bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of different catalysts on recovery and reuse of waste polyurethane rigid foam
Authors: Gu Xiaohua , Lyu Shiwei , Cheng Weidong , Liu Siwen
Published: March 2021

The sharp increase of waste polyurethane rigid foam has caused great harm to the natural environment. Ethylene glycol (EG) and propylene glycol (PG) was the alcoholysis agents, and KOH and Zn3[Co(CN)6]2(DMC) were used as catalysts for alcoholysis of waste polyurethane rigid foam. Regenerated polyols were prepared. The effects of different catalysts on the infrared, viscosity and hydroxyl content of alcoholysis products were discussed. Regenerated polyurethane rigid foam was prepared from alcoholysis products and analyzed by compression strength, thermal conductivity, water absorption, scanning and thermogravimetry. The effects of different catalysts on the recycling of waste polyurethane rigid foam were studied. The experimental results show that DMC catalyst is more effective than KOH catalyst under the same conditions.The alcoholysis product of DMC system has lower viscosity and higher hydroxyl content, which is more suitable for the preparation of regenerated polyurethane rigid foam., The compressive strength of the prepared regenerated polyurethane rigid foam is 254 Kpa, and the thermal conductivity is 0.0213 W m−1·K−1 when the amount of DMC added is 0.04%. Meanwhile, the regenerated polyurethane rigid foam has good hydrophobicity, excellent heat preservation performance, complete cell morphology and good thermal stability. It can replace the traditional polyols to prepare the regenerated polyurethane material which meets the national standard ‘rigid polyurethane foam for building insulation’ (GB/ T21558-2005).
Modelling of electronegative collisional warm plasma for plasma-surface interaction process
Authors: DHAWAN Rajat , MALIK Hitendra K
Published: March 2021

An electronegative collisional plasma having warm and massive positive ions, non-extensive distributed electrons and Boltzmann distributed negative ions is modelled for the plasma-surface interaction process that is used for the surface nitriding. Specifically the sheath formation is evaluated through the Bohm’s criterion, which is found to be modified, and the variation of the sheath thickness and profiles of the density of plasma species and the net space charge density in the sheath region in addition to the electric potential. The effect of ion temperature, non-extensivity and collisional parameter is examined in greater detail considering the collisional cross-section to obey power-law dependency on the positive ion velocity. The positive ions are found to enter in the sheath region at lower velocities in the collisional plasma compared to the case of collision-less plasma; this velocity sees minuscule reduction with increasing non-extensivity. The increasing ion temperature and collisional parameter lead to the formation of sheath with smaller thickness.
multiTFA: a Python package for multi-variate thermodynamics-based flux analysis
Authors: Mahamkali Vishnuvardhan , McCubbin Tim , Beber Moritz Emanuel , Noor Elad , Marcellin Esteban , Nielsen Lars Keld
Published: March 2021

Motivation

We achieve a significant improvement in thermodynamic-based flux analysis (TFA) by introducing multivariate treatment of thermodynamic variables and leveraging component contribution, the state-of-the-art implementation of the group contribution methodology. Overall, the method greatly reduces the uncertainty of thermodynamic variables.

Results

We present multiTFA, a Python implementation of our framework. We evaluated our application using the core Escherichia coli model and achieved a median reduction of 6.8 kJ/mol in reaction Gibbs free energy ranges, while three out of 12 reactions in glycolysis changed from reversible to irreversible.

Availability and implementation

Our framework along with documentation is available on https://github.com/biosustain/multitfa.

Supplementary information

Supplementary data are available at Bioinformatics online.
The tryptophan pathway and nicotinamide supplementation in ischaemic acute kidney injury
Authors: Piedrafita Alexis , Balayssac Stéphane , Mayeur Nicolas , Gazut Stéphane , Grossac Julia , Buleon Marie , Alves Melinda , Klein Julie , Minville Vincent , Marcheix Bertrand , Schanstra Joost P , Faguer Stanislas
Published: March 2021

Background

Down-regulation of the enzymes involved in tryptophan-derived nicotinamide (NAM) adenine dinucleotide (NAD+) production was identified after acute kidney injury (AKI), leading to the hypothesis that supplementation with NAM may increase the kidney NAD+ content, rescuing tryptophan pathways and subsequently improving kidney outcomes.

Methods

Urinary measurement of tryptophan and kynurenin using liquid chromatography–mass spectrometry metabolomics was used in a cohort of 167 cardiac bypass surgery patients along with tests for correlation to the development of postoperative AKI. A mouse model of ischaemic AKI using ischaemia–reperfusion injury (bilateral clamping of renal arteries for 25 min) was also used.

Results

We identified a significant decrease in urinary tryptophan and kynurenin in patients developing AKI, irrespective of the Kidney Disease: Improving Global Outcomes (KDIGO) stage. Although a significant difference was observed, tryptophan and kynurenin moderately discriminated for the development of all AKI KDIGO stages {area under the curve [AUC] 0.82 [95% confidence interval (CI) 0.75–0.88] and 0.75 [0.68–0.83], respectively} and severe KDIGO Stages 2–3 AKI [AUC 0.71 (95% CI 0.6–0.81) and 0.66 (0.55–0.77), respectively]. Sparked by this confirmation in humans, we aimed to confirm the potential preventive effect of NAM supplementation in wild-type male and female C57BL/6 mice subjected to ischaemic AKI. NAM supplementation had no effect on renal function (blood urea nitrogen at Day 1, sinistrin–fluorescein isothiocyanate glomerular filtration rate), architecture (periodic acid–Schiff staining) and injury or inflammation (kidney injury molecule 1 and IL18 messenger RNA expression). In addition, NAM supplementation did not increase post-AKI NAD+ kidney content.

