bluuebunny/crossref_metadata_2025 huggingface dataset:
Two‐Way Reversible Shape Memory Properties of Benzoyl Peroxide Crosslinked Poly(ethylene‐co‐vinyl acetate) under Different Stress Conditions
Authors: Hui Jin , Xia Hong , Fu Yaqin , Qiu Yiping , Ni Qing‐Qing
Published: March 2020

Two‐way (reversible) chemically crosslinked semicrystalline shape memory polymers are synthesized using poly(ethylene‐co‐vinyl acetate) (PEVA) with benzoyl peroxide (BPO). The two‐way shape memory effect (2W‐SME) is achieved under both constant stress and stress‐free conditions. It is found that the stress‐free 2W‐SME can be achieved by the relationship between the initial prestretching strain (Rprestretch) and recovery strain (Rrec). Under the same prestretching stress, the stress‐free two‐way shape memory behavior can be controlled by variation of Rrec using a different setting temperature (Tset) in the recovery process. More importantly, the driving force and recovery force, as one of the key indicators for two‐way shape memory materials, are investigated, and they significantly change depending on the BPO content. The sample with high BPO content shows excellent high‐temperature creep resistant performance. A highly crosslinked structure can suppress viscous flow and provides sufficient force to allow the sample to recover its initial shape after crystal melting. Therefore, the PEVA/BPO samples are able to contract during heating. The presence of an oriented crystal structure with high applied stress that causes sample elongation during cooling is also investigated. These findings for PEVA/BPO two‐way shape memory polymers will contribute to their applications as soft actuators in various fields.
Striatal Dopamine Denervation Impairs Gait Automaticity in Drug‐Naïve Parkinson's Disease Patients
Authors: Hirata Kosei , Hattori Takaaki , Kina Satoko , Chen Qingmeng , Ohara Masahiro , Yokota Takanori
Published: March 2020

Background

Gait automaticity, which is impaired in patients with Parkinson's disease (PD), can be quantified by gait variability analysis. Among the 3 regions of the striatum (sensorimotor, executive, and limbic), the sensorimotor region may play a crucial role in motor automaticity in healthy individuals. However, neural correlates of impaired gait automaticity are poorly investigated in PD.

Objective

We aimed to examine the relationship between gait automaticity and striatal dopaminergic depletion in drug‐naïve PD patients.

Methods

A total of 21 drug‐naïve PD patients and 12 healthy controls were enrolled. Gait parameters were measured via wearable inertial sensors under fast‐paced gait or cognitive dual‐task conditions, and their respective coefficient of variation (CV) and dual‐task cost were calculated. The extent of striatal dopaminergic depletion was evaluated by dopamine transporter (DAT) imaging with single‐photon emission computed tomography using N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐[123I]iodophenyl)nortropane. Correlation between DAT uptake and gait variables was analyzed using the region‐of‐interest analysis for the 3 right or left striatal regions and voxel‐based analysis.

Results

PD had higher mean bilateral CV and dual‐task cost of stride length than healthy controls. The mean bilateral CV of stride length was negatively correlated with DAT uptake in the bilateral executive regions of the striatum. Voxel‐based analysis revealed a negative correlation between the mean bilateral CV of stride length and DAT uptake in the anteromedial striatum.

Conclusions

Dopaminergic denervation in the anteromedial striatum, a part of the executive region, is associated with impaired gait automaticity in drug‐naïve PD patients. This region may compensate for the posterior sensorimotor striatum, maintaining gait automaticity. © 2020 International Parkinson and Movement Disorder Society
Label‐free in situ pH monitoring in a single living cell using an optical nanoprobe
Authors: Yang Qingbo , Zhang Xiaobei , Song Yang , Li Ke , Shi Honglan , Xiao Hai , Ma Yinfa
Published: March 2020

Intracellular pH plays critical roles in cell and tissue functions during processes such as metabolism, proliferation, apoptosis, ion transportation, endocytosis and muscle contraction. It is thus an important biomarker that can readily be used to monitor the physiological status of a cell. Thus, disrupted intracellular pH may serve as an early indicator of cell dysfunction and deterioration. Various methods have been developed to detect cellular pH, such as pH‐sensitive labelling reagents with fluorescent or Raman signals. However, excessive cellular uptake of these reagents will not only disrupt cell viability but also compromise effective long‐term monitoring. Here, we present a novel fibre‐optic fluorescent nanoprobe with a high spatial resolution for label‐free, subcellular pH sensing. The probe has a fast response time (~20 s) with minimum invasiveness and excellent pH resolution (0.02 pH units) within a biologically relevant pH environment ranging from 6.17 to 8.11. Its applicability was demonstrated on cultured A549 lung cancer cells, and its efficacy was further testified in two typical cytotoxic cases using carbonylcyanide 3‐chlorophenyl hydrazine, titanium dioxide and nanoparticles. The probe can readily detect the pH variations among cells under toxin/nanoparticles administration, enabling direct monitoring of the early onset of physiological or pathological events with high spatiotemporal resolution. This platform has excellent promise as a minimum invasive diagnostic tool for pH‐related cellular mechanism studies, such as inflammation, cytotoxicity, drug resistance, carcinogenesis and stem cell differentiation.
Weather‐data‐based model: an approach for forecasting leaf and stripe rust on winter wheat
Authors: Rodríguez‐Moreno Victor M. , Jiménez‐Lagunes Alejandro , Estrada‐Avalos Juan , Mauricio‐Ruvalcaba Jorge E. , Padilla‐Ramírez José S.
Published: March 2020

