bluuebunny/crossref_metadata_2025 huggingface dataset:
Mammals on mountainsides revisited: Trait‐based tests of assembly reveal the importance of abiotic filters
Authors: Kohli Brooks A. , Stevens Richard D. , Rickart Eric A. , Rowe Rebecca J.
Published: March 2021

Aim

Mountains provide uniquely informative systems for examining how biodiversity is distributed and identifying the causes of those patterns. Elevational patterns of species richness are well‐documented for many taxa but comparatively few studies have investigated patterns in multiple dimensions of biodiversity along mountainsides, which can reveal the underlying processes at play. Here, we use trait‐based diversity patterns to determine the role of abiotic filters and competition in the assembly of communities of small mammals across elevation and evaluate the surrogacy of taxonomic, functional, and phylogenetic dimensions of diversity.

Location

Great Basin ecoregion, western North America.

Taxon

Rodents and shrews.

Methods

The elevational distributions of 34 species were determined from comprehensive field surveys conducted in three arid, temperate mountain ranges. Elevation–diversity relationships and community assembly processes were inferred from phylogenetic (PD) and functional diversity (FD) patterns of mean pairwise and mean nearest‐neighbor distances while accounting for differences in species richness. FD indices were calculated separately for traits related to either abiotic filtering (β‐niche traits) or biotic interactions (α‐niche traits) to test explicit predictions of the role of each across elevation.

Results

Trait‐based tests of processes indicated that abiotic filtering tied to a strong aridity gradient drives the assembly of both low‐ and high‐elevation communities. Support for competition was not consistent with theoretical expectations under the stress‐dominance hypothesis, species interactions‐abiotic stress hypothesis, or guild assembly rule. Mid‐elevation peaks in species richness contrasted with overall FD and PD, which generally increased with elevation. PD and total FD were correlated on two of three mountains.

Main conclusions

The functional diversity of small mammal communities in these arid, temperate mountains is most consistent with abiotic filters, whereas support for competition is weak. Decomposing FD into traits related to separate assembly processes and examining ecoregional variation in diversity were critical for uncovering the generality of mechanisms. Divergent patterns among dimensions revealed species richness to be a poor surrogate for PD and FD across elevation and reflect the effect of biogeographic and evolutionary history. This first analysis of elevational multidimensional diversity gradients for temperate mammals provides a versatile framework for future comparative studies.
On packaging and product returns in online retail—Mailing boxes or sending signals?
Authors: Wallenburg Carl Marcus , Einmahl Lukas , Lee Kang‐Bok , Rao Shashank
Published: March 2021

Considerable research on merchandise returns has looked at marketing elements of the sales process (e.g., product display) and how they influence returns. However, marketing and order fulfillment processes are temporally decoupled in remote purchase situations such as online retail. While both are intricate parts of the overall sales transaction, it is logical to believe that elements of order fulfillment may also be influential in explaining and controlling merchandise return. This study focuses on the packaging aspect of the order fulfillment process to explore how it may influence return incidents in online retail. Following insights from Signaling Theory, we propose that a product's package is a signal that communicates valuable information about the product to the buyer. We partner with an online retailer to study the outcome of a natural experiment involving product packaging during order fulfillment. Our results show that packaging influences returns, reducing them most significantly if the signaling is consistent across packaging levels.
The relation between quality of life and future expectations for refugee adolescents
Authors: Özçevik Subaşi Damla , Akça Sümengen Aylin , Ekim Ayfer , Ocakçı Ayşe Ferda , Beşer Ayşe
Published: March 2021

Problem

Refugee children and their families encounter various challenges in a new country. Studies on this issue reveal the presence of negative expectations on the future and life among refugees. This study was conducted to investigate the relationship between quality of life and future expectations in refugee adolescents.

Methods

This descriptive and cross‐sectional study was conducted in Turkey. In this study, 76 refugee adolescents between the ages of 12 and 18 participated. The study data were collected between September and December 2019 from two of the schools located in Istanbul. Study data were collected by using Future Expectation Scale for Adolescents (FESA) and Pediatric Quality of Life Questionnaire (PedsQL).

Findings

The mean ages of the participants were 15.7 ± 1.1 and all of them were females. A positive relationship was found between future expectations and quality of life.

Conclusions

The results showed that a positive significant relation was detected between quality‐of‐life scores and future expectations' scores. Understanding the factors affecting future expectations of refugee adolescents will help to plan interventions compatible with issues confronting adolescents.
Transvenous lead extraction in patients with persistent left superior vena cava
Authors: Curnis Antonio , Aboelhassan Mohamed , Cerini Manuel , Salghetti Francesca , Fabbricatore Davide , Maiolo Vincenzo , Arabia Gianmarco , Giacopelli Daniele , Fouad Doaa A. , Bontempi Luca
Published: March 2021

Purpose

Predictors of difficulty and complications of transvenous lead extraction (TLE) have been investigated in several studies; however, little is known about the venous anatomical characteristics that can have an impact on procedural outcomes. Among them, the persistent left superior vena cava (PLSVC) is a common anomaly often discovered incidentally during cardiac device implantation and could raise concerns if TLE is indicated.

