bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the Demand for Service Bundles under Three‐Part Tariffs
Authors: Chen Liang , Luo Yao , Xiao Ping
Published: February 2020

Consumers may face demand uncertainty when choosing a service plan under three‐part tariffs, and preferences for multiple services may be inter‐dependent. To examine such a demand system, we construct a two‐stage discrete/continuous choice model for service bundles, allowing for interactive utility and preference correlations. Implementing a piecewise maximization approach to consumers’ non‐differentiable utility maximization problem, we estimate the model via simulated method of moments. We empirically illustrate the model using data from a Chinese wireless service provider. Our counterfactual analysis shows that the three‐part tariffs with interchangeable units show no significant loss of revenue, compared to existing tariffs.
Next Generation External Venturing Practices in Family Owned Businesses
Authors: Ramírez‐Pasillas Marcela , Lundberg Hans , Nordqvist Mattias
Published: February 2020

Drawing on an Entrepreneurship as Practice (EaP) approach, this article examines how next generation members in family owned businesses (FOBs) engage in external venturing. Our study builds on longitudinal qualitative research in two Mexican FOBs where the next generation launched ten ventures. It reveals five different practices of external venturing used by next generation family members: ‘obtaining family approval’, ‘bypassing family’, ‘family venture mimicking’, ‘jockeying in family’, and ‘jockeying around family’. The five practices are combined into three routes for external venturing: ‘imitating the family business’, ‘splitting the family business’, and ‘surpassing the family business’. Building on notions from Michel de Certeau’s practice theory, this study contributes to theorizing the five practices as ways of operating and the routes as modes of sensing to better understand how next generation family members deal with settings featured by dominant orders within the family and the FOB in their attempts to originate and launch their new ventures.
Bubbling up or cascading down? Public servants, political advisers and politicization
Authors: Shaw Richard , Eichbaum Chris
Published: February 2020

One of the strands in the growing scholarship on political advisers in parliamentary democracies proposes that advisers can reduce the risk of civil service politicization by furnishing partisan advice to ministers, freeing civil servants to focus on the provision of expert competence. This benign narrative generates a significant hypothesis, which is that the institutionalization of the partisan role diminishes the risk of civil service politicization. That hypothesis has yet to be fully tested. Several studies have assessed the impact of advisers' actions on civil service impartiality, but the consequences of bureaucrats' own agency for that dependent variable have received far less attention. Drawing on data from a survey of New Zealand public servants, this article challenges the assumption in the political advisers literature that civil service politicization is primarily driven by exogenous factors and calls for a more nuanced theoretical approach to endogenous aspects of politicization.
Association of methylphenidate use and traditional and cyberbullying in adolescents with ADHD
Authors: Tural Hesapcıoglu Selma , Kandemir Gözde
Published: February 2020

Background

This study aimed to determine whether there is a difference in terms of traditional/cyberbullying or victimization among adolescents receiving methylphenidate for attention‐deficit/hyperactivity disorder (ADHD) and treatment‐naïve adolescents with ADHD during a 1‐year period.

Methods

The Sociodemographic Data Form, Schedule for Affective Disorders and Schizophrenia for School‐Aged Children (Present and Lifetime Version), Peer Bullying Scale–Adolescent Form and the Cyberbully/Victim Scale were administered to male adolescents with ADHD.

Results

Adolescents who did not receive methylphenidate during the last 1‐year were exposed to higher rates of physical victimization, isolation, destroying of property by others, and sexual victimization, all of which are subtypes of traditional victimization; they also reported higher rates of destroying others' property. Furthermore, cyberbullying victimization and cyberbullying behaviors were more common in the non‐treated group.

Conclusion

Effective treatment of ADHD could lessen involvement in the bullying cycle in adolescents with ADHD.
The categorization of Hispanics in biomedical research: US and Latin American perspectives
Authors: Liz Jordan
Published: February 2020

Contemporary genetic and biomedical research on race and ethnicity has reignited the debate over the biological significance of these categories. This article provides an overview of the critical literature concerning the categorization of Hispanic and Hispanic populations within these research programs. More specifically, this article focuses on issues regarding: The conceptualization of Hispanic identity, issues of data collection and generalization (e.g., the use of a specific Hispanic nationality as a stand‐in for all Hispanics), the tension between social and biological classifications of ethnic populations, and the social, political, and scientific implications of genetic research for Latin America.
Genome‐wide analysis and phosphorylation sites identification of the 14‐3‐3 gene family and functional characterization of MeGRF3 in cassava
Authors: Chang Lili , Tong Zheng , Peng Cunzhi , Wang Dan , Kong Hua , Yang Qian , Luo Minghua , Guo Anping , Xu Bingqiang
Published: February 2020

The biological functionality of many members of the 14‐3‐3 gene family is regulated via phosphorylation at multiple amino acid residues. The specific phosphorylation‐mediated regulation of these proteins during cassava root tuberization, however, is not well understood. In this study, 15 different 14‐3‐3 genes (designated MeGRF1 – 15) were identified within the cassava genome. Based upon evolutionary conservation and structural analyses, these cassava 14‐3‐3 proteins were grouped into ε and non‐ε clusters. We found these 15 MeGRF genes to be unevenly distributed across the eight cassava chromosomes. When comparing the expression of these genes during different developmental stages, we found that three of these genes (MeGRF9, 12 and 15) were overexpressed at all developmental stages at 75, 104, 135, 182 and 267 days post‐planting relative to the fibrous root stage, whereas two (MeGRF5 and 7) were downregulated during these same points. In addition, the expression of most MeGRF genes changed significantly in the early and middle stages of root tuberization. This suggests that these different MeGRF genes likely play distinct regulatory roles during cassava root tuberization. Subsequently, 18 phosphorylated amino acid residues were detected on nine of these MeGRF proteins. A phosphomimetic mutation at serine‐65 in MeGRF3 in Arabidopsis thaliana (Arabidopsis) slightly influenced starch metabolism in these plants, and significantly affected the role of MeGRF3 in salt stress responses. Together these results indicate that 14‐3‐3 genes play key roles in responses to abiotic stress and the regulation of starch metabolism, offering valuable insights into the functions of these genes in cassava.
Inference for longitudinal data from complex sampling surveys: An approach based on quadratic inference functions
Authors: Dumitrescu Laura , Qian Wei , Rao J. N. K.
Published: February 2020

We propose a survey weighted quadratic inference function method for the analysis of data collected from longitudinal surveys, as an alternative to the survey weighted generalized estimating equation method. The procedure yields estimators of model parameters, which are shown to be consistent and have a limiting normal distribution. Furthermore, based on the inference function, a pseudolikelihood ratio type statistic for testing a composite hypothesis on model parameters and a statistic for testing the goodness of fit of the assumed model are proposed. We establish their asymptotic distributions as weighted sums of independent chi‐squared random variables and obtain Rao‐Scott corrections to those statistics leading to a chi‐squared distribution, approximately. We examine the performance of the proposed methods in a simulation study.
The Role of Basal Ganglia Reinforcement Learning in Lexical Ambiguity Resolution
Authors: Ceballos Jose M. , Stocco Andrea , Prat Chantel S.
Published: February 2020

The current study aimed to elucidate the contributions of the subcortical basal ganglia to human language by adopting the view that these structures engage in a basic neurocomputation that may account for its involvement across a wide range of linguistic phenomena. Specifically, we tested the hypothesis that basal ganglia reinforcement learning (RL) mechanisms may account for variability in semantic selection processes necessary for ambiguity resolution. To test this, we used a biased homograph lexical ambiguity priming task that allowed us to measure automatic processes for resolving ambiguity toward high‐frequency word meanings. Individual differences in task performance were then related to indices of basal ganglia RL, which were used to group subjects into three learning styles: (a) Choosers who learn by seeking high reward probability stimuli; (b) Avoiders, who learn by avoiding low reward probability stimuli; and (c) Balanced participants, whose learning reflects equal contributions of choose and avoid processes. The results suggest that balanced individuals had significantly lower access to subordinate, or low‐frequency, homograph word meanings. Choosers and Avoiders, on the other hand, had higher access to the subordinate word meaning even after a long delay between prime and target. Experimental findings were then tested using an ACT‐R computational model of RL that learns from both positive and negative feedback. Results from the computational model simulations confirm and extend the pattern of behavioral findings, providing an RL account of individual differences in lexical ambiguity resolution.
COM1, a factor of alternative non‐homologous end joining, lagging behind the classic non‐homologous end joining pathway in rice somatic cells
Authors: Xu Zhan , Zhang Jianxiang , Cheng Xinjie , Tang Yujie , Gong Zhiyun , Gu Minghong , Yu Hengxiu
Published: February 2020

The role of rice (Oryza sativa) COM1 in meiotic homologous recombination (HR) is well understood, but its part in somatic double‐stranded break (DSB) repair remains unclear. Here, we show that for rice plants COM1 conferred tolerance against DNA damage caused by the chemicals bleomycin and mitomycin C, while the COM1 mutation did not compromise HR efficiencies and HR factor (RAD51 and RAD51 paralogues) localization to irradiation‐induced DSBs. Similar retarded growth at the post‐germination stage was observed in the com1‐2 mre11 double mutant and the mre11 single mutant, while combined mutations in COM1 with the HR pathway gene (RAD51C) or classic non‐homologous end joining (NHEJ) pathway genes (KU70, KU80, and LIG4) caused more phenotypic defects. In response to γ‐irradiation, COM1 was loaded normally onto DSBs in the ku70 mutant, but could not be properly loaded in the MRE11RNAi plant and in the wortmannin‐treated wild‐type plant. Under non‐irradiated conditions, more DSB sites were occupied by factors (MRE11, COM1, and LIG4) than RAD51 paralogues (RAD51B, RAD51C, and XRCC3) in the nucleus of wild‐type; protein loading of COM1 and XRCC3 was increased in the ku70 mutant. Therefore, quite differently to its role for HR in meiocytes, rice COM1 specifically acts in an alternative NHEJ pathway in somatic cells, based on the Mre11–Rad50–Nbs1 (MRN) complex and facilitated by PI3K‐like kinases. NHEJ factors, not HR factors, preferentially load onto endogenous DSBs, with KU70 restricting DSB localization of COM1 and XRCC3 in plant somatic cells.
Not in the genotype: can unexplained hemophilia A result from “micro(RNA) management”?
Authors: Selvaraj Sundar R. , Pipe Steven W.
Published: February 2020

See article on page 401–413, in this issue
Quantitative Experimental Investigation on the Flow Characteristics of Nanofluids in Turbulent Flow
Authors: Lv Jizu , Hu Chengzhi , Zhang Zhenxian , Bai Minli
Published: February 2020

In addition to the increase of thermal conductivity, heat transfer enhancement mechanism for nanofluids also includes the changes of the flow characteristics, therefore it is needed to take an in-depth research on nanofluids flow characteristics. In this paper, the flow characteristics of H2O and SiO2-H2O nanofluids in a rectangular convex channel (channel composed of continuous staggered rectangular convex platform) at the Reynolds numbers 2300, 2500, 3000 and 4000 are studied by the quantitative PIV method (Fig. 1a). The rectangular convex channel (Fig. 1b) has periodic perturbation effect on the fluid flow, so that the flow direction is changed for several times, and vortexes are generated, which makes turbulence enhanced. In this way, flow is in the intense turbulent state under a low flow rate. Results show that the flow fields becomes more chaotic by the addition of nanoparticles (Fig. 2 and 3). Both the number and the size of vortices increase observably. The vorticity of nanofluids is also enhanced compared with H2O, and with the increase of Reynolds number, the increased ratio in the vorticity magnitude is getting higher (Fig. 4). At different Reynolds number, the pressure loss of nanofluids increases by 2.27%, 2.23%, 1.5% and 14.7%, respectively. As shown the flow resistance does not increase significantly compared to base fluids, especially at low Reynolds number. It can be concluded that the interaction between nanoparticles and the basic fluid strengthens the flow field disturbance, which is benefit to the heat transfer of nanofluids.
Optimization of a Radial Turbine for Pulsating Flows
Authors: Liu Zheng , Copeland Colin
Published: February 2020

A turbocharger turbine is exposed to pulsating flow conditions when it is connected to an engine exhaust system due to the opening and closing of the exhaust valves. However, many radial turbines are designed and tested under steady-state conditions without taking into account these unsteady exhaust flows. In order to seek the optimal aerodynamic design of a radial flow turbine (RFT) under pulsating flow conditions, the present research utilizes a numerical simulation approach to optimize the blade shape of a small-scale mixed flow turbine (MFT) under 50 Hz pulses. This corresponds to a four-stroke, three-cylinder engine rotating at 2000 rpm. In order to understand how a less computationally intensive, steady-state optimization compares, the blade shape was also optimized using the peak power point of the pulse. Three turbine features were modified during the optimization process, including blade cone angle, blade axial location, and blade camber angles. The optimization was carried out using a computational fluid dynamics (CFD)–genetic algorithm (GA) coupled approach, targeting at maximizing both energy-weighted efficiency and energy output during a predefined pulse period. To ensure that the new design maintains a similar matching to the engine, the maximum deviation of turbine swallowing capacity is controlled to within ±5% of the baseline for all new blade designs. The design that achieves the maximum pulse cycle-averaged efficiency was produced from unsteady optimization, with a performance benefit of 0.66%. The unsteady optimization also produced a blade shape that delivers the maximum energy output, with an improvement of 5.42%.
Analytical Reason for Smaller Lateral Sway in Angled-Plane Scissor Linkage
Authors: Singh Sunil Kumar , Deepak Sangamesh R.
Published: February 2020

Scissor linkages are widely used with scissor links arranged in two parallel planes. When small misalignment of revolute joint axes are permissible, the linkage can undergo lateral sway. This paper, using rigid-body kinematics and a modeling of misalignment, converts the task of finding lateral sway into a non-linear constrained optimization problem. Through linearization of the optimization problem, this paper analytically proves that (1) maximum lateral sway increases as the number of units in the parallel-plane scissor linkage increases whereas in angled-plane scissor linkage, the lateral sway tends to a finite limit as the number of units is increased and (2) the lateral sway is independent of connector length in parallel-plane scissor linkage whereas it is dependent on the length of the connector in angled-plane scissor linkage. These results are further substantiated with numerical solution of the non-linear optimization problem. The results imply that the angled-plane scissor linkage can substantially limit lateral sway in comparison to parallel-plane scissor linkage under similar conditions of joint misalignment. The analytical expression derived in this paper helps in identifying the influence of design parameters on lateral sway.
Tracking of multiple surface vessels based on passive acoustic underwater arrays
Authors: Tesei Alessandra , Meyer Florian , Been Robert
Published: February 2020

This paper introduces an approach to localize and track an unknown number of non-cooperative surface vessels based on passive acoustic sensing of their noise radiated underwater. Time-Difference of Arrival (TDOA) measurements are extracted from pairs of hydrophones, and a recently introduced Bayesian framework for multi-object tracking is employed to detect and track vessels from TDOA measurements. Results based on data from a three-dimensional compact hydrophone array towed by an autonomous vehicle confirm that non-cooperative surface vessels can be detected and tracked.
The Antillean manatee produces broadband vocalizations with ultrasonic frequencies
Authors: Ramos Eric A. , Maust-Mohl Maria , Collom Kristi A. , Brady Beth , Gerstein Edmund R. , Magnasco Marcelo O. , Reiss Diana
Published: February 2020

Antillean manatees produce vocalizations reported to be important for communication, but their vocal behavior throughout their geographic range is poorly understood. A SoundTrap recorder (sample rates: 288/576 kHz) was deployed in Belize to record vocalizations of wild manatees in a seagrass channel and of a young rehabilitated and released manatee in a shallow lagoon. Spectral analysis revealed broadband vocalizations with frequencies up to 150 kHz and a high proportion of calls with ultrasonic components. Ultrasonic frequency components appear prevalent in their vocal repertoire and may be important to manatee communication.
Temporal-pitch sensitivity in electric hearing with amplitude modulation and inserted pulses with short inter-pulse intervals
Authors: Lindenbeck Martin J. , Laback Bernhard , Majdak Piotr , Srinivasan Sridhar
Published: February 2020

Listeners with cochlear implants (CIs) typically show poor sensitivity to the temporal-envelope pitch of high-rate pulse trains. Sensitivity to interaural time differences improves when adding pulses with short inter-pulse intervals (SIPIs) to high-rate pulse trains. In the current study, monaural temporal-pitch sensitivity with SIPI pulses was investigated for six CI listeners. Amplitude-modulated single-electrode stimuli, representing the coding of the fundamental frequency (F0) in the envelope of a high-rate carrier, were used. Two SIPI-insertion approaches, five modulation depths, two typical speech-F0s, and two carrier rates were tested. SIPI pulses were inserted either in every amplitude-modulation period (full-rate SIPI) to support the F0 cue or in every other amplitude-modulation period (half-rate SIPI) to circumvent a potential rate limitation at higher F0s. The results demonstrate that full-rate SIPI pulses improve temporal-pitch sensitivity across F0s and particularly at low modulation depths where envelope-pitch cues are weak. The half-rate SIPI pulses did not circumvent the limitation and further increased variability across listeners. Further, no effect of the carrier rate was found. Thus, the SIPI approach appears to be a promising approach to enhance CI listeners' access to temporal-envelope pitch cues at pulse rates used clinically.
London Calling: A Semester in the World’s Sporting Capital
Authors: Tingle Jacob K. , Squires Callum , Griffiths Randall
Published: February 2020

This case follows four American college students from a small, Liberal Arts institution during a semester-long, faculty-led study abroad trip to London, England. The case presents the experiences of these students as they integrate into London society. Mainly viewed through the lens of sport, the students encounter many differences to their preconceived notion of how sports work, providing an obvious platform for discussion and comparison of how sport is organized in different parts of the world. Specifically, the case offers students the opportunity to learn about new sports they may not have encountered before, evaluate the U.S. system of sport management, and suggest ways to improve sports both at home and abroad. The international aspect of this case also provides an added cultural element by focusing on specific events in the United Kingdom sporting calendar that can be used to teach students about another country’s sporting identity.
Capsid Structure of a Marine Algal Virus of the Order
Picornavirales
Authors: Munke Anna , Kimura Kei , Tomaru Yuji , Okamoto Kenta
Published: February 2020

Identifying the acquired structural traits in virus capsids is important for elucidating what functions are essential among viruses that infect different hosts. The
Picornavirales
viruses infect a broad spectrum of hosts, ranging from unicellular algae to insects and mammals and include many human pathogens. Those viruses that infect unicellular protists, such as algae, are likely to have undergone fewer structural changes during the course of evolution compared to those viruses that infect multicellular eukaryotes and thus still share some characteristics with the
Picornavirales
ancestor. This article describes the first atomic capsid structure of an alga
Marnavirus
, CtenRNAV-II. A comparison to capsid structures of the related invertebrate and vertebrate viruses identified a number of structural traits that have been functionally acquired or lost during the course of evolution. These observations provide new insights on past theories on the viability and evolution of
Picornavirales
viruses.
Draft Genome Sequence of Raphidiopsis raciborskii Strain GIHE 2018, Isolated from a Shallow Freshwater Pond in South Korea
Authors: Jeong Ju-Yong , Lee Sang-Hoon , Yun Mi-Ra , Oh Seung-Eun , Hwang Chan-Won , Yoon Mi-Hye , Park Hee-Deung
Published: February 2020

The draft genome sequence of
Raphidiopsis
(
Cylindrospermopsis
)
raciborskii
strain GIHE 2018, a filamentous nitrogen-fixing and potentially harmful cyanobacterium, is reported here. This is the first strain isolated from a shallow freshwater pond in South Korea. This information is expected to improve our understanding of the phylogeography of this species.
Are low and middle-income countries prioritising high-value healthcare interventions?
Authors: Leech Ashley A , Kim David D , Cohen Joshua T , Neumann Peter J
Published: February 2020

Introduction

Since resources are finite, investing in services that produce the highest health gain ‘return on investment’ is critical. We assessed the extent to which low and middle-income countries (LMIC) have included cost-saving interventions in their national strategic health plans.

Methods

We used the Tufts Medical Center Global Health Cost-Effectiveness Analysis Registry, an open-source database of English-language cost-per-disability-adjusted life year (DALY) studies, to identify analyses published in the last 10 years (2008–2017) of cost-saving health interventions in LMICs. To assess whether countries prioritised cost-saving interventions within their latest national health strategic plans, we identified 10 countries, all in sub-Saharan Africa, with the highest measures on the global burden of disease scale and reviewed their national health priority plans.

Results

We identified 392 studies (63%) targeting LMICs that reported 3315 cost-per-DALY ratios, of which 207 ratios (6%) represented interventions reported to be cost saving. Over half (53%) of these targeted sub-Saharan Africa. For the 10 countries we investigated in sub-Saharan Africa, 58% (79/137) of cost-saving interventions correspond with priorities identified in country plans. Alignment ranged from 95% (21/22 prioritised cost-saving ratios) in South Africa to 17% (2/12 prioritised cost-saving ratios) in Cameroon. Human papillomavirus vaccination was a noted priority in 70% (7/10) of national health prioritisation plans, while 40% (4/10) of countries explicitly included prenatal serological screening for syphilis. HIV prevention and treatment were stated priorities in most country health plans, whereas 40% (2/5) of countries principally outlined efforts for lymphatic filariasis. From our sample of 45 unique interventions, 36% of interventions (16/45) included costs associated directly with the implementation of the intervention.

Conclusion

Our findings indicate substantial variation across country and disease area in incorporating economic evidence into national health priority plans in a sample of sub-Saharan African countries. To make health economic data more salient, the authors of cost-effectiveness analyses must do more to reflect implementation costs and other factors that could limit healthcare delivery.
Comprehensive survey among statistical members of medical ethics committees in Germany on their personal impression of completeness and correctness of biostatistical aspects of submitted study protocols
Authors: Rauch Geraldine , Hafermann Lorena , Mansmann Ulrich , Pigeot Iris
Published: February 2020

Objectives

To assess biostatistical quality of study protocols submitted to German medical ethics committees according to personal appraisal of their statistical members.

Design

We conducted a web-based survey among biostatisticians who have been active as members in German medical ethics committees during the past 3 years.

Setting

The study population was identified by a comprehensive web search on websites of German medical ethics committees.

Participants

The final list comprised 86 eligible persons. In total, 57 (66%) completed the survey.

Questionnaire

The first item checked whether the inclusion criterion was met. The last item assessed satisfaction with the survey. Four items aimed to characterise the medical ethics committee in terms of type and location, one item asked for the urgency of biostatistical training addressed to the medical investigators. The main 2×12 items reported an individual assessment of the quality of biostatistical aspects in the submitted study protocols, while distinguishing studies according to the German Medicines Act (AMG)/German Act on Medical Devices (MPG) and studies non-regulated by these laws.

Primary and secondary outcome measures

The individual assessment of the quality of biostatistical aspects corresponds to the primary objective. Thus, participants were asked to complete the sentence ‘In x% of the submitted study protocols, the following problem occurs’, where 12 different statistical problems were formulated. All other items assess secondary endpoints.

Results

For all biostatistical aspects, 45 of 49 (91.8%) participants judged the quality of AMG/MPG study protocols much better than that of ‘non-regulated’ studies. The latter are in median affected 20%–60% more often by statistical problems. The highest need for training was reported for sample size calculation, missing values and multiple comparison procedures.

Conclusions

Biostatisticians being active in German medical ethics committees classify the biostatistical quality of study protocols as low for ‘non-regulated’ studies, whereas quality is much better for AMG/MPG studies.
Protocol for the process and feasibility evaluations of a new model of primary care service delivery for managing pain and function in patients with knee osteoarthritis (PARTNER) using a mixed methods approach
Authors: Bowden Jocelyn L , Egerton Thorlene , Hinman Rana S , Bennell Kim L , Briggs Andrew M , Bunker Stephen J , Kasza Jessica , French Simon D , Pirotta Marie , Schofield Deborah J , Zwar Nicholas A , Hunter David J
Published: February 2020

Introduction

This protocol outlines the rationale, design and methods for the process and feasibility evaluations of the primary care management on knee pain and function in patients with knee osteoarthritis (PARTNER) study. PARTNER is a randomised controlled trial to evaluate a new model of service delivery (the PARTNER model) against ‘usual care’. PARTNER is designed to encourage greater uptake of key evidence-based non-surgical treatments for knee osteoarthritis (OA) in primary care. The intervention supports general practitioners (GPs) to gain an understanding of the best management options available through online professional development. Their patients receive telephone advice and support for OA management by a centralised, multidisciplinary ‘Care Support Team’. We will conduct concurrent process and feasibility evaluations to understand the implementation of this new complex health intervention, identify issues for consideration when interpreting the effectiveness outcomes and develop recommendations for future implementation, cost effectiveness and scalability.

Methods and analysis

The UK Medical Research Council Framework for undertaking a process evaluation of complex interventions and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) frameworks inform the design of these evaluations. We use a mixed-methods approach including analysis of survey data, administrative records, consultation records and semistructured interviews with GPs and their enrolled patients. The analysis will examine fidelity and dose of the intervention, observations of trial setup and implementation and the quality of the care provided. We will also examine details of ‘usual care’. The semistructured interviews will be analysed using thematic and content analysis to draw out themes around implementation and acceptability of the model.

Ethics and dissemination

The primary and substudy protocols have been approved by the Human Research Ethics Committee of The University of Sydney (2016/959 and 2019/503). Our findings will be disseminated to national and international partners and stakeholders, who will also assist with wider dissemination of our results across all levels of healthcare. Specific findings will be disseminated via peer-reviewed journals and conferences, and via training for healthcare professionals delivering OA management programmes. This evaluation is crucial to explaining the PARTNER study results, and will be used to determine the feasibility of rolling-out the intervention in an Australian healthcare context.

Trial registration number

ACTRN12617001595303; Pre-results.
Removal of distal fragments of liquid embolic agents during arteriovenous malformation embolization using the TIGERTRIEVER 13: a technical report
Authors: Ho Faith LY , Chapot René
Published: February 2020

Background

Arteriovenous malformations (AVMs) are vascular lesions that may be treated by an endovascular approach using liquid embolic agents but the control of the liquid embolic agent remains poor and a potential complication may be distal migration of embolic material. The TIGERTRIEVER 13 is a new stent retriever designed for stroke thrombectomy and has a version ideal for distal occlusions. We report our experience in the removal of embolic agent which had migrated into the distal vessels using the TIGERTRIEVER during PHIL/Onyx embolization of AVMs.

Clinical presentations

Three patients with brain and spinal AVMs underwent endovascular embolization. During trans-arterial embolization of the AVM with PHIL/Onyx, retrograde filling of distal arterial feeders was followed by migration into the normal arterial branches (cortical middle cerebral artery, distal posterior cerebral artery, and anterior spinal artery). This resulted in occlusion or sluggish distal flow in these branches with potential significant neurological deficits. In all three cases, a Headway Duo microcatheter was navigated distally in the occluded vessel beyond the embolic material using a Traxcess microwire. The TIGERTRIEVER 13 was deployed with recanalization of the vessel after a single attempt. In all three patients there were no complications related to the retrieval of embolic agent.

Conclusion

Distal migrated embolic agents such as PHIL or Onyx can be removed from various arterial vascular territories using stent retrievers dedicated to small vessels.
Evolution of non-flat cosmos via GGPDE f(R) model
Authors: Javed Wajiha , Nawazish Iqra , Shahid Fatima , Irshad Nimra
Published: February 2020

This paper is devoted to explore the cosmic evolution of non-flat Friedmann Robertson Walker universe through generalized ghost pilgrim dark energy model in the background of f(R) gravity. For this purpose, we consider two well known scale factors, i.e., power-law and unified scale factors in terms of red shift parameter. For these scale factors, we reconstruct the given dark energy model in f(R) gravity and determine its stability/instability through squared speed of sound parameter. In order to discuss the behavior of reconstructed and dark energy models, we evaluate well known cosmological parameter such as equation of state parameter along with $$\omega $$ω–$$\omega '$$ω′ plane. In addition to this, we also investigate compatibility of new models with standard cosmological models through state-finder parameters. The density parameter is formulated for both ordinary matter as well as dark energy components and results are compared with Planck 2018 constraints. It is concluded that cosmological parameters reveal consistency with recent observations while the value of density parameter suggested by Planck 2018 is achieved by power-law scale factor in most of the cases as compared to unified scale factor.
Building maps of protein structure spaces in template-free protein structure prediction
Authors: Zaman Ahmed Bin , Shehu Amarda
Published: February 2020

An important goal in template-free protein structure prediction is how to control the quality of computed tertiary structures of a target amino-acid sequence. Despite great advances in algorithmic research, given the size, dimensionality, and inherent characteristics of the protein structure space, this task remains exceptionally challenging. It is current practice to aim to generate as many structures as can be afforded so as to increase the likelihood that some of them will reside near the sought but unknown biologically-active/native structure. When operating within a given computational budget, this is impractical and uninformed by any metrics of interest. In this paper, we propose instead to equip algorithms that generate tertiary structures, also known as decoy generation algorithms, with memory of the protein structure space that they explore. Specifically, we propose an evolving, granularity-controllable map of the protein structure space that makes use of low-dimensional representations of protein structures. Evaluations on diverse target sequences that include recent hard CASP targets show that drastic reductions in storage can be made without sacrificing decoy quality. The presented results make the case that integrating a map of the protein structure space is a promising mechanism to enhance decoy generation algorithms in template-free protein structure prediction.
A Mathematical Model toward Real-Time Monitoring of Automotive PEM Fuel Cells
Authors: Goshtasbi Alireza , Pence Benjamin L. , Chen Jixin , DeBolt Michael A. , Wang Chunmei , Waldecker James R. , Hirano Shinichi , Ersal Tulga
Published: February 2020

A computationally efficient model toward real-time monitoring of automotive polymer electrolyte membrane (PEM) fuel cell stacks is developed. Computational efficiency is achieved by spatio-temporal decoupling of the problem, developing a new reduced-order model for water balance across the membrane electrode assembly (MEA), and defining a new variable for cathode catalyst utilization that captures the trade-off between proton and mass transport limitations without additional computational cost. Together, these considerations result in the model calculations to be carried out more than an order of magnitude faster than real time. Moreover, a new iterative scheme allows for simulation of counter-flow operation and makes the model flexible for different flow configurations. The proposed model is validated with a wide range of experimental performance measurements from two different fuel cells. Finally, simulation case studies are presented to demonstrate the prediction capabilities of the model.
Daytime QT by Routine 12-Lead ECG Is Prolonged in Patients with Severe Obstructive Sleep Apnea
Authors: Walker McCall , Blackwell Jacob N. , Stafford Patrick , Patel Paras , Mazimba Sula , Mehta Nishaki , Cho Yeilim , Mangrum Michael , Nazarian Saman , Bilchick Kenneth , Kwon Younghoon
Published: February 2020

Background. Obstructive sleep apnea (OSA) has been linked to sudden cardiac death (SCD). Prolonged QT is a recognized electrocardiographic (ECG) marker of abnormal ventricular repolarization linked to increased risk of SCD. We hypothesized that individuals with OSA have more pronounced abnormality in daytime QT interval. Methods. We reviewed consecutive patients who underwent clinically indicated polysomnography with 12-lead ECG within 1 year at a single center. Heart rate-corrected QT interval (QTc) was compared by OSA severity class (normal/mild: apnea‐hypopnea index AHI<15/hr (n=72); moderate: 15-30 (n=72); severe: >30 (n=105)) adjusting for body mass index, age, sex, hypertension, and heart failure. Further evaluation was performed by dividing patients into severe (AHI>30) and nonsevere (<30) OSA. Logistic analysis was used to determine association of OSA severity and abnormal QTc (>450/>470 ms for men/women, respectively). Results. A total of 249 patients were included. QTc was similar between the normal/mild and moderate groups, and the overall QTc trend increased across OSA (normal/mild: 435.6 ms; moderate: 431.36; severe: 444.4; p trend=0.03). Abnormal QTc was found amongst 34% of male and 31% of female patients. Patients with severe OSA had longer QTc compared with normal/mild OSA (mean difference (95% CI): 10.0 ms (0.5, 19.0), p=0.04). When stratified dichotomously (as opposed to three groups), patients with severe OSA again had longer QTc (vs. nonsevere OSA) (444.4 ms vs. 433.48 ms, p=0.004). Severe OSA was also associated with abnormal QTc (OR (95% CI): 2.68 (1.34, 5.48), p=0.006). Conclusions. In a sleep clinic cohort, severe OSA was associated with higher QTc and clinically defined abnormal QTc compared with nonsevere OSA.
Identification and Repair of Left-Sided Paraduodenal Hernia Using Both Laparoscopic and Robotic Techniques
Authors: John Muhonen , Michael Hsu , Matthew Sturdivant , Anthony Unger , David Dexter , Pablo Giuseppucci , Christopher Esper
Published: February 2020

Internal hernias are an uncommon cause of small bowel obstruction and present a challenging clinical diagnostic scenario. They result from the abnormal protrusion of an abdominal organ through a peritoneal defect and can cause intermittent obstructive symptoms, diffuse abdominal discomfort, and postprandial pain. Paraduodenal hernias comprise 53% of all internal hernias1and occur due to failure of the fixation of either the left or transverse mesocolon to the posterior abdominal wall. Its relative rarity results in mortality between 20 and 50%2because of delayed diagnosis and consequent obstruction, strangulation, and bowel ischemia. Our case series describes three patients before and after operative fixation of paraduodenal hernia. Only one of the three was identified by preoperative radiologist interpretation. Subsequent diagnosis and definitive treatment were completed by surgical staff to resolve undiagnosed undulating abdominal pain and obstructive-type symptoms. We further analyze left-sided paraduodenal hernias after laparoscopic and robotic repair to define common symptomatology, typical CT findings, and preferred laparoscopic repair techniques.
Depression of lncRNA NEAT1 Antagonizes LPS-Evoked Acute Injury and Inflammatory Response in Alveolar Epithelial Cells via HMGB1-RAGE Signaling
Authors: Zhou Hongchao , Wang Xinhui , Zhang Bin
Published: February 2020

Sepsis-evoked acute lung injury (ALI) and its extreme manifestation, acute respiratory distress syndrome (ARDS), constitute a major cause of mortality in intensive care units. High levels of the long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) have been positively correlated with increased severity and unfavorable prognoses in patients with sepsis. Nevertheless, the function and molecular mechanism of NEAT1 in ALI remain elusive. In the current study, high levels of NEAT1 were confirmed in lipopolysaccharide- (LPS-) induced ALI mice models and in LPS-stimulated cells from the alveolar epithelial A549 cell line. Intriguingly, cessation of NEAT1 led to increased cell viability and decreased lactate dehydrogenase release, apoptosis, and caspase-3/9 activity, which conferred protection against LPS-induced injury in these cells. NEAT1 inhibition also restrained LPS-evoked transcripts and production of inflammatory cytokines IL-6, IL-1β, and TNF-α. A mechanism analysis corroborated the activation of high-mobility group box1 (HMGB1)/receptors for advanced glycation end products (RAGE) and NF-κB signaling in LPS-treated A549 cells. NEAT1 suppression reversed the activation of this pathway. Notably, reactivating HMGB1/RAGE signaling via HMGB1 overexpression blunted the anti-injury and anti-inflammation effects of NEAT1 knockdown. These findings suggest that NEAT1 may aggravate the progression of ALI and ARDS by inducing alveolar epithelial cell injury and inflammation via HMGB1/RAGE signaling, implying a promising treatment target for these conditions.
IgG-Dependent Dismutation of Superoxide in Patients with Different Types of Multiple Sclerosis and Healthy Subjects
Authors: Smirnova Liudmila P. , Mednova Irina A. , Krotenko Nina M. , Alifirova Valentina M. , Ivanova Svetlana A.
Published: February 2020

This work is the first to demonstrate that class G immunoglobulins (IgGs) in patients with multiple sclerosis and healthy individuals have the ability to catalyze the dismutation reaction of the superoxide anion radical. Thus, superoxide dismutase (SOD) activity is an intrinsic property of antibodies, which is confirmed by a number of stringent criteria. SOD activity of IgGs in patients with multiple sclerosis statistically significantly exceeds such activity in healthy individuals by 2-4 times. Moreover, the maximum activity has been registered in patients with relapsing remitting multiple sclerosis. The kinetic characteristics of the SOD reaction of IgGs are several orders of magnitude lower than those for the SOD enzyme but do not differ between patients with multiple sclerosis and healthy individuals. Consequently, abzymes with SOD activity have a lower catalysis rate than that of the enzymes and form a stronger complex with the substrates. Inhibitory analysis showed that this activity is inhibited by classical metal-dependent SOD inhibitors. The activity of IgGs was inhibited by classical metal-dependent inhibitors EDTA and TETA (triethylenetetramine). Also, high catalase activity of IgGs was detected in these patients. We suggest that these abzymes help protect the body from oxidative stress.
Epigenetic Modulation of the Tumor Immune Microenvironment to Potentiate Immune Checkpoint Blockade Therapy
Authors: Menzel Johannes , Black Joshua C.
Published: February 2020

Response rates to immune checkpoint blockade (ICB) in KRAS-mutant lung adenocarcinoma remain poor. In this issue of Cancer Discovery, Li and colleagues report an in vivo CRISPR screen of epigenetic regulators of the tumor immune microenvironment that uncovers Asf1a as a tumor-intrinsic suppressor of ICB through suppression of GM-CSF expression.

See related article by Li et al., p. 270.
Cost-Effectiveness of a Multifaceted Quality Improvement Intervention for Acute Ischemic Stroke in China
Authors: Pan Yuesong , Zhang Lei , Li Zixiao , Meng Xia , Wang Yilong , Li Hao , Liu Liping , Wang Yongjun
Published: February 2020

Background and Purpose—

Multifaceted quality improvement interventions of stroke care have been shown to improve hospital personnel adherence to evidence-based performance measures and subsequent stroke outcomes. This study aimed to evaluate the cost-effectiveness of a multifaceted quality improvement intervention for stroke care in China, the world’s largest low- and middle-income country.

Methods—

A short-term decision tree model and a long-term Markov model were used to analyze the cost-effectiveness of a multifaceted quality improvement intervention for patients with acute ischemic stroke. Outcomes, transition probability, and cost data were obtained from a recent clinical trial and the published literature. The benefit of the intervention was assessed by the costs per quality-adjusted life-years gained in the short- and long-term. One-way and probabilistic sensitivity analyses were performed to assess the uncertainty of the findings.

Results—

Compared with usual care, a multifaceted quality improvement intervention for stroke care was found to be cost-effective in the first year and highly cost-effective from the second year onward. In the long-term, the intervention yielded a lifetime gain of 0.246 quality-adjusted life-years at an additional cost of Chinese Yuan Renminbi 1510 (US $230), resulting in a cost of Chinese Yuan Renminbi 6138 (US $940) per quality-adjusted life-year gained. Probabilistic sensitivity analysis indicated that the intervention was highly cost-effective in 99.9% of the simulation runs at a willingness-to-pay threshold of Chinese Yuan Renminbi 59 700 (1× gross domestic product per capita of China in 2017, US $9200) per quality-adjusted life-year.

Conclusions—

A multifaceted quality improvement intervention for stroke care was highly cost-effective in China. The results of this study may be used as a reference for delivering such interventions in low- and middle-income countries and in underserved areas of high-income countries.
Henry Care, Roger L’ Estrange and the Contested Memory of Erasmus and the Reformation in Restoration England
Authors: Dodds Gregory D.
Published: February 2020

Henry Care and Roger L’ Estrange fought a bitter battle in the public press in Restoration England. Exploring the ways in which each employed the writings and reputation of Desiderius Erasmus provides insight into the deep fault lines dividing English society in the decade from 1678 to 1688. Their divergent uses of Erasmus demonstrate how late-seventeenth-century interpretations of the early sixteenth-century Reformation became critical points of conflict in the most significant political and religious debates of the period. Paying attention to the reception of Erasmus also helps explain how these two bitter enemies eventually joined William Penn in supporting James II’s Indulgence for Liberty of Conscience.