Classification and regression trees (CARTs) for data analysis, an hourly weather dataset, and a 3 year field incidence and severity dataset of winter wheat rust were integrated to forecast pathogens’ presence/absence. The field dataset of incidence and severity was collected for three production cycles. Measured records of 88 Automatic Meteorological Stations and the indirect weather dataset generated in the Weather Research and Forecasting environment interpolated to each Automatic Meteorological Station location were analysed in the Python ecosystem. The focal point of the analysis was the severity of the disease. The analysis of direct weather data revealed the association of leaf rust severity with a night temperature of <14.25°C and global radiation of <521.67 W·m–2, while the estimated dataset showed that its severity is better explained by the dew point temperature of <13.7°C and a mean temperature of <19.06°C. The direct dataset also indicated that stripe rust severity was associated with relative humidity of <88.73%, global radiation of <597.39 W·m–2 and dew point temperature of <16.09°C, whereas the estimated data revealed that pathogen severity is better explained by a model composed of a dew point temperature of <14.6°C, night temperature of <20.4°C and a maximum temperature of <27.9°C. The severity and intensity analysis indicated the pathogen's preference for non‐dry ambient conditions and the preference of stripe rust pathogen for humid and warmer temperatures than leaf rust. The weather thresholds of both pathogens, and CART analysis, unveiled that winter wheat rust can be forecasted. This constitutes the foundation of a more efficient extension programme based on the internet of things.
In Silico Prediction of Metabolic Epoxidation for Drug‐like Molecules via Machine Learning Methods
Authors: Hu Jiajing , Cai Yingchun , Li Weihua , Liu Guixia , Tang Yun
Published: March 2020

Epoxidation is one of the reactions in drug metabolism. Since epoxide metabolites would bind with proteins or DNA covalently, drugs should avoid epoxidation metabolism in the body. Due to the instability of epoxide, it is difficult to determine epoxidation experimentally. In silico models based on big data and machine learning methods are hence valuable approaches to predict whether a compound would undergo epoxidation. In this study, we collected 884 epoxidation data manually from various sources, and finally got 829 unique sites of epoxidation. Three types of molecular fingerprints with different lengths (1024, 2048 or 4096 bits) were used to describe the reaction sites. Six machine learning methods were used to build the classification models. The training set and test set were randomly divided into 8 : 2, and 54 models were constructed and evaluated. Four best models were selected for feature selection. The features were then chosen and verified by external validation set. The resulted optimal model had the accuracy and AUC (area under the curve) values at 0.873 and 0.944 for the test set, 0.838 and 0.987 for the external validation set, respectively. The models built in this study could accurately predict whether a compound will undergo epoxidation and which part is most susceptible to epoxidation, which is of great significance for drug design.
Fully automated and robust analysis technique for popliteal artery vessel wall evaluation (FRAPPE) using neural network models from standardized knee MRI
Authors: Chen Li , Canton Gador , Liu Wenjin , Hippe Daniel S. , Balu Niranjan , Watase Hiroko , Hatsukami Thomas S. , Waterton John C. , Hwang Jenq‐Neng , Yuan Chun
Published: March 2020

Purpose

To develop a fully automated vessel wall (VW) analysis workflow (fully automated and robust analysis technique for popliteal artery evaluation, FRAPPE) on the popliteal artery in standardized knee MR images.

Methods

Popliteal artery locations were detected from each MR slice by a deep neural network model and connected into a 3D artery centerline. Vessel wall regions around the centerline were then segmented using another neural network model for segmentation in polar coordinate system. Contours from vessel wall segmentations were used for vascular feature calculation, such as mean wall thickness and wall area. A transfer learning and active learning framework was applied in training the localization and segmentation neural network models to maintain accuracy while reducing manual annotations. This new popliteal artery analysis technique (FRAPPE) was validated against manual segmentation qualitatively and quantitatively in a series of 225 cases from the Osteoarthritis Initiative (OAI) dataset.

Results

FRAPPE demonstrated high accuracy and robustness in locating popliteal arteries, segmenting artery walls, and quantifying arterial features. Qualitative evaluations showed 1.2% of slices had noticeable major errors, including segmenting the wrong target and irregular vessel wall contours. The mean Dice similarity coefficient with manual segmentation was 0.79, which is comparable to inter‐rater variations. Repeatability evaluations show most of the vascular features have good to excellent repeatability from repeated scans of same subjects, with intra‐class coefficient ranging from 0.80 to 0.98.

Conclusion

This technique can be used in large population‐based studies, such as OAI, to efficiently assess the burden of atherosclerosis from routine MR knee scans.
Gadolinium retention in rat abdominal organs after administration of gadoxetic acid disodium compared to gadodiamide and gadobutrol
Authors: Oh Hyewon , Chung Yong Eun , You Je Sung , Joo Chan Gyu , Kim Pan Ki , Lim Joon Seok , Kim Myeong‐Jin
Published: March 2020

Purpose

To compare gadolinium retention in the abdominal organs after administration of gadoxetic acid disodium, a liver‐specific contrast agent, compared to gadodiamide and gadobutrol.

