bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite element modeling of electro‐viscoelasticity in fiber reinforced electro‐active polymers
Authors: Kanan Anas , Kaliske Michael
Published: December 2020

In this work, aspects considering material modeling of electro‐mechanical coupling in fiber reinforced electro‐active polymers (EAP) and the corresponding finite element implementation are considered. We propose a constitutive model that takes into account the electro‐viscoelastic behavior of the isotropic matrix and the influence of unidirectional fibers on both the hyperelastic response and the viscous behavior of the whole composite. Two distinct existing models that describe the electro‐mechanical coupling, are demonstrated and implemented, moreover, a numerical link between both models for three‐dimensional continua in terms of tensor calculus, is identified. We propose the extended‐tube model for the elastic response with some of its parameters evolving in response to the electric field, in order to fit electro‐viscoelastic experiments. Regarding the finite element implementation, in addition to the deformation field and the electric potential, two pairs of field variables are introduced on the element level, to enforce quasi‐incompressibility and quasi‐inextensibility. It is shown that using the mixed finite element improves the convergence behavior for the simulation of soft EAP with relatively stiff fibers. Moreover, the choice of the model that expresses the nature of the underlying coupling is shown to noticeably affect the degree of simulated actuation in fiber reinforced actuators.
A mixed finite element method for the Poisson problem using a biorthogonal system with Raviart–Thomas elements
Authors: Banz Lothar , Ilyas Muhammad , Lamichhane Bishnu P. , McLean William , Stephan Ernst P.
Published: December 2020

We use a three‐field mixed formulation of the Poisson equation to develop a mixed finite element method using Raviart–Thomas elements. We use a locally constructed biorthogonal system for Raviart–Thomas finite elements to improve the computational efficiency of the approach. We analyze the existence, uniqueness and stability of the discrete problem and show an a priori error estimate. We also develop an a posteriori error estimate for our formulation. Numerical results are presented to demonstrate the performance of our approach.
Wärmebrücken im Metallleichtbau – vorgehängte hinterlüftete Fassaden und Falzprofildächer
Authors: Kuhnhenne Markus , Pyschny Dominik , Vontein Marius , Lüdecke Marvin
Published: December 2020

Vorgehängte hinterlüftete Fassaden (VHF) und Falzprofildächer (FPD) aus Metall bilden als leichte Bauweise aufgrund ihrer hohen Rückbau‐ und Recyclingfähigkeit, ihrer bauphysikalischen Eigenschaften sowie ihrer langen Lebensdauer einen Baustein nachhaltiger Gebäudearchitektur. Der prinzipielle Aufbau von VHF und FPD weist analoge thermische Eigenschaften auf. In beiden Bauweisen werden z. B. punktförmige Halter auf einem Verankerungsgrund befestigt, durchdringen dabei die Wärmedämmung und leiten die Lasten der Fassaden‐ oder Dachbekleidungen in den Verankerungsgrund ein. Die Halter bilden dabei Wärmebrücken und erhöhen den flächenbezogenen Wärmedurchgangskoeffizienten der flächigen Fassaden‐ oder Dachkonstruktion. In der Praxis ist der Einfluss der Durchdringungen auf den Wärmedurchgangskoeffizienten bereits in einem frühen Planungsstadium zu berücksichtigen, da insbesondere Wärmedämmdicken nur unter Berücksichtigung der punkt‐ und linienbezogenen Wärmedurchgangskoeffizienten planungssicher festgelegt werden können. Typische Halter unterscheiden sich in ihrer Größe, Geometrie und Materialität und haben so unterschiedlichen Einfluss auf die zu wählende Dämmdicke. Zur effizienteren Umsetzung in der Praxis veröffentlicht der Internationale Verband für den Metallleichtbau (IFBS) im ersten Quartal 2021 eine Neufassung des Wärmebrückenatlas mit wärmetechnischen Untersuchungen zu VHF und FPD im Metallleichtbau. Im vorliegenden Beitrag werden dazu ausgewählte Ergebnisse vorgestellt.
The role of training in student examiner rating performance in a student-led mock OSCE
Authors: Koo Jian Hui , Ong Kim Yao , Yap Yun Ting , Tham Kum Ying
Published: December 2020

Introduction Peer assessments are increasingly prevalent in medical education, including student-led mock Objective Structured Clinical Examinations (OSCE). While there is some evidence to suggest that examiner training may improve OSCE assessments, few students undergo training before becoming examiners. We sought to evaluate an examiner training programme in the setting of a student-led mock OSCE.

Methods A year‑2 mock OSCE comprised of history taking (Hx) and physical examination (PE) stations was conducted involving 35 year‑3 (Y3) student examiners and 21 year‑5 (Y5) student examiners who acted as reference examiners. Twelve Y3 student-examiners attended an OSCE examiner training programme conducted by senior faculty. During the OSCE, Y3 and Y5 student examiners were randomly paired to grade the same candidates and scores were compared. Scores for checklist rating (CR) and global rating (GR) domains were assigned for both Hx and PE stations.

Results There was moderate to excellent correlation between Y3 and Y5 student examiners for both Hx (ICC 0.71–0.96) and PE stations (ICC 0.71–0.88) across all domains. For both Hx and PE stations, GR domain had poorer correlation than CR domains. Examiner training resulted in better correlations for PE but not Hx stations. Effect sizes were lower than the minimum detectible effect (MDE) sizes for all comparisons made.