Conclusion

Notwithstanding the potential role of NAM supplementation in the setting of basal NAD+ deficiency, our findings in mice and the reanalysis of published data do not confirm that NAM supplementation can actually improve renal outcomes after ischaemic AKI in unselected animals and probably patients.
Dominant monoallelic variant in the PAK2 gene causes Knobloch syndrome type 2
Authors: Antonarakis Stylianos E , Holoubek Aleš , Rapti Melivoia , Rademaker Jesse , Meylan Jenny , Iwaszkiewicz Justyna , Zoete Vincent , Wilson Callum , Taylor Juliet , Ansar Muhammad , Borel Christelle , Menzel Olivier , Kuželová Kateřina , Santoni Federico A
Published: March 2021

Knobloch syndrome is an autosomal recessive phenotype mainly characterized by retinal detachment and encephalocele caused by biallelic pathogenic variants in the COL18A1 gene. However, there are patients clinically diagnosed as Knobloch syndrome with unknown molecular etiology not linked to COL18A1. We studied an historical pedigree (published in 1998) designated as KNO2 (Knobloch type 2 syndrome with intellectual disability, autistic behavior, retinal degeneration, encephalocele). Whole exome sequencing of the two affected siblings and the normal parents resulted in the identification of a PAK2 non-synonymous substitution p.(Glu435Lys) as a causative variant. The variant was monoallelic and apparently de novo in both siblings indicating a likely germ-line mosaicism in one of the parents; the mosaicism, however, could not be observed after deep sequencing of blood parental DNA. PAK2 encodes a member of a small group of serine/threonine kinases; these P21-activating kinases (PAKs) are essential in signal transduction and cellular regulation (cytoskeletal dynamics, cell motility, death and survival signaling and cell cycle progression). Structural analysis of the PAK2 p.(Glu435Lys) variant that is located in the kinase domain of the protein predicts a possible compromise in the kinase activity. Functional analysis of the p.(Glu435Lys) PAK2 variant in transfected HEK293T cells results in a partial loss of the kinase activity. PAK2 has been previously suggested as an autism-related gene. Our results show that PAK2-induced phenotypic spectrum is broad and not fully understood. We conclude that the KNO2 syndrome in the studied family is dominant and caused by a deleterious variant in the PAK2 gene.
Tracing the Source of Influenza A Virus Zoonoses in Interconnected Circuits of Swine Exhibitions
Authors: McBride Dillon S , Perofsky Amanda C , Nolting Jacqueline M , Nelson Martha I , Bowman Andrew S
Published: March 2021

Background

Since 2011, influenza A viruses circulating in US swine exhibited at county fairs are associated with >460 zoonotic infections, presenting an ongoing pandemic risk. Swine “jackpot shows” that occur before county fairs each summer intermix large numbers of exhibition swine from diverse geographic locations. We investigated the role of jackpot shows in influenza zoonoses.

Methods

We collected snout wipe or nasal swab samples from 17 009 pigs attending 350 national, state, and local swine exhibitions across 8 states during 2016–2018.

Results

Influenza was detected in 13.9% of swine sampled at jackpot shows, and 76.3% of jackpot shows had at least 1 pig test positive. Jackpot shows had 4.3-fold higher odds of detecting at least 1 influenza-positive pig compared to county fairs. When influenza was detected at a county fair, almost half of pigs tested positive, clarifying why zoonotic infections occur primarily at county fairs.

Conclusions

The earlier timing of jackpot shows and long-distance travel for repeated showing of individual pigs provide a pathway for the introduction of influenza into county fairs. Mitigation strategies aimed at curtailing influenza at jackpot shows are likely to have downstream effects on disease transmission at county fairs and zoonoses.
French Abstracts for Volume 32, Issue 9, 2020
Authors: Anthony Staines , Estelle Lécureux , Pascal Rubin , Christian Baralon , Alexandre Farin
Published: March 2021

Objectif: évaluer l’impact de la mise en œuvre du concept d’amélioration du travail en équipe TeamSTEPPS sur la culture de sécurité des patients.

Plan: évaluation de la culture avant/après à l’aide du questionnaire hospitalier sur la culture de sécurité des patients, avant et un an après la mise en œuvre de TeamSTEPPS.

Contexte: deux services de maternité dans un même hôpital universitaire de 480 lits.

Intervention: mise en œuvre du concept d’amélioration du travail en équipe TeamSTEPPS.

Mesures principales: analyse de la variation du pourcentage de réponses positives (score) dans les deux services (intervention et contrôle).