Methods

Three types of gadolinium‐based contrast agents (GBCAs) were administered to rats. A single (gadodiamide and gadobutrol, 0.1 mmol/kg; gadoxetic acid disodium, 0.025 mmol/kg) or double label‐recommended dose was intravenously administered once (Group 1), a single dose was administered 4 times (Group 2) and a single dose with or without a chelating agent (intraperitoneal injection immediately after each GBCA administration) was administered (Group 3). Rats were sacrificed after 1, 4, and 12 weeks and gadolinium concentrations in the liver, spleen, kidney, muscle, and bone were measured by inductively coupled plasma mass spectrometry. P values less than 0.05 were considered statistically significant.

Results

More gadolinium was retained with a double dose compared to a single dose, but there was no observed significant difference in gadolinium retention after a double dose compared to a single dose (P > .05). Gadodiamide was retained the most in all tissues followed by gadobutrol and gadoxetic acid disodium. Residual gadolinium was significantly less at 4 weeks compared to 1 week (P < .05), but no further decrease was observed after 4 weeks (P > .05). The presence of the chelating agent did not significantly decrease the concentration of residual gadolinium (P > .05).

Conclusion

Gadolinium was retained the least in abdominal organs after gadoxetic acid disodium was administered and most of the residual gadolinium was excreted 4 weeks after GBCA administration when a label‐recommended dose was administered. A commercially available chelation therapy agent could not reduce gadolinium retention.
Impact of age, sex, and global function on normal aortic hemodynamics
Authors: Scott Michael B. , Huh Hyungkyu , van Ooij Pim , Chen Vincent , Herrera Brenda , Elbaz Mohammed , McCarthy Patrick , Malaisrie S. Chris , Carr James , Fedak Paul W. M. , Markl Michael , Barker Alex J.
Published: March 2020

Purpose

To examine the effects of age, sex, and left ventricular global function on velocity, helicity, and 3D wall shear stress (3D‐WSS) in the aorta of N = 100 healthy controls.

Methods

Fifty female and 50 male volunteers with no history of cardiovascular disease, with 10 volunteers per age group (18‐30, 31‐40, 41‐50, 51‐60, and 61‐80 years) underwent aortic 4D‐flow MRI. Quantification of systolic aortic peak velocity, helicity, and 3D‐WSS distribution and the calculation of age group–averaged peak systolic velocity and 3D‐WSS maps (“atlases”) were computed. Age‐related and sex‐related changes in peak velocity, helicity, and 3D‐WSS were computed and correlated with standard metrics of left ventricular function derived from short‐axis cine MRI.

Results

No significant differences were found in peak systolic velocity or 3D‐WSS based on sex except for the 18‐ to 30‐year‐old group (males 8% higher velocity volume and 3D‐WSS surface area). Between successively older groups, systolic velocity decreased (13%, <1%, 7%, and 55% of the aorta volume) and 3D‐WSS decreased (21%, 2%, 30%, and 62% of the aorta surface area). Mean velocity, mean 3D‐3D‐WSS, and median helicity increased with cardiac output (r = 0.27‐0.43, all P < .01), and mean velocity and 3D‐WSS decreased with increasing diameter (r > 0.35, P < .001). Arch and descending aorta systolic mean velocity, mean 3D‐WSS, and median helicity increased with normalized left ventricular volumes: end diastolic volume (r = 0.31‐0.37, P < .01), end systolic volume (r = 0.27‐0.35, P < .01), and stroke volume (r = 0.28‐0.35, P < .01).

Conclusion

Healthy aortic hemodynamics are dependent on subject age, and correlate with vessel diameter and cardiac function.
Constitutive modelling of fine‐grained gassy soil: A composite approach
Authors: Gao Zhiwei , Hong Yi , Wang Lizhong
Published: March 2020

Fine‐grained marine sediments containing large undissolved gas bubbles are widely distributed around the world. Presence of the bubbles could degrade the undrained shear strength (su) of the soil, when the gas pressure ug is relatively high as compared with the effective stress in the saturated soil matrix. Meanwhile, the addition of bubbles may also increase su when the difference between ug and pore water pressure uw becomes smaller than the water entry value, causing partial water drainage from the saturated matrix into the bubbles (bubble flooding) during globally undrained shearing. A new constitutive model for describing the two competing effects on the stress‐strain relationship of fine‐grained gassy soil is proposed within the framework of critical state soil mechanics. The gassy soil is considered as a three‐phase composite material with compressible cavities, which allows water entry from the saturated matrix. Bubble flooding is modelled by introducing an additional positive volumetric strain increment of the saturated clay matrix, which is dependent on the difference between pore gas and pore water pressure based on experimental observations. A modified hardening law based on that of the modified Cam clay model is employed, which in conjunction with the expression for bubble flooding, can describe both the detrimental and beneficial effects of gas bubbles on soil strength and plastic hardening in shear. Only two extra parameters in addition to those in the modified Cam clay model are used. It is shown that the key features of the stress‐strain relationship of three fine‐grained gassy soils can be reproduced satisfactorily.
Relationship between desire to void and bladder capacity and rectal sensory function in patients with multiple sclerosis and anorectal disorders
Authors: Pouyau Camille , Grasland Matthieu , Leroux Camille , Chesnel Camille , Turmel Nicolas , Sheikh Ismael Samer , Le Breton Frederique , Amarenco Gérard , Hentzen Claire
Published: March 2020

Aims

The primary aim of this study was to assess the relationship between a strong desire to void (SDV) and rectal sensory function in patients with multiple sclerosis (PwMS) and anorectal disorders. The secondary aim was to identify clinical, urodynamic or manometric factors associated with greater rectal sensory function impairment in this population.

