bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of randomized controlled trials discontinued or revised for poor recruitment and completed trials with the same research question: a matched qualitative study
Authors: Briel Matthias , Speich Benjamin , von Elm Erik , Gloy Viktoria
Published: December 2019

Background

More than a quarter of randomized controlled trials (RCTs) are prematurely discontinued, mostly due to poor recruitment of patients. In this study, we systematically compared RCTs discontinued or revised for poor recruitment and completed RCTs with the same underlying research question to better understand the causes of poor recruitment, particularly related to methodological aspects and context-specific study settings.

Methods

We compared RCTs that were discontinued or revised for poor recruitment to RCTs that were completed as planned, matching in terms of population and intervention. Based on an existing sample of RCTs discontinued or revised due to poor recruitment, we identified matching RCTs through a literature search for systematic reviews that cited the discontinued or revised RCT and matching completed RCTs without poor recruitment. Based on extracted data, we explored differences in the design, conduct, and study settings between RCTs with and without poor recruitment, separately for each research question using semi-structured discussions.

Results

We identified 15 separate research questions with a total of 29 RCTs discontinued or revised for poor recruitment and 48 RCTs completed as planned. Prominent research areas in the sample were cancer and acute care. The mean number of RCTs with poor recruitment per research question was 1.9 ranging from 1 to 4 suggesting clusters of research questions or settings prone to recruitment problems. The reporting quality of the recruitment process in RCT publications was generally low. We found that RCTs with poor recruitment often had narrower eligibility criteria, were investigator- rather than industry-sponsored, were associated with a higher burden for patients and recruiters, sometimes used outdated control interventions, and were often launched later in time than RCTs without poor recruitment compromising uncertainty about tested interventions through emerging evidence. Whether a multi- or single-center setting was advantageous for patient recruitment seemed to depend on the research context.

Conclusions

Our study confirmed previously identified causes for poor recruitment, i.e., narrow eligibility criteria, investigator sponsorship, and a reduced motivation of patients and recruiters. Newly identified aspects were that researchers need to be aware of all other RCTs on a research question so that compromising effects on the recruitment can be minimized and that a larger number of centers is not always advantageous.
INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer’s Symptomatic Expression (INCREASE), a randomized controlled trial: rationale, study design, and protocol
Authors: Moga Daniela C. , Beech Brooke F. , Abner Erin L. , Schmitt Frederick A. , El Khouli Riham H. , Martinez Ashley I. , Eckmann Lynne , Huffmyer Mark , George Rosmy , Jicha Gregory A.
Published: December 2019

Background

The course of Alzheimer’s disease (AD) includes a 10–20-year preclinical period with progressive accumulation of amyloid β (Aβ) plaques and neurofibrillary tangles in the absence of symptomatic cognitive or functional decline. The duration of this preclinical stage in part depends on the rate of pathologic progression, which is offset by compensatory mechanisms, referred to as cognitive reserve (CR). Comorbid medical conditions, psychosocial stressors, and inappropriate medication use may lower CR, hastening the onset of symptomatic AD. Here, we describe a randomized controlled trial (RCT) designed to test the efficacy of a medication therapy management (MTM) intervention to reduce inappropriate medication use, bolster cognitive reserve, and ultimately delay symptomatic AD.

Methods/design

Our study aims to enroll 90 non-demented community-dwelling adults ≥ 65 years of age. Participants will undergo positron emission tomography (PET) scans, measuring Aβ levels using standardized uptake value ratios (SUVr). Participants will be randomly assigned to MTM intervention or control, stratified by Aβ levels, and followed for 12 months via in-person and telephone visits. Outcomes of interest include: (1) medication appropriateness (measured with the Medication Appropriateness Index (MAI)); (2) scores from Trail Making Test B (TMTB), Montreal Cognitive Assessment (MoCA), and California Verbal Learning Test (CVLT); (3) perceived health status (measured with the SF-36). We will also evaluate pre- to post-intervention change in: (1) use of inappropriate medications as measured by MAI; 2) CR Change Score (CRCS), defined as the difference in scopolamine-challenged vs unchallenged cognitive scores at baseline and follow-up. Baseline Aβ SUVr will be used to examine the relative impact of preclinical AD (pAD) pathology on CRCS, as well as the interplay of amyloid burden with inappropriate medication use.

Discussion

This manuscript describes the protocol of INCREASE (“INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer’s Symptomatic Expression”): a randomized controlled trial that investigates the impact of deprescribing inappropriate medications and optimizing medication regimens on potentially delaying the onset of symptomatic AD and AD-related dementias.

Trial registration

ClinicalTrials.gov, NCT02849639. Registered on 29 July 2016.
Evaluating the therapeutic efficacy of the Chinese herbal medicine Yishen Tongbi decoction in patients with active rheumatoid arthritis: protocol for a randomized, controlled, noninferiority trial
Authors: Zhao Lianyu , Li Meilin , Xu Yanping , Liu Lijuan , Zhang Mingying , Chen Guangxing
Published: December 2019

Background

Rheumatoid arthritis (RA) is a common chronic autoimmune disease that seriously affects the quality of life of patients because of damage to joints. Presently, RA is mainly treated with disease-modifying antirheumatic drugs (DMARDs) or biological agents; however, they offer limited efficacy in some patients. Therefore, additional therapeutic strategies need to be developed. Yishen Tongbi decoction is a traditional Chinese medicine formulation widely used to treat RA in China. However, currently, there is insufficient evidence to recommend its use for the treatment of RA. Therefore, we aim to verify the efficacy of Yishen Tongbi decoction to treat RA by a noninferiority trial, and to provide a basis for its use with a full-scale clinical trial.

Methods/design

One hundred eligible patients with RA will be randomized into two groups of 50 patients. One group will receive Yishen Tongbi decoction and placebo replacing methotrexate (MTX), while the other group will receive MTX and placebo replacing Yishen Tongbi decoction. Patient’s whose visual analogue scale score for pain is greater than 40 mm will be administered nonsteroidal anti-inflammatory drugs (such as enteric-coated diclofenac sodium, 25 mg three times a day); administration of all medications will be recorded. The clinical indicators of patients and their disease activity will be assessed at baseline and at 4, 12 and 24 weeks after treatment initiation. The primary outcome of efficacy will be the proportion of patients who demonstrate a favourable response based on their Clinical Disease Activity Index score at 24 weeks after treatment. All adverse events will be reported.

Discussion

Traditional Chinese medicine theory and modern western medicine research have identified the efficacy of Yishen Tongbi decoction to treat RA. Previous clinical observation and efficacy trials of Yishen Tongbi decoction in animal models for the treatment of RA has demonstrated significant effect. Because of the potential benefits of Yishen Tongbi decoction in the treatment of patients with RA, we designed this double-blind, prospective, randomized controlled trial; the results and conclusions of the trail will be published after the completion of the study.

Trial registration

Chinese Clinical Trials Registry,ChiCTR1900024902. Registered on 3 August 2019.
Significant association between clinical characteristics and changes in peripheral immuno-phenotype in large vessel vasculitis
Authors: Matsumoto Kotaro , Suzuki Katsuya , Yoshimoto Keiko , Seki Noriyasu , Tsujimoto Hideto , Chiba Kenji , Takeuchi Tsutomu
Published: December 2019

Background

Large vessel vasculitis (LVV) is a type of vasculitis characterized by granulomatous inflammation of medium- and large-sized arteries. Clinical assessment of acute phase reactants has been conventionally used to diagnose and monitor diseases; however, accurate assessment of vascular disease activity status can be difficult. In this study, we investigated comprehensive immuno-phenotyping to explore useful biomarkers associated with clinical characteristics.

Methods

Consecutive patients with newly diagnosed LVV who visited our institution between May 2016 and May 2019 were enrolled. The number of circulating T cells, B cells, natural killer cells, dendritic cells, monocytes, and granulocytes was examined and chronologically followed. Baseline and time-course changes in immuno-phenotyping associated with disease activity were assessed.

Results

Comprehensive immuno-phenotyping data from 90 samples from each of 20 patients with LVV were compared with those from healthy controls (HCs). The number of helper T (Th), follicular helper T (Tfh), CD8+ T, CD14++ CD16+ monocytes, and neutrophils were higher in patients with giant cell arteritis (GCA) and/or Takayasu arteritis (TAK) than in HCs. Among them, the number of CD8+ T and CD8+ Tem were higher in patients with TAK than in GCA. Notably, memory CD4+ and CD8+ T cells in patients with TAK remained high even in the remission phase. Further analysis revealed that the number of Th1, Th17, and Tfh cells was associated with disease relapse in GCA and TAK and that the number of CD8+ T cells was associated with relapse in TAK. Th1, Th17, and Tfh cells decreased after treatment with biologic agents, while CD8+ T cells did not.

Conclusions

Our results from peripheral immuno-phenotyping analysis indicate that the numbers of Th and Tfh cells changed along with the disease condition in both GCA and TAK, while that of CD8+ T cells did not, especially in TAK. Treatment with biologic agents decreased the proportion of Th and Tfh cells, but not CD8+ T cells, in the patients. Chronological immuno-phenotyping data explained the difference in therapeutic response, such as reactivities against biologics, between GCA and TAK.
The effect of home-based low-volume, high-intensity interval training on cardiorespiratory fitness, body composition and cardiometabolic health in women of normal body mass and those with overweight or obesity: protocol for a randomized controlled trial
Authors: Frimpong Emmanuel , Dafkin Chloe , Donaldson Janine , Millen Aletta Maria Esterhuyse , Meiring Rebecca Mary
Published: December 2019

Background

There is a high prevalence of women in South Africa with overweight and obesity which is associated with an increased risk of cardiometabolic disorders. Perceived barriers such as lack of time and motivation reduce engagement in beneficial activity behaviours for health. High-intensity interval training (HIIT) is a time-efficient and effective way to improve cardiometabolic risk profile regardless of a loss in body mass or change in body composition. This randomized controlled trial aims to determine the effects on cardiorespiratory fitness, body composition and cardiometabolic health and feasibility of a home-based 14-week HIIT program in women with overweight/obesity or normal body mass.

Methods

One hundred and twenty women (18–40 years old) with a body mass index between 20 and 35 kg/m2, will be stratified according to their BMI (normal, BMI 20–24.9 kg/m2; or high BMI ≥25 kg/m2) and randomized into a HIIT exercising group (HIIT) or a non-exercising control group (CON). HIIT participants will perform exercises for 11 min/session six times per week for a period of 14 weeks. The 2 × 4 HIIT protocol will require a work phase of own-body weight exercise lasting 2 minutes (85% VO2peak), repeated four times and separated by a one-minute active rest phase (65% VO2peak). CON participants will be asked to maintain their normal habitual lifestyle. Outcomes of cardiorespiratory fitness, body composition, echocardiography, central blood pressure, arterial stiffness and biomarkers of cardiometabolic health will be measured before and after the 14-week intervention. Every 4 weeks during the intervention, an objective estimation of compliance to the study protocol will be assessed by measuring participant physical activity over 7 days using an Actigraph GT3X accelerometer.

Discussion

Supervised laboratory-based HIIT interventions are effective in improving cardiometabolic health. More pragmatic exercise protocols may however show to be successful for mitigating barriers to the engagement in physical activity and exercise resulting in positive benefits to health. Investigation into home-based HIIT regimens are important in women, where globally the rising trend of overweight and obesity overshadows that of men. The results from this study may therefore inform future research on effective exercise prescription for women’s health.

Trial registration

Pan African Clinical Trial Registry (www.pactr.org - id no: PACTR201806003434299), 6th June 2018.
Increased Ca2+ signaling in NRXN1α+/− neurons derived from ASD induced pluripotent stem cells
Authors: Avazzadeh Sahar , McDonagh Katya , Reilly Jamie , Wang Yanqin , Boomkamp Stephanie D. , McInerney Veronica , Krawczyk Janusz , Fitzgerald Jacqueline , Feerick Niamh , O’Sullivan Matthew , Jalali Amirhossein , Forman Eva B. , Lynch Sally A. , Ennis Sean , Cosemans Nele , Peeters Hilde , Dockery Peter , O’Brien Timothy , Quinlan Leo R. , Gallagher Louise , Shen Sanbing
Published: December 2019

Background

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases.

Methods

Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1α+/− deletions. Seven control and six NRXN1α+/− iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca2+) imaging was performed using Fluo4-AM, and the properties of Ca2+ transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1α+/− neurons.

Results

NRXN1α+/− neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca2+ transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1α+/− neurons identified by STRING and GSEA analyses.

Conclusions

This is the first report to show that human NRXN1α+/− neurons derived from ASD patients’ iPSCs present novel phenotypes of upregulated VGCCs and increased Ca2+ transients, which may facilitate the development of drug screening assays for the treatment of ASD.
OHMI: the ontology of host-microbiome interactions
Authors: He Yongqun , Wang Haihe , Zheng Jie , Beiting Daniel P. , Masci Anna Maria , Yu Hong , Liu Kaiyong , Wu Jianmin , Curtis Jeffrey L. , Smith Barry , Alekseyenko Alexander V. , Obeid Jihad S.
Published: December 2019

Background

Host-microbiome interactions (HMIs) are critical for the modulation of biological processes and are associated with several diseases. Extensive HMI studies have generated large amounts of data. We propose that the logical representation of the knowledge derived from these data and the standardized representation of experimental variables and processes can foster integration of data and reproducibility of experiments and thereby further HMI knowledge discovery.

Methods

Through a multi-institutional collaboration, a community-based Ontology of Host-Microbiome Interactions (OHMI) was developed following the Open Biological/Biomedical Ontologies (OBO) Foundry principles. As an OBO library ontology, OHMI leverages established ontologies to create logically structured representations of (1) microbiomes, microbial taxonomy, host species, host anatomical entities, and HMIs under different conditions and (2) associated study protocols and types of data analysis and experimental results.

Results

Aligned with the Basic Formal Ontology, OHMI comprises over 1000 terms, including terms imported from more than 10 existing ontologies together with some 500 OHMI-specific terms. A specific OHMI design pattern was generated to represent typical host-microbiome interaction studies. As one major OHMI use case, drawing on data from over 50 peer-reviewed publications, we identified over 100 bacteria and fungi from the gut, oral cavity, skin, and airway that are associated with six rheumatic diseases including rheumatoid arthritis. Our ontological study identified new high-level microbiota taxonomical structures. Two microbiome-related competency questions were also designed and addressed. We were also able to use OHMI to represent statistically significant results identified from a large existing microbiome database data analysis.

Conclusion

OHMI represents entities and relations in the domain of HMIs. It supports shared knowledge representation, data and metadata standardization and integration, and can be used in formulation of advanced queries for purposes of data analysis.
Molecular surveillance of carbapenemase-producing Pseudomonas aeruginosa at three medical centres in Cologne, Germany
Authors: Schäfer Elena , Malecki Monika , Tellez-Castillo Carlos J. , Pfennigwerth Niels , Marlinghaus Lennart , Higgins Paul G. , Mattner Frauke , Wendel Andreas F.
Published: December 2019

Background

Pseudomonas aeruginosa is a common pathogen causing hospital-acquired infections. Carbapenem resistance in P. aeruginosa is either mediated via a combination of efflux pumps, AmpC overexpression, and porin loss, or through an acquired carbapenemase. Carbapenemase-producing P. aeruginosa (CPPA) strains are known to cause outbreaks and harbour a reservoir of mobile antibiotic resistance genes, however, few molecular surveillance data is available. The aim of this study was to analyse the prevalence and epidemiology of CPPA in three German medical centres from 2015 to 2017.

Methods

Identification and susceptibility testing were performed with VITEK 2 system. P. aeruginosa non-susceptible to piperacillin, ceftazidime, cefepime, imipenem, meropenem and ciprofloxacin (4MRGN according to the German classification guideline) isolated from 2015 to 2017 were analysed. A two-step algorithm to detect carbapenemases was performed: phenotypic tests (EDTA- and cloxacillin-combined disk tests) followed by PCR, Sanger sequencing, and eventually whole genome sequencing. CPPA isolates were further genotyped by RAPD and PFGE. In-hospital transmission was investigated using conventional epidemiology.

Results

Sixty two P. aeruginosa isolates were available for further analysis, of which 21 were CPPA as follows: blaVIM-1 (n = 2), blaVIM-2 (n = 17), blaNDM-1/blaGES-5 (n = 1) and the newly described blaIMP-82 (n = 1). CPPA were mostly hospital-acquired (71.4%) and isolated on intensive care units (66.7%). All (except one) were from the tertiary care centre. PFGE typing revealed one large cluster of VIM-2-producing CPPA containing 13 isolates. However, using conventional epidemiology, we were only able to confirm three patient-to-patient transmissions, and one room-to-patient transmission, on several intensive care units.

Conclusions

These data give insight into the epidemiology of CPPA in three centres in Germany over a period of 3 years. Carbapenemases are a relevant resistance mechanism in 4MRGN-P. aeruginosa, illustrated by genetically related VIM-2-producing strains that seem to be endemic in this region. Our data suggest that infection control measures should especially focus on controlling transmission on the ICU and support the need for a local molecular surveillance system.
Investigating Various Factors Affecting the Long-Term Compressive Strength of Heat-Cured Fly Ash Geopolymer Concrete and the Use of Orthogonal Experimental Design Method
Authors: Zhang Hongen , Li Lang , Sarker Prabir Kumar , Long Tao , Shi Xiaoshuang , Wang Qingyuan , Cai Gaochuang
Published: December 2019

This work quantified the hierarchy of the influence of three common mixture design parameters on the compressive strength and the rate of strength increase over the long term of low-calcium fly ash geopolymer concrete (FAGC) through designing 16 mixtures by the orthogonal experimental design (OED) method. The parameters used in the study were liquid to fly ash (L/FA) ratio, sodium hydroxide concentration (SHC) and sodium silicate solution to sodium hydroxide solution (SS/SH) ratio. The L/FA ratio showed little effect on compressive strength when it was varied from 0.40 to 0.52. SHC showed the greatest influence on compressive strength with little impact on the rate of strength increase after the initial heat curing. Even though the SS/SH ratio showed a small effect on the initial compressive strength, it had a considerable influence on the rate of strength increase over the long term. It was found that the compressive strength at 480 days was positively related to the Na2O/SiO2 molar ratio when it was varied from 0.49 to 0.80 and the Si/Al molar ratio was increased up to 1.87. Analysis of the failure types of specimens demonstrated that compressive strength of FAGC was associated with the strength of the mortar–aggregate interface zone (MAIZ).
A clinical trial of group-based body psychotherapy to improve bodily disturbances in post-treatment cancer patients in combination with randomized controlled smartphone-triggered bodily interventions (KPTK): study protocol
Authors: Grossert Astrid , Meffert Cornelia , Hess Viviane , Rochlitz Christoph , Pless Miklos , Hunziker Sabina , Wössmer Brigitta , Geuter Ulfried , Meinlschmidt Gunther , Schaefert Rainer
Published: December 2019

Background

Disturbances in bodily well-being represent one key source of suffering and impairment related to cancer. There is growing evidence that body psychotherapy (BPT) is efficacious for the treatment of various mental disorders. However, with regard to cancer patients, evidence is scarce. The aims of this project are to evaluate whether bodily disturbances in post-treatment cancer patients can be improved by group BPT, and to estimate the efficacy of intermittent smartphone-triggered bodily interventions.

Methods

The project is a bi-center study with two participating centers in Switzerland, applying a pre-post convergent parallel design of a weekly group BPT using a waiting-period comparator, including a nested RCT during the group BPT phase. During the BPT phase, either a smartphone-triggered bodily intervention or a smartphone-triggered control intervention is provided at random over 5 consecutive weeks, on 6 days weekly. Patients who had received curatively intended treatment for any malignant neoplasm (treatment being completed ≥3 months) and are suffering from bodily disturbances are screened to assess eligibility. Sample size estimation is based on an a priori power analysis. We plan to include a total of N = 88 subjects, aiming at at least 52 completers.

Patients are surveyed three times (baseline assessment (T0), pre- (T1) and post-intervention assessment (T2)), and on a daily basis along BPT during five consecutive weeks. The primary outcome, bodily disturbances, is assessed using the ‘Body Image Scale‘(BIS). For the secondary outcomes standardized questionnaires are used to assess changes in experience of presence and vitality, mood, body mindfulness, somatic symptoms and somatic symptom disorder, quality of life, anxiety, and depression including suicidal tendency, vitality and mental health, as well as group cohesion. Using semi standardized interviews (at T0 and T2), we aim to explore the relation of BPT with bodily disturbances and body image in post-treatment cancer patients, as well as the acceptance and burden of the intervention.

Discussion

The proposed study has strong potential benefits for cancer patients, as it may pave the way for new therapeutic approaches to treat bodily disturbances, which persist despite curative tumor therapy. These may considerably improve patients’ biopsychosocial well-being and quality of life.

Trial registration

ClinicalTrials.govNCT03707548 (registered 9 October 2018; retrospectively registered).
A phase 1, randomized, open-label, single-dose study to assess the relative bioavailability of a subcutaneous dose of FKB327 when administered using a prefilled syringe, a prefilled auto-injector, or a vial with disposable syringe in healthy subjects
Authors: Bush Jim , Kawakami Kazuki , Muniz Rafael
Published: December 2019

Background/objective

FKB327 is a biosimilar of the adalimumab reference product (RP). The primary objective was to assess the relative bioavailability of FKB327 after a single subcutaneous (SC) dose via prefilled syringe (PFS), auto-injector (AI), or vial with a disposable syringe (vial), in healthy subjects.

Methods

This randomized, open-label, parallel-group, single SC-dose study was conducted in 195 healthy male and female subjects who were randomized 1:1:1 to receive FKB327 40 mg via PFS, AI, or vial. The primary pharmacokinetic (PK) parameters, areas under the serum concentration-time curve to the last detectable value (AUC0-t) and extrapolated to infinity (AUC0-∞), and maximum concentration (Cmax), were compared. Relative bioavailability was established if the ratio of geometric least squares (LS) means of the test product was within the predefined bioequivalence (BE) range of 0.80 to 1.25 of the RP for each comparison. Safety and immunogenicity were assessed.

Results

The mean serum FKB327 concentration-time profiles appeared similar across all 3 presentations. AUC0-t, AUC0-∞, and Cmax were within the predefined BE range for PFS compared with vial, suggesting comparable bioavailability. AUC0-∞ and Cmax of AI compared with vial and PFS were fully contained within BE range, although the upper limit of 90% confidence intervals of the geometric LS means ratios for AUC0-t was slightly high. Treatment-emergent adverse events in all 3 groups were mild, with no new safety concern with FKB327 identified. Similar immunogenicity was observed among administrations.

Conclusion

Among all 3 delivery methods, PK characteristics, safety profiles, and immunogenicity were similar.

Trial registration

EU Clinical Trials Registry EudraCTN2014–004469-26, registered October 14, 2014.
Time and energy costs of different foraging choices in an avian generalist species
Authors: Sotillo Alejandro , Baert Jan M. , Müller Wendt , Stienen Eric W. M. , Soares Amadeu M. V. M. , Lens Luc
Published: December 2019

Background

Animals can obtain a higher foraging yield by optimizing energy expenditure or minimizing time costs. In this study, we assessed how individual variation in the relative use of marine and terrestrial foraging habitats relates to differences in the energy and time investments of an avian generalistic feeder (the Lesser Black-backed Gull, Larus fuscus), and how this changes during the course of the chick-rearing period.

Methods

We analyzed 5 years of GPS tracking data collected at the colony of Zeebrugge (Belgium). Cost proxies for energy expenditure (overall dynamic body acceleration) and time costs (trip durations and time spent away from the colony), together with trip frequency, were analyzed against the relative use of the marine and terrestrial habitats.

Results

The marine habitat was most often used by males and outside weekends, when fisheries are active. Marine trips implied higher energetic costs and lower time investments. As chicks became older, terrestrial trips became more prevalent, and trip frequency reached a peak towards 20 days after hatching of the first egg. Over a full chick rearing period, energy costs varied widely between individuals, but no trends were found across the marine foraging gradient. Conversely, a higher use of marine foraging implied lower overall amounts of time spent away from the colony.

Conclusions

Foraging habitat choice was related to overall time costs incurred by gulls, but not to energy costs. The effect of chick age on foraging habitat choice and effort may be driven by energy expenditure constraints on the amount of marine foraging that can be performed. If time is less constraining to them, Lesser Black-backed Gulls may meet the increasing chick demand for food by switching from high to low energy demanding foraging strategies.
Examining seasonal variation in epistaxis in a maritime climate
Authors: McMullin Ben , Atkinson Paul , Larivée Natasha , Chin Christopher J.
Published: December 2019

Background

Epistaxis is a common reason patients present to the emergency department. There is significant variation in climate across Canada. Our study aimed to determine if epistaxis is related to season, temperature and humidity in a Maritime climate.

Methods

Ethics approval was obtained. A retrospective chart review was performed. Patients who presented to the Saint John Regional Hospital Emergency Room between July 2015 and December 2017 with a diagnosis of epistaxis were identified. Weather data was collected from Environment Canada. We performed multiple univariate analyses examining confounding variables.

Results

In total, 476 cases of epistaxis were identified. There was a significant seasonal variation; the highest number of epistaxis cases occurred in the winter ( p < 0.001). A negative correlation was seen between mean daily humidity and epistaxis ( R2 = 0.7794).

Conclusion

The highest number of cases presented in the winter and a negative correlation was found between epistaxis and mean daily humidity.
Superb microvascular imaging technique in depicting vascularity in focal liver lesions: more hypervascular supply patterns were depicted in hepatocellular carcinoma
Authors: Yang Fan , Zhao Jing , Liu Chunwei , Mao Yiran , Mu Jie , Wei Xi , Jia Jinyan , Zhang Sheng , Xin Xiaojie , Tan Jian
Published: December 2019

Purpose

To investigate the capacity of Superb Microvascular Imaging (SMI) to detect microvascular details and to explore the different SMI features in various focal liver lesions (FLLs) and the correlation between SMI and microvessel density (MVD).

Method: Eighty-three liver lesions were enrolled in our study, including 35 hepatocellular carcinomas (HCCs) and 48 non-HCCs. All patients underwent color Doppler flow imaging (CDFI) and SMI examination and were categorized into subgroups according to Adler semiquantitative grading (grade 0–3) or the microvascular morphologic patterns (pattern a-f). The correlation between SMI blood flow signal percentage and MVD was assessed.

Results

Compared with CDFI, SMI detected more high-level blood flow signals (grade 2–3) and more hypervascular supply patterns (pattern e-f) in HCCs (p < 0.05). Furthermore, more hypervascular supply patterns and fewer hypovascular supply patterns were detected in HCC compared with non-HCC (p < 0.05). Based on Adler’s grading or microvascular morphologic patterns, the areas under the receiver operating characteristic curve were 0.696 and 0.760 for SMI, 0.583 and 0.563 for CDFI. The modality of “SMI-microvascular morphologic pattern” showed the best diagnostic performance. There was significant correlation between MVD and the SMI blood flow signal percentage (vascular index, VI) in malignant lesions (r = 0.675, p < 0.05).

Conclusion

SMI was superior to CDFI in detecting microvascular blood flow signals. More hypervascular supply patterns were depicted in HCC than in non-HCC, suggesting a promising diagnostic value for SMI in the differentiation between HCC and non-HCC. Meanwhile, we were the first to demonstrate that SMI blood flow signal percentage (VI) was correlated with MVD in malignant lesions.
Determinants of non-adherence to inhaled steroids in adult asthmatic patients on follow up in referral hospital, Ethiopia: cross-sectional study
Authors: Kebede Bezie , Mamo Girma
Published: December 2019

Background

Asthma is one of the major non-communicable diseases worldwide. The prevalence of asthma has continuously increased over the last five decades, resulting in 235 million people suffering from it. One of the main challenges in asthma control is adherence to pharmaceutical treatment (4) and leads to poor outcome and increases the economic and clinical burden. Non-adherence could be intentional or non-intentional.

Objective

To identify the determinants of inhaled steroid adherence among adult asthmatic patients.

Setting

The study was done in Jimma university medical center (JUMC) from March–August 22/2018.

Method

Cross-sectional observational study was conducted. Patient assessment was conducted (patient demography, inhalation technique, adherence, and asthma control status). Independent predictors of outcome identified and strength of association between dependent and independent variables determined by using binary logistic regression and statistical significance was considered at p < 0.05. Before computing binary logistic regression analysis, the presence of colinearity between independent factor and model fitness was checked.

Results

One hundred forty patients were included in the analysis. Substantial number of patients 53(37.9, 95%CI: 30–45) were non-adherent. Patient experience of previous adverse drug reaction (p = 0.011), educational status (p = 0.02), patient knowledge status (p = 0.028), previous education (p = 0.0001) and co-morbidity (p = 0.031) were significantly associated with adherence.

Conclusions

The rate of non-adherence to inhalational anti-asthmatics is high and different factors contributed. The health care provider should try to counsel patients about the effect of non-adherence on asthma control. Reassurance concerning adverse drug reactions should be an integral part of patient counseling.
Assessing the endocrine disrupting potentials and genotoxicity in environmental samples from Taiwanese rivers
Authors: Chou Pei-Hsin , Chen Chien-Hsun , Chen Kuang-Yu , Ko Fung-Chi , Tsai Tsung-Ya , Yeh Yi-Po
Published: December 2019

Background

Surface waters receive a variety of organic pollutants via wastewater discharge, and sediment represents a sink for hydrophobic contaminants. In this study, we used in vitro yeast-based reporter gene assays and a Bacillus subtilis Rec-assay to examine the occurrence of endocrine disrupting activities and genotoxic potentials in samples collected from three Taiwanese rivers. Levels of 51 polycyclic aromatic hydrocarbons (PAHs) in muscles of fish captured from same rivers were also analyzed to assess in vivo pollution of PAHs.

Results

Antagonist activities for androgen receptor and retinoid X receptor (RXR) were detected in river water extracts at environmentally relevant concentrations., and sediment extracts exhibited RXR agonist, RXR antagonist, and genotoxic potentials concurrently. Σ16 PAHs in fish muscles ranged from 44.9–242.4 ng g− 1 dry weight, representing 38 to 59% of the total 51 PAHs concentrations, and methylated PAHs of low molecular weight PAHs were often detected as well.

Conclusion

Taiwanese river sediment samples concomitantly exhibited RXR disrupting potentials and genotoxic activities, whereas RXR agonist and antagonist activities were simultaneously detected in several dry-season sediment extracts. PAH levels in fish muscles were categorized as minimally polluted by aromatic compounds, nonetheless, the presence of methylated PAHs in muscles samples may be of concern owing to the higher toxic potentials than their parent compounds.
Correction to: Ictal semiology, functional anatomy and multimodal diagnostic in patients with insular epilepsies
Authors: Stefan Hermann , Gollwitzer Stephanie
Published: December 2019

After publication of this article [1], it is noticed there are errors with figure numbering and matching between figure artwork and caption with Figs. 3, 4, 5 and 6.
Signalling, sorting and scaffolding adaptors for Toll-like receptors
Authors: Luo Lin , Lucas Richard M. , Liu Liping , Stow Jennifer L.
Published: December 2019

Toll-like receptors (TLRs) are danger-sensing receptors that typically propagate self-limiting inflammatory responses, but can unleash uncontrolled inflammation in non-homeostatic or disease settings. Activation of TLRs by pathogen- and/or host-derived stimuli triggers a range of signalling and transcriptional pathways to programme inflammatory and anti-microbial responses, including the production of a suite of inflammatory cytokines and other mediators. Multiple sorting and signalling adaptors are recruited to receptor complexes on the plasma membrane or endosomes where they act as scaffolds for downstream signalling kinases and effectors at these sites. So far, seven proximal TLR adaptors have been identified: MyD88, MAL, TRIF (also known as TICAM1), TRAM (TICAM2), SARM (SARM1), BCAP (PIK3AP1) and SCIMP. Most adaptors tether directly to TLRs through homotypic Toll/interleukin-1 receptor domain (TIR)–TIR interactions, whereas SCIMP binds to TLRs through an atypical TIR–non-TIR interaction. In this Review, we highlight the key roles for these adaptors in TLR signalling, scaffolding and receptor sorting and discuss how the adaptors thereby direct the differential outcomes of TLR-mediated responses. We further summarise TLR adaptor regulation and function, and make note of human diseases that might be associated with mutations in these adaptors.
Efficient Child Care Subsidies
Authors: Ho Christine , Pavoni Nicola
Published: December 2019

We study the design of child care subsidies in an optimal welfare problem with heterogeneous private market productivities. The optimal subsidy schedule is qualitatively similar to the existing US scheme. Efficiency mandates a subsidy on formal child care costs, with higher subsidies paid to lower income earners and a kink as a function of child care expenditure. Marginal labor income tax rates are set lower than the labor wedges, with the potential to generate negative marginal tax rates. We calibrate our simple model to features of the US labor market and focus on single mothers with children aged below 6. The optimal program provides stronger participation but milder intensive margin incentives for low-income earners with subsidy rates starting very high and decreasing with income more steeply than those in the United States. (JEL D82, H21, H24, J13, J16, J32)
Diffusion Games
Authors: Sadler Evan
Published: December 2019

Behaviors and information often spread via person-to-person diffusion. This paper highlights how diffusion processes can facilitate coordination. I study contagion in a discrete network with Bayesian players. In addition to characterizing the extent and rate of adoption, we uncover a new effect: when large cascades are possible in equilibrium, exposure conveys information about a player’s network position. This effect underscores a novel trade-off in the design of marketing campaigns, suggesting conditions under which word-of-mouth is relatively more effective. A generalization of the model to multi-type networks suggests a new approach to targeted seeding. (JEL D83, D85, M31, M37, Z13)
Regulating Innovation with Uncertain Quality: Information, Risk, and Access in Medical Devices
Authors: Grennan Matthew , Town Robert J.
Published: December 2019

We study the impact of regulating product entry and quality information requirements on an oligopoly equilibrium and consumer welfare. Product testing can reduce consumer uncertainty, but also increase entry costs and delay entry. Using variation between EU and US medical device regulations, we document patterns consistent with valuable learning from more stringent US requirements. To derive welfare implications, we pair the data with a model of supply, demand, and testing regulation. US policy is indistinguishable from the policy that maximizes total surplus in our estimated model, while the European Union could benefit from more testing. “Post-market surveillance” could further increase surplus. (JEL D43, I18, L13, L51, L64, O31, O38)
Recent advances in liver transplantation with HCV seropositive donors
Authors: Murag Soumya , Dennis Brittany B. , Kim Donghee , Ahmed Aijaz , Cholankeril George
Published: December 2019

The paradigm shift from interferon-based to direct-acting antiviral (DAA) therapy for the treatment of hepatitis C virus (HCV) infection has revolutionized the field of liver transplantation. These advances in effective HCV treatment, along with the persistent shortage in available liver grafts, have encouraged investigators to assess the need for adopting more inclusive donor policies. Owing to the poor outcomes following liver transplantation with recurrent HCV infection, liver transplantation using HCV seropositive donors (non-viremic and viremic) had been restricted. However, as a result of the growing supply of HCV seropositive donors from the recent opioid epidemic along with the advent of efficacious DAA therapy to treat HCV recurrence, there has been an increasing trend to use HCV seropositive donors for both HCV seropositive and seronegative recipients. The review aims to discuss recent advances and associated outcomes related to the use of HCV seropositive grafts for liver transplantation.
The Adolescent Knee Pain (AK-Pain) prognostic tool: protocol for a prospective cohort study
Authors: Andreucci Alessandro , Holden Sinead , Bach Jensen Martin , Skovdal Rathleff Michael
Published: December 2019

Background: One in three children and adolescents experience knee pain. Approximately one in two adolescents with knee pain will continue to experience pain even five years later and have low quality of life. The general practitioner (GP) is the first point of contact for children and adolescents with knee pain in Denmark. There is a variety of treatments being delivered in general practice, despite similar symptoms and patients’ characteristics. This suggests a need to support the GPs in identifying those at high risk of a poor outcome early on, in order to better allocate resources. The aim of this study is to develop a user-friendly prognostic tool to support GPs’ management of children and adolescents’ knee pain.

Methods: A preliminary set of items in the prognostic tool were identified using systematic reviews and meta-analysis of individual participant data. Following feedback from GPs and children and adolescents on the content and understanding, the tool was piloted and implemented in general practice. A cohort of approximately 300 children and adolescents (age 8-19 years old) is being recruited from general practices (recruitment period, July 2019 – June 2020). Clinically meaningful risk groups (e.g. low/medium/high) for the recurrence/persistence of knee pain (at 3 and 6 months) will be identified.

Discussion: If successful, this prognostic tool will allow GPs to gain insights into the likely prognosis of adolescents with knee pain and subsequently provide the first building blocks towards stratified care, where treatments will be matched to the patients’ prognostic profile. This has the potential to improve the recovery of children and adolescents from knee pain, to improve the allocation of resources in primary care, and to avoid the decline in physical activity and potential associated health and social consequences due to adolescent knee pain.

Registration: Registered with ClinicalTrials.gov on 24 June 2019 (ID NCT03995771).
What Do News Aggregators Do? Evidence from Google News in Spain and Germany
Authors: Calzada Joan , Gil Ricard
Published: December 2019

This paper shows the existence of a net market expansion effect of news aggregators through which news outlets increase their number of visits.
Pengatur Intensitas Cahaya Ruangan dengan Metode Fuzzy Logic Menggunakan PLC
Authors: Setiawan Arif Budi , Puriyanto Riky Dwi
Published: December 2019

Sistem penerangan ruangan konvensional kurang efisien dalam penggunaan energi karena hanya menggunakan prinsip menyalakan (on) dan mematikan (off) lampu serta tidak menghiraukan pengaruh dan kontribusi dari luar atau pencahayaan matahari. Untuk mengatasi permasalahan tersebut dibuatlah sistem pengendalian cahaya lampu penerangan secara otomatis menggunakan Programmable Logic Controller (PLC) Omron sebagai pengendali. Proses pengendalian intensitas cahaya lampu, pada ruangan memanfaatkan dua sensor cahaya berjenis Light Dependent Resistance (LDR) dengan menggunakan metode fuzzy Sugeno sebagai cara pengambilan keputusan dengan dua himpunan dan tiga variabel disetiap himpunan, sedangkan untuk mengubah kembali ke bentuk bilangan crisp atau defuzzyfikasi menggunakan metode Centroid. Kendali fuzzy logic sangat tepat digunakan untuk pengendalian sistem yang bersifat non-linear dan adaptif. Berdasarkan hasil pengujian, sistem yang dibangun dapat berjalan dengan baik dengan tingkat akurasi pengendalian sebesar 99,38% yang diperoleh dari perbandingan antara pengujian sistem langsung dan pengujian dengan Matlab.Conventional room lighting systems are less efficient in energy use because they only use the principle of turning on (off) and turning off (off) lights and ignoring the influence and contribution of outside or solar lighting. To overcome these problems, a lighting control system was made automatically using the Omron Programmable Logic Controller (PLC) as a controller. The process of controlling light intensity, in a room utilizing two light sensors, type Light Dependent Resistance (LDR) using the Sugeno fuzzy method as a way of making decisions with two sets and three variables in each set, while to change back to the form of crisp numbers or defuzzification using the Centroid method. Fuzzy logic control is very appropriate to be used for controlling systems that are non-linear and adaptive. Based on the test results, the system built can run well with a level of accuracy of control of 99.38% obtained from the comparison between direct system testing and testing with Matlab.
Perbandingan Model Cox Proportional Hazard dan Regresi Weibull untuk Menganalisis Ketahanan Bank Syariah
Authors: Afni Yusrillah Ihza Zianita , Fatekurohman Mohamad , Anggraeni Dian
Published: December 2019

On July 1, 2014 Financial Services Authority (OJK) issued a new regulation number 8/PJOK.13/2014 concerning the health of general sharia banks that can be valued from several aspects including credit risk, liquidity risk, Return on Asset (ROA), Net of Margin (NOM) and Capital Adequacy Ratio (CAR). The purpose of this study is to compare the models of Cox proportional hazard and Weibull regression for the resistance of sharia bank in 2017-2018 for 24 data. The data were analyzed by describing each variable and modeling in each method. Comparison result shows that Weibull regression model is better than the Cox proportional hazard model because it has smaller AIC and MSE.

Keywords : Sharia Bank, Survival Analysis, AIC, MSE