bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation and Application of Constrained Interaction Test Suites Using Base Forbidden Tuples with a Mixed Neighborhood Tabu Search
Authors: Hasan Imad H. , Ahmed Bestoun S. , Potrus Moayad Y. , Zamli Kamal Z.
Published: April 2020

To ensure the quality of current highly configurable software systems, intensive testing is needed to test all the configuration combinations and detect all the possible faults. This task becomes more challenging for most modern software systems when constraints are given for the configurations. Here, intensive testing is almost impossible, especially considering the additional computation required to resolve the constraints during the test generation process. In addition, this testing process is exhaustive and time-consuming. Combinatorial interaction strategies can systematically reduce the number of test cases to construct a minimal test suite without affecting the effectiveness of the tests. This paper presents a new efficient search-based strategy to generate constrained interaction test suites to cover all possible combinations. The paper also shows a new application of constrained interaction testing in software fault searches. The proposed strategy initially generates the set of all possible [Formula: see text]-[Formula: see text] combinations; then, it filters out the set by removing the forbidden [Formula: see text]-[Formula: see text] using the Base Forbidden Tuple (BFT) approach. The strategy also utilizes a mixed neighborhood tabu search (TS) to construct optimal or near-optimal constrained test suites. The efficiency of the proposed method is evaluated through a comparison against two well-known state-of-the-art tools. The evaluation consists of three sets of experiments for 35 standard benchmarks. Additionally, the effectiveness and quality of the results are assessed using a real-world case study. Experimental results show that the proposed strategy outperforms one of the competitive strategies, ACTS, for approximately 83% of the benchmarks and achieves similar results to CASA for 65% of the benchmarks when the interaction strength is 2. For an interaction strength of 3, the proposed method outperforms other competitive strategies for approximately 60% and 42% of the benchmarks. The proposed strategy can also generate constrained interaction test suites for an interaction strength of 4, which is not possible for many strategies. The real-world case study shows that the generated test suites can effectively detect injected faults using mutation testing.
Automated Test Input Generation via Model Inference Based on User Story and Acceptance Criteria for Mobile Application Development
Authors: Nguyen Duc-Man , Huynh Quyet-Thang , Ha Nhu-Hang , Nguyen Thanh-Hung
Published: April 2020

There has been observed explosive growth in the development of mobile applications (apps) for Android and iOS operating systems, which has led to the direct impact towards mobile app development. In order to design and propose quality-oriented apps, it is the primary responsibility of developers to devote time and sufficient efforts towards testing to make the apps bug-free and operational in the hands of end-users without any hiccup. Manual testing procedures take a prolonged amount of time in writing test cases, and in some cases, the full testing requirements are not met. Besides, the insufficient knowledge of tester also impacts the overall quality and bug-free apps. To overcome the obstacles of testing, we propose a new testing methodology cum tool called “AgileUATM” which works primarily towards white-box and black-box testing. To evaluate the validity of the proposed tool, we put the tool in a real-time operational environment concerning mobile test apps. By using this tool, all the acceptance criteria are determined via user stories. The testers/developers specify requirements with formal specifications based on programs properties, predicates, invariants, and constraints. The results show that the proposed tool generated effective and accurate test cases, test input. Meanwhile, expected output was also generated in a unified fashion from the user stories to meet acceptance criteria. The proposed solution also reduced the development time to identify test data as compared to manual Behavior-Driven Development (BDD) methodologies. This tool can support the developers to get a better idea about the required tests and able to translate the customer’s natural languages to computer languages as well. This paper fulfills an approach to suitably test mobile application development.
China’s VAT Tax Reform: A Boon for the Economy or an Opportunity for Moral Hazard?
Authors: Sopranzetti Ben , Ma Yue
Published: April 2020

In 2012, the Chinese government replaced the existing business sales tax with a Value-added tax for some, but not all, Shanghainese firms. The change was intended to reduce the effective tax rate for firms and stimulate capital investment and employment. Of concern is the potential for managerial moral hazard, whereby self-interested managers might appropriate some of the tax savings for themselves rather than use the tax savings as intended. This paper examines the impact of the tax change on the affected firms and finds no significant evidence that the intended positive effects were achieved. Moreover, it also finds no strong evidence of moral hazard. Instead, the paper documents that the tax change seems to have had a deleterious effect on firm performance. Specifically, employee compensation, capital expenditures, and free cash flow are all lower when the tax changes became effective, with the negative impact on cash flows lingering through 2014. An examination of the effective tax rate reveals that the tax change increased rather than decreased the effective tax rate in 2012 and 2013.
The Influence of the Honeycomb Design Parameters on the Mechanical Behavior of Non-Pneumatic Tires
Authors: Ganniari-Papageorgiou Evangelia , Chatzistergos Panagiotis , Wang Xiaoxu
Published: April 2020

