bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional safety and reliability for innovative vehicle braking system and integration with electric traction units
Authors: Favilli T. , Delogu M. , Pugi L. , Berzi L.
Published: March 2021

Newly electric vehicle architectures require intensive virtual and physical testing for safety assessment, due to the increasing relevance of By-Wire systems and the presence of innovative control algorithms for ordinary driving scenario, potential emergency situations or Advanced Driver-Assistance Systems implementation purpose. To reduce the development time while increasing system reliability and the a priori knowledge about its safety requirements, the evaluation of such aspects should be performed. In accordance to ISO26262 standard, authors propose a systematic approach based on Virtual FMEA, in order to assess the functional safety level of hybrid brake plant. Plant modification and securing strategy as been presented and implemented in target vehicle model, evaluating their performances in simulation environments, in order to met required Automotive Safety Integrity Level. This work is developed in the ambit of OBELICS European Project.
Single-lap joints of similar and dissimilar adherends bonded with a polyurethane adhesive used in the automotive industry
Authors: Ciardiello R , Boursier Niutta C , Di Sciullo F , Goglio L
Published: March 2021

The mechanical performances of single-lap joints between similar and dissimilar adherends bonded with a bi-component polyurethane adhesive have been studied in the present work. The substrate materials include both carbon fibre reinforced composite material (CRFP) and painted metal substrates (PMS). The following substrate combinations were tested: CFRP/CFRP, PMS/PMS, and CFRP/PMS. Two adhesive overlaps, 12 mm and 24 mm, with a fixed thickness were studied to assess the mechanical behaviour of the adhesive joints. The experimental results have been used to construct a finite element model of the single lap joint tests. The objective is to determine the material cohesive properties, in particular the maximum shear stress and the corresponding energy release rate, of the adhesive layer for each retained combination of substrates. An optimization scheme based on transient nonlinear finite element analysis has been here considered, where cohesive parameters of the adhesive layer are handled as design variables. Material parameters are firstly identified for the 12 mm overlap, minimizing the discrepancy between the experimental and numerical force-displacement curves. Then, to validate the obtained properties, results of the 24 mm overlap single lap joint tests are used. The comparison between the experimental and numerical results shows a very good agreement.
Design of a non-destructive test for validating models of hydrogen migration
Authors: Beghini M , Bertini L , Macoretta G , Monelli B D , Valentini R
Published: March 2021

High-strength steels, despite their excellent mechanical properties in normal conditions, can be susceptible to hydrogen embrittlement. Due to the service loads or residual stresses, hydrogen migrates within the component and accumulates in the regions where the highest tensile hydrostatic stress occurs. As a consequence, component brittle failure can occur even if the initial or mean hydrogen concentration is lower than the critical value. The availability of models predicting the hydrogen diffusion within the component is a crucial task for the design. Several diffusive models have been presented in the literature and some general-purpose finite element codes have already implemented some of them. However, the validation of those models is still an open issue due to the difficulty in performing accurate local measurements of the hydrogen concentration. This study deals with the design of a test potentially able to validate hydrogen migration models. In the test, a four-point bending configuration is applied to a properly shaped hourglass specimen, previously charged with hydrogen, extracted from thin high-strength steel sheets. The specimen geometry and the loading configuration were designed to obtain a central region in which the stress and strain field is uniform in plane and exhibits a quasi-uniform gradient in the thickness direction. As a consequence, it is expected a large enough central region of the specimen in which the Hydrogen can migrate only in the thickness direction during the typical duration of the test. The local hydrogen concentration is evaluated by measuring the flux leaving the tensile surface of the specimen by a solid-state hydrogen sensor.
Development of a wearable device for the early diagnosis of neurodegenerative diseases
Authors: Avalle M , Belotti V , Frascio M , Razzoli R
Published: March 2021

The progressive evolution of information and sensing technologies is giving pulse to the development of wearable mobile devices in search of life quality improvement. A relevant field of application is healthcare, with the development of wireless unobtrusive wearable solutions for the continuous remote health monitoring of patients. These wearable devices are particularly important for neurodegenerative diseases due to the possibility of early stage diagnoses through continuous monitoring to collect earlier significant data. Discovering specific symptoms and early defining medical treatments can delay, if not stop, the pathology progress whereas, once major symptoms like restricted or impaired mobility has appeared, the patients already underwent relevant and irreversible brain damage. The aim of this work is to show the development of the Neuroglass, a wearable smart glasses device for early stage diagnosis and monitoring of Parkinsonian-type neurodegenerative diseases. The designed frame is compliant to the standards and in order to embed the sensors to collect data from head and eyes movements since one of the early symptoms of Parkinson’s disease has proven to be eye tremors. Preliminary laboratory tests, e.g. head accelerations measurements for different body movements, were carried out in order to choose properly the characteristics and positioning of the sensors; afterwards the device’s frame was designed by means of a 3D parametric CAD and built by additive manufacturing. The design was validated by first experimental test on monitoring eye movements and blinks.
A statistical study on long freight trains equipped with radio communication within Shift2Rail
Authors: Cantone L , Laghi D , La Rovere S
Published: March 2021

