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1.
Article in English | MEDLINE | ID: mdl-38878021

ABSTRACT

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events.

2.
J Chem Phys ; 160(17)2024 May 07.
Article in English | MEDLINE | ID: mdl-38748036

ABSTRACT

Quantum dynamics simulations are becoming a powerful tool for understanding photo-excited molecules. Their poor scaling, however, means that it is hard to study molecules with more than a few atoms accurately, and a major challenge at the moment is the inclusion of the molecular environment. Here, we present a proof of principle for a way to break the two bottlenecks preventing large but accurate simulations. First, the problem of providing the potential energy surfaces for a general system is addressed by parameterizing a standard force field to reproduce the potential surfaces of the molecule's excited-states, including the all-important vibronic coupling. While not shown here, this would trivially enable the use of an explicit solvent. Second, to help the scaling of the nuclear dynamics propagation, a hierarchy of approximations is introduced to the variational multi-configurational Gaussian method that retains the variational quantum wavepacket description of the key quantum degrees of freedom and uses classical trajectories for the remaining in a quantum mechanics/molecular mechanics like approach. The method is referred to as force field quantum dynamics (FF-QD), and a two-state ππ*/nπ* model of uracil, excited to its lowest bright ππ* state, is used as a test case.

3.
J Math Biol ; 88(6): 61, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38607408

ABSTRACT

We present a mathematical model of an experiment in which cells are cultured within a gel, which in turn floats freely within a liquid nutrient medium. Traction forces exerted by the cells on the gel cause it to contract over time, giving a measure of the strength of these forces. Building upon our previous work (Reoch et al. in J Math Biol 84(5):31, 2022), we exploit the fact that the gels used frequently have a thin geometry to obtain a reduced model for the behaviour of a thin, two-dimensional cell-seeded gel. We find that steady-state solutions of the reduced model require the cell density and volume fraction of polymer in the gel to be spatially uniform, while the gel height may vary spatially. If we further assume that all three of these variables are initially spatially uniform, this continues for all time and the thin film model can be further reduced to solving a single, non-linear ODE for gel height as a function of time. The thin film model is further investigated for both spatially-uniform and varying initial conditions, using a combination of analytical techniques and numerical simulations. We show that a number of qualitatively different behaviours are possible, depending on the composition of the gel (i.e., the chemical potentials) and the strength of the cell traction forces. However, unlike in the earlier one-dimensional model, we do not observe cases where the gel oscillates between swelling and contraction. For the case of initially uniform cell and gel density, our model predicts that the relative change in the gels' height and length are equal, which justifies an assumption previously used in the work of Stevenson et al. (Biophys J 99(1):19-28, 2010). Conversely, however, even for non-uniform initial conditions, we do not observe cases where the length of the gel changes whilst its height remains constant, which have been reported in another model of osmotic swelling by Trinschek et al. (AIMS Mater Sci 3(3):1138-1159, 2016; Phys Rev Lett 119:078003, 2017).


Subject(s)
Nutrients , Polymers , Gels , Seeds
4.
J Community Genet ; 15(1): 49-58, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37864742

ABSTRACT

Individuals who carry BRCA1 or BRCA2 pathogenic variants are recommended to have extensive cancer prevention screening and risk-reducing surgeries. Uptake of these recommendations is variable, and there remains room for improvement in the risk management of BRCA carriers. This paper explores female BRCA carriers' experiences with the current model of care and their perspectives on (and interest in) an inherited cancer registry. Findings can inform the development of a dedicated high-risk screening and management program for these patients. Quantitative and qualitative data were gathered through a provincial descriptive survey and semi-structured qualitative interviews to assess BRCA carriers' opinions toward risk management services in the province of Newfoundland and Labrador (NL), Canada. Survey (n = 69) and interview data (n = 15) revealed continuity and coordination challenges with the current system of care of high-risk individuals. Respondents suggested an inherited cancer registry would help identify high-risk individuals and provide a centralized system of risk management for identified carriers. Respondents identified concerns about the privacy of their registry data, including who could access it. Findings suggest BRCA carriers see great value in an inherited cancer registry. Specifically, participants noted it could provide a centralized system to help improve the coordination of burdensome, life-long risk management. Important patient concerns about protecting their privacy and their health data confidentiality must be addressed in patient and public information and informed consent documents about a registry.