Résultats: nous avons observé une augmentation significative des scores pour trois dimensions de la culture de sécurité des patients dans le service avec intervention: le score pour Attentes du superviseur/manager et Actions promouvant la sécurité a augmenté de 48,7% en 2015 à 70,8% en 2016 (P < 0,005); le score Travail d’équipe au sein des unités a augmenté de 35,5% en 2015 à 54,5% en 2016 (P < 0,005); le score Réponse non punitive aux erreurs a augmenté de 16,7% en 2015 à 32,3% en 2016 (P < 0,005). Les autres dimensions n’ont connu aucune modification significative. Dans le service témoin, une diminution significative des scores a été observée pour une dimension. Une analyse secondaire des différences continue à montrer une amélioration significative d’une dimension (Attentes du superviseur/manager et Actions de promotion de la sécurité, P < 0,005).

Conclusion: Après la mise en place du concept de travail en équipe TeamSTEPPS, la culture de sécurité des patients a été significativement améliorée dans trois des douze dimensions dans le groupe intervention. Après contrôle des différences dans les scores initiaux entre les services mise en œuvre et témoin, une amélioration significative persiste pour une dimension. Ceci semble indiquer que l’utilisation de TeamSTEPPS pourrait être envisagée dans le cadre d’une recherche d’amélioration de la culture de sécurité des patients, en particulier dans les environnements à haut risque comme les services de maternité.
Prevalence of RND efflux pump regulator variants associated with tigecycline resistance in carbapenem-resistant Acinetobacter baumannii from a worldwide survey
Authors: Lucaßen Kai , Müller Carina , Wille Julia , Xanthopoulou Kyriaki , Hackel Meredith , Seifert Harald , Higgins Paul G
Published: March 2021

Objectives

To determine the most common tigecycline resistance mechanisms in carbapenem-resistant Acinetobacter baumannii isolates obtained during the global Tigecycline Evaluation Surveillance Trial (TEST).

Methods

Tigecycline MICs were determined by broth microdilution. WGS was used to screen for the previously identified tigecycline resistance mechanisms, as well as mutations in resistance-nodulation-cell division (RND)-type efflux pump regulators.

Results

From a total 313 isolates, 113 genetically unique tigecycline-resistant isolates were analysed. The most frequent and worldwide distributed mechanism associated with tigecycline resistance was disruption of adeN, which encodes the repressor of the RND efflux pump AdeIJK, either by IS elements or nucleotide deletions causing premature stop codons. However, mutations leading to amino acid substitutions and disruption by IS elements within the two-component regulatory system adeRS, which regulates expression of the AdeABC efflux pump, correlate with higher tigecycline MICs, but these were found less frequently and were mainly restricted to Southern European countries. Furthermore, an altered version of tviB was identified in several tigecycline-resistant isolates that did not have putative resistance mutations within RND-type regulators. The resistance determinants tet(A) and tet(X), as well as resistance mutations in putative resistance determinants trm, plsC, rrf, msbA and genes encoding 30S ribosomal proteins, were not identified in any isolate.

Conclusions

The most prevalent tigecycline resistance mechanisms were caused by alterations in the regulators of RND-type efflux pumps. These data provide the basis for further characterization of regulator alterations and their contribution to increased efflux and tigecycline resistance, and also should be taken into account in drug discovery programmes to overcome the contribution of efflux pumps.
Determinants of the Implementation of Telemedicine in the German Navy—A Mixed Methods Study
Authors: Hötker Ensign Daniel Valentin , Ring Markus Matthias , Steinhäuser Jost
Published: March 2021

Introduction

The history of the use of telemedicine in maritime medicine dates back to the 1930s. In the early 2000s, the German Navy built up a telemedicine network which today is installed in all ships and provides a connection to the medical infrastructure ashore. The objective of this study was to optimize the implementation of telemedicine based on the experience gained in the German Navy. For this purpose, qualitative and quantitative methods were used to identify determinants which affect the use of telemedicine in order to determine whether there is any need for optimization.

Methods

The study was conducted using a mixed methods design. First, guideline-based interviews were conducted with Navy medical officers who had been recruited via various email distribution lists. The interviews were then transcribed and coded. In an analysis, deductive and inductive categories were derived from the codes. Hypotheses were deduced from the interviews, too, and used to develop a questionnaire.

Besides the medical officers, other Navy medical personnel with experience in the field of telemedicine took part in the survey. The study was concluded by a descriptive analysis of the quantitative data.

Results

The analysis of the interviews revealed that a regular use of telemedicine workstations increased the users’ confidence and, in their opinion, improved medical treatment. Technical and organizational problems posed obstacles, which increased the use of partly insecure alternatives. A proper technical support was regarded as a precondition for effectively using telemedicine.

The results of the quantitative analysis showed that consultation was mainly sought for dermatological (46%), surgical (24%), and internal (22%) conditions.

