bluuebunny/crossref_metadata_2025 huggingface dataset:
Dielectric breakdown in epitaxial BaTiO3 thin films
Authors: Wu HsinWei , Ponath Patrick , Lin Edward L. , Wallace Robert M. , Young Chadwin , Ekerdt John G. , Demkov Alexander A. , McCartney Martha R. , Smith David J.
Published: July 2020

In this work, thin epitaxial layers of dielectric barium titanate (BaTiO3 or BTO) were grown on Nb-doped strontium titanate (001) substrates using either molecular beam epitaxy or atomic layer deposition and then electrically stressed to the point of breakdown. The BTO layer thicknesses were in the range of 20–60 nm, and typical breakdown fields were in the range of 1.5–3.0 MV/cm. Electron microscopy and electron energy-loss spectroscopy (EELS) were used to provide information about the degradation mechanism. High-resolution imaging revealed widespread structural damage in the BTO films after breakdown had occurred, with substantial polycrystallinity as well as amorphous regions. EELS analysis of the stressed films showed characteristic signatures of valence change in the Ti L23 EELS spectra associated with the accumulation of oxygen vacancies. Stressed heterostructures that had been patterned by electron lithography showed similar trends, including degraded crystallinity as well as oxygen loss.
Indirect Markers of Muscle Damage Throughout the Menstrual Cycle
Authors: Romero-Parra Nuria , Alfaro-Magallanes Victor Manuel , Rael Beatriz , Cupeiro Rocío , Rojo-Tirado Miguel A. , Benito Pedro J. , Peinado Ana B. , _ _
Published: July 2020

Context: The indirect markers of muscle damage have been previously studied in females. However, inconclusive results have been found, possibly explained by the heterogeneity regarding monitoring and verification of menstrual-cycle phase. Purpose: To determine whether the fluctuations in sex hormones during the menstrual cycle influence muscle damage. Methods: A total of 19 well-trained eumenorrheic women (age 28.6 [5.9] y; height 163.4 [6.1] cm; weight 59.6 [5.8] kg body mass) performed an eccentric-based resistance protocol consisting of 10 × 10 back squats at 60% of their 1-repetition maximum on the early follicular phase (EFP), late follicular phase, and midluteal phase of the menstrual cycle. Range of motion, muscle soreness, countermovement jump, and limb circumferences were evaluated prior to 24 and 48 hours postexercise. Perceived exertion was evaluated after each set. Results: Differences in sex hormones indicated that tests were adequately performed in the different menstrual-cycle phases. Prior to exercise, muscle soreness was higher in the EFP (4.7 [7.7]) than in the late follicular phase (1.1 [3.2]; P = .045). No other variables showed significant differences between phases. Time-point differences (baseline, 24, and 48 h) were observed in knee range of motion (P = .02), muscle soreness, countermovement jump, and between sets for perceived exertion (P < .001). Conclusion: Although the protocol elicited muscle damage, hormonal fluctuations over the menstrual cycle did not seem to affect indirect markers of muscle damage, except for perceived muscle soreness. Muscle soreness was perceived to be more severe before exercise performed in EFP, when estrogen concentrations are relatively low. This may impair women’s predisposition to perform strenuous exercise during EFP.
Quantifying Segmental Contributions to Center-of-Mass Motion During Dynamic Continuous Support Surface Perturbations Using Simplified Estimation Models
Authors: Schinkel-Ivy Alison , Komisar Vicki , Duncan Carolyn A.
Published: July 2020

Investigating balance reactions following continuous, multidirectional, support surface perturbations is essential for improving our understanding of balance control in moving environments. Segmental motions are often incorporated into rapid balance reactions following external perturbations to balance, although the effects of these motions during complex, continuous perturbations have not been assessed. This study aimed to quantify the contributions of body segments (ie, trunk, head, upper extremity, and lower extremity) to the control of center-of-mass (COM) movement during continuous, multidirectional, support surface perturbations. Three-dimensional, whole-body kinematics were captured while 10 participants experienced 5 minutes of perturbations. Anteroposterior, mediolateral, and vertical COM position and velocity were calculated using a full-body model and 7 models with reduced numbers of segments, which were compared with the full-body model. With removal of body segments, errors relative to the full-body model increased, while relationship strength decreased. The inclusion of body segments appeared to affect COM measures, particularly COM velocity. Findings suggest that the body segments may provide a means of improving the control of COM motion, primarily its velocity, during continuous, multidirectional perturbations, and constitute a step toward improving our understanding of how the limbs contribute to balance control in moving environments.
Direct Comparison of SARS-CoV-2 Analytical Limits of Detection across Seven Molecular Assays
Authors: Fung Becky , Gopez Allan , Servellita Venice , Arevalo Shaun , Ho Coral , Deucher Anne , Thornborrow Ed , Chiu Charles , Miller Steve
Published: July 2020

Analytical sensitivity for SARS-CoV-2 detection is a key performance metric for the evaluation of viral detection assays. We determined analytical limits of detection for seven SARS-CoV-2 assays using serial dilutions of pooled patient material quantified with droplet digital PCR. Limits of detection ranged from ≤10 to 74 copies/ml for commercial high-throughput laboratory analyzers (Roche Cobas, Abbott m2000, and Hologic Panther Fusion) and 167 to 511 copies/ml for sample-to-answer (DiaSorin Simplexa, GenMark ePlex) and point-of-care instruments (Abbott ID NOW).
An Optimized Reverse Genetics System Suitable for Efficient Recovery of Simian, Human, and Murine-Like Rotaviruses
Authors: Sánchez-Tacuba Liliana , Feng Ningguo , Meade Nathan J. , Mellits Kenneth H. , Jaïs Philippe H. , Yasukawa Linda L. , Resch Theresa K. , Jiang Baoming , López Susana , Ding Siyuan , Greenberg Harry B.
Published: July 2020