Paper reports the main results of a systematic study on longitudinal train dynamics (LTD) of long freight trains equipped with radio communication. It is divided in two parts: the first addresses the global sensitivity analysis aiming to find the most relevant parameters that, with their associated uncertainty, mainly affect the LTD of coupled trains, independently by the train length or train operation. The second part studies the LTD of classic freight trains in Germany (i.e. with one Traction Unit -TU- at the beginning of the train), considering the variation of the parameters identified during the sensitivity analysis. Finally, several train-consists with two up to four TU and having train length up to 1500 m are found to be as safe as the classic trains and therefore can put in service, as long as the LTD is concerned, allowing a relevant increase of efficiency.
Friction dissipation in reciprocating internal combustion engines: cam tappet contact
Authors: Sansone P , Lavella M
Published: March 2021

The interest towards fuel consumption reduction in reciprocating internal combustion engines has achieved a key role starting from the first energy crisis during the 70’s. Even if in alternate phases, such interest had further increased during the following years assuming a fundamental role in the last years. The reason lies in the introduction of regulations that limit the emissions of carbon dioxide, as it belongs to the family of greenhouse gasses. A reduction of the friction dissipation reflects directly on consumption reduction and consequently in an improvement of emissions. The main goal of this research is to model the friction dissipation at the cam tappet interface. In this research an analytic model is proposed, it allows to estimate the dissipation due to friction with a complexity appropriate to that of the design phase and which allows to select between different design solutions in order to optimize the efficiency of the cam tappet interfaces. Model results are coherent with experimental results reported in literature.
Multiscale three-dimensional stress analysis of voids clusters for the modelling of degenerated graphite in cast iron
Authors: Rizzoni R , Livieri P , Tovo R
Published: March 2021

We propose a multiscale three-dimensional model for the stress analysis of a cluster of degenerated graphite in spheroidal cast iron. The model allows to study the effect of graphite microstructure on the average stress distribution inside the cluster. At the microscale, precipitates of degenerated graphite are modelled as spheroidal voids. At the mesoscale, clusters of degenerated graphite are viewed as spheroidal inclusions made of equivalent porous elastic material. The equivalent elastic properties of the porous material are calculated using an approach proposed by Tandon and Weng and based on Eshelby’s equivalent principle and the Mori-Tanaka’s estimate. FE simulations at the microscale and at the mesoscale are performed in order to numerically validate the multiscale model.
Fatigue crack-growth predictions for a railway axle under material data variability
Authors: Giannella V
Published: March 2021

This document reports a probabilistic approach for residual fatigue life predictions of a cracked railway axle with allowance for variability of the input data. A NASGRO formulation was used for such a purpose, with its main parameters considered as uncorrelated random variables varying in given ranges. A load spectrum was considered in order to take into account of the actual loading conditions that these components undergo. The presented approach aimed to perform residual fatigue life predictions in terms of both mean value and dispersion around it. The results were also used to drive deterministic approaches in calculating conservative crack-growth assessments.
Influence of coil contact on static behavior of helical compression springs
Authors: De Crescenzo F , Salvini P
Published: March 2021

Large deformations of helical springs are affected by coil contact, but most available spring modelling techniques only account for nonlinear vertical motion, and Finite Elements (FE) nonlinear analysis that considers contact between coils can be very expensive. A 2D model based on equivalent beam and penalty-based contact algorithm is developed for efficient yet realistic prediction of non-uniform spring deflection. The proposed model is tested versus FE, where the helical wire is modelled using beam elements. Two scenarios are taken into account: a cylindrical spring in compression/bending and a progressive conical spring under simple compression. It is shown that the proposed model matches FE at a very low computational cost.
Amplification of laser diode-induced photoacoustic signals for non-destructive testing of mechanical components
Authors: Gulino Michelangelo-Santo , Banelli Luca , Vangi Dario
Published: March 2021

The present work highlights that the laser diode, acting as an ultrasonic source by photoacoustic effect, can be successfully employed for defect detection in mechanical components; the performed investigation specifically involves a railway axle with cracks on the body and fillets, respectively 13 mm-deep and 2 mm-deep. To ease the inspection process, a methodology for amplification of the ultrasound is introduced which is based on the appropriate choice of the TTL signal modulating the diode; amplification is achieved by constructive interference between two ultrasonic signals: the first is induced by the dilation resulting from the laser ignition, the second conversely derives from the contraction obtained when the laser is powered off. The proposed amplification methodology allows ultrasonic energy to be focused in a narrow range of frequencies, promoting the use of traditional detection devices like narrowband probes. The developed inspection system, which takes advantage of a 20 W source, enables the identification of the ultrasonic pattern and defect detection regardless of the application of post-processing techniques on the acquired signals: allowing for excitation of high-amplitude ultrasound without directly contacting the component, the laser diode represents a suitable source for the non-destructive inspection of the axle while it rotates (i.e., during operation). Thanks to the cost reduction achieved in comparison with the use of more traditional pulsed lasers, the diode lends itself to large-scale application in the field of non-destructive testing on mechanical structures.
Magnetostructural assessment of DEMO TF coils with ENEA Winding Pack configuration
Authors: Giorgetti F , Mercuri A , Boso D , Calabrò G , Corato V , Fanelli P , Muzzi L , Stefanini C
Published: March 2021

