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1. Optimal efficiency of high frequency chest wall oscillations and links with resistance and compliance in a model of the lung

Author

Brunengo, Michaël, Mitchell, Barrett R., Nicolini, Antonello, Rousselet, Bernard, and Mauroy, Benjamin

Subjects
Physics - Medical Physics, Physics - Computational Physics, Quantitative Biology - Tissues and Organs
Abstract

Chest physiotherapy is a set of techniques used to help the draining of the mucus from the lung in pathological situations. The choice of the techniques, and their adjustment to the patients or to the pathologies, remains as of today largely empirical. High Frequency Chest Wall Oscillation (HFCWO) is one of these techniques, performed with a device that applies oscillating pressures on the chest. However, there is no clear understanding of how HFCWO devices interact with the lung biomechanics. Hence, we study idealised HFCWO manipulations applied to a mathematical and numerical model of the biomechanics of the lung. The lung is represented by a fluid--structure interaction model based on an airway tree that is coupled to an homogeneous elastic medium. We show that our model is driven by two dimensionless numbers that drive the effect of the idealised HFCWO manipulation on the model of the lung. Our model allow to analyze the stress applied to an idealised mucus by the air--mucus interaction and by the airway walls deformation. This stress behaves as a buffer and has the effect of reducing the stress needed to overcome the idealised mucus yield stress. Moreover, our model predicts the existence of an optimal range of the working frequencies of HFCWO. This range is in agreement with the frequencies actually used by practitioners during HFCWO maneuvers. Finally, our model suggests that analyzing the mouth airflow during HFCWO maneuvers could allow to estimate the compliance and the hydrodynamic resistance of the lung of a patient.

Published
2021
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2. Towards the modeling of mucus draining from human lung: role of airways deformation on air-mucus interaction

Author

Mauroy, Benjamin, Flaud, Patrice, Pelca, Dominique, Fausser, Christian, Merckx, Jacques, and Mitchell, Barrett R.

Subjects
Physics - Medical Physics, Physics - Biological Physics, Physics - Computational Physics, Quantitative Biology - Tissues and Organs
Abstract

Chest physiotherapy is an empirical technique used to help secretions to get out of the lung whenever stagnation occurs. Although commonly used, little is known about the inner mechanisms of chest physiotherapy and controversies about its use are coming out regularly. Thus, a scientific validation of chest physiotherapy is needed to evaluate its effects on secretions. We setup a quasi-static numerical model of chest physiotherapy based on thorax and lung physiology and on their respective biophysics. We modeled the lung with an idealized deformable symmetric bifurcating tree. Bronchi and their inner fluids mechanics are assumed axisymmetric. Static data from the literature is used to build a model for the lung's mechanics. Secretions motion is the consequence of the shear constraints apply by the air flow. The input of the model is the pressure on the chest wall at each time, and the output is the bronchi geometry and air and secretions properties. In the limit of our model, we mimicked manual and mechanical chest physiotherapy techniques. We show that for secretions to move, air flow has to be high enough to overcome secretion resistance to motion. Moreover, the higher the pressure or the quicker it is applied, the higher is the air flow and thus the mobilization of secretions. However, pressures too high are efficient up to a point where airways compressions prevents air flow to increases any further. Generally, the first effects of manipulations is a decrease of the airway tree hydrodynamic resistance, thus improving ventilation even if secretions do not get out of the lungs. Also, some secretions might be pushed deeper into the lungs; this effect is stronger for high pressures and for mechanical chest physiotherapy. Finally, we propose and tested two adimensional numbers that depend on lung properties and that allow to measure the efficiency and comfort of a manipulation.

Published
2015

3. An analysis of the storyline method in primary school : its theoretical underpinnings and its impact on pupils’ intrinsic motivation

Author

Mitchell-Barrett, Rhonda

Subjects
371.3
Abstract

This study explores the relationship between the Scottish Storyline teaching method and pupils’ levels of motivation when engaged in a Storyline topic. It also examines the theoretical underpinnings for Storyline drawn from constructivism, progressive education, drama methodology and intrinsic motivation. Storyline as a pedagogy emerged in Scotland during the late 1960s, as a means to support primary school teachers in teaching a topic based curriculum. Storyline as a teaching methodology has been widely adopted across Europe and America and in these countries, the method continues to grow in popularity. In order to meet the demands of the Scottish ‘Curriculum for Excellence’, there was recently a Storyline revival in Scotland. Yet in England, Storyline remains little known or virtually unheard of. However, with changing curriculum demands, teachers are searching for a pedagogy to teach topic based, cross curricular learning themes and as this paper will demonstrate, the Storyline method presents one such approach. For the purposes of this study, pupils’ levels of intrinsic motivation were attained using an intrinsic motivation itemised questionnaire and the views and opinions of a sample group of pupils were gained through semi-structured interviews. This blend of data provides an insight into the scoring of pupils’ motivational levels and also their thoughts and experiences of the Storyline method. This research was then viewed within the wider context of the primary school curriculum, making links to recent developments in education policy making, and considering Storyline as a methodology to meet the needs of an unknown future curriculum.

Published
2010

5. Efficacy and safety of intramuscular administration of tixagevimab-cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial

Author

Hugh Montgomery, F D Richard Hobbs, Francisco Padilla, Douglas Arbetter, Alison Templeton, Seth Seegobin, Kenneth Kim, Jesus Abraham Simón Campos, Rosalinda H Arends, Bryan H Brodek, Dennis Brooks, Pedro Garbes, Julieta Jimenez, Gavin C K W Koh, Kelly W Padilla, Katie Streicher, Rolando M Viani, Vijay Alagappan, Menelas N Pangalos, Mark T Esser, Wakana Abe, Tania Adan De Varona, Daria Adiatullina, Daniel Aguilar Zapata, Kevin Ahlers, Carolina Aimo, Ayoade Akere, Elena Akimova, Jorge Alatorre Alexander, Logan Aldrich, Ismael Ali Garcia, Karim Ali García, Lee Allison, Rosa Alonso Zuñiga, Ivan Aloysius, Javier Altclas, Andres Alvarisqueta, Martti Antila, Camila Anton, Elisabet Árboix Alamo, Samir Arora, Ramón Alejandro Avilés Felix, Natalya Bakhtina, Varenka Barbero-Becerra, Armando Barragan-Reyes, Alejandro Barreira, Mitchell Barrett, Jiri Beran, Nikolett Berki, Viktoria Berki, Richard Betten, Claudia Binelli, Lenka Brunzová, Cecilia Bussolari, Karianna Byargeon, Justyna Bytnar, Carlos Camberos, Pedro Campos Corzo, Grazia Cannon, Valentina Canovi, Simone Carla da Rosa, Ana Caroline Moser, Luis Carrera Rivas, Marcelo Martin Casas, Paulo Castañeda-Méndez, Ana Cavalcante, Eugenia Cherepova, Alexei Chermenskii, Lauren Clark, Mauro Codeluppi, Flavia Coelho, Belinda Contreras, Alex Cran, Taylor Dao, Chrisette Dharma, Cosimo Di Castri, Victoria Diaz Balocchi, Omar Durán, Kara Earl, Adam Ellery, Tomoko Endo, Andrea Everding, Rainald Fischer, Benedito Fonseca, Chelsea C. Franklin, Susan-Beatrice Franz, Anna Fumagalli, Mauricio Galindo-Amaya, Mariagiulia Galli, Laura Gerna, Karolly Gil Ureña, Henrikki Gomes Antila, Laura Ines Gomes Maricato, Gabriela Goncalvez, Martin Gonzalez, Jesús González-Lama, Stephen Granier, Jacob Granier, Stephan Grunwald, David Guardeño-Ropero, Monica Guberti, Sridhar Guduri, Carolina Guerrero García, Jehad Haggiagi, Kacie Hale, Toshimasa Hayashi, Maiara Hermes, Dante Hernandez Colin, Yuji Hirai, Masayuki Hojo, Tetsuya Homma, Billy Hour, Andreas Huber, Diego Iacovelli, Noriomi Ishibashi, Yutaro Iwabe, Shinyu Izumi, Arne Jessen, Heiko Jessen, Wilner Jeudy, Marta Jiménez Marcos, Rebecca Johnson, Eva Juárez-Hernández, Kiyomi Kabasawa, Katarzyna Kamińska, Megumi Kawabe, Angela Kemp, Oleg Khmelnitskiy, Carina Klassen, Olena Kobrynska, Pavel Koleckar, Stephanie Korn, Marc Kornmann, Viktor Kostenko, Evgenii Kovalchuk, Yana Kovalchuk, Tim Kümmerle, Ulrike Lachmund, Kerstin Lammersmann, Flávio Lastebasse, Ivana Lattuada, Felicitas Lauer, Kyrylo Lebed, Olga Lebed, Diego Lecona-Garcia, Maria Christina Leoni, Marina Lima, Raymond Little, Holly Little, Andrea Lizardi-Díaz, Michele Lobo-Becker, Francesco Luppi, Veronica Macias, Shigefumi Maesaki, Cristiano Magnaghi, Annalisa Mancini, Stanisław Mazur, Tatiana Melnikova, Sergio Menchaca, Ibrahim Menendez-Perez, Ewa Międlar, Shuuichi Mizunuma, Anastasiya Mochalova, Mihad Mohamed, Theresa Moll, Camila Montalvo, Amber Mottola, Birgit Mück, Rebeca Mussi Brugnolli, Akanksha Nanda, Dörthe Neuner, Agatha Ngwueke, Sebastian Noe, Martin Novacek, Laura Nuzzolo-Shihadeh, Emeka Obiekwe, Isaias G. Ocampo Gaytán, Norio Ohmagari, Shin Ohta, Ptuonye Onyewuchi, Iurii Pankov, Maurício Pedrosa, Yael Peré, Alejandro Pereyra, Eliana Perez, Eduardo Perez-Alba, Paloma Perpiña Lozano, Tanya Perrei, Dena Peterson, Ligia Pierroti, Felipe Pineda-Cárdenas, Teresa Plascencia Sanchez, Camila Poletti, Chiara Pomaranzi, Lisette Portes, Nils Postel, Monica Ramirez, Isabel Ramírez, Miguel Ramirez-Baena, Mahadev Ramjee, Giovanna Ratti, Jackie Reeve, Petr Reichert, Petra Reichertová, Edgar Alejandro Reyes Garcia, Celso Ricardo, Nicomedes Rodríguez Rodríguez, Jaun Roldán Sánchez, Matilde Romero-Lopez, Tyrone Rosales, Harvey Rosales, Mohamed Roshan, Simran Roshan, Patrizia Rovere Querini, Heather Rutter, Sadaf Sachwani, Hironori Sagara, Jun Sakai, Nina Samson, José Héctor Sánchez Mijangos, Liliana Sánchez, Ana Sánchez-González, Micko Sandford, Laura Santana, Felipe Santos de Carvalho, Reiko Sasao, Lubna Sato, Elizabeth Scheuermann, Olaf Schmidt, Masafumi Seki, Safia Shaikh, Daishi Shimada, Masaharu Shinkai, Masahiro Shinoda, Jackie Smith, Fernando Solorzano, Silvia Soncini, Katalin Soregine, Erica Sosa, Olalekan Sowade, Veronika Špinková, Ruth Staniford, Iska Steigemann, Vivien Steiner, Vladimir Strelkov, Cintya R. Suárez Pineda, Hiroki Suenaga, Shintaro Suzaki, Hannah Swayze, Yuji Tada, Yuichiro Takeshita, Yasuo Takiguchi, Akihiko Tanaka, Norihito Tarumoto, Albina Tatarintseva, Michelle Taubert, Elizaveta Terenya, César Tinoco, Tomohiro Tomiyasu, Gladys Torres-Vidal, Gabriela Trejo-Aguiar, Kenji Tsushima, Emma Tunstall, Caterina Turrà, Yoandy Valdes, Nelly Valencia Castro, Guilherme Visconti, Giordano Vitali, Apinya Vutikullird, Jezdancher Watti, Doreen Werth, Cheyanne Wilson, Philippe Wilson, Amy Workman, Pamela Wörle, Christoph Wyen, Yoshiko Yamaguchi, and Kei Yamamoto

Subjects
Adult, Pulmonary and Respiratory Medicine, Treatment Outcome, Double-Blind Method, SARS-CoV-2, Outpatients, Antibodies, Monoclonal, Humans, Middle Aged, COVID-19 Drug Treatment
Abstract

Background: Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab–cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab–cilgavimab in preventing progression to severe COVID-19 or death. Methods: TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab–cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov, NCT04723394. Findings: Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab–cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab–cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6–71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1–8·0; p Interpretation: A single intramuscular tixagevimab–cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab–cilgavimab might lead to more favourable outcomes.

Published
2022

7. On Ramsey-Minimal Infinite Graphs

Author

Jordan Mitchell Barrett and Valentino Vito

Subjects
Matching (graph theory), Applied Mathematics, Ramsey theory, Finite case, Mathematics - Logic, Star (graph theory), Graph, Theoretical Computer Science, Combinatorics, Compact space, Computational Theory and Mathematics, FOS: Mathematics, Mathematics - Combinatorics, Discrete Mathematics and Combinatorics, Combinatorics (math.CO), Geometry and Topology, Logic (math.LO), 05C55, 05D10, 05C63, 05C60, Mathematics
Abstract

For fixed finite graphs $G$, $H$, a common problem in Ramsey theory is to study graphs $F$ such that $F \to (G,H)$, i.e. every red-blue coloring of the edges of $F$ produces either a red $G$ or a blue $H$. We generalize this study to infinite graphs $G$, $H$; in particular, we want to determine if there is a minimal such $F$. This problem has strong connections to the study of self-embeddable graphs: infinite graphs which properly contain a copy of themselves. We prove some compactness results relating this problem to the finite case, then give some general conditions for a pair $(G,H)$ to have a Ramsey-minimal graph. We use these to prove, for example, that if $G=S_\infty$ is an infinite star and $H=nK_2$, $n \ge 1$ is a matching, then the pair $(S_\infty,nK_2)$ admits no Ramsey-minimal graphs., 14 pages, 4 figures. The published version on EJC contains a minor error: in the proof of Lemma 20 on p10, in the last sentence of the last paragraph, it says "The induced subgraph $F := \Gamma[x_1,\ldots,x_n]$". This should read "The subgraph of $\Gamma$ induced by all edges that are incident to at least one of $x_1, \ldots, x_n$", and has been corrected in this arXiv version

Published
2021

8. On Rado conditions for nonlinear Diophantine equations

Author

Jordan Mitchell Barrett, Martino Lupini, Joel Moreira, Barrett J M, Lupini M, and Moreira J

Subjects
Conjecture, Mathematics - Number Theory, Diophantine equation, 010102 general mathematics, Mathematics - Logic, 0102 computer and information sciences, 01 natural sciences, Combinatorics, Nonlinear system, 05D10, 11D99 (Primary) 11U10 (Secondary), 010201 computation theory & mathematics, Homogeneous, Partition regularity, None, FOS: Mathematics, Mathematics - Combinatorics, Discrete Mathematics and Combinatorics, Partition (number theory), Combinatorics (math.CO), Number Theory (math.NT), 0101 mathematics, QA, Logic (math.LO), Mathematics
Abstract

Building on previous work of Di Nasso and Luperi Baglini, we provide general necessary conditions for a Diophantine equation to be partition regular. These conditions are inspired by Rado's characterization of partition regular linear homogeneous equations. We conjecture that these conditions are also sufficient for partition regularity, at least for equations whose corresponding monovariate polynomial is linear. This would provide a natural generalization of Rado's theorem. We verify that such a conjecture hold for the equations $x^{2}-xy+ax+by+cz=0$ and $x^{2}-y^{2}+ax+by+cz=0$ for $a,b,c\in \mathbb{Z}$ such that $abc=0$ or $% a+b+c=0$. To deal with these equations, we establish new results concerning the partition regularity of polynomial configurations in $\mathbb{Z}$ such as $\left\{ x,x+y,xy+x+y\right\} $, building on the recent result on the partition regularity of $\left\{ x,x+y,xy\right\} $., Comment: 22 pages

Published
2019
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