Group A rotavirus (RV) remains as the single most important cause of severe acute gastroenteritis among infants and young children worldwide. An entirely plasmid-based reverse genetics (RG) system was recently developed, opening new ways for in-depth molecular study of RV. Despite several improvements to further optimize the RG efficiency, it has been reported that current strategies do not enable the rescue of all cultivatable RV strains. Here, we described a helpful modification to the current strategies and established a tractable RG system for the rescue of the simian RRV strain, the human CDC-9 strain, and a murine-like RV strain, which is suitable for both
in vitro
and
in vivo
studies. This improved RV reverse genetics system will facilitate study of RV biology in both
in vitro
and
in vivo
systems that will facilitate the improved design of RV vaccines, better antiviral therapies, and expression vectors.
eIF2B as a Target for Viral Evasion of PKR-Mediated Translation Inhibition
Authors: Wuerth Jennifer Deborah , Habjan Matthias , Kainulainen Markus , Berisha Besim , Bertheloot Damien , Superti-Furga Giulio , Pichlmair Andreas , Weber Friedemann
Published: July 2020

RNA-activated protein kinase (PKR) is one of the most powerful antiviral defense factors of the mammalian host. PKR acts by phosphorylating mRNA translation initiation factor eIF2α, thereby converting it from a cofactor to an inhibitor of mRNA translation that strongly binds to initiation factor eIF2B. To sustain synthesis of their proteins, viruses are known to counteract this on the level of PKR or eIF2α or by circumventing initiation factor-dependent translation altogether. Here, we report a different PKR escape strategy executed by sandfly fever Sicilian virus (SFSV), a member of the increasingly important group of phleboviruses. We found that the nonstructural protein NSs of SFSV binds to eIF2B and protects it from inactivation by PKR-generated phospho-eIF2α. Protein synthesis is hence maintained and the virus can replicate despite ongoing full-fledged PKR signaling in the infected cells. Thus, SFSV has evolved a unique strategy to escape the powerful antiviral PKR.
Feasibility of computer-generated telephonic message-based follow-up system among healthcare workers with diabetes: a randomized controlled trial
Authors: Sadanshiv Mahima , Jeyaseelan Lakshmanan , Kirupakaran Henry , Sonwani Vikas , Sudarsanam Thambu David
Published: July 2020

Introduction

To assess the feasibility of computer-generated educational messaging system in healthcare workers of a tertiary care hospital. The secondary objectives were glycemic control, patient satisfaction and adherence to lifestyle modifications.

Research design and methods

Single-center parallel-group open-labeled randomized controlled trial with computer generated block randomization.

Setting

Healthcare workers with diabetes working in Christian Medical College Vellore, Tamil Nadu.

Participants

431 assessed, 341 met the selection criteria, 320 participants were randomized and 161 were taken into intervention arm and 159 in the control arm.

Intervention

Computer-generated short message service (SMS) based on transtheoretical model of behavioral change, 2 messages per week for 3 months, along with standard of care diabetic care. Messages had educational material regarding healthy eating habits and exercise and these messages were sent twice weekly. The messages were scheduled via an automatic calendar in a way that each subject in the intervention arm received 15 educational messages per month.

Control group received only standard of care diabetic care which included dietary advice, exercise regimen and diabetic medications under supervision of their physician every 3 months.

Follow-up

6 months.

Results

95.65% of people in the intervention arm (n=154) received regular messages, out of which 93.17% read the messages regularly. 80.12% acted on the messages. 93.17% felt more satisfied with their healthcare.

While both groups showed improvement in body mass index (BMI) and hemoglobin A1c (HbA1c), the difference was greater in the intervention with regard to both decrease in BMI (−0.6, p<0.001) and HBA1c (−0.48, p<0.001).

Conclusions

SMS-based education system is feasible in improving healthcare among healthcare workers with diabetes. It improves patient satisfaction, adherence and improves healthcare among individuals with diabetes by decreasing their BMI and decreasing HbA1c.
Development of a physiotherapy-led atraumatic back pain pathway: a novel initiative to improve the management of complex back pain in the emergency village
Authors: Angus Michelle Louise , Martin Bruce , Dickens Victoria , Mohammad Saeed , Siddique Irfan
Published: July 2020

Objectives

To see if consultant physiotherapists could effectively manage spinal patients within the emergency village of a tertiary spinal referral centre.

Design

A change was made to the traditional medical model for managing patients presenting to the emergency department with low back pain that could not be managed within the national 4-hour standard.

Participants

A convenience sample of patients presenting to the emergency department of a tertiary spinal surgical centre who are unable to be managed in a timely manner by the clinicians in the emergency department.

Intervention

Consultant physiotherapists took on autonomous ownership of this group of patients, including clinical assessment, management and appropriate follow-up often without the need for medical input.

Outcomes

The new model showed a reduction in the number of admissions, a significant reduction in length of stay and an improvement in overall staff and patient satisfaction along with a reduction in patients returning to the emergency department.