Discussion Y3 student examiners are effective substitutes for Y5 student examiners in a Y2 mock OSCE. Our findings suggest that examiner training may further improve marking behaviour especially for PE stations.
Interview with Tunde Kelani
Authors: Onikoyi Tunde
Published: December 2020

In this interview with the Nigerian filmmaker, Tunde Kelani, film scholar Tunde Onikoyi explores the universe of Kelani’s cinematic vision, particularly as it relates to Thunderbolt (2002) and Dazzling Mirage (2014). Although produced twelve years apart, what binds them is a common humanitarian narrative temperament. Onikoyi and Kelani discuss his films in broader terms, exploring literary references, Kelani’s interest in health, and how cinema convey his creative tendencies. The interlocutors investigate the effects of “magun,” male chauvinism, and patriarchal idiosyncrasies in contemporary Nigeria. Kelani shares his filmmaking vision, and reflects on the future of Nigerian cinema in framing African story-telling.
A meta-analysis of the association between obesity and COVID-19
Authors: Yang Jiao , Ma ZhiYing , Lei YanChang
Published: December 2020

Owing to limited data, we conducted a meta-analysis to re-evaluate the relationship between obesity and coronavirus-2019 (COVID-19). Literature published between 1 January 2020 and 22 August 2020 was comprehensively analysed, and RevMan3.5 was used for data analysis. A total of 50 studies, including data on 18 260 378 patients, were available. Obesity was associated with a higher risk of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) infection (odds ratio (OR): 1.39, 95% confidence interval (CI) 1.25–1.54; P < 0.00001) and increased severity of COVID-19 (hospitalisation rate: OR: 2.45, 95% CI 1.78–3.39; P < 0.00001; severe cases: OR: 3.74, 95% CI 1.18–11.87; P: 0.02; need for intensive care unit admission: OR: 1.30, 95% CI 1.21–1.40; P < 0.00001; need for invasive mechanical ventilation: OR: 1.59, 95% CI 1.35–1.88; P < 0.00001 and mortality: OR: 1.65, 95% CI 1.21–2.25; P: 0.001). However, we found a non-linear association between BMI and the severity of COVID-19. In conclusion, we found that obesity could increase the risk of SARS-CoV2 infection and aggregate the severity of COVID-19. Further studies are needed to explore the possible mechanisms behind this association.
Tracking Changes in Climate Sensitivity in CNRM Climate Models
Authors: Saint‐Martin D. , Geoffroy O. , Voldoire A. , Cattiaux J. , Brient F. , Chauvin F. , Chevallier M. , Colin J. , Decharme B. , Delire C. , Douville H. , Guérémy J.‐F. , Joetzjer E. , Ribes A. , Roehrig R. , Terray L. , Valcke S.
Published: December 2020

The equilibrium climate sensitivity (ECS) in the latest version of CNRM climate model, CNRM‐CM6‐1, and in its high‐resolution counterpart, CNRM‐CM6‐1‐HR, is significantly larger than in the previous version (CNRM‐CM5.1). The traceability of this climate sensitivity change is investigated using coupled ocean‐atmosphere model climate change simulations. These simulations show that the increase in ECS is the result of changes in the atmospheric component. A particular attention is paid to the method used to decompose the equilibrium temperature response difference, by using a linearized decomposition of the individual radiative agents diagnosed by a radiative kernel technique. The climate sensitivity increase is primarily due to the cloud radiative responses, with a predominant contribution of the tropical longwave response (including both feedback and forcing adjustment) and a significant contribution of the extratropical and tropical shortwave feedback changes. A series of stand‐alone atmosphere experiments is carried out to quantify the contributions of each atmospheric development to this difference between CNRM‐CM5.1 and CNRM‐CM6‐1. The change of the convection scheme appears to play an important role in driving the cloud changes, with a large effect on the tropical longwave cloud feedback change.
A conditional gradient algorithm for distributed online optimization in networks
Authors: Shen Xiuyu , Li Dequan , Fang Runyue , Dong Qiao
Published: December 2020

This paper addresses a network of computing nodes aiming to solve an online convex optimisation problem in a distributed manner, that is, by means of the local estimation and communication, without any central coordinator. An online distributed conditional gradient algorithm based on the conditional gradient is developed, which can effectively tackle the problem of high time complexity of the distributed online optimisation. The proposed algorithm allows the global objective function to be decomposed into the sum of the local objective functions, and nodes collectively minimise the sum of local time‐varying objective functions while the communication pattern among nodes is captured as a connected undirected graph. By adding a regularisation term to the local objective function of each node, the proposed algorithm constructs a new time‐varying objective function. The proposed algorithm also utilises the local linear optimisation oracle to replace the projection operation such that the regret bound of the algorithm can be effectively improved. By introducing the nominal regret and the global regret, the convergence properties of the proposed algorithm are also theoretically analysed. It is shown that, if the objective function of each agent is strongly convex and smooth, these two types of regrets grow sublinearly with the order of , where is the time horizon. Numerical experiments also demonstrate the advantages of the proposed algorithm over existing distributed optimisation algorithms.
Identifying single‐phase to ground fault based on line multi‐dimensional data in cyber‐physical distribution system
Authors: Chen Qing , Yang Shiwu , Li Hongbin , Wen Xue , Wang Xinggang , Bao Zhiwei , Peng Junran
Published: December 2020