Conclusion

The study revealed determinants for the use of telemedicine in the German Navy. Factors improving the motivation of the users should be strengthened in order to optimize the use of telemedicine. Furthermore, it can be assumed that a successful implementation will be supported by reducing or eliminating obstacles. The findings on the main reasons for seeking medical advice could be taken into account in the further planning of specific training.
Carbon dust in the evolved born-again planetary nebulae A 30 and A 78
Authors: Toalá J A , Jiménez-Hernández P , Rodríguez-González J B , Estrada-Dorado S , Guerrero M A , Gómez-González V M A , Ramos-Larios G , García-Hernández D A , Todt H
Published: March 2021

We present an infrared (IR) characterization of the born-again planetary nebulae (PNe) A 30 and A 78 using IR images and spectra. We demonstrate that the carbon-rich dust in A 30 and A 78 is spatially coincident with the H-poor ejecta and coexists with hot X-ray-emitting gas up to distances of 50 arcsec from the central stars of PNe (CSPNe). Dust forms immediately after the born-again event and survives for 1000 yr in the harsh environment around the CSPN as it is destroyed and pushed away by radiation pressure and dragged by hydrodynamical effects. Spitzer IRS spectral maps showed that the broad spectral features at 6.4 and 8.0 μm, attributed to amorphous carbon formed in H-deficient environments, are associated with the disrupted disc around their CSPN, providing an optimal environment for charge exchange reactions with the stellar wind that produces the soft X-ray emission of these sources. Nebular and dust properties are modelled for A 30 with cloudy taking into account different carbonaceous dust species. Our models predict dust temperatures in the 40–230 K range, five times lower than predicted by previous works. Gas and dust masses for the born-again ejecta in A 30 are estimated to be $M_\mathrm{gas}=4.41^{+0.55}_{-0.14}\times 10^{-3}$ M⊙ and $M_\mathrm{dust}=3.20^{+3.21}_{-2.06}\times 10^{-3}$ M⊙, which can be used to estimate a total ejected mass and mass-loss rate for the born-again event of $7.61^{+3.76}_{-2.20}\times 10^{-3}$ M⊙ and $\dot{M}=(5{\!-\!}60)\times 10^{-5}$ M⊙ yr−1, respectively. Taking into account the carbon trapped into dust grains, we estimate that the C/O mass ratio of the H-poor ejecta of A 30 is larger than 1, which favours the very late thermal pulse model over the alternate hypothesis of a nova-like event.
Astraeus I: the interplay between galaxy formation and reionization
Authors: Hutter Anne , Dayal Pratika , Yepes Gustavo , Gottlöber Stefan , Legrand Laurent , Ucci Graziano
Published: March 2021

We introduce a new self-consistent model of galaxy evolution and reionization, astraeus (seminumerical rAdiative tranSfer coupling of galaxy formaTion and Reionization in N-body dArk mattEr simUlationS), which couples a state-of-the-art N-body simulation with the semi-analytical galaxy evolution delphi and the seminumerical reionization scheme cifog. astraeus includes all the key processes of galaxy formation and evolution (including accretion, mergers, supernova, and radiative feedback) and follows the time and spatial evolution of the ionized regions in the intergalactic medium (IGM). Importantly, it explores different radiative feedback models that cover the physically plausible parameter space, ranging from a weak and delayed to a strong and immediate reduction of gas mass available for star formation. From our simulation suite that covers the different radiative feedback prescriptions and ionization topologies, we find that radiative feedback continuously reduces star formation in galaxies with $M_\mathrm{ h}\lesssim 10^{9.5}\, {\rm \rm M_\odot }$ upon local reionization; larger mass haloes are unaffected even for the strongest and immediate radiative feedback cases during reionization. For this reason, the ionization topologies of different radiative feedback scenarios differ only on scales smaller than 1–2 comoving Mpc, and significant deviations are found only when physical parameters (e.g. the escape fraction of ionizing photons) are altered based on galactic properties. Finally, we find that observables (the ultraviolet luminosity function, stellar mass function, reionization histories and ionization topologies) are hardly affected by the choice of the used stellar population synthesis models that model either single stars or binaries.
Collisions between micro-sized aggregates: role of porosity, mass ratio, and impact velocity
Authors: Planes María Belén , Millán Emmanuel N , Urbassek Herbert M , Bringa Eduardo M
Published: March 2021

Dust aggregate collisions usually occur between mass-asymmetric collision partners. Granular-mechanics simulations are used to study the influence of filling factor, φ, and impact velocity in collisions of spherical granular aggregates with different values of their mass ratio, but the same filling factor. Three possible outcomes are observed: (i) sticking, which might include penetration of the smaller aggregate into the larger aggregate; (ii) fragmentation of the largest aggregate into two large fragments, particularly due to the so-called piston effect for low filling factors; and (iii) total destruction of the aggregates. Most of the impact energy is spent by friction, with some fraction leading to compaction of the porous material. The erosion efficiency varies significantly with impact velocity, mass ratio, and porosity, but the accretion efficiency does not show such strong variations. For highly asymmetric collisions with high impact velocities (≃100 m s−1), grain accretion (growth) can occur for a ‘window’ in the filling factor (0.20 < φ < 0.35). This window becomes wider as the impact velocity decreases. As the mass ratio of the aggregates decreases, the impact velocities that enable growth can also decrease. The mass distribution of the fragments follows a power-law distribution that is almost independent of the mass ratio, filling factor, and velocity.
Reputation Concerns and Slow-Moving Capital
Authors: Malliaris Steven , Yan Hongjun
Published: March 2021

We analyze fund managers’ reputation concerns in an equilibrium model, in which we tie together a number of seemingly unrelated phenomena. The model shows that because of reputation concerns, hedge fund managers, especially those with an average reputation, prefer strategies with negatively skewed return distributions. One subtle consequence of this preference is that capital sometimes appears slow moving, leaving profitable investment opportunities unexploited, yet other times appears fast moving, causing large capital relocation and price fluctuations in the absence of fundamental news. More broadly, the analysis demonstrates a limitation of market discipline: fund managers may distort their investments precisely because of market discipline.
On anomalous localized resonance and plasmonic cloaking beyond the quasi-static limit
Authors: Li Hongjie , Liu Hongyu
Published: March 2021

