bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical Expressions for Principal Strains
Authors: Thomson W. T.
Published: March 2021

Recent methods by G. Murphy (1) and N. J. Hoff (2) enable the graphical evaluation of principal strains from strains measured along any three intersecting lines. When the two angles between gage lines are equal, the principal strains may be determined from simple analytical expressions without reference to the graphical solution.
Cylindrical Buckling of Sandwich Plates
Authors: Goodier J. N.
Published: March 2021

In the buckling of “sandwich plates” with a relatively easily deformed interior, or core, material, the core is not stiff enough to keep plane sections plane when the bending occurs. The core must then be analyzed according to the equations of plane strain, but the fact that the bending takes place in the presence of thrust means that terms representing the destabilizing tendency of the thrust must be included. The resulting problem is solved in the present paper for a sandwich plate in “cylindrical buckling”—that is in a mode analogous to that of the hinged column.
Forced Torsional Vibrations With Damping: An Extension of Holzer’s Method
Authors: Den Hartog J. P. , Li J. P.
Published: March 2021

An extension of Holzer’s method is given for the case of damped systems of discreet as well as of uniformly distributed inertias and flexibilities. For discreet systems the modification in the Holzer table consists of replacing I by I − jc0/ω, and of replacing k by k + jωci, whereby most numbers in the tables become complex. The meaning of the real part of any complex number is that quantity which is in time-phase with the motion at the free end, while the imaginary part is 90 deg out of time-phase with that motion. For distributed systems the results are given by Equations [12] and [12a] for a free forward end; by Equations [13] and [13a] for a damped forward end, while the letters a and b appearing in these results are defined by Equations [8] and [8a].
Heat Transfer Measurements Using Multiple Thermochromic Liquid Crystals in Symmetric Cooling Channels
Authors: Krille Tobias , Retzko Stefan , Poser Rico , von Wolfersdorf Jens
Published: March 2021

The transient thermochromic liquid crystal (TLC) method is applied to determine the distribution of the local heat transfer coefficients using a configuration with parallel cooling channels at an engine-relevant Reynolds number. The rectangular channels with a moderate aspect ratio and a high length-to-diameter ratio are equipped with one-sided oblique ribs with high blockage, which is a promising configuration for turbine near-wall cooling applications. In this arrangement, the three inner channels should experience same flow and thermal conditions. Numerical simulations are performed to substantiate this assumption. The symmetric single channels are sprayed with narrowband TLC with various indication temperatures. Multiple experiments were conducted. All start at ambient conditions before the fluid is heated up to several temperatures between 46 °C and 73 °C. The results show that the determined local heat transfer coefficients and therefore the Nusselt numbers vary significantly for the different experimental conditions especially at locations of high heat transfer coefficient behind the ribs. A simplified procedure with respect to measurement uncertainties is applied to enable an easy and fast valuation of the data quality. This might be used within the data reduction analysis for such experiments directly. The approach is illustrated using the obtained experimental data.
Large-Eddy Simulation of Variable Speed Power Turbine Cascade With Inflow Turbulence
Authors: Miki Kenji , Ameri Ali
Published: March 2021

Numerical results are presented from the National Aeronautics and Space Administration (NASA) Glenn Research Center's in-house turbomachinery code Glenn-HT applied to the variable-speed power turbine (VSPT) experiment at the NASA Transonic Turbine Blade Cascade Facility. The main goal of this paper is to implement a digital filtering method to generate turbulence upstream and a subgrid model (localized dynamic k-equation model (LDKM)) in the framework of large-eddy simulation (LES) in order to investigate the effect of inflow turbulence on the transition seen in the VSPT experimental data at the cruise condition (incidence angle of 40 deg and Tu = 0.5%, 5%, 10%, and 15%). Although the boundary layer on the suction side and pressure side of the blades is initially laminar due to favorable pressure gradient, the laminar flow can transition to turbulent flow past a separation zone on the suction side or by natural or bypass transition. This process determines the total pressure losses in the wake. Therefore, it is desirable to develop a reliable prediction tool to accurately capture the transition mechanism in blade rows operated under the conditions of low Reynolds number and at a variety of freestream turbulence conditions. Our numerical studies reveal that the location of separation is rather insensitive to the level of Tu; however, the effect of increasing Tu seems to be in reducing the size and ultimately suppressing the separation bubble. In addition, we performed spectral analysis to identify the peak frequencies in the region where the separation bubble is formed, which provides valuable insights into the transition/separation mechanism.
Aerodynamic Effects of an Incoming Vortex on Turbines With Different Tip Geometries
Authors: Zhou Kai , Zhou Chao
Published: March 2021

