bluuebunny/crossref_metadata_2025 huggingface dataset:
Consensus of the Brazilian Association of Nutrology on Milky Feeding of Children Aged 1–5 Years Old
Authors: Nogueira-de-Almeida Carlos Alberto , Falcão Mario Cicero , Ribas-Filho Durval , Zorzo Renato Augusto , Konstantyner Tulio , Ricci Raquel , Gioia Nathalia , Fisberg Mauro
Published: July 2020

Objective To publish a consensus on the milky feeding of children aged between 1 and 5 years old, in the face of the nonuniformity of indication and the lack of standardization, in Brazil, on the nomenclature and classification of milky products produced for this stage.

Methods Literature review and members discussion.

Results The review showed the nutrition deficiencies among Brazilian children and the position of different medical societies.

Conclusions Recommendations of milky feeding are proposed for government area, industry and health care professionals.
Computed Tomography Enhances Diagnostic Accuracy in Challenging Medial Coronoid Disease Cases: An Imaging Study in Dog Breeding Appeal Cases
Authors: Wennemuth Jan , Tellhelm Bernd , Eley Nele , von Pückler Kerstin
Published: July 2020

Objectives The aim of this study was to determine the radiographic sensitivity in detecting medial coronoid disease (MCD), using computed tomography (CT) as reference in dogs presented for an official second opinion, and to compare the medial coronoid process (MCP) in fragmented and fissured MCP as well as those unaffected by MCD.

Materials and Methods The data of dogs, presented for official second opinion radiographs and CT, were reviewed by three board-certified observers and in accordance with the International Elbow Working Group guidelines regarding MCD. Radiographic delineation, radiopacity and Hounsfield Units (HU) of the MCP were recorded additionally and the correlation between radiography and CT was investigated.

Results Sensitivity and specificity of radiography compared with CT yielded values of 83.6% for the former and 83.5% for the latter. False-negative grading in radiography correlated significantly (p = 0.0001) with a present fissure line in CT. The mean delineation (p = 0.03) and mean HU of fragmented MCP (p = 0.0045) were significantly reduced compared with fissured MCP and no significant differences in measured HU for fissured MCP were detected in comparison to elbows unaffected by MCD.

Conclusion The results of the present study show substantial agreement between radiography and CT in second opinion cases. However, sensitivity is reduced compared with not preselected cases. A present fissure line in CT was significantly associated with a false-negative grading in radiography. Therefore, CT imaging of the elbows is strongly recommended in cases of appeal.
Comparison between Different Perforator Imaging Modalities for the Anterolateral Thigh Perforator Flap Transfer: A Prospective Study
Authors: Ritschl Lucas M. , Fichter Andreas M. , Bomhard Achim von , Koerdt Steffen , Kehl Victoria , Kolk Andreas , Wolff Klaus-Dietrich , Grill Florian D.
Published: July 2020

Background Perforator imaging is routinely performed before perforator flap harvest. Hand-held Doppler (hhD) and color duplex ultrasonography (CDU) are currently the most popular radiation-free methods for this purpose that can be applied by the surgeon alone. The aim of this study was to compare the accuracy, reliability, and feasibility of hhD and CDU with indocyanine green angiography (ICGA) in the anterolateral thigh perforator flap (ALTPF).

Methods All consecutive ALTPF procedures between May 2017 and April 2018 were included in this prospective study. The perforators were visualized by three investigators independently and randomized, applying hhD, CDU, and ICGA. The presence and the distance to the identified perforator were registered. Further, body mass index (BMI), American Society of Anesthesiologists-status, and the patient's history regarding smoking, alcohol use, and diabetes mellitus were registered alongside gender and age to analyze possible confounders.

Results A total of 12 patients were enrolled with a median age of 67 (52–87) years. In total, 30 perforators were detected intraoperatively as well as with the ICGA. The latter visualized the perforators significantly more precisely than hhD and CDU (p < 0.001 and p = 0.001). The sensitivity and positive predictive value were 67 and 62% for hhD, 73 and 64% for CDU, and 100 and 100% for ICGA, respectively.

Conclusion According to this study, ICGA visualized perforators more accurately than the standard methods hhD and CDU. Further, it was associated with the highest sensitivity and positive predictive value. ICGA consistently delivered excellent results, whereas hhD and CDU showed variability.
The pragmeme of disagreement and its allopracts in English and Serbian political interview discourse
Authors: Radulović Milica , Jovanović Vladimir Ž.
Published: July 2020

The paper explores the disagreement pragmeme as a culture-bound notion (Mey 2016a,2016b,2001) in the language use of English-speaking and Serbian-speaking politicians. The objectives are to establish the types, frequencies and cultural specificities of disagreement allopracts in political interviews. Furthermore, the research analyses allopracts in relation to the single and multiple dispute profiles (van Eemeren, Houtlosser and Henkemans 2007). The starting assumption is that allopracts will be realised in culturally specific ways despite the fact that the analysed pragmeme belongs to the same communication genre, which is the Immediately Relevanttertium comparationis(Krzeszowski 1990) of the research. The hypothesis to be verified is that the Serbian sub-corpus will yield more examples of strong disagreement. Another aim is to classify the obtained allopracts according to their degrees of strength. The analysis is based on the corpus of 50 political interviews, involving 30 politicians and 262 allopracts.
Enacting ‘Being with You’
Authors: Droste Pepe , Günthner Susanne
Published: July 2020