Conclusions

Consultant physiotherapists are in an ideal position to manage this cohort of patients autonomously in the emergency village allowing medics to be released to manage other patient groups.
Preliminary design and testing of neck chamber device for baroreflex sensitivity assessment
Authors: Paliwal Pratik V , Kamble Prathamesh H , Desai K A , Sharma Rajesh , Singhal Anish
Published: July 2020

This paper presents the design, development and testing of a novel neck chamber device for non-invasive stimulation of an individual carotid baroreceptor in a graded manner. The proposed neck chamber device is a strap-free design that avoids discomfort during testing due to tight seal generated by the neck collar design, and facilitates unilateral testing and targeted assessment without stimulating other neck baroreceptors. The device consists of two independent components to achieve these requirements: an outer suction mechanism and an inner chamber. The outer mechanism consists of multiple suction cups to grip the device over the human neck, while the inner chamber creates controlled positive and negative pressure for stimulation of baroreceptors using a pump. The indigenously developed device was employed for the testing by providing neck chamber stimulation in discrete steps of –20 mm Hg, –40 mm Hg, −60 mm Hg, 0 mm Hg, 20 mm Hg, 40 mm Hg and 60 mm Hg with the gap of 60 s between each stimulation as per the standard test protocol of autonomic function test. The changes in heart rate and RR interval were recorded to determine the baroreceptor gain using the logistic equation derivative and gain curve plot. The results of the present study show that the estimated baroreceptor gain is –0.109±0.04, which is consistent with the previous studies conducted using neck collar devices. The testing results showed that the desired objectives are achieved successfully by the prototype device, opening up the possibility of its use for the treatment of resistant hypertension.
Tales of a department: how the COVID-19 pandemic transformed Detroit’s Henry Ford Hospital, Department of Neurology—part I: the surge
Authors: Ramadan Ahmad Riad , Alsrouji Owais K , Cerghet Mirela , Chopp Michael , Danoun Omar , Grover Kavita M , Ismail Mohammed , Katramados Angelos M , Mohamed Ghada A , Mehta Chandan B , Newman Daniel S , Osman Gamaleldin , Reuther Jackie , Sallowm Yamin , Zaman Iram F , Barkley Gregory L
Published: July 2020

The COVID-19 pandemic has reshaped the way healthcare systems operate around the world. The major hurdles faced have been availability of personal protective equipment, intensive care unit beds, ventilators, treatments and medical personnel. Detroit, Michigan has been an epidemic ‘hotspot’ in the USA with Wayne County among the hardest hit counties in the nation. The Department of Neurology at Henry Ford Hospital, in the heart of Detroit, has responded effectively to the pandemic by altering many aspects of its operations. The rapid engagement of the department and enhanced utilisation of teleneurology were two of the pivotal elements in the successful response to the pandemic. In this review, we describe the transformation our department has undergone, as it relates to its infrastructure redesigning, coverage restructuring, redeployment strategies, medical education adaptations and novel research initiatives.
Barriers and facilitators to neonatal health and care-seeking behaviours in rural Cambodia: a qualitative study
Authors: Watson Gabriella , Patel Kaajal , Leng Daly , Vanna Dary , Khut Sophanou , Prak Manila , Turner Claudia
Published: July 2020

Objectives

Neonatal mortality remains persistently high in low-income and middle-income countries. In Cambodia, there is a paucity of data on the perception of neonatal health and care-seeking behaviours at the community level. This study aimed to identify influencers of neonatal health and healthcare-seeking behaviour in a rural Cambodian province.

Design

A qualitative study using focus group discussions and thematic content analysis.

Setting

Four health centres in a rural province of Northern Cambodia.

Participants

Twenty-four focus group discussions were conducted with 85 community health workers in 2019.

Results

Community health workers recognised an improvement in neonatal health over time. Key influencers to neonatal health were identified as knowledge, sociocultural behaviours, finances and transport, provision of care and healthcare engagement. Most influencers acted as both barriers and facilitators, with the exception of finances and transport that only acted as a barrier, and healthcare engagement that acted as a facilitator.

Conclusion

Understanding health influencers and care-seeking behaviours is recognised to facilitate appropriate community health programmes. Key influencers and care-seeking behaviours have been identified from rural Cambodia adding to the current literature. Where facilitators have already been established, they should be used as building blocks for continued change.
Role of unsafe medical practices and sexual behaviours in the hepatitis B and C syndemic and HIV co-infection in Rwanda: a cross-sectional study
Authors: Makuza Jean Damascene , Nisingizwe Marie Paul , Rwema Jean Olivier Twahirwa , Dushimiyimana Donatha , Habimana Dominique Savio , Umuraza Sabine , Serumondo Janvier , Ngwije Alida , Semakula Muhamed , Gupta Neil , Nsanzimana Sabin , Janjua Naveed Zafar
Published: July 2020

Objectives

This study describes the burden of the hepatitis B, C and HIV co-infections and assesses associated risk factors.

Setting

This analysis used data from a viral hepatitis screening campaign conducted in six districts in Rwanda from April to May 2019. Ten health centres per district were selected according to population size and distance.

Participants

The campaign collected information from 156 499 participants (51 496 males and 104 953 females) on sociodemographic, clinical and behavioural characteristics. People who were not Rwandan by nationality or under 15 years old were excluded.