Experimental and numerical methods were used to investigate the aerodynamic effects of a near-casing streamwise incoming vortex flow on the tip leakage flow of different tip geometries in an unshrouded high-pressure turbine. A flat tip, a cavity tip, and a suction side winglet tip were investigated with the quasi-steady method first. A swirl generator was used to produce the incoming vortex in a linear cascade. In the flat tip case, the incoming vortex interacts with the tip leakage flow and the two vortices gradually mix together. The tip leakage loss is reduced due to the streamwise momentum supplement within the tip leakage vortex core. For the cavity tip, the tip leakage vortex appears at a location relatively downstream in the blade passage compared with the flat tip and no evident vortex interaction is observed. The incoming vortex causes extra viscous dissipation within the blade passage and increases the aerodynamic loss for the cavity tip. For the winglet tip, the extension of the suction side winglet tends to push the incoming vortex and the tip leakage vortex move and mix together, thus reducing the loss. Then, the effects of periodic unsteady vortex transportations were investigated by conducting unsteady Reynolds-Averaged Navier–Stokes (URANS) simulations. The incoming vortex is stretched as it transports downstream. The unsteady incoming vortex is easier to interact with the tip leakage vortex for the winglet tip. As a result, the winglet tip is the most efficient tip design with unsteady incoming flow among the three tips and achieves a 3.7% reduction of mixed-out loss coefficient compared with the flat tip, larger than 2.8% reduction in the uniform inlet condition. The detailed loss mechanism is discussed in this paper.
Assessment of MULTALL as Computational Fluid Dynamics Code for the Analysis of Tube-Axial Fans
Authors: Danieli Piero , Masi Massimo , Delibra Giovanni , Corsini Alessandro , Lazzaretto Andrea
Published: March 2021

This work deals with the application of the open-source computational fluid dynamics (CFD) code MULTALL to the analysis of tube-axial fans. The code has been widely validated in the literature for high-speed turbomachine flows but not applied yet to low-speed tutbomachines. The aim of this work is to assess the degree of reliability of MULTALL as a tool for simulating the internal flow in industrial axial-flow fan rotors. To this end, the predictions of the steady-state air-flow field in the annular sector of a 315 mm tube-axial fan obtained by MULTALL 18.3 are compared with those obtained by two state-of-the-art CFD codes and experimental data of the global aerodynamic performance of the fan and the pitch-wise averaged velocity distribution downstream of the rotor. All the steady-state Reynolds-averaged Navier–Stokes (RANS) calculations were performed on either fully structured hexahedron or hexa-dominant grids using classical formulations of algebraic turbulence models. The pressure curve and the trend of the aeraulic efficiency in the stable operation range of the fan predicted by MULTALL show very good agreement with both the experimental data and the other CFD results. Although the estimation of the fan efficiency predicted by MULTALL can be noticeably improved by the more sophisticated state-of-the-art CFD codes, the analysis of the velocity distribution at the rotor exit supports the use of MULTALL as a reliable CFD analysis tool for designers of low-speed axial fans.
Toward Sub-Surface Pore Prediction Capabilities for Laser Powder Bed Fusion Using Data Science
Authors: Ertay Deniz Sera , Kamyab Shima , Vlasea Mihaela , Azimifar Zohreh , Ma Thanh , Rogalsky Allan D. , Fieguth Paul
Published: March 2021

Achieving defect-free parts is traditionally challenging in laser powder bed fusion (LPBF). The mechanical properties of additively manufactured parts are highly affected by their density; as such, research in defect detection and pore prediction has gained significant interest. The process parameters, the powder characteristics, and the process environment conditions play an important role in defect occurrence. Moreover, the laser scan path affects density, especially at scan path discontinuities. In this work, the complex interaction between the process parameters and the scan path on the occurrence of subsurface pores is investigated. In the data preparation step, a synthetic data set is generated to model the melt pool morphology along the scan path. A secondary data set containing the pore space of the resulting parts is obtained via X-ray computed tomography (CT) and is registered with the synthetic data set. Machine learning models, namely, a Conditional Variational AutoEncoder (CVAE) and a Convolutional Neural Network (CNN), are then trained based on the input features to predict pore occurrence. The performance evaluation of both CNN and CVAE models on synthetic data indicates that the scan path and process parameters can be utilized in predicting pore locations. Quantitative results show that employing offline CT images a priori in training the CVAE, without the need to have CT information in the test phase, leads the CVAE model to superior performance over the CNN.
An Investigation into the Texture Transfer in the Process of Lubricated Skin Pass Rolling
Authors: Wu Chuhan , Zhang Liangchi , Qu Peilei , Li Shanqing , Jiang Zhenglian , Li Wei
Published: March 2021

This article investigates the surface texture transfer mechanisms in lubricated skin pass rolling of metal strips with three-dimensional rough surfaces of both regular patterns and random surface asperity distributions. Two important steps have been completed. The first is the successful establishment of an efficient numerical method for predicting the 3D texture transfer. It was identified that the new method can be used reliably with the key complex factors coupled in skin pass rolling, such as the effects of lubricant and surface roughness. The second is the exploration of the texture transfer mechanisms with the aid of this new method. In addition, the effects of hydrodynamic pressure on the texture transfer efficiency were comprehensively investigated by a dynamic explicit finite element analysis. It was found that lubrication plays a critical role in determining the surface texture transfer. The texture transfer ratio decreases with increasing the lubricant viscosity. A larger pressure coefficient brings about a lower texture transfer ratio, but a larger reduction ratio leads to a greater texture transfer.
Study of a thermoacoustic-Stirling engine connected to a piston-crank-flywheel assembly
Authors: Penelet Guillaume , Watanabe Takumaru , Biwa Tetsushi
Published: March 2021