Non-Pneumatic Tires with honeycomb structure have complex design and their mechanical behavior is influenced by their geometry. As a result, deep understanding of the effect of various design parameters is very important for design optimization. In this numerical analysis, the effect of a wide range of internal geometrical parameters on the tire’s weight and mechanical behavior was quantified. For this purpose, a parametric finite element model was designed and subjected to vertical loading to assess its maximum stress, contact pressure, maximum vertical displacement and energy absorbed during loading. The analysis indicated that vertical stiffness is strongly affected by the density, thickness and internal angles of the honeycomb cells. The internal angles of the honeycomb also appeared capable of changing the tire’s vertical stiffness without changing its weight, which is associated with the tire’s fuel efficiency and dynamic properties. A decrease in cell length or an increase in cell density was capable of significantly reducing the internal stresses. Proper tuning of cell thickness or cell length could also significantly reduce the magnitude of contact pressure developed by producing a more even distribution of loading between the tread and the road.
Communication—Layered Double Hydroxide as Intermediate-Temperature Electrolyte for Efficient Water Splitting
Authors: Lohmann-Richters Felix P. , Müller Martin , Carmo Marcelo
Published: April 2020

Highly efficient electrolyzers will be a key component of our future energy infrastructure. An intermediate operating temperature between 100 °C and 250 °C could offer increased efficiency and advantages in system design. However, electrolytes for electrolysis in this temperature range have received little attention so far. In this study, layered double hydroxides are demonstrated as solid-state electrolytes for water splitting at an intermediate temperature of 146 °C and a remarkable gain in efficiency is observed with increasing temperature. This opens new opportunities for electrolyzers and other electrochemical devices in the promising intermediate temperature range.
An Improved VMD-Based Denoising Method for Time Domain Load Signal Combining Wavelet with Singular Spectrum Analysis
Authors: Fu Jingjing , Cai Fuyou , Guo Yonghao , Liu Hongda , Niu Wentie
Published: April 2020

Measured load data play a crucial role in the fatigue durability analysis of mechanical structures. However, in the process of signal acquisition, time domain load signals are easily contaminated by noise. In this paper, a signal denoising method based on variational mode decomposition (VMD), wavelet threshold denoising (WTD), and singular spectrum analysis (SSA) is proposed. Firstly, a simple criterion based on mutual information entropy (MIE) is designed to select the proper mode number for VMD. Detrended fluctuation analysis (DFA) is adopted to obtain the noise level of the noisy signal, which can optimize the selection of MIE threshold. Meanwhile, the noisy signal is adaptively decomposed into band-limited intrinsic mode functions (BLIMFs) by using VMD. In addition, weighted-permutation entropy (WPE) is applied to divide the BLIMFs into signal-dominant BLIMFs and noise-dominant BLIMFs. Then, the signal-dominant BLIMFs are reconstructed with the noise-dominant BLIMFs processed by WTD. Finally, SSA is implemented for the reconstructed signal. Experimental results of synthetic signals demonstrate that the presented method outperforms the conventional digital signal denoising methods and the related methods proposed recently. Effectiveness of the proposed method is verified through experiments of the measured load signals.
Somatic Acupoint Stimulation for Cancer‐Related Sleep Disturbance: A Systematic Review of Randomized Controlled Trials
Authors: Liu Xian-Liang , Cheng Hui Lin , Moss Simon , Wang Carol Chunfeng , Turner Catherine , Tan Jing-Yu
Published: April 2020

Aim. The aim of this systematic review was to analyze and synthesize available evidence for the effects of somatic acupoint stimulation (SAS) on cancer‐related sleep disturbance in adults with cancer. Methods. Nine databases and four clinical trial registries were searched from their inception to July 2019 to identify potential articles and registered trials. Two authors independently extracted data and appraised the methodological quality of the included studies. The included studies could not be subjected to meta‐analysis due to the significant variations in SAS intervention protocols and outcome measurement instruments. This systematic review therefore reported the results of the included trials narratively. Results. Seven studies were identified, which involved 906 cancer patients. SAS protocols varied across trials without an optimal evidence‐based standard intervention protocol to manage cancer‐related sleep disturbance. Sanyinjiao (SP6) was the most commonly selected acupoint. Manual acupuncture was typically 15–30 min in duration and was conducted once a day or once a week for a period of 1–5 weeks, whereas self‐administered acupressure was typically 1–3 min in duration per point and was conducted once a day, such as during night time before going to bed, for a period of 1–5 months. The results indicated that SAS could potentially relieve cancer‐related sleep disturbance and improve quality of life. Mild adverse effects were reported in three of the included studies, but none of them performed a causality analysis to clarify the association between the reported adverse events and the intervention. Conclusions. This systematic review showed that SAS is a useful approach to relieving cancer‐related sleep disturbance. However, research evidence on SAS for managing cancer‐related sleep disturbance has not been fully conclusive due to the limited number of existing clinical studies with relatively small sample size and suboptimal methodological quality. Clinical trials with large sample size and robust methodology are warranted in future research.
Community Causes of Death in the Central Region of Ghana, the Missing Piece in Mortality Data
Authors: Akakpo Patrick Kafui , Imbeah Emmanuel Gustav , Agyarko-Wiredu Francis , Awlavi Kennedy , Baah-Amoh Kwame , Derkyi-Kwarteng Leonard
Published: April 2020

