such as change leadtime, on the design of the EC process are analysed. The current use of computer support is surveyed and the possibility to apply a modern product data management (PDM) system to support the process is analysed. The paper also presents different strategies for improving the engineering change management process as well as of the product data management systems in order to achieve an optimal process.
Stochastic Tolerance Synthesis for Globoidal Cam Mechanisms With the Least Manufacturing Cost
Authors: Cheng Hong-Yih , Yan Hong-Sen
Published: February 2021

This paper proposes a systematic process to analyze the mechanical error and to synthesize the tolerances for individual dimensions of spatial cam mechanisms. The mathematical expressions of geometry surface of the cam are determined by the generating method. Based on these expressions and Taylor’s series expansion, the output variables are expressed by sensitivity factors and the mean of design variables. And, the mechanical error is also calculated according to the measured coordinate data on the manufactured cam surface and misalignments. By applying statistics and cost-tolerance function, the objective function subjected to the variance of the assembly tolerance is established. Then, the Lagrange multiplier is involved to synthesize the optimum tolerances with the least manufacturing cost. A numerical example is given.
Performance Based Redundancy Resolution With Multiple Criteria
Authors: Kapoor Chetan , Cetin Murat , Tesar Delbert
Published: February 2021

This paper presents a scaleable approach to redundancy resolution problems involving multiple criteria. The proposed scheme relies on the disintegration of the inverse kinematics solution from multicriteria decision making. The scheme is composed of systematic generation of a set of inverse kinematics solutions and evaluating these solutions using multiple criteria. The proposed approach is especially promising for problems that can accommodate extensive number of criteria. Weights assigned to different criteria are monitored and adjusted to achieve desired performance goals. The scheme is implemented using an object-oriented operational software framework, and its functionality is tested under interactive real-time control of a 10 degrees of freedom manipulator.
Solving the Inverse Dynamics of Parallel Manipulators by the Principle of Virtual Work
Authors: Tsai Lung-Wen
Published: February 2021

This paper presents a systematic methodology for solving the inverse dynamics of parallel manipulators. Based on the principle of virtual work and the concept of link Jacobian matrices, a methodology for deriving the dynamical equations of motion is developed. It is shown that the dynamics of a parallel manipulator can be reduced to solving a system of six linear equations. To demonstrate the methodology, the dynamical equations of a Stewart-Gough platform are derived. A computer algorithm is developed and several different trajectories of the moving platform are simulated.
Kinematically Generated Dual Tensor-Product Surfaces
Authors: Ge Q. J. , Kang D. , Sirchia M.
Published: February 2021

This paper takes advantage of the duality between point and plane geometries and studies a class of tensor-product surfaces that can be generated kinematically as surfaces enveloped by a plane under two-parameter rational Bézier motions. The results of this cross-disciplinary work, between the field of Computer Aided Geometric Design and Kinematics, can be used as a basis for studying geometric and kinematic issues associated with the design and manufacture of freeform surfaces.
Synthesis of Stiffnesses by Springs
Authors: Ciblak Namik , Lipkin Harvey
Published: February 2021

A new, systematic approach to the synthesis of stiffness by springs is presented using screw (spatial vector) algebra. The space of solutions is fully characterized for all stiffnesses realizable by springs. The main result shows that a rank r stiffness can always be synthesized by r springs. Further, a stiffness can be synthesized by an arbitrarily large number of springs greater than r. Algorithms and numerical results support the theory.
A Classification Scheme for Planar 4R, Spherical 4R, and Spatial RCCC Linkages to Facilitate Computer Animation
Authors: Murray Andrew P. , Larochelle Pierre M.
Published: February 2021

In this paper we develop a complete classification scheme for planar, spherical and spatial four-bar linkages. The goal of this classification is to note all of the subtleties of motion that an arbitrary set of four link lengths can define. A classification should exist only between the mechanisms that exhibit similar ranges of motion at both the input and output. In the planar case, three parameters being identified as either positive, negative, or zero are necessary to completely characterize all possible ranges of motion. In the spherical and spatial cases, four parameters being identified as positive, negative or zero are needed. The result is 27 classifications of planar mechanisms and 81 for spherical and spatial RCCC mechanisms.
Forward Kinematics in Polynomial Form of the General Stewart Platform
Authors: Innocenti Carlo
Published: February 2021

The paper presents a new algorithm to solve, in polynomial form, the forward kinematics of the general-geometry 6-6 fully-parallel manipulator. The forty solutions that the problem at hand admits in the complex domain are found by determining the roots of a 40th-order univariate polynomial equation. Unlike the existing algorithm, the proposed one is suitable for implementation in a standard floating-point computation environment. A numerical example shows application of the new algorithm to a case study.
A Tool for Third Order Kinematic Analysis of Spatial Mechanisms
Authors: Urbinati Fabrizio , Pennestrì Ettore
Published: February 2021