Primary and secondary outcomes

The outcomes of interest included chronic hepatitis C virus (HCV) infection, chronic hepatitis B virus (HBV) infection, HIV infection, co-infection HIV/HBV, co-infection HIV/HCV, co-infection HBV/HCV and co-infection HCV/HBV/HIV. Multivariable logistic regressions were used to assess factors associated with HBV, HCV and HIV, mono and co-infections.

Results

Of 156 499 individuals screened, 3465 (2.2%) were hepatitis B surface antigen positive and 83% (2872/3465) of them had detectable HBV desoxy-nucleic acid (HBV DNA). A total of 4382 (2.8%) individuals were positive for antibody-HCV (anti-HCV) and 3163 (72.2%) had detectable HCV ribo-nucleic acid (RNA). Overall, 36 (0.02%) had HBV/HCV co-infection, 153 (0.1%) HBV/HIV co-infection, 238 (0.15%) HCV/HIV co-infection and 3 (0.002%) had triple infection. Scarification or receiving an operation from traditional healer was associated with all infections. Healthcare risk factors—history of surgery or transfusion—were associated with higher likelihood of HIV infection with OR 1.42 (95% CI 1.21 to 1.66) and OR 1.48 (1.29 to 1.70), respectively, while history of physical traumatic assault was associated with a higher likelihood of HIV and HBV/HIV co-infections with OR 1.69 (95% CI 1.51 to 1.88) and OR 1.82 (1.08 to 3.05), respectively.

Conclusions

Overall, mono-infections were common and there were differences in significant risk factors associated with various infections. These findings highlight the magnitude of co-infections and differences in underlying risk factors that are important for designing prevention and care programmes.
Novel education-based intervention to reduce inappropriate antibiotic prescribing for treatment of gonorrhoea in China: protocol for a cluster randomised controlled trial
Authors: Jiang Ting-Ting , Yang Yun-Qing , Cao Ning-Xiao , Yin Yue-Ping , Chen Xiang-Sheng
Published: July 2020

Introduction

Inappropriate use of antibiotics to treat gonorrhoea can lead to antibiotic resistance. Education programmes may be helpful for improving physician prescribing behaviours in accordance with treatment guidelines. As traditional education based on printed materials may have limited effect on guideline-based treatment, innovative education strategies are needed. The current trial aims to assess the effectiveness of a novel education intervention to increase guideline-based treatment of gonorrhoea in China.

Methods and analysis

We will conduct a two-arm cluster randomised control trial at 144 hospitals (clusters) in eight Chinese provinces. The intervention will include an online training video developed on the WenJuanXing platform that covers workflows and requirements for managing a patient with uncomplicated gonorrhoea. Outpatient physicians in dermatology (dermatovenerology), urology, andrology and gynaecology will be given access to the video via a quick response code. In hospitals allocated to the control arm, physicians will continue to participate in their standard of care training programme. The primary outcome is the proportion of gonorrhoea antibiotic prescriptions adherent to Chinese national guidelines at the cluster level. In addition, to understand the reasons of physician’s non-adherence to the intervention by conducting a questionnaire survey will be considered as the secondary outcome of the study.

Ethics and dissemination

Ethical approval was obtained from the Medical Ethics Committee of the Chinese Academy of Medical Sciences Institute of Dermatology (2020-LS-004). All physicians will provide an informed consent prior to participating in the study. Findings of the trial will be disseminated through conferences and peer-reviewed journals, and will be used to develop training programmes for physicians.

Trial registration number

ChiCTR2000029591.
Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with
patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort
Authors: Bajaj Jasmohan S , Garcia-Tsao Guadalupe , Biggins Scott W , Kamath Patrick S , Wong Florence , McGeorge Sara , Shaw Jawaid , Pearson Meredith , Chew Micheal , Fagan Andrew , de la Rosa Rodriguez Randolph , Worthington Janelle , Olofson Amy , Weir Vanessa , Trisolini Calvin , Dwyer Sarah , Reddy K Rajender
Published: July 2020

Objective

Comorbid conditions are associated with poor prognosis in COVID-19. Registry
data show that patients with cirrhosis may be at high risk. However, outcome
comparisons among patients with cirrhosis+COVID-19 versus patients with COVID-19 alone
and cirrhosis alone are lacking. The aim of this study was to perform these
comparisons.

Design

A multicentre study of inpatients with cirrhosis+COVID-19 compared with
age/gender-matched patients with COVID-19 alone and cirrhosis alone was performed.
COVID-19 and cirrhosis characteristics, development of organ failures and
acute-on-chronic liver failure (ACLF) and mortality (inpatient death+hospice) were
compared.

Results

37 patients with cirrhosis+COVID-19 were matched with 108 patients with COVID-19
and 127 patients with cirrhosis from seven sites. Race/ethnicity were similar.
Patients with cirrhosis+COVID-19 had higher mortality compared with patients with
COVID-19 (30% vs 13%, p=0.03) but not between patients with cirrhosis+COVID-19 and
patients with cirrhosis (30% vs 20%, p=0.16). Patients with cirrhosis+COVID-19 versus
patients with COVID-19 alone had equivalent respiratory symptoms, chest findings and
rates of intensive care unit transfer and ventilation. However, patients with
cirrhosis+COVID-19 had worse Charlson Comorbidity Index (CCI 6.5±3.1 vs 3.3±2.5,
p<0.001), lower presenting GI symptoms and higher lactate. Patients with cirrhosis
alone had higher cirrhosis-related complications, maximum model for end-stage liver
disease (MELD) score and lower BiPAP/ventilation requirement compared with patients
with cirrhosis+COVID-19, but CCI and ACLF rates were similar. In the entire group, CCI
(OR 1.23, 95% CI 1.11 to 1.37, p<0.0001) was the only variable predictive of
mortality on multivariable regression.