5.
Compr Psychiatry ; 127: 152428, 2023 11.
Article in English | MEDLINE | ID: mdl-37778180

ABSTRACT

BACKGROUND: Patients in the forensic mental health services (FMHS) with a mental disorder, a co-occurring substance use disorder (SUD), and high risk of aggressive antisocial behavior (AAB) are sometimes referred to as the 'triply troubled'. They suffer poor treatment outcomes, high rates of criminal recidivism, and increased risk of drug related mortality. To improve treatment for this heterogeneous patient group, more insight is needed concerning their co-occurring mental disorders, types of substances used, and the consequent risk of AAB. METHODS: A three-step latent class analysis (LCA) was used to identify clinically relevant subgroups in a sample of patients (n = 98) from a high-security FMHS clinic in Sweden based on patterns in their history of mental disorders, SUD, types of substances used, and AAB. RESULTS: A four-class model best fit our data: class 1 (42%) had a high probability of SUD, psychosis, and having used all substances; class 2 (26%) had a high probability of psychosis and cannabis use; class 3 (22%) had a high probability of autism and no substance use; and class 4 (10%) had a high probability of personality disorders and having used all substances. Both polysubstance classes (1 and 4) had a significantly more extensive history of AAB compared to classes 2 and 3. Class 3 and class 4 had extensive histories of self-directed aggression. CONCLUSIONS: The present study helps disentangle the heterogeneity of the 'triply troubled' patient group in FMHS. The results provide an illustration of a more person-oriented perspective on patient comorbidity and types of substances used which could benefit clinical assessment, treatment planning, and risk-management among patients in forensic psychiatric care.


Subject(s)
Mental Disorders , Substance-Related Disorders , Humans , Antisocial Personality Disorder/diagnosis , Antisocial Personality Disorder/epidemiology , Antisocial Personality Disorder/psychology , Sweden/epidemiology , Latent Class Analysis , Mental Disorders/diagnosis , Mental Disorders/epidemiology , Mental Disorders/psychology , Substance-Related Disorders/diagnosis , Substance-Related Disorders/epidemiology , Substance-Related Disorders/psychology , Comorbidity , Aggression
6.
J Theor Biol ; 575: 111631, 2023 11 07.
Article in English | MEDLINE | ID: mdl-37804941

ABSTRACT

We consider the uniaxial growth of a tissue or colony of cells, where a nutrient (or some other chemical) required for cell proliferation is supplied at one end, and is consumed by the cells. An example would be the growth of a cylindrical yeast colony in the experiments described by Vulin et al. (2014). We develop a reaction-diffusion model of this scenario which couples nutrient concentration and cell density on a growing domain. A novel element of our model is that the tissue is assumed to be compressible. We define replicative regions, where cells have sufficient nutrient to proliferate, and quiescent regions, where the nutrient level is insufficient for this to occur. We also define pathlines, which allow us to track individual cell paths within the tissue. We begin our investigation of the model by considering an incompressible tissue where cell density is constant before exploring the solution space of the full compressible model. In a large part of the parameter space, the incompressible and compressible models give qualitatively similar results for both the nutrient concentration and cell pathlines, with the key distinction being the variation in density in the compressible case. In particular, the replicative region is located at the base of the tissue, where nutrient is supplied, and nutrient concentration decreases monotonically with distance from the nutrient source. However, for a highly-compressible tissue with small nutrient consumption rate, we observe a counter-intuitive scenario where the nutrient concentration is not necessarily monotonically decreasing, and there can be two replicative regions. For parameter values given in the paper by Vulin et al. (2014), the incompressible model slightly overestimates the colony length compared to experimental observations; this suggests the colony may be somewhat compressible. Both incompressible and compressible models predict that, for these parameter values, cell proliferation is ultimately confined to a small region close to the colony base.