Objective. Mortality data from hospitals in Ghana suggest a changing mortality trend with noncommunicable diseases (cardiovascular disorders) replacing communicable diseases as the leading cause of death. Our objective was to find out the causes of deaths in the communities of the Central Region of Ghana and raise awareness of these causes of deaths while highlighting the differences that exist between data obtained from the community and that obtained from the hospital. Method. Mortality data from Coroner’s autopsies mostly provide data about the causes of deaths in the community (out of hospital). A retrospective descriptive study of Coroner’s autopsy data at the Cape Coast Teaching Hospital was carried out over a six-year period. The various causes of death were categorized according to broad headings (accidents/injuries/poisoning, cardiovascular, infections, metabolic, neoplasms, and others). Results. A total of 1187 autopsies were reviewed of which 990 (83.4%) were Coroner’s cases. Of these Coroner’s cases, 719 (72.6%) were male and 271 (27.4%) were female. 521 (52.6%) of victims were young adults (18–44 years), and majority of deaths were unnatural (due to accidents, injuries, and poisoning) (64.1%), followed by the general category of others (15.3%). Cardiovascular deaths (6.6%) were fourth after infections (9.8%). In the leading category, most deaths were due to road traffic accidents (50.4%) as occupants of vehicles and motorcycles (28.7%) and as pedestrians (21.7%). Deaths due to road traffic accidents were followed by deaths due to drowning (14.96%). Conclusion. Although noncommunicable diseases are still the leading causes of death outside the hospital, most of the deaths are due to road traffic accidents and drowning. This is at variance with hospital data that suggest that the leading noncommunicable diseases are cardiovascular disorders and cancer. Again, like data derived from hospitals, infections remain a major cause of death in the Central Region of Ghana. Studies combining the causes of death derived from Coroner’s autopsies and communities and from medical certificates of cause of death will present a better picture of the leading causes of death in the Central Region and reveal the true nature of noncommunicable diseases that currently form our largest disease burden.
Transcatheter Closure of Patent Ductus Arteriosus in Elderly Patients: Initial and One-Year Follow-Up Results—Do We Have the Proper Device?
Authors: Galeczka Michal , Szkutnik Malgorzata , Bialkowski Jacek , Smerdzinski Sebastian , Knop Mateusz , Sukiennik Adam , Fiszer Roland
Published: April 2020

Objectives. Patent ductus arteriosus (PDA) in elderly patients is an uncommon anomaly, and the duct itself is often calcified and fragile; therefore, transcatheter closure is more difficult. The aim is to analyse periprocedural and one-year follow-up results of transcatheter closure of PDA in such patients. Methods and results. Retrospective analysis of 33 elective patients aged ≥55 years (median 63; 56–85; 29 women), in whom PDA was closed percutaneously between 2002 and 2018 in two tertiary centres. All but three patients were symptomatic, with most in NYHA II (n = 14) and III (n = 11) class; pulmonary hypertension (n = 22), arterial hypertension (n = 22), duct calcifications (n = 17), atrial fibrillation (n = 15), significant mitral regurgitation (n = 5), and decompensated renal failure (n = 2) were observed. Different devices were applied depending on PDA morphology; nitinol wire mesh occluders with symmetrical articulating discs have been the most used in recent years (n = 11). Follow-up was conducted at an outpatient clinic (28/33 patients). The procedure was successful in all patients. There was one embolisation, followed by implantation of a larger device. No major complications were noted. A small residual shunt was present in echocardiography in one patient after one year. NYHA class improved in all but two patients (with multiple comorbidities). Conclusions. Transcatheter PDA closure in elderly patients is safe and efficient with a high complete closure rate and few complications. Amplatzer duct occluder type II is an attractive device in such patients.
Coordinated Control Using Backstepping of DFIG-Based Wind Turbine for Frequency Regulation in High Wind Energy Penetrated System
Authors: Nadour Mohamed , Essadki Ahmed , Nasser Tamou
Published: April 2020

The expansion of renewable generation has raised some red flags in terms of power system stability, control, and management. For instance, unlike traditional synchronous energy sources, the doubly-fed induction generator- (DFIG-) based wind turbines (WTs) do not instinctively act against frequency deviations. In fact, the power electronics interfacing the generator, merely controlled to warrant maximum wind power conversion, make its output power and mechanical speed immune to the characteristics of the electric network frequency. Moreover, significant wind power penetration (WPP) promotes the retirement of many traditional generation groups, consequently curtailing the power system corresponding inertia and displacing the primary reserves that are essential to retain the frequency within an acceptable range of variation. This paper explores different control approaches, using backstepping, allowing DFIG-based WTs to engage actively in frequency regulation using a coordinated control of the rotor speed and pitch angle to regulate the system during both partial- and full-load operation modes. The first method momentarily discharges part of the kinetic energy stored in the WT spinning masses, and the second method follows a deloaded operation characteristic, so as to keep a specific power reserve that can be automatically activated at the events of frequency excursions. A study case considering an isolated power system that consists of synchronous generators, DFIG-based wind farm, static load, and a sudden frequency disturbance was performed. The simulation result in a Matlab/Simulink environment highlights the robustness and capability of the coordinated control scheme to furnish, under variant operation conditions, active power aid, consequently lifting the frequency nadir up to a superior level than that obtained with 0% wind power penetration in the system.
Occupational Therapy Goal Achievement for People with Stroke: A Retrospective Study
Authors: Abu Tariah Hashem , Aljehani Amal Saud , Alenazi Dana Yasser , Alturaif Dona Abdularhman , Alsarhani Malak Nabit
Published: April 2020