This paper deals with the theoretical description of self-sustained oscillations resulting from the coupling of a piston-crank-flywheel assembly with a thermoacoustic-Stirling prime mover. The governing equations of the piston-flywheel motion are coupled to those of the thermoacoustic system, which is described in the time domain through a rational differential operator relating acoustic pressure fluctuations inside the cavity to the piston's velocity. As a result, the complete device is described by means of a fourth-order nonlinear dynamical system and solved numerically. The dynamical behavior of the system is studied as a function of the temperature difference along the thermoacoustic unit, and it is shown that the regime of stable rotations of the flywheel appears through a saddle-node bifurcation above a threshold value of the temperature difference. Moreover, the simulation results show good agreement with experiments.
Physiological Determinants of Ultramarathon Trail-Running Performance
Authors: Coates Alexandra M. , Berard Jordan A. , King Trevor J. , Burr Jamie F.
Published: March 2021

Context: The physiological determinants of ultramarathon success have rarely been assessed and likely differ in their contributions to performance as race distance increases. Purpose: To examine predictors of performance in athletes who completed either a 50-, 80-, or 160-km trail race over a 20-km loop course on the same day. Methods: Measures of running history, aerobic fitness, running economy, body mass loss, hematocrit alterations, age, and cardiovascular health were examined in relation to race-day performance. Performance was defined as the percentage difference from the winning time at a given race distance, with 0% representing the fastest possible time. Results: In the 50-km race, training volumes, cardiovascular health, aerobic fitness, and a greater loss of body mass during the race were all related to better performance (all P < .05). Using multiple linear regression, peak velocity achieved in the maximal oxygen uptake test (β = −11.7, P = .002) and baseline blood pressure (β = 3.1, P = .007) were the best performance predictors for the men’s 50-km race (r = .98, r2 = .96, P < .001), while peak velocity achieved in the maximal oxygen uptake test (β = −13.6, P = .001) and loss of body mass (β = 12.8, P = .03) were the best predictors for women (r = .94, r2 = .87, P = .001). In the 80-km race, only peak velocity achieved in the maximal oxygen uptake test predicted performance (β = −20.3, r = .88, r2 = .78, P < .001). In the 160-km race, there were no significant performance determinants. Conclusions: While classic determinants of running performance, including cardiovascular health and running fitness, predict 50-km trail-running success, performance in longer-distance races appears to be less influenced by such physiological parameters.
Development and Validation of the Diet-Related Beliefs of Exercisers Scale
Authors: Dohle Simone , Duncan Mitch J. , Bucher Tamara
Published: March 2021

Many exercise-based weight-loss interventions result in considerably less weight loss than predicted. One possible explanation could be that people have certain beliefs about the interplay of exercise and food that also influence their eating behavior, such as the belief that food is a reward for exercise. The current research outlines a systematic multiphase process to develop a psychometrically sound scale to assess these beliefs. In Study 1, regular exercisers (N = 520) completed an exploratory questionnaire on their beliefs related to diet and exercise. In Study 2 (N = 380), the factor structure of the newly developed scale was corroborated by confirmatory factor analysis. In addition, a test–retest (N = 166) was used to confirm reliability and stability. In sum, the Diet-Related Beliefs of Exercisers Scale with its four subscales (“Refrain from Eating,” “Food as Reward,” “Healthy Eating,” and “Nutritional Replenishment”) represents a valid and reliable measure of exercisers’ diet-related beliefs.
Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color
Authors: Simcoe Mark , Valdes Ana , Liu Fan , Furlotte Nicholas A. , Evans David M. , Hemani Gibran , Ring Susan M. , Smith George Davey , Duffy David L. , Zhu Gu , Gordon Scott D. , Medland Sarah E. , Vuckovic Dragana , Girotto Giorgia , Sala Cinzia , Catamo Eulalia , Concas Maria Pina , Brumat Marco , Gasparini Paolo , Toniolo Daniela , Cocca Massimiliano , Robino Antonietta , Yazar Seyhan , Hewitt Alex , Wu Wenting , Kraft Peter , Hammond Christopher J. , Shi Yuan , Chen Yan , Zeng Changqing , Klaver Caroline C. W. , Uitterlinden Andre G. , Ikram M. Arfan , Hamer Merel A. , van Duijn Cornelia M. , Nijsten Tamar , Han Jiali , Mackey David A. , Martin Nicholas G. , Cheng Ching-Yu ,   the 23andMe Research Team,   the International Visible Trait Genetics Consortium, Hinds David A. , Spector Timothy D. , Kayser Manfred , Hysi Pirro G.
Published: March 2021

A GWAS including 192,986 European and 1636 Asian participants identifies 50 novel discrete associations with eye color.
Oxidative phosphorylation enhances the leukemogenic capacity and resistance to chemotherapy of B cell acute lymphoblastic leukemia
Authors: Chen Chiqi , Hao Xiaoxin , Lai Xiaoyun , Liu Ligen , Zhu Jun , Shao Hongfang , Huang Dan , Gu Hao , Zhang Tinghua , Yu Zhuo , Xie Li , Zhang Xiaocui , Yang Yi , Xu Jun , Zhao Yuzheng , Lu Zhigang , Zheng Junke
Published: March 2021

B cell acute lymphoid leukemia uses the mitochondrial respiration as the main energy source that enhances drug resistance.
Shaping quantum photonic states using free electrons
Authors: Ben Hayun A. , Reinhardt O. , Nemirovsky J. , Karnieli A. , Rivera N. , Kaminer I.
Published: March 2021

The interactions of free electrons with optical cavities enable the creation of novel quantum photonic states.
Porcine Sapovirus-Induced Tight Junction Dissociation via Activation of the RhoA/ROCK/MLC Signaling Pathway
Authors: Sharif Muhammad , Baek Yeong-Bin , Naveed Ahsan , Stalin Nattan , Kang Mun-Il , Park Sang-Ik , Soliman Mahmoud , Cho Kyoung-Oh
Published: March 2021

PSaV, one of the most important enteric pathogens, is known to disrupt TJ integrity to expose its buried coreceptor occludin in polarized LLC-PK cells. However, the cellular signaling pathways that facilitate TJ dissociation are not yet completely understood.
Direct Priming of CD8+T Cells Persists in the Face of Cowpox Virus Inhibitors of Antigen Presentation
Authors: Lin Leon C. W. , Croft Sarah N. , Croft Nathan P. , Wong Yik Chun , Smith Stewart A. , Tang Swee-Seong , Purcell Anthony W. , Tscharke David C.
Published: March 2021

CD8+T cells are key to antiviral immunity, so it is important to understand how they are activated. Many viruses have proteins that protect infected cells from T cell attack by interfering with the process that allows virus infection to be recognized by CD8+T cells.
Sarco/Endoplasmic Reticulum Ca
2+
-Transporting ATPase (SERCA) Modulates Autophagic, Inflammatory, and Mitochondrial Responses during Influenza A Virus Infection in Human Lung Cells
Authors: Peng Jiaojiao , Ran Yeqian , Xie Haojun , Deng Ling , Li Chufang , Chen Ling
Published: March 2021

IAV is a major cause of infectious respiratory diseases, characterized by a marked respiratory tract inflammatory response that causes morbidity and mortality in seasonal epidemics or pandemic outbreaks. SERCA is a critical component in maintaining cellular calcium levels and is positively correlated with autophagic flux.
Draft Genome Sequence of the Sattazolin-Producing Strain
Pseudonocardia
sp. C8, Isolated from a Mud Dauber Wasp Nest in Nepal
Authors: Aryal Niraj , Aziz Saefuddin , Rajbhandari Prajwal , Gross Harald
Published: March 2021

Here, we report a 6.2-Mbp draft genome sequence of the bacterium
Pseudonocardia
sp. strain C8, which gave insight into the complete secondary metabolite production capacity of the strain and hinted that the strain possibly represents a new species.
Draft Genome Sequence of the Type Strain Bacillus subtilis subsp.
subtilis
DSM10
Authors: Lilge Lars , Hertel Robert , Morabbi Heravi Kambiz , Henkel Marius , Commichau Fabian M. , Hausmann Rudolf
Published: March 2021

The
Bacillus subtilis
subsp.
subtilis
type strain DSM10 has been used as a reference in various studies. However, detailed information about the genome has not been available. Therefore, whole-genome sequencing was performed, and the sequence was compared with that of the related
B. subtilis
strain NCIB3610.
Complete Annotated Genome Sequence of the Salmonella enterica Serovar Typhimurium LT7 Strain STK003, Historically Used in Gene Transfer Studies
Authors: Zaworski Julie , Guichard Anne , Fomenkov Alexey , Morgan Richard D. , Raleigh Elisabeth A.
Published: March 2021

The genome of
Salmonella enterica
serovar Typhimurium LT7 comprises a chromosome and two plasmids. One plasmid is very close to pSLT of
Salmonella
Typhimurium LT2; the second harbors a shufflon region. Prophage content is distinct: LT7 lacks Fels-1, while Gifsy-1 and Fels-2 show island-like divergence and likely programmed inversion, respectively.
The Recombinant Luciferase of the Fungus Neonothopanus nambi: Obtaining and Properties
Authors: Gorokhovatsky A. Yu. , Chepurnykh T. V. , Shcheglov A. S. , Mokrushina Yu. A. , Baranova M. N. , Goncharuk S. A. , Purtov K. V. , Petushkov V. N. , Rodionova N. S. , Yampolsky I. V.
Published: March 2021

A key component of the recently described bioluminescent system of higher fungi is luciferase, a new class of proteins. The properties of fungal luciferase and their relationship with its structure are interesting both for improving autoluminescent systems already created on its basis and for creating new ones. Therefore, it is extremely important to understand the spatial structure of this protein. We have performed heterologous expression and purification of Neonothopanus nambi luciferase, obtained a protein suitable for subsequent crystallization, and also determined some biochemical properties of the recombinant luciferase.
Cowden syndrome: new clinical features in a large family; joint hyperextensibility, dental abnormalities and gingival enlargement
Authors: Sabir Ataf , Parry Gabriella , Heaton Tricia , Ong Kai Ren
Published: March 2021