We report technical considerations and outcomes of TLE for two patients with leads implanted via PLSVC.

Methods and Results

Two cardiac implantable electronic device recipients with isolated PLSVC required TLE due to infective endocarditis in one case and lead failure in the other. In the first case, TLE procedure was performed in a hybrid operating room with minimally invasive video‐assisted thoracoscopic monitoring due to the high procedural risk. Two active fixation 20‐year‐old pacing leads were removed with a relatively short fluoroscopy time. In the second case, we successfully extracted a single‐coil active fixation lead without the need of a locking stylet or advanced extraction tools. There were no procedural complications or adverse events at 1‐year follow‐up.

Conclusion

TLE procedures for two patients with isolated PLSVC were successfully completed with less difficulty and tools than expected based on the characteristics of the targeted leads. If indicated, TLE in the presence of a PLSVC should be considered in experienced centers.
Early language screening and intervention can be delivered successfully at scale: evidence from a cluster randomized controlled trial
Authors: West Gillian , Snowling Margaret J. , Lervåg Arne , Buchanan‐Worster Elizabeth , Duta Mihaela , Hall Alexandra , McLachlan Henrietta , Hulme Charles
Published: March 2021

Background

It is well established that oral language skills provide a critical foundation for formal education. This study evaluated the effectiveness of the Nuffield Early Language Intervention (NELI) programme in ameliorating language difficulties in the first year of school when delivered at scale.

Methods

We conducted a cluster randomized controlled trial (RCT) in 193 primary schools (containing 238 Reception classrooms). Schools were randomly allocated to either a 20‐week oral language intervention or a business‐as‐usual control group. All classes (N = 5,879 children) in participating schools were screened by school staff using an automated App to assess children’s oral language skills. Screening identified 1,173 children as eligible for language intervention: schools containing 571 of these children were allocated to the control group and 569 to the intervention group.

Results

Children receiving the NELI programme made significantly larger gains than the business‐as‐usual control group on a latent variable reflecting standardized measures of language ability (d = .26) and on the school‐administered automated assessment of receptive and expressive language skills (d = .32). The effects of intervention did not vary as a function of home language background or gender.

Conclusions

This study provides strong evidence for the effectiveness of a school‐based language intervention programme (NELI) delivered at scale. These findings demonstrate that language difficulties can be identified by school‐based testing and ameliorated by a TA delivered intervention; this has important implications for educational and social policy.
Lower insulin secretion is associated with hippocampal and parahippocampal gyrus atrophy in elderly patients with type 2 diabetes mellitus
Authors: Adachi Yuko , Ota Kazuki , Minami Isao , Yamada Tetsuya , Watanabe Takayuki
Published: March 2021

Aims/Introduction

We aimed to examine the association between diabetes‐related parameters and hippocampal and parahippocampal gyrus atrophy (HPGA) in patients with type 2 diabetes mellitus to elucidate the risk factors for HPGA, which is often accompanied by Alzheimer’s disease.

Materials and methods

A total of 137 patients aged ≥50 years with type 2 diabetes mellitus (mean age 67.8 ± 9.8 years) underwent brain magnetic resonance imaging scans and comprehensive health examinations. We measured the volume of interest – a portion of the inner temporal lobe that includes the hippocampus, amygdala and entorhinal cortex (frontal part of the parahippocampal gyrus) – using the voxel‐based specific regional analysis system for Alzheimer’s disease in each patient. The diabetes‐related parameters included glycated hemoglobin, fasting plasma glucose, C‐peptide (CPR) index (serum CPR / fasting plasma glucose × 100) and duration of diabetes.

Results

The mean glycated hemoglobin was 9.3 ± 2.2%, the median CPR index was 1.29 (interquartile range 0.85–1.74) and the median duration of diabetes was 10 years (interquartile range 3–20 years). The severity score of volume of interest atrophy was >1.0 in 36 patients. Using multivariate logistic regression analysis, we found that age (odds ratio 1.09, 95% confidence interval 1.02–1.15) and CPR index (odds ratio 0.451, 95% confidence interval 0.216–0.940) were significantly associated with HPGA.

Conclusions

Lower insulin secretion was significantly associated with HPGA in patients with type 2 diabetes mellitus. The results of this study support the hypothesis that insulin‐signaling abnormalities are involved in the pathophysiology of Alzheimer’s disease.
Automated analysis of rabbit knee calcified cartilage morphology using micro‐computed tomography and deep learning
Authors: Rytky Santeri J. O. , Huang Lingwei , Tanska Petri , Tiulpin Aleksei , Panfilov Egor , Herzog Walter , Korhonen Rami K. , Saarakkala Simo , Finnilä Mikko A. J.
Published: March 2021