In this paper, we give the mathematical construction of novel core-shell
plasmonic structures that can induce anomalous localized resonance and
invisibility cloaking at certain finite frequencies beyond the quasi-static
limit. The crucial ingredient in our study is that the plasmon constant and the
loss parameter are constructed in a delicate way that are correlated and depend
on the source and the size of the plasmonic structure. As a significant
by-product of this study, we also derive the complete spectrum of the
Neumann–Poincáre operator associated with the Helmholtz equation with finite
frequencies in the radial geometry. The spectral result is the first one in its
type and is of significant mathematical interest for its own sake.
Towards advancing scientific knowledge of climate change impacts on short-duration rainfall extremes
Authors: Fowler Hayley J. , Ali Haider , Allan Richard P. , Ban Nikolina , Barbero Renaud , Berg Peter , Blenkinsop Stephen , Cabi Nalan Senol , Chan Steven , Dale Murray , Dunn Robert J. H. , Ekström Marie , Evans Jason P. , Fosser Giorgia , Golding Brian , Guerreiro Selma B. , Hegerl Gabriele C. , Kahraman Abdullah , Kendon Elizabeth J. , Lenderink Geert , Lewis Elizabeth , Li Xiaofeng , O'Gorman Paul A. , Orr Harriet G. , Peat Katy L. , Prein Andreas F. , Pritchard David , Schär Christoph , Sharma Ashish , Stott Peter A. , Villalobos-Herrera Roberto , Villarini Gabriele , Wasko Conrad , Wehner Michael F. , Westra Seth , Whitford Anna
Published: March 2021

A large number of recent studies have aimed at understanding short-duration rainfall extremes, due to their impacts on flash floods, landslides and debris flows and potential for these to worsen with global warming. This has been led in a concerted international effort by the INTENSE Crosscutting Project of the GEWEX (Global Energy and Water Exchanges) Hydroclimatology Panel. Here, we summarize the main findings so far and suggest future directions for research, including: the benefits of convection-permitting climate modelling; towards understanding mechanisms of change; the usefulness of temperature-scaling relations; towards detecting and attributing extreme rainfall change; and the need for international coordination and collaboration. Evidence suggests that the intensity of long-duration (1 day+) heavy precipitation increases with climate warming close to the Clausius–Clapeyron (CC) rate (6–7% K
−1
), although large-scale circulation changes affect this response regionally. However, rare events can scale at higher rates, and localized heavy short-duration (hourly and sub-hourly) intensities can respond more strongly (e.g. 2 × CC instead of CC). Day-to-day scaling of short-duration intensities supports a higher scaling, with mechanisms proposed for this related to local-scale dynamics of convective storms, but its relevance to climate change is not clear. Uncertainty in changes to precipitation extremes remains and is influenced by many factors, including large-scale circulation, convective storm dynamics andstratification. Despite this, recent research has increased confidence in both the detectability and understanding of changes in various aspects of intense short-duration rainfall. To make further progress, the international coordination of datasets, model experiments and evaluations will be required, with consistent and standardized comparison methods and metrics, and recommendations are made for these frameworks.

This article is part of a discussion meeting issue ‘Intensification of short-duration rainfall extremes and implications for flash flood risks’.
Response of extreme precipitation to uniform surface warming in quasi-global aquaplanet simulations at high resolution
Authors: O’Gorman P. A. , Li Z. , Boos W. R. , Yuval J.
Published: March 2021

Projections of precipitation extremes in simulations with global climate models are very uncertain in the tropics, in part because of the use of parameterizations of deep convection and model deficiencies in simulating convective organization. Here, we analyse precipitation extremes in high-resolution simulations that are run without a convective parameterization on a quasi-global aquaplanet. The frequency distributions of precipitation rates and precipitation cluster sizes in the tropics of a control simulation are similar to the observed distributions. In response to climate warming, 3 h precipitation extremes increase at rates of up to

9
%
 

K

−
1

in the tropics because of a combination of positive thermodynamic and dynamic contributions. The dynamic contribution at different latitudes is connected to the vertical structure of warming using a moist static stability. When the precipitation rates are first averaged to a daily timescale and coarse-grained to a typical global climate-model resolution prior to calculating the precipitation extremes, the response of the precipitation extremes to warming becomes more similar to what was found previously in coarse-resolution aquaplanet studies. However, the simulations studied here do not exhibit the high rates of increase of tropical precipitation extremes found in projections with some global climate models.

This article is part of a discussion meeting issue ‘Intensification of short-duration rainfall extremes and implications for flash flood risks’.
COVID-19 Vaccine hesitancy in Addis Ababa, Ethiopia: A mixed-methods study
Authors: Dereje Nebiyu , Tesfaye Abigel , Tamene Beamlak , Alemeshet Dina , Abe Haymanot , Tesfa Nathnael , Gedion Saron , Biruk Tigist , Lakew Yabets
Published: March 2021

Background

COVID-19 infection is a global pandemic threatening the public health. Due to the development and initiation of vaccination, currently significant difference upon vaccine acceptance is seen between developed and developing countries. However, there are no data on the level of COVID-19 vaccine hesitancy and its associated factors in Addis Ababa, Ethiopia.