The paper describes a Maple program for the generation in symbolic form of all the equations needed for the kinematic analysis, up to the third order, of a large class of spatial mechanisms. By means of this program the user can easily model mechanisms with spherical, cylindrical or other types of common kinematic pairs. Since the orientation of each link is described by Euler parameters, all the output equations are in polynomial form. This makes the output in an suitable format for further symbolic processing.
Error Transfer of Planar Linkages With Pair Clearance: Part 1 — The Error Transfer Coefficient of Experimental and Practical Mechanism
Authors: Li Song , Xianmin Zhang , Jian Yang
Published: February 2021

In this paper, the regression equations of the error transfer coefficient (ETC) for the experimental planar linkage mechanism for pair clearances are obtained by utilizing the Monte-Carlo simulation method. Based upon this, a correction procedure and the correction coefficient of the regression equation are presented for the practical planar linkage mechanism. The study result shows that the ETC of planar linkages with pair clearance have the same form while the dimension type is identical.
Generalized Kinematic Modeling Method for Reconfigurable Machine Tools
Authors: Moon Yong-Mo , Kota Sridhar
Published: February 2021

Using a library of machine modules, modular machine tools are being developed by many machine tool manufacturers to reduce design lead time. To accommodate frequent changes in product design in a timely and cost-effective manner, the next generation of machine tools should be reconfigurable to process a family of products. This enables reduction not only in machine design lead time but more significantly a reduction in machine set-up and ramp-up time. The essential characteristics of Reconfigurable Machine Tools (RMTs) include modularity, convertibility, flexibility, and cost-effectiveness. Currently there is no systematic method of designing modular machines, let alone reconfigurable machines. This paper presents a methodology for kinematic synthesis of machine tools using screw theory. The motion characteristics of a set of desired machining tasks as well as stored library of machine modules are captured in a common representation scheme. A simple design example to illustrate the application of this methodology for systematic selection and synthesis of reconfigurable machine tools is presented. The proposed methodology can be extended to include the dynamic characteristics and control schemes to enable integrated design of machines and controllers.
Static Balancing of Spatial and Planar Parallel Manipulators With Prismatic Actuators
Authors: Leblond Marc , Gosselin Clément M.
Published: February 2021

In this paper, the static balancing of existing spatial and planar parallel manipulators by the addition of balancing elements is addressed. Static balancing is defined here as the set of conditions on manipulator dimensional and inertial parameters which, when satisfied, ensure that the weight of the links does not produce any force (or torque) at the actuators for any configuration of the manipulator, under static conditions. These conditions are derived here for spatial six-degree-of-freedom parallel manipulators and it is shown that planar three-degree-of-freedom parallel manipulators can be treated as a particular case of the spatial 6-dof mechanisms. The static balancing conditions associated with planar mechanisms can therefore easily be found, but are not given here because of space limitations. A brief geometric interpretation of the balancing conditions which are associated with statically balanced spatial mechanisms is then carried out. It is shown that balancing is generally possible even when the dimensional parameters are imposed, which is a useful property since dimensional parameters are usually obtained from kinematic design or optimization. Finally, examples of balanced planar and spatial parallel manipulators are given. Static balancing leads to considerable reduction in the actuator forces (or torques), which in turn leads to less powerful actuators and more efficient designs. Moreover, the possibility of balancing existing systems by introducing additional elements, as demonstrated here, is of interest for retrofitting existing parallel mechanisms.
Displacement Analysis of a Six-DOF Parallel Manipulator With 3R3P and 4R2P Chains
Authors: Kamra R. , Kohli D. , Dhingra A. K.
Published: February 2021

This paper addresses the forward displacement analysis of a six degree of freedom platform manipulator which is actuated by three different configurations involving six chains with six joints in each chain. The displacement analysis problem involves finding all possible positions and orientations of the platform along with all the joint variables in response to the inputs supplied. The forward displacement analysis problem is solved using the “Suppressed Tangent method.” The proposed solution procedure is illustrated through three numerical examples. The first example deals with forward displacement analysis of a platform manipulator actuated by six 3R3P chains whereas the second and third examples deal with a manipulator actuated by five 3R3P and one 4R2P, and four 3R3P and two 4R2P chains respectively.
Type Synthesis of Baranov Truss With Multiple Joints and Multiple-Joint Links
Authors: Chu Jinkui , Cao Weiqing , Yang Tingli
Published: February 2021