Structural dynamics of calcified cartilage (CC) are poorly understood. Conventionally, CC structure is analyzed using histological sections. Micro‐computed tomography (µCT) allows for three‐dimensional (3D) imaging of mineralized tissues; however, the segmentation between bone and mineralized cartilage is challenging. Here, we present state‐of‐the‐art deep learning segmentation for µCT images to assess 3D CC morphology. The sample includes 16 knees from 12 New Zealand White rabbits dissected into osteochondral samples from six anatomical regions: lateral and medial femoral condyles, lateral and medial tibial plateaus, femoral groove, and patella (n = 96). The samples were imaged with µCT and processed for conventional histology. Manually segmented CC from the images was used to train segmentation models with different encoder–decoder architectures. The models with the greatest out‐of‐fold evaluation Dice score were selected. CC thickness was compared across 24 regions, co‐registered between the imaging modalities using Pearson correlation and Bland–Altman analyses. Finally, the anatomical CC thickness variation was assessed via a Linear Mixed Model analysis. The best segmentation models yielded average Dice of 0.891 and 0.807 for histology and µCT segmentation, respectively. The correlation between the co‐registered regions was strong (r = 0.897, bias = 21.9 µm, standard deviation = 21.5 µm). Finally, both methods could separate the CC thickness between the patella, femoral, and tibial regions (p < 0.001). As a conclusion, the proposed µCT analysis allows for ex vivo 3D assessment of CC morphology. We demonstrated the biomedical relevance of the method by quantifying CC thickness in different anatomical regions with a varying mean thickness. CC was thickest in the patella and thinnest in the tibial plateau. Our method is relatively straightforward to implement into standard µCT analysis pipelines, allowing the analysis of CC morphology. In future research, µCT imaging might be preferable to histology, especially when analyzing dynamic changes in cartilage mineralization. It could also provide further understanding of 3D morphological changes that may occur in mineralized cartilage, such as thickening of the subchondral plate in osteoarthritis and other joint diseases.
An Automated Algorithm for Optic Nerve Sheath Diameter Assessment from B‐mode Ultrasound Images
Authors: Stevens Raoul R. F. , Huberts Wouter , Gommer Erik D. , Ertl Michael , Aries Marcel , Mess Werner H. , Delhaas Tammo
Published: March 2021

BACKGROUND AND PURPOSE

The optic nerve sheath diameter (ONSD) is a promising surrogate marker for the detection of raised intracranial pressure (ICP). However, inconsistencies in manual ONSD assessment are thought to affect ONSD and the corresponding ONSD cutoff values for the diagnosis of elevated ICP, hereby hampering the full potential of ONSD. In this study, we developed an image intensity‐invariant algorithm to automatically estimate ONSD from B‐mode ultrasound images at multiple depths.

METHODS

The outcomes of the algorithm were validated against manual ONSD measurements by two human experts. Each expert analyzed the images twice (M1 and M2) in unknown order.

RESULTS

The algorithm proved capable of segmenting the ONSD in 39 of 42 images, hereby showing mean differences of −.08 ± .45 and −.05 ± .41 mm compared to averaged ONSD values (M1 + M2/2) of Operator 1 and Operator 2, respectively, whereas the mean difference between the two experts was .03 ± .26 mm. Moreover, differences between algorithm‐derived and expert‐derived ONSD values were found to be much smaller than the 1 mm difference that is expected between patients with normal and elevated ICP, making it likely that our algorithm can distinguish between these patient groups.

CONCLUSIONS

Our algorithm has the potential to improve the accuracy of ONSD as a surrogate marker for elevated ICP because it has no intrinsic variability. However, future research should be performed to validate if the algorithm does indeed result in more accurate noninvasive ICP predictions.
What Materials and Reproducible Techniques May Be Used in Recording Centric Relation? Best Evidence Consensus Statement
Authors: Kattadiyil Mathew T. , Alzaid Abdulaziz A. , Campbell Stephen D.
Published: March 2021

Purpose

The purpose of this Best Evidence Consensus Statement was to evaluate the existing literature relative to two focus questions: What are the techniques used and their reproducibility in recording centric relation (CR) in a dentate and partially dentate population and what effect do different recording materials have on the reproducibility of CR?

Materials and Methods

Keywords used in the initial search were: CR, interocclusal records, CR accuracy, CR reproducibility, and CR technique. The search was then limited to Systematic Reviews, Randomized Controlled Studies, Meta‐analyses, and Clinical Trials.

Results

Initial search related to the selected search terms resulted in more than 3500 articles. When subsequent search was limited to Systematic Reviews, Randomized Controlled Studies, and Meta‐Analysis and Clinical Trials, this resulted in 291 articles selected for further analysis.

Conclusions

Techniques using chin point guidance, bimanual manipulation, power centric, Gothic arch tracing, leaf gauge, and anterior deprogramming devices to record CR can all be comparable in precision and clinical accuracy in regards to clinical relevance. Practitioner experience and familiarity with a particular technique is critical for accuracy when recording CR. Polyvinyl siloxane and polyether consistently performed better in the broad range of studies on recording materials. Virtual capture of CR could serve as a comparable recording medium but requires further clinical study.
The Impact of Pessimistic Expectations on the Effects of COVID‐19‐Induced Uncertainty in the Euro Area*
Authors: Pellegrino Giovanni , Ravenna Federico , Züllig Gabriel
Published: March 2021