Background/Aims. The process of occupational therapy services starts with assessing the occupational performance problems, setting goals, and implementing various intervention strategies to achieve the goals. The aim of this study was to assess the extent of achieving occupational therapy goals for people with stroke and categorize the goals according to the aspects of the domain of occupational therapy. Methods. A cross-sectional retrospective study design was used. People with stroke receiving rehabilitation services at King Abdulaziz Medical City (KAMC) were the target of this study. Data about the extent of achieving occupational therapy goals were collected using the Goal Attainment Scaling (GAS). Results. Of the 100 medical records of people with stroke included in this study, only 30% of the goals were functional. Only 54% of the goals were achieved. No association was found between the number of achieved goals and variables such as age, gender, type of stroke, and stroke hemisphere/side. Conclusion. People with stroke included in this study have not shown significant progress toward achieving their therapy goals. As for clinical practice, this study could guide therapists in the future to improve the process of achieving their patients’ goals.
O selo de Jade Imperial Taiping e o Reino do Filho Chinês de Deus
Authors: Artuza Victor
Published: April 2020

Em meio a um período conturbado (século XIX), os manchus, detentores do domínio sobre a Dinastia Qing enfrentaram grandes dificuldades, seja pelas relações estabelecidas com o exterior ou pelas agitações internas, causadas por inúmeras revoltas. No entanto, uma delas merece especial atenção, seja por sua magnitude ou pelareverberação tanto no exterior como também na história da China. Esta seria a Rebelião Taiping, que através de seu líder, Hong Xiuquan, toma forma e se expande juntamente com a fé cristã, estabelecida pelo mesmo. Tal rebelião assume impactante extensão, na união de um cristianismo próprio e a crença de seus fiéis seguidores para com o seu líder – o “Filho Chinês de Deus”, que reivindicava o título de “Rei Celestial” – que constituíramo então “Reino Celestial Taiping”. Deste modo, a descrição e o aprofundamento no estudo da Rebelião pode ser obtido através do chamado Selo de Jade Imperial Taiping (太平玉玺), trazido aqui como um objeto que em primeira instancia se traduz, para que seja passível da explicação analítica, suscitando assim um maior aprofundamento sobre as caracterizações e a compreensão do que foi esta rebelião.
Alterations in Vascular Function Associated With the Use of Combustible and Electronic Cigarettes
Authors: Fetterman Jessica L. , Keith Rachel J. , Palmisano Joseph N. , McGlasson Kathleen L. , Weisbrod Robert M. , Majid Sana , Bastin Reena , Stathos Mary Margaret , Stokes Andrew C. , Robertson Rose Marie , Bhatnagar Aruni , Hamburg Naomi M.
Published: April 2020

Background

Electronic cigarettes (e‐cigarettes) have been proposed as a potential harm reduction tool for combustible cigarette smokers. The majority of adult e‐cigarette users continue to smoke combustible cigarettes and are considered dual users. The vascular impact of e‐cigarettes remains incompletely defined.

Methods and Results

We examined the association of e‐cigarette use with measures of vascular function and tonometry, preclinical measures of cardiovascular injury. As part of the
CITU
(Cardiovascular Injury due to Tobacco Use) study, we performed noninvasive vascular function testing in individuals without known cardiovascular disease or cardiovascular disease risk factors who were nonsmokers (n=94), users of combustible cigarettes (n=285), users of e‐cigarettes (n=36), or dual users (n=52). In unadjusted analyses, measures of arterial stiffness including carotid‐femoral pulse wave velocity, augmentation index, carotid‐radial pulse wave velocity, and central blood pressures differed across the use groups. In multivariable models adjusted for age, sex, race, and study site, combustible cigarette smokers had higher augmentation index compared with nonusers (129.8±1.5 versus 118.8±2.7,
P
=0.003). The augmentation index was similar between combustible cigarette smokers compared with sole e‐cigarette users (129.8±1.5 versus 126.2±5.9,
P
=1.0) and dual users (129.8±1.5 versus 134.9±4.0,
P
=1.0). Endothelial cells from combustible cigarette smokers and sole e‐cigarette users produced less nitric oxide in response to A23187 stimulation compared with nonsmokers, suggestive of impaired endothelial nitric oxide synthase signaling.

Conclusions

Our findings suggest that e‐cigarette use is not associated with a more favorable vascular profile. Future longitudinal studies are needed to evaluate the long‐term risks of sustained e‐cigarette use.
Abdominal aortic calcification: from ancient friend to modern foe
Authors: Bartstra Jonas W , Mali Willem P Th M , Spiering Wilko , de Jong Pim A
Published: April 2020

Background

Abdominal aortic calcifications were already ubiquitous in ancient populations from all continents. Although nowadays generally considered as an innocent end stage of stabilised atherosclerotic plaques, increasing evidence suggests that arterial calcifications contribute to cardiovascular risk. In this review we address abdominal aortic calcification from an evolutionary perspective and review the literature on histology, prevalence, risk factors, clinical outcomes and pharmacological interventions of abdominal aortic calcification.

Design

The design of this study was based on a literature review.

Methods

Pubmed and Embase were systematically searched for articles on abdominal aortic calcification and its synonyms without language restrictions. Articles with data on histology, prevalence, risk factors clinical outcomes and/or pharmacological interventions were selected.