The present paper deals with a multiphysics study of the DEMO Toroidal Field (TF) coils with Winding Pack (WP) layout proposed by the Italian agency ENEA. The latest WP configuration, so far designed adopting the Wind&React technique, is composed of 202 Nb3Sn rectangular conductors, with steel jacket thickness progressively increased from the plasma-facing side, arranged in 6 double layers. Each conductor is designed to carry an operative current of 73.4 kA (14.8 MAt for one TF coil) and to ensure the requirement of 12 T of magnetic peak field. The electromagnetic (EM) Lorentz forces have been preliminary evaluated with a magnetostatic 3D analysis at different instants of plasma scenario and then used to perform the 3D structural assessment of the TF coil. For both models (i.e., electromagnetic and mechanical), the WP has been represented as a homogenized material with the cyclic symmetry boundary conditions, allowing to reduce the computational effort. In the structural model, a preliminary design of outer inter-coil structures and gravity support have been included allowing them to identify critical locations in a reliable way. In addition to the EM loads at different plasma scenario instants also the cooling down has been considered as loading condition. The stress assessment on the steel Casing was performed, exploiting the stress linearization along several paths chosen in the most critical locations.
Experimental setup for the evaluation of large displacements in the inflected beams sustained to ground
Authors: Marotta E , Iandiorio C , Salvini P
Published: March 2021

In engineering practice, it often occurs to tackle structures with systems of forces such as to induce displacements beyond the linear response. If the material remains in the elastic field, the behaviour is generally addressed as geometric non-linearity. Taking into consideration beam structures subjected to distributed and concentrated loads, the differential equations that describe the structural behavior need to be solved with numerical methods (e.g. Runge-Kutta algorithm or F.E.M.) or analytical perturbative approaches. This work presents experimental results concerning a beam, sustained to the ground, loaded to own weight and lifted by concentrated loads at the free-end. The loads are such as to cause very large displacements. The work describes some useful tricks to carry out the tests with good precision and repeatability. Several experimental data are compared with numerical results.
Analysis of the blast wave – structure interface phenomenon in case of explosive events
Authors: Lomazzi L , Giglio M , Manes A
Published: March 2021

Several structures need their response to blast loads to be investigated to grant an acceptable survivability level. To this purpose, experimental campaigns are complex, but some numerical methods are commonly exploited. The explosion pressure-time history is typically estimated characterizing the detonation of an energetically equivalent explosion involving the detonation of a specific amount of TNT. The pressure-time history at a point, fixed in space, involved by the blast wave is described by the Friedlander equation. A specific approach to modelling the complex blast wave–target structure coupling is reported in the UFC 3-340-02. This method, although consolidated and valid for aerospace, civil and mechanical structure, is not adopted in predictive simulations, which involve naïve methods for characterizing that interface phenomenon. This work aims to give an insight on the blast wave–structure interaction event. A methodological approach combining the Friedlander equation and the theory reported in the UFC 3-340-02 is presented, which confidently characterizes the effects of explosive loads on common structures. This fully analytical method may be implemented into numerical codes to perform simple, but effective, preliminary characterizations of the structural response to explosive loads. Finally, a possible application of the proposed method to thin-walled structures is shown.
Different roles of stacking fault energy and diffusivity in the creep performance of nickel-based single-crystal superalloys
Authors: He Chuang , Huang Taiwen , Yang Wenchao , Wang Xiaojuan , Zhang Jun , Guo Min , Liu Lin
Published: March 2021

Two nickel-based single-crystal (SC) superalloys (designated T6 and T13) were investigated in order to reveal the effects of stacking fault (SF) energy and diffusion on their high-temperature creep behavior. In this study, the effect of dislocation spacing on creep was the same between T6 and T13. The microstructure and deformation rate attained prior to 1% creep were investigated in detail. Several differences were detected in the two superalloys, the reasons for these differences were discussed. The results suggested that the SF energy of the γ matrix was the key factor affecting development of the dislocation network. Because the matrix of the T6 superalloy has lower SF energy than T13, the cross-slipping of dislocation was more difficult in the early stages of creep, which resulted in lower levels of dislocation propagation and of formation of the dislocation network. When creep had entered the steady stage, the key process controlling high-temperature creep was atomic migration in the γ matrix, and the creep rupture life was lengthened by reducing the penetration of dislocations into the γ′ raft and slowing down its topological inversion.
Highly viscous fluids made to flow faster than water
Authors: Jarman Sam
Published: March 2021

Honey and other highly viscous fluids can flow faster than water in specially coated capillary tubes, Maja Vuckovac and colleagues at Finland’s Aalto University have shown
Accelerators gear up for new collision regime
Authors: Cartlidge Edwin
Published: March 2021

Gear-changing in particle colliders could allow the smashing together of particles with different velocities, as Edwin Cartlidge finds out
Nader Engheta wins Isaac Newton Medal
Authors: Banks Michael
Published: March 2021