A 4-year-old boy presented with his mother to genetics in the 1980s, with a family history (FH) of macrocephaly and intellectual disability (ID). He remained undiagnosed until his mother developed multiple cancers and was diagnosed with Cowden syndrome (CS) in 2017, a rare, multisystem cancer predisposition syndrome. CS was then confirmed in multiple family members. Clinical examination revealed potentially novel features; gingival enlargement, dental abnormalities and joint hyperextensibility. These features could contribute to revised PTEN hamartoma tumour syndrome, National Comprehensive Cancer Network, minor diagnostic criteria. The paediatric CS phenotype is still emerging and features expressed in this family during childhood could potentially aid paediatric diagnosis. This case reminds clinicians to seek genetic input for PTEN testing when macrocephaly is identified alongside, a personal or FH of ID, early-onset tumours (especially breast, bowel or thyroid) or multiple tumours. Thus detailed FH is pivotal to earlier CS diagnosis and improved patient outcomes.
A new simple endoscopic incision therapy for refractory benign oesophageal anastomotic stricture
Authors: Choi Jeongmin , Choi Soo In
Published: March 2021

Oesophageal anastomotic stricture is a frequent complication after esophagectomy. In most cases, endoscopic bougination or balloon dilation usually resolves anastomotic stricture. However, some refractory oesophageal strictures remain difficult to treat and cause significant morbidity. Recently, successful treatment using endoscopic incisional therapy has been reported in several cases. We report a case of refractory benign oesophageal anastomotic stricture after oesophagectomy. A 72-year-old man underwent three consecutive bouginations. However, he developed progressive stricture. Stricture was successfully treated with an endoscopic knife incision. We performed only three incisions without a cutting method, which was new compared with previous reports. A new simple endoscopic incision technique is effective and safe for stricture management. In conclusion, endoscopic incisional therapy may be recommended as a salvage treatment for properly selected patients with refractory benign stricture who do not respond to conventional therapy.
Double inferior vena cava in a monochorionic twin pregnancy with selective fetal growth restriction
Authors: Mosimann Beatrice , Amylidi-Mohr Sofia , Surbek Daniel V , Raio Luigi
Published: March 2021

Congenital anomalies of the infrarenal inferior vena cava (IVC) are well described in adult life, however, little information exists on their associations in fetal life. Here, we describe a case of a monochorionic diamniotic (MCDA) twin pregnancy complicated by selective fetal growth restriction (sFGR) with an incidental finding of a double IVC in one child. In fetal life, variants of the infrarenal IVC are strongly associated with heart defects, which might suggest haemodynamic alterations or genetic causes, even more so in our case with MCDA twins complicated by sFGR.
Three-year OCT predictive factors of disease recurrence in eyes with successfully treated myopic choroidal neovascularisation
Authors: Borrelli Enrico , Battista Marco , Vella Giovanna , Sacconi Riccardo , Querques Lea , Grosso Domenico , Bandello Francesco , Querques Giuseppe
Published: March 2021

Purpose

To assess the relationship of demographics, clinical characteristics and structural optical coherence tomography (OCT) findings to disease recurrence in a cohort of patients with newly diagnosed myopic choroidal neovascularisation (CNV)

Methods

In this retrospective, longitudinal study, a total of 64 participants (64 eyes) with successfully treated myopic CNV had obtained resolution of exudation after treatment (study baseline) and with 3 years of regular follow-ups. Several baseline OCT qualitative features and quantitative measurements were assessed at baseline and included in the analysis. Main outcome measures included incidence of disease recurrence and HR for demographics, clinical characteristics and OCT risk factors.

Results

At month 36, 40 eyes (62.5%) developed disease recurrence (active CNV). Multivariate linear regression analysis revealed that final visual acuity (dependent variable) was associated with visual acuity at the first visit after complete resolution of exudation (p<0.0001), baseline size of patchy atrophy (p=0.010), baseline subfoveal choroidal thickness (p=0.008), baseline maximum CNV height and width (p=0.011 and p=0.003) and recurrence of CNV exudation (p=0.007). The following factors were associated with an increased risk of disease recurrence: size of patchy atrophy had an HR of 1.14 (95% CI 1.01 to 1.29; p=0.036); maximum CNV width had an HR of 1.02 (95% CI 1.01 to 1.04; p<0.0001).

Conclusion

We identified OCT risk factors for the disease recurrence in eyes with successfully treated myopic CNV. Assuming that disease recurrence is a sight-threatening event, our findings may help in the identification of high-risk patients and eventually ameliorate their outcome.
Years of potential life lost in pre-diabetes and diabetes mellitus: data from a 40-year follow-up of the Israel study on Glucose intolerance, Obesity and Hypertension
Authors: Rapoport Micha , Chetrit Angela , Cantrell Dror , Novikov Ilya , Roth Jesse , Dankner Rachel
Published: March 2021

Introduction

We examined years of potential life lost (YPLL) associated with pre-diabetes as compared with either normoglycemia or diabetes, using data of the Israel cohort of Glucose intolerance, Obesity and Hypertension 40-year follow-up.

Research design and methods

Men and women (N=2844, mean age 52.0±8.2 years) who underwent oral glucose tolerance test and anthropometric measurements, during 1976–1982, were followed for mortality until May 2019. Multiple imputation procedures for missing mortality dates and multivariable regression mixed models were applied.