Subject(s)
Models, Biological , Models, Theoretical , Saccharomyces cerevisiae , Cell Proliferation , Nutrients
7.
Nat Ecol Evol ; 7(11): 1844-1855, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37749400

ABSTRACT

The influence of depth and associated gradients in light, nutrients and plankton on the ecological organization of tropical reef communities was first described over six decades ago but remains untested across broad geographies. During this time humans have become the dominant driver of planetary change, requiring that we revisit historic ecological paradigms to ensure they capture the dynamics of contemporary ecological systems. Analysing >5,500 in-water reef fish surveys between 0 and 30 m depth on reef slopes of 35 islands across the Pacific, we assess whether a depth gradient consistently predicts variation in reef fish biomass. We reveal predictable ecological organization at unpopulated locations, with increased biomass of planktivores and piscivores and decreased primary consumer biomass with increasing depth. Bathymetric steepness also had a striking influence on biomass patterns, primarily for planktivores, emphasizing potential links between local hydrodynamics and the upslope propagation of pelagic subsidies to the shallows. However, signals of resource-driven change in fish biomass with depth were altered or lost for populated islands, probably due to depleted fish biomass baselines. While principles of depth zonation broadly held, our findings expose limitations of the paradigm for predicting ecological dynamics where human impacts confound connections between ecological communities and their surrounding environment.


Subject(s)
Anthropogenic Effects , Coral Reefs , Animals , Humans , Ecosystem , Biomass , Fishes
8.
Sci Adv ; 9(24): eadd5032, 2023 06 16.
Article in English | MEDLINE | ID: mdl-37315146

ABSTRACT

Marine heatwaves are triggering coral bleaching events and devastating coral populations globally, highlighting the need to identify processes promoting coral survival. Here, we show that acceleration of a major ocean current and shallowing of the surface mixed layer enhanced localized upwelling on a central Pacific coral reef during the three strongest El Niño-associated marine heatwaves of the past half century. These conditions mitigated regional declines in primary production and bolstered local supply of nutritional resources to corals during a bleaching event. The reefs subsequently suffered limited post-bleaching coral mortality. Our results reveal how large-scale ocean-climate interactions affect reef ecosystems thousands of kilometers away and provide a valuable framework for identifying reefs that may benefit from such biophysical linkages during future bleaching events.


Subject(s)
Anthozoa , Animals , El Nino-Southern Oscillation , Ecosystem , Coral Reefs , Oceans and Seas
9.
Resusc Plus ; 13: 100365, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36860989

ABSTRACT

Background: AIRWAYS-2 was a large multi-centre cluster randomised controlled trial investigating the effect on functional outcome of a supraglottic airway device (i-gel) versus tracheal intubation (TI) as the initial advanced airway during out-of-hospital cardiac arrest. We aimed to understand why paramedics deviated from their allocated airway management algorithm during AIRWAYS-2. Methods: This study employed a pragmatic sequential explanatory design utilising retrospective study data collected during the AIRWAYS-2 trial. Airway algorithm deviation data were analysed to categorise and quantify the reasons why paramedics did not follow their allocated strategy of airway management during AIRWAYS-2. Recorded free text entries provided additional context to the paramedic decision-making related to each category identified. Results: In 680 (11.7%) of 5800 patients the study paramedic did not follow their allocated airway management algorithm. There was a higher percentage of deviations in the TI group (399/2707; 14.7%) compared to the i-gel group (281/3088; 9.1%). The predominant reason for a paramedic not following their allocated airway management strategy was airway obstruction, occurring more commonly in the i-gel group (109/281; 38.7%) versus (50/399; 12.5%) in the TI group. Conclusion: There was a higher proportion of deviations from the allocated airway management algorithm in the TI group (399; 14.7%) compared to the i-gel group (281; 9.1%). The most frequent reason for deviating from the allocated airway management algorithm in AIRWAYS-2 was obstruction of the patient's airway by fluid. This occurred in both groups of the AIRWAYS-2 trial, but was more frequent in the i-gel group.