The German second person personal pronounduis commonly described as a deictic “shifter” or a T-address term, which is incorporated as an argument of a predicate. Exploring the ways in which participants use pronouns in everyday interaction, however, shows that these are not the only uses ofdu. In this paper, we examine vocative uses ofduin German everyday interaction. Drawing on methods of Conversation Analysis and Interactional Linguistics, we will show that speakers use vocativedufor the management of being ‘with’ the other in terms of alignment as well as affiliation. Whatdulocally accomplishes, however, is sensitive to its positioning within the temporal unfolding of turns and sequences as well as to the sequential environments in which it is used. Our findings demonstrate the context-sensitivity ofduand underscore the importance of linguistic resources for the interactional establishment and maintenance of social togetherness and sociability.
Eigenfrequency loci crossings, veerings and mode splittings of two cantilevers coupled by an overhang
Authors: Zhang Yin , Petrov Yuri , Zhao Ya-Pu
Published: July 2020

Eigenfrequency loci veering, which indicates strong mode coupling and sometimes mode localization, is a much sought-after property in the applications of mass sensing and opto/electromechanics. A weak physical coupling is the mechanism responsible for the eigenfrequency loci veering and overhang is a widely used structure to realize such mechanism. A continuum model, which is more accurate and straightforward as compared with the discrete models, is presented for the structure of two overhanged cantilevers. The eigenvalue problem formulation based on this continuum model leads to a direct computation of the eigenfrequencies, which does not involve any numerical discretization procedure. A comprehensive study on the eigenfrequency loci veerings and mode splittings of the overhanged structure is presented. The influences of various parameters on the eigenfrequency loci crossing and veerings are also systematically studied. An efficient optimum design tool for the eigenfrequency loci veering of an overhanged structure is provided by the continuum model together with a direct computation method.
Ravenna on the Grand Tour: A View of Late Antiquity in the Eighteenth Century
Authors: Thomas Brittany
Published: July 2020

Ravenna, the former grand capital of the late Roman and early Byzantine Empires and a popular modern UNESCO World Heritage site, is a city rarely included in major historical surveys of Italy during the Grand Tour. An exploration of period sources may reveal why: it was, for many centuries between the Middle Ages and the nineteenth century, a rundown parish town that was incredibly difficult to reach by conventional transportation. This article collates and deconstructs a number of Grand Tour sources in order to gain an understanding of Ravenna in the eighteenth century, and, further, an understanding of the contemporary attitudes towards post-Classical monuments and artwork. This exploration allows us to ask broader questions about Ravenna’s place on the Grand Tour. As a city with very little to offer in the way of Classical monuments, it slightly complicates our idea of classical reception on the Grand Tour and shows us how travellers navigated a place replete with late antique basilicas and Byzantine mosaics instead of marble sculptures and tombs.
Enterococcus faecalis and Vibrio harveyicolonize low-density polyethylene and biodegradable plastics under marine conditions
Authors: Hchaichi Ilef , Bandini Francesca , Spini Giulia , Banni Mohamed , Cocconcelli Pier Sandro , Puglisi Edoardo
Published: July 2020

Conventional plastics and bioplastics are known to accumulate in aquatic ecosystems, emerging as new surfaces for biofilm formation and gene exchanges. On the other hand, the fate of non-conventional bioplastics in the marine environment is still unclear. In this study we have measured, by means of crystal violet test and scanning electron microscopy (SEM), the ability of two model bacteria, Vibrio harveyi and Enterococcus faecalis, to form biofilms on low-density polyethylene (PE), polylactic acid (PLA) and starch-based bioplastic (SBB) surfaces. Experiments were conducted in artificial sea water, incubating squares of 3 cm2 of the three plastics with the two model microorganisms and sampling overnight, and at 3 and 6 days. The presence of biofilms on plastic surfaces was detected from day one of incubation and SBB was the material with the highest biofilm formation. E. faecalis formed the thickest biofilm after 3 days with PLA and SBB, but did not remain stable, and after 6 days with PE. The maximum biofilm formation of V. harveyi was obtained overnight with SBB and PE, and after 3 days with PLA. Our data indicate that both plastic and bioplastics support the formation of biofilms of model pathogenic bacteria, highlighting potential concerns for human health.
Does Visual Speed of Processing Training Improve Health-Related Quality of Life in Assisted and Independent Living Communities?: A Randomized Controlled Trial
Authors: Wolinsky Fredric D , Jones Michael P , Dotson Megan M
Published: July 2020

Background and Objectives

Visual speed of processing training had clinically and statistically significant beneficial effects on health-related quality of life among 2,802 healthy community-dwelling adults aged 65–94 years at 2 and 5 years post-training in the Advanced Cognitive Training for Independent and Vital Elderly randomized controlled trial. We examined whether that effect would be found among older adults in assisted and independent living communities.