The optical physicist Nader Engheta has won the 2020 Isaac Newton Medal and Prize for “groundbreaking innovation and transformative contributions to electromagnetic complex materials and nanoscale optics, and for pioneering development of the fields of near-zero-index metamaterials, and materialinspired analogue computation and optical nanocircuitry”.
Hot time for hard disks
Authors: McKenzie James
Published: March 2021

James McKenzie looks at the power of incremental improvement and the commercial success of magnetic-recording technology
‘Smart speaker, tell me about your acoustic sensor’
Authors: Knight Pip
Published: March 2021

Smart speakers that can register our everyday commands have become commonplace in homes around the world. While the acoustics sensors inside these devices are far flung from the first microphone, the technology is still evolving, as Pip Knight explains
Thirty years of ‘against measurement’
Authors: Baggott Jim
Published: March 2021

Despite its many successes, physicists are still struggling to nail down a coherent interpretation of quantum mechanics, as it best represents “reality”. Jim Baggott explores the arguments first put forth by John Bell three decades ago, and looks at theoretical and experimental evidence accumulated since
On the road less travelled
Authors: Russell Brooke , Williams Tamia
Published: March 2021

Postdoc Brooke Russell and graduate student Tamia Williams share their stories of being #BlackInPhysics, from the importance of finding your community and creating a good mentoring environment, to having the determination to succeed
Resolving the squoon
Authors: Porter Nicholas
Published: March 2021

Children’s author Julia Donaldson and illustrator Axel Scheffler recently put forth a new book, whimsically titled The Smeds and the Smoos, featuring an irregular, wonky natural satellite called a squoon
Efficient solution of linear inverse problems using an iterative linear neural network with a generalization training approach
Authors: Tieng Quang M , Su Jiasheng , Vegh Viktor , Reutens David C
Published: March 2021

Inverse problems are some of the most important mathematical problems in science and mathematics because their solution yields information about parameters that are not directly observable. Artificial neural networks have long been used as a mathematical modelling method and have been used successfully to solve inverse problems for application including denoising and medical image reconstruction. Many inverse problems result from integral processes that can be modelled using a linear formulation. These can be efficiently solved via simple networks which are easily trained with reasonable datasets. An innovative simple neural network architecture, the iterative linear neural network (ILNN), consisting of two non-hidden layer networks, one for the forward model and one for the inverse model, is proposed to solve linear inverse problems. Iteration between the two models refines network outcomes with greater accuracy than a network with only the inverse model. A training procedure accompanying the network is also introduced. The network needs to train only the inverse model with one-hot vectors as targets. The training inputs of the inverse model define the weights of the forward model. The number of targets is finite and equal to the length of the vector. With the defined targets, the training process ensures that the inverse model is at least a left inverse of the forward model. This leads to generalizable networks. The experimental results show that the ILNN produces good results even if its inverse model is not perfectly trained. The proposed network is applied to solve two linear inverse problems, deconvolution and the inverse Radon transform. The network successfully reconstructed original data following blurring and Radon transformation.
Fourier decay for self-similar measures
Authors: Solomyak Boris
Published: March 2021

We prove that, after removing a zero Hausdorff dimension exceptional set of parameters, all self-similar measures on the line have a power decay of the Fourier transform at infinity. In the homogeneous case, when all contraction ratios are equal, this is essentially due to Erdős and Kahane. In the non-homogeneous case the difficulty we have to overcome is the apparent lack of convolution structure.
Instability of rational and polynomial convexity
Authors: Nemirovski Stefan
Published: March 2021

It is shown that rational and polynomial convexity of totally real submanifolds is in general unstable under perturbations that are

C
α

C^\alpha

-small for any Hölder exponent

α
>
1

\alpha >1

. This complements the result of Løw and Wold that these properties are

C
1

C^1

-stable.
Finite metric and 𝑘-metric bases on ultrametric spaces
Authors: Corregidor Samuel , Martínez-Pérez Álvaro
Published: March 2021

Given a metric space

(
X
,
d
)

(X,d)

, a set

S
⊆
X

S\subseteq X

is called a

k
k

-metric generator for

X
X

if any pair of different points of

X
X

is distinguished by at least

k
k

elements of

S
S

. A

k
k

-metric basis is a

k
k

-metric generator of the minimum cardinality in

X
X

. We prove that ultrametric spaces do not have finite

k
k

-metric bases for

k
>
2

k>2

. We also characterize when the metric and 2-metric bases of an ultrametric space are finite and, when they are finite, we characterize them. Finally, we prove that an ultrametric space can be easily recovered knowing only the metric basis and the coordinates of the points in it.
Sharp nonzero lower bounds for the Schur product theorem
Authors: Khare Apoorva
Published: March 2021

By a result of Schur [J. Reine Angew. Math. 140 (1911), pp. 1–28], the entrywise product

M
∘
N

M \circ N

of two positive semidefinite matrices

M
,
N

M,N

is again positive. Vybíral [Adv. Math. 368 (2020), p. 9] improved on this by showing the uniform lower bound

M
∘

M
¯

≥

E
n

/

n

M \circ \overline {M} \geq E_n / n

for all

n
×
n

n \times n

real or complex correlation matrices

M
M

, where

E
n

E_n

is the all-ones matrix. This was applied to settle a conjecture of Novak [J. Complexity 15 (1999), pp. 299–316] and to positive definite functions on groups. Vybíral (in his original preprint) asked if one can obtain similar uniform lower bounds for higher entrywise powers of

M
M

, or for

M
∘
N

M \circ N

when

N
≠
M
,

M
¯

N \neq M, \overline {M}

. A natural third question is to ask for a tighter lower bound that does not vanish as

n
→
∞

n \to \infty

, i.e., over infinite-dimensional Hilbert spaces.