Methods

An embedded mixed method study [QUAN(quali)] was conducted among residents of Akaki Kality sub-city in Addis Ababa, Ethiopia. For the quantitative part, a multi-stage sampling technique was used to recruit the study participants (n = 422). Twenty four adults were included purposively for the qualitative in-depth interview. Data was collected by face-to-face interview by using a semi-structured questionnaire. Factors associated with COVID-19 vaccine hesitancy were identified by multivariable binary logistic regression model.

Result

The mean age of the participants was 34.1 years (±12.9). Nearly half (46.7%) of the participants exhibited poor level of knowledge and 51.8% had negative attitude towards COVID-19 and its preventive measures. One out five (19.1%) participants were not willing to get vaccinated when it becomes available. In the multivariable analysis, vaccine hesitancy was significantly associated with being female (aOR=1.97; 95% CI: 1.10 - 3.89, p=0.03), negative attitude towards COVID-19 and its preventive measures (aOR=1.75; 95% CI: 1.08 - 3.02, p=0.04), and information source being social media (internet) (aOR=3.59; 95% CI: 1.75 - 7.37, P <0.0001).

Conclusion

A considerable proportion of the people in Addis Ababa have concerns on COVID-19 vaccine and unwilling to accept once it is available. Several conspiracy theories were put forth to justify their stance and this was mainly due to the misconceptions distributed from the use of social media as source of information. Overall, providing the community with health education and consistent government efforts in uphold the prevention measures are of paramount importance to tackle this pandemic.
A Statistical Framework to Identify Cell Types Whose Genetically Regulated Proportions are Associated with Complex Diseases
Authors: Liu Wei , Deng Wenxuan , Chen Ming , Dong Zihan , Zhu Biqing , Yu Zhaolong , Tang Daiwei , Sauler Maor , Wain Louise V. , Cho Michael H. , Kaminski Naftali , Zhao Hongyu
Published: March 2021

Finding disease-relevant tissues and cell types can facilitate the identification and investigation of functional genes and variants. In particular, cell type proportions can serve as potential disease predictive biomarkers. Here, we introduce a novel statistical framework, cell-type Wide Association Study (cWAS), that integrates genetic data with transcriptomics data to identify cell types whose genetically regulated proportions (GRPs) are disease/trait-associated. On simulated and real GWAS data, cWAS showed substantial statistical power with newly identified significant GRP associations in disease-associated tissues. More specifically, GRPs of endothelial and myofibroblasts in lung tissue were associated with Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease, respectively. For breast cancer, the GRP of blood CD8+ T cells was negatively associated with breast cancer (BC) risk as well as survival. Overall, cWAS is a powerful tool to reveal cell types associated with complex diseases mediated by GRPs.
Co-occurrence of apathy and impulsivity in progressive supranuclear palsy
Authors: Kok Zi Qi , Murley Alexander G. , Rittman Timothy , Rowe James B. , Passamonti Luca
Published: March 2021

Background

Apathy and impulsivity are common problems in progressive supranuclear palsy (PSP) and can worsen its prognosis. They can co-exist in the same patients although their concomitant prevalence remains unclear. Their relationship to emotional lability is also unknown.

Objectives

To estimate the co-occurrence of apathy and impulsivity and their relationship to emotional lability in PSP. To characterize the demographic, clinical, and cognitive features of PSP patients with apathy and impulsivity.

Methods

In a retrospective study of a long-term clinical cohort, we assessed the prevalence of apathy, impulsivity, and emotional lability from clinical interviews, medical records, and contemporary carer questionnaires. N=154 patients with a diagnosis of probable or possible PSP (according to the 2017 Movement Disorder Society criteria) were identified. N=64 of these patients had neuropathological confirmation of PSP. PSP patients with both apathy and impulsivity were compared in terms of demographic, clinical, and cognitive characteristics to PSP patients with either one or neither of these neuropsychiatric features.

Results

Apathy and impulsivity co-existed in two-thirds of people with PSP. A fifth displayed emotional lability in addition to apathy and impulsivity. Apathy and impulsivity were more commonly co-expressed than by chance. There was no single demographic, clinical or cognitive feature that distinguished between PSP patients with versus patients without apathy and impulsivity.

Conclusions

The co-existence of apathy and impulsivity in PSP suggests that these neuropsychiatric features may share similar risk factors and etio-pathogenetic mechanisms. Apathy and impulsivity should be jointly assessed when planning symptomatic treatments for behavioural problems in PSP.
Impact of the COVID-19 pandemic on cognitive function in Japanese community-dwelling older adults in a class for preventing cognitive decline
Authors: Kouzuki Minoru , Furukawa Shota , Mitani Keisuke , Urakami Katsuya
Published: March 2021