We estimate a monthly interacted‐VAR model for euro area macroeconomic aggregates allowing for the impact of uncertainty shocks to depend on the state of the average outlook for the economy measured by survey data. We find that, in response to an uncertainty shock, the peak decrease in industrial production and inflation is around three and a half times larger during pessimistic times. We build an assessment of the role of uncertainty for a path of innovations consistent with the increase in the observed VSTOXX measure of uncertainty since the outset of the COVID‐19 epidemics in February and March 2020. Industrial production is predicted to experience a year‐over‐year peak loss of around 9.2% in the fourth quarter of 2020, and subsequently to recover with a rebound to pre‐crisis levels roughly in June 2021. The large impact is the result of an extreme shock to uncertainty occurring at a time of very negative expectations for the economic outlook. We conduct simulations that quantify the potential benefit of recovered confidence in reducing the uncertainty‐induced losses associated with a possible third wave of the pandemic.
Price Competition Under Mixed Multinomial Logit Demand: Sufficiency Conditions for Validating the Model
Authors: Lee Chung‐seung , Çakanyildirim Metin
Published: March 2021

This study is motivated by a fundamental question among researchers: do price data correspond to a pure strategy Nash equilibrium of an estimated econometric model of Bertrand competition? The affirmative answer to this question is essential for validating the estimated model. Despite the extensive empirical applications of Bertrand competition over the last three decades, answering the question remains a daunting task for the researchers. This study takes a step to fill this gap, identifying a set of easy‐to‐verify and easy‐to‐interpret conditions under which, by checking how closely the price data fit the system of first‐order conditions, one can easily obtain an answer to the question.
Certification effect of R&D subsidies on debt financing: do institutional forces matter?
Authors: Wu Ruirui , Liu Zhiying , Chen Xiafei , Liao Suqin
Published: March 2021

This study extends the extant literature on the direct outcome additionality of R&D subsidies by investigating whether R&D subsidies can have an indirect certification effect. Based on the panel data of Chinese listed firms, we argue that in emerging economies, such as China, obtaining R&D subsidies can serve as a quality signal of firms’ R&D projects to banks, thereby allowing firms to attract more bank loans. Specifically, 1% increase in R&D subsidies can increase firms’ access to bank loans by 0.06%. In addition, by using the lens of institutional contingency, we further examine the effect of institutional forces on the signal‐conveying mechanism of R&D subsidies. The results show that firm‐level state ownership weakens the positive signal effect of R&D subsidies, whereas region‐ and industry‐level institutional forces strengthen the positive signal effect. Our study has important implications for policy makers and firms.
Partner technological heterogeneity and innovation performance of R&D alliances
Authors: Zhang Si , Li Jizhen , Li Na
Published: March 2021

This study investigates the impacts of partner technology heterogeneity on innovation performance of alliance firms both in terms of R&D output and the enhancement of partners’ innovation capability. We apply a generalized semi‐parametric model on a questionnaire survey result of 413 High and New Technology Enterprises in China. In order to ensure the robustness and practicability of our result, PCA is applied to extract comprehensive information and SiZer analysis is employed to test the linearity and significance of the nonparametric functions in the model. Our results indicate that collaborations between partners with different industry technologies exert inversed U‐shaped R&D output pattern and affect very little the innovation ability of focal firms. The impact of industry domain divergence is no longer significant when partner technology heterogeneity is added in the model of analysis. Partner technology heterogeneity leads to an ascending S‐shaped R&D output pattern and contributes positively to innovation capabilities. One of the implications of our findings is that when choosing R&D alliance partners, firms are better off avoiding candidates from a different industry domain but opt for potential collaborators who are in the same industry but in the different technical domain, which may facilitate more effective organizational learning. Further, we argue that the reasons behind the S‐shaped R&D output pattern led by technology heterogeneity being the co‐existence of competition and cooperation between partners where firms collaborate in value‐creation by combining diverse resources and compete for acquiring partner’s distinct technology and resources. Therefore, we suggest that, for the sustainability of collaborative innovation outcome, both cooperation and competition amongst alliance partners should be encouraged and well balanced at different stages of joint R&D projects.
Exogenous shocks and the adaptive capacity of family firms: exploring behavioral changes and digital technologies in the COVID‐19 pandemic
Authors: Soluk Jonas , Kammerlander Nadine , De Massis Alfredo
Published: March 2021

The COVID‐19 pandemic has been and is currently still affecting organizations of all sizes and in many industries, and research still lacks profound insights into the managerial implications of this phenomenon. In particular, it is unclear how family firms, which are the economic backbone of most of the countries affected by the pandemic, have adapted to COVID‐19. This paper addresses this gap by drawing on a rich body of evidence collected from 90 interviews and secondary data in a longitudinal case study of four German family firms. We develop a framework for understanding how family firms adapt to exogenous shocks such as the COVID‐19 pandemic and find that the exogenous shock further reinforces the family firm’s resource constraints and the family’s fear of losing their socioemotional wealth. These motivational sources, in turn, trigger behavioral changes in both the firm and the family. In addition to a temporarily induced short‐term orientation, these changes manifest in (pseudo)family cohesion, less rigid mental models, and the utilization of digital technologies. Organizational outcomes such as new alliances, digital platforms, and the adaptive capacity of family firms are the result of these behavioral changes. By providing a comprehensive understanding of how COVID‐19 affects family firms, the insights from our study contribute to innovation research, business practice, and policymaking alike. More broadly, we provide innovation scholars with a theoretical comprehension of how exogenous shocks can challenge our canonical understanding of organizations’ (innovative) behavior.
A Numerical Framework for Geometrically Nonlinear Deformation of Flexoelectric Solids Immersed in an Electrostatic Medium
Authors: Kim Moonhong
Published: March 2021