Conclusions

In this multicentre North American contemporaneously enrolled study,
age/gender-matched patients with cirrhosis+COVID-19 had similar mortality compared
with patients with cirrhosis alone but higher than patients with COVID-19 alone. CCI
was the only independent mortality predictor in the entire matched cohort.
Chronobiological patterns of acute aortic dissection in central China
Authors: Xia Liangtao , Huang Lu , Feng Xin , Xiao Jiewen , Wei Xiang , Yu Xinyu
Published: July 2020

Background

Acute aortic dissection (AAD) is a life-threatening emergency with poor clinical outcomes. Understanding the chronological patterns of AAD onset would be helpful for identifying the triggers of AAD and preventing this catastrophic event.

Methods

We collected data from 2048 patients diagnosed with AAD at Tongji Hospital (Wuhan, China) from 2011 to 2018. The χ2test was used to determine whether a specific period had significantly different seasonal/weekly distributions from other periods. Fourier models were used to analyse the rhythmicity in monthly/circadian distribution.

Results

The mean age was 53.4±10.9 years, and 1161 patients (56.7%) were under 55 years. One thousand six hundred fifty-seven patients (80.9%) were male, and 935 cases (45.7%) were type A dissections. The proportions of patients with comorbid hypertension/diabetes were 60.3% (1234 cases) and 1.8% (36 cases), respectively. A peak was identified in colder periods (winter/December) and a trough in warmer periods (summer/June). No significant variation was observed in weekly distribution. Fourier analysis showed a statistically significant circadian variation (p<0.001) with a nocturnal trough in 2:00–3:00, a morning peak in 9:00–10:00, and an afternoon peak in 16:00–17:00. Subgroup analyses identified circadian rhythmicity in all subgroups except for the female group and younger group (younger than 55 years).

Conclusion

Our results confirmed that the onset of AAD exhibits significant seasonal, monthly and circadian patterns. Patients with AAD with different Stanford-type dissections, sexes, ages and hypertension statuses could present different circadian variations. These findings may provide novel perspectives for identifying the triggers of AAD and better preventing this catastrophic event.
Correlates of clinical benefit from immunotherapy and targeted therapy in metastatic renal cell carcinoma: comprehensive genomic and transcriptomic analysis
Authors: Dizman Nazli , Lyou Yung , Salgia Nicholas , Bergerot Paulo Gustavo , Hsu JoAnn , Enriquez Daniel , Izatt Tyler , Trent Jeffrey M , Byron Sara , Pal Sumanta
Published: July 2020

Background

The clinical significance of tumor-specific genomic alterations in metastatic renal cell carcinoma (mRCC) is emerging, with several studies suggesting an association between PBRM1 mutations and response with immunotherapy (IO). We sought to determine genomic predictors of differential response to vascular endothelial growth factor–tyrosine kinase inhibitors (VEGF-TKIs) and IO.

Methods

Consecutive patients who underwent genomic profiling were identified; patients receiving either VEGF-TKIs or IO were included. Clinical tumor-normal whole exome sequencing and tumor whole transcriptome sequencing test were performed using a Clinical Laboratory Improvement Amendments (CLIA)-certified assay (Ashion Analytics; Phoenix, Arizona, USA). Genomic findings were compared between patients with clinical benefit (CB; complete/partial response or stable disease for >6 months) and no clinical benefit (NCB) in VEGF-TKI-treated patient cohort and IO-treated patient cohort.

Results

91 patients received genomic profiling and 58 patients received VEGF-TKI and/or IO therapy. 17 received sequenced treatment involving both VEGF-TKI and IO, resulting in 32 patients in the IO cohort and 43 patients in the VEGF-TKI cohort. The most commonly used IO and VEGF-TKIs were nivolumab (66%) and sunitinib (40%). The most frequently detected alterations in the overall cohort were in VHL (64%), PBRM1 (38%), SETD2 (24%), KDM5C (17%) and TERT (12%). TERT promoter mutations were associated with NCB in the IO cohort (p=0.038); transcriptomic analysis revealed multiple differentially regulated pathways downstream of TERT. TERT promoter mutations and PBRM1 mutations were found to be mutually exclusive. While PBRM1 mutations were more prevalent in patients with CB with IO and VEGF-TKIs, no statistically significant association was found.