Methods

Thirty PwMS (mean age 49.2 ± 10.9 years) with anorectal disorders (constipation and/or fecal incontinence) participated in this observational study. Rectal sensory parameters during anorectal manometry were recorded at a strong desire to void and after urination (PV, post‐void). The primary outcome was the desire to defecate volume. Secondary outcomes were first perception and maximum tolerated threshold volumes, presence and modulation of recto‐anal inhibitory reflex.

Results

The mean desire to defecate volume was 125 ± 59 mL at SDV and 104 ± 64 mL at PV (P < .001). The mean maximum tolerated volume was 167 ± 61 mL at SDV vs 141 ± 64 mL after urination (P = .01). The other parameters were not different between SVD and PV conditions. No predictive factors for greater impairment of rectal sensory function were identified.

Conclusion

This study suggests a relationship between bladder sensation and thus bladder capacity, and rectal sensory function in PwMS and with anorectal disorders.
Promoting and maintaining urinary continence: Follow‐up from a cluster‐randomized trial of elderly village women in Bangladesh
Authors: Haque Rezaul , Kabir Fardous , Naher Kamrun , Cherry Nicola , MacDonald Dianna , Wagg Adrian , Chowdhury Zafrullah
Published: March 2020

Aims

Pelvic floor and mobility exercises were shown to be effective in managing incontinence in a cluster‐randomized trial (CRT) of village women aged 60 to 75 years in Bangladesh. The present analysis examines continence 12 months after the CRT and exercise program implementation with village paramedics as preceptors.

Methods

Women from nine villages in the exercise arm of the CRT were followed‐up 12 months after the 6‐month intervention. They provided information about exercise since the CRT and a 3‐day continence record (3DCR). Posttrial, a further 6‐month exercise intervention led by village paramedics was initiated in 20 villages. Women completed the two‐item Sandvik severity questionnaire before and after the intervention. Paramedics kept a record of each woman's attendance at the 48 exercise sessions

Results

A total of 130 of 150 women from the CRT completed the 12‐month follow‐up; 61.5% were dry on the 3DCR at follow‐up. Total continence was related to the continuation of exercises carried out in the home and absence of urinary tract infection at follow‐up. Those exercising at follow‐up had an odds ratio (OR) of 3.49 (95% confidence interval [CI], 1.86‐6.58) of being continent at follow‐up. Higher end‐of‐CRT body mass index was associated with greater follow‐up leakage. In the 20‐village roll‐out, with 316 incontinent women, improvement in both severity and total continence on the Sandvik questionnaire were related to a total number of sessions attended (OR = 1.09; 95% CI, 1.05‐1.13). At roll‐out, 38.6% achieved continence, comparable to 43.0% in the CRT using physiotherapy preceptors

Conclusions

Group exercise classes led by paramedics resulted in a marked improvement in continence but maintenance requires exercise postintervention.
Serum level of soluble interleukin 6 receptor is a useful biomarker for identification of treatment‐resistant major depressive disorder
Authors: Yamasaki Katsuhiko , Hasegawa Tomonori , Takeda Masatoshi
Published: March 2020

Aim

A substantial proportion of major depressive disorder patients are treatment‐resistant to antidepressant therapy, who require augmentation drugs, or other treatments including electroconvulsive therapy or transcranial magnetic stimulation. Identifying treatment‐resistant major depressive disorder patients before the actual administration of antidepressant is, however, often difficult. Accordingly, the serum biomarker to identify treatment‐resistant patients will be helpful in clinical settings. This study aims to clarify the appropriate biomarkers for identification of treatment‐resistant major depressive disorder.

Method

Given that immune‐inflammatory processes are involved in the pathogenesis of major depressive disorder, it is possible that certain cytokine‐related molecules could serve as clinically useful biomarkers of treatment‐resistant major depressive disorder patients. In this study, we measured serum levels of tumor necrosis factor‐α, interleukin 6, and soluble interleukin 6 receptor after major depressive disorder patients underwent antidepressant therapy.

Results

The serum level of soluble interleukin 6 receptor, but not interleukin 6 or tumor necrosis factor‐α, was significantly higher in treatment‐resistant major depressive disorder patients than in remitted patients, suggesting that serum soluble interleukin 6 receptor could be a good biomarker of treatment‐resistant major depressive disorder. Receiver operating characteristic analysis confirmed that serum soluble interleukin‐6 receptor level measurement was useful for identification of treatment‐resistant major depressive disorder patients. Multiple regression analysis using the serum levels of the aforementioned cytokines as explanatory variables and the Quick Inventory of Depressive Symptomatology‐Self Report score (QIDS‐SR16) as a target variable showed that only serum soluble interleukin‐6 receptor level could explain the severity of major depressive disorder.