Results

Abdominal aortic calcification is highly prevalent in the general population and prevalence and extent increase with age. Prevalence and risk factors differ between males and females and different ethnicities. Risk factors include traditional cardiovascular risk factors and decreased bone mineral density. Abdominal aortic calcification is shown to contribute to arterial stiffness and is a strong predictor of cardiovascular events and mortality. Several therapies to inhibit arterial calcification have been developed and investigated in small clinical trials.

Conclusions

Abdominal aortic calcification is from all eras and increasingly acknowledged as an independent contributor to cardiovascular disease. Large studies with long follow-up must be carried out to show whether inhibition of abdominal aortic calcification will further reduce cardiovascular risk.
Incidence and characteristics of acute aortic dissection in patients with out-of-hospital cardiopulmonary arrest evaluated by non-contrast computed tomography
Authors: Takeuchi Shinsuke , Yamaguchi Yoshihiro , Soejima Kyoko , Yoshino Hideaki
Published: April 2020

Background

The exact epidemiology of acute aortic dissection, including cases of out-of-hospital cardiopulmonary arrest, is unclear. We aimed to investigate the incidence and characteristics of acute aortic dissection in patients with out-of-hospital cardiopulmonary arrest transferred to our institution and validate the related factors to out-of-hospital cardiopulmonary arrest in Stanford type A acute aortic dissection.

Methods

We retrospectively reviewed the acute-phase computed tomography data of patients with out-of-hospital cardiopulmonary arrest who visited our hospital between 1 January 2015 and 31 December 2017.

Results

Among 1011 consecutive patients with out-of-hospital cardiopulmonary arrest, excluding those aged 17 years and younger and exogenous out-of-hospital cardiopulmonary arrest, such as suicide and trauma, 934 underwent computed tomography examination and 71 (7.6%) were diagnosed with acute aortic dissection: 66 with Stanford type A and five with type B acute aortic dissection (out-of-hospital cardiopulmonary arrest group). Seventy-five patients without out-of-hospital cardiopulmonary arrest with Stanford type A acute aortic dissection visited our institution during the same period (non-out-of-hospital cardiopulmonary arrest group). Age, incidence of massive bloody pericardial effusion and massive intrathoracic haemorrhage were significantly higher in the out-of-hospital cardiopulmonary arrest than in the non-out-of-hospital cardiopulmonary arrest group (78 ± 8 years, 72.7% and 24.2% vs. 70 ± 13 years, 26.7% and 1.3%, respectively; all P < 0.01). These variables were independently related to out-of-hospital cardiopulmonary arrest.

Conclusions

There may be more patients with acute aortic dissection with out-of-hospital cardiopulmonary arrest than previously thought. Aortic rupture into the pericardial space or thoracic cavity is the major cause of out-of-hospital cardiopulmonary arrest in these cases. Non-contrast computed tomography can be used to diagnose acute aortic dissection in patients with out-of-hospital cardiopulmonary arrest. Our study is one of a few to evaluate the real circumstances surrounding acute aortic dissection and its epidemiology.
GrAPFI: predicting enzymatic function of proteins from domain similarity graphs
Authors: Sarker Bishnu , Ritchie David W. , Aridhi Sabeur
Published: April 2020

An amendment to this paper has been published and can be accessed via the original article.
Obstetric fistulas in Uganda: scoping review using a determinant of health approach to provide a framework for health policy improvement
Authors: den Hollander Geerte C. , Janszen Erica W. M.
Published: April 2020

Background

The uneven global and national distribution of obstetric fistulas suggests a complex network of determinants contributing to fistula development. This study aims to create an understanding of the determinants of obstetric fistula in Uganda and to give a framework for health policy improvement.

Methods

A scoping review of existing literature was performed, searching the PubMed/MEDLINE database, Ugandan Demographic and Health Surveys, and official sources of Ugandan statistics. Data was analysed using the model for the determinants of health by Dahlgren and Whitehead.

Results

Obstetric fistulas are associated with different personal lifestyle factors, certain social and community networks, as well as poor working and living conditions. Malnutrition, early childbearing, limited female empowerment, lack of awareness of childbearing risks, low socioeconomic status, and long distances to emergency obstetric care play a part. Certain regions of Uganda are in particular associated with obstetric fistula, where an accumulation of determinants is notable.

Conclusion

Analysis using the model of Dahlgren and Whitehead shows that obstetric fistulas are associated with determinants at different levels of society. Poverty and low education link these in a web that is disproportionately hard to escape from for the poorest women. This inequity asks for co-operation between ministries to dismantle the environment for obstetric fistula.
Online cognitive behavioral therapy enhanced for binge eating disorder: study protocol for a randomized controlled trial
Authors: van den Berg Elske , Melisse Bernou , Koenders Jitske , de Jonge Margo , Blankers Matthijs , de Beurs Edwin , Dekker Jack
Published: April 2020

Background

Binge eating disorder is characterized by recurrent episodes of binge eating accompanied by a sense of lack of control. Of the different treatments available, Cognitive Behavioral Therapy-Enhanced and guided self-help treatment are recommended. As online treatment offers several additional advantages, we have developed a CBT-Enhanced online guided self-help intervention. The aim of this study is to determine whether this intervention reduces eating disorder pathology and increases the amount of binge free days in adults classified with binge eating disorder or other specified feeding or eating disorder- binge eating disorder, compared to an untreated waiting list condition. The experimental condition is hypothesized to be superior to the waiting list condition.

