bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of the Alfven eigenmodes stability in CFQS plasma using a Landau closure model
Authors: Varela J. , Shimizu A. , Spong D.A. , Garcia L. , Ghai Y.
Published: December 2020

The aim of this study is to analyze the stability of the Alfven eigenmodes (AE) in the Chinese First Quasi-axisymmetric Stellarator (CFQS). The AE stability is calculated using the code FAR3d that solves the reduced MHD equations to describe the linear evolution of the poloidal flux and the toroidal component of the vorticity in a full 3D system, coupled with equations of density and parallel velocity moment for the energetic particles (EP) species including the effect of the helical couplings and acoustic modes. The Landau damping and resonant destabilization effects are added in the model by a given closure relation. The simulation results indicate the destabilization of n = 1 to 4 AEs by EP during the slowing down process, particularly n = 1 and n = 2 toroidal AEs (TAE), n = 3 elliptical AE (EAE) and n = 4 non circular AE (NAE). If the resonance is caused by EPs with an energy above 17 keV (weakly thermalized EP), n = 2 EAEs and n = 3 NAEs are unstable. On the other hand, EPs with an energy below 17 keV (late thermalization stage) lead to the destabilization of n = 3 and n = 4 TAEs. The simulations for an off-axis NBI injection indicate the further destabilization of n = 2 to 4 AEs although the growth rate of the n = 1 AEs slightly decreases, so no clear optimization trend with respect to the NBI deposition region is identified. In addition, n = 2, 4 helical AE (HAE) are unstable above an EP β threshold. Also, if the thermal β of the simulation increases (higher thermal plasma density) the AE stability of the plasma improves. The simulations including the effect of the finite Larmor radius and electron-ion Landau damping show the stabilization of the n = 1 to 4 EAE/NAEs as well as a decrease of the growth rate and frequency of the n = 1 to 4 BAE/TAEs.
Proteomics of exhaled breath condensate in lung cancer and controls using data-independent acquisition (DIA): a pilot study
Authors: Ma Lin , Muscat Joshua E , Sinha Raghu , Sun Dongxiao , Xiu Guangli
Published: December 2020

Lung cancer, the leading cause of cancer mortality worldwide has a poor prognosis. To develop a non-invasive method for early lung cancer detection, exhaled breath condensate (EBC) was explored in this study. EBC samples were collected from lung cancer patients (n = 10) and healthy controls (n = 10), and a proteomic study was performed to identify potential biomarkers. Data-dependent acquisition was used to build the spectral library, and a data-independent acquisition (DIA) approach was applied for quantification of EBC proteomics. A total of 1151 proteins were identified, and several proteins were significantly upregulated in the lung cancer group compared to the control group. The Gene Ontology analysis revealed that most of the proteins were located within several organelles in the cells and were involved in binding and catalytic activity, and the Kyoto Encyclopedia Genes and Genomes results revealed that the proteins were mainly related to organismal systems and human disease. And S100A11, ANXA1, ENO1, and FABP5 might play a vital role in the EBC proteome. In summary, we demonstrated that the DIA-based quantification method was efficient in performing proteomic analysis in individual EBC samples, and some of the proteins might be novel biomarkers for lung cancer.
Renewable Energy in Africa: A Discussion of the Feasibility and Socio-Economic Effects of Solar Photovoltaic(PV) System
Authors: Long C , Zhang X
Published: December 2020

The development and expansion of the modern world cannot be separated from the support of electricity. The ‘pollution-free’ and unlimited renewable energy plays an increasingly important role in the energy supply market. Started with the interpretation of world energy consumption from 2008 to 2017, this paper takes Africa (primarily rural Africa), which has a shallow electricity connection rate, as an example to discuss the feasibility of deploying solar photovoltaic(PV) systems through analyzing its natural resources, government policies, and other factors. It briefly described both off-grid and grid-connected solar PV systems and their possible technical issues. Moreover, the potential socio-economic effects of the deployment of solar PV systems in the region have been predicted. Solar PV systems can solve the power supply issues for the people who live in rural areas with unsound infrastructure. Further research will quantify the benefits and analyze the impact factors to optimize the utility equation.
Application of Absolute Sustainability Assessment to New Zealand Residential Dwellings
Authors: McLaren S J , Chandrakumar C , Dowdell D , Bullen L. , Jaques R
Published: December 2020

One approach to supporting the implementation of sustainable activities by industry sectors is the use of climate targets. Such climate targets have potential to be used in design and rating tools for buildings and to support government regulation for the building and construction sector. In this study, the climate targets for New Zealand residential dwellings were calculated based on assigning the global carbon budget (for limiting temperature increase to 1.5 or 2.0 °C during 2018-2050) to three building typologies: detached, medium-density housing and apartments. These budgets were assigned to the pre-existing and new-built dwellings using building stock projections for the nominated period. Separately, the climate impact of new-built dwellings in each of the three residential typologies were assessed using Life Cycle Assessment methodology. For New Zealand residential buildings, new-built dwellings exceed their 1.5 °C climate targets by a factor of 6.7, 6.8 and 10.9 for detached, medium-density housing, and apartments respectively. For the 2.0 °C climate target, these factors are 4.8, 4.8 and 7.7 for detached, medium-density housing, and apartments respectively. The results show that about two-thirds of the climate impact of residential dwellings for the period 2018-2050 is associated with preexisting dwellings rather than new-builds. The operational energy used for space heating, water heating, lighting and plug loads makes the biggest contribution to the climate impact for all typologies of pre-built residential dwellings. For new-built residential dwellings, both the operational energy and the construction materials/products contribute most of the climate impact.
Strategies to mitigate the effects of future extreme heat waves - a new method for mapping
Authors: Özüm Durgun Yetkin , Håkansson Maria
Published: December 2020