Conclusion

Based on these results, we recommend measurement of serum soluble interleukin‐6 receptor level to discriminate treatment‐resistant major depressive disorder patients. High serum soluble interleukin‐6 receptor level is associated with the pathogenesis of treatment‐resistant major depressive disorder, suggesting the involvement of the interleukin 6 trans‐signaling system in onset of treatment‐resistant major depressive disorder.
Preconcentration of digoxin using a synthetic imprinted polymer deposited upon the surface of double‐layered hydroxides on porous anodised aluminium wire a triple solid‐phase microextraction fibre
Authors: Piryaei Marzieh , Nazemiyeh Hossein
Published: March 2020

Introduction

A new solid‐phase microextraction fibre is fabricated through polymerisation of molecularly imprinted polymer on the surface of a layered double hydroxide framework that has been fabricated via the in situ synthesis on a non‐porous anodic aluminium oxide/aluminium wire as both the substrate and the aluminium source.

Objective

The synthesized SPME fiber was performed to analyze trace digoxin in real samples.

Material and method

A one‐at‐a‐time optimization strategy was applied for optimizing the important extraction parameters such as extraction solvent, extraction time, stirring rate, pH, ionic strength, and desorption time.

Result

Aluminum surface before and after anodizing and LDH structure reveal that anodizing and preparation LDH increases the surface area and adsorption capacity of aluminum wire.

Conclusion

Under optimum conditions, the repeatability for one fibre (n = 3), expressed as relative standard deviation (RSD %), was 5.2%.
Dual renin‐angiotensin‐aldosterone blockade: Implementation of published research and Dear Doctor letters in ambulatory care: A retrospective observational study using prescription data
Authors: Angelow Aniela , Ploner Tina , Grimmsmann Thomas , Walker Jochen , Chenot Jean‐François
Published: March 2020

Purpose

This study aims to assess the implementation of published research, contraindications, and warnings on the prescription of dual renin‐angiotensin‐hormone system (RAS) blockade in ambulatory care in Germany.

Methods

Cohort study based on health claims data of 6.7 million subjects from 2008 to 2015. Yearly prevalence and incidence for dual RAS blockade with (a) angiotensin‐converting enzyme inhibitors and angiotensin‐receptor blockers (ACEI + ARB) and (b) aliskiren and ACEI or ARB (aliskiren + ACEI/ARB) were calculated. We assessed prescriber specialty and associations between discontinuing dual RAS blockade with specialist (internal medicine, cardiology, nephrology) visits and hospital discharge in the previous year.

Results

A total of 2 984 517 patients were included (age 51.4 ± SD 18.4 y, 48.5% male). Prescription rates for ACEI + ARB decreased from 0.6% (n = 17 907) to 0.4% (n = 12 237) and for aliskiren + ACEI/ARB from 0.23% (n = 6634) to 0.03% (n = 818). Incident prescriptions decreased from 0.23% (n = 6705) to 0.19% (n = 5055) (ACE + ARB) and from 0.1% (n = 2796) to 0.005% (n = 142) (aliskiren + ACE/ARB); 59% of ACEI + ARB and 48% of aliskiren + ACE/ARB combinations were prescribed only by one physician. Of those, 73% (ACEI + ARB) and 58% (aliskiren + ACE/ARB) were primary care providers (PCPs). Discontinuing dual RAS blockade was associated with specialist care and hospital discharge in the previous year (specialist care: RR 1.4, 95% CI, 1.3‐1.6; hospital visit: RR 1.5, 95% CI, 1.3‐1.6).

Conclusions

Our results suggest a delayed uptake of treatment recommendation for ACEI + ARB and a higher impact of Dear Doctor letters addressing PCPs directly compared with published research, contraindications, and warnings. Targeted continuous medical education, practice software alerts, and stronger involvement of pharmacists might improve the implementation of medication safety recommendations in ambulatory care.
Real‐world evidence to support regulatory decision‐making for medicines: Considerations for external control arms
Authors: Burcu Mehmet , Dreyer Nancy A. , Franklin Jessica M. , Blum Michael D. , Critchlow Cathy W. , Perfetto Eleanor M. , Zhou Wei
Published: March 2020

Randomized clinical trials (RCTs) are the gold standard in producing clinical evidence of efficacy and safety of medical interventions. More recently, a new paradigm is emerging—specifically within the context of preauthorization regulatory decision‐making—for some novel uses of real‐world evidence (RWE) from a variety of real‐world data (RWD) sources to answer certain clinical questions. Traditionally reserved for rare diseases and other special circumstances, external controls (eg, historical controls) are recognized as a possible type of control arm for single‐arm trials. However, creating and analyzing an external control arm using RWD can be challenging since design and analytics may not fully control for all systematic differences (biases). Nonetheless, certain biases can be attenuated using appropriate design and analytical approaches. The main objective of this paper is to improve the scientific rigor in the generation of external control arms using RWD. Here we (a) discuss the rationale and regulatory circumstances appropriate for external control arms, (b) define different types of external control arms, and (c) describe study design elements and approaches to mitigate certain biases in external control arms. This manuscript received endorsement from the International Society for Pharmacoepidemiology (ISPE).
Nonisothermal analysis of a couple stress fluid in blade coating process
Authors: Mughees Muhammad , Sajid Muhammad , Ali Nasir , Shahzad Hasan
Published: March 2020