We examined the effects of lifestyle and thoughts on cognitive function and change in cognitive function due to restrictions in daily life during the coronavirus disease 2019 (COVID-19) pandemic in community-dwelling older adults with mild cognitive decline. This was a retrospective case-control study. The participants were 88 older adults with mild cognitive decline who participated in a class designed to help prevent cognitive decline. The class was suspended from early-March to end of May 2020 to prevent the spread of COVID-19, and resumed in June 2020. We collected demographic and cognitive function test data (Touch Panel-type Dementia Assessment Scale [TDAS]) before and after class suspension and questionnaire data on their lifestyle and thoughts during the suspension. Change in TDAS scores from before and after the suspension was used to divide the participants into decline (2 or more points worsening) and non-decline (all other participants) groups, with 16 (18.2%) and 72 (81.8%) participants in each group, respectively. A logistic regression model showed that the odds ratio (OR) for cognitive decline was lower in participants whose responses were “engaged in hobbies” (OR = 0.07, p = 0.015), “worked on a worksheet about cognitive training provided by the town hall” (OR = 0.19, p = 0.026), and “had conversations over the phone” (OR = 0.28, p = 0.0495). There was a significant improvement in TDAS scores after class was resumed (p < 0.01). A proactive approach to intellectual activities and social ties may be important for the prevention of cognitive decline during periods of restrictions due to COVID-19. We found that cognitive function test scores before class suspension significantly improved after resuming classes. We speculate that continued participation in the class led to positive behavioral changes in daily life during periods of restriction due to COVID-19.
Clinical Decision Support in Cardiovascular Medicine: Effectiveness, Implementation Barriers, and Regulation
Authors: Lu Yuan , Melnick Edward R. , Krumholz Harlan M.
Published: March 2021

Despite considerable progress in addressing cardiovascular disease (CVD) over the past 50 years, there remain many gaps in CVD care quality. Multiple missed opportunities have been identified at every step in the prevention and treatment of CVD, such as failure to make risk factor modifications, failure to diagnose CVD, and failure to use proper evidence-based treatments. With the digital transformation of medicine and advances in health information technology, clinical decision support (CDS) tools offer promise to enhance the efficiency and effectiveness of cardiovascular care delivery. Yet, to date, the promise of CDS delivering scalable and sustained value for patient care in clinical practice has not been realized. Here, we review evidence on key emerging questions around the development, implementation, and regulation of CDS with a focus on CVD. We first review evidence on the effectiveness of CDS on patient health and health delivery outcomes related to CVD and features predictive of effectiveness. We then review the barriers encountered during CDS implementation in cardiovascular care with a focus on unintended consequences and strategies to promote successful implementation. Finally, we review the current legal and regulatory environment of CDS with specific examples for CVD.
The intestinal microbiota-driven dopamine level influences social interaction and innate color preference in zebrafish larvae
Authors: Wang Ju , Zheng Feng , Yin Lifen , Shi Shengnan , Hu Bing , Zheng Lei
Published: March 2021

Gut microbiota influence neurodevelopment of brain and programing of behaviors. However, the mechanism underlining the relationship between shoals’ behaviors and intestinal microbiota remain controversial and the roles of neurotransmitters are still unclear. Here we show that, shoaling behavior affected the innate color preference of shoals, indicating that shoals tended to choose a favorable color environment that benefits social contact. Meanwhile, administration of D1-R antagonist disrupted the social interaction which led to the deficits of color preference. More importantly, the altered microbiota caused by an antibiotic OTC decreased the sociability and weakened shoals’ color preference. When given a supplement of LGG after OTC exposure, fish exhibited an unexpectedly recovery capability in social cohesion and color preference. Our findings show that dopamine level of brain could mediate both social recognition and color preference, and highlight the pathway of microbial metabolites through the microbiota-gut-brain axis that coordinate the production of dopamine.
Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study
Authors: Dobbs T D , Gibson J A G , Fowler A J , Abbott T E , Shahid T , Torabi F , Griffiths R , Lyons R A , Pearse R M , Whitaker I S
Published: March 2021

Objectives

To report the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic.

Design and setting

Analysis of electronic health record data from the National Health Service (NHS) in England and Wales.

Methods

We used hospital episode statistics for all adult patients undergoing surgery between 1st January 2020 and 31st December 2020. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from the years 2016-2019 with the actual number of procedures in 2020. We estimated the cumulative number of cancelled procedures by 31st December 2021 according patterns of activity in 2020.

Results

The total number of surgical procedures carried out in England and Wales in 2020 was 3,102,674 compared to the predicted number of 4,671,338. This represents a 33.6% reduction in the national volume of surgical activity. There were 763,730 emergency surgical procedures (13.4% reduction), compared to 2,338,944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1,568,664. We estimate that this will increase to 2,358,420 by 31st December 2021.

Conclusions

The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in over 1,568,664 cancelled operations. This deficit will continue to grow in 2021.