A numerical formulation coupling finite and boundary element methods is developed to analyze the mechanical deformation and electric polarization of flexoelectric solids experiencing geometrically nonlinear deformation. The proposed method considers the electrical interactions among flexoelectric solids, electric charges, and their surrounding medium. First, a higher-order gradient theory is proposed based on the skew-symmetric couple-stress model to analyze the geometrically nonlinear deformation of flexoelectric solids. This theory includes a total Lagrangian weak form that satisfies linear momentum conservation, angular momentum conservation, and Gauss’s law. Based on the proposed theory, a finite element is developed using basis functions that satisfy C1 continuity. Second, a coupled formulation is developed to consider the electrical interactions among solids, electric charges, and their surrounding medium. In this formulation, conventional boundary elements are adopted to account for the electrostatic surroundings. Besides, electric boundary conditions are naturally imposed on solid boundaries according to the electrical interactions between solids and their electrostatic surroundings. Finally, the proposed method is validated via the comparisons of the numerical results with closed-form solutions.
Analytical Models for Predicting the Nonlinear Stress–Strain Relationships and Behaviors of Two-Dimensional Carbon Materials
Authors: Xiong Zixin , Zhang Teng , Li Xiaoyan
Published: March 2021

Due to having a single atom layer, two-dimensional (2D) materials represented by graphene monolayers exhibit unique and excellent mechanical properties, such as ultrahigh moduli and strengths. A large number of experiments and atomistic simulations have demonstrated nonlinear stress–strain responses. However, there is no theoretical model that analytically describes the relationships between nonlinear mechanical properties and interatomic interaction parameters of 2D materials. Here, we developed a nonlinear stick-spiral model for four typical 2D materials (including graphene, γ-graphyne, β-graphyne, and hexagonal boron nitride) based on a molecular mechanics model. By using the perturbation method, we derived a series of analytical expressions for nonlinear stress–strain relationships and elastic constants of these 2D materials under uniaxial tension along the zigzag and armchair directions. Our analytic models indicated that both Young’s moduli and Poisson’s ratios of these 2D materials are isotropic and dominate the linear elastic deformation, while their third-order moduli are orientation-dependent and essentially characterize the nonlinear stress–strain responses. The nonlinear stress–strain relationships, elastic constants, and atomic behaviors (such as bond elongation and bond angle variation during deformation) predicted from our analytical models are in good agreement with those from atomistic simulations and previous experiments. Our analytical models further demonstrated that the mechanical properties and behaviors of 2D materials are linked with their bonding and atomic structures (from a quantitative perspective) and are mainly determined by stiffnesses for bond stretching, angle variation, and bond lengths. Our current study provides an effective and accurate analytical approach for investigating the nonlinear behaviors of 2D materials.
Failure Strain and Fracture Prediction During Shock Tube Impact Forming of AA 5052-H32 Sheet
Authors: Barik Saibal Kanchan , Ganesh Narayanan R. , Sahoo Niranjan
Published: March 2021

The present study deals with both numerical and experimental evaluation of failure strain and fracture pattern during shock tube impact forming of 1.5 mm thick AA 5052-H32 sheet. A hemispherical end nylon striker is propelled to deform the sheet at different velocities. Here, the main objective is to understand the effect of flow stress models and fracture models on the forming outputs. The experimental situation is modeled in two stages, i.e., incorporating the pressure in the first stage and displacement of the striker in the second stage in finite element simulation using the finite element (FE) code (DEFORM-3D). A new strategy followed to evaluate the rate-dependent flow stress data from the tensile test of samples sectioned from shock tube-based deformed sheet is acceptable, and finite element simulations incorporating these properties predicted accurate failure strain and fracture pattern. Out of all the flow stress models, the modified Johnson–Cook model has a better flow stress predictability due to the inclusion of the non-linear strain rate sensitivity term in the model. During the prediction of the failure strain and necking location, the Cockcroft–Latham failure model, Brozzo failure model, and Freudenthal failure model have a fair agreement with experimental data in combination with the two flow stress models, i.e., Johnson–Cook model and modified Johnson–Cook model.
Influence of Roller-End Axial Profiling Type on Lubrication Performance in Thermal Elastohydrodynamic Finite Line Contacts
Authors: Habchi W.
Published: March 2021