Single‐phase to ground fault is the most common line fault in power distribution systems, which may result in an electrical fire and personal safety problems. Particularly, it is more difficult to identify the fault occurring in the system in which the neutral point is grounded via Petersen coil. This paper proposes a new scheme based on line multi‐dimensional data in cyber‐physical distribution system, where line multi‐dimensional data is used to extract the fault characteristics and thus to identify the faulty line. First, the circuit is analyzed and the difference‐like algorithm is used to extract the current signal difference value from the line multi‐dimensional data as the feature quantity. In order to reduce the impact of the measurement error on the result, the authors employ the deep neural networks to process the line multi‐dimensional data, and demonstrate that this method can effectively resist the error interference. A simulation based on a previously studied model has been carried out and the results show the superiority compared to the fifth harmonic identification method. In addition, the test results obtained in the Dynamic Simulation Laboratory of Huazhong University of Science and Technology also demonstrate the practicality of the scheme.
Models of optimization of combination of production of agrarian products and harvesting of wild food resources
Authors: Ivanyo Yaroslav , Petrova Sofia , Barsukova Margarita , Gombo Gantulga
Published: December 2020

The article is devoted to the results of modeling the combination of agricultural production and harvesting of wild food resources. Agricultural enterprise models that are able to expand food production activities through the use of wild plants are proposed. A prerequisite for the application of the developed linear programming models with uncertain parameters is the availability of sufficient reserves of wild food resources located at relatively small distances from the farm. This condition is acceptable for many farms in the Irkutsk region. As optimization problems, linear parametric problems with interval and random estimates are used. With sustainable agriculture, the uncertain values are yield, labor costs and prices for harvesting and selling wild plants. The models used to manage the activities of agricultural producers of the Irkutsk region showed additional opportunities for the development of the regional agro-industrial complex.
Vaccinal prevention of nodular dermatitis in Hereford cattle (clinical and immunological implications)
Authors: Burkov P.V. , Scherbakov P.N. , Slobodyansky S.R.
Published: December 2020

Animal vaccination is the principal method of preventing nodular dermatitis in cattle. Objective: to analyze the impact of using a specific transfer factor in vaccination of Hereford cattle against nodular dermatitis on the development of immunity and indices of animal homeostasis. Application of the transfer factor and the vitamin preparation Asidivit in the vaccination of animals against nodular dermatitis has reduced the reactogenicity of the vaccine in the form of a lower temperature reaction to the medicinal preparation of biological origin. The combined application of the immunoamplifier and Asidivit decreased the negative impact of vaccination on the liver of animals. The greatest quantitative decrease in bilirubin in the blood serum by 14% was observed. It made it possible to achieve a significant increase in antibodies in the blood serum by 72.4% compared to the initial analysis and an increase in the number of antibody-positive animals up to 80%.
Model of creation of productive agrocenosis of Echinacea
Authors: Pospelov Sergey , Zdor Viacheslav , Mishchenko Oleg , Pospelova Anna , Kovalenko Ninel
Published: December 2020

The results of many years of field research on the effect of stocking density of different types of Echinacea spp. on its productivity are discussed. It was found that when the Echinacea purpurea crops were thickened, the collected raw material had a high percentage (more than 50%) of stems, which negatively affected its quality. An increase in the density of Echinacea pallida crops has less effect on the formation of generative shoots. Long-term research has revealed patterns that determine the productivity of Echinacea spp. at different planting densities. This made it possible to calculate and recommend for production the density of plants at which the optimal yield of the agrocenosis will be achieved: for Echinacea purpurea – 100-110 thousand/ha, and for Echinacea pallida – 120-140 thousand/ha.
Biochemical composition of potato tubers of various varieties and the economic efficiency of its cultivation in the conditions of the Middle Urals
Authors: Karpukhin M.Yu. , Keita F.
Published: December 2020

The purpose of the research is to study the effect of the feeding area of Gala potato, the use of fungicides on the yield and quality of tubers in the Middle Urals. This research was carried out on the experimental field of the educational and experimental farm “Uralets” of the Ural State Agrarian University, the village “Studencheskiy”, during 2016-2018, in the climatic zone of the Middle Urals. The feeding area influenced the mineral and biochemical composition of tubers, especially the content of nitrogen, phosphorus, potassium, dry matter, vitamin C and others. The calculation of the economic efficiency of potato showed that during the years of research, the production cost fluctuated within the range of 4446 - 9446 rubles/ton, the profit from 63 724 to 269 172 rubles/ha and the level of profitability in the range of 24.66-165.43%.
Bioindicators and environmental protection
Authors: Khanieva I.M. , Bekuzarova S.A. , Abdulkhalikov R.Z. , Boziev A.L. , Shogenov Yu.M.
Published: December 2020

The plants capable to occlude the maximum quantity of the heavy metals (HM) from soil solution are studied. Plants - indicators of accumulation of heavy metals are allocated, the new directions on decrease in toxicity of the soil are offered. For the purpose of studying of sorption abilities of bean herbs studied accumulation of heavy metals on phases of development of plants. Biological features bean which are capable to occlude heavy metals from the soil and air and by that to clear the polluted site are established. Plants can be the main bioindicators of impurity of soils. For a start in different environments the content of heavy metals by means of a method of chemical analysis control was defined, then compared maximum permissible concentration and drew a conclusion about danger of complex influence to the person and a biota For strengthening of sorption brought tseolitsoderzhashchy clays of Alanit of a local origin at crops of bean herbs. It is revealed that the maximum sorption abilities are found in plants vyazelya motley, and in mix with an amaranth, sowed cherezryadno the maximum effect on decrease in heavy metals on the polluted site is reached. A plant the ambrosia polynnolistny most of all accumulates doses of heavy metals.
Problem of improving information technologies for managing agricultural enterprises in the context of macroeconomic instability and risks
Authors: Stozhko Dmitrii , Ergunova Olga
Published: December 2020