In this paper, a nonisothermal analysis for the process of blade coating of an incompressible couple stress fluid is presented using both plane and exponential coaters. The governing system is simplified using lubrication approximation theory (LAT). The interesting quantities from engineering point of view like normalized pressure, maximum pressure, pressure gradient, velocity, and effects of involved parameters on temperature distribution, which influence the coating process are evaluated. It is observed that pressure is at maximum near the edge of the blade whereas fluid velocity and temperature are at maximum near the substrate. An increasing couple stress parameter increases the load and decreases the coating thickness. It is worth mentioning that load and pressure are the most significant outcomes of the present exertion as these two physical quantities ensure thickness and the quality of coating.
A comparison of ray tracing and view factor simulations of locally resolved rear irradiance with the experimental values
Authors: Berrian Djaber , Libal Joris
Published: March 2020

One of the prerequisites for a reliable energy yield prediction of bifacial photovoltaic (PV) systems is the capability of modeling the backside irradiance of those systems with high accuracy. Currently, the most important optical models used to quantify the reflected irradiance on the backside of a bifacial solar panel are view factor and ray tracing. The MoBiDiG simulation tool has been developed at ISC Konstanz uses the view factor (VF) concept to model the rear irradiance. In addition to the VF concept, ray tracing (RT) has been adopted to determine the backside irradiance of bifacial modules by using the open‐source tool bifacial_radiance that has been developed by the National Renewable Energy Laboratory (NREL). A customized monocrystalline silicon solar panel has been built in order to evaluate the accuracy of the existing optical models by locally resolved rear irradiance measurement. The performance of rear irradiance has been investigated along the rows of the customized PV module during sunny and cloudy days with typical back irradiance values of
 50 and
. The comparison of measured and modeled data has been carried out on hourly, daily, and monthly basis, and the results show lower deviations for solar cells located in the center of the PV module than on the edge. Moreover, the concept of decisive solar cells has been introduced and applied to both measured and modeled data, solar cells located in the center rows were found to act as the most decisive solar cells. Finally, considering the installation configuration studied here, ie, bifacial mounting with low clearance height (below 0.2 m), both hourly RT and VF approaches are able to model long‐term cumulative irradiance received by decisive solar cells with a very high accuracy ranging from
 0.5% to
 2%.
Phase I and pharmacokinetic study of the vascular‐disrupting agent CKD‐516 (NOV120401) in patients with refractory solid tumors
Authors: Kim Hark Kyun , Kang Jeong Won , Park Young‐Whan , Kim Jung Young , Kim Minchae , Kim Soo Jin , Kim Se‐mi , Ho Ryu Keun , Yoon Seonghae , Kim Yun , Cho Joo‐Youn , Lee Keun Seok , Yun Tak , Kim Kiwon , Kwak Mi Hyang , Kim Tae‐Sung , Chung Jinsoo , Park Joong‐Won
Published: March 2020

We report a phase I pharmacological study of an oral formulation of CKD‐516, a vascular‐disrupting agent, in patients with refractory solid tumors. Twenty‐seven patients (16 in the dose‐escalation cohort and 11 in the expansion cohort) received a single daily dose (5‐25 mg) of CKD‐516 five days per week. Nausea (67%) and diarrhea (63%) were the most common treatment‐related adverse events. The recommended phase II dose of oral CKD‐516 was 20 mg/d (15 mg/d with a body surface area (BSA) <1.65 m2). Notably, S‐516 half‐lives in patients receiving 15‐20 mg CKD‐516/d significantly differed between patients with and without splenomegaly that is suggestive of portal hypertension associated with liver cirrhosis (6.1 vs 4.6 hours, respectively). Of 11 patients without splenomegaly who completed at least one cycle of a daily CKD‐516 dose of either 15 or 20 mg, only one patient (9.1%) suffered from any dose‐limiting toxicity. We conclude that a daily oral dose of 15 or 20 mg CKD‐516 five days per week could be tolerable in patients without liver cirrhosis.
The effect of salt and temperature on the conformational changes of P1LEA‐22, a repeat unit of plant Late Embryogenesis Abundant proteins
Authors: Léon David , Vermeuel Michael P. , Gupta Priya , Bunagan Michelle R.
Published: March 2020

The effect of choline chloride on the conformational dynamics of the 11‐mer repeat unit P1LEA‐22 of group 3 Late Embryogenesis Abundant (G3LEA) proteins was studied. Circular dichroism data of aqueous solutions of P1LEA‐22 revealed that the peptide favors a polyproline II (PPII) helix structure at low temperature, with increasing temperature promoting a gain of unstructured conformations. Furthermore, increases in sample FeCl3 or choline chloride concentrations causes a gain in PPII helical structure at low temperature. The potential role of PPII structure in intrinsically disordered and G3LEA proteins is discussed, including its ability to easily access other secondary structural conformations such as α‐helix and β‐sheet, which have been observed for dehydrated G3LEA proteins. The observed effect of FeCl3 and choline chloride salts on P1LEA‐22 suggests favorable cation interactions with the PPII helix, supporting ion sequestration as a G3LEA protein function. As choline chloride is suggested to improve salt tolerance and protect cell membrane in plants at low temperature, our results support adoption of the PPII structure as a possible damage‐preventing measure of Late Embryogenesis Abundant proteins.
Immigrant internal migration in a new destination country: Do immigrants suburbanise in Czechia and why?
Authors: Křížková Ivana , Ouředníček Martin
Published: March 2020