Results

At baseline, 35.8%, 48.8% and 15.4% individuals were found with normoglycemia, pre-diabetes, and diabetes, respectively. The average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 4.3 years (95% CI 3.3 to 5.2; p<0.001). YPLL were 1 year higher in women with pre-diabetes than in men with pre-diabetes. These differences persisted mainly in individuals younger than 60 years, and those with body mass index (BMI) <25 kg/m2, at baseline. Adjusting for age, sex, country of origin, smoking status, BMI, and blood pressure, the average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 2.0 years (95% CI 1.2 to 2.8; p<0.001). Significant reductions of 5.9 years (95% CI 4.8 to 7.0) on average were observed for diabetes as compared with pre-diabetes and 7.9 years (95% CI 6.7 to 9.1) as compared with individuals with normoglycemia.

Conclusions

This study reveals that life expectancy of middle-aged individuals with pre-diabetes is shorter than of normoglycemic ones. These findings are especially relevant in view of the rising worldwide prevalence of pre-diabetes within younger age groups and underscore the crucial importance of interventions by either lifestyle modification or drug therapy capable of delaying progression from pre-diabetes to diabetes to reduce the YPLL in this high-risk group.
Beyond deaths per capita: comparative COVID-19 mortality indicators
Authors: Heuveline Patrick , Tzen Michael
Published: March 2021

Objectives

Following well-established practices in demography, this article discusses several measures based on the number of COVID-19 deaths to facilitate comparisons over time and across populations.

Settings

National populations in 186 United Nations countries and territories and populations in first-level subnational administrative entities in Brazil, China, Italy, Mexico, Peru, Spain and the USA.

Participants

None (death statistics only).

Primary and secondary outcome measures

An unstandardised occurrence/exposure rate comparable to the Crude Death Rate; an indirectly age-and-sex standardised rate that can be derived even when the breakdown of COVID-19 deaths by age and sex required for direct standardisation is unavailable; the reduction in life expectancy at birth corresponding to the 2020 number of COVID-19 deaths.

Results

To date, the highest unstandardised rate has been in New York, at its peak exceeding the state 2017 crude death rate. Populations compare differently after standardisation: while parts of Italy, Spain and the USA have the highest unstandardised rates, parts of Mexico and Peru have the highest standardised rates. For several populations with the necessary data by age and sex for direct standardisation, we show that direct and indirect standardisation yield similar results. US life expectancy is estimated to have declined this year by more than a year (−1.26 years), far more than during the worst year of the HIV epidemic, or the worst 3 years of the opioid crisis, and to reach its lowest level since 2008. Substantially larger reductions, exceeding 2 years, are estimated for Panama, Peru, and parts of Italy, Spain, the USA and especially, Mexico.

Conclusions

With lesser demand on data than direct standardisation, indirect standardisation is a valid alternative to adjust international comparisons for differences in population distribution by sex and age-groups. A number of populations have experienced reductions in 2020 life expectancies that are substantial by recent historical standards.
Scheduled Prophylactic 6-Hourly IV AcetaminopheN to Prevent Postoperative Delirium in Older CaRdiac SurgicAl Patients (PANDORA): protocol for a multicentre randomised controlled trial
Authors: Khera Tanvi , Mathur Pooja A , Banner-Goodspeed Valerie M , Narayanan Shilpa , Mcgourty Marie , Kelly Lauren , Palihnich Kerry , Novack Lena , Davis Roger , Talmor Daniel , Marcantonio Edward R , Subramaniam Balachundhar
Published: March 2021

Introduction

Postoperative delirium is common among older cardiac surgery patients. Often difficult to predict and address prophylactically, delirium complicates the postoperative course by increasing morbidity and mortality as well as prolonging both hospital and intensive care unit (ICU) lengths of stay. Based on our pilot trial, we intend to study the effect of scheduled 6-hourly acetaminophen administration for 48 hours post-cardiac surgery with cardiopulmonary bypass (CPB) on the incidence of in-hospital delirium and long-term neurocognitive outcomes. Additionally, effect on duration and severity of delirium, rescue analgesic consumption, acute and chronic pain scores and lengths of hospital and ICU stay will also be explored.

Methods and analysis

This multicentre, randomised, placebo-controlled, quadruple-blinded trial will include 900 older (>60 years) cardiac surgical patients requiring CPB. Patients meeting the inclusion criteria and not meeting any exclusion criteria will be enrolled at seven centres across the USA with Beth Israel Deaconess Medical Center (BIDMC), Boston, as the central coordinating centre. Additional sites may be included to broaden or speed accrual. The primary outcome measure is the incidence of in-hospital delirium till day 30. Secondary outcomes include the duration and severity of in-hospital delirium, hospital and ICU lengths of stay, postoperative pain scores, postoperative rescue analgesic consumption, postoperative cognitive function and chronic sternal pain. Creation of a biorepository and the use of intraoperative-blinded electroencephalogram (EEG) and cerebral oximetry data will support exploratory endpoints to determine mechanistic predictors of postoperative delirium.