The method called Single-Open-Chain (SOC) proposed in the literature is a very effective one for structural synthesis of mechanisms; in particular the method suits the synthesis process with the computer. In this paper, a new representation for mechanisms, called Double-Color-Graph (DCG) is introduced. Application of the SOC concept with the help of DCG representation, a new procedure for type synthesis for multiple joints and multiple-joint links, is presented. Baranov Trusses are extensively studied, which results in the finding of 158 independent types of Baranov Trusses with the number of loops being (1–4). A computer program system has been developed to generate all these types.
Concurrent Engineering of Toothed Bodies for Generalized Function Transmission
Authors: Dooner David B. , Seireg Ali A.
Published: February 2021

This paper presents a novel interactive computerized approach for the integrated design and manufacture of different types of toothed bodies based on mathematical derivations from theories of kinematic geometry. An important feature of the developed methodology is that the design and manufacturing data for the toothed bodies which satisfy specified functional requirements and the corresponding cutters used to produce them are synthesized concurrently. The procedure is applicable to any case of conventional or non-conventional gearing as well as transmission function and is particularly useful for the design and manufacture of skew axis gearing. An example of a hypoidal gear pair and the cutters used to produce them are presented to illustrate features of the developed methodology and interactive software.
Profile Modifications for Minimum Static Transmission Error in Cylindrical Gears
Authors: Regalado Isaias , Houser Donald R.
Published: February 2021

The theoretical advantage of conjugate action in involute gears is lost due to the deflection of the teeth under load and due to manufacturing and assembling errors. These factors produce instantaneous variations in the gear ratio commonly referred to as transmission error. The transmission error has been proven to have a strong relationship with the noise emitted by the transmission. In order to reduce the transmission error, the contacting surfaces of the gears are modified to compensate for the deflections and errors. These modifications may be performed in the direction of the profile, the lead or in a more general sense it may be topographical (defined point by point). This paper describes a non-iterative procedure for the calculation of the modifications for minimum transmission error based on a predefined load distribution. The results presented agree with the common practice for spur gears of tip relief in the direction of the profile and crowning in the direction of the lead, but for helical gears the need for a more complicated modification is observed.
Atomic layer etching of GaN using Cl2 and He or Ar plasma
Authors: Ruel Simon , Pimenta-Barros Patricia , Le Roux Frédéric , Chauvet Nicolas , Massardier Michel , Thoueille Philippe , Tan Shirley , Shin Daniel , Gaucher François , Posseme Nicolas
Published: February 2021

During the fabrication of a MOS-HEMT, the plasma-etching steps are critical because they can damage the GaN materials and lead to electrical degradation effects. In this paper, we propose to evaluate GaN etching performances through comparing the Cl2-based atomic layer etching (ALE) process with He or Ar as the sputtering gas. The self-limiting synergy and process window of ALE has been investigated. Based on these results, we propose the reasons for the nonself-limiting behavior of the He ALE process. Both ALE processes were compared to a steady-state process by investigating roughness, and electrical measurements, in order to evaluate the induced damage.
Making the Grade: An Exploration of Incline Running on a Bodyweight-Supportive Treadmill
Authors: Wagner Megan , Dames Kevin D.
Published: February 2021

Context: Bodyweight-supporting treadmills are popular rehabilitation tools for athletes recovering from impact-related injuries because they reduce ground reaction forces during running. However, the overall metabolic demand of a given running speed is also reduced, meaning athletes who return to competition after using such a device in rehabilitation may not be as fit as they had been prior to their injury. Objective: To explore the metabolic effects of adding incline during bodyweight-supported treadmill running. Design: Cross-sectional. Setting: Research laboratory. Participants: Fourteen apparently healthy, recreational runners (6 females and 8 males; 21 [3] y, 1.71 [0.08] m, 63.11 [6.86] kg). Interventions: The participants performed steady-state running trials on a bodyweight-supporting treadmill at 8.5 mph. The control condition was no incline and no bodyweight support. All experimental conditions were at 30% bodyweight support. The participants began the sequence of experimental conditions at 0% incline; this increased to 1%, and from there on, 2% incline increases were introduced until a 15% grade was reached. Repeated-measures analysis of variance was used to compare all bodyweight-support conditions against the control condition. Main Outcome Measures: Oxygen consumption, heart rate, and rating of perceived exertion. Results: Level running with 30% bodyweight support reduced oxygen consumption by 21.6% (P < .001) and heart rate by 12.0% (P < .001) compared with the control. Each 2% increase in incline with bodyweight support increased oxygen consumption by 6.4% and heart rate by 3.2% on average. A 7% incline elicited similar physiological measures as the unsupported, level condition. However, the perceived intensity of this incline with bodyweight support was greater than the unsupported condition (P < .001). Conclusions: Athletes can maintain training intensity while running on a bodyweight-supporting treadmill by introducing incline. Rehabilitation programs should rely on quantitative rather than qualitative data to drive exercise prescription in this modality.
Study disputes carbon dioxide-fish behavior link
Authors: Enserink Martin
Published: February 2021

Three-year effort fails to replicate alarming findings about effects of ocean acidification.
How safe is a popular gene therapy vector?
Authors: Kaiser Jocelyn
Published: February 2021

Dog study suggests virus-delivered DNA can invade chromosomes near cancer genes.
Searching for the true attrition rate of UK paediatric trainees
Authors: Redman Melody Grace , Carzedda Davide , Jay Nicola , Clark Simon J , Rogers Marie
Published: February 2021

Objective

To quantitatively analyse the number of doctors leaving the paediatric specialty training (ST) programme in the UK, to assist with evidence-based workforce planning.