The study provides an assessment of the state and prospects for the development of information management systems (IMS) of agricultural enterprises in the context of modern macroeconomic instability, uncertainty and risks. The features of agricultural production that affect the nature and efficiency of the IMS use are defined. A modern functional approach to IMS assessment in the context of electronic modeling of business processes in the agro-industrial complex is revealed. A convergent feature of the current stage of the IMS development, due to the nature of the current macroeconomic situation, is defined. The role of IMS in the development of risk-oriented management is clarified. The article describes the existing theoretical and methodological approaches to risk morphology, as well as the strengths and weaknesses of centralized and decentralized risk management systems. Special attention is paid to the “modernization” risks that are most closely related to the IMS development.
Deep Levels in GaN
Authors: Narita Tetsuo , Tokuda Yutaka
Published: December 2020

Deep levels in GaN are summarized. E1 and E3 electron traps at the respective energies of around EC − 0.25 eV and EC − 0.6 eV have been commonly observed in n-type GaN layers. H1 hole trap at around EV + 0.9 eV is reported in both n-type and p-type GaN layers, and likely associates the yellow luminescence band in a photoluminescence spectrum. The concentration of Ha hole trap at around EV + 0.3 eV in p-type GaN layers is detected with a nearly equal concentration of H1 hole trap. Based on the comparison with the first-principles calculations using hybrid functionals and the photoluminescence studies, the origins of E3, H1 and Ha traps are most likely attributed to 0/- charged state of iron on Ga site (FeGa), 0/− and +/0 charged states of carbon on nitrogen site (CN), respectively. Among deep levels induced by irradiation, EE1 and EE2 at around EC − 0.12 eV and EC − 1 eV correspond to the calculated energy levels of the nitrogen vacancy (VN) and the interstitial (NI). Finally, deep levels compensating carriers in n-type and p-type GaN layers are extracted.
Combined APT and STEM Analyses
Authors: Kumar Ashutosh , Ohkubo Tadakatsu
Published: December 2020

Atom probe tomography (APT) provides the three-dimensional imaging of materials and their compositional information at atomic-scale resolution. However, various factors such as the limited volume and/or the imperfect detection efficiency sometimes make it difficult to fully understand a material only by APT. The combination of APT with scanning transmission electron microscopy (STEM) in GaN-based systems allows more reliable information of complex problems such as magnesium (Mg) segregations in extended defects or indium (In) fluctuations in multiple quantum wells. The combined analyses have revealed that Mg atoms in GaN are likely to be segregated in polarity inversion domains formed through post-implantation annealing. This combinational approach also provided a direct evidence of Mg atoms diffusing along threading dislocations in the p-n junction of GaN; such information is useful to understand the mechanism of leakage current in the junction. Combined use of APT and STEM also revealed the existence of In clusters and compositional fluctuations in InGaN/GaN multiple quantum wells, which can be used to understand carrier localization in these system. This chapter reviews the remarkable achievements obtained via combined APT and STEM analyses in GaN based materials and devices, and discusses the future outlook.
Refinement of the German Day-to-Day Impact of Vaginal Aging questionnaire in perimenopausal and postmenopausal women using item response theory and classical test theory
Authors: Gabes Michaela , Stute Petra , Apfelbacher Christian J.
Published: December 2020

Objective:

We aimed to assess the structural validity of the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire using item response theory/Rasch analysis and classical test theory and refine the current version of the DIVA if necessary.

Methods:

Postmenopausal women reporting vaginal symptoms related to menopause participated in the study. Item characteristic curves were analyzed to see whether the response categories were functioning optimally. The assumptions of the Rasch model were tested for the whole DIVA as well as for each domain separately. Exploratory factor analyses were carried out and correlations of the single items with the DIVA domains were analyzed to identify the most-fitting items. Finally, validation analyses were carried out on the refined version.

Results:

We registered 185 eligible postmenopausal women. Revising the response categories of each of the four domains led to adequate looking item characteristic curves. The whole DIVA represented a multidimensional construct, however, each of the four domains fulfilled the Rasch requirements of unidimensionality, local independence, monotonicity, and an adequate model fit. Integrating item response theory/Rasch and classical test theory, two items (item 5 and item 17) showing relevant issues were identified and removed from the refined version. In the subsequent validation, the refined DIVA showed similar validation results like its original equivalent.

Conclusions:

We created a validated refined version of the DIVA, having now three response categories instead of five. With 17 items (short-version) or rather 21 items (long-version for women with recent sexual activity), the refined DIVA is more feasible and showed several excellent measurement properties.
Association of waist-to-height ratio with estimated glomerular filtration rate in middle-aged and elderly Chinese
Authors: Tian Lu , Zheng Han , Li Yanzhi , Jia Chongqi
Published: December 2020

Objective:

This study aimed to assess the relationship between waist-to-height (WHtR) and estimated glomerular filtration rate (eGFR) in men, non-menopausal, and postmenopausal women among middle-aged and elderly Chinese.