In this note, we affirmatively answer all three questions by extending and refining Vybíral’s result to lower-bound

M
∘
N

M \circ N

, for arbitrary complex positive semidefinite matrices

M
,
N

M,N

. Specifically: we provide tight lower bounds, improving on Vybíral’s bounds. Second, our proof is ‘conceptual’ (and self-contained), providing a natural interpretation of these improved bounds via tracial Cauchy–Schwarz inequalities. Third, we extend our tight lower bounds to Hilbert–Schmidt operators. As an application, we settle Open Problem 1 of Hinrichs–Krieg–Novak–Vybíral [J. Complexity 65 (2021), Paper No. 101544, 20 pp.], which yields improvements in the error bounds in certain tensor product (integration) problems.
Commodifying Mexico: OnAmerican Dirtand the Cultural Politics of a Manufactured Bestseller
Authors: Sánchez Prado* Ignacio M
Published: March 2021

Following the publication and controversy surrounding American Dirt (2020) by Jeanine Cummins, this essay discusses the process by which American Dirt'™s bestseller status was manufactured in correlation with Flatiron☳ aim to capitalize on a growing Latinx market and on the political visibility of the questions of immigration. It argues that the misrepresentation and commodification of Mexico in the book's form and construction is a central feature of its marketability and success and studies the ways in which the book☳ errors align themselves with representations in Hollywood cinema and television that forward a negative view of Mexico aligned with anti-immigrant and anti-Mexican politics. Finally, the essay discusses the coexistence of these two factors with a growing infrastructure of Hispanophone and translated Latin American literature that competes with, and seeks to challenge, the existence of books like American Dirt.
eQTLHap: a tool for comprehensive eQTL analysis considering haplotypic and genotypic effects
Authors: Al Bkhetan Ziad , Chana Gursharan , Soon Ong Cheng , Goudey Benjamin , Ramamohanarao Kotagiri
Published: March 2021

Motivation

The high accuracy of recent haplotype phasing tools is enabling the integration of haplotype (or phase) information more widely in genetic investigations. One such possibility is phase-aware expression quantitative trait loci (eQTL) analysis, where haplotype-based analysis has the potential to detect associations that may otherwise be missed by standard SNP-based approaches.

Results

We present eQTLHap, a novel method to investigate associations between gene expression and genetic variants, considering their haplotypic and genotypic effect. Using multiple simulations based on real data, we demonstrate that phase-aware eQTL analysis significantly outperforms typical SNP-based methods when the causal genetic architecture involves multiple SNPs. We show that phase-aware eQTL analysis is robust to phasing errors, showing only a minor impact ($<4\%$) on sensitivity. Applying eQTLHap to real GEUVADIS and GTEx datasets detects numerous novel eQTLs undetected by a single-SNP approach, with 22 eQTLs replicating across studies or tissue types, highlighting the utility of phase-aware eQTL analysis.

Availability and implementation

https://github.com/ziadbkh/eQTLHap.

Contact

ziad.albkhetan@gmail.com

Supplementary information

Supplementary data are available at Briefings in Bioinformatics online.
Pandemic and Social Work: Exploring Finnish Social Workers’ Experiences through a SWOT Analysis
Authors: Harrikari Timo , Romakkaniemi Marjo , Tiitinen Laura , Ovaskainen Sanna
Published: March 2021

This article addresses the experiences of Finnish frontline social workers during the first wave of the COVID-19 pandemic in the spring of 2020. Two questions are addressed. First, ‘what types of challenges social work professionals faced’ in their everyday, ‘glocal’ pandemic setting and, second, what types of solutions they developed to meet these challenges. The data consist of 33 personal diaries that social work professionals created from mid-March to the end of May 2020. The diaries are analysed by a thematic content analysis and placed within the framework of a strengths, weaknesses, opportunities and threats analysis. The results suggest that the pandemic challenged social work at all levels, from face-to-face interactions to its global relations. The pandemic revealed not only the number of existing problems of social work, but also created new types of challenges. It demanded ultimate resilience from social workers and a new type of adaptive governance from social welfare institutions.
Biallelic loss-of-function variations in PRDX3 cause cerebellar ataxia
Authors: Rebelo Adriana P , Eidhof Ilse , Cintra Vivian P , Guillot-Noel Léna , Pereira Claudia V , Timmann Dagmar , Traschütz Andreas , Schöls Ludger , Coarelli Giulia , Durr Alexandra , Anheim Mathieu , Tranchant Christine , van de Warrenburg Bart , Guissart Claire , Koenig Michel , Howell Jack , Moraes Carlos T , Schenck Annette , Stevanin Giovanni , Züchner Stephan , Synofzik Matthis ,   the PREPARE network
Published: March 2021