Design

Data were sought on those leaving the UK paediatrics training programme between 2014 and 2019 from Heads of Schools of Paediatrics and Freedom of Information Act requests.

Setting

Retrospective data analysis.

Outcome measures

Overall attrition rate, attrition rate across level of training, attrition rate across geographical area, recorded reason for leaving.

Results

All results must be interpreted with caution due to limitations in record keeping and analysis. The annual attrition rate across all ST levels between 2014 and 2019 is estimated at 3.7%–4.2% (ie, 749–845 trainees may have left the paediatric training programme over 2014–2019). No reason for leaving was recorded for three-quarters of individuals, around 630 doctors. Of those leaving paediatrics, significantly more (χ², p=0.015) did so at ST3 (20.3%) versus the next highest training year, ST2 (13.6%).

Conclusions

This project seems to demonstrate worryingly poor record-keeping of the true attrition rate of paediatric trainees by organisations responsible for workforce planning, including Health Education England, the Royal College of Paediatrics and Child Health and individual paediatric schools across the UK. To allow evidence-based workforce planning for the benefit of UK children, it is vital that accurate records on trainees who leave the training programme are kept and shared across the UK.
Investigating the feasibility and acceptability of the HOLOBalance system compared with standard care in older adults at risk for falls: study protocol for an assessor blinded pilot randomised controlled study
Authors: Liston Matthew , Genna Gregory , Maurer Christoph , Kikidis Dimitris , Gatsios Dimitris , Fotiadis Dimitris , Bamiou Doris-Eva , Pavlou Marousa
Published: February 2021

Introduction

Approximately one in three of all older adults fall each year, with wide ranging physical, psychosocial and healthcare-related consequences. Exercise-based interventions are the cornerstone for falls prevention programmes, yet these are not consistently provided, do not routinely address all components of the balance system and are often not well attended. The HOLOBalance system provides an evidence-based balance training programme delivered to patients in their home environment using a novel technological approach including an augmented reality virtual physiotherapist, exergames and a remote monitoring system. The aims of this proof-of-concept study are to (1) determine the safety, acceptability and feasibility of providing HOLOBalance to community dwelling older adults at risk for falls and (2) provide data to support sample size estimates for a future trial.

Methods

A single (assessor) blinded pilot randomised controlled proof of concept study. 120 participants will be randomised to receive an 8-week home exercise programme consisting of either: (1) HOLOBalance or (2) The OTAGO Home Exercise Programme. Participants will be required to complete their exercise programme independently under the supervision of a physiotherapist. Participants will have weekly telephone contact with their physiotherapist, and will receive home visits at weeks 0, 3 and 6. Outcome measures of safety, acceptability and feasibility, clinical measures of balance function, disability, balance confidence and cognitive function will be assessed before and immediately after the 8 week intervention. Acceptability and feasibility will be explored using descriptive statistics, and trends for effectiveness will be explored using general linear model analysis of variance.

Ethics and dissemination

This study has received institutional ethical approvals in Germany (reference: 265/19), Greece (reference: 9769/24-6-2019) and the UK (reference: 19/LO/1908). Findings from this study will be submitted for peer-reviewed publications.

Trial registration number

NCT04053829.

Protocol version

V.2, 20 January 2020
Assessing the efficacy, safety and utility of closed-loop insulin delivery compared with sensor-augmented pump therapy in very young children with type 1 diabetes (KidsAP02 study): an open-label, multicentre, multinational, randomised cross-over study protocol
Authors: Fuchs Julia , Allen Janet M , Boughton Charlotte K , Wilinska Malgorzata E , Thankamony Ajay , de Beaufort Carine , Campbell Fiona , Yong James , Froehlich-Reiterer Elke , Mader Julia K , Hofer Sabine E , Kapellen Thomas M , Rami-Merhar Birgit , Tauschmann Martin , Hood Korey , Kimbell Barbara , Lawton Julia , Roze Stephane , Sibayan Judy , Cohen Nathan , Hovorka Roman
Published: February 2021

Introduction

Diabetes management in very young children remains challenging. Glycaemic targets are achieved at the expense of high parental diabetes management burden and frequent hypoglycaemia, impacting quality of life for the whole family. Our objective is to assess whether automated insulin delivery can improve glycaemic control and alleviate the burden of diabetes management in this particular age group.