International migrants are often a major force reshaping settlement geography. However, their role in urbanisation processes has predominantly been explored in more established immigration countries, whereas such knowledge remains limited in Central and Eastern Europe. This paper investigates trends in participation of different groups of foreign residents in urbanisation processes in Czechia, which has recently become a new immigration destination. Using a longitudinal dataset of the Czech migration registers (2005–2017), it assesses the extent of participation in urbanisation processes. It also evaluates the strength of sociodemographic and place‐based factors contributing to suburbanisation, a process which makes the Czech suburbs the settlement type with highest net migration and to which both the Czech majority and the immigrant population contribute. The paper finds similarities between the internal migration of different immigrant groups and that of the Czech majority, indicating the predominance of suburbanisation of affluence, notably in culturally and economically well‐off groups.
Non‐governmental/civil society organisations and the European Union‐externalisation of migration management in Tunisia and Egypt
Authors: Cuttitta Paolo
Published: March 2020

This paper sheds light on the role of non‐governmental/civil society organisations, as well as the United Nations High Commissioner for Refugees, in the externalisation of migration management in Tunisia and Egypt. These organisations are involved in migration‐related activities, which, from the externalisation perspective, should prevent people from attempting the sea‐crossing to Europe, thus immobilising them in North Africa. The paper is an ethnographic border regime analysis drawing on extensive fieldwork. It shows that European Union‐externalisation is not a univocal and smooth process. Instead, externalisation is entangled in a complex network of actors and dynamics. Measures meant to support externalisation may produce effects contrary to those envisaged, whereas practices accomplishing externalisation goals may be in fact the result of internalisation. By analysing the various actors in their diverse practices and in their—sometimes conflictual—relationships, the paper also tries to minimise state‐centrism and Euro‐centrism in the study of externalisation.
Foldable Kirigami Paper Electronics
Authors: Yang Tilo H. , Hida Hikaru , Ichige Daiki , Mizuno Jun , Robert Kao C. , Shintake Jun
Published: March 2020

Significant attention is focused on paper electronics (PEs) for developing flexible and recyclable devices. These devices use paper as the substrate on which electrode materials are successively patterned. Among various conductive materials used for PEs, nanosilver ink is the most commonly used material due to its low cost and easy printing process. However, nanosilver electrodes tend to fracture when a paper substrate is bent or folded, leading to disconnections in printed circuits. To maintain the integrity of the circuit pattern during folding, a novel Kirigami fabrication method for PEs is proposed, in which a paper substrate is prepared by cutting along the edge of the printed electrode prior to use. The Kirigami method is experimentally proven to turn the deformation mode of nanosilver electrodes from bending to twisting, which effectively prevents electrodes from fracture. Experimental measurements reveal that the electrical resistance of the Kirigami electrode increases by merely 30% under full folding. Conductivity is maintained after full folding for 100 cycles. Finally, the Kirigami strategy is applied to different foldable PEs including angle sensors, electrostatic actuators, and locomotion robots. The successful implementation of the Kirigami strategy demonstrates high potential for use in diverse PEs with complicated foldable 3D architectures.
Magnetic Structure of Bulk GdMnO3: Influence of Strain
Authors: Ben Hamed Hichem , Hoffmann Martin , Adeagbo Waheed A. , Ernst Arthur , Hergert Wolfram
Published: March 2020

Internal structural distortions are of great interest in the determination of electronic and magnetic properties of the strong correlated rare earth manganites. When combined with external structural modifications like uniaxial or biaxial strains, structural distortions can lead to the emergence of new magnetic ground states. This realization is seemingly more probable with the low‐band‐width manganite GdMnO3 on the grounds that it is located in the magnetoelectric phase diagram of orthorhombic rare earth manganites between the A‐type antiferromagnetic (AFM) order and the cycloidal spin orders. Herein, a thorough analysis of the magnetic structure of GdMnO3 based on the density functional theory connected with a classical Heisenberg model together with Monte Carlo calculations is presented. It is found whether a compressive uniaxial strain along the c direction or biaxial strain on the ab plane favors a ferromagnetic (FM) ground state over the AFM one. On the contrary, a tensile strain also on the ab plane is likely to stabilize the E‐type AFM order.
The use of gamma distributions to quantify the dependence of cloud particle size distributions in hurricanes on cloud and environmental conditions
Authors: Mascio Jeana , McFarquhar Greg M. , Hsieh Tsung‐Lin , Freer Matt , Dooley Amanda , Heymsfield Andrew J.
Published: March 2020