Methods

The efficacy of an online guided self-help intervention for binge eating disorder will be assessed by conducting a randomized controlled trial. The trial will target adult individuals classified with binge eating disorder or other specified feeding or eating disorder- binge eating disorder with a body mass index between 19.5 and 40, referred to an eating disorder treatment center. Dual arm allotment will be performed in a 1:1 ratio stratified for BMI above or below 30. Randomization will be blinded to the online intervention (n = 90), or to the control waiting list condition (n = 90). Assessors will be blinded and assessments will be administered at baseline, week 5, at end-of-treatment, and at 12 and 24 weeks follow-up. Primary outcome will be eating disorder pathology, operationalized as number of days on which binge eating occurred between the two conditions during the period of the intervention. Secondary outcome measures will be differences in other eating disorder pathology, clinical impairment and in quality of life, while therapeutic alliance, demographic characteristics and followed treatment module will serve as effect moderators. Several types of costs will be assessed.

Discussion

This paper presents an online guided self-help Cognitive Behavioral Therapy- Enhanced study protocol for individuals classified with binge eating disorder or other specified feeding or eating disorder. Efficacy will be examined through a Randomized Controlled Trial.

Trial registration

The study protocol is registered with the Netherlands Trial Registry NTR (NTR 7994) since 6 September 2019.
The effects of pricing policy on the prices and supply of low-cost medicines in Shandong, China: evidence from an interrupted time series analysis
Authors: Rong Xuejing , Yin Jia , Duan Shuoyun , Sun Qiang , Babar Zaheer-Ud-Din
Published: April 2020

Background

In China, some medicines had a supply problem. In 2015, to address this problem, the Chinese government issued a policy to raise the price cap for some shorted low-cost medicines (LCMs). The objective was to assess the effects on medicine prices and supply of medicines from a medicine pricing policy reform point of view.

Methods

This study was conducted in Shandong, an eastern province of China with a population of 99.4 million. We collected procurement data of all (n = 1494) LCM medicines available between April 2014 and February 2017 from the web-based Provincial Drug Centralized Bidding Procurement System. This study used the Drug Price index and the average price to reveal the price change of LCMs and used the interrupted time series to evaluate the effects of LCM policy on medicine supply by measuring the change of monthly procurement volume, the number of products, and the average delivery time of LCMs.

Results

After the policy implementation in October 2015, the quarterly average price of all LCM products, especially traditional Chinese medicines, showed a sudden growth trend. Then after two-quarter implementation of policy, the price recovered to the same trend before policy intervention, which is consistent with the trend of the Drug price index. There were 466 of LCM products available in October 2015. After the policy intervention, the number of products available increased by 109.87% (n = 978) in February 2017, at a growth rate of 6.44% per month (Value = 30.02, P < 0.001). Besides after the intervention in October 2015, the monthly procurement volumes of LCMs increased rapidly, on average, at a rate of 28.93% per month (Value = 474,000, P < 0.001) for all LCMs. The average delivery time of LCMs kept on decreasing from 33.37 days to 10.69 days at a reduced rate of 3.63% (Value = − 1.21, P < 0.001) per month before the policy, while no significant changes were noted. Also, average monthly delivery time was stable at 9 days after the intervention.

Conclusions

The policy promoted the supply of low-cost medicines, which is beneficial for the Universal Health Coverage. However, future policies should focus on monitoring price change and reducing the delivery time of generic medicines.
The incidence of significant venous sinus stenosis and cerebral hyperemia in childhood hydrocephalus: prognostic value with regards to differentiating active from compensated disease
Authors: Bateman Grant Alexander , Yap Swee Leong , Subramanian Gopinath Musuwadi , Bateman Alexander Robert
Published: April 2020

Background

Symptomatic or active hydrocephalus in children is linked to an elevation in intracranial pressure (ICP), which is likely to be multifactorial in origin. The CSF outflow resistance, venous sinus resistance and total cerebral blood flow are likely factors in the ICP elevation. The purpose of this paper is to define the incidence, site and significance of venous sinus stenosis and/or cerebral hyperemia in a cohort of children diagnosed with hydrocephalus at a tertiary referral hospital.

Methods

The imaging database was reviewed over a 10 year period and the index MRI of all children between the ages of 4 months and 15 years, who were diagnosed with treatment naive hydrocephalus of any type (excluding secondary to tumor) and had magnetic resonance venography (MRV) and flow quantification were selected. Patients were compared with children undergoing an MRI with MRV and flow quantification who were subsequently shown to have no abnormality. The cross-sectional area and circumference of the sinuses were measured at 4 levels. The hydraulic and effective diameters were calculated. An area stenosis of 65% or greater was deemed significant. A total cerebral blood flow greater than two standard deviations above the mean for controls was taken to be abnormal.

Results

There were a total of 55 children with hydrocephalus compared to 118 age matched control MRV’s and 35 control flow quantification studies. A high grade stenosis occurred in 56% of patients but in none of the controls (p < 0.0001). The commonest site of narrowing was in the distal sigmoid sinus. Cerebral hyperemia occurred in 13% of patients but did not occur in the controls.