Methods and analysis

The study adopts an open-label, multinational, multicentre, randomised, crossover design and aims to randomise 72 children aged 1–7 years with type 1 diabetes on insulin pump therapy. Following screening, participants will receive training on study insulin pump and study continuous glucose monitoring devices. Participants will be randomised to 16-week use of the hybrid closed-loop system (intervention period) or to 16-week use of sensor-augmented pump therapy (control period) with 1–4 weeks washout period before crossing over to the other arm. The order of the two study periods will be random. The primary endpoint is the between-group difference in time spent in the target glucose range from 3.9 to 10.0 mmol/L based on sensor glucose readings during the 16-week study periods. Analyses will be conducted on an intention-to-treat basis. Key secondary endpoints are between group differences in time spent above and below target glucose range, glycated haemoglobin and average sensor glucose. Participants’ and caregivers’ experiences will be evaluated using questionnaires and qualitative interviews, and sleep quality will be assessed. A health economic analysis will be performed.

Ethics and dissemination

Ethics approval has been obtained from Cambridge East Research Ethics Committee (UK), Ethics Committees of the University of Innsbruck, the University of Vienna and the University of Graz (Austria), Ethics Committee of the Medical Faculty of the University of Leipzig (Germany) and Comité National d’Ethique de Recherche (Luxembourg). The results will be disseminated by peer-reviewed publications and conference presentations.

Trial registration number

NCT03784027.
Development and evaluation of a decision aid for family surrogate decision-makers for patients with acute kidney injury requiring renal replacement therapy (RRT) in ICUs: a study protocol
Authors: Zheng Miao , Yin Changlin , Cao Ying , Zhang Yonghui , Zhang Kuoliang , Zhang Xiaoqin , Bian Wei , Wang Lihua
Published: February 2021

Introduction

Shared decision making is endorsed by guidelines for both acute kidney injury and critical care medicine. However, there is still a huge need for effective interventions, especially those focusing on decisions about renal replacement therapy for intensive care unit (ICU) patients with acute kidney injury. The decision aids provide evidence-based support for shared decision making, to achieve better decisions through enhanced knowledge of treatment options and treatment aligns with patients’ preferences and values. Therefore, our objectives are to develop and evaluate a decision aid systematically and rigorously for family surrogate decision makers of ICU patients with acute kidney injury who need renal replacement therapy.

Methods and analysis

We will use a systematic development process that focuses on user-centred design to develop and evaluate the decision aid in three phases: (1) development of a draft prototype for the decision aid based on extensive literature reviews, interviews with key stakeholders and evidence synthesis; (2) alpha testing (‘near live’ usability) the decision aid during simulated clinical encounters to test its comprehensibility, acceptability and usability and (3) beta testing (‘live’ usability) to examine the aid’s clinical feasibility. User testing will be conducted using mixed-methods approach to support iterative revision of the decision aid. The IPDASi (V.4.0) will be used for following qualitative assessment. All interviews will be analysed by Colaizzi’s seven-step approach to qualitative analysis. The coding scheme will use to analyse user interactions. Questionnaire surveys will be analysed using paired sample t-tests when related to the before-and-after survey, otherwise using one-sample t-test.

Ethics and dissemination

Ethical approval for this research was obtained from the Ethics Committee of the First Affiliated Hospital of Army Medical University, PLA (Ref: KY2020104). All participants will sign a formal informed consent form. The findings will be published in peer-reviewed journals and reported in appropriate meetings.

Trial registration number

ChiCTR2000031613.
Retrospective cohort study evaluating clinical, biochemical and pharmacological prognostic factors for prostate cancer progression using primary care data
Authors: Merriel Samuel William David , Ingle Suzanne Marie , May Margaret T , Martin Richard M
Published: February 2021

Objectives

To confirm the association of previously reported prognostic factors with future progression of localised prostate cancer using primary care data and identify new potential prognostic factors for further assessment in prognostic model development and validation.

Design

Retrospective cohort study, employing Cox proportional hazards regression controlling for age, prostate specific antigen (PSA), and Gleason score, was stratified by diagnostic stage.

Setting

Primary care in England.

Participants

Males with localised prostate cancer diagnosedbetween 01/01/1987 and 31/12/2016 within the Clinical Practice ResearchDatalink database, with linked data from the National Cancer Registration andAnalysis Service and Office for National Statistics.

Primary and secondary outcomes

Primary outcome measure was prostate cancer mortality. Secondary outcome measures were all-cause mortality and commencing systemic therapy. Up-staging after diagnosis was not used as a secondary outcome owing to significant missing data.