10.
Glob Chang Biol ; 29(3): 631-647, 2023 02.
Article in English | MEDLINE | ID: mdl-36394183

ABSTRACT

Distributional shifts in species ranges provide critical evidence of ecological responses to climate change. Assessments of climate-driven changes typically focus on broad-scale range shifts (e.g. poleward or upward), with ecological consequences at regional and local scales commonly overlooked. While these changes are informative for species presenting continuous geographic ranges, many species have discontinuous distributions-both natural (e.g. mountain or coastal species) or human-induced (e.g. species inhabiting fragmented landscapes)-where within-range changes can be significant. Here, we use an ecosystem engineer species (Sabellaria alveolata) with a naturally fragmented distribution as a case study to assess climate-driven changes in within-range occupancy across its entire global distribution. To this end, we applied landscape ecology metrics to outputs from species distribution modelling (SDM) in a novel unified framework. SDM predicted a 27.5% overall increase in the area of potentially suitable habitat under RCP 4.5 by 2050, which taken in isolation would have led to the classification of the species as a climate change winner. SDM further revealed that the latitudinal range is predicted to shrink because of decreased habitat suitability in the equatorward part of the range, not compensated by a poleward expansion. The use of landscape ecology metrics provided additional insights by identifying regions that are predicted to become increasingly fragmented in the future, potentially increasing extirpation risk by jeopardising metapopulation dynamics. This increased range fragmentation could have dramatic consequences for ecosystem structure and functioning. Importantly, the proposed framework-which brings together SDM and landscape metrics-can be widely used to study currently overlooked climate-driven changes in species internal range structure, without requiring detailed empirical knowledge of the modelled species. This approach represents an important advancement beyond predictive envelope approaches and could reveal itself as paramount for managers whose spatial scale of action usually ranges from local to regional.


Subject(s)
Climate Change , Ecosystem , Humans
11.
J Subst Abuse Treat ; 144: 108899, 2023 01.
Article in English | MEDLINE | ID: mdl-36270196

ABSTRACT

INTRODUCTION: Patients with substance use disorders (SUD) and co-occurring mental disorders (COD) within forensic psychiatric care often suffer poor treatment outcomes and high rates of criminal recidivism, substance use, and psychiatric problems. This study aimed to describe the conditions for, and mental health care staff's experiences with, implementing integrated SUD-focused clinical guidelines, including assessment and treatment for patients with COD at a high-security forensic mental health services (FMHS) facility in Sweden. METHODS: Study staff conducted nineteen semi-structured interviews with health care staff experienced in administering the new SUD assessment and treatment. The study conducted a thematic analysis to describe the health care staff's experiences with these guidelines and suggestions for improvement. RESULTS: Most participants reported appreciation for the implementation of clinical guidelines with an SUD focus, an area they considered to have previously been neglected, but also noted the need for more practical guidance in the administration of the assessments. Participants reported the dual roles of caregiver and warden as difficult to reconcile and a similar, hindering division was also present in the health care staff's attitudes toward SUD. Participants' reports also described an imbalance prior to the implementation, whereby SUD was rarely assessed but treatment was still initiated. One year after the implementation, an imbalance still existed, but in reverse: SUD was more frequently assessed, but treatment was difficult to initiate. CONCLUSIONS: Despite indications of some ambivalence among staff regarding the necessity of the assessment and treatment guidelines, many participants considered it helpful to have a structured way to assess and treat SUD in this patient group. The imbalance between frequent assessment and infrequent treatment may have been due to difficulties transitioning patients across the "gap" between assessment and treatment. To bridge this gap, mental health services should make efforts to increase patients' insight concerning their SUD, flexibility in the administration of treatment, and the motivational skills of the health care staff working with this patient group. Participants considered important for enhancing treatment quality a shared knowledge base regarding SUD, and increased collaboration between different professions and between in- and outpatient services.


Subject(s)
Mental Disorders , Substance-Related Disorders , Humans , Sweden , Forensic Psychiatry , Mental Health , Substance-Related Disorders/therapy , Mental Disorders/complications , Mental Disorders/therapy , Qualitative Research
12.
Int J Transgend Health ; 23(Suppl 1): S1-S259, 2022.
Article in English | MEDLINE | ID: mdl-36238954

ABSTRACT

Background: Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8. Aim: The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment. Methods: The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings. Results: A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health. Conclusions: The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.