Global warming is increasingly causing extreme weather events, such as heat waves. One-way heat waves are problematic in society, particularly in urban areas, is because of their negative impact on vulnerable groups including elderly people and children. Organizations such as municipalities that are responsible for local schools, day care centres and/or elderly homes, may struggle to provide the necessary care and function during extreme heat waves. This work explores how remote sensing images providing historical data of land surface temperatures (LST) can be used to create summer urban heat island maps and heat wave intensity, and in the longer run, how such information could be used by municipalities and other actors to mitigate effects of future heat waves. The method presented in this study was used to detect the “hot spots” in two participating Swedish municipalities and identify the municipal services located within these spots based on MODIS (1 km) and Landsat (30 m) LST datasets. Furthermore, this study showed that urban heat island phenomenon existed in the two participating municipalities. In general, this methodology can be applicable at both local and regional scale, although it might require additional site-specific data.
Enhancement Data In Term Of Material Selection And Design Consideration For Bulletproof Vest
Authors: Kin Lau Meng , Bukhari Mohabattul Z
Published: December 2020

Bulletproof vest is also known as ballistic vest and it is used to provide ballistic protection to the body of law enforcement and military personnel from injury through bullet impact, fragments, stab attacks and other treats. In this project, shear thickening fluid/ultra-high molecular weight polyethylene, STF/UHMWPE fabrics composites were prepared in order to design a low cost and lightweight bulletproof vest with high mechanical properties (impact energy and stab resistance). There are 2 categories that are prepared (UHMWPE with and without STF) and each category has 10 different numbers of layers. For the “UHMWPE with STF”, 10 of them were impregnated with shear thickening fluid that prepared by sonochemical method by mixing dry silica nanopowders, polyethylene glycol and ethanol. The effects of number of layers of UHMWPE fabrics and STF/UHMWPE fabrics on the impact properties for both UHMWPE without STF and UHMWPE with STF fabrics were investigated by using drop tower impact testing. Results from this study showed, absorption of impact energy is increased with increase in the number of penetrated witness papers. Besides, it is also indicated that the impact energy absorbed by witness paper/s is increased when the number of UHMWPE fabric and STF/UHMWPE layers are increased. The comparison between 2 categories is discussed. The result showed that STF/UHMWPE fabrics have better performance than UHMWPE fabrics in term of impact energy absorption, stab resistance and number of fabrics layers.
An experimental study on the feasibility of using combination of industrial by-products and wastes as highway construction materials
Authors: Judes Sujatha S. , Sahaya Ruben J. , Sumil Kumaran A.
Published: December 2020

Use of industrial by-products and wastes as highway construction materials help achieving sustainable development. This paper presents and discusses the results of the experimental studies carried out to determine the effect of combination of different industrial by-products and wastes on unconfined compressive strength variation of the mixtures. The effect of different stabilizing agents such as cement and lime, and the effect of different curing periods such as 7-days, 14-days and 28-days on the strength variation are also examined.
Concrete-filled steel tube columns of different cross-sectional shapes under axial compression: A review
Authors: Ilanthalir A , Jerlin Regin J , Maheswaran J
Published: December 2020

This paper presents a review on the axial compression behavior of different cross-sectional shaped concrete-filled steel tube (CFST) columns such as circular, rectangular, square, elliptical, hexagonal, octagonal and round-ended. A discussion on some special shapes like triangular, D-shape, ¼ circular, fan shape etc. is also done in this paper. Confinement offered by the varying cross-sectional shape steel tubes to concrete core, material strength limits and slenderness limits available in different codes of practices and the proposed yield slenderness limits for rectangular, elliptical and octagonal cross-sections are discussed. The failure modes encountered during the axial compression test on CFST columns are mentioned. An analysis on the parameters that influence the behavior of the columns, design equations in the current codes of practice, modifications made on the code design equations, equations proposed on the determination of compressive strength of different cross-sectional shapes of CFST columns is done. Unified formulas for two different cross-sectional shapes and solid and hollow concrete-filled steel tubes are also included. Conclusions are finally made based on the discussion done.
Defluoridation of Water by Using Modified Material Developed from Ficus benghalensis Leaf: Characterization, Kinetic and Thermodynamic Study
Authors: Telkapalliwar Nandkishor G.
Published: December 2020