Ethics and dissemination

This trial is approved and centrally facilitated by the Institutional Review Board at BIDMC. An independent Data Safety and Monitoring Board is responsible for maintaining safety oversight. Protocol # 2019 P00075, V.1.4 (dated 20 October 2020).

Trial registration number

NCT04093219.
Association between urbanisation and the risk of hyperuricaemia among Chinese adults: a cross-sectional study from the China Health and Nutrition Survey (CHNS)
Authors: Yu Xixi , Zhu Cheng , Zhang Han , Shen Ziyan , Chen Jing , Gu Yulu , Lv Shiqi , Zhang Di , Wang Yulin , Ding Xiaoqiang , Zhang Xiaoyan
Published: March 2021

Objective

To explore the association between urbanicity and hyperuricaemia (HUA) and whether urbanicity is an independent risk factor for HUA in Chinese adults.

Design

Data analysis from a cross-sectional survey.

Setting and participants

8579 subjects aged 18 years or older were enrolled in the study from the 2009 wave of the China Health and Nutrition Survey to analyse the association between urbanicity and HUA. We divided them into three categories according to urbanisation index (low, medium and highly urbanised groups).

Main outcome measures

HUA was defined as serum uric acid ≥7 mg/dL in men and ≥6 mg/dL in women.

Results

The prevalence of HUA in low, medium and highly urbanised groups was 12.2%, 14.6% and 19.8%, respectively. The independent factors influencing serum uric acid included age, gender, hypertension, diabetes, chronic kidney disease, drinking, obesity and community-level urbanisation index (β=0.016, p<0.001). The risk of HUA in the highly urbanised group was significantly higher than that of the low urbanised group (OR 1.771, 95% CI 1.545 to 2.029, p<0.001), even after adjusting for other covariates (OR 1.661, 95% CI 1.246 to 2.212, p=0.001). In a subgroup analysis, we found that age, gender, comorbidity (such as hypertension, diabetes, obesity and chronic kidney disease) and physical activity affected the association between urbanisation and the risk of HUA.

Conclusions

Our findings suggest that living in highly urbanised areas is linked with higher risk of HUA independent of cardiometabolic and health-related behavioural risk factors, which have been shown to increase along with urbanisation.
Is the public supportive and willing to pay for a national assistive reproductive therapies programme? Results from a multicountry survey
Authors: Skedgel Chris , Ralphs Eleanor , Finn Elaine , Whitty Jennifer A , Markert Marie , Samuelsen Carl
Published: March 2021

Objectives

To understand attitudes towards infertility and willingness to pay (WTP) towards a publicly funded national assistive reproductive therapies (ART) programme.

Design

Attitudes survey with dichotomous and open-ended WTP questions.

Setting

Online survey administered in the USA, UK, Spain, Norway, Sweden, Finland, Denmark and China.

Participants

7945 respondents, analysed by country. Nordic respondents were pooled into a regionally representative sample.

Primary and secondary outcome measures

Primary outcome measures were proportion of sample agreeing with different infertility-related and ART-related value statements and supporting a monthly contribution to fund a national ART programme, expressed in local currency. Secondary outcome measure was maximum WTP.

Results

Across the nationally representative samples, 75.5% of all respondents agreed with infertility as a medical condition and 82.3% and 83.7% with ART eligibility for anyone who has difficulty having a baby or a medical problem preventing them from having a baby, respectively. 56.4% of respondents supported a defined monthly contribution and 73.9% supported at least some additional contribution to fund a national ART programme. Overall, converting to euros, median maximum WTP was €3.00 and mean was €15.47 (95% CI 14.23 to 16.72) per month. Maximum WTP was highest in China and the USA and lowest in the European samples.

Conclusions

This large, multicountry survey extends our understanding of public attitudes towards infertility and fertility treatment beyond Europe. It finds evidence that a majority of the public in all sampled countries/regions views infertility as a treatable medical condition and supports the idea that all infertile individuals should have access to treatments that improve the chance of conception. There was also strong agreement with the idea that the desire for children is a basic human need. WTP questions showed that a majority of respondents supported a monthly contribution to fund a national ART programme, although there is some evidence of an acquiescence bias that may overstate support among specific samples.
ROP screening and treatment in four district-level special newborn care units in India: a cross-sectional study of screening and treatment rates
Authors: Sabherwal Shalinder , Gilbert Clare , Foster Allen , Kumar Praveen
Published: March 2021

Objective

Blindness from retinopathy of prematurity (ROP) in middle-income countries is generally due to absence of screening or inadequate screening. The objective of this study was to assess uptake of services in an ROP programme in four district-level special newborn care units in India.

Design

Cross-sectional study.

Setting

All four neonatal units of a state in India where model programme for ROP had been introduced

Patients

Infants eligible for screening and treatment of ROP between March and May 2017.

Intervention

Data on sex, birth weight and gestational age of eligible infants were collected and medical records reviewed for follow-up.

Main outcome measures

Proportion of eligible infants screened and for those screened, age at first screening, completion of screening, diagnosis and treatment received if indicated. The characteristics of infants screened and not screened were compared.

Results

137 (18%) of the 751 infants eligible for screening were screened at least once, with no statistically significant difference by sex. The mean birth weight and gestational age of those screened were significantly lower than those not screened. Among those screened, 43% underwent first screening later than recommended and 44% had incomplete follow-up. Fourteen infants (11% of those screened) were diagnosed with ROP. Five were advised laser treatment and all complied.