Conclusions

The elevation in ICP in symptomatic hydrocephalus is multifactorial. Both high grade venous stenosis and cerebral hyperemia are common in childhood hydrocephalus. High grade stenosis was noted to be a risk factor for conservative management failure. Hyperemia was a good prognostic indicator.
Preliminary evaluation of a candidate international reference for Epstein–Barr virus capsid antigen immunoglobulin A in China
Authors: Chen Hao , Zhong Qiaohua , Wu Xiaobin , Ding Yanling , Chen Qi , Xue Ning , Xu Yiwei , Chen Shulin
Published: April 2020

Background

The detection of the Epstein–Barr capsid antigen (VCA) immunoglobulin A (IgA) is widely used in the diagnosis of nasopharyngeal carcinoma (NPC), but a reference standard for evaluating the presence of VCA-IgA is not yet available. Therefore, a reference standard is urgently needed for a uniform and quantitative detection of VCA-IgA.

Methods

A mixed reference serum from three NPC patients diluted with healthy subject serum was made as a potential first international standard for VCA-IgA. VCA-IgA was detected in twenty NPC patients by four ELISA kits and two chemiluminescent immunoassays kits using the reference as a calibration curve. The performance of these six kits was evaluated, and the quantitative results were compared.

Results

Our results showed a good linearity of the reference in different kits. Without reference, the difference of the total coefficient of variation (from 3.98 to 43.11%) and Within-run coefficient of variation (from 2.47 to 19.66%) was large in the 6 kits. The positive and negative coincidence rate between the 6 kits and indirect immunofluorescence for NPC diagnosis was 75% overall agreement, but a difference among the six kits was found, ranging from 55 to 90%. The concentration of VCA-IgA in the 20 NPC samples led in the division into three categories such as negative, low, or medium/high positive, but these concentrations were significantly different within these three categories depending on the kit used of the 6 considered. However,a good correlation (R2 = 0.986) was observed between Antu and Beier ELISA kits.

Conclusions

The reference serum mightbe used as a reference standard for a better comparison of the results from different kits/laboratories. However, the quantitative results of some kits are still inconsistent due to the diversity of VCA antigens.
CCR2 is localized in microglia and neurons, as well as infiltrating monocytes, in the lumbar spinal cord of ALS mice
Authors: Komiya Hiroyasu , Takeuchi Hideyuki , Ogawa Yuki , Hatooka Yuki , Takahashi Keita , Katsumoto Atsuko , Kubota Shun , Nakamura Haruko , Kunii Misako , Tada Mikiko , Doi Hiroshi , Tanaka Fumiaki
Published: April 2020

It remains controversial whether circulating monocytes expressing CCR2 infiltrate the central nervous system (CNS) and contribute to pathogenicity of amyotrophic lateral sclerosis (ALS). A previous report used conventional immunohistochemistry to show that CCR2 is exclusively expressed by astrocytes, but not infiltrating monocytes/microglia or neurons, in the spinal cords of ALS model mice. In this study, we assessed the cellular distribution of CCR2 in the CNS of ALS mice using CCR2-reporter mice (Ccr2rfp/+-Cx3cr1gfp/+-SOD1G93A Tg mice), a more sophisticated method for directly detecting the distribution of CCR2 protein. We found that infiltration of CCR2+ monocytes in the lumbar spinal cord increased over the course of disease progression. Moreover, from the middle stage of disease, CCR2 was partially distributed in microglia and neurons, but not astrocytes, in striking contrast to the previous findings. These novel observations suggested that CCR2+ monocyte infiltration leads to CNS environmental deterioration due to toxic conversion of microglia and neurons, creating a vicious cycle of neuroinflammation and leading to acceleration of ALS pathology. Our findings also show that this reporter mouse is a useful and powerful tool for obtaining new insights into the pathomechanisms of ALS.
Regenerative and protective effects of dMSC-sEVs on high-glucose-induced senescent fibroblasts by suppressing RAGE pathway and activating Smad pathway
Authors: Bian Xiaowei , Li Bingmin , Yang Jie , Ma Kui , Sun Mengli , Zhang Cuiping , Fu Xiaobing
Published: April 2020

Background

Fibroblasts are crucial for supporting normal wound healing. However, the functional state of these cells is impaired in diabetics because of a high-glucose (HG) microenvironment. Small extracellular vesicles (sEVs) have emerged as a promising tool for skin wound treatment. The aim of this study was to investigate the effects of sEVs derived from human decidua-derived mesenchymal stem cells (dMSC-sEVs) on HG-induced human dermal fibroblast (HDF) senescence and diabetic wound healing and explore the underlying mechanism.

Methods

We first created a HDF senescent model induced by HG in vitro. dMSC-conditioned medium (dMSC-CM) and dMSC-sEVs were collected and applied to treat the HG-induced HDFs. We then examined the proliferation, migration, differentiation, and senescence of these fibroblasts. At the same time, the expressions of RAGE, p21 RAS, Smad2/3, and pSmad2/3 were also analyzed. Furthermore, pSmad2/3 inhibitor (SB431542) was used to block the expression of pSmad2/3 to determine whether dMSC-sEVs improved HDF senescence by activating Smad pathway. Finally, we assessed the effect of dMSC-sEVs on diabetic wound healing.