In the present study, microwave-assisted and chemically treated carbonized Ficus benghalensis leaf (MACFBL) material was used as an adsorbent material for the removal of fluoride from water. The results of the characterization of MAFBL carbon material exhibited ideal adsorbent properties. The fluoride adsorption experiments were performed under the batch mode to improve the different affecting parameters such as contact time (0-300 min) and temperature (303-343K) at predetermined pH (5), agitation speed (120 strokes/min), fluoride concentration (2 mg/L) and adsorbent dose (5 g/L). The maximum fluoride removal efficiency of fluoride on MACFBL material was found 86.5 %. The fluoride adsorption data applied for four well known kinetic models such as pseudo first-order, pseudo second-order, intra-particle diffusion, and Elovich kinetic models. The pseudo second-order kinetic study shows the most favourable mechanism for the removal of fluoride. Thermodynamic investigation proposed that the fluoride adsorption process onto MACFBL was exothermic. The instrumental study of MACFBL adsorbent material before and after adsorption during FTIR, SEM, EDX and XRD techniques established the fluoride adsorption on the carbon surface. The developed adsorbent material (MACFBL) is efficient for the removal of fluoride.
Prediction of Gas Composition of a Fluidized Bed Gasifier in a Sugarcane Bagasse-Modeling
Authors: Manikandan P , Christus Jeya Singh V
Published: December 2020

The assessment of the performance of various biomass fuel sources in gasifier is a significant zone of study for the execution of this innovation in different applications, pertinent to remote villages. This paper reveals the prediction of the composition of producer gas in a fluidized bed gasifier using Sugarcane Bagasse as feedstock where air to be used as gasifying agent. The model dependent on equilibrium constant and material balance has been created to assess the syngas compositions. The developed model has been used to predict the composition of constituent gases by varying equivalence ratio (ER) between 0.1 and 0.35 and keeping the moisture content (MC) constant. The outcomes show that the mole portion of CO from sugarcane bagasse is higher as compared to rice husk and coir pith and the composition of H2 and CH4 where absorbed very close to rice husk. Hence it recommended that the sugarcane bagasse and coir pith shall replace the rice husk and coir pith in fluidized bed gasifier for rural applications.
Conservation Strategies for Protecting Tiger Beetles and Their Habitats in the United States: Studies With Listed Species (Coleoptera: Carabidae: Cicindelidae)
Authors: Knisley C Barry , Gwiazdowski Rodger
Published: December 2020

Tiger beetles are a popular, widely studied group of charismatic insects that are a flagship taxon for insect conservation. Five species are currently listed in the United States as Federally Endangered or Threatened, two others have recently been delisted, and many more are listed by individual states. To date, the status of some of these species has been improved or their decline slowed by various conservation strategies. In this article, we review the background and the recent conservation activities for all federally listed tiger beetle species. These species have lost much of their historic habitat and remain at risk because of continuing impacts from vegetation encroachment of native or invasive plants, water-level changes, and other human-related activities. Conservation efforts are limited because for most species there is little or no potential habitat remaining, even following restoration activities. Effective strategies have included long-term monitoring of population size and research activities, acquisition and protection of occupied sites, methods for controlling vegetation encroachment to improve habitat quality, and recent efforts with translocations using beetles from existing populations or from captive rearing. Because tiger beetle life histories are similar, successful management and research methods for any one species can be applicable to others. This presents an opportunity to coordinate taxon-level conservation for all U.S. species through cataloged information and conservation leadership
Wage Growth across Fields of Study among Young College Graduates: Is There a Gender Gap?
Authors: Sánchez-Mangas Rocío , Sánchez-Marcos Virginia
Published: December 2020

We use the Flexible Professional in the Knowledge Society data set to learn about gender gaps during the early career of college graduates in Europe. We document substantial heterogeneity across fields of education in the gender wage gap at the entrance to the labour market. We find that the gap evolves against women over the five years after graduation in Social Science and in Economics, Business, and Law. Finally, we estimate a significant female wage growth penalty after we control for observable characteristics only within the Economics, Business, and Law category. Within this field, we estimate a female annual wage growth penalty of 1.1 percentage points among individuals who remained childless and 2.5 percentage points among individuals who became parents. A small fraction of the wage growth gap disappears after we control for variables capturing individual differences in job mobility or in labour market attachment during the early career. (JEL codes: J16, J24, J31)
Optic Nerve Sheath Ultrasound for the Detection and Monitoring of Raised Intracranial Pressure in Tuberculous Meningitis
Authors: Donovan Joseph , Oanh Pham Kieu Nguyet , Dobbs Nicholas , Phu Nguyen Hoan , Nghia Ho Dang Trung , Summers David , Thuong Nguyen Thuy Thuong , Thwaites Guy E ,   Vietnam ICU Translational Applications Laboratory (VITAL) Investigators
Published: December 2020

Background

Neurological complications of tuberculous meningitis (TBM) often lead to raised intracranial pressure (ICP) resulting in high morbidity and mortality. Measurement of optic nerve sheath diameter (ONSD) by point-of-care ultrasound may aid in the identification of raised ICP in TBM.

Methods

From June 2017 to December 2019, 107 Vietnamese adults with TBM, enrolled in the ACT HIV or LAST ACT trials (NCT03092817, NCT03100786), underwent ONSD ultrasound at ≥1 of days 0, 3, 7, 14, 21, and day ±30 after enrollment. Demographic data, TBM severity grade, HIV coinfection status, and clinical endpoints by 3 months were recorded. ONSD values were correlated with disease severity, baseline brain imaging, cerebrospinal fluid parameters, and clinical endpoints.