Research Design and Methods

We conducted a two-arm, parallel randomized controlled trial stratified by assisted versus independent settings in 31 senior living communities and enrolled 351 adults aged 55–102 years. The targeted intervention dose was 10 hr at baseline with 4-hr boosters at 5 and 11 months. The intervention group received computerized visual speed of processing training, while the attention control group solved computerized crossword puzzles. The health-related quality of life outcomes were the Short-Form 36-item Health Survey’s mental and physical component T scores. Linear mixed-effect models were used.

Results

Visual speed of processing, assisted living, and their interaction had no clinically or statistically significant effects on the physical component T scores. However, visual speed of processing (p = .022), assisted living (p = .022), and their interaction (p = .007) had clinically and statistically significant effects on the mental component T scores. The estimated marginal means revealed a small effect-sized positive 2.2 point visual speed of processing training effect in the independent living communities, but a clinically important harmful −4.2 point visual speed of processing training effect in the assisted living communities.

Discussion and Implications

Given the medium-sized harmful effect of visual speed of processing training among those in the assisted living communities, caution is advised when using these two visual speed of processing training modalities in assisted living communities until further research verifies or refutes our findings and the underlying etiological pathways.
Variable order, directional ℋ2-matrices for Helmholtz problems with complex frequency
Authors: Börm Steffen , Lopez-Fernandez Maria , Sauter Stefan A
Published: July 2020

The sparse approximation of high-frequency Helmholtz-type integral operators has many important physical applications such as problems in wave propagation and wave scattering. The discrete system matrices are huge and densely populated; hence, their sparse approximation is of outstanding importance. In our paper, we will generalize the directional $\mathcal{H}^{2}$-matrix techniques from the ‘pure’ Helmholtz operator $\mathcal{L}u=-\varDelta u+\zeta ^{2}u$ with $\zeta =-\operatorname *{i}k$, $k\in \mathbb{R}$ to general complex frequencies $\zeta \in \mathbb{C}$ with $\operatorname{Re}\zeta\geq0$. In this case, the fundamental solution decreases exponentially for large arguments. We will develop a new admissibility condition that contains $\operatorname{Re}\zeta $ in an explicit way, and introduces the approximation of the integral kernel function on admissible blocks in terms of frequency-dependent directional expansion functions. We develop an error analysis that is explicit with respect to the expansion order and with respect to $\operatorname{Re}\zeta $ and $\operatorname{Im}\zeta $. This allows for choosing the variable expansion order in a quasi-optimal way, depending on $\operatorname{Re}\zeta $, but independent of, possibly large, $\operatorname{Im}\zeta $. The complexity analysis is explicit with respect to $\operatorname{Re}\zeta $ and $\operatorname{Im}\zeta $, and shows how higher values of $\operatorname{Re} \zeta $ reduce the complexity. In certain cases, it even turns out that the discrete matrix can be replaced by its nearfield part. Numerical experiments illustrate the sharpness of the derived estimates and the efficiency of our sparse approximation.
Backlash and Judicial Restraint: Evidence from the European Court of Human Rights
Authors: Stiansen Øyvind , Voeten Erik
Published: July 2020

How does backlash from consolidated democracies affect the behavior of liberal international institutions? We argue that liberal international institutions have incentives to appease their democratic critics. Liberal institutions rely on democratic support for their continued effectiveness and can accommodate democratic critics at a lower legitimacy cost than non-democratic challengers. We examine this theory in the context of the European Court of Human Rights using a new dataset of rulings until 2019 and a coding of government positions during multiple reform conferences. Combining matching and a difference-in-differences design, we find strong evidence that the Court exercises restraint towards consolidated democracies that have criticized the Court in multilateral reform conferences by rendering fewer violation judgments against these states. We find some evidence that governments have also recently appointed more deferential judges. The findings suggest that backlash can affect liberal international institutions even without membership exit.
Log-aesthetic curves and their relation to fluid flow patterns in terms of streamlines☆
Authors: Wo Mei Seen , Gobithaasan R U , Miura Kenjiro T , Loy Kak Choon , Yasmeen Sadaf , Harun Fatimah Noor
Published: July 2020