Methods:

This study analyzed the data of 7,807 participants in a cross-sectional survey, ie, the third wave of the China Health and Retirement Longitudinal Study. Restrictive cubic-spline regression with three knots was used to assess the dose–response association of WHtR with eGFR. Piecewise linear regression models were further established to calculate the slope of each segment and their 95% confidence interval (CI).

Results:

After adjusting for potential confounders, an inverse L-shaped dose–response relationship was found between WHtR and eGFR among men (P
nonlinear = 0.024, threshold = 0.513) and postmenopausal women (P
nonlinear = 0.009, threshold = 0.503). The slopes on the right sides of the threshold were statistically significant among men (β

2
 = −33.77, 95% CI: −53.23 to −14.31) and postmenopausal women (β

2
 = −36.53, 95% CI: −49.71 to −23.35), respectively. A weak negative linear relationship existed between WHtR and eGFR in non-menopausal women.

Conclusions:

The relationship between WHtR and eGFR tended to be inverse-L-shaped in men and postmenopausal women, but may vary with postmenopausal status in women.
The Physiological Impact of Masking Is Insignificant and Should Not Preclude Routine Use During Daily Activities, Exercise, and Rehabilitation
Authors: Haraf Rebecca H. , Faghy Mark A. , Carlin Brian , Josephson Richard A.
Published: December 2020

Purpose:

Masking has been employed as a strategy for reducing transmission of a variety of communicable diseases. With the outbreak of SARS-CoV-2, many countries have implemented mandatory public masking. However, the perceived impact of mask use on pulmonary function has been a deterrent to public compliance with recommendations. COVID-19 has shed light on the impact that comorbid cardiac and pulmonary conditions may have on disease severity. This knowledge has led to increased primary and secondary prevention efforts for which exercise and rehabilitation are central. The importance of safe methods of exercise while mitigating risk of viral transmission is paramount to global recovery from the pandemic and prevention of future outbreaks.

Methods:

We constructed a focused literature review of the impact of various masks on pulmonary function at rest and with exercise. This was then incorporated into recommendations for the integration of masks with exercise and rehabilitation in the COVID-19 era.

Results:

While there is a paucity of evidence, we identified the physiological effects of masking at rest and during exercise to be negligible. The perceived impact appears to be far greater than the measured impact, and increased frequency of mask use leads to a physiological and psychological adaptive response.

Conclusions:

Masking during daily activities, exercise, and rehabilitation is safe in both healthy individuals and those with underlying cardiopulmonary disease. Rehabilitation participants should be reassured that the benefits of masking during COVID-19 far outweigh the risks, and increased frequency of mask use invokes adaptive responses that make long-term masking tolerable.
Price Differences Between Otic and Ophthalmic Drops
Authors: Valentini Chris , Lin Jiahui , Golub Justin S. , Lustig Lawrence
Published: December 2020

Objective:

Otic drops are one of the most frequently prescribed medications in otolaryngology. However, some forms of these drops can be very expensive, and ophthalmic formulations are sometimes used by practitioners to decrease the cost for their patients. The goal of this study is to determine the cost differential between otic and ophthalmic drops.

Methods:

Pharmacies in New York City, Chicago, and Portland were surveyed in the span of 6 weeks by telephone to evaluate the current prices of various otic and ophthalmic drops commonly prescribed by otolaryngologists.

Results:

A total of 83 pharmacies were surveyed. Surveyed drugs included ciprofloxacin/dexamethasone (cip/dex) otic, neomycin/polymyxin B sulfates/hydrocortisone (neo/poly/HC) otic, acetic acid (AA) otic, acetic acid/hydrocortisone (AA/HC) otic, ofloxacin otic, ofloxacin ophthalmic, and tobramycin/dexamethasone (tob/dex) ophthalmic. Per milliliter, cip/dex otic was consistently the most expensive, with a median price of $38.00 per milliliter. Among the antibiotic drops, neo/poly/HC otic was the least expensive formulation with a median price of $11.60 per milliliter. Ofloxacin ophthalmic was significantly less expensive than the otic formulation, at $11.00 and $31.00 per milliliter, respectively (adjusted p < 0.001). In general, otic and ophthalmic formulations were not significantly different according to manufacturing information, although ophthalmic drops were more often packaged in a sterile fashion and with less abrasive ingredients for use in the more sensitive tissue of the eye.

Conclusion:

Significant and meaningful price differences exist between otic and ophthalmic drops. Given the safety of ophthalmic drops used in the ears, they may be a more cost-effective alternative to traditionally prescribed otic drops when clinically appropriate.
Effects of Presentation Level on Spatial Hearing With and Without Bone-Conduction Amplification in Congenital Unilateral Aural Atresia
Authors: Canfarotta Michael W. , Kane Stacey L.G. , Buss Emily
Published: December 2020

Objective:

This study assessed the effect of ipsilateral bone-conduction amplification on spatial hearing abilities in subjects with congenital unilateral aural atresia (CUAA).

Patients:

Twelve patients with unilateral conductive hearing loss secondary to CUAA and normal hearing in the contralateral ear were tested. Most (75%) had limited experience with a bone-conduction hearing aid (BCHA).