This study presents a finite-element-based numerical investigation of the influence of roller-end axial profiling type on the lubrication performance of thermal elastohydrodynamic finite line contacts. Performance is evaluated with respect to the reference case of straight rollers. The two most commonly used profiling types (i.e., dub-off and logarithmic) are compared under similar profiling length and height. It is found that a logarithmic profile outperforms a dub-off one by all accounts (i.e., frictional dissipation, lubricant film thickness, pressure buildup, and temperature rise), unless an extremely steep logarithmic shape is adopted. In the latter case, lubricant film thickness and pressure buildup may end up being negatively affected.
Bradyrhizobium diazoefficiens Requires Chemical Chaperones To Cope with Osmotic Stress during Soybean Infection
Authors: Ledermann Raphael , Emmenegger Barbara , Couzigou Jean-Malo , Zamboni Nicola , Kiefer Patrick , Vorholt Julia A. , Fischer Hans-Martin
Published: March 2021

The
Bradyrhizobium
-soybean symbiosis is of great agricultural significance and serves as a model system for fundamental research in bacterium-plant interactions. While detailed molecular insight is available about mutual recognition and early nodule organogenesis, our understanding of the host-imposed conditions and the physiology of infecting rhizobia during the transition from a free-living state in the rhizosphere to endosymbiotic bacteroids is currently limited.
Shared Environment and Genetics Shape the Gut Microbiome after Infant Adoption
Authors: Tavalire Hannah F. , Christie Diana M. , Leve Leslie D. , Ting Nelson , Cresko William A. , Bohannan Brendan J. M.
Published: March 2021

Our results demonstrate that the early life home environment can significantly alter the gut microbiome in childhood, potentially altering health outcomes or risk for adverse health outcomes. A better understanding of the drivers of gut microbiome variation during childhood could lead to more effective intervention strategies for overall health starting in early life.
Microbial Community Resilience across Ecosystems and Multiple Disturbances
Authors: Philippot Laurent , Griffiths Bryan S. , Langenheder Silke
Published: March 2021

The ability of ecosystems to withstand disturbances and maintain their functions is being increasingly tested as rates of change intensify due to climate change and other human activities. Microorganisms are crucial players underpinning ecosystem functions, and the recovery of microbial communities from disturbances is therefore a key part of the complex processes determining the fate of ecosystem functioning.
Dynamic Bayesian Networks for Integrating Multi-omics Time Series Microbiome Data
Authors: Ruiz-Perez Daniel , Lugo-Martinez Jose , Bourguignon Natalia , Mathee Kalai , Lerner Betiana , Bar-Joseph Ziv , Narasimhan Giri
Published: March 2021

While a number of large consortia collect and profile several different types of microbiome and genomic time series data, very few methods exist for joint modeling of multi-omics data sets. We developed a new computational pipeline, PALM, which uses dynamic Bayesian networks (DBNs) and is designed to integrate multi-omics data from longitudinal microbiome studies.
Severe urticarial rash as the initial symptom of COVID-19 infection
Authors: Pagali Sandeep , Parikh Riddhi S
Published: March 2021

A 54-year-old woman presented with pruritic rash and hives of 3 days’ duration followed by shortness of breath for 1 day. SARS-CoV-2 PCR test for COVID-19 was positive. Cutaneous manifestations of COVID-19 include acral lesions, urticarial rash, erythematous maculopapular rash, vascular rashes and vesicular rash. The cutaneous manifestations are mostly described as self-limiting. Urticarial rashes are not reported as the initial presentation symptom of COVID-19 infection but mostly noted to occur at the same time or after the onset of non-cutaneous symptoms. Management of cutaneous manifestations of COVID-19 affecting quality of life has not been well studied. Antihistamine therapy is the primary recommended therapy. Role of antiviral therapy for severe cases of rash needs to be further assessed.
Publication by association: how the COVID-19 pandemic has shown relationships between authors and editorial board members in the field of infectious diseases
Authors: Locher Clara , Moher David , Cristea Ioana Alina , Naudet Florian
Published: March 2021

During the COVID-19 pandemic, the rush to scientific and political judgements on the merits of hydroxychloroquine was fuelled by dubious papers which may have been published because the authors were not independent from the practices of the journals in which they appeared. This example leads us to consider a new type of illegitimate publishing entity, ‘self-promotion journals’ which could be deployed to serve the instrumentalisation of productivity-based metrics, with a ripple effect on decisions about promotion, tenure and grant funding, but also on the quality of manuscripts that are disseminated to the medical community and form the foundation of evidence-based medicine.
Serious game versus standard care for rehabilitation after distal radius fractures: a protocol for a multicentre randomised controlled trial
Authors: Meijer Henriëtte A W , Graafland Maurits , Obdeijn Miryam C , van Dieren Susan , Goslings J Carel , Schijven Marlies P
Published: March 2021

Introduction

Distal radius fractures are among the most prevalent traumatic injuries worldwide. These injuries are associated with high healthcare-related and socioeconomic costs, mainly resulting from loss of productivity. To optimise recovery and return to work, wrist exercises are recommended. However, adherence to standard exercise regimens is low. Serious games provide a treatment platform for standardised postoperative care, uniting meaningful recovery with entertainment. Also, mobile serious games, for example, smartphone or tablet applications, are able to send practice reminders believed to improve self-efficacy.