Conclusions

Our analysis found that TERT promoter mutations may be a negative predictor of outcome with IO and are mutually exclusive with PBRM1 loss-of-function mutations.
Why continuing uncertainties are no reason to postpone challenge trials for coronavirus vaccines
Authors: Steel Robert , Buchak Lara , Eyal Nir
Published: July 2020

To counter the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some have proposed accelerating SARS-CoV-2 vaccine development through controlled human infection (or ‘challenge’) trials. These trials would involve the deliberate exposure of relatively few young, healthy volunteers to SARS-CoV-2. We defend this proposal against the charge that there is still too much uncertainty surrounding the risks of COVID-19 to responsibly run such a trial.
Clinical management of lipomas in dogs under primary care in the UK
Authors: Pegram Camilla Leonie , Rutherford Lynda , Corah Caroline , Church David B , Brodbelt David C , O'Neill Dan G
Published: July 2020

Lipomas are relatively common and biologically benign masses of mesenchymal origin consisting of adipocytes. This study reports benchmark data on the clinical management and outcomes of lipomas in dogs under UK primary veterinary care. The study used a cross-sectional analysis of cohort clinical data from dogs that were under veterinary care at practices participating within VetCompass from January 1, 2013 to December 31, 2013. Descriptive and analytic statistics characterised the clinical management and outcomes following presumptive lipoma diagnosis. The study included 2765 lipoma cases from 384 284 dogs under UK veterinary care during 2013. Diagnostics included fine needle aspirate in 1119 (40.5 per cent) cases, biopsy in 215 (7.8 per cent) cases and diagnostic imaging in 11 (0.4 per cent) cases. Overall, 525 (19.0 per cent) cases were managed surgically. Of the surgical cases, 307 (58.5 per cent) solely had mass removal whilst 218 (41.5 per cent) included another procedure during the same surgical episode. A surgical drain was placed during surgery in 90 (17.1 per cent) cases. Wound breakdown was reported in 14 (2.7 per cent) surgical procedures. Wound infection followed surgery in 11 (2.1 per cent) dogs. The findings provide veterinarians with an evidence base that benchmarks how lipoma cases are currently managed in the UK, but these results do not necessarily reflect optimal management or best practice.
Extended galactic rotational velocity profiles in f(R) gravity background
Authors: Sharma Vipin Kumar , Yadav Bal Krishna , Verma Murli Manohar
Published: July 2020

An attempt has been made to explore the geometric effects of f(R) action on the galactic dynamics under the weak field approximation. The rotational velocity is calculated beyond the Einstein’s geometric theory of gravity. It is inspired by the cosmological geometric relation obtained in the power-law f(R) gravity model in vacuum. We analyse the action with a small positive deviation from the Einstein–Hilbert gravity action (taking R as $$f(R)\propto R^{1+\delta }$$f(R)∝R1+δ) at the galactic scales for the explanation of the flatness paradox associated with the clustered galactic dark matter. We obtain the contribution of a dynamical f(R) cosmological background geometry on accelerating the test mass. Furthermore, the integrated effective acceleration of the test mass due to a massive spherically symmetric source in f(R) background is calculated via the study of geodesics for the suitable spacetime metric and an equation for the effective rotational velocity has been developed. We test the viability of the proposed model by tracing the motion of a test mass far from the disk of galactic matter for smaller $$\delta $$δ. The possible galactic rotational velocity curves in f(R) background are discussed for the formula obtained with $$\delta<< 1$$δ<<1. We also obtain constraints on $$\delta $$δ$$O(10^{-6})$$O(10-6) confirmed by observations.
Thin domain limit and counterexamples to strong diamagnetism
Authors: Helffer Bernard , Kachmar Ayman
Published: July 2020

We study the magnetic Laplacian and the Ginzburg–Landau functional in a thin planar, smooth, tubular domain and with a uniform applied magnetic field. We provide counterexamples to strong diamagnetism, and as a consequence, we prove that the transition from the superconducting to the normal state is non-monotone. In some nonlinear regime, we determine the structure of the order parameter and compute the super-current along the boundary of the sample. Our results are in agreement with what was observed in the Little–Parks experiment, for a thin cylindrical sample.
THE ENVIRONMENTAL VALUE OF SOUTH KOREA’S MOUNTAINS: A CONTINGENT VALUATION STUDY
Authors: KIM DONG-PIL , KANG KEE-RAE , LEE HAE-JOO , KIM HEE-CHAE , LEE WOO-SUNG , CHUNG BO-KWANG , CHAE SU-BOK , KIM CHA-KWON
Published: July 2020

To address the lack of awareness on environmental values, this study estimates the environmental value of mountain ranges (Jeongmaek) connected to the Baekdudaegan mountain system in South Korea. Seven Jeongmaek are studied during 2011–2016 using a questionnaire survey and the contingent valuation method. Based on willingness to pay (WTP) for biodiversity, this study finds that the lowest estimated WTP was KRW 5813 for Geumbuk and Hannam-Geumbuk Jeongmaek, and the highest value was KRW 120,471 for Hanbuk Jeongmaek. These differences in WTP appear to be significantly determined by education level and number of visits of respondents.
SPICE Behavioral Modeling of TiO2 Memristors for Digital Logic Applications
Authors: Gergel-Hackett Nadine , Wright Anna , Fullerton Farrah-Amoy , Joe Aaleyah
Published: July 2020

This work presents a behavior-based memristor model for the simulation of novel digital logic architectures. This model exhibits the nonvolatile hard switching current–voltage curves of the experimentally realized memristors. Because the model is implemented via the widely available traditional SPICE (Simulation Program with Integrated Circuit Emphasis) circuit components, its accuracy is not dependent on still-emerging device transport theory and auxiliary variables. The memristor model is used in material implication (IMPLY) gates to perform both combinational and sequential logics. As IMPLY gates exhibit the complete functionality required for digital logic, this work presents a simple realistic memristor model for use in the simulation of novel digital logic architectures.
Mathematical analysis and simulation study of a phase-field model of prostate cancer growth with chemotherapy and antiangiogenic therapy effects
Authors: Colli Pierluigi , Gomez Hector , Lorenzo Guillermo , Marinoschi Gabriela , Reali Alessandro , Rocca Elisabetta
Published: July 2020