Intervention:

Performance was evaluated with and without a BCHA fitted acutely on a softband.

Main Outcome Measures:

Spatial hearing abilities were evaluated in two paradigms. Spatial release from masking was evaluated by comparing masked sentence recognition with a target and two speech maskers either colocated at 0 degree or with the maskers separated at +90 degrees and −90 degrees. Sound source localization was evaluated in a 180 degrees arc of loudspeakers on the horizontal plane. Performance was evaluated at 50 and 75 dB SPL, and results were compared for patients tested with and without a BCHA.

Results:

Group level results indicate similar spatial release from masking in the aided and unaided conditions at both presentation levels. Localization at 50 dB SPL was similar aided and unaided, but at 75 dB SPL the root mean square error was lower unaided than aided (17.2 degrees vs 41.3 degrees; p = 0.010).

Conclusions:

Use of a BCHA in patients with CUAA may interfere with auditory cues required for sound source localization when the signal level is intense enough to overcome the patient's conductive hearing loss. These findings have potential clinical implications in fitting of BCHAs to support optimal spatial hearing in patients with CUAA.
What’s in a diagnosis? A genetic decomposition of major depression
Authors: Jermy Bradley S , Glanville Kylie P , Coleman Jonathan RI , Lewis Cathryn M , Vassos Evangelos
Published: December 2020

Determining a diagnosis of major depressive disorder (MDD) is complex, involving consideration and rating of a variety of different components. These include number of symptoms over an agreed threshold, symptom duration, functional impairment, persistence of symptoms within an episode, and symptom recurrence. While these components are generally accepted amongst physicians, it is unknown whether they reflect partly distinct biology between phenotypes. The aim of this study was to investigate how the genetic aetiology varies in the presence of different MDD components.

Thirty-two depression phenotypes which systematically incorporate the MDD components were created using the mental health questionnaire data within the UK Biobank. SNP-based heritabilities and genetic correlations with three previously defined major depression phenotypes were calculated (broad depression, Psychiatric Genomics Consortium (PGC) defined depression and 23andMe, Inc. self-reported depression) and differences between estimates analysed.

All phenotypes were heritable (h2SNPrange: 0.102 – 0.162) and showed substantial genetic correlations with other major depression phenotypes (Rg range: 0.651 – 0.894 (PGC); 0.652 – 0.837 (23andMe); 0.699 – 0.900 (broad depression)). The requirement for 5 or more symptoms and for a long episode duration had the strongest effect on SNP-based heritability, in the positive and negative direction respectively (1.4% average increase; 2.7% average decrease). No significant differences were noted between genetic correlations.

While there is some variation, the two cardinal symptoms, depressed mood and anhedonia, largely reflect the genetic aetiology of phenotypes incorporating more MDD components. These components may appropriately index for severity, however, the genetic component between phenotypes incorporating none and all components is comparable.
Covid Fast Fax: A system for real-time triage of Covid-19 case report faxes
Authors: Lavertu Adam , Stribling Alison , White Matt , McInnes Greg , Altman Russ B. , Pramanik Rajiv , Kaushal Amit
Published: December 2020

The scale and speed of the COVID-19 pandemic has strained many parts of the national healthcare infrastructure, including communicable disease monitoring and prevention. Many local health departments now receive hundreds or thousands of COVID-19 case reports a day. Many arrive via faxed handwritten forms, often intermingled with other faxes sent to a general fax line, making it difficult to rapidly identify the highest priority cases for outreach and monitoring. We present an AI-based system capable of real-time identification and triage of handwritten faxed COVID-19 forms. The system relies on two models: one model to identify which received pages correspond to case report forms, and a second model to extract information from the set of identified case reports. We evaluated the system on a set of 1,224 faxes received by a local health department over a two-week period. For the 88% of faxes of sufficient quality, the system detects COVID-19 reports with high precision, 0.98, and high recall, 0.91. Among all received COVID-19 faxes, the system identifies high priority cases with a specificity of 0.87, a precision of 0.46 and recall of 0.83. Our system can be adapted to new forms, after a brief training period. Covid Fast Fax can support local health departments in their efforts to control the spread of COVID-19 and limit its impact on the community. The tool is freely available.
Functional genomics atlas of synovial fibroblasts defining rheumatoid arthritis heritability
Authors: Ge Xiangyu , Frank-Bertoncelj Mojca , Klein Kerstin , Mcgovern Amanda , Kuret Tadeja , Houtman Miranda , Burja Blaž , Micheroli Raphael , Marks Miriam , Filer Andrew , Buckley Christopher D. , Orozco Gisela , Distler Oliver , Morris Andrew P , Martin Paul , Eyre Stephen , Ospelt Caroline
Published: December 2020