Results

10 901 men (mean age 74.38±9.03 years) with localised prostate cancer were followed up for a mean of 14.12 (±6.36) years. 2331 (21.38%) men underwent systemic therapy and 3450 (31.65%) died, including 1250 (11.47%) from prostate cancer. Factors associated with an increased risk of prostate cancer mortality included age; high PSA; current or ex-smoker; ischaemic heart disease; high C reactive protein; high ferritin; low haemoglobin; high blood glucose and low albumin.

Conclusions

This study identified several new potential prognostic factors for prostate cancer progression, as well as confirming some known prognostic factors, in an independent primary care data set. Further research is needed to develop and validate a prognostic model for prostate cancer progression.
Comparison of high-flow nasal oxygen therapy and non-invasive ventilation in ICU patients with acute respiratory failure and a do-not-intubate orders: a multicentre prospective study OXYPAL
Authors: Robert René , Frasca Denis , Badin Julie , Girault C , Guitton Christophe , Djibre Michel , Beuret Pascal , Reignier Jean , Benzekri-Llefevre Dalila , Demiri Suela , Rahmani Hassène , Argaud Laurent Argaud , I"her Erwan , Ehrmann Stephan , Lesieur Olivier , Kuteifan Khaldoune , Thouy Francois , Federici Laura , Thevenin Didier , Contou Damien , Terzi Nicolas , Nseir Saad , Thyrault Martial , Vinsonneau Christophe , Audibert Juliette , Masse Juliette , Boyer Alexandre , Guidet Bertrand , Chelha Riad , Quenot Jean-Pierre , Piton G , Aissaoui Nadia , Thille Arnaud W , Frat Jean-Pierre
Published: February 2021

Introduction

A palliative approach to intensive care unit (ICU) patients with acute respiratory failure and a do-not-intubate order corresponds to a poorly evaluated target for non-invasive oxygenation treatments. Survival alone should not be the only target; it also matters to avoid discomfort and to restore the patient’s quality of life. We aim to conduct a prospective multicentre observational study to analyse clinical practices and their impact on outcomes of palliative high-flow nasal oxygen therapy (HFOT) and non-invasive ventilation (NIV) in ICU patients with do-not-intubate orders.

Methods and analysis

This is an investigator-initiated, multicentre prospective observational cohort study comparing the three following strategies of oxygenation: HFOT alone, NIV alternating with HFOT and NIV alternating with standard oxygen in patients admitted in the ICU for acute respiratory failure with a do-not-intubate order. The primary outcome is the hospital survival within 14 days after ICU admission in patients weaned from NIV and HFOT. The sample size was estimated at a minimum of 330 patients divided into three groups according to the oxygenation strategy applied. The analysis takes into account confounding factors by modelling a propensity score.

Ethics and dissemination

The study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.

Trial registration number

NCT03673631
Exacerbation of visual hallucinations in Charles Bonnet syndrome due to the social implications of COVID-19
Authors: Jones Lee , Ditzel-Finn Lara , Potts Judith , Moosajee Mariya
Published: February 2021

Objective

Charles Bonnet syndrome (CBS) occurs secondary to sight loss, characterised by spontaneous visual hallucinations. Symptom manifestation can be influenced by social isolation. This research aims to evaluate the effect of the COVID-19 pandemic lockdown on patients with CBS.

Methods and analysis

A prospective cross-sectional survey of 45 individuals with active CBS. Open and closed ended questions were used to measure patient-reported features of hallucinatory experiences during the COVID-19 lockdown and perceived episode triggers. Analysis comprised of descriptive statistics, analysis of variance and associations, supplemented with qualitative descriptions.

Results

The survey was operational for 31 days during the COVID-19 pandemic (June–July 2020). The mean (±SD) age of respondents was 69.3 (±18) years and the majority (42.2%) had macular disease. Loneliness during the lockdown was associated with changes in the nature of visual hallucinations (p=0.04). Individuals experiencing greater loneliness were, on average, older than those with no changes to their feelings of loneliness (mean age 73.3±17 vs 60.2±19 years; p=0.03). Despite experiencing greater feelings of loneliness (67%), most individuals (60%) had not accessed support services for this reason.

