bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-related quality of life among patients with hypertension: population-based survey using EQ-5D-5L in Hong Kong SAR, China
Authors: Wong Eliza Lai Yi , Xu Richard Huan , Cheung Annie Wai Ling
Published: September 2019

Objectives

To evaluate the effect of hypertension and related comorbidities on the health-related quality of life (HRQoL) using EuroQol 5-dimensions instrument with five-level scale (EQ-5D-5L) Hong Kong (HK) version.

Design

Data were analysed by a secondary data analysis based on a cross-sectional study assessing experience on public specialist outpatient service.

Setting

A representative sample was recruited from 26 specialist outpatient clinics in HK.

Participants

A total of 4528 patients with hypertension aged 18 or above who responded to the survey.

Intervention

EQ-5D-5L HK was applied to assess the HRQoL. The five-dimension descriptive system and the utility index of EQ-5D-5L were treated as the dependent variable in the current study. Regression modelling was applied to estimate the effect of hypertension and related comorbidities on health-related quality of life.

Results

More respondents were women (53.9%), aged ≥65 years old (60.1%), and with primary educational attainment or below (52.3%). A total of 1466 respondents (32.4%) also reported suffering from diabetes, heart disease (20.8%), vision problem (1.7%) and cancer (1.5%). In the ordinal least squares model, utility decreased most when patients reported having physical disability associated with hypertension (beta=−0.395, SE=0.047), and 0.128, 0.064, 0.05 and 0.048 for mental problem, cancer, vision problem and heart problem. In the Tobit model, the utility reduced most for comorbidity of physical disability, and then mental problem, cancer, vision problem, heart problem and diabetes. For first part of two-part model, respondents coliving with mental problem were 10% less likely to report a full health. For the second part of two-part model, the respondents with physical disability had 0.294 lower in utility.

Conclusions

Respondents with hypertension reported a low EQ-5D utility score. Respondents were women, with a high education, fully employed and living with families reported better HRQoL. There is a significant effect of comorbidity influence on the decreased HRQoL, particularly those with physical disability and mental problem.
Comparing single-best-answer and very-short-answer questions for the assessment of applied medical knowledge in 20 UK medical schools: Cross-sectional study
Authors: Sam Amir H , Westacott Rachel , Gurnell Mark , Wilson Rebecca , Meeran Karim , Brown Celia
Published: September 2019

Objectives

The study aimed to compare candidate performance between traditional best-of-five single-best-answer (SBA) questions and very-short-answer (VSA) questions, in which candidates must generate their own answers of between one and five words. The primary objective was to determine if the mean positive cue rate for SBAs exceeded the null hypothesis guessing rate of 20%.

Design

This was a cross-sectional study undertaken in 2018.

Setting

20 medical schools in the UK.

Participants

1417 volunteer medical students preparing for their final undergraduate medicine examinations (total eligible population across all UK medical schools approximately 7500).

Interventions

Students completed a 50-question VSA test, followed immediately by the same test in SBA format, using a novel digital exam delivery platform which also facilitated rapid marking of VSAs.

Main outcome measures

The main outcome measure was the mean positive cue rate across SBAs: the percentage of students getting the SBA format of the question correct after getting the VSA format incorrect. Internal consistency, item discrimination and the pass rate using Cohen standard setting for VSAs and SBAs were also evaluated, and a cost analysis in terms of marking the VSA was performed.

Results

The study was completed by 1417 students. Mean student scores were 21 percentage points higher for SBAs. The mean positive cue rate was 42.7% (95% CI 36.8% to 48.6%), one-sample t-test against ≤20%: t=7.53, p<0.001. Internal consistency was higher for VSAs than SBAs and the median item discrimination equivalent. The estimated marking cost was £2655 ($3500), with 24.5 hours of clinician time required (1.25 s per student per question).

Conclusions

SBA questions can give a false impression of students’ competence. VSAs appear to have greater authenticity and can provide useful information regarding students’ cognitive errors, helping to improve learning as well as assessment. Electronic delivery and marking of VSAs is feasible and cost-effective.
Factors influencing access to kidney transplantation: a research protocol of a qualitative study on stakeholders’ perspectives
Authors: Kloss Katja , Ismail Sohal , Redeker Steef , van Hoogdalem Lothar , Luchtenburg Annemarie , Busschbach Jan J V , van de Wetering Jacqueline
Published: September 2019

Introduction

Unequal access to kidney transplantation is suggested, but no systematic inventory exists about factors influencing access to kidney transplantation. There is an absence of any research that has combined stakeholder perspectives along the complete trajectory of transplantation. The present qualitative study explores the contributing factors from the perspectives of multiple stakeholders in this trajectory, including patients, health professionals and health insurance and financial representatives in the Netherlands. Moreover, stakeholders will be invited to suggesting strategies and solutions for handling the facilitating and hindering factors found. By means of interaction, stakeholder groups will arrive at a consensus for new policymaking in the field of a Dutch transplantation care.

Methods and analysis

The different stakeholders’ perspectives and possible solutions will be explored by interviewing in three phases. In the first phase, stakeholders’ group perspectives will be explored with individual interviews and focus group interviews without confrontation of views from other perspectives. In the second phase of focus group interviewing, perspectives will be confronted with the other stakeholders’ perspectives assessed. Finally, in the third phase, stakeholders will be invited to focus group discussions for suggesting solutions to overcome barriers and promote facilitators for improving access to transplantation. Approximately, groups from six to twelve participants per focus group and four to maximal six focus groups will be held per stakeholder, depending on the level of saturation, as prescribed by grounded theory. The interviews will be audio-recorded and transcribed verbatim, and qualitative data will be analysed according to the principles of grounded theory supported by using NVivo software.