Genome-wide association studies have reported >100 risk loci for rheumatoid arthritis (RA). These loci have been shown to be enriched in immune cell-specific enhancers, but analysis so far has excluded stromal cells, such as synovial fibroblasts (FLS), despite their crucial involvement in the pathogenesis of RA. Here we integrated DNA architecture (ChIP-seq), 3D chromatin interactions (HiC, capture HiC), DNA accessibility (ATAC-seq) and gene expression (RNA-seq) in FLS, B cells and T cells with genetic fine mapping of RA loci. We identified putative causal variants, enhancers, genes, and cell types for 30 - 60% of RA loci and demonstrated that FLS account for up to 24% of RA heritability. TNF stimulation of FLS altered the organization of topologically associating domains (TADs), chromatin state and the expression of putative causal genes (e.g.TNFAIP3, IFNAR1). Several putative causal genes constituted RA-relevant functional networks in FLS with roles in cellular proliferation and activation. Finally, we demonstrated that risk variants can have joint-specific effects on target gene expression in RA FLS, which may contribute to the development of the characteristic pattern of joint involvement in RA. Overall, our research provides the first direct evidence for a causal role of FLS in the genetic susceptibility for RA accounting for up to a quarter of RA heritability.
Etiological Group Analysis of Cytokine Response To Influenza-Like Illnesses
Authors: Plotnikova Marina A. , Klotchenko Sergey A. , Lozhkov Alexey A. , Lebedev Kirill I , Taraskin Alexander S. , Baranovskaya Irina L. , Egorova Maria A , Ramsay Edward S. , Vasin Andrey V.
Published: December 2020

Respiratory infections, collectively, are one of the world’s most common and serious illness groups. As recent observations have shown, the most severe courses of acute respiratory infection, often leading to death, are due to uncontrolled cytokine production (hypercytokinemia). The research presented is devoted to assessment of mRNA expression of specific cytokines (IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-λ) and MxA in whole blood leukocytes, by means of real-time PCR. This study involved 364 patients with respiratory illness being treated in clinics in St. Petersburg (Russia) in 2018-2019 and 30 healthy subjects. In 70% of patients, bacterial or viral pathogens were identified, with influenza viral infections (types A, B) prevailing. Cytokine analysis was carried out in the acute phase of illness (2-3 days from onset of initial symptoms) and in the stage of recovery (days 9-10). Significant increases in the expression of IL-18, TNF, and IL-10 were observed, relative to controls, only with influenza viral infections. We have shown a difference in IL-6 mRNA expression in patients with bacterial or viral pathogens. No significant difference was found in WBC IL-4 expression levels between patients and healthy subjects. Investigation of the nuances of systemic cytokine production, in response to specific viral and bacterial pathogens, makes it possible to: assess the risks of developing hypercytokinemia during respiratory infection with agents circulating in the human population; and to predict the pathogenicity and virulence of circulating threats.
Cerebrospinal fluid Aβ42 and fractalkine are associated with Parkinson’s disease with freezing of gait
Authors: Hatcher-Martin J. M. , McKay J.L. , Sommerfeld B. , Howell J.C. , Goldstein F. C. , Hu W.T. , Factor S.A.
Published: December 2020

Objective

To evaluate the association of Alzheimer’s disease-related and inflammation-related cerebrospinal fluid (CSF) markers with freezing of gait (FOG) in patients with Parkinson’s disease (PD).

Method

The study population included well-characterized PD patients with FOG (PD-FOG), without FOG (PD-NoFOG) and healthy controls (HC). CSF was collected using standard protocols. Three Alzheimer’s disease-related markers and 10 inflammation-related markers were measured in a Luminex 200 platform. Differences in marker expression across groups were evaluated with multivariate linear models.

Results

CSF was collected from PD-FOG (N=12), PD-NoFOG (N=20) and HC (N=11) for analysis. Age was not significantly different between the three groups. Duration of PD was not significantly different between the two PD groups. After adjusting for covariates and multiple comparisons, the anti-inflammatory marker, fractalkine, was significantly decreased in the PD groups compared to HC (P=0.022), and further decreased in PD-FOG compared to PD-NoFOG or HC (P=0.032). The Alzheimer’s disease-related protein, Aβ42, was increased in PD-FOG compared to PD-NoFOG or HC (P=0.004). p-Tau181 was also decreased in both PD groups compared to HC (P=0.010).

Conclusions

We found high levels of Aβ42 in PD-FOG patients and cross-sectional data which supports an increase over time from early to advanced state. We also found low levels of fractalkine which might suggest anti-inflammatory effect. This is the first time an association between fractalkine and FOG has been shown. Whether these changes are specific to FOG requires further exploration.
DNA demethylation switches the drivers of Foxp3 expression to maintain regulatory T cell identity
Authors: Li Jun , Xu Beisi , Zong Xinying , He Minghong , Fan Yiping , Cross Richard , Hanna Jacob H. , Feng Yongqiang
Published: December 2020

Maintenance of differentiated cellular states is crucial for numerous biological processes, yet its molecular basis remains unclear. Here, we investigate how mechanistically regulatory T (Treg) cell fate is “locked in” during lineage commitment via transcriptional regulation of its lineage-specifying factor Foxp3. Tet-mediated DNA demethylation ofFoxp3enhancer CNS2 was proposed to be a key mechanism maintaining Foxp3 transcription. However, this model has not been directly tested. Therefore, we integrated genetic, pharmacological, and epigenetic approaches to examine the function and mechanism of DNA demethylation in Treglineage maintenance. We observed an abrupt switch of the transcriptional drivers of Foxp3 upon DNA demethylation, which was abolished by CNS2 deficiency. Demethylation of CNS2 increased chromatin accessibility and protein binding, conferring on Tregfate substantial resistance to adverse environments. Thus, our study consolidated the role of DNA demethylation in stabilizing Foxp3 expression incisand revealed a novel regulatory mode governing Tregidentity.
Master Transcription Factors Regulate the DNA Methylation Landscape During Hepatocyte Differentiation
Authors: Suzuki Takahiro , Furuhata Erina , Maeda Shiori , Kishima Mami , Miyajima Yurina , Tanaka Yuki , Lim Joanne , Nishimura Hajime , Nakanish Yuri , Shojima Aiko , Suzuki Harukazu
Published: December 2020

Background

Hepatocytes are the dominant cell type of the human liver, with functions in metabolism, detoxification, and in producing secreted proteins. During the process of hepatocyte differentiation, gene regulation and master transcription factors have been extensively investigated, whereas little is known about how the epigenome is regulated, particularly the dynamics of DNA methylation, and the upstream factors that have critical roles.