Results

267 ONSD ultrasound scans were performed in 107 participants over the first 30 days of treatment, with measurements from 0.38–0.74 cm. Paired baseline ONSD and brain imaging were performed in 63 participants. Higher baseline ONSD was associated with more severe disease and abnormal brain imaging (abnormal imaging 0.55 cm vs 0.50 cm normal imaging, P = .01). Baseline median ONSD was significantly higher in participants who died by 3 months (0.56 cm [15/72]) versus participants who survived by 3 months (0.52 cm [57/72]) (P = .02). Median ONSD was higher at all follow-up times in participants who died by 3 months.

Conclusions

Higher ONSD was associated with increased disease severity, brain imaging abnormalities, and increased death by 3 months. ONSD ultrasound has a potential role as a noninvasive, affordable bedside tool for predicting brain pathology and death in TBM.
A Meta-analysis on the Role of Children in Severe Acute Respiratory Syndrome Coronavirus 2 in Household Transmission Clusters
Authors: Zhu Yanshan , Bloxham Conor J , Hulme Katina D , Sinclair Jane E , Tong Zhen Wei Marcus , Steele Lauren E , Noye Ellesandra C , Lu Jiahai , Xia Yao , Chew Keng Yih , Pickering Janessa , Gilks Charles , Bowen Asha C , Short Kirsty R
Published: December 2020

The role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains highly controversial. To address this issue, we performed a meta-analysis of the published literature on household SARS-CoV-2 transmission clusters (n = 213 from 12 countries). Only 8 (3.8%) transmission clusters were identified as having a pediatric index case. Asymptomatic index cases were associated with a lower secondary attack in contacts than symptomatic index cases (estimate risk ratio [RR], 0.17; 95% confidence interval [CI], 0.09-0.29). To determine the susceptibility of children to household infections the secondary attack rate in pediatric household contacts was assessed. The secondary attack rate in pediatric household contacts was lower than in adult household contacts (RR, 0.62; 95% CI, 0.42-0.91). These data have important implications for the ongoing management of the COVID-19 pandemic, including potential vaccine prioritization strategies.
Wound-healing capabilities of whale sharks (Rhincodon typus) and implications for conservation management
Authors: Womersley Freya , Hancock James , Perry Cameron T , Rowat David
Published: December 2020

Wound healing is important for marine taxa such as elasmobranchs, which can incur a range of natural and anthropogenic wounds throughout their life history. There is evidence that this group shows a high capacity for external wound healing. However, anthropogenic wounds may become more frequent due to increasing commercial and recreational marine activities. Whale sharks are particularly at risk of attaining injuries given their use of surface waters and wildlife tourism interest. There is limited understanding as to how whale sharks recover from injuries, and often insights are confined to singular opportunistic observations. The present study makes use of a unique and valuable photographic data source from two whale shark aggregation sites in the Indian Ocean. Successional injury-healing progression cases were reviewed to investigate the characteristics of injuries and quantify a coarse healing timeframe. Wounds were measured over time using an image standardization method. This work shows that by Day 25 major injury surface area decreased by an average of 56% and the most rapid healing case showed a surface area reduction of 50% in 4 days. All wounds reached a point of 90% surface area closure by Day 35. There were differences in healing rate based on wound type, with lacerations and abrasions taking 50 and 22 days to reach 90% healing, respectively. This study provides baseline information for wound healing in whale sharks and the methods proposed could act as a foundation for future research. Use of a detailed classification system, as presented here, may also assist in ocean scale injury comparisons between research groups and aid reliable descriptive data. Such findings can contribute to discussions regarding appropriate management in aggregation areas with an aim to reduce the likelihood of injuries, such as those resulting from vessel collisions, in these regions or during movements between coastal waters.
Use of high-density activation and voltage mapping in combination with entrainment to delineate gap-related atrial tachycardias post atrial fibrillation ablation
Authors: Vlachos Konstantinos , Efremidis Michael , Derval Nicolas , Martin Claire A , Takigawa Masateru , Bazoukis George , Frontera Antonio , Gkalapis Charis , Duchateau Josselin , Nakashima Takashi , Letsas Konstantinos P , Mililis Panagiotis , Pambrun Thomas , Bourier Felix , André Clémentine , Krisai Philipp , Ramirez F Daniel , Kamakura Tsukasa , Takagi Takamitsu , Nakatani Yosuke , Kitamura Takeshi , Cheniti Ghassen , Sacher Frédéric , Hocini Mélèze , Haïssaguerre Michel , Jaïs Pierre
Published: December 2020

Aims

An incomplete understanding of the mechanism of atrial tachycardia (AT) is a major determinant of ablation failure. We systematically evaluated the mechanisms of AT using ultra-high-resolution mapping in a large cohort of patients.

Methods and results

We included 107 consecutive patients (mean age: 65.7 ± 9.2 years, males: 81 patients) with documented endocardial gap-related AT after left atrial ablation for persistent atrial fibrillation (AF). We analysed the mechanism of 134 AT (94 macro-re-entries and 40 localized re-entries) using high-resolution activation mapping in combination with high-density voltage and entrainment mapping. Voltage in the conducting channels may be extremely low, even <0.1 mV (0.14 ± 0.095 mV, 51 of 134 AT, 41%), and almost always <0.5 mV (0.03–0.5 mV, 133 of 134 AT, 99.3%). The use of multipolar Orion, HDGrid, and Pentaray catheters improved our accuracy in delineating ultra-low-voltage areas critical for maintenance of the circuit of endocardial gap-related AT. Conventional ablation catheters often do not detect any signal (noise level) even using adequate contact force, and only multipolar catheters of small electrodes and shorter interelectrode space can detect clear fractionated low-amplitude and high frequency signals, critical for re-entry maintenance. We performed a diagnosis in 112 out of 134 AT (83.6%) using only activation mapping and in 134 out of 134 AT (100%) using the combination of activation and entrainment mapping.