The log-aesthetic curve (LAC) is a family of aesthetic curves with linear logarithmic curvature graphs (LCGs). It encompasses well-known aesthetic curves such as clothoid, logarithmic spiral, and circle involute. LAC has been playing a pivotal role in aesthetic design. However, its application for functional design is an uncharted territory, e.g. the relationship between LAC and fluid flow patterns may aid in designing better ship hulls and breakwaters. We address this problem by elucidating the relationship between LAC and flow patterns in terms of streamlines at a steady state. We discussed how LAC pathlines form under the influence of pressure gradient via Euler's equation and how LAC streamlines are formed in a special case. LCG gradient ($\alpha $) for implicit and explicit functions is derived, and it is proven that the LCG gradient at the inflection points of explicit functions is always 0 when its third derivative is nonzero. Due to the complexity of the parametric representation of LAC, it is almost impossible to derive the general representation of LAC streamlines. We address this by analyzing the streamlines formed by incompressible flow around an airfoil-like obstacle generated with LAC having various shapes, ${\alpha _r} = \ \{ { - 20,{\rm{\ }} - 5,{\rm{\ }} - 1,{\rm{\ }} - 0.5,{\rm{\ }} - 0.15,{\rm{\ }}0,{\rm{\ }}1,{\rm{\ }}2,{\rm{\ }}3,{\rm{\ }}4,{\rm{\ }}20} \}$, and simulating the streamlines using FreeFem++ reaching a steady state. We found that the LCG gradient of the resultant streamlines is close to that of a clothoid. When the obstacle shape is almost the same as that of a circle ($\alpha \ = \ 20$), the streamlines adjacent to the obstacles have numerous curvature extrema despite nearing steady state. The flow speed variation is the lowest for $\alpha \ = \ - 1.43$ and gets higher as $\alpha$ is increased or decreased from $\alpha \ = \ - 1.43$.
Traumatic bilateral ureteral tear in a pregnant woman after a motor vehicle crash: a case report
Authors: Abu-Rmaileh Muhammad , Jensen Hanna , Kimbrough Mary Katherine
Published: July 2020

Bilateral ureteropelvic junction (UPJ) tears are rare. Trauma can obscure this diagnosis. The objective of this case report is to highlight the rapid diagnosis of this injury and care in the case of pregnancy. A 22-year-old pregnant female was ejected from her car and presented with abdominal pain. The patient got a computed tomography (CT)-chest, abdomen, pelvis (CT-CAP) revealing bilateral ureteral injury, which was confirmed on retrograde cystoscopy. Her injuries were treated with nephrostomy tubes with plans for definitive repair after pregnancy. Fetus remained stable throughout her care and the patient was discharged with no complications. Due to the rapid diagnosis and effective stabilization, the patient and fetus recovered well from the injuries and multiple procedures. While there are many explanations for bilateral UPJ tears, deceleration and hyperextension seem to be the two major mechanisms of this injury.
Necrology of Ontology: Putnam, Ethics, Realism
Authors: Laugier Sandra
Published: July 2020

This article aims at putting in context and at pursuing the concept elaborated by the later Putnam of an ethics without ontology, which I associate with certain other contemporary philosophers like Stanley Cavell and Cora Diamond; and in general of a philosophy without ontology. Putnam’s ambition is to get rid of ontology by refocusing reflection on ethics in a realistic spirit. This calls for a reappraisal of the entirety of Putnam’s evolution after the 1980s, especially his “Wittgensteinian turn,” which has sometimes been underappreciated. To say that ethics has nothing to do with ontology is to make a claim not only about ethics, but also about realism. That is why Putnam’s later work matters today, especially his radical break with the fact/value distinction (reflected in his claim that facts and values are entangled together in our statements and in our lives). This does not only concern ethics, for as Diamond has said and as Putnam reiterates in his own style and culture, we must refocus reflection on ethics and on the place of ethics in our forms of life and of language.
The Possibilities and Constraints for Intersectional Practice in Gender Budgeting Activism
Authors: Cavaghan Rosalind
Published: July 2020

This article examines how gender budgeting (GB) activists in the United Kingdom have sought to practice intersectionality. It draws on Black feminists’ critiques of white feminists’ tendency to deploy intersectionality as a “cooled out buzz word” that relies on modernist, Western feminist epistemology. Results highlight the limitations of modernist positivist epistemologies, which are often used in economic policy and GB, and the importance of knowledge creation practices and explicit engagement with white women’s privilege in intersectional practice. These findings aim to inform European feminists’ responses to Black feminists’ critiques.
Shared Numerosity Representations Across Formats and Tasks Revealed with 7 Tesla fMRI: Decoding, Generalization, and Individual Differences in Behavior
Authors: Wilkey Eric D , Conrad Benjamin N , Yeo Darren J , Price Gavin R
Published: July 2020

Debate continues on whether encoding of symbolic number is grounded in nonsymbolic numerical magnitudes. Nevertheless, fluency of perceiving both number formats, and translating between them, predicts math skills across the life span. Therefore, this study asked if numbers share cortical activation patterns across formats and tasks, and whether neural response to number predicts math-related behaviors. We analyzed patterns of neural activation using 7 Tesla functional magnetic resonance imaging in a sample of 39 healthy adults. Discrimination was successful between numerosities 2, 4, 6, and 8 dots and generalized to activation patterns of the same numerosities represented as Arabic digits in the bilateral parietal lobes and left inferior frontal gyrus (IFG) (and vice versa). This indicates that numerosity-specific neural resources are shared between formats. Generalization was also successful across tasks where participants either identified or compared numerosities in bilateral parietal lobes and IFG. Individual differences in decoding did not relate to performance on a number comparison task completed outside of the scanner, but generalization between formats and across tasks negatively related to math achievement in the parietal lobes. Together, these findings suggest that individual differences in representational specificity within format and task contexts relate to mathematical expertise.
Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear
Authors: Ma Cassandra , Jean-Richard-dit-Bressel Philip , Roughley Stephanie , Vissel Bryce , Balleine Bernard W , Killcross Simon , Bradfield Laura A
Published: July 2020

Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsive disorders and related behaviors. Although rodent studies have established a causal link between mOFC excitation and compulsive-like actions, no such link has been made with mOFC inhibition. Here, we use excitotoxic lesions of mOFC to investigate its role in sensitivity to punishment; a core characteristic of many compulsive disorders. In our first experiment, we demonstrated that mOFC lesions prevented rats from learning to avoid a lever that was punished with a stimulus that coterminated with footshock. Our second experiment demonstrated that retrieval of punishment learning is also somewhat mOFC-dependent, as lesions prevented the extended retrieval of punishment contingencies relative to shams. In contrast, mOFC lesions did not prevent rats from reacquiring the ability to avoid a punished lever when it was learned prior to lesions being administered. In both experiments, Pavlovian fear conditioning to the stimulus was intact for all animals. Together, these results reveal that the mOFC regulates punishment learning and retrieval in a manner that is separate from any role in Pavlovian fear conditioning. These results imply that aberrant mOFC activity may contribute to the punishment insensitivity that is observed across multiple compulsive disorders.
A Causal Role of Area hMST for Self-Motion Perception in Humans
Authors: Schmitt Constanze , Baltaretu Bianca R , Crawford J Douglas , Bremmer Frank
Published: July 2020

Previous studies in the macaque monkey have provided clear causal evidence for an involvement of the medial-superior-temporal area (MST) in the perception of self-motion. These studies also revealed an overrepresentation of contraversive heading. Human imaging studies have identified a functional equivalent (hMST) of macaque area MST. Yet, causal evidence of hMST in heading perception is lacking. We employed neuronavigated transcranial magnetic stimulation (TMS) to test for such a causal relationship. We expected TMS over hMST to induce increased perceptual variance (i.e., impaired precision), while leaving mean heading perception (accuracy) unaffected. We presented 8 human participants with an optic flow stimulus simulating forward self-motion across a ground plane in one of 3 directions. Participants indicated perceived heading. In 57% of the trials, TMS pulses were applied, temporally centered on self-motion onset. TMS stimulation site was either right-hemisphere hMST, identified by a functional magnetic resonance imaging (fMRI) localizer, or a control-area, just outside the fMRI localizer activation. As predicted, TMS over area hMST, but not over the control-area, increased response variance of perceived heading as compared with noTMS stimulation trials. As hypothesized, this effect was strongest for contraversive self-motion. These data provide a first causal evidence for a critical role of hMST in visually guided navigation.
In VitroEffects of Emerging Bisphenols on Myocyte Differentiation and Insulin Responsiveness
Authors: Jing Jiongjie , Pu Yong , Veiga-Lopez Almudena , Lyu Lihua
Published: July 2020

Bisphenols are endocrine disrupting chemicals to which humans are ubiquitously exposed to. Prenatal bisphenol A exposure can lead to insulin resistance. However, the metabolic effects of other emerging bisphenols, such as bisphenol S (BPS) and bisphenol F (BPF), are less understood. Because the skeletal muscle is the largest of the insulin target tissues, the goal of this study was to evaluate the effects of 2 emerging bisphenols (BPS and BPF) on cytotoxicity, proliferation, myogenic differentiation, and insulin responsiveness in skeletal muscle cells. We tested this using a dose-response approach in C2C12 mouse and L6 rat myoblast cell lines. The results showed that C2C12 mouse myoblasts were more susceptible to bisphenols compared with L6 rat myoblasts. In both cell lines, bisphenol A was more cytotoxic, followed by BPF and BPS. C2C12 myoblast proliferation was higher upon BPF exposure at the 10−4 M dose and the fusion index was increased after exposure to either BPF or BPS at doses over 10−10 M. Exposure to BPS and BPF also reduced baseline expression of p-AKT (Thr) and p-GSK-3β, but not downstream effectors such as mTOR and glucose transporter-4. In conclusion, at noncytotoxic doses, BPS and BPF can alter myoblast cell proliferation, differentiation, and partially modulate early effectors of the insulin receptor signaling pathway. However, BPS or BPF short-term exposure evaluated here does not result in impaired insulin responsiveness.
A Novel Framework Using Remote Telesimulation With Standardized Parents to Improve Research Staff Preparedness for Informed Consent in Pediatric Critical Care Research*
Authors: LaMarra Denise , French Jaclyn , Bailey Christine , Sisko Martha T. , Coughlin-Wells Kerry , Agus Michael S. D. , Srinivasan Vijay , Nadkarni Vinay M.
Published: July 2020

Objectives:

The Heart And Lung Failure—Pediatric INsulin Titration study was experiencing poor subject enrollment due to low rates of informed consent. Heart And Lung Failure—Pediatric INsulin Titration investigators collaborated with the Perelman School of Medicine Standardized Patient Program to explore the novel use of telesimulation with standardized parents to train research staff to approach parents of critically ill children for informed consent. We describe the feasibility, learner acceptance, and financial costs of this novel intervention and performed a post hoc analysis to determine if this intervention improved study consent rates.