Results

By examining changes in the transcriptome and the methylome duringin vitrohepatocyte differentiation, we identified putative DNA methylation-regulating transcription factors, which are likely involved in DNA demethylation and maintenance of hypo-methylation in a differentiation stage-specific manner. Of these factors, we further reveal that GATA6 induces DNA demethylation together with chromatin activation at a binding-site-specific manner during endoderm differentiation.

Conclusions

These results provide an insight into the spatiotemporal regulatory mechanisms exerted on the DNA methylation landscape by transcription factors, and uncover a new role for transcription factors in early liver development.
Maximum Antigen Diversification in a Lyme Bacterial Population and Evolutionary Strategies to Overcome Pathogen Diversity
Authors: Di Lia , Akther Saymon , Bezrucenkovas Edgaras , Ivanova Larisa , Sulkow Brian , Wu Bing , Gomes-Solecki Maria , Qiu Wei-Gang
Published: December 2020

Natural populations of microbes and their hosts are engaged in an arms race in which microbes diversify to escape host immunity while hosts evolve novel immunity. This co-evolutionary process, known as the “Red Queen” hypothesis, poses a fundamental challenge to the development of broadly effective vaccines and diagnostics against a diversifying pathogen. Based on surveys of natural allele frequencies and experimental immunization of mice, we show minimal antigenic cross-reactivity among natural variants of the outer surface protein C (OspC), a dominant antigen of a Lyme Disease-causing bacterium (Borrelia burgdorferi). To overcome the challenge of OspC antigenic diversity to clinical development of preventive measures, we implemented a number of evolution-based strategies to broaden OspC immunological cross-reactivity. In particular, the centroid algorithm – a genetic algorithm to minimize sequence differences with natural variants – generated synthetic OspC analogs with the greatest promise as diagnostic and vaccine candidates against diverse Lyme pathogen strains coexisting in the Northeast United States. Mechanistically, we propose a model of runaway maximum antigen di-versification (MAD) mediated by amino-acid variations distributed across hypervariable regions on the OspC molecule. Under the MAD model, evolutionary centroids display high cross-reactivity by occupying the central void in the antigenic space excavated by diversifying natural variants. In contrast to the vaccine design based on concatenated epitopes, the centroid algorithm generates analogs of native antigens and is automated. The MAD model and evolution-inspired antigen designs have broad implications for combating diversifying pathogens driven by pathogen-host coevolution.

Importance

Microbial pathogens rely on molecular diversity of cell surface antigens to escape host immunity. Vaccines based on one antigen variant often fail to protect the host against pathogens carrying other variants. Here we show evolution-based designs of synthetic antigens that are broadly reactive to all natural variants. The evolutionary analogs of a major surface antigen of a Lyme disease bacterium (Borrelia burgdorferi) showed promise as vaccine candidates against diverse pathogen strains coexisting in the endemic areas of Lyme disease in Northeast United States. Our evolution-based computational design is automated, generates molecular analogs of natural antigens, and opens a novel path to combating fast-evolving microbial pathogens.
CRISPR-cas13 enzymology rapidly detects SARS-CoV-2 fragments in a clinical setting
Authors: Khan Wahab A. , Barney Rachael E. , Tsongalis Gregory J.
Published: December 2020

The well-recognized genome editing ability of the CRISPR-Cas system has triggered significant advances in CRISPR diagnostics. This has prompted an interest in developing new biosensing applications for nucleic acid detection. Recently, such applications have been engineered for detection of SARS-CoV-2. Increased demand for testing and consumables of RT-qPCR assays has led to the use of alternate testing options in some cases. Here we evaluate the accuracy and performance of a novel fluorescence based assay that received EUA authorization from the FDA for detecting SARS-CoV-2 in clinical samples. The Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK) technology forms the basis of the Sherlock CRISPR SARS-CoV-2 kit using the CRISPR-Cas13a system. Our experimental strategy included selection of COVID-19 patient samples from previously validated RT-qPCR assays. Positive samples were selected based on a broad range of cycle thresholds. A total of 50 COVID-19 patient samples were correctly diagnosed with 100% accuracy (relative fluorescence ratios: N gene 95% CI 23.2-36.3, ORF1ab gene 95% CI 27.6-45.4). All controls, including RNase P, showed expected findings. Overall ratios were robustly distinct between positive and negative cases relative to the pre-established 5-fold change in fluorescence read output. We have evaluated the accuracy of detecting conserved targets of SARS-CoV-2 across a range of viral loads using the SHERLOCK CRISPR collateral detection reaction in a clinical setting. These findings demonstrate encouraging results, especially at a time when COVID-19 clinical diagnosis is in high demand; often with limited resources. This approach highlights new thinking in infectious disease identification and can be expanded to measure nucleic acids in other clinical isolates.