Peroxiredoxin 3 (PRDX3) belongs to a superfamily of peroxidases that function as protective antioxidant enzymes. Among the six isoforms (PRDX1–PRDX6), PRDX3 is the only protein exclusively localized to the mitochondria, which are the main source of reactive oxygen species. Excessive levels of reactive oxygen species are harmful to cells, inducing mitochondrial dysfunction, DNA damage, lipid and protein oxidation and ultimately apoptosis. Neuronal cell damage induced by oxidative stress has been associated with numerous neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. Leveraging the large aggregation of genomic ataxia datasets from the PREPARE (Preparing for Therapies in Autosomal Recessive Ataxias) network, we identified recessive mutations in PRDX3 as the genetic cause of cerebellar ataxia in five unrelated families, providing further evidence for oxidative stress in the pathogenesis of neurodegeneration. The clinical presentation of individuals with PRDX3 mutations consists of mild-to-moderate progressive cerebellar ataxia with concomitant hyper- and hypokinetic movement disorders, severe early-onset cerebellar atrophy, and in part olivary and brainstem degeneration. Patient fibroblasts showed a lack of PRDX3 protein, resulting in decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity. Moreover, PRDX3 knockdown in cerebellar medulloblastoma cells resulted in significantly decreased cell viability, increased H2O2 levels and increased susceptibility to apoptosis triggered by reactive oxygen species. Pan-neuronal and pan-glial in vivo models of Drosophila revealed aberrant locomotor phenotypes and reduced survival times upon exposure to oxidative stress. Our findings reveal a central role for mitochondria and the implication of oxidative stress in PRDX3 disease pathogenesis and cerebellar vulnerability and suggest targets for future therapeutic approaches.
Effect of concentration and duration of particulate matter exposure on the transcriptome and DNA methylome of bronchial epithelial cells
Authors: Huang Steven K , Tripathi Priya , Koneva Lada A , Cavalcante Raymond G , Craig Nathan , Scruggs Anne M , Sartor Maureen A , Deng Furong , Chen Yahong
Published: March 2021

Exposure to particulate matter (PM) from ambient air pollution is a well-known risk factor for many lung diseases, but the mechanism(s) for this is not completely understood. Bronchial epithelial cells, which line the airway of the respiratory tract, undergo genome-wide level changes in gene expression and DNA methylation particularly when exposed to fine (<2.5 µm) PM (PM2.5). Although some of these changes have been reported in other studies, a comparison of how different concentrations and duration of exposure affect both the gene transcriptome and DNA methylome has not been done. Here, we exposed BEAS-2B, a bronchial epithelial cell line, to different concentrations of PM2.5, and compared how single or repeated doses of PM2.5 affect both the transcriptome and methylome of cells. Widespread changes in gene expression occurred after cells were exposed to a single treatment of high-concentration (30 µg/cm2) PM2.5 for 24 h. These genes were enriched in pathways regulating cytokine–cytokine interactions, Mitogen-Activated Protein Kinase (MAPK) signaling, PI3K-Akt signaling, IL6, and P53. DNA methylomic analysis showed that nearly half of the differentially expressed genes were found to also have DNA methylation changes, with just a slightly greater trend toward overall hypomethylation across the genome. Cells exposed to a lower concentration (1 µg/cm2) of PM2.5 demonstrated a comparable, but more attenuated change in gene expression compared to cells exposed to higher concentrations. There were also many genes affected by lower concentrations of PM2.5, but not higher concentrations. Additionally, repeated exposure to PM2.5 (1 µg/cm2) for seven days resulted in transcriptomic and DNA methylomic changes that were distinct from cells treated with PM2.5 for only one day. Compared to single exposure, repeated exposure to PM2.5 caused a more notable degree of hypomethylation across the genome, though certain genes and regions demonstrated increased DNA methylation. The overall increase in hypomethylation, especially with repeated exposure to PM2.5, was associated with an increase in expression of ten–eleven translocation enzymes. These data demonstrate how variations in concentration and duration of PM2.5 exposure induce distinct differences in the transcriptomic and DNA methylomic profile of bronchial epithelial cells, which may have important implications in the development of both acute and chronic lung disease.
Management of aortic stenosis: a systematic review of clinical practice guidelines and recommendations
Authors: Khanji Mohammed Y , Ricci Fabrizio , Galusko Victor , Sekar Baskar , Chahal C Anwar A , Ceriello Laura , Gallina Sabina , Kennon Simon , Awad Wael I , Ionescu Adrian
Published: March 2021