Chemotherapy is a common treatment for advanced prostate cancer. The standard approach relies on cytotoxic drugs, which aim at inhibiting proliferation and promoting cell death. Advanced prostatic tumors are known to rely on angiogenesis, i.e. the growth of local microvasculature via chemical signaling produced by the tumor. Thus, several clinical studies have been investigating antiangiogenic therapy for advanced prostate cancer, either as monotherapy or in combination with standard cytotoxic protocols. However, the complex genetic alterations that originate and sustain prostate cancer growth complicate the selection of the best chemotherapeutic approach for each patient’s tumor. Here, we present a mathematical model of prostate cancer growth and chemotherapy that may enable physicians to test and design personalized chemotherapeutic protocols in silico. We use the phase-field method to describe tumor growth, which we assume to be driven by a generic nutrient following reaction–diffusion dynamics. Tumor proliferation and apoptosis (i.e. programmed cell death) can be parameterized with experimentally-determined values. Cytotoxic chemotherapy is included as a term downregulating tumor net proliferation, while antiangiogenic therapy is modeled as a reduction in intratumoral nutrient supply. An additional equation couples the tumor phase field with the production of prostate-specific antigen, which is a prostate cancer biomarker that is extensively used in the clinical management of the disease. We prove the well posedness of our model and we run a series of representative simulations leveraging an isogeometric method to explore untreated tumor growth as well as the effects of cytotoxic chemotherapy and antiangiogenic therapy, both alone and combined. Our simulations show that our model captures the growth morphologies of prostate cancer as well as common outcomes of cytotoxic and antiangiogenic mono therapy and combined therapy. Additionally, our model also reproduces the usual temporal trends in tumor volume and prostate-specific antigen evolution observed in experimental and clinical studies.
A Sample Truncation Rule for Product Reliability Estimation in Multiple Censoring Data Conditions
Authors: Xie Liyang , Song Jiaxin , Li Chenggang , Li Haiyang
Published: July 2020

This paper studies the method to estimate the location parameter of a three-parameter Weibull life distribution in the situation of multiple censoring life data available, the effect of sample size and minimal outcome on life and reliability estimation, and the policy to choose favorable data from operation records. First of all, a method to estimate the location parameter of the Weibull distribution is presented in the scenario of product probabilistic life and reliability estimation. Relationships between the estimated life distribution parameter and the right-censored life data applied is demonstrated, a rule is proposed to choose the appropriate number of censoring life data by discarding some shorter operation time records. It is illustrated that an appropriate combination of sample size and the minimum observation value (right-censored life time) is reasonable for the balance between estimation confidence level and reliability value.
ReS-Algorithm for Converting Normalized Values of Cost Criteria Into Benefit Criteria in MCDM Tasks
Authors: Mukhametzyanov Irik Z.
Published: July 2020

A review of modern methods of data normalization in the tasks of multicriteria decision-making and multidimensional classification is presented. The invariant properties of linear normalization methods are determined. Two basic principles of normalization of multidimensional data are defined: preservation of dispositions of natural and normalized values on the measurement scale and the absence of a displacement in the areas of normalized values of various criteria relative to each other. A method is proposed for converting normalized values of cost criteria to profit criteria based on the reverse sorting algorithm (ReS-algorithm). The ReS-algorithm preserves the dispositions of the natural and normalized values of the attributes of the alternatives and eliminates the displacement the areas of normalized values of the cost criteria relative to the profit criteria, which ensures the equality of the contributions of various criteria to the performance indicator of the alternatives.
Studies on the structure and conformational flexibility of secondary structures in amyloid beta — A quantum chemical study
Authors: Ganesan Mahendiraprabu , Paranthaman Selvarengan
Published: July 2020

Density functional theory (DFT) calculations are performed to study the conformational flexibility of secondary structures in amyloid beta (A[Formula: see text]) polypeptide. In DFT, M06-2X/6-31[Formula: see text]G(d, p) method is used to optimize the secondary structures of 2LFM and 2BEG in gas phase and in solution phase. Our calculations show that the secondary structures are energetically more stable in solution phase than in gas phase. This is due to the presence of strong solvent interaction with the secondary structures considered in this study. Among the backbone [Formula: see text] and [Formula: see text] dihedral angles, [Formula: see text] varies significantly in sheet structure. This is due to the absence of intermolecular hydrogen bond (H-bond) interactions in sheets considered in this study. Our calculations show that the conformational transition of helix/coil to sheet or vice-versa is due to the floppiness of the amino acid residues. This is observed from the Ramachandran map of the studied secondary structures. Further, it is noted that the intramolecular H-bond interactions play a significant role in the conformational transition of secondary structures of A[Formula: see text].
Identification of therapeutic target in S2 domain of SARS nCov-2 Spike glycoprotein: Key to design and discover drug candidates for inhibition of viral entry into host cell
Authors: Somadi Gururaj , Sivan Sree Kanth
Published: July 2020