Summary boxes

What is already known on this topic

The COVID-19 pandemic necessitated a rapid change in the provision of care, including the suspension of a large proportion of surgical activity

Surgical activity has yet to return to normal and has been further impacted by subsequent waves of the pandemic

This will lead to a large backlog of cases

What this study adds

3,102,674 surgical procedures were performed in England and Wales during 2020, a 33.6% reduction on the expected yearly surgical activity

Over 1.5 million procedures were not performed, with this deficit likely to continue to grow to 2.3 million by the end of 2021

This deficit is the equivalent of more than 6 months of pre-pandemic surgical activity, requiring a monumental financial and logistic challenge to manage
Data variability in standardised cell culture experiments
Authors: Reddin Ian G. , Fenton Tim , Wass Mark N. , Michaelis Martin
Published: March 2021

Despite much debate about a perceived ‘reproducibility crisis’ in the life sciences, it remains unclear what level of replicability is technically possible [1,2]. Here, we analysed the variation among drug response data of the NCI60 project, which for decades has tested anti-cancer agents in a 60-cell line panel following a standardised protocol [3]. In total, 2.8 million compound/cell line experiments are available in the NCI60 resource CellMiner [4]. The largest fold change between the lowest and highest GI50 (concentration that reduces cell viability by 50%) in a compound/cell line combination was 3.16 x 1010. All compound/cell line combinations with >100 experiments displayed maximum GI50 fold changes >5, 99.7% maximum fold changes >10, 87.3% maximum fold changes >100, and 70.5% maximum fold changes >1000. FDA-approved drugs and experimental agents displayed similar variation. The variability remained very high after removal of outliers and among experiments performed in the same month. Hence, our analysis shows that high variability is an intrinsic feature of experimentation in biological systems, even among highly standardised experiments in a world-leading research environment. Thus, a narrow focus on experiment standardisation does not ensure a high level of replicability on its own.
Supergene origin and maintenance in Atlantic cod
Authors: Matschiner Michael , Barth Julia Maria Isis , Tørresen Ole Kristian , Star Bastiaan , Baalsrud Helle Tessand , Brieuc Marine Servane Ono , Pampoulie Christophe , Bradbury Ian , Jakobsen Kjetill Sigurd , Jentoft Sissel
Published: March 2021

Supergenes are sets of genes that are inherited as a single marker and encode complex phenotypes through their joint action. They are identified in an increasing number of organisms, yet their origins and evolution remain enigmatic. In Atlantic cod, four megabase-scale supergenes have been identified and linked to migratory lifestyle and environmental adaptations. Here, we investigate the origin and maintenance of these four supergenes through analysis of whole-genome-sequencing data, including a new long-read-based genome assembly for a non-migratory Atlantic cod individual. We corroborate that chromosomal inversions underlie all four supergenes, and show that they originated at different times between 0.40 and 1.66 million years ago. While we found no evidence for a role of introgression in the origin of the four supergenes, we reveal gene flux between supergene haplotypes with derived and ancestral arrangements, occurring both through gene conversion and double crossover. Our results suggest that supergenes can be maintained over long timescales in the same way as hybridizing species, through the purging of introduced genetic variation.
Butterfly eyespots evolved via co-option of the antennal gene-regulatory network
Authors: Murugesan Suriya Narayanan , Connahs Heidi , Matsuoka Yuji , Gupta Mainak das , Huq Manizah , Gowri V , Monroe Sarah , Deem Kevin D. , Werner Thomas , Tomoyasu Yoshinori , Monteiro Antónia
Published: March 2021

Butterfly eyespots are beautiful novel traits with an unknown developmental origin. Here we show that eyespots likely originated via co-option of the antennal gene-regulatory network (GRN) to novel locations on the wing. Using comparative transcriptome analysis, we show that eyespots cluster with antennae relative to multiple other tissues. Furthermore, three genes essential for eyespot development (Distal-less(Dll),spalt(sal), andAntennapedia(Antp)) share similar regulatory connections as those observed in the antennal GRN. CRISPR knockout ofcis-regulatory elements (CREs) forDllandsalled to the loss of eyespots and antennae, and also legs and wings, demonstrating that these CREs are highly pleiotropic. We conclude that eyespots likely re-used the ancient antennal GRN, a network previously implicated also in the development of legs and wings.
CAMSAP2 organizes a γ-tubulin-independent microtubule nucleation centre
Authors: Imasaki Tsuyoshi , Kikkawa Satoshi , Niwa Shinsuke , Saijo-Hamano Yumiko , Shigematsu Hideki , Aoyama Kazuhiro , Mitsuoka Kaoru , Aoki Mari , Sakamoto Ayako , Tomabechi Yuri , Sakai Naoki , Shirouzu Mikako , Taguchi Shinya , Yamagishi Yosuke , Setsu Tomiyoshi , Sakihama Yoshiaki , Shimizu Takahiro , Nitta Eriko , Takeichi Masatoshi , Nitta Ryo
Published: March 2021

Microtubules are dynamic polymers consisting of αβ-tubulin heterodimers. The initial polymerization process, called microtubule nucleation, occurs spontaneously via αβ-tubulin. Since a large energy barrier prevents microtubule nucleation in cells, the γ-tubulin ring complex is recruited to the centrosome to overcome the nucleation barrier. However, detachment of a considerable number of microtubules from the centrosome is known to contribute to fundamental processes in cells. Here, we present evidence that minus-end-binding calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) serves as a strong nucleator for microtubule formation from soluble αβ-tubulin independent of γ-tubulin. CAMSAP2 significantly reduces the nucleation barrier close to the critical concentration for microtubule polymerization by stabilizing the longitudinal contacts among αβ-tubulins. CAMSAP2 clusters together with αβ-tubulin to generate nucleation intermediates, from which numerous microtubules radiate, forming aster-like structures. Our findings suggest that CAMSAP2 supports microtubule growth by organizing a nucleation centre as well as by stabilizing microtubule nucleation intermediates.