Conclusions

Around half of respondents in this survey experienced exacerbation of visual hallucinations during the COVID-19 pandemic, which may partly be explained by loneliness and/or environmental triggers. We provide suggestions to promote effective patient self-management of symptoms.
Assessment of Synovial Fluid and Serum Cytokine Levels in Children with Septic Arthritis
Authors: Dehority Walter , Plaster Scott , Helmig Kathryn C , Huff Nathan , Parsons Andrew , Tigert Susan L , Silva Selina
Published: February 2021

Acute septic arthritis (ASA) is a common orthopedic infection of children which may produce devastating sequelae and chronic morbidity. Improved understanding of the intra-articular inflammatory response in ASA may identify cytokine targets with diagnostic or therapeutic potential, though no detailed investigations to this end have been performed. Given this, we used a multiplex cytokine assay for assessment of levels of 40 different cytokines in the synovial fluid and blood of children with ASA. Twelve children (8 controls undergoing orthopedic surgery for non-infectious conditions and 4 with ASA) were prospectively enrolled. Blood and synovial fluid were collected intraoperatively from each subject, and the levels of 40 cytokines were determined using a multiplex assay. Cytokines were organized by function and structure into 12 groups for analysis. The Benjamini-Hochberg method was used to control for type 1 errors, with an a priori false discovery rate of 10%. Subjects with ASA were younger than controls (mean age 8.0 vs 13.1 years, p=0.0400). Significant elevations were seen in interleukins (IL) with chemokine properties, IL-6 and those in the common-γ chain group in the blood and synovial fluid of children with ASA compared with controls, while significant elevations in 5 additional cytokine groups were seen in synovial fluid from children with ASA compared with controls, most notably IL-6 (median 8294.3 vs 10.7 pg/mL, p=0.0066). Our pilot study is the first to describe in detail the cytokine response in children with ASA, and highlights the need for additional study.
Intratumoral virotherapy with 4-1BBL armed modified vaccinia Ankara eradicates solid tumors and promotes protective immune memory
Authors: Hinterberger Maria , Giessel Raphael , Fiore Giovanna , Graebnitz Fabienne , Bathke Barbara , Wennier Sonia , Chaplin Paul , Melero Ignacio , Suter Mark , Lauterbach Henning , Berraondo Pedro , Hochrein Hubertus , Medina-Echeverz José
Published: February 2021

BackgroundHuman cancers are extraordinarily heterogeneous in terms of tumor antigen expression, immune infiltration and composition. A common feature, however, is the host′s inability to mount potent immune responses that prevent tumor growth effectively. Often, naturally primed CD8+T cells against solid tumors lack adequate stimulation and efficient tumor tissue penetration due to an immune hostile tumor microenvironment.

MethodsTo address these shortcomings, we cloned tumor-associated antigens (TAA) and the immune-stimulatory ligand 4-1BBL into the genome of modified vaccinia Ankara (MVA) for intratumoral virotherapy.

ResultsLocal treatment with MVA-TAA-4-1BBL resulted in control of established tumors. Intratumoral injection of MVA localized mainly to the tumor with minimal leakage to the tumor-draining lymph node. In situ infection by MVA-TAA-4-1BBL triggered profound changes in the tumor microenvironment, including the induction of multiple proinflammatory molecules and immunogenic cell death. These changes led to the reactivation and expansion of antigen-experienced, tumor-specific cytotoxic CD8+T cells that were essential for the therapeutic antitumor effect. Strikingly, we report the induction of a systemic antitumor immune response including tumor antigen spread by local MVA-TAA-4-1BBL treatment which controlled tumor growth at distant, untreated lesions and protected against local and systemic tumor rechallenge. In all cases, 4-1BBL adjuvanted MVA was superior to MVA.

ConclusionIntratumoral 4-1BBL-armed MVA immunotherapy induced a profound reactivation and expansion of potent tumor-specific CD8+T cells as well as favorable proinflammatory changes in the tumor microenvironment, leading to elimination of tumors and protective immunological memory.
Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome
Authors: Sabria-Back Joan , Monteagudo-Sánchez Ana , Sánchez-Delgado Marta , Ferguson-Smith Anne C , Gómez Olga , Pertierra Cartada Africa , Tenorio Jair , Nevado Julián , Lapunzina Pablo , Pereda Aguirre Arrate , Giménez Sevilla Carles , Toro Toro Estefanía , Perez de Nanclares Guiomar , Monk David
Published: February 2021

Introduction

Kagami-Ogata syndrome (KOS14) and Temple syndrome (TS14) are two disorders associated with reciprocal alterations within the chr14q32 imprinted domain. Here, we present a work-up strategy for preimplantation genetic testing (PGT) to avoid the transmission of a causative micro-deletion.

Methods

We analysed DNA from the KOS14 index case and parents using methylation-sensitive ligation-mediated probe amplification and methylation pyrosequencing. The extent of the deletion was mapped using SNP arrays. PGT was performed in trophectoderm samples in order to identify unaffected embryos. Samples were amplified using multiple displacement amplification, followed by genome-wide SNP genotyping to determine the at-risk haplotype and next-generation sequencing to determine aneuploidies.