Methods and analysis

To test the effectiveness of a mobile serious game for distal radius fracture rehabilitation compared with standard care, a multicentre, randomised controlled clinical trial was designed. Primary outcome will be the Patient-Rated Wrist Evaluation (PRWE) score after 6 weeks of treatment. Secondary outcomes are range of motion, grip strength, pain scores, and self-reported treatment adherence after 2, 6 and 12 weeks of treatment.

Adult patients with any type of closed distal radius fracture are included directly after non-operative or operative fracture treatment. Patients are recruited in the outpatient clinics of four teaching hospitals. The intended sample size is 92 patients, based on the minimal clinically important difference of the PRWE score at 6 weeks, using a superiority model.

Patients are randomised between using the wearable-controlled mobile serious gameReValidate!(intervention group) and standard care consisting of unsupervised exercises and a referral for physiotherapy or exercise therapy upon request or recommendation by the treating clinician (control group).

Ethics and dissemination

The protocol has been approved by the Medical Ethical Review Board of the Amsterdam University Medical Centres, location Academic Medical Centre in Amsterdam, the Netherlands. Results will be made available to involved healthcare providers, funders, and to the general public including patients via peer-reviewed academic journals and international conferences.

Trial registration number

Dutch Trial Registry (NTR), NL6140, protocol V.2.
First-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy (oxaliplatin) for isolated unresectable colorectal peritoneal metastases: protocol of a multicentre, single-arm, phase II study (CRC-PIPAC-II)
Authors: Lurvink Robin J. , Rauwerdink Paulien , Rovers Koen P. , Wassenaar Emma C.E. , Deenen Maarten J. , Nederend Joost , Huysentruyt Clément J.R. , van "t Erve Iris , Fijneman Remond J.A. , van der Hoeven Erik J.R.J. , Seldenrijk Cornelis A. , Constantinides Alexander , Kranenburg Onno , Los Maartje , Herbschleb Karin H. , Thijs Anna M.J. , Creemers Geert-Jan M. , Burger Jacobus W.A. , Wiezer Marinus J. , Nienhuijs Simon W. , Boerma Djamila , de Hingh Ignace H.J.T.
Published: March 2021

Introduction

Despite its increasing use, first-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX), hereinafter referred to as first-line bidirectional therapy, has never been prospectively investigated in patients with colorectal peritoneal metastases (CPM). As a first step to address this evidence gap, the present study aims to assess the safety, feasibility, antitumour activity, patient-reported outcomes, costs and systemic pharmacokinetics of first-line bidirectional therapy in patients with isolated unresectable CPM.

Methods and analysis

In this single-arm, phase II study in two Dutch tertiary referral centres, 20 patients are enrolled. Key eligibility criteria are a good performance status, pathologically proven isolated unresectable CPM, no previous palliative systemic therapy for colorectal cancer, no (neo)adjuvant systemic therapy ≤6 months prior to enrolment and no previous pressurised intraperitoneal aerosol chemotherapy (PIPAC). Patients receive three cycles of bidirectional therapy. Each cycle consists of 6 weeks first-line palliative systemic therapy at the medical oncologists’ decision (CAPOX-bevacizumab, FOLFOX-bevacizumab, FOLFIRI-bevacizumab or FOLFOXIRI-bevacizumab) followed by ePIPAC-OX (92 mg/m2) with an intraoperative bolus of intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Study treatment ends after the third ePIPAC-OX. The primary outcome is the number of patients with—and procedures leading to—grade ≥3 adverse events (Common Terminology Criteria for Adverse Events V.5.0) up to 4 weeks after the last procedure. Key secondary outcomes include the number of bidirectional cycles in each patient, treatment-related characteristics, grade ≤2 adverse events, tumour response (histopathological, cytological, radiological, biochemical, macroscopic and ascites), patient-reported outcomes, systemic pharmacokinetics of oxaliplatin, costs, progression-free survival and overall survival.

Ethics and dissemination

This study is approved by the Dutch competent authority, a medical ethics committee and the institutional review boards of both study centres. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals.

Trial registration number

NL8303.
Impact of the COVID-19 pandemic on remote mental healthcare and prescribing in psychiatry: an electronic health record study
Authors: Patel Rashmi , Irving Jessica , Brinn Aimee , Broadbent Matthew , Shetty Hitesh , Pritchard Megan , Downs Johnny , Stewart Robert , Harland Robert , McGuire Philip
Published: March 2021

Objectives

The recent COVID-19 pandemic has disrupted mental healthcare delivery, with many services shifting from in-person to remote patient contact. We investigated the impact of the pandemic on the use of remote consultation and on the prescribing of psychiatric medications.

Design and setting

The Clinical Record Interactive Search tool was used to examine deidentified electronic health records of people receiving mental healthcare from the South London and Maudsley (SLaM) NHS Foundation Trust. Data from the period before and after the onset of the pandemic were analysed using linear regression, and visualised using locally estimated scatterplot smoothing.

Participants

All patients receiving care from SLaM between 7 January 2019 and 20 September 2020 (around 37 500 patients per week).

Outcome measures

(i) The number of clinical contacts (in-person, remote or non-attended) with mental healthcare professionals per week.

(ii) Prescribing of antipsychotic and mood stabiliser medications per week.