Conclusion

Uptake, completion and timing of first screening was suboptimal. Some planned interventions including training of nursing staff, use of integrated data-management software and providing material for parent counselling, which have been initiated, need to be fully implemented to improve uptake of ROP screening services.
Smart agent system for insulin infusion protocol management: a simulation-based human factors evaluation study
Authors: Rosen Michael A , Romig Mark , Demko Zoe , Barasch Noah , Dwyer Cynthia , Pronovost Peter J , Sapirstein Adam
Published: March 2021

Objective

To compare the insulin infusion management of critically ill patients by nurses using either a common standard (ie, human completion of insulin infusion protocol steps) or smart agent (SA) system that integrates the electronic health record and infusion pump and automates insulin dose selection.

Design

A within subjects design where participants completed 12 simulation scenarios, in 4 blocks of 3 scenarios each. Each block was performed with either the manual standard or the SA system. The initial starting condition was randomised to manual standard or SA and alternated thereafter.

Setting

A simulation-based human factors evaluation conducted at a large academic medical centre.

Subjects

Twenty critical care nurses.

Interventions

A systems engineering intervention, the SA, for insulin infusion management.

Measurements

The primary study outcomes were error rates and task completion times. Secondary study outcomes were perceived workload, trust in automation and system usability, all measured with previously validated scales.

Main results

The SA system produced significantly fewer dose errors compared with manual calculation (17% (n=20) vs 0, p<0.001). Participants were significantly faster, completing the protocol using the SA system (p<0.001). Overall ratings of workload for the SA system were significantly lower than with the manual system (p<0.001). For trust ratings, there was a significant interaction between time (first or second exposure) and the system used, such that after their second exposure to the two systems, participants had significantly more trust in the SA system. Participants rated the usability of the SA system significantly higher than the manual system (p<0.001).

Conclusions

A systems engineering approach jointly optimised safety, efficiency and workload considerations.
Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer
Authors: Seo Incheol , Lee Hye Won , Byun Sang Jun , Park Jee Young , Min Hyeonji , Lee Sung Hwan , Lee Ju-Seog , Kim Shin , Bae Sung Uk
Published: March 2021

Background

Neoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.

Methods

We analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.

Results

Gene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.

Conclusions

Taken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.
CXCR6 deficiency impairs cancer vaccine efficacy and CD8+resident memory T-cell recruitment in head and neck and lung tumors
Authors: Karaki Soumaya , Blanc Charlotte , Tran Thi , Galy-Fauroux Isabelle , Mougel Alice , Dransart Estelle , Anson Marie , Tanchot Corinne , Paolini Lea , Gruel Nadege , Gibault Laure , Lepimpec-Barhes Francoise , Fabre Elizabeth , Benhamouda Nadine , Badoual Cecile , Damotte Diane , Donnadieu Emmanuel , Kobold Sebastian , Mami-Chouaib Fathia , Golub Rachel , Johannes Ludger , Tartour Eric
Published: March 2021

Background

Resident memory T lymphocytes (TRM) are located in tissues and play an important role in immunosurveillance against tumors. The presence of TRMprior to treatment or their induction is associated to the response to anti-Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1) immunotherapy and the efficacy of cancer vaccines. Previous work by our group and others has shown that the intranasal route of vaccination allows more efficient induction of these cells in head and neck and lung mucosa, resulting in better tumor protection. The mechanisms of in vivo migration of these cells remains largely unknown, apart from the fact that they express the chemokine receptor CXCR6.

Methods

We usedCXCR6-deficient mice and an intranasal tumor vaccination model targeting the Human Papillomavirus (HPV) E7 protein expressed by the TC-1 lung cancer epithelial cell line. The role of CXCR6 and its ligand, CXCL16, was analyzed using multiparametric cytometric techniques and Luminex assays.

Human biopsies obtained from patients with lung cancer were also included in this study.

Results

We showed that CXCR6 was preferentially expressed by CD8+TRMafter vaccination in mice and also on intratumoral CD8+TRMderived from human lung cancer. We also demonstrate that vaccination of Cxcr6-deficient mice induces a defect in the lung recruitment of antigen-specific CD8+T cells, preferentially in the TRMsubsets. In addition, we found that intranasal vaccination with a cancer vaccine is less effective in theseCxcr6-deficient mice compared with wild-type mice, and this loss of efficacy is associated with decreased recruitment of local antitumor CD8+TRM. Interestingly, intranasal, but not intramuscular vaccination induced higher and more sustained concentrations of CXCL16, compared with other chemokines, in the bronchoalveolar lavage fluid and pulmonary parenchyma.

Conclusions

This work demonstrates the in vivo role of CXCR6-CXCL16 axis in the migration of CD8+resident memory T cells in lung mucosa after vaccination, resulting in the control of tumor growth. This work reinforces and explains why the intranasal route of vaccination is the most appropriate strategy for inducing these cells in the head and neck and pulmonary mucosa, which remains a major objective to overcome resistance to anti-PD-1/PD-L1, especially in cold tumors.