13.
J Insect Physiol ; 143: 104443, 2022.
Article in English | MEDLINE | ID: mdl-36208774

ABSTRACT

Density dependent phase polyphenism is the exhibiting of two or more distinct phenotypes from a single genotype depending on local population density. The most well known insect to exhibit this phenomenon is the locust, with whom the profound effect on behaviour leads to the classification of the two phases; solitarious, where locusts actively avoid other locusts, and gregarious, where locusts are strongly attracted to other locusts. It has been shown that food distributions at both small and large scales have an effect on the process of gregarisation. While gregarisation offers advantages, such as greater predator avoidance, the relationship between phase polyphenism and potential foraging benefits is still not fully understood. In this paper, we explore the effect of gregarisation on foraging within increasingly heterogeneous environments using a partial differential equation model. We first consider a single two dimensional simulation of a spatially heterogeneous environment to understand the mechanics of gregarious/solitarious foraging. We then look at the steady state foraging advantage (measured as the ratio of per-capita contact with food) in environments ranging from homogeneous to very spatially heterogeneous. Finally, we perform a parameter sensitivity analysis to find which model parameters have the greatest effect on foraging advantage. We find that during the aggregation stage, prior to the onset of marching (which we do not model here), in increasingly heterogeneous food environments it is better to be gregarious than solitarious. In addition, we find that this is intrinsic to the gregarious/solitarious behavioural dynamic as it occurs almost regardless of the model parameters. That is to say, it doesn't matter how fast the organisms disperse or how strong their long range interactions as long as there is the solitarious/gregarious behaviour the gregarious foraging advantage will exist.


Subject(s)
Grasshoppers , Animals , Population Density
14.
Phys Rev Lett ; 129(11): 114801, 2022 Sep 09.
Article in English | MEDLINE | ID: mdl-36154426

ABSTRACT

Premature relativistic transparency of ultrathin, laser-irradiated targets is recognized as an obstacle to achieving a stable radiation pressure acceleration in the "light sail" (LS) mode. Experimental data, corroborated by 2D PIC simulations, show that a few-nm thick overcoat surface layer of high Z material significantly improves ion bunching at high energies during the acceleration. This is diagnosed by simultaneous ion and neutron spectroscopy following irradiation of deuterated plastic targets. In particular, copious and directional neutron production (significantly larger than for other in-target schemes) arises, under optimal parameters, as a signature of plasma layer integrity during the acceleration.

15.
J Am Coll Health ; : 1-9, 2022 Jul 26.
Article in English | MEDLINE | ID: mdl-35882066

ABSTRACT

OBJECTIVE: This review evaluates current literature on intensity selection, perceptual responses, activity enjoyment and adherence rates of exergaming. METHODS: The literature search identified manuscripts that investigated exercise intensity, perceptual responses, or exercise adherence of exergaming in young adults. RESULTS: Based on results of 29 studies, the current review suggest some exergaming activities have the potential to elicit moderate to vigorous exercise intensity and could potentially be substituted for traditional exercise. Additionally, exergame activities may aid in the start of exercise adherence by lowering the individual's perceived exertion when playing exergames. Exergaming not only has the potential to enhance enjoyment through an exercise objective but also through the distracting nature of video games. CONCLUSIONS: Exergaming shows potential to be substituted for traditional exercise and could offer a new, varied form of exercise for sedentary individuals. Future research should examine the influence of exergaming experience on intensity selection and adherence rates.

16.
Rev Sci Instrum ; 93(5): 053303, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35649771

ABSTRACT

Image plates (IPs) are a popular detector in the field of laser driven ion acceleration, owing to their high dynamic range and reusability. An absolute calibration of these detectors to laser-driven protons in the routinely produced tens of MeV energy range is, therefore, essential. In this paper, the response of Fujifilm BAS-TR IPs to 1-40 MeV protons is calibrated by employing the detectors in high resolution Thomson parabola spectrometers in conjunction with a CR-39 nuclear track detector to determine absolute proton numbers. While CR-39 was placed in front of the image plate for lower energy protons, it was placed behind the image plate for energies above 10 MeV using suitable metal filters sandwiched between the image plate and CR-39 to select specific energies. The measured response agrees well with previously reported calibrations as well as standard models of IP response, providing, for the first time, an absolute calibration over a large range of proton energies of relevance to current experiments.