Results

The HG microenvironment impaired the proliferation, migration, and differentiation abilities of the HDFs and accelerated their senescence. dMSC-CM containing sEVs improved the proliferation and migration abilities of the HG-induced fibroblasts. dMSC-sEVs internalized by HG-induced HDFs not only significantly promoted HDF proliferation, migration, and differentiation, but also improved the senescent state. Furthermore, dMSC-sEVs inhibited the expression of RAGE and stimulated the activation of Smad signaling pathway in these cells. However, SB431542 (pSmad2/3 inhibitor) could partially alleviate the anti-senescent effects of dMSC-sEVs on HG-induced HDFs. Moreover, the local application of dMSC-sEVs accelerated collagen deposition and led to enhanced wound healing in diabetic mice. The detection of PCNA, CXCR4, α-SMA, and p21 showed that dMSC-sEVs could enhance HDF proliferation, migration, and differentiation abilities and improve HDF senescent state in vivo.

Conclusion

dMSC-sEVs have regenerative and protective effects on HG-induced senescent fibroblasts by suppressing RAGE pathway and activating Smad pathway, thereby accelerating diabetic wound healing. This indicates that dMSC-sEVs may be a promising candidate for diabetic wound treatment.
Hayes Yard virus: a novel ephemerovirus isolated from a bull with severe clinical signs of bovine ephemeral fever is most closely related to Puchong virus
Authors: Blasdell Kim R. , Davis Steven S. , Voysey Rhonda , Bulach Dieter M. , Middleton Deborah , Williams Sinead , Harmsen Margaret B. , Weir Richard P. , Crameri Sandra , Walsh Susan J. , Peck Grantley R. , Tesh Robert B. , Boyle David B. , Melville Lorna F. , Walker Peter J.
Published: April 2020

Bovine ephemeral fever is a vector-borne disease of ruminants that occurs in tropical and sub-tropical regions of Africa, Asia and Australia. The disease is caused by a rhabdovirus, bovine ephemeral fever virus (BEFV), which occurs as a single serotype globally. Although several other closely related ephemeroviruses have been isolated from cattle and/or arthropods, only kotonkan virus from Nigeria and (tentatively) Mavingoni virus from Mayotte Island in the Indian Ocean have been previously associated with febrile disease. Here, we report the isolation of a novel virus (Hayes Yard virus; HYV) from blood collected in February 2000 from a bull (Bos indicus) in the Northern Territory of Australia. The animal was suffering from a severe ephemeral fever-like illness with neurological involvement, including recumbency and paralysis, and was euthanised. Histological examination of spinal cord and lung tissue identified extensive haemorrhage in the dura mata with moderate perineuronal oedema and extensive emphysema. HYV displayed cone-shaped morphology, typical of rhabdoviruses, and was found to be most closely related antigenically to Puchong virus (PUCV), isolated in 1965 from mosquitoes in Malaysia. Analysis of complete genome sequences of HYV (15 025 nt) and PUCV (14 932 nt) indicated that each has a complex organisation (3′ N-P-M-G-GNS-α1-α2-β-γ-L 5′) and expression strategy, similar to that of BEFV. Based on an alignment of complete L protein sequences, HYV and PUCV cluster with other rhabdoviruses in the genus Ephemerovirus and appear to represent two new species. Neutralising antibody to HYV was also detected in a retrospective survey of cattle sera collected in the Northern Territory.
Development of an integrated digital health intervention to promote engagement in and adherence to medication for opioid use disorder
Authors: Langdon Kirsten J. , Ramsey Susan , Scherzer Caroline , Carey Kate , Ranney Megan L. , Rich Josiah
Published: April 2020

Background

Buprenorphine-naloxone is an evidence-based treatment for Opioid Use Disorder. However, despite its efficacy, nearly half of participants are unsuccessful in achieving stabilization (i.e., period of time following medication induction in which medication dose is adjusted to be effective in reducing cravings/withdrawal, minimize potential side effects, and eliminate illicit substance use). This paper presents the study design and protocol for a digital health intervention designed to promote engagement in and adherence to buprenorphine treatment, offered through an outpatient addiction treatment center, through motivational enhancement and distress tolerance skills training. Personalized feedback interventions represent a promising method to effectively motivate engagement in and adherence to buprenorphine treatment. These interventions are generally brief, individually tailored, and have the potential to be delivered via mobile platforms. Distress tolerance, a transdiagnostic vulnerability factor, has been implicated in the development and maintenance of substance use. Targeting distress tolerance may improve substance use treatment outcomes by promoting the ability to persist in goal-directed activity even when experiencing physical or emotional distress.

Methods

The study aims are to: (1) develop and refine an interactive computer- and text message-delivered personalized feedback intervention that incorporates distress tolerance skills training for persons who have elected to initiate outpatient buprenorphine treatment (iCOPE); (2) examine the feasibility, acceptability, and preliminary efficacy of iCOPE for increasing abstinence, adherence, and retention in treatment compared to a treatment as usual comparison condition; and, (3) examine potential mechanisms that may underlie the efficacy of iCOPE in improving outcomes, including motivation, distress tolerance, self-regulation, and negative affect.

Discussion

Results of this study will be used to determine whether to proceed with further testing through a large-scale trial. This work has the potential to improve treatment outcomes by reducing illicit opioid use, increasing adherence/retention, and preventing future overdose and other complications of illicit opioid use.

Trial Registration NCT03842384