Multiple guidelines exist for the management of aortic stenosis (AS). We systematically reviewed current guidelines and recommendations, developed by national or international medical organizations, on management of AS to aid clinical decision-making. Publications in MEDLINE and EMBASE between 1 June 2010 and 15 January 2021 were identified. Additionally, the International Guideline Library, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, and websites of relevant organizations were searched. Two reviewers independently screened titles and abstracts. Two reviewers assessed rigour of guideline development and extracted the recommendations. Of the seven guidelines and recommendations retrieved, five showed considerable rigour of development. Those rigourously developed, agreed on the definition of severe AS and diverse haemodynamic phenotypes, indications and contraindications for intervention in symptomatic severe AS, surveillance intervals in asymptomatic severe AS, and the importance of multidisciplinary teams (MDTs) and shared decision-making. Discrepancies exist in age and surgical risk cut-offs for recommending surgical aortic valve replacement (SAVR) vs. transcatheter aortic valve implantation (TAVI), the use of biomarkers and complementary multimodality imaging for decision-making in asymptomatic patients and surveillance intervals for non-severe AS. Contemporary guidelines for AS management agree on the importance of MDT involvement and shared decision-making for individualized treatment and unanimously indicate valve replacement in severe, symptomatic AS. Discrepancies exist in thresholds for age and procedural risk used in choosing between SAVR and TAVI, role of biomarkers and complementary imaging modalities to define AS severity and risk of progression in asymptomatic patients.
The incidence and management of shoulder complaints in general practice: a retrospective cohort study
Authors: van Doorn Pieter F , de Schepper Evelien I T , Rozendaal Rianne M , Ottenheijm Ramon P G , van der Lei Johan , Bindels Patrick J , Schiphof Dieuwke
Published: March 2021

Background

Shoulder pain is the third most common musculoskeletal complaint in primary care. The international guidelines for general practitioners (GPs) recommend a stepwise treatment of shoulder pain. Little is known about the actual distribution of these treatments in current practice.

Objective

To gain insight in the incidence and current management of shoulder complaints in Dutch general practice.

Methods

A retrospective cohort study was conducted using a health care database containing the full electronic medical records of approximately 200 000 patients in Dutch general practice. A search algorithm was constructed to identify incident cases of shoulder complaints from January 2012 to December 2017. Data on the management of shoulder complaints were manually validated in a random sample of 1000 cases.

Results

The overall incidence of shoulder complaints was 30.3 (95% confidence interval 29.9–30.7) per 1000 person-years. More than half of the patients (58.6%) consulted their GP only once, 44.4% two times or more and 19.7% three times or more. For most patients (58.1%), the GP applied a wait-and-see policy or prescription of oral medication in the first consultation. However, no less than 42.9% of the patients were referred or received an injection already in the first consultation.

Conclusions

There is a wide variety of treatments for shoulder complaints applied by the GP. Some patients are referred or received an injection already in the first consultation. The stepwise approach recommended by the guideline, might not always be applicable due to the diversity of patient- and shoulder characteristics presented in general practice.
Scoping review: Development and assessment of evaluation frameworks of mobile health apps for recommendations to consumers
Authors: Hensher Martin , Cooper Paul , Dona Sithara Wanni Arachchige , Angeles Mary Rose , Nguyen Dieu , Heynsbergh Natalie , Chatterton Mary Lou , Peeters Anna
Published: March 2021

Objective

The study sought to review the different assessment items that have been used within existing health app evaluation frameworks aimed at individual, clinician, or organizational users, and to analyze the scoring and evaluation methods used in these frameworks.

Materials and Methods

We searched multiple bibliographic databases and conducted backward searches of reference lists, using search terms that were synonyms of “health apps,” “evaluation,” and “frameworks.” The review covered publications from 2011 to April 2020. Studies on health app evaluation frameworks and studies that elaborated on the scaling and scoring mechanisms applied in such frameworks were included.

Results

Ten common domains were identified across general health app evaluation frameworks. A list of 430 assessment criteria was compiled across 97 identified studies. The most frequently used scaling mechanism was a 5-point Likert scale. Most studies have adopted summary statistics to generate the total scoring of each app, and the most popular approach taken was the calculation of mean or average scores. Other frameworks did not use any scaling or scoring mechanism and adopted criteria-based, pictorial, or descriptive approaches, or “threshold” filter.

Discussion

There is wide variance in the approaches to evaluating health apps within published frameworks, and this variance leads to ongoing uncertainty in how to evaluate health apps.

Conclusions

A new evaluation framework is needed that can integrate the full range of evaluative criteria within one structure, and provide summative guidance on health app rating, to support individual app users, clinicians, and health organizations in choosing or recommending the best health app.
Iron metabolism strategies in diatoms
Authors: Gao Xia , Bowler Chris , Kazamia Elena
Published: March 2021

Diatoms are one of the most successful group of photosynthetic eukaryotes in the contemporary ocean. They are ubiquitously distributed and are the most abundant primary producers in polar waters. Equally remarkable is their ability to tolerate iron deprivation and respond to periodic iron fertilization. Despite their relatively large cell sizes, diatoms tolerate iron limitation and frequently dominate iron-stimulated phytoplankton blooms, both natural and artificial. Here, we review the main iron use strategies of diatoms, including their ability to assimilate and store a range of iron sources, and the adaptations of their photosynthetic machinery and architecture to iron deprivation. Our synthesis relies on published literature and is complemented by a search of 82 diatom transcriptomes, including information collected from seven representatives of the most abundant diatom genera in the world’s oceans.
Negative Vaccine Attitudes and Intentions to Vaccinate Against Covid-19 in Relation to Smoking Status: A Population Survey of UK Adults
Authors: Jackson Sarah E , Paul Elise , Brown Jamie , Steptoe Andrew , Fancourt Daisy
Published: March 2021

Introduction

We examined differences in negative attitudes toward vaccines in general, and intentions to vaccinate against Covid-19 specifically, by smoking status in a large sample of adults in the UK.