Design:

Observational, comparative effectiveness study.

Setting:

Heart And Lung Failure—Pediatric INsulin Titration study enrolling sites.

Subjects:

Research staff (at the remote site).

Interventions:

Individual 90-minute Skype telesimulation sessions with standardized parent and simulation facilitator (at the training site).

Measurements and Main Results:

Forty telesimulation sessions with 79 Heart And Lung Failure—Pediatric INsulin Titration research staff (participants) at 24 remote sites were conducted. Despite some technical delays, 40 out of 40 simulations (100%) were completed. Based on feedback surveys, 100% of respondents agreed (81% strongly agreed) that telesimulation sessions achieved intended learning objectives to prepare research staff to approach parents of eligible critically ill children to obtain informed consent. Additionally, 100% of respondents agreed (74% strongly agreed) that they would use lessons from the telesimulation when approaching parents to obtain informed consent for research. Telesimulation with standardized parents achieved lower financial costs (approximately $85 per session) compared with traditional in-person site visits for training research staff. There was no significant improvement in study consent rates with the intervention (pre: 46% vs post: 48%; p = 0.78).

Conclusions:

Remote telesimulation with standardized parents is feasible, acceptable, and associated with lower financial costs to prepare research staff to obtain informed consent from parents of critically ill children eligible for clinical research trials. Despite this novel approach, Heart And Lung Failure—Pediatric INsulin Titration study consent rates did not improve, suggesting that other factors influence parental consent and decision making in complex multicenter clinical research trials.
Multi-scale analysis and modelling of collective migration in biological systems
Authors: Deutsch Andreas , Friedl Peter , Preziosi Luigi , Theraulaz Guy
Published: July 2020

Collective migration has become a paradigm for emergent behaviour in systems of moving and interacting individual units resulting in coherent motion. In biology, these units are cells or organisms. Collective cell migration is important in embryonic development, where it underlies tissue and organ formation, as well as pathological processes, such as cancer invasion and metastasis. In animal groups, collective movements may enhance individuals' decisions and facilitate navigation through complex environments and access to food resources. Mathematical models can extract unifying principles behind the diverse manifestations of collective migration. In biology, with a few exceptions, collective migration typically occurs at a ‘mesoscopic scale’ where the number of units ranges from only a few dozen to a few thousands, in contrast to the large systems treated by statistical mechanics. Recent developments in multi-scale analysis have allowed linkage of mesoscopic to micro- and macroscopic scales, and for different biological systems. The articles in this theme issue on ‘Multi-scale analysis and modelling of collective migration’ compile a range of mathematical modelling ideas and multi-scale methods for the analysis of collective migration. These approaches (i) uncover new unifying organization principles of collective behaviour, (ii) shed light on the transition from single to collective migration, and (iii) allow us to define similarities and differences of collective behaviour in groups of cells and organisms. As a common theme, self-organized collective migration is the result of ecological and evolutionary constraints both at the cell and organismic levels. Thereby, the rules governing physiological collective behaviours also underlie pathological processes, albeit with different upstream inputs and consequences for the group.

This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Modelling collective cell motion: are on- and off-lattice models equivalent?
Authors: Nava-Sedeño Josué Manik , Voß-Böhme Anja , Hatzikirou Haralampos , Deutsch Andreas , Peruani Fernando
Published: July 2020

Biological processes, such as embryonic development, wound repair and cancer invasion, or bacterial swarming and fruiting body formation, involve collective motion of cells as a coordinated group. Collective cell motion of eukaryotic cells often includes interactions that result in polar alignment of cell velocities, while bacterial patterns typically show features of apolar velocity alignment. For analysing the population-scale effects of these different alignment mechanisms, various on- and off-lattice agent-based models have been introduced. However, discriminating model-specific artefacts from general features of collective cell motion is challenging. In this work, we focus on equivalence criteria at the population level to compare on- and off-lattice models. In particular, we define prototypic off- and on-lattice models of polar and apolar alignment, and show how to obtain an on-lattice from an off-lattice model of velocity alignment. By characterizing the behaviour and dynamical description of collective migration models at the macroscopic level, we suggest the type of phase transitions and possible patterns in the approximative macroscopic partial differential equation descriptions as informative equivalence criteria between on- and off-lattice models.

This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Comparison of solitary and collective foraging strategies of
Caenorhabditis elegans
in patchy food distributions
Authors: Ding Siyu Serena , Muhle Leah S. , Brown André E. X. , Schumacher Linus J. , Endres Robert G.
Published: July 2020

Collective foraging has been shown to benefit organisms in environments where food is patchily distributed, but whether this is true in the case where organisms do not rely on long-range communications to coordinate their collective behaviour has been understudied. To address this question, we use the tractable laboratory model organism
Caenorhabditis elegans
, where a social strain (
npr-1
mutant) and a solitary strain (N2) are available for direct comparison of foraging strategies. We first developed an on-lattice minimal model for comparing collective and solitary foraging strategies, finding that social agents benefit from feeding faster and more efficiently simply owing to group formation. Our laboratory foraging experiments with
npr-1
and N2 worm populations, however, show an advantage for solitary N2 in all food distribution environments that we tested. We incorporated additional strain-specific behavioural parameters of
npr-1
and N2 worms into our model and computationally identified N2's higher feeding rate to be the key factor underlying its advantage, without which it is possible to recapitulate the advantage of collective foraging in patchy environments. Our work highlights the theoretical advantage of collective foraging owing to group formation alone without long-range interactions and the valuable role of modelling to guide experiments.

This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems'.
Collective dynamics of sperm cells
Authors: Schoeller Simon F. , Holt William V. , Keaveny Eric E.
Published: July 2020

While only a single sperm may fertilize the egg, getting to the egg can be facilitated, and possibly enhanced, by sperm group dynamics. Examples range from the trains formed by wood mouse sperm to the bundles exhibited by echidna sperm. In addition, observations of wave-like patterns exhibited by ram semen are used to score prospective sample fertility for artificial insemination in agriculture. In this review, we discuss these experimental observations of collective dynamics, as well as describe recent mechanistic models that link the motion of individual sperm cells and their flagella to observed collective dynamics. Establishing this link in models involves negotiating the disparate time- and length scales involved, typically separated by a factor of 1000, to capture the dynamics at the greatest length scales affected by mechanisms at the shortest time scales. Finally, we provide some outlook on the subject, in particular, the open questions regarding how collective dynamics impacts fertility.

This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Autocrine inhibition of cell motility can drive epithelial branching morphogenesis in the absence of growth
Authors: Rens Elisabeth G. , Zeegers Mathé T. , Rabbers Iraes , Szabó András , Merks Roeland M. H.
Published: July 2020

Epithelial branching morphogenesis drives the development of organs such as the lung, salivary gland, kidney and the mammary gland. It involves cell proliferation, cell differentiation and cell migration. An elaborate network of chemical and mechanical signals between the epithelium and the surrounding mesenchymal tissues regulates the formation and growth of branching organs. Surprisingly, when cultured in isolation from mesenchymal tissues, many epithelial tissues retain the ability to exhibit branching morphogenesis even in the absence of proliferation. In this work, we propose a simple, experimentally plausible mechanism that can drive branching morphogenesis in the absence of proliferation and cross-talk with the surrounding mesenchymal tissue. The assumptions of our mathematical model derive fromin vitroobservations of the behaviour of mammary epithelial cells. These data show that autocrine secretion of the growth factor TGFβ1 inhibits the formation of cell protrusions, leading to curvature-dependent inhibition of sprouting. Our hybrid cellular Potts and partial-differential equation model correctly reproduces the experimentally observed tissue-geometry-dependent determination of the sites of branching, and it suffices for the formation of self-avoiding branching structures in the absence and also in the presence of cell proliferation.

This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Rules of collective migration: from the wildebeest to the neural crest
Authors: Shellard Adam , Mayor Roberto
Published: July 2020

Collective migration, the movement of groups in which individuals affect the behaviour of one another, occurs at practically every scale, from bacteria up to whole species' populations. Universal principles of collective movement can be applied at all levels. In this review, we will describe the rules governing collective motility, with a specific focus on the neural crest, an embryonic stem cell population that undergoes extensive collective migration during development. We will discuss how the underlying principles of individual cell behaviour, and those that emerge from a supracellular scale, can explain collective migration.

This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Collective invasion of glioma cells through OCT1 signalling and interaction with reactive astrocytes after surgery
Authors: Kim Yangjin , Lee Donggu , Lawler Sean
Published: July 2020

Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer with a short median survival time. GBM is characterized by the hallmarks of aggressive proliferation and cellular infiltration of normal brain tissue. miR-451 and its downstream molecules are known to play a pivotal role in regulation of the balance of proliferation and aggressive invasion in response to metabolic stress in the tumour microenvironment (TME). Surgery-induced transition in reactive astrocyte populations can play a significant role in tumour dynamics. In this work, we develop a multi-scale mathematical model of miR-451-LKB1-AMPK-OCT1-mTOR pathway signalling and individual cell dynamics of the tumour and reactive astrocytes after surgery. We show how the effects of fluctuating glucose on tumour cells need to be reprogrammed by taking into account the recent history of glucose variations and an AMPK/miR-451 reciprocal feedback loop. The model shows how variations in glucose availability significantly affect the activity of signalling molecules and, in turn, lead to critical cell migration. The model also predicts that microsurgery of a primary tumour induces phenotypical changes in reactive astrocytes and stem cell-like astrocytes promoting tumour cell proliferation and migration by Cxcl5. Finally, we investigated a new anti-tumour strategy by Cxcl5-targeting drugs.