Results

A fully methylated pattern at the normally paternally methylated IG-DMR and MEG3 DMR in the KOS14 proband, accompanied by an unmethylated profile in the TS14 mother was consistent with maternal and paternal transmission of a deletion, respectively. Further analysis revealed a 108 kb deletion in both cases. The inheritance of the deletion on different parental alleles was consistent with the opposing phenotypes. In vitro fertilisation with intracytoplasmatic sperm injection and PGT were used to screen for deletion status and to transfer an unaffected embryo in this couple. A single euploid-unaffected embryo was identified resulting in a healthy baby born.

Discussion

We identify a microdeletion responsible for multigeneration KOS14 and TS14 within a single family where carriers have a 50% risk of transmitting the deletion to their offspring. We show that PGT can successfully be offered to couples with IDs caused by genetic anomalies.
Indirect versus direct effects of freshwater browning on larval fish foraging
Authors: Leech Dina M. , Clift Troy L. , Littlefield Jessica L. , Ravagli Nicholas R. , Spain Jacob E.
Published: February 2021

Fish foraging and energy flow between trophic levels are predicted to decline with freshwater browning due to decreased light availability. Studies investigating these predictions have focused on juvenile and adult fishes; however, the larval stage represents a “critical period” in development. We investigated the indirect (i.e., prey availability) versus direct (i.e., visual foraging) effects of browning on zooplankton–larval fish interactions by altering water colour with SuperHume (absorbance at 440 nm = 1.6–10.8 m−1). Phytoplankton and zooplankton densities were monitored across treatments for 1 month to simulate the time leading up to fish spawning in the spring. Larval largemouth bass (Micropterus salmoides) were then introduced to assess indirect effects on fish feeding, growth, and survival. Direct effects on largemouth bass and bluegill (Lepomis macrochirus) foraging on zooplankton were determined with separate short-term experiments. Browning did not directly alter the ability of larvae to capture prey. However, indirect effects on larval fish foraging, growth, and survival were observed as phytoplankton and zooplankton abundance decreased with increased browning. Our data suggest browning may reduce energy transfer to larval fish due to a reduction in prey but not visual foraging.
Statistical analysis and information theory of screened Kratzer–Hellmann potential model
Authors: Osobonye G.T. , Okorie U.S. , Amadi P.O. , Ikot A.N.
Published: February 2021

In this research, the radial Schrödinger equation for a newly proposed screened Kratzer–Hellmann potential model was studied via the conventional Nikiforov–Uvarov method. The approximate bound state solution of the Schrödinger equation was obtained using the Greene–Aldrich approximation in addition to the normalized eigenfunction for the new potential model, both analytically and numerically. These results were employed to evaluate the rotational–vibrational partition function and other thermodynamic properties for the screened Kratzer–Hellmann potential. The results obtained have been graphically discussed. Also, the normalized eigenfunction has been used to calculate some information-theoretic measures including Shannon entropy and Fisher information for low-lying states in both position and momentum spaces numerically. The Shannon entropy results obtained agreed with the Bialynicki-Birula and Mycielski inequality, while the Fisher information results obtained agreed with the Stam, Cramér–Rao inequality. Also, alternating increasing and decreasing localization across the screening parameter for both eigenstates was observed.
Charged rho superconductor in the presence of magnetic field and rotation
Authors: Cao Gaoqing
Published: February 2021

In this work, we mainly explore the possibility of charged rho ($$\rho ^\pm $$

ρ
±

) superconductor in the presence of parallel magnetic field and rotation within three-flavor Nambu–Jona-Lasino model. By following similar schemes as in the previous studies of charged pion ($$\pi ^\pm $$

π
±

) superfluid, the $$\rho ^\pm $$

ρ
±

superconductor is found to be favored for both choices of Schwinger phase in Minkowski and curved spaces. Due to the stability of the internal spin structure, charged rho begins to condensate at a smaller threshold of angular velocity than charged pion for the given large magnetic fields. Even the axial vector meson condensation is checked – the conclusion is that $$\rho ^\pm $$

ρ
±

superconductor is the robust ground state at strong magnetic field and fast rotation, which actually sustains to very large angular velocity.
Current computational methods for enzyme design
Authors: Coates Talmage L. , Young Naomi , Jarrett Austin J. , Morris Connor J. , Moody James D. , Corte Dennis Della
Published: February 2021

Computational enzyme design has made great strides over the last five years. Traditional methods of enzyme design require synthesis and evaluation of many mutations. Computational enzyme design has emerged as a powerful tool to predict how specific mutations modify a protein’s activity, stability, and/or selectivity. Such computational approaches can evaluate many mutations and reduce the load of in vitro work by identifying mutations likely to accomplish design objectives. Computational approaches can explore mutational spaces inaccessible in traditional mutagenesis. Computational methods reduce cost and time compared with experimental approaches. We review the efficacy and key differences of computational enzyme design methods as published in recent studies. The included articles used computational methods to design enzymes, were published no earlier than 2015, met design objectives, and verified results in vitro.