Humanity is facing a grieve danger of coronavirus disease-19 caused by severe acute respiratory syndrome novel coronavirus-2 (SARS nCov-2). There is an urgent need of therapeutics that can help in overcoming this global pandemic. Identifying novel therapeutic target and screening already approved drug is a faster approach in this situation. Spike glycoprotein (Sgp) of SARS nCoV-2 is potentials target where in researchers have targeted receptor binding domain (RBD) of S1 domain. The S2 domain of Sgp also plays a pivotal role in viral entry, but the mechanism is less understood. We analyzed the structure of Sgp S2 domain in pre-fusion state and Heptad repeat region in its post-fusion state available from protein data bank. Sgp shows three major regions in S2 domain, the fusion peptide (FP), heptad repeat 1 (HR1) and central helical (CH) region. The HR1 region undergoes structural changes by flipping approximately 180∘ and coil up to form a rod like structure during fusion process implying its role in viral entry into the host cell. This structural change in S2 domain helices is crucial step, if this process is hindered by targeting the HR1 and CH region then the progression of virus can be stopped. Possible binding cavity was identified near the HR1 and CH region in S2 domain and docking-based virtual screening of FDA approved drugs was performed. Promising candidates like Troxerutin, Thymopentin and Daclatasvir can be used as therapeutics provided an immediate in-vitro and clinical studies are carried out by research groups.
Estimation of Thermal Contact Conductances on Irregular Interfaces Using the Generalized Integral Transform Technique and the Reciprocity Functional Method
Authors: de Freitas Guilherme C. , Colaço Marcelo J.
Published: July 2020

The reciprocity functional method, associated to the Classic Integral Transform Technique (CITT), has been successfully applied, obtaining analytical solutions for the inverse heat transfer problem that seeks to estimate the thermal contact conductance (TCC) distribution on the interface of a body composed of two materials. Yet, the theoretical development upon which this approach is based is not limited to the need of this interface to have a regular format. This work proposes to extend the method, thus obtaining an analytical development for the estimation of the TCC distribution on interfaces which are not necessarily regular. Several test problems were solved using the techniques described in this work, leading to very good results, with low CPU time usage by the computational implementation.
OWNERSHIP, COMPENSATION AND BOARD DIVERSITY AS INNOVATION DRIVERS: A COMPARISON OF U.S. AND CANADIAN FIRMS
Authors: ATALLAH GAMAL , DE FUENTES CLAUDIA , PANASIAN CHRISTINE A.
Published: July 2020

Using a large sample of North American firms, from 1999 to 2016, we investigate the effect of corporate governance structures, specifically ownership, board characteristics, and executive compensation contracts on innovation intensity and output. We consider both R[Formula: see text]D expenditures and patents as innovation proxies and evaluate consequences of the economic downturns of 2000 and 2008. We find that R[Formula: see text]D investment increases with ownership by institutional blockholders and with the number of institutional owners, confirming the key role institutions play in innovation activities of firms. We observe higher R[Formula: see text]D levels for firms with more independent boards, more females board members and more outside directorships held by directors. We report that firms with CEO/chair of the board duality have lower R[Formula: see text]D intensity, as do firms with higher ownership by directors and with a higher mean board age. Innovation is negatively related to CEO salary levels, but positively related to the ratio of incentives to total compensation, confirming that incentives contribute to aligning shareholders and management interests, which leads to better long-term decisions. However, those incentives reduce the number of patents. We do not find any systematic changes in R[Formula: see text]D for the 2000 recession, however there is an increase for the 2008 financial crisis.
3D Thermal Stresses in Composite Laminates Under Steady-State Through-Thickness Thermal Conduction
Authors: Guo Yan , Jiang Yanan , Wang Ji , Huang Bin
Published: July 2020

In this study, 3D thermal stresses in composite laminates under steady-state through thickness thermal conduction are investigated by means of a stress function-based approach. One-dimensional thermal conduction is solved for composite laminate and the layerwise temperature distribution is calculated first. The principle of complementary virtual work is employed to develop the governing equations. Their solutions are obtained by using the stress function-based approach, where the stress functions are taken from the Lekhnitskii stress functions in terms of in-plane stress functions and out-of-plane stress functions. With the Rayleigh–Ritz method, the stress fields can be solved by first solving a standard eigenvalue problem. The proposed method is not merely computationally efficient and accurate. The stress fields also strictly satisfy the prescribed boundary conditions validated by the results of finite element method (FEM) results. Finally, some of the results will be given for discussion considering different layup stacking sequences, thermal conductivities and overall temperature differences. From the results, we find that the thermal conductivity greatly affects the stress distributions and peak values of stresses increase linearly for the present model. The proposed method can be used for predicting 3D thermal stresses in composite laminates when subjected to thermal loading.
A multi-delay model for pest control with awareness induced interventions — Hopf bifurcation and optimal control analysis
Authors: Al Basir Fahad
Published: July 2020

Farming awareness is an important measure for pest controlling in agricultural practice. Time delay in controlling pest may affect the system. Time delay occurs in organizing awareness campaigns, also time delay may takes place in becoming aware of the control strategies or implementing suitable controlling methods informed through social media. Thus we have derived a mathematical model incorporating two time delays into the system and Holling type-II functional response. The existence and the stability criteria of the equilibria are obtained in terms of the basic reproduction number and time delays. Stability changes occur through Hopf-bifurcation when time delays cross the critical values. Optimal control theory has been applied for cost-effectiveness of the delayed system. Numerical simulations are carried out to justify the analytical results. This study shows that optimal farming awareness through radio, TV etc. can control the delay induced bifurcation in a cost-effective way.