17.
Rev Sci Instrum ; 93(3): 033304, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35364990

ABSTRACT

The response of the BAS-TR image plate (IP) was absolutely calibrated using a CR-39 track detector for high linear energy transfer Au ions up to ∼1.6 GeV (8.2 MeV/nucleon), accelerated by high-power lasers. The calibration was carried out by employing a high-resolution Thomson parabola spectrometer, which allowed resolving Au ions with closely spaced ionization states up to 58+. A response function was obtained by fitting the photo-stimulated luminescence per Au ion for different ion energies, which is broadly in agreement with that expected from ion stopping in the active layer of the IP. This calibration would allow quantifying the ion energy spectra for high energy Au ions, which is important for further investigation of the laser-based acceleration of heavy ion beams.

18.
J Math Biol ; 84(5): 31, 2022 03 16.
Article in English | MEDLINE | ID: mdl-35294632

ABSTRACT

Biological tissues are composed of cells surrounded by the extracellular matrix (ECM). The ECM can be thought of as a fibrous polymer network, acting as a natural scaffolding to provide mechanical support to the cells. Reciprocal mechanical and chemical interactions between the cells and the ECM are crucial in regulating the development of tissues and maintaining their functionality. Hence, to maintain in vivo-like behaviour when cells are cultured in vitro, they are often seeded in a gel, which aims to mimic the ECM. In this paper, we present a mathematical model that incorporates cell-gel interactions together with osmotic pressure to study the mechanical behaviour of biological gels. In particular, we consider an experiment where cells are seeded within a gel, which gradually compacts due to forces exerted on it by the cells. Adopting a one-dimensional Cartesian geometry for simplicity, we use a combination of analytical techniques and numerical simulations to investigate how cell traction forces interact with osmotic effects (which can lead to either gel swelling or contraction depending on the gel's composition). Our results show that a number of qualitatively different behaviours are possible, depending on the composition of the gel (i.e. its chemical potentials) and the strength of the cell traction forces. A novel prediction of our model is that there are cases where the gel oscillates between swelling and contraction; to our knowledge, this behaviour has not been reported in experiments. We also consider how physical parameters like drag and viscosity affect the manner in which the gel evolves.


Subject(s)
Extracellular Matrix , Models, Theoretical , Extracellular Matrix/physiology , Gels/analysis , Viscosity
19.
Mol Psychiatry ; 27(4): 1920-1935, 2022 04.
Article in English | MEDLINE | ID: mdl-35194166

ABSTRACT

The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (ß-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.


Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Gastrointestinal Microbiome , Schizophrenia , Brain , Gastrointestinal Microbiome/physiology , Humans
20.
Phys Rev E ; 105(1-1): 014408, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35193209

ABSTRACT

Understanding microbial biofilm growth is important to public health because biofilms are a leading cause of persistent clinical infections. In this paper, we develop a thin-film model for microbial biofilm growth on a solid substratum to which it adheres strongly. We model biofilms as two-phase viscous fluid mixtures of living cells and extracellular fluid. The model explicitly tracks the movement, depletion, and uptake of nutrients and incorporates cell proliferation via a nutrient-dependent source term. Notably, our thin-film reduction is two dimensional and includes the vertical dependence of cell volume fraction. Numerical solutions show that this vertical dependence is weak for biologically feasible parameters, reinforcing results from previous models in which this dependence was neglected. We exploit this weak dependence by writing and solving a simplified one-dimensional model that is computationally more efficient than the full model. We use both the one- and two-dimensional models to predict how model parameters affect expansion speed and biofilm thickness. This analysis reveals that expansion speed depends on cell proliferation, nutrient availability, cell-cell adhesion on the upper surface, and slip on the biofilm-substratum interface. Our numerical solutions provide a means to qualitatively distinguish between the extensional flow and lubrication regimes, and quantitative predictions that can be tested in future experiments.

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