Mesoscale models that predict the evolution of tropical cyclones (TCs) are sensitive to the representation of cloud microphysical processes. Bulk cloud parametrizations used in such models make assumptions about the particle size distributions (PSDs) of different ice species, and their representativeness for TCs is not well known. In situ cloud probe data acquired in tropical storms, depressions and waves during the NASA African Monsoon Multidisciplinary Analyses (NAMMA) project are used to define PSDs of snow and graupel, and of all ice hydrometeors combined. These PSDs are fitted to gamma functions to determine how the intercept (N0), shape (μ), and slope (λ) vary with cloud and environmental conditions. Families of PSDs are determined for each condition (e.g. PSDs found in updraughts, downdraughts and stratiform regions, for different ranges of ice water content (IWC) and temperature (T), and for differing stages of TC development). A volume of equally plausible solutions in (N0‐μ‐λ) phase space is defined for each environmental condition sampled based on the goodness of the fits and the uncertainty in the measured PSDs due to statistical sampling. Per cent overlap between two families in each environmental and cloud condition was calculated, and results show that areas with sustained vertical velocity with a magnitude of at least 1 m·s−1 lie in a different phase space than stratiform regions, and PSDs corresponding to IWC < 0.01 g·m−3 lie in a different phase space than PSDs corresponding to IWC > 0.1 g·m−3. All other environmental and cloud conditions did not have significant impacts on either the location or uncertainty in the family of ellipsoids.
Background error statistics in the Tropics: Structures and impact in a convective‐scale numerical weather prediction system
Authors: Lee Joshua C. K. , Huang Xiang‐Yu
Published: March 2020

The background error covariance matrix plays a vital role in any data assimilation system. Proper specification, which is determined by the forecast system set‐up, is often required. Previous studies have investigated its relevance in various global and regional numerical weather prediction (NWP) systems; however, very few have explored it in tropical NWP systems. Here, we present and evaluate the structures of the background error covariance matrix for a tropical convective‐scale NWP system. A total of 12 background error covariance matrices are modelled using differences between pairs of forecasts of different lengths but valid at the same time, based on the application of the vertical‐first and horizontal‐first transform order formulations on six permutations of the training data. Through pseudo‐single observation tests, we extract and test the sensitivity of their structures to the training data period (seasons), forecast lag and transform order. The structures typically exhibit more dependence on forecast lag and transform order; horizontal‐first transform order covariances had structures with shorter horizontal length‐scales for wind and larger wind background error standard deviations. We also note that some covariances had horizontal and vertical structures with stronger mass–wind coupling, closely resembling an equatorial Kelvin wave. To assess the performance of each of the covariances, 12 month‐long data assimilation trials in May 2018 (characterised by frequent occurrences of localised thunderstorm events) are performed. We show improved short‐range precipitation forecasts in trials using some of the covariances compared to the current operational covariance. These covariances generally have structures with weak mass–wind coupling, shorter horizontal length‐scales for wind and larger wind background error standard deviations, compared to other covariances which led to poorer forecasts. These may be desirable factors when modelling the background error covariance matrix for tropical convective‐scale data assimilation systems.
Test sample allocation method for testability verification test
Authors: Qiu Wenhao , Lian Guangyao , Zhou Peng , Huang Kaoli
Published: March 2020

An extended failure mode effect and criticality analysis (FMECA)‐based sample allocation method for testability verification is presented in this study to deal with the poor representativeness of test sample sets and the randomness of the testability evaluation results caused by unreasonable selection of failure samples. First, the fault propagation intensity is introduced as part of the extended information of FMECA, and the sample allocation impact factors of component units and failure modes are determined under this framework. Then, the failure mode similarity and impact factor support are defined, and the game decision method for weighing the relationship between similarity and support is proposed to obtain the weight of failure mode impact factor. Finally, a two‐step allocation framework of test samples is formulated to realize the sample allocation of component units and failure modes. This method is applied to the testability verification test of a launch control system. Results show that this method can obtain more representative test samples compared with the traditional sample allocation method while effectively reducing randomness of single testability evaluation result.
Eigenvector delocalization for non‐Hermitian random matrices and applications
Authors: Luh Kyle , O'Rourke Sean
Published: March 2020

Improving upon results of Rudelson and Vershynin, we establish delocalization bounds for eigenvectors of independent‐entry random matrices. In particular, we show that with high probability every eigenvector is delocalized, meaning any subset of its coordinates carries an appropriate proportion of its mass. Our results hold for random matrices with genuinely complex as well as real entries. As an application of our methods, we also establish delocalization bounds for normal vectors to random hyperplanes. The proofs of our main results rely on a least singular value bound for genuinely complex rectangular random matrices, which generalizes a previous bound due to the first author, and may be of independent interest.
Interplay between topography, fog and vegetation in the central South Arabian mountains revealed using a novel Landsat fog detection technique
Authors: Ball Lawrence , Tzanopoulos Joseph
Published: March 2020

In the central South Arabian mountains of Yemen and Oman, monsoon fog interception by the endemic cloud forest is essential for ecosystem functions and services. Yet, we know little about the local factors affecting fog distributions and their cumulative effects on vegetation. To examine these relationships, we developed a novel method of high‐resolution fog detection using Landsat data, and validated the results using occurrence records of eight moisture‐sensitive plant species. Regression tree analysis was then used to examine the topographic factors influencing fog distributions and the topoclimatic factors influencing satellite‐derived vegetation greenness. We find that the interplay between the complex mountain topography and the incoming fog results in heterogeneous fog densities. Specifically, fog accumulates against steep windward slopes and landforms, resulting in hotspots of fog interception, while lower fog densities occur in leeward locations. We also find that fog distributions correlate with patterns of vegetation greenness, and overall, that greenness increases with fog density. The layer of fog density describes patterns of vegetation greenness more accurately than topographic variables alone, and thus, we propose that regional vegetation patterns more closely follow a fog gradient, than an altitudinal gradient as previously supposed. The layer of fog density will enable an improved understanding of how species and communities, many of which are endemic, range‐restricted and in decline, respond to local variability in topoclimatic conditions.