Ethics and dissemination

The Medical Ethical Committee of Erasmus MC, Rotterdam, The Netherlands, has approved this study. The results will be disseminated in peer-reviewed journals and major international conferences.
Long-term impact of giving antibiotics before skin incision versus after cord clamping on children born by caesarean section: protocol for a longitudinal study based on UK electronic health records
Authors: Šumilo Dana , Nirantharakumar Krishnarajah , Willis Brian H , Rudge Gavin , Martin James , Gokhale Krishna , Thayakaran Rasiah , Adderley Nicola J , Chandan Joht Singh , Okoth Kelvin , Hewston Ruth , Skrybant Magdalena , Deeks Jonathan J , Brocklehurst Peter
Published: September 2019

Introduction

In the UK, about a quarter of women give birth by caesarean section (CS) and are offered prophylactic broad-spectrum antibiotics to reduce the risk of maternal postpartum infection. In 2011, national guidance was changed from recommending antibiotics after the umbilical cord was cut to giving antibiotics prior to skin incision based on evidence that earlier administration reduces maternal infectious morbidity. Although antibiotics cross the placenta, there are no known short-term harms to the baby. This study aims to address the research gap on longer term impact of these antibiotics on child health.

Methods and analysis

A controlled interrupted time series study will use anonymised mother-baby linked routine electronic health records for children born during 2006–2018 recorded in UK primary care (The Health Improvement Network, THIN and Clinical Practice Research Datalink, CPRD) and secondary care (Hospital Episode Statistics, HES) databases. The primary outcomes of interest are asthma and eczema, two common allergy-related diseases in childhood. In-utero exposure to antibiotics immediately prior to CS will be compared with no exposure when given after cord clamping. The risk of outcomes in children delivered by CS will also be compared with a control cohort delivered vaginally to account for time effects. We will use all available data from THIN, CPRD and HES with estimated power of 80% and 90% to detect relative increase in risk of asthma of 16% and 18%, respectively at the 5% significance level.

Ethics and dissemination

Ethical approval has been obtained from the University of Birmingham Ethical Review Committee with scientific approvals obtained from the independent scientific advisory committees from the Medicines and Healthcare products Regulatory Agency for CPRD and the data provider, IQVIA for THIN. The results will be published in peer-reviewed journals, presented at national and international conferences and disseminated to stakeholders.
Pharmacokinetics of prednisolone in children: an open-label, randomised, two-treatment cross-over trial investigating the bioequivalence of different prednisolone formulations in children with airway disease
Authors: Haslund-Krog Sissel Sundell , Schmidt Maria , Mathot Ron , Kryger Jensen Andreas , Jørgensen Inger Merete , Holst Helle
Published: September 2019

Introduction

One in three Danish children under 3 years of age experience asthma-like symptoms, and one-third will later be diagnosed with asthma. Oral prednisolone is used in various formulations to treat acute asthma. However, the potential differences in bioequivalence between these formulations have never been examined in children despite interchangeable use in clinical practice.

Methods and analysis

An open-label, randomised, two-treatment cross-over trial investigating the bioequivalence of different prednisolone formulations in children with airway disease.

The included patients (6 months–11 years of age) are admitted to the Department of Paediatric and Adolescent Medicine Nordsjællands University Hospital, Hillerød, with asthma or asthma-like symptoms.

The primary objective is to assess the bioequivalence between different prednisolone formulations herein area under the concentration time curve, Cmax and Tmax using saliva samples. The secondary objectives are to evaluate tolerability (five-point face scale), adverse events and severity of the disease. If the patient has an intravenous access for other purposes, the saliva samples will be validated with plasma samples.

A total of 66 evaluable patients are needed according to European Medicines Agency Guideline on bioequivalence.

Ethics and dissemination

Traditional pharmacokinetic trials are burdensome due to the extent of blood samples necessary to capture the time-dependant drug profile. Saliva sampling is far more acceptable for paediatric patients. In addition, this trial adheres to standard dosing strategies. No additional venepunctures are performed, and no additional prednisolone doses are administered.

Guidelines for paediatric bioequivalence trials are warranted.

Trial registration number

The Danish Medicines Agency EudraCT: 2017-003590-33, The Ethics Committee case no: H-17027252, and the Danish Data Protection Agency: BFH-2017–103, I-Suite no.: 05935.
The relationship of gross upper and lower limb motor competence to measures of health and fitness in adolescents aged 13–14 years
Authors: Weedon Benjamin David , Liu Francesca , Mahmoud Wala , Metz Renske , Beunder Kyle , Delextrat Anne , Morris Martyn G , Esser Patrick , Collett Johnny , Meaney Andy , Howells Ken , Dawes Helen
Published: September 2019

Introduction

Motor competence (MC) is an important factor in the development of health and fitness in adolescence.

Aims

This cross-sectional study aims to explore the distribution of MC across school students aged 13–14 years old and the extent of the relationship of MC to measures of health and fitness across genders.

Methods

A total of 718 participants were tested from three different schools in the UK, 311 girls and 407 boys (aged 13–14 years), pairwise deletion for correlation variables reduced this to 555 (245 girls, 310 boys). Assessments consisted of body mass index, aerobic capacity, anaerobic power, and upper limb and lower limb MC. The distribution of MC and the strength of the relationships between MC and health/fitness measures were explored.

Results

Girls performed lower for MC and health/fitness measures compared with boys. Both measures of MC showed a normal distribution and a significant linear relationship of MC to all health and fitness measures for boys, girls and combined genders. A stronger relationship was reported for upper limb MC and aerobic capacity when compared with lower limb MC and aerobic capacity in boys (t=−2.21, degrees of freedom=307, P=0.03, 95% CI −0.253 to –0.011).

Conclusion

Normally distributed measures of upper and lower limb MC are linearly related to health and fitness measures in adolescents in a UK sample.

Trial registration number

NCT02517333.
$$dS_5$$ vacua from matter-coupled 5D $$N=4$$ gauged supergravity
Authors: Dao H. L. , Karndumri Parinya
Published: September 2019

We study $$dS_5$$dS5 vacua within matter-coupled $$N=4$$N=4 gauged supergravity in five dimensions using the embedding tensor formalism. With a simple ansatz for solving the extremization and positivity of the scalar potential, we derive a set of conditions for the gauged supergravity to admit $$dS_5$$dS5 as maximally symmetric background solutions. The results provide a new approach for finding $$dS_5$$dS5 vacua in five-dimensional $$N=4$$N=4 gauged supergravity and explain a number of notable features pointed out in previous works. These conditions also determine the form of the gauge groups to be $$SO(1,1)\times G_{\text {nc}}$$SO(1,1)×Gnc with $$G_{\text {nc}}$$Gnc being a non-abelian non-compact group. In general, $$G_{\text {nc}}$$Gnc can be a product of SO(1, 2) and a smaller non-compact group $${G^{\prime }}_{{\text {nc}}}$$G′nc together with (possibly) a compact group. The SO(1, 1) factor is gauged by one of the six graviphotons, that is singlet under $$SO(5)\sim USp(4)$$SO(5)∼USp(4) R-symmetry. The compact parts of SO(1, 2) and $${G^{\prime }}_{{\text {nc}}}$$G′nc are gauged by vector fields from the gravity and vector multiplets, respectively. In addition, we explicitly study $$dS_5$$dS5 vacua for a number of gauge groups and compute scalar masses at the vacua. As in the four-dimensional $$N=4$$N=4 gauged supergravity, all the $$dS_5$$dS5 vacua identified here are unstable.
Topological invariants of plane curve singularities: Polar quotients and Łojasiewicz gradient exponents
Authors: Nguyen Hong-Duc , Phạm Tien-Son , Hoàng Phi-Dũng
Published: September 2019

In this paper, we study polar quotients and Łojasiewicz exponents of plane curve singularities, which are not necessarily reduced. We first show that, for complex plane curve singularities, the set of polar quotients is a topological invariant. We next prove that the Łojasiewicz gradient exponent can be computed in terms of the polar quotients, and so it is also a topological invariant. For real plane curve singularities, we also give a formula computing the Łojasiewicz gradient exponent via real polar branches. As an application, we give effective estimates of the Łojasiewicz exponents in the gradient and classical inequalities of polynomials in two (real or complex) variables.
Bound states in functional renormalization group
Authors: Jakovác Antal , Patkós András
Published: September 2019

Equivalence criteria are established for an effective Yukawa-type theory of composite fields representing two-particle fermion bound states with the original “microscopic” theory of interacting fermions based on the spectral decomposition of the 2-to-2 fermion scattering amplitude. Functional renormalization group equations of the effective theory are derived exploiting relations expressing the equivalence. The effect of truncating the spectral decomposition is investigated quantitatively on the example of the nonrelativistic bound states of two oppositely charged fermions.
THE IMPACTS OF INFORMALITY ON ENTERPRISE INNOVATION, SURVIVAL AND PERFORMANCE: SOME EVIDENCE FROM PAKISTAN
Authors: ULLAH SANA , WILLIAMS COLIN C. , ARIF BABUR WASIM
Published: September 2019

The aim of this paper is to evaluate the relationship between informality, innovation and firm survival. To do so, a study of a cluster of electrical fittings firms in Pakistan is reported. Reporting bivariate and multivariate probit models to analyze two surveys conducted between 2008 and 2017, the finding is that there is a significant relationship between informality and the extent of innovation, firm survival and firm performance. Informality has an adverse negative effect on firm-level innovation, firm survival and firm performance. Given that formal enterprises in this cluster are better performing in terms of innovation, survival and employment growth than informal businesses, the paper concludes by discussing the theoretical, policy and research implications.
Magnetocaloric behavior of REE porphyrin-based paramagnets at room temperature
Authors: Korolev V. V. , Lomova T. N. , Ramazanova A. G. , Balmasova O. V. , Mozhzhukhina E. G.
Published: September 2019

REE complexes with cyclic aromatic ligands are ranked as the molecular materials with both electronic functionality and a single-molecule magnet behavior at temperatures lower 80 K. At the temperature close to room, they display a positive magnetocaloric effect (MCE) often comparable with one in ferromagnetics. We were determined MCE during the magnetization of both (5,10,15,20-tetra(4-tert-butylphenylporphinato))ytterbium(III)chloride, (Cl)YbT[Formula: see text]BuPP and (5,10,15,20-tetraphenylporphinato)ytterbium(III)chloride, (Cl)YbTPP in their aqueous suspensions over the temperature range of 278–320 K and in magnetic fields from zero to 1 T by the direct microcalorimetric method. Specific heat capacity in the solid of (Cl)YbT[Formula: see text]BuPP/(Cl)YbTPP has been directly determined in zero magnetic fields using differential scanning calorimetry. Thermodynamic parameters of ytterbium(III) complexes magnetization namely enthalpy/entropy change was determined. To improve understanding of the correlation between (Cl)YbT[Formula: see text]BuPP/(Cl)YbTPP magnetic properties and its electronic structure, we have compared magnetic behavior of paramagnets studied with those for (Cl)MTPP where M = Gd, Eu, Tm.
Oxygen reduction reaction catalyzed by overhanging carboxylic acid strapped iron porphyrins adsorbed on carbon nanotubes
Authors: Boitrel Bernard , Bouget Morgane , Das Pradip K. , Le Gac Stéphane , Roisnel Thierry , Hanana Manel , Arcostanzo Hélène , Cornut Renaud , Jousselme Bruno , Campidelli Stéphane
Published: September 2019

A series of hybrid catalysts for the oxygen reduction reaction (ORR) has been investigated. They are composed of multi-wall carbon nanotubes (MWNTs) coated with iron strapped porphyrins. Two porphyrins have been probed; both are strapped with the same skeleton and differ only by the number of overhung carboxylic acid(s), either one or two. In this structure, the carboxylic acid group can act as a proton relay between the medium and the catalyst or as a polar group surrounding the dioxygen binding cavity. While the number of carboxylic acid group(s) does not exhibit a significant influence on the catalytic properties, the combination of both components–MWNTs and porphyrin–leads to a better catalytic activity than those of the nanotubes or the porphyrins taken separately.
Synthesis, characterization and modeling of self-assembled porphyrin nanorods
Authors: Laurencin Danielle , Yot Pascal G. , Gervais Christel , Guari Yannick , Clément Sébastien , Elkaim Erik , Paillet Matthieu , Cot Didier , Richeter Sébastien
Published: September 2019

Porphyrin nanorods were prepared by ion-association between free-base meso 5,10,15,20-tetrakis-(4-[Formula: see text]-methylpyridinium)porphyrin cations and tetraphenylborate anions. The nanorods have variable lengths (up to a few micrometers long) and diameters ([Formula: see text]50–500 nm). Their structure at the molecular level was elucidated by combining multinuclear solid state NMR spectroscopy, synchrotron X-ray powder diffraction and DFT calculations.
Epitaxial growth of β-Ga2O3 thin films on Ga2O3 and Al2O3 substrates by using pulsed laser deposition
Authors: An Yuxin , Dai Liyan , Wu Ying , Wu Biao , Zhao Yanfei , Liu Tong , Hao Hui , Li Zhengcheng , Niu Gang , Zhang Jinping , Quan Zhiyong , Ding Sunan
Published: September 2019

In this work, we have successfully grown high quality epitaxial [Formula: see text]-Ga2O3 thin films on [Formula: see text]-Ga2O3 (100) and Al2O3(0001) substrates using pulsed laser deposition (PLD). By optimizing temperature and oxygen pressure, the best conditions were found to be 650–700∘C and 0.5[Formula: see text]Pa. To further improve the quality of hetero-epitaxial [Formula: see text]-Ga2O3, the sapphire substrates were pretreated for atomic terraced surface by chemical cleaning and high temperature annealing. From the optical transmittance measurements, the films grown at 600–750∘C exhibit a clear absorption edge at deep ultraviolet region around 250–275[Formula: see text]nm wavelength. High resolution transmission electron microscope (HRTEM) images and X-ray diffraction (XRD) patterns demonstrate that [Formula: see text]-Ga2O3(-201)//Al2O3(0001) epitaxial texture dominated the epitaxial oxide films on sapphire substrate, which opens up the possibilities of high power electric devices.
Coseismic and monsoon-triggered landslide impacts on remote trekking infrastructure, Langtang Valley, Nepal
Authors: Jones J. N. , Stokes M. , Boulton S. J. , Bennett G. L. , Whitworth M. R. Z.
Published: September 2019

In 2015, the M
w
7.8 Gorkha earthquake struck Nepal, triggering thousands of landslides across the central and eastern Himalayas. These landslides had many adverse effects, including causing widespread damage to low-grade transport routes (e.g. tracks, footpaths) in rural regions that depend on tourism for survival. Langtang Valley is a glacial–periglacial landscape located 60 km north of Kathmandu. It is one of the most popular trekking regions in Nepal and has been severely affected by Gorkha earthquake-triggered and monsoon-triggered landsliding. Here, qualitative and quantitative observations from fieldwork and remote sensing are used to describe the materials and geomorphology of the landslides across Langtang Valley, and to quantify the extent to which coseismic and monsoon-triggered landslides have affected Langtang's trekking infrastructure. The dominant bedrock materials involved within Langtang landslides are found to be a range of gneisses and intruded leucogranites. In total, 64 landslides are found to have intersected trekking paths across Langtang, with coseismic and monsoon-triggered landslides having an impact on
c.
3 km and 0.8 km of path respectively. It is observed that the practice of reconstructing paths through unstable landslide deposits is leaving the trekking infrastructure across Langtang increasingly vulnerable to future failure.
Relationship between V̇o2peak, cycle economy, and mitochondrial respiration in untrained/trained
Authors: Hunter Gary R. , Moellering Douglas R. , Windham Samuel T. , Mathis Shannon L. , Bamman Marcas M. , Fisher Gordon
Published: September 2019

Aerobic capacity is negatively related to locomotion economy. The purpose of this paper is to determine what effect aerobic exercise training has on the relationship between net cycling oxygen uptake (inverse of economy) and aerobic capacity [peak oxygen uptake (V̇o2peak)], as well as what role mitochondrial coupled and uncoupled respiration may play in whole body aerobic capacity and cycling economy. Cycling net oxygen uptake and V̇o2peak were evaluated on 31 premenopausal women before exercise training (baseline) and after 8–16 wk of aerobic training. Muscle tissue was collected from 15 subjects at baseline and post-training. Mitochondrial respiration assays were performed using high-resolution respirometry. Pre- ( r = 0.46, P < 0.01) and postexercise training ( r = 0.62, P < 0.01) V̇o2peak and cycling net oxygen uptake were related. In addition, uncoupled and coupled fat respiration were related both at baseline ( r = 0.62, P < 0.01) and post-training ( r = 0.89, P < 01). Post-training coupled ( r = 0.74, P < 0.01) and uncoupled carbohydrate respiration ( r = 0.52, P < 05) were related to cycle net oxygen uptake. In addition, correlations between V̇o2peak and cycle net oxygen uptake persist both at baseline and after training, even after adjusting for submaximal cycle respiratory quotient (an index of fat oxidation). These results suggest that the negative relationship between locomotion economy and aerobic capacity is increased following exercise training. In addition, it is proposed that at least one of the primary factors influencing this relationship has its foundation within the mitochondria. Strong relationships between coupled and uncoupled respiration appear to be contributing factors for this relationship.

NEW & NOTEWORTHY The negative relationship between cycle economy and aerobic capacity is increased following exercise training. The strong relationship between coupled and uncoupled respiration, especially after training, appears to be contributing to this negative relationship between aerobic capacity and cycling economy, suggesting that mitochondrial economy is not increased following aerobic exercise training. These results are suggestive that training programs designed to improve locomotion economy should focus on changing biomechanics.
Time-based pulmonary features from electrical impedance tomography demonstrate ventilation heterogeneity in chronic obstructive pulmonary disease
Authors: Milne Stephen , Huvanandana Jacqueline , Nguyen Chinh , Duncan Joseph M. , Chapman David G. , Tonga Katrina O. , Zimmermann Sabine C. , Slattery Alexander , King Gregory G. , Thamrin Cindy
Published: September 2019

Pulmonary electrical impedance tomography (EIT) is a functional imaging technique that allows real-time monitoring of ventilation distribution. Ventilation heterogeneity (VH) is a characteristic feature of chronic obstructive pulmonary disease (COPD) and has previously been quantified using features derived from tidal variations in the amplitude of the EIT signal. However, VH may be better described by time-based metrics, the measurement of which is made possible by the high temporal resolution of EIT. We aimed 1) to quantify VH using novel time-based EIT metrics and 2) to determine the physiological relevance of these metrics by exploring their relationships with complex lung mechanics measured by the forced oscillation technique (FOT). We performed FOT, spirometry, and tidal-breathing EIT measurements in 11 healthy controls and 9 volunteers with COPD. Through offline signal processing, we derived 3 features from the impedance-time ( Z- t) curve for each image pixel: 1) tE, mean expiratory time; 2) PHASE, mean time difference between pixel and global Z- t curves; and 3) AMP, mean amplitude of Z- t curve tidal variation. Distribution was quantified by the coefficient of variation (CV) and the heterogeneity index (HI). Both CV and HI of the tE and PHASE features were significantly increased in COPD compared with controls, and both related to spirometry and FOT resistance and reactance measurements. In contrast, distribution of the AMP feature showed no relationships with lung mechanics. These novel time-based EIT metrics of VH reflect complex lung mechanics in COPD and have the potential to allow real-time visualization of pulmonary physiology in spontaneously breathing subjects.

NEW & NOTEWORTHY Pulmonary electrical impedance tomography (EIT) is a real-time imaging technique capable of monitoring ventilation with exquisite temporal resolution. We report novel, time-based EIT measurements that not only demonstrate ventilation heterogeneity in chronic obstructive pulmonary disease (COPD), but also reflect oscillatory lung mechanics. These EIT measurements are noninvasive, radiation-free, easy to obtain, and provide real-time visualization of the complex pathophysiology of COPD.
Study of Demarcation Line Depth in Transepithelial versus Epithelium-Off Accelerated Cross-Linking (AXL) in Keratoconus
Authors: Salah Yehia , Omar Kholoud , Sherif Ahmed , Azzam Sarah
Published: September 2019

Aim. This is a prospective interventional clinical trial to assess the depth of the demarcation line in transepithelial versus epithelium-off accelerated corneal cross-linking (AXL) in keratoconus patients. Methods. This prospective clinical trial was conducted on 40 eyes of 20 patients. Each patient had transepithelial AXL in one eye and epithelium-off AXL in the contralateral eye applying UVA light with an irradiance of 45 mW/cm2 for 2.4 minutes and 30 mW/cm2 for 4 minutes. The depth of the demarcation line was measured using anterior segment OCT (Topcon 3D OCT-2000) one month postoperative for both eyes. Results. The demarcation line was patchy in 50% of the transepithelial AXL eyes, the other half showing a demarcation line at a mean depth of 183 ± 41.6 μm. In the epithelium-off AXL technique, the demarcation line was well defined in all cases with a mean depth of 219 ± 27.3 μm. There was a statistically significant difference in corneal demarcation line depth between transepithelial and epithelium-off techniques (P = 0.008 and P < 0.05). The shallower demarcation line in the transepithelial group suggests that it is less effective. Conclusion. Based on the depth of the demarcation line, the cross-linking effect of epi-off AXL seems more efficacious than after transepithelial AXL. The future will show if the biomechanical effect will be sufficient to stop progression of keratoconus similarly after standard CXL. This trial is registered with NCT04045626.
A Deterministic Construction for Jointly Designed Quasicyclic LDPC Coded-Relay Cooperation
Authors: Asif Muhammad , Zhou Wuyang , Yu Qingping , Li Xingwang , Khan Nauman Ali
Published: September 2019

This correspondence presents a jointly designed quasicyclic (QC) low-density parity-check (LDPC) coded-relay cooperation with joint-iterative decoding in the destination node. Firstly, a design-theoretic construction of QC-LDPC codes based on a combinatoric design approach known as optical orthogonal codes (OOC) is presented. Proposed OOC-based construction gives three classes of binary QC-LDPC codes with no length-4 cycles by utilizing some known ingredients including binary matrix dispersion of elements of finite field, incidence matrices, and circulant decomposition. Secondly, the proposed OOC-based construction gives an effective method to jointly design length-4 cycles free QC-LDPC codes for coded-relay cooperation, where sum-product algorithm- (SPA-) based joint-iterative decoding is used to decode the corrupted sequences coming from the source or relay nodes in different time frames over constituent Rayleigh fading channels. Based on the theoretical analysis and simulation results, proposed QC-LDPC coded-relay cooperations outperform their competitors under same conditions over the Rayleigh fading channel with additive white Gaussian noise.
Sensor Fault Detection and Diagnosis Method for AHU Using 1-D CNN and Clustering Analysis
Authors: Liu Jingjing , Zhang Min , Wang Hai , Zhao Wei , Liu Yan
Published: September 2019

This paper presents a fault detection and diagnosis (FDD) method, which uses one-dimensional convolutional neural network (1-D CNN) and WaveCluster clustering analysis to detect and diagnose sensor faults in the supply air temperature (Tsup) control loop of the air handling unit. In this approach, 1-D CNN is employed to extract man-guided features from raw data, and the extracted features are analyzed by WaveCluster clustering. The suspicious sensor faults are indicated and categorized by denoting clusters. Moreover, the Tc acquittal procedure is introduced to further improve the accuracy of FDD. In validation, false alarm ratio and missing diagnosis ratio are mainly used to demonstrate the efficiency of the proposed FDD method. Results show that the abrupt sensor faults in Tsup control loop can be efficiently detected and diagnosed, and the proposed method is equipped with good robustness within the noise range of 6 dBm∼13 dBm.
Influence of Rock Strength on the Propagation of Slotted Cartridge Blasting‐Induced Directional Cracks
Authors: Shu Yun , Shao Peng , Dong Chao , Cao Zhen , Yi Xinwei
Published: September 2019

Based on theories of explosive mechanics and rock fracture mechanics, the influence mechanism of rock strength on the propagation length of the primary crack in the directional fracture blasting with slotted cartridge has been investigated deeply to propose the relation equation between the rock strength and the propagation length of the primary crack. Theoretically, the maximum length am of the primary crack increases with the enhancing rock strength parameters. The explicit dynamic analysis software LS‐DYNA has been used to simulate the slotted cartridge blasting in the mudstone, sandstone, and granite with different strengths in order to reveal the effect of rock strength on the propagation length and velocity of the primary crack and the stress distribution characteristics in rock. The numerical results show the primary crack easily bifurcates and attain a much shorter propagation length in the mudstone with the minimum strength, and there are radial cracks appearing in the nonslotted direction. When rock strength rises, the propagation length, velocity, and duration of the primary crack and the concentration degree of effective stress in the slotted direction will all increase in the sandstone and granite, but there is an opposite influence trend of rock strength in the stage of the initial guide crack’s formation. The cracking velocity has an overall oscillation downtrend whose swing amplitude enhances clearly with the increasing rock strength, signifying the more unsteady propagation of the primary crack in the higher strength rock.
IL-2 Induces Transient Arrest in the G1 Phase to Protect Cervical Cancer Cells from Entering Apoptosis
Authors: Lagunas-Cruz María del Carmen , Valle-Mendiola Arturo , Trejo-Huerta Jonathan , Rocha-Zavaleta Leticia , Mora-García María de Lourdes , Gutiérrez-Hoya Adriana , Weiss-Steider Benny , Soto-Cruz Isabel
Published: September 2019

Interleukin 2 (IL-2) has been used for the treatment of different types of cancer that express the IL-2 receptor (IL-2R). However, the effect of IL-2 on cervical cancer cells is unknown. IL-2R is present in normal cells of the immune system but not in the healthy cervix. We report that IL-2R is expressed in cervical cancer cells. IL-2 decreases cervical cancer cell proliferation via transient arrest of the G1 phase, which does not result in apoptosis or senescence. IL-2 upregulates the expression of p53 and p21 and downregulates cyclin D. In addition, we report the resistance of cervical cancer cells to treatments that induce apoptosis in HeLa and INBL cells. When arrested cells were treated with cisplatin, the cytokine protected cells from apoptosis induced by cisplatin. The effects of IL-2 on the cell cycle do not induce cellular senescence or activate the proapoptotic protein Bax. The cell arrest induced by IL-2 is conferring protection to cells against apoptosis.
Immobilization of Alkaline Collagenase from Bacillus subtilis onto Sulfonated Polystyrene Nanospheres for Hydrolysis of Tilapia Collagen
Authors: Zhang Ling , Yang Xiaocui , Xiao Kaijun , Lu Yuyi , Li Chunhai , Zhang Zijin
Published: September 2019

The structure of an alkaline protease from Bacillus subtilis used by a tilapia collagen peptide manufacturer was analyzed, and the technology of the enzyme immobilized by sulfonated polystyrene (SPS) nanoparticles was studied. The particle size distribution, SEM, EDS, TEM, and FT-IR spectroscopy of the carrier before and after immobilization were analyzed. The results showed that the molecular weight of the purified enzyme protein was 31.0 kDa. The amino acid sequence with a consistency of 64.04% and one three-dimensional structure simulation diagram of the purified enzyme protein were obtained by LC-MS-MS, which suggested that the protein might belong to subtilisin. The optimal immobilization conditions were as follows: the volume ratio of the immobilization carrier to the enzyme was 3 : 50 (mL : mL), the immobilized temperature was 25°C, and the system pH was 4.5. Under this condition, the immobilization ratio of collagenase was 73.48%, the specific activity was 274.05 U/μg, and the specific activity of the immobilized enzyme was about 53.74% that of the free enzyme. The average particle size of SPS nanospheres was 155.1 nm. The characterization results of SEM, EDS, TEM, and FT-IR spectroscopy showed that the collagenase was successfully immobilized onto SPS nanospheres. The experimental results also showed that the collagenase could be immobilized effectively under the optimal conditions by using SPS nanospheres, and the operation process was simple, feasible, and of low cost with good prospect of industrial application.
Modeling Cellular Response in Large-Scale Radiogenomic Databases to Advance Precision Radiotherapy
Authors: Manem Venkata SK. , Lambie Meghan , Smith Ian , Smirnov Petr , Kofia Victor , Freeman Mark , Koritzinsky Marianne , Abazeed Mohamed E. , Haibe-Kains Benjamin , Bratman Scott V.
Published: September 2019

Radiotherapy is integral to the care of a majority of patients with cancer. Despite differences in tumor responses to radiation (radioresponse), dose prescriptions are not currently tailored to individual patients. Recent large-scale cancer cell line databases hold the promise of unravelling the complex molecular arrangements underlying cellular response to radiation, which is critical for novel predictive biomarker discovery. Here, we present RadioGx, a computational platform for integrative analyses of radioresponse using radiogenomic databases. We fit the dose–response data within RadioGx to the linear-quadratic model. The imputed survival across a range of dose levels (AUC) was a robust radioresponse indicator that correlated with biological processes known to underpin the cellular response to radiation. Using AUC as a metric for further investigations, we found that radiation sensitivity was significantly associated with disruptive mutations in genes related to nonhomologous end joining. Next, by simulating the effects of different oxygen levels, we identified putative genes that may influence radioresponse specifically under hypoxic conditions. Furthermore, using transcriptomic data, we found evidence for tissue-specific determinants of radioresponse, suggesting that tumor type could influence the validity of putative predictive biomarkers of radioresponse. Finally, integrating radioresponse with drug response data, we found that drug classes impacting the cytoskeleton, DNA replication, and mitosis display similar therapeutic effects to ionizing radiation on cancer cell lines. In summary, RadioGx provides a unique computational toolbox for hypothesis generation to advance preclinical research for radiation oncology and precision medicine.

Significance:

The RadioGx computational platform enables integrative analyses of cellular response to radiation with drug responses and genome-wide molecular data.
Urinary Leukotriene E4 and 2,3-Dinor Thromboxane B2 Are Biomarkers of Potential Harm in Short-Term Tobacco Switching Studies
Authors: Makena Patrudu , Liu Gang , Chen Peter , Yates Charles R. , Prasad G.L.
Published: September 2019

Background:

Modified risk tobacco products (MRTP) can reduce harm by decreasing exposure to combustion-related toxicants. In the absence of epidemiologic data, biomarkers of potential harm (BoPH) are useful to evaluate the harm-reducing potential of MRTPs. This study evaluated whether arachidonic acid (AA)-derived metabolites serve as short-term BoPH for predicting harm reduction in tobacco product–switching studies.

Methods:

We used 24-hour urine samples from participants in a series of short-term studies in which smokers switched from combustible to noncombustible tobacco products [oral smokeless tobacco products or electronic nicotine delivery system (ENDS)] or abstinence. Pre- and postswitching samples were analyzed by LC/MS-MS for alterations in select AA metabolites, including prostaglandins, isoprostanes, thromboxanes, and leukotrienes.

Results:

Switching to abstinence, dual use of combustible and noncombustible products, or exclusive use of noncombustible products resulted in reduced 2,3-d-TXB2 levels. Moreover, switching smokers to either abstinence or exclusive use of oral tobacco products resulted in reduced LTE4, but dual use of combustible and oral tobacco products or ENDS did not. A two-biomarker classification model comprising 2,3-d-TXB2 and LTE4 demonstrated the highest performance in distinguishing smokers switched to either abstinence or to ENDS and oral smokeless tobacco products.

Conclusions:

Urinary 2,3-d-TXB2 and LTE4 can discriminate between combustible tobacco users and combustible tobacco users switched to either abstinence or noncombustible products for 5 days.

Impact:

2,3-d-TXB2 and LTE4, which are linked to platelet activation and inflammation, represent BoPH in short-term tobacco product–switching studies. Thus, from a regulatory perspective, 2,3-d-TXB2 and LTE4 may aid in assessing the harm reduction potential of MRTPs.
Associations of Tobacco and Alcohol Use with Risk of Neuroendocrine Tumors of the Small Intestine in Utah
Authors: Curtin Karen , Cannon-Albright Lisa A. , VanDerslice James , Yu Zhe , Herget Kimberly A. , Thota Ramya , Neklason Deborah W.
Published: September 2019

Background:

Incidence of small-intestine neuroendocrine tumors (SINT) has been increasing in the United States over the past 40 years, with higher incidence in Utah than elsewhere. As information about how these tumors arise is limited, elucidating lifestyle factors associated with SINT in a statewide cohort could potentially identify those at risk to help mitigate their effects.

Methods:

Cases of SINT with a carcinoid histology (8240 or 8241) diagnosed in Utah from 1996 to 2014 with no prior history of cancer within 5 years (n = 433) were matched to population controls (1:10 ratio). Tobacco and alcohol exposures before case diagnosis were identified from International Classification of Diseases codes in statewide medical records and from self-reported data captured at patient encounters beginning in 1996. Multivariate logistic regression was used to estimate risk of SINT associated with tobacco and alcohol in cases compared with controls.

Results:

An increased risk of SINT was observed in tobacco-exposed individuals compared with unexposed [OR, 1.44; 95% confidence interval (CI), 1.11–1.86; P = 0.006]. Those who were exposed to alcohol exhibited an increased risk of SINT (OR, 1.62; 95% CI, 1.05–2.49; P = 0.03).

Conclusions:

This study supports tobacco and alcohol use as risk factors for SINT, independent of family history. However, low rates of smoking and alcohol use in Utah coupled with higher rates of SINT suggest other factors may contribute to development of these tumors.

Impact:

Although tobacco and alcohol modestly contribute to risk, our study suggests in addition to greater detection of tumors, other as-of-yet undefined exposures may drive rising SINT incidence.
Esophageal Thermal Exposure to Hot Beverages: A Comparison of Metrics to Discriminate Distinct Consumption Habits
Authors: Middleton Daniel R.S. , Xie Shuang-Hua , Bouaoun Liacine , Byrnes Graham , Song Guo-Hui , Schüz Joachim , Wei Wen-Qiang , McCormack Valerie A.
Published: September 2019

Background:

Hot beverage consumption is a probable risk factor for esophageal squamous cell carcinoma (ESCC). No standardized exposure assessment protocol exists.

Methods:

To compare how alternative metrics discriminate distinct drinking habits, we measured sip temperatures and sizes in an international group of hot beverage drinkers in France (n = 20) and hot porridge consumers (n = 52) in a high ESCC incidence region of China. Building on the knowledge that sip size and temperature affect intraesophageal liquid temperature (IELT), IELTs were predicted by modeling existing data, and compared with first sip temperature and, across all sips, mean temperature and sip-weighted mean temperature.

Results:

Two contrasting exposure characteristics were observed. Compared with the international group, Chinese porridge consumers took larger first sips [mean difference +17 g; 95% confidence interval (CI), 13.3–20.7] of hotter (+9.5°C; 95% CI, 6.2–12.7) liquid, and their mean sip size did not vary greatly across sips, but the former groups increased in size as temperature decreased. This resulted in higher predicted IELTs (mean 61°C vs. 42.4°C) and sip-weighted temperatures (76.9°C vs. 56°C) in Chinese porridge consumers, and compared with first sip and mean temperature, these two metrics separated the groups to a greater extent.

Conclusions:

Distinguishing thermal exposure characteristics between these groups was greatly enhanced by measuring sip sizes. Temperature at first sip alone is suboptimal for assessing human exposure to hot foods and beverages, and future studies should include sip size measurements in exposure assessment protocols.

Impact:

This study provides a logistically feasible framework for assessing human exposure to hot beverages.
Clinical Assessment of 5-Fluorouracil/Leucovorin, Nab-Paclitaxel, and Irinotecan (FOLFIRABRAX) in Untreated Patients with Gastrointestinal Cancer Using UGT1A1 Genotype–Guided Dosing
Authors: Joshi Smita S. , Catenacci Daniel V.T. , Karrison Theodore G. , Peterson Jaclyn D. , Zalupski Mark M. , Sehdev Amikar , Wade James , Sadiq Ahad , Picozzi Vincent J. , Amico Andrea , Marsh Robert , Kozloff Mark F. , Polite Blase N. , Kindler Hedy L. , Sharma Manish R.
Published: September 2019

Purpose:

5-Fluorouracil (5-FU)/leucovorin, irinotecan, and nab-paclitaxel are all active agents in gastrointestinal cancers; the combination, FOLFIRABRAX, has not been previously evaluated. UDP Glucuronosyltransferase 1A1 (UGT1A1) clears SN-38, the active metabolite of irinotecan. UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity and predisposes to toxicity. We performed a trial to assess the safety and tolerability of FOLFIRABRAX with UGT1A1 genotype–guided dosing of irinotecan.

Patients and Methods:

Patients with previously untreated, advanced gastrointestinal cancers received FOLFIRABRAX with prophylactic pegfilgrastim every 14 days. UGT1A1 *1/*1, *1/*28, and *28/*28 patients received initial irinotecan doses of 180, 135, and 90 mg/m2, respectively. 5-FU 2,400 mg/m2 over 46 hours, leucovorin 400 mg/m2, and nab-paclitaxel 125 mg/m2 were administered. Doses were deemed tolerable if the dose-limiting toxicity (DLT) rate during cycle 1 was ≤35% in each genotype group. DLTs were monitored using a sequential procedure.

Results:

Fifty patients enrolled, 30 pancreatic, 9 biliary tract, 6 gastroesophageal, and 5 others. DLTs occurred in 5 of 23 (22%) *1/*1 patients, 1 of 19 (5%) *1/*28 patients, and 0 of 7 *28/*28 patients. DLTs were all grade 3: diarrhea (3 patients), nausea (2 patients), and febrile neutropenia (1 patient). The overall response rate was 31%. Response rates in pancreatic, gastroesophageal, and biliary tract cancers were 34%, 50%, and 11%, respectively. Eighteen patients (36%) received therapy for at least 24 weeks.

Conclusions:

FOLFIRABRAX with genotype-guided dosing of irinotecan is tolerable in patients with advanced gastrointestinal cancer and UGT1A1*1*1 or UGT1A1*1*28 genotypes. Too few *28/*28 patients were enrolled to provide conclusive results. Responses occurred across multiple tumor types.