Results

Following the onset of the pandemic, the frequency of in-person contacts was significantly reduced compared with that in the previous year (β coefficient: −5829.6 contacts, 95% CI −6919.5 to −4739.6, p<0.001), while the frequency of remote contacts significantly increased (β coefficient: 3338.5 contacts, 95% CI 3074.4 to 3602.7, p<0.001). Rates of remote consultation were lower in older adults than in working age adults, children and adolescents. Despite this change in the type of patient contact, antipsychotic and mood stabiliser prescribing remained at similar levels.

Conclusions

The COVID-19 pandemic has been associated with a marked increase in remote consultation, particularly among younger patients. However, there was no evidence that this has led to changes in psychiatric prescribing. Nevertheless, further work is needed to ensure that older patients are able to access mental healthcare remotely.
Disease burden and quality of life of patients with chronic cough in Japan: a population-based cross-sectional survey
Authors: Kubo Takekazu , Tobe Keisuke , Okuyama Kotoba , Kikuchi Masashi , Chen Yirong , Schelfhout Jonathan , Abe Machiko , Tokita Shigeru
Published: March 2021

Background

Cough lasting 3–8 and >8 weeks are defined as subacute/prolonged cough and chronic cough (CC), respectively. Studies have revealed that CC negatively impact patients’ quality of life (QoL). In Japan, there is limited data on the impact of CC on health-related quality of life (HRQoL), work productivity and activity impairment (WPAI) and healthcare resource utilisation (HRU) using validated instruments. This study aimed to estimate the burden of CC and to compare the burden among patients with CC between subgroups.

Methods

Data from two cross-sectional online surveys conducted between September and November 2019 were combined for the analysis. Eligible patients with cough were propensity score matched to non-cough respondents. Comparisons of general HRQoL, WPAI, HRU and other symptoms experienced were conducted between matched non-cough respondents and patients with cough. Among patients with CC, subgroup comparisons were performed to understand general HRQoL, WPAI, HRU, cough-related QoL (Leicester Cough Questionnaire and Hull Airway Reflux Questionnaire) between patients with CC of different severities, patients with refractory CC and patients with non-refractory CC and patients with CC whose underlying diseases were unknown and others.

Results

Patients with CC (n=568) in Japan reported significantly poorer HRQoL, increased WPAI, more HRU and higher proportion of psychological and sleep problems, compared with matched non-cough respondents selected from 21 415 non-cough respondents. More patients with severe CC reported significantly poorer HRQoL, increased WPAI and worse cough-related QoL. Patients with refractory CC experienced significantly greater burden measured by cough-related QoL. No significant differences were observed between patients with CC whose underlying diseases were unknown and other patients with CC in terms of general HRQoL and cough-related QoL.

Conclusions

This study showed that patients with CC in Japan experienced significant burden compared with non-cough respondents. Patients with more severe cough and refractory CC experienced worse cough-related QoL. These results highlighted the unmet need for better interventions and treatments to reduce the burden among patients with CC.
Talimogene laherparepvec upregulates immune-cell populations in non-injected lesions: findings from a phase II, multicenter, open-label study in patients with stage IIIB–IVM1c melanoma
Authors: Malvehy Josep , Samoylenko Igor , Schadendorf Dirk , Gutzmer Ralf , Grob Jean-Jacques , Sacco Joseph J , Gorski Kevin S , Anderson Abraham , Pickett Cheryl A , Liu Kate , Gogas Helen
Published: March 2021

Background

Talimogene laherparepvec (T-VEC), an oncolytic virus, was designed to selectively replicate in and lyse tumor cells, releasing tumor-derived antigen to stimulate a tumor-specific immune response.

Methods

In this phase II study in patients with unresectable stage IIIB–IV melanoma, we evaluated non-injected lesions to establish whether baseline or change in intratumoral CD8+ T-cell density (determined using immunohistochemistry) correlated with T-VEC clinical response.

Results

Of 112 enrolled patients, 111 received ≥1 dose of T-VEC. After a median follow-up of 108.0 weeks, objective/complete response rates were 28%/14% in the overall population and 32%/18% in patients with stage IIIB–IVM1a disease. No unexpected toxicity occurred. Baseline and week 6 change from baseline CD8+ T-cell density results were available for 91 and 65 patients, respectively. Neither baseline nor change in CD8+ T-cell density correlated with objective response rate, changes in tumor burden, duration of response or durable response rate. However, a 2.4-fold median increase in CD8+ T-cell density in non-injected lesions from baseline to week 6 was observed. In exploratory analyses, multiparameter immunofluorescence showed that after treatment there was an increase in the proportion of infiltrating CD8+ T-cells expressing granzyme B and checkpoint markers (programmed death-1, programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen-4) in non-injected lesions, together with an increase in helper T-cells. Consistent with T-cell infiltrate, we observed an increase in the adaptive resistance marker PD-L1 in non-injected lesions.

Conclusions

This study indicates that T-VEC induces systemic immune activity and alters the tumor microenvironment in a way that will likely enhance the effects of other immunotherapy agents in combination therapy.

Trial registration number

NCT02366195.