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We establish through numerical simulation conditions for optimal undulatory propulsion for a single fish, and for a pair of hydrodynamically interacting fish, accounting for linear and angular recoil. We first employ systematic two-dimensional (2-D) simulations to identify conditions for minimal propulsive power of a self-propelled fish, and continue with targeted 3-D simulations for a danio-like fish; all at Reynolds number 5000. We find that the Strouhal number, phase angle between heave and pitch at the trailing edge, and angle of attack are principal parameters. For 2-D simulations, imposing a deformation based on measured displacement for carangiform swimming provides, at best, efficiency of 35 %, which increases to 50 % for an optimized motion; for a 3-D fish, the efficiency increases from 22 % to 34 %. Indeed, angular recoil has significant impact on efficiency, and optimized body bending requires maximum bending amplitude upstream of the trailing edge. Next, we turn to 2-D simulation of two hydrodynamically interacting fish. We find that the upstream fish benefits energetically only for small distances. In contrast, the downstream fish can benefit at any position that allows interaction with the upstream wake, provided its body motion is timed appropriately with respect to the oncoming vortices. For an in-line configuration, one body length apart, the efficiency of the downstream fish can increase from 50 % to 60 %; for an offset arrangement it can reach 80 %. This proves that in groups of fish, energy savings can be achieved for downstream fish through interaction with oncoming vortices, even when the downstream fish lies directly inside the jet-like flow of an upstream fish.

First Nations people in Canada experience a disproportionate burden of type 2 diabetes mellitus. To increase our understanding of this evolving epidemic, we compared the epidemiology of diabetes between First Nations and non-First Nations adults in Saskatchewan from 1980 to 2005. We used administrative databases to perform a population-based study of diabetes frequency, incidence and prevalence in adults by ethnic background, year, age and sex. We identified 8275 First Nations and 82 306 non-First Nations people with diabetes from 1980 to 2005. Overall, the incidence and prevalence of diabetes were more than 4 times higher among First Nations women than among non-First Nations women and more than 2.5 times higher among First Nations men than among non-First Nations men. The number of incident cases of diabetes was highest among First Nations people aged 40–49, while the number among non-First Nations people was greatest in those aged 70 or more years. The prevalence of diabetes increased over the study period from 9.5% to 20.3% among First Nations women and from 4.9% to 16.0% among First Nations men. Among non-First Nations people, the prevalence increased from 2.0% to 5.5% among women and from 2.0% to 6.2% among men. By 2005, almost 50% of First Nations women and more than 40% of First Nations men aged 60 or older had diabetes, compared with less than 25% of non-First Nations men and less than 20% of non-First Nations women aged 80 or older. First Nations adults are experiencing a diabetes epidemic that disproportionately affects women during their reproductive years. This ethnicity-based pattern suggests diverse underlying mechanisms that may include differences in the diabetogenic impact of gestational diabetes.

We present the case of an African American man in his mid-to-late 40s with no prior vascular risk factors who developed an acute ischaemic stroke. Imaging revealed an unstable carotid plaque with an associated floating thrombus, resembling a carotid web. The patient demonstrated near-complete neurological recovery within 30 min following intravenous tenecteplase administration. More than 1 year after the initial event, the patient remains stroke-free on antiplatelet and statin therapy. This case highlights the diagnostic challenge of distinguishing between unstable carotid plaque and carotid web, two entities with overlapping imaging features but differing management strategies. While unstable plaques are typically managed with intensive medical therapy and possible endarterectomy, carotid webs often require early surgical or endovascular intervention due to a high risk of recurrence. Early and accurate differentiation is crucial to guide appropriate treatment and prevent future cerebrovascular events.

The developmental origin, anatomical location, and other factors contribute to aortic heterogeneity in a physiological state. On this basis, vascular diseases occur at different ratios based on position specificity, even with the same risk factor. However, the continuous intersegmental aortic profile has been rarely reported at the single-cell level. To reveal aortic heterogeneity, we identified 15 cell subtypes from five continuous aortic segments by marker genes and functional definitions. The EC1 subtype highly expressed Vcam1 and Scarb2 genes in the aortic arch, which were reported to be associated with atherosclerosis. The newly identified Fbn1 + fibroblasts were found highly expressed in thoracic segments. More importantly, vascular smooth muscle cells (VSMCs) demonstrated a novel composition in which VSMC 4 marked with the gene Malat1 were mainly distributed in the abdominal segment. Malat1 knockout reduced MMPs and inflammatory factor production induced by Ang II in smooth muscle cells, and the Malat1 inhibitor exerted preventive, inhibitory, and reversing effects on AngII-induced abdominal aortic aneurysm (AAA) in vivo revealed by a series of animal experiments. Single-cell analysis of AngII-induced AAA tissues treated with or without the inhibitor further clarified the key role of Malat1 + VSMC in the occurrence and progression of AAA. In summary, segmental gene expression and cell subtype features in normal aorta associated with different vascular diseases might provide potential therapeutic targets.

ObjectivesTo explore experiences of physiotherapists working with adults living with Long COVID in Canada.DesignCross-sