Abstract: The COVID-19 pandemic is the most severe pandemic caused by a respiratory virus since the 1918 influenza pandemic. As is the case with other respiratory viruses, three modes of transmission have been invoked: contact (direct and through fomites), large droplets and aerosols. This narrative review makes the case that aerosol transmission is an important mode for COVID-19, through reviewing studies about bioaerosol physiology, detection of infectious SARS-CoV-2 in exhaled bioaerosols, prolonged SARS-CoV-2 infectivity persistence in aerosols created in the laboratory, detection of SARS-CoV-2 in air samples, investigation of outbreaks with manifest involvement of aerosols, and animal model experiments. SARS-CoV-2 joins influenza A virus as a virus with proven pandemic capacity that can be spread by the aerosol route. This has profound implications for the control of the current pandemic and for future pandemic preparedness.

Abstract: Aerosol particles of respirable size are exhaled when individuals breathe, speak and sing and can transmit respiratory pathogens between infected and susceptible individuals. The COVID-19 pandemic has brought into focus the need to improve the quantification of the particle number and mass exhalation rates as one route to provide estimates of viral shedding and the potential risk of transmission of viruses. Most previous studies have reported the number and mass concentrations of aerosol particles in an exhaled plume. We provide a robust assessment of the absolute particle number and mass exhalation rates from measurements of minute ventilation using a non-invasive Vyntus Hans Rudolf mask kit with straps housing a rotating vane spirometer along with measurements of the exhaled particle number concentrations and size distributions. Specifically, we report comparisons of the number and mass exhalation rates for children (12–14 years old) and adults (19–72 years old) when breathing, speaking and singing, which indicate that child and adult cohorts generate similar amounts of aerosol when performing the same activity. Mass exhalation rates are typically 0.002–0.02 ng s−1 from breathing, 0.07–0.2 ng s−1 from speaking (at 70–80 dBA) and 0.1–0.7 ng s−1 from singing (at 70–80 dBA). The aerosol exhalation rate increases with increasing sound volume for both children and adults when both speaking and singing.

Abstract: The generation of cellular diversity during development involves differentiating cells transitioning between discrete cell states. In the 1940s, the developmental biologist Conrad Waddington introduced a landscape metaphor to describe this process. The developmental path of a cell was pictured as a ball rolling through a terrain of branching valleys with cell fate decisions represented by the branch points at which the ball decides between one of two available valleys. Here we discuss progress in constructing quantitative dynamical models inspired by this view of cellular differentiation. We describe a framework based on catastrophe theory and dynamical systems methods that provides the foundations for quantitative geometric models of cellular differentiation. These models can be fit to experimental data and used to make quantitative predictions about cellular differentiation. The theory indicates that cell fate decisions can be described by a small number of decision structures, such that there are only two distinct ways in which cells make a binary choice between one of two fates. We discuss the biological relevance of these mechanisms and suggest the approach is broadly applicable for the quantitative analysis of differentiation dynamics and for determining principles of developmental decisions.

Abstract: From growing cells in spheroids to arranging them on complex engineered scaffolds, three-dimensional cell culture protocols are rapidly expanding and diversifying. While these systems may often improve the physiological relevance of cell culture models, they come with technical challenges, as many of the analytical methods used to characterize traditional two-dimensional (2D) cells must be modified or replaced to be effective. Here we review the advantages and limitations of quantification methods based either on biochemical measurements or microscopy imaging. We focus on the most basic of parameters that one may want to measure, the number of cells. Precise determination of this number is essential for many analytical techniques where measured quantities are only meaningful when normalized to the number of cells (e.g. cytochrome p450 enzyme activity). Thus, accurate measurement of cell number is often a prerequisite to allowing comparisons across different conditions (culturing conditions or drug and treatment screening) or between cells in different spatial states. We note that this issue is often neglected in the literature with little or no information given regarding how normalization was performed, we highlight the pitfalls and complications of quantification and call for more accurate reporting to improve reproducibility.

Abstract: Entrainment is a phenomenon in which two oscillators interact with each other, typically through physical or chemical means, to synchronize their oscillations. This phenomenon occurs in biology to coordinate processes from the molecular to organismal scale. Biological oscillators can be entrained within a single cell, between cells or to an external input. Using six illustrative examples of entrainable biological oscillators, we discuss the distinctions between entrainment and synchrony and explore features that contribute to a system's propensity to entrain. Entrainment can either enhance or reduce the heterogeneity of oscillations within a cell population, and we provide examples and mechanisms of each case. Finally, we discuss the known functions of entrainment and discuss potential functions from an evolutionary perspective.

Abstract: Hypoxic wounds are tough to heal and are associated with chronicity, causing major healthcare burden. Available treatment options offer only limited success for accelerated and scarless healing. Traditional skin substitutes are widely used to improve wound healing, however, they lack proper vascularization. Mesenchymal stem cells (MSCs) offer improved wound healing; however, their poor retention, survival and adherence at the wound site negatively affect their therapeutic potential. The aim of this study is to enhance skin regeneration in a rat model of full-thickness dermal wound by transplanting genetically modified MSCs seeded on a three-dimensional collagen scaffold. Rat bone marrow MSCs were efficiently incorporated in the acellular collagen scaffold. Skin tissues with transplanted subcutaneous scaffolds were histologically analysed, while angiogenesis was assessed both at gene and protein levels. Our findings demonstrated that three-dimensional collagen scaffolds play a potential role in the survival and adherence of stem cells at the wound site, while modification of MSCs with jagged one gene provides a conducive environment for wound regeneration with improved proliferation, reduced inflammation and enhanced vasculogenesis. The results of this study represent an advanced targeted approach having the potential to be translated in clinical settings for targeted personalized therapy.

Abstract: The dynamics of blood flow in the smallest vessels and passages of the human body, where the cellular character of blood becomes prominent, plays a dominant role in the transport and exchange of solutes. Recent studies have revealed that the microhaemodynamics of a vascular network is underpinned by its interconnected structure, and certain structural alterations such as capillary dilation and blockage can substantially change blood flow patterns. However, for extravascular media with disordered microstructure (e.g. the porous intervillous space in the placenta), it remains unclear how the medium's structure affects the haemodynamics. Here, we simulate cellular blood flow in simple models of canonical porous media representative of extravascular biological tissue, with corroborative microfluidic experiments performed for validation purposes. For the media considered here, we observe three main effects: first, the relative apparent viscosity of blood increases with the structural disorder of the medium; second, the presence of red blood cells (RBCs) dynamically alters the flow distribution in the medium; third, symmetry breaking introduced by moderate structural disorder can promote more homogeneous distribution of RBCs. Our findings contribute to a better understanding of the cell-scale haemodynamics that mediates the relationship linking the function of certain biological tissues to their microstructure.

Abstract: Bacterial biofilms are communities living in a matrix consisting of self-produced, hydrated extracellular polymeric substances. Most microorganisms adopt the biofilm lifestyle since it protects by conferring resistance to antibiotics and physico-chemical stress factors. Consequently, mechanical removal is often necessary but rendered difficult by the biofilm’s complex, viscoelastic response, and adhesive properties. Overall, the mechanical behaviour of biofilms also plays a role in the spreading, dispersal and subsequent colonization of new surfaces. Therefore, the characterization of the mechanical properties of biofilms plays a crucial role in controlling and combating biofilms in industrial and medical environments. We performed in situ shear rheological measurements of Bacillus subtilis biofilms grown between the plates of a rotational rheometer under well-controlled conditions relevant to many biofilm habitats. We investigated how the mechanical history preceding rheological measurements influenced biofilm mechanics and compared these results to the techniques commonly used in the literature. We also compare our results to measurements using interfacial rheology on bacterial pellicles formed at the air–water interface. This work aims to help understand how different growth and measurement conditions contribute to the large variability of mechanical properties reported in the literature and provide a new tool for the rigorous characterization of matrix components and biofilms.

Abstract: The Upper Rio Negro regional social system is made up of more than 30 languages belonging to six linguistic families. This results from socio-historical processes stretching back at least two millennia, which have built a system with different levels of autonomy and hierarchy associated with a mythical and ritual complex, and with social and linguistic exchanges. The analysis of these processes require an interdisciplinary outlook to understand the ways in which people from different linguistic families interacted and created it. More specifically, we ask how linguistic and cultural diversity have been created in the context of intense relations of multilingualism and inter-ethnic contact. To this end, we integrate perspectives from historical linguistics (regarding languages from the Tukanoan, Arawakan and Naduhup families) with archaeological data from the Amazonian past. Through this multidisciplinary approach, we seek to develop a linguistic–anthropological understanding of the dynamics shaping the region's diversity and inter-ethnic relations. We show that processes creating diversity are interrelated with changes in social histories, and are especially tied to the establishment of new forms of social organization as a result of pre-colonial inter-ethnic relations. This has led to the construction of various local multilingual ecologies connected to macro-regional processes in Amazonia.

Abstract: Outbreaks of COVID-19 in hospices for palliative care patients pose a unique and difficult situation. Staff, relatives and patients may be possible sources and recipients of infection. We present an outbreak of COVID-19 in a hospice setting, during the UK's first pandemic wave. During the outbreak period, 26 patients and 30 staff tested SARS-CoV-2 positive by laboratory-based RT-PCR testing. Most infected staff exhibited some mild, non-specific symptoms so affected staff members may not have voluntarily self-isolated or had themselves tested on this basis. Similarly, for infected patients, most became symptomatic and were then isolated. Additional, enhanced aerosol infection control measures were implemented, including opening of all windows where available; universal masking for all staff, including in non-clinical areas and taking breaks separately; screening for asymptomatic infection among staff and patients, with appropriate isolation (at home for staff) if infected; performing a ventilation survey of the hospice facility. After these measures were instigated, the numbers of COVID-19 cases decreased to zero over the following three weeks. This outbreak study demonstrated that an accurate understanding of the routes of infection for a new pathogen, as well as the nature of symptomatic versus asymptomatic infection and transmission, is crucial for controlling its spread.

Abstract: Many biological materials contain fibrous protein networks as their main structural components. Understanding the mechanical properties of such networks is important for creating biomimicking materials for cell and tissue engineering, and for developing novel tools for detecting and diagnosing disease. In this work, we develop continuum models for isotropic, athermal fibrous networks by combining a single-fiber model that describes the axial response of individual fibers, with network models that assemble individual fiber properties into overall network behavior. In particular, we consider four different network models, including the affine, three-chain, eight-chain, and micro-sphere models, which employ different assumptions about network structure and kinematics. We systematically investigate the ability of these models to describe the mechanical response of athermal collagen and fibrin networks by comparing model predictions with experimental data. We test how each model captures network behavior under three different loading conditions: uniaxial tension, simple shear, and combined tension and shear. We find that the affine and three-chain models can accurately describe both the axial and shear behavior, whereas the eight-chain and micro-sphere models fail to capture the shear response, leading to an unphysical zero shear moduli at infinitesimal strains. Our study is the first to systematically investigate the applicability of popular network models for describing the macroscopic behavior of athermal fibrous networks, offering insights for selecting efficient models that can be used for large-scale, finite-element simulations of athermal networks.

Abstract: Biofilms are biological viscoelastic gels composed of bacterial cells embedded in a self-secreted polymeric extracellular matrix (ECM). In environmental settings, such as in the rhizosphere and phyllosphere, biofilm colonization occurs at the solid–air interface. The biofilms’ ability to colonize and expand over these surfaces depends on the formation of osmotic gradients and ECM viscoelastic properties. In this work, we study the influence of biofilm ECM components on its viscoelasticity and expansion, using the model organism Bacillus subtilis and deletion mutants of its three major ECM components, TasA, EPS and BslA. Using a multi-scale approach, we quantified macro-scale viscoelasticity and expansion dynamics. Furthermore, we used a microsphere assay to visualize the micro-scale expansion patterns. We find that the viscoelastic phase angle Φ is likely the best viscoelastic parameter correlating to biofilm expansion dynamics. Moreover, we quantify the sensitivity of the biofilm to changes in substrate water potential as a function of ECM composition. Finally, we find that the deletion of ECM components significantly increases the coherence of micro-scale colony expansion patterns. These results demonstrate the influence of ECM viscoelasticity and substrate water potential on the expansion of biofilm colonies on wet surfaces at the air–solid interface, commonly found in natural environments.

Abstract: To survive and reproduce, a cell must process information from its environment and its own internal state and respond accordingly, in terms of metabolic activity, gene expression, movement, growth, division and differentiation. These signal–response decisions are made by complex networks of interacting genes and proteins, which function as biochemical switches and clocks, and other recognizable information-processing circuitry. This theme issue of Interface Focus (in two parts) brings together articles on time-keeping and decision-making in living cells—work that uses precise mathematical modelling of underlying molecular regulatory networks to understand important features of cell physiology. Part I focuses on time-keeping: mechanisms and dynamics of biological oscillators and modes of synchronization and entrainment of oscillators, with special attention to circadian clocks.

Abstract: Organisms are non-equilibrium, stationary systems self-organized via spontaneous symmetry breaking and undergoing metabolic cycles with broken detailed balance in the environment. The thermodynamic free-energy (FE) principle describes an organism’s homeostasis as the regulation of biochemical work constrained by the physical FE cost. By contrast, recent research in neuroscience and theoretical biology explains a higher organism’s homeostasis and allostasis as Bayesian inference facilitated by the informational FE. As an integrated approach to living systems, this study presents an FE minimization theory overarching the essential features of both the thermodynamic and neuroscientific FE principles. Our results reveal that the perception and action of animals result from active inference entailed by FE minimization in the brain, and the brain operates as a Schrödinger’s machine conducting the neural mechanics of minimizing sensory uncertainty. A parsimonious model suggests that the Bayesian brain develops the optimal trajectories in neural manifolds and induces a dynamic bifurcation between neural attractors in the process of active inference.

Abstract: Small cell clusters exhibit numerous phenomena typically associated with complex systems, such as division of labour and programmed cell death. A conserved class of such clusters occurs during oogenesis in the form of germline cysts that give rise to oocytes. Germline cysts form through cell divisions with incomplete cytokinesis, leaving cells intimately connected through intercellular bridges that facilitate cyst generation, cell fate determination and collective growth dynamics. Using the well-characterized Drosophila melanogaster female germline cyst as a foundation, we present mathematical models rooted in the dynamics of cell cycle proteins and their interactions to explain the generation of germline cell lineage trees (CLTs) and highlight the diversity of observed CLT sizes and topologies across species. We analyse competing models of symmetry breaking in CLTs to rationalize the observed dynamics and robustness of oocyte fate specification, and highlight remaining gaps in knowledge. We also explore how CLT topology affects cell cycle dynamics and synchronization and highlight mechanisms of intercellular coupling that underlie the observed collective growth patterns during oogenesis. Throughout, we point to similarities across organisms that warrant further investigation and comment on the extent to which experimental and theoretical findings made in model systems extend to other species.

Abstract: In eukaryotes, intracellular physicochemical properties like macromolecular crowding and cytoplasmic viscoelasticity influence key processes such as metabolic activities, molecular diffusion, and protein folding. However, mapping crowding and viscoelasticity in living cells remains challenging. One approach uses passive rheology in which diffusion of exogenous fluorescent particles internalised in cells is tracked and physicochemical properties inferred from derived mean square displacement relations. Recently, the crGE2.3 Förster Resonance Energy Transfer (FRET) biosensor was developed to quantify crowding in cells, though it is unclear how this readout depends on viscoelasticity and the molecular weight of the crowder. Here, we present correlative, multidimensional data to explore diffusion and molecular crowding characteristics of molecular crowding agents using super-resolved fluorescence microscopy and ensemble time-resolved spectroscopy. We firstly characterise in vitro and then apply these insights to live cells of budding yeast Saccharomyces cerevisiae. It is to our knowledge the first time this has been attempted. We demonstrate that these are usable both in vitro and in the case of endogenously expressed sensors in live cells. Finally, we present a method to internalise fluorescent beads as in situ viscoelasticity markers in the cytoplasm of live yeast cells, and discuss limitations of this approach including impairment of cellular function.

Abstract: The intercellular interactions between peripheral circadian clocks, located in tissues and organs other than the suprachiasmatic nuclei of the hypothalamus, are still very poorly understood. We propose a theoretical and computational study of the coupling between two or more clocks, using a calibrated, reduced model of the circadian clock to describe some synchronization properties between peripheral cellular clocks. Based on a piecewise linearization of the dynamics of the mutual CLOCK:BMAL1/PER:CRY inactivation term, we suggest a segmentation of the circadian cycle into six stages, to help analyse different types of synchronization between two clocks, including single stage duration, total period and maximal amplitudes. Finally, our model reproduces some recent experimental results on the effects of different regimes of time-restricted feeding in liver circadian clocks of mice.

Abstract: During development, cells from a population of common progenitors evolve towards different fates characterized by distinct levels of specific transcription factors, a process known as cell differentiation. This evolution is governed by gene regulatory networks modulated by intercellular signalling. In order to evolve towards distinct fates, cells forming the population of common progenitors must display some heterogeneity. We applied a modelling approach to obtain insights into the possible sources of cell-to-cell variability initiating the specification of cells of the inner cell mass into epiblast or primitive endoderm cells in early mammalian embryo. At the single-cell level, these cell fates correspond to three possible steady states of the model. A combination of numerical simulations and bifurcation analyses predicts that the behaviour of the model is preserved with respect to the source of variability and that cell–cell coupling induces the emergence of multiple steady states associated with various cell fate configurations, and to a distribution of the levels of expression of key transcription factors. Statistical analysis of these time-dependent distributions reveals differences in the evolutions of the variance-to-mean ratios of key variables of the system, depending on the simulated source of variability, and, by comparison with experimental data, points to the rate of synthesis of the key transcription factor NANOG as a likely initial source of heterogeneity.

Abstract: Department of Biological Sciences, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, 1088 Budapest, Hungary Unit of Theoretical Chronobiology, Université Libre de Bruxelles, 1050 Brussels, Belgium Department of Mathematical Sciences, KAIST, Daejeon 34141, South Korea Biomedical Mathematics Group, Institute for Basic Science, Daejeon 34126, South Korea Quantitative Stem Cell Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK Mathematical Modeling of Cellular Processes, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany Department of Mathematics and Computer Science, Free University, 14195 Berlin, Germany

Abstract: This paper identifies time calibration points for accurately rooting and dating the phylogeny of Arawakan, the largest Indigenous linguistic family of the Americas. We present and model a methodology for extracting calibration points from the archaeological record, based on principles of geographical overlap between archaeological sites and Arawakan peoples, and on continuity in material culture between archaeological finds and modern Arawakan practices. Based on a consensus model of the expansion of the Arawakan family from Central Amazonia, we focus on archaeological finds in Arawakan expansion zones, where Arawakan material culture abruptly appears in a given region, and where only a single major Arawakan subgroup/clade is present. We find 12 calibration points from archaeological sites in Arawakan expansion zones and also identify more recent calibration points from the historical record based on first mentions of ethnonyms and early sources of lexical data.

Abstract: Muscle-on-chip devices aim to recapitulate the physiological characteristics of in vivo muscle tissue and so maintaining levels of oxygen transported to cells is essential for cell survival and for providing the normoxic conditions experienced in vivo. We use finite-element method numerical modelling to describe oxygen transport and reaction in a proposed three-dimensional muscle-on-chip bioreactor with embedded channels for muscle cells and growth medium. We determine the feasibility of ensuring adequate oxygen for muscle cell survival in a device sealed from external oxygen sources and perfused via medium channels. We investigate the effects of varying elements of the bioreactor design on oxygen transport to optimize muscle tissue yield and maintain normoxic conditions. Successful co-culturing of muscle cells with motor neurons can boost muscle tissue function and so we estimate the maximum density of seeded neurons supported by oxygen concentrations within the bioreactor. We show that an enclosed bioreactor can provide sufficient oxygen for muscle cell survival and growth. We define a more efficient arrangement of muscle and perfusion chambers that can sustain a predicted 50% increase in maximum muscle volume per perfusion vessel. A study of simulated bioreactors provides functions for predicting bioreactor designs with normoxic conditions for any size of perfusion vessel, muscle chamber and distance between chambers.

Abstract: Northwestern Amazonia is home to a great degree of linguistic diversity, and the human societies in that region are part of complex networks of interaction that predate the arrival of Europeans. This study investigates the population and language contact dynamics between two languages found within this region, Yukuna and Tanimuka, which belong to the Arawakan and Tukanoan language families, respectively. We use evidence from linguistics, ethnohistory, ethnography and population genetics to provide new insights into the contact dynamics between these and other human groups in NWA. Our results show that the interaction between these groups intensified in the last 500 years, to the point that it is difficult to differentiate between them genetically. However, this close interaction has led to more substantial contact-induced language changes in Tanimuka than in Yukuna, consistent with a scenario of language shift and asymmetrical power relations.

Abstract: The rheological properties of cells have vital functional implications. Depending, for instance, on the life cycle, cells show large cell-to-cell variations making it cumbersome to quantify average viscoelastic properties of cells by single-cell techniques. Microfluidic devices, typically working in the nonlinear viscoelastic range, allow fast analysis of single-cell deformation. Averaging over a large number of cells can also be achieved by studying them in a monolayer between rheometer discs. This technique allows applying well-established rheological standard procedures to cell rheology. It offers further advantages like studying cells in the linear viscoelastic range while quantifying cell vitality. Here, we study the applicability of the technique to rather adverse conditions, like for microtubule-active anti-cancer drugs and for a cell line with large size variation. We found a strong impact of the gap width and of normal forces on the moduli and obtained high vitality levels during the rheological study. To enable studying the impact of microtubule-active drugs on vital cells at concentrations several orders of magnitude beyond the half maximal effective concentration for cytotoxicity, we arrested the cell cycle with hydroxyurea. Irrespective of the high concentrations, we observed no clear impact of the microtubule-active drugs.

Abstract: The fluid mechanical processes that govern the spread of infectious agents through the air in complex spaces are reviewed and the scientific gaps and challenges identified and discussed. Air, expelled from the nose and mouth, creates turbulent jets that form loosely coherent structures which quickly slow. For the transport and dispersion of aerosols, the suitability of the Eulerian as well as the Lagrangian approaches are brought into context. The effects of buoyancy and external turbulence are explored and shown to influence the horizontal extent of expulsion through distinct mechanisms which both inhibit penetration and enhance mixing. The general influence of inhomogeneous turbulence and stratification on the spread of infectious agents in enclosed complex spaces is discussed.

Abstract: Three-dimensional (3D) spheroid cultures are generating increasing interest in cancer research, e.g. for the evaluation of pharmacological effects of novel small molecule inhibitors. This is mainly due to the fact that such 3D structures reflect physiological characteristics of tumours and the cellular microenvironments they reside in more faithfully than two-dimensional (2D) cell cultures; in addition, they allow the reduction of animal experiments while providing significantly relevant human-based models. Quantification of such organoid structures as well as the mainly slice-based acquisition and thus forced 2D representation of 3D spheroids provide a challenge for the interpretation of the associated generated data. Here, we provide a novel open-source workflow to reconstruct a 3D entity from slice-recorded microscopical images with or without treatment with anti-migratory small molecule inhibitors. This reconstruction produces distinct point clouds as basis for subsequent comparison of basic readout parameters using average computer processor, memory and graphics resources within an acceptable time frame. We were able to validate the usefulness of this workflow using 3D data generated by various imaging techniques, including z-stacks from confocal microscopy and histochemically labelled spheroid sectioning, and demonstrate the possibility to accurately characterize inhibitor effects in great detail.

Abstract: The COVID-19 pandemic, caused by the virus SARS-CoV-2, has touched most parts of the world and devastated the lives of many. The high transmissibility coupled with the initial poor outcome for the elderly led to crushingly high fatalities. The scientific response to the pandemic has been formidable, aided by advancements in virology, computing, data analysis, instrumentation, diagnostics, engineering and infection control. This has led to improvements in understanding and has helped to challenge some established orthodoxies. Sufficient time has elapsed since the start of the COVID-19 pandemic that a clearer view has emerged about transmission and infection risks, public health responses and related societal and economic impacts. This timely volume has provided an opportunity for the science community to report on these new developments.

Abstract: The Americas are home to patches of extraordinary linguistic (genealogical) diversity. These high-diversity areas are particularly unexpected given the recent population of the Americas. In this paper, we zoom in on one such area, the Northwest Amazon, and address the question of how the diversity in this area has persisted to the present. We contrast two hypotheses that claim opposite mechanisms for the maintenance of diversity: the isolation hypothesis suggests that isolation facilitates the preservation of diversity, while the integration hypothesis proposes that conscious identity preservation in combination with contact drives diversity maintenance. We test predictions for both hypotheses across four disciplines: biogeography, cultural anthropology, population genetics and linguistics. Our results show signs of both isolation and integration, but they mainly suggest considerable diversity in how groups of speakers have interacted with their surroundings.

Abstract: [This corrects the article DOI: 10.1098/rsfs.2022.0020.][This corrects the article DOI: 10.1098/rsfs.2022.0020.].

Abstract: Mechanistic understanding of anorectal (patho)physiology is missing to improve the medical care of patients suffering from defaecation disorders. Our objective is to show that complex fluid dynamics modelling of video defaecography may open new perspectives in the diagnosis of defaecation disorders. Based on standard X-ray video defaecographies, we developed a bi-dimensional patient-specific simulation of the expulsion of soft materials, the faeces, by the rectum. The model quantified velocity, pressure and stress fields during the defaecation of a neostool with soft stool-like rheology for patients showing normal and pathological defaecatory function. In normal defaecation, the proximal–distal pressure gradient resulted from both the anorectal junction which formed a converging channel and the anal canal. The flow of the neostool through these anatomical parts was dominated by its shear-thinning viscous properties, rather than its yield stress. Consequently, the evacuation flow rate was significantly affected by variations in pressure applied by the rectum, and much less by the geometry of the anorectal junction. Lastly, we simulated impaired defaecations in the absence of obvious obstructive phenomena. Comparison with normal defaecation allowed us to discuss critical elements which should lead to effective medical management.