This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Dynamic heterogeneity influences the leader–follower dynamics during epithelial wound closure
Authors: Vishwakarma Medhavi , Thurakkal Basil , Spatz Joachim P. , Das Tamal
Published: July 2020

Cells of epithelial tissue proliferate and pack together to attain an eventual density homeostasis. As the cell density increases, spatial distribution of velocity and force show striking similarity to the dynamic heterogeneity observed elsewhere in dense granular matter. While the physical nature of this heterogeneity is somewhat known in the epithelial cell monolayer, its biological relevance and precise connection to cell density remain elusive. Relevantly, we had demonstrated how large-scale dynamic heterogeneity in the monolayer stress field in the bulk could critically influence the emergence of leader cells at the wound margin during wound closure, but did not connect the observation to the corresponding cell density. In fact, numerous previous reports had essentially associated long-range force and velocity correlation with either cell density or dynamic heterogeneity, without any generalization. Here, we attempted to unify these two parameters under a single framework and explored their consequence on the dynamics of leader cells, which eventually affected the efficacy of collective migration and wound closure. To this end, we first quantified the dynamic heterogeneity by the peak height of four-point susceptibility. Remarkably, this quantity showed a linear relationship with cell density over many experimental samples. We then varied the heterogeneity, by changing cell density, and found this change altered the number of leader cells at the wound margin. At low heterogeneity, wound closure was slower, with decreased persistence, reduced coordination and disruptive leader–follower interactions. Finally, microscopic characterization of cell–substrate adhesions illustrated how heterogeneity influenced orientations of focal adhesions, affecting coordinated cell movements. Together, these results demonstrate the importance of dynamic heterogeneity in epithelial wound healing.

This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems'.
3D Printed frames to enable reuse and improve the fit of N95 and KN95 respirators
Authors: McAvoy Malia , Bui Ai-Tram N. , Hansen Christopher , Plana Deborah , Said Jordan T. , Yu Zizi , Yang Helen , Freake Jacob , Van Christopher , Krikorian David , Cramer Avilash , Smith Leanne , Jiang Liwei , Lee Karen J. , Li Sara J. , Beller Brandon , Short Michael , Yu Sherry H. , Mostaghimi Arash , Sorger Peter K. , LeBoeuf Nicole R.
Published: July 2020

Background

In response to supply shortages during the COVID-19 pandemic, N95 filtering facepiece respirators (FFRs or “masks”), which are typically single-use devices in healthcare settings, are routinely being used for prolonged periods and in some cases decontaminated under “reuse” and “extended use” policies. However, the reusability of N95 masks is often limited by degradation or breakage of elastic head bands and issues with mask fit after repeated use. The purpose of this study was to develop a frame for N95 masks, using readily available materials and 3D printing, which could replace defective or broken bands and improve fit.

Results

An iterative design process yielded a mask frame consisting of two 3D-printed side pieces, malleable wire links that users press against their face, and cut lengths of elastic material that go around the head to hold the frame and mask in place. Volunteers (n= 41; average BMI= 25.5), of whom 31 were women, underwent qualitative fit with and without mask frames and one or more of four different brands of FFRs conforming to US N95 or Chinese KN95 standards. Masks passed qualitative fit testing in the absence of a frame at rates varying from 48 – 92% (depending on mask model and tester). For individuals for whom a mask passed testing, 75-100% (average = 86%) also passed testing with a frame holding the mask in place. Among users for whom a mask failed in initial fit testing, 41% passed using a frame. Success varied with mask model and across individuals.

Conclusions

The use of mask frames can prolong the lifespan of N95 and KN95 masks by serving as a substitute for broken or defective bands without adversely affecting fit. Frames also have the potential to improve fit for some individuals who cannot fit existing masks. Frames therefore represent a simple and inexpensive way of extending the life and utility of PPE in short supply. For clinicians and institutions interested in mask frames, designs and specifications are provided without restriction for use or modification. To ensure adequate performance in clinical settings, qualitative fit testing with user-specific masks and frames is required.
Daily Forecasting of New Cases for Regional Epidemics of Coronavirus Disease 2019 with Bayesian Uncertainty Quantification
Authors: Lin Yen Ting , Neumann Jacob , Miller Ely F. , Posner Richard G. , Mallela Abhishek , Safta Cosmin , Ray Jaideep , Thakur Gautam , Chinthavali Supriya , Hlavacek William S.
Published: July 2020

To increase situational awareness and support evidence-based policy-making, we formulated a mathematical model for COVID-19 transmission within a regional population. This compartmental model accounts for quarantine, self-isolation, social distancing, a non-exponentially distributed incubation period, asymptomatic individuals, and mild and severe forms of symptomatic disease. Using Bayesian inference, we have been calibrating region-specific models daily for consistency with new reports of confirmed cases from the 15 most populous metropolitan statistical areas in the United States and quantifying uncertainty in parameter estimates and predictions of future case reports. This online learning approach allows for early identification of new trends despite considerable variability in case reporting.

Article Summary Line

We report models for regional COVID-19 epidemics and use of Bayesian inference to quantify uncertainty in daily predictions of expected reporting of new cases, enabling identification of new trends in surveillance data.