Method

Data were from 29 148 adults participating in the Covid-19 Social Study in September–October 2020. Linear regression analyses examined associations between smoking status (current/former/never) and four types of general negative vaccine attitudes: mistrust of vaccine benefit, worries about unforeseen effects, concerns about commercial profiteering, and preference for natural immunity. Multinomial logistic regression examined associations between smoking status and uncertainty and unwillingness to be vaccinated for Covid-19. Covariates included sociodemographic characteristics and diagnosed health conditions.

Results

Relative to never and former smokers, current smokers reported significantly greater mistrust of vaccine benefit, were more worried about unforeseen future effects, had greater concerns about commercial profiteering, and had a stronger preference for natural immunity (Badjs 0.16–0.36, p < .001). Current smokers were more likely to be uncertain (27.6% vs. 22.7% of never smokers, RRadj 1.43 [95% confidence interval = 1.31–1.56]; vs. 19.3% of former smokers, RRadj 1.55 [1.41–1.73]) or unwilling (21.5% vs. 11.6% of never smokers, RRadj 2.12 [1.91–2.34]; vs. 14.7% of former smokers, RRadj 1.53 [1.37–1.71]) to receive a Covid-19 vaccine.

Conclusions

Current smokers hold more negative attitudes toward vaccines in general, and are more likely to be undecided or unwilling to vaccinate against Covid-19, compared with never and former smokers. With a disproportionately high number of smokers belonging to socially clustered and disadvantaged socioeconomic groups, lower vaccine uptake in this group could also exacerbate health inequalities.

Implications

These results suggest that without intervention, smokers will be less likely than nonsmokers to take up the offer of a Covid-19 vaccine when offered. Targeted policy action may be required to ensure that low uptake of Covid-19 vaccination programs does not compound health inequalities between smokers and nonsmokers.
Changes in astaxanthin and fatty acid concentrations during the developmental process in the calanoidArctodiaptomus walterianusin an alpine lake at low latitudes
Authors: Cui Suzhen , Li Yun , Liu Le , Wang Qianhong , Chen Feizhou
Published: March 2021

Astaxanthin is ubiquitous in calanoid copepods in high latitude or altitude regions and is well studied. However, the dynamics of astaxanthin in calanoids at low latitudes are less studied. We collected samples during the ice-free season from Lake Mubanghai, an alpine lake located in a low-latitude and high-altitude region, and analyzed astaxanthin content changes among different developmental stages in Arctodiaptomus walterianus. The total astaxanthin content in A. walterianus varied from 1.66 to 4.49 μg/mg dry weight and was highest in October, the month with the lowest temperature among the three sampling dates. Both free astaxanthin and astaxanthin esters content per biomass and the ratio of free astaxanthin increased from the nauplius to adult stage, and astaxanthin esters dominated in total astaxanthin in all developmental stages. The concentrations of polyunsaturated fatty acids were low in seston but were the main fatty acids in the calanoid. The total fatty acid concentration was positively correlated with the concentrations of total astaxanthin, free astaxanthin and astaxanthin esters in the calanoid. These results suggested that astaxanthin may be beneficial to the accumulation of fatty acids. This strategy may benefit calanoids in adaptation to high mountain environments at low latitudes.
Determining the acceptability of testing contacts of confirmed COVID-19 cases to improve secondary case ascertainment
Authors: Marchant E , Ready D , Wimbury G , Smithson R , Charlett A , Oliver I
Published: March 2021

Background

UK asymptomatic contacts of confirmed COVID-19 cases are not routinely tested for SARS-CoV-2. Testing contacts may improve case ascertainment and reduce onward transmission. This study investigated the acceptability of SARS-CoV-2 testing among contacts of confirmed cases as an integral part of the contact-tracing process.

Methods

A cross-sectional descriptive survey of case contacts was conducted in the UK. All contacts who completed a telephone call with the NHS Test and Trace Agile Lighthouse team were eligible for inclusion and were offered a molecular test. Consenting participants were sent a self-swab kit.

Results

Of the 1523 individuals contacted, 602 (39.5%) accepted the test offer. Of the 240 (39.9%) samples returned for testing, 16.3% tested polymerase chain reaction-positive for SARS-CoV-2.

Most individuals who declined with a reason (638/905; 70.5%) reported they had already taken or booked a SARS-CoV-2 test, or were part of a testing programme. Matched laboratory records confirmed 73.1% of those who declined were tested by another route.

Conclusions

Most case contacts were tested, either through arranging a test by themselves or by accepting the study offer. Results demonstrate high acceptability, with substantial test positivity, indicating that there is public health benefit in offering tests to contacts as a routine part of the contact-tracing process.