Conclusion 

High-resolution activation mapping in combination with high-density voltage and entrainment mapping is the ideal strategy to delineate the critical part of the circuit in endocardial gap-related re-entrant AT after AF ablation.
Reactive, Agentic, Apathetic, or Challenged? Aging, Emotion, and Coping During the COVID-19 Pandemic
Authors: Young Nathaniel A , Waugh Christian E , Minton Alyssa R , Charles Susan T , Haase Claudia M , Mikels Joseph A
Published: December 2020

Background and Objectives

Advanced age is generally associated with improved emotional well-being, but the coronavirus 2019 pandemic unleashed a global stressor that gravely threatened the physical well-being and ostensibly challenged the emotional well-being of older adults disproportionately. The current study investigated differences in emotional experiences and coping strategies between younger and older adults during the pandemic, and whether these differences were accounted for by age differences in appraisal of the pandemic.

Research Design and Methods

We asked younger (n = 181) and older (n = 176) adult participants to report their stress, appraisals of the pandemic, emotions, and the ways in which they were coping with the pandemic.

Results

Results indicated that older adults experienced less stress and less negative affect and used greater problem-focused coping and less avoidant coping in response to the pandemic than younger adults. Furthermore, age differences in affect and coping were partially accounted for by age differences in appraisals of the pandemic.

Discussion and Implications

Despite their objectively higher risk of illness and death due to the pandemic, older adults experienced less negative affect and used more agentic coping strategies than younger adults.
Free-Riding for the Common Good? Generics, Biosimilars and References to Originator Trademarks in Comparative Advertising in France
Authors: Rouvinen Markus
Published: December 2020

Generic and biosimilar medicines are fiscally advantageous products in relation to which the generally applicable EU rules governing comparative advertising seemingly conflict with national healthcare policy. This article argues that the permissive stance of the French courts on the use of the trademarked names of originator medicines in advertising for generics appears inconsistent with the case law of the Court of Justice of the European Union as it stands in relation to Art. 4(f) of Directive 2006/114/EC on misleading and comparative advertising. This gives rise to an undesirable divergence in the application of the Directive between Member States, suggesting that further guidance is needed on the application of the provision to generic-originator comparisons. It is submitted that treating generic drugs with particular leniency is unjustified given the detrimental effect the use of originator trademarks by the marketers of generics and biosimilars may have on the ability of the originator trademark to stimulate investment into manufacturing quality. The issue of the degree to which the use of originator trademarks in advertising promoting generics and biosimilars should be permitted serves as a poignant example of the delicate balance required for comparative advertising to increase consumer choice whilst simultaneously protecting competitors from advertising that may ultimately be detrimental to undistorted competition in the Single Market.
Bayesian spatio-temporal modelling and prediction of areal demands for ambulance services
Authors: Nicoletta Vittorio , Guglielmi Alessandra , Ruiz Angel , Bélanger Valérie , Lanzarone Ettore
Published: December 2020

Careful planning of an ambulance service is critical to reduce response times to emergency calls and make assistance more effective. However, the demand for emergency services is highly variable, and good prediction of the number of future emergency calls, and their spatial and temporal distribution, is challenging. In this work, we propose a Bayesian approach to predict the number of emergency calls in future time periods for each zone of the served territory. The number of calls is described by a generalized linear mixed effects model, and inference, in terms of posterior predictive distributions, is obtained through Markov chain Monte Carlo simulation. Our approach is applied in a large city in Canada. The paper demonstrates that using a model for areal data provides good results in terms of predictive accuracy and allows flexibility in accounting for the main features of the dataset. Moreover, it shows the computational efficiency of the approach despite the huge dataset.
Burden of Respiratory Syncytial Virus Infection During the First Year of Life
Authors: Thomas Emilia , Mattila Janna-Maija , Lehtinen Pasi , Vuorinen Tytti , Waris Matti , Heikkinen Terho
Published: December 2020

Background

Although many infants with respiratory syncytial virus (RSV) infection are hospitalized, most infants are treated as outpatients. Limited data are available on the burden of RSV in outpatient infants.

Methods

In a prospective study, we enrolled 431 newborn infants and followed them up for a 10-month period (September–June). During each respiratory illness, we examined the infants and obtained nasopharyngeal specimens for the detection of RSV. The parents completed daily symptom diaries throughout the study.

Results

Among 408 active participants, the seasonal incidence rate of RSV illness was 328.4 per 1000 (95% confidence interval [CI], 275.2–389.0). Infants with ≥1 sibling had a 1.9-fold higher incidence of RSV illness than those without siblings (95% CI, 1.3–2.8; P < .001). Acute otitis media developed in 103 (76.9%) of 134 infants with RSV infection, and 95 (70.9%) were treated with antibiotics. Nine infants with RSV (6.7%) were hospitalized, for a seasonal incidence rate of RSV hospitalization of 22.1 per 1000 (95% CI, 10.1–41.9).

Conclusions

The outpatient burden of RSV is heavy on infants during the first year of life. Acute otitis media is a frequent complication of RSV, and it should be included in cost-effectiveness analyses of prevention or treatment of RSV infections in infants.
Synthesis, inhibitory activity and oral dosing formulation of AV5124, the structural analogue of influenza virus endonuclease inhibitor baloxavir
Authors: Ivashchenko Andrei A , Mitkin Oleg D , Jones Jeremy C , Nikitin Alexander V , Koryakova Angela G , Karapetian Ruben N , Kravchenko Dmitry V , Mochalov Stephan V , Ryakhovskiy Alexey A , Aladinskiy Vladimir , Leneva Irina A , Falynskova Irina N , Glubokova Ekaterina A , Govorkova Elena A , Ivachtchenko Alexandre V
Published: December 2020

Background

The development and clinical implementation of the cap-dependent endonuclease (CEN) inhibitor baloxavir marboxil was a breakthrough in influenza therapy, but it was associated with the emergence of drug-resistant variants.

Objectives

To design and synthesize structural analogues of CEN inhibitors and evaluate their safety, pharmacokinetics and antiviral potency in vitro and in vivo.

Methods

The drug candidate AV5124 and its active metabolite AV5116 were synthesized based on pharmacophore modelling. Stability in plasma and microsomes, plasma protein binding, cytotoxicity and antiviral activities were assessed in vitro. Pharmacokinetics after IV or oral administration were analysed in CD-1 mice. Acute toxicity and protective efficacy against lethal A(H1N1)pdm09 influenza virus challenge were examined in BALB/c mice.

Results

Pharmacophore model-assisted, 3D molecular docking predicted key supramolecular interactions of the metal-binding group and bulky hydrophobic group of AV5116 with the CEN binding site (Protein Data Bank code: 6FS6) that are essential for high antiviral activity. AV5116 inhibited influenza virus polymerase complexes in cell-free assays and replication of oseltamivir-susceptible and -resistant influenza A and B viruses at nanomolar concentrations. Notably, AV5116 was equipotent or more potent than baloxavir acid (BXA) against WT (I38-WT) viruses and viruses with reduced BXA susceptibility carrying an I38T polymerase acidic (PA) substitution. AV5116 exhibited low cytotoxicity in Madin–Darby canine kidney cells and lacked mitochondrial toxicity, resulting in favourable selective indices. Treatment with 20 or 50 mg/kg AV5124 prevented death in 60% and 100% of animals, respectively.

Conclusions

Overall, AV5124 and A5116 are promising inhibitors of the influenza virus CEN and warrant further development as potent anti-influenza agents.
Fully Automated Optical Hematocrit Measurement from Dried Blood Spots
Authors: Luginbühl Marc , Fischer Yannick , Gaugler Stefan
Published: December 2020

The impact of the hematocrit (HCT) on the dried blood spot (DBS)’s spreading area is one of the most important hurdles, which prevents the full acceptance of quantitative microsampling strategies. Several destructive and non-destructive strategies to assess the HCT from a DBS post-sampling have been presented. Unfortunately, the current methods are either labor-intensive, require a complicated algorithm or are not automatable. Here, we present a novel setup that permits the fully automated reflectance analysis to measure the HCT from a DBS. The underlying principle is based on the concept of the non-destructive single-wavelength HCT measurement. The novel module was embedded within the DBS-MS 500 platform to enable high-throughput analysis of HCT values in combination with automated DBS extraction. The novel setup was assessed and optimized for the probe to card distance, stability, anti-coagulant, spotting volume, scan number, calibration variability, accuracy and precision. It showed excellent inter-day (≤3.7%) and intra-day (≤1.16%) precision as well as high accuracy when analyzing authentic samples (101% ± 7% [range: 87–127%]). Besides, the simple and straightforward application of an HCT correction for DBS was demonstrated during a pharmacokinetic study with diclofenac involving three subjects. Thereby, the sample’s HCT and the HCT impact on the analyte were assessed and compensated. In conclusion, the novel setup enables quantitative analysis of non-volumetric samples in an automated fashion without compromising the concept of cost-effective, minimally invasive sampling.
The WOX family transcriptional regulator SlLAM1 controls compound leaf and floral organ development inSolanum lycopersicum
Authors: Wang Chaoqun , Zhao Baolin , He Liangliang , Zhou Shaoli , Liu Ye , Zhao Weiyue , Guo Shiqi , Wang Ruoruo , Bai Quanzi , Li Youhan , Wang Dongfa , Wu Qing , Yang Yuanfan , Liu Yu , Tadege Million , Chen Jianghua
Published: December 2020

Plant-specific WOX family transcription factors play important roles ranging from embryogenesis to lateral organ development. The WOX1 transcription factors, which belong to the modern clade of the WOX family, are known to regulate outgrowth of the leaf blade specifically in the mediolateral axis; however, the role of WOX1 in compound leaf development remains unknown. Phylogenetic analysis of the whole WOX family in tomato (Solanum lycopersicum) indicates that there are 10 members that represent the modern, intermediate, and ancient clades. Using phylogenetic analysis and a reverse genetic approach, in this study we identified SlLAM1 in the modern clade and examined its function and tissue-specific expression pattern. We found that knocking out SlLAM1 via CRISPR/Cas9-mediated genome editing led to narrow leaves and a reduced number of secondary leaflets. Overexpression of tomato SlLAM1 could rescue the defects of the tobacco lam1 mutant. Anatomical and transcriptomic analyses demonstrated that floral organ development, fruit size, secondary leaflet initiation, and leaf complexity were altered due to loss-of-function of SlLAM1. These findings demonstrate that tomato SlLAM1 plays an important role in the regulation of secondary leaflet initiation, in addition to its conserved function in blade expansion.
Abortion Rights after Artificial Wombs: Why Decriminalisation is Needed Ahead of Ectogenesis
Authors: Horn Claire
Published: December 2020

Significant scientific progress has been made toward artificial womb technology, which would allow part of human gestation to occur outside the body. Bioethical and legal scholars have argued that artificial wombs will challenge defences of abortion based in arguments for protecting bodily autonomy, for a pregnant person could have the foetus transferred to an artificial womb instead of being terminated. Drawing on examples from the common law jurisdictions of Canada, the USA, and the UK, I assess three ways scholars have argued abortion might be defended after ectogenesis (through redefining foetal viability, through a property right, and through a right to avoid genetic parenthood). I argue that while each of these proposals has strategic merit, each has significant legal and ethical limitations. Taking the normative position that abortion will remain a vital healthcare resource, I make the case for protecting abortion rights from a challenge posed by ectogenesis by focusing on decriminalisation.
Phylogenetic Analysis of SARS-CoV-2 Data Is Difficult
Authors: Morel Benoit , Barbera Pierre , Czech Lucas , Bettisworth Ben , Hübner Lukas , Lutteropp Sarah , Serdari Dora , Kostaki Evangelia-Georgia , Mamais Ioannis , Kozlov Alexey M , Pavlidis Pavlos , Paraskevis Dimitrios , Stamatakis Alexandros
Published: December 2020

Numerous studies covering some aspects of SARS-CoV-2 data analyses are being published on a daily basis, including a regularly updated phylogeny on nextstrain.org. Here, we review the difficulties of inferring reliable phylogenies by example of a data snapshot comprising a quality-filtered subset of 8,736 out of all 16,453 virus sequences available on May 5, 2020 from gisaid.org. We find that it is difficult to infer a reliable phylogeny on these data due to the large number of sequences in conjunction with the low number of mutations. We further find that rooting the inferred phylogeny with some degree of confidence either via the bat and pangolin outgroups or by applying novel computational methods on the ingroup phylogeny does not appear to be credible. Finally, an automatic classification of the current sequences into subclasses using the mPTP tool for molecular species delimitation is also, as might be expected, not possible, as the sequences are too closely related. We conclude that, although the application of phylogenetic methods to disentangle the evolution and spread of COVID-19 provides some insight, results of phylogenetic analyses, in particular those conducted under the default settings of current phylogenetic inference tools, as well as downstream analyses on the inferred phylogenies, should be considered and interpreted with extreme caution.
Splicing at the phase-separated nuclear speckle interface: a model
Authors: Liao Susan E , Regev Oded
Published: December 2020

Phase-separated membraneless bodies play important roles in nucleic acid biology. While current models for the roles of phase separation largely focus on the compartmentalization of constituent proteins, we reason that other properties of phase separation may play functional roles. Specifically, we propose that interfaces of phase-separated membraneless bodies could have functional roles in spatially organizing biochemical reactions. Here we propose such a model for the nuclear speckle, a membraneless body implicated in RNA splicing. In our model, sequence-dependent RNA positioning along the nuclear speckle interface coordinates RNA splicing. Our model asserts that exons are preferentially sequestered into nuclear speckles through binding by SR proteins, while introns are excluded through binding by nucleoplasmic hnRNP proteins. As a result, splice sites at exon-intron boundaries are preferentially positioned at nuclear speckle interfaces. This positioning exposes splice sites to interface-localized spliceosomes, enabling the subsequent splicing reaction. Our model provides a simple mechanism that seamlessly explains much of the complex logic of splicing. This logic includes experimental results such as the antagonistic duality between splicing factors, the position dependence of splicing sequence motifs, and the collective contribution of many motifs to splicing decisions. Similar functional roles for phase-separated interfaces may exist for other membraneless bodies.
Differential activation mechanisms of two isoforms of Gcr1 transcription factor generated from spliced and un-spliced transcripts inSaccharomyces cerevisiae
Authors: Cha Seungwoo , Hong Chang Pyo , Kang Hyun Ah , Hahn Ji-Sook
Published: December 2020

Gcr1, an important transcription factor for glycolytic genes in Saccharomyces cerevisiae, was recently revealed to have two isoforms, Gcr1U and Gcr1S, produced from un-spliced and spliced transcripts, respectively. In this study, by generating strains expressing only Gcr1U or Gcr1S using the CRISPR/Cas9 system, we elucidate differential activation mechanisms of these two isoforms. The Gcr1U monomer forms an active complex with its coactivator Gcr2 homodimer, whereas Gcr1S acts as a homodimer without Gcr2. The USS domain, 55 residues at the N-terminus existing only in Gcr1U, inhibits dimerization of Gcr1U and even acts in trans to inhibit Gcr1S dimerization. The Gcr1S monomer inhibits the metabolic switch from fermentation to respiration by directly binding to the ALD4 promoter, which can be restored by overexpression of the ALD4 gene, encoding a mitochondrial aldehyde dehydrogenase required for ethanol utilization. Gcr1U and Gcr1S regulate almost the same target genes, but show unique activities depending on growth phase, suggesting that these isoforms play differential roles through separate activation mechanisms depending on environmental conditions.
COVD-30. A SNAPSHOT OF THE IMPACT OF COVID-19 ON PATIENTS WITH NERVOUS SYSTEM TUMORS
Authors: Aaroe Ashley ,   D3CODE Team, Harrison Rebecca , Majd Nazanin , O’Brien Barbara , Weathers Shiao-Pei , Loghin Monica , Kamiya-Matsuoka Carlos , Yung W K Alfred , de Groot John , Woodman Karin
Published: December 2020

BACKGROUND

The impact of COVID-19 on patients with nervous system tumors is not known. This population is often immunosuppressed, susceptible to neurological complications, and requiring of frequent cancer care, all of which may confer vulnerability to poorer outcomes after infection.

METHODS

Clinical data were obtained from structured electronic medical record elements, clinical note text and laboratory RESULTS: Each source was identified, integrated and analyzed using the Palantir Foundry platform (Syntropy), part of the Context Engine Data Management System through the MD Anderson Cancer Center (MDACC) IRB approved D3CODE initiative. The population of interest was patients diagnosed with COVID-19 who had been seen at the Brain and Spine Center for nervous system tumors.

RESULTS

8,177 ambulatory patients were seen at the Brain and Spine Center from 3/1/20–9/1/20. COVID status was known for 1,753 (21%). Sixty-one (0.7%) were COVID-19 positive. Of these, 17 had primary nervous system tumors. Seven (41%) were treated in the emergency department or hospital for infection. Two were symptomatic but did not require further care. Eight were asymptomatic. Nine (53%) had alterations in cancer management within one week of COVID-19 diagnosis – delayed surgery (3), delayed/interrupted chemotherapy (2), delayed/interrupted radiation (2), cancer treatment discontinued (2). Eight patients (47%) had no clear impact of infection on their cancer treatment, three were on surveillance. Three (18%) unique patients had neurological symptoms attributed to/exacerbated by COVID-19 – encephalopathy (2), seizure (2), stroke (1).

CONCLUSION

No deleterious effects of alterations in cancer management after COVID-19 infection have been identified thus far, though longitudinal follow up is warranted. Our results suggest that COVID-19 infection frequently incurs medical complications or alterations in cancer treatment. The potential impacts of COVID-19 on our vulnerable neuro-oncology patient population should be further explored, and attention to these potential implications for our patients is warranted by treating clinicians.
Investigating Changes in Patients’ Smoking Behavior, Tobacco Dependence, and Motivation to Stop Smoking Following a “Smoke-Free” Mental Health Inpatient Stay: Results From a Longitudinal Survey in England
Authors: Ainscough Tom S , Mitchell Alex , Hewitt Catherine , Horspool Michelle , Stewart Pete , Ker Suzy , Colley Lesley , Paul Claire , Hough Phil , Hough Simon , Britton John , Ratschen Elena
Published: December 2020

Introduction

In line with national guidance, mental health Trusts in England are implementing complete smoke-free policies. We investigated inpatients’ changes in smoking behavior, tobacco dependence, vaping, and motivation to stop smoking between pre-admission and post-discharge.

Methods

We surveyed acute adult mental health inpatients from 14 wards in three mental health Trusts in England in 2019. Structured face-to-face and telephone interviews with patients who smoked on or during admission were conducted during the admission period and at one week and one month after discharge. Data on smoking status; daily cigarette consumption; Heaviness of Smoking Index (HSI); Strength of Urges to Smoke (SUTS); Motivation to Stop Smoking (MTSS) and vaping were collected and analyzed using regression and probit models.

Results

Inpatient smoking prevalence was 51.9%, and a total of 152 of all 555 eligible smokers (27%) were recruited. Attrition was high: 49.3% at the first and 50.7% at the second follow-up interview. Changes in self-reported smoking status, motivation to quit, and vaping did not change significantly over the study period. Cigarette consumption (p < 0.001) and Heaviness of Smoking Index (p < 0.001) modestly reduced. The frequency and strength of urges to smoke (p = 0.011 and 0.012, respectively) decreased modestly after discharge but were scored as high by 57% and 60% of participants during admission respectively. Just over half (56%) reported being offered smoking cessation support on admission.

Conclusions

This study identified very modest changes in smoking-related outcomes during and after admission and indicates major challenges to smoke-free policy implementation, including limited support for patients who smoke.

Implications

Despite mental health Trusts in England had developed and implemented smoke-free policies to meet national guidelines, adherence to these policies and provision of effective smoking cessation and temporary abstinence support for inpatients admitted to acute adult mental health wards appear to be limited. Patients who smoke on admission are likely to continue to do so during admission and after discharge, and only a very modest change in smoking behaviors appears to take place. Important opportunities to promote smoking cessation in this population are missed. Barriers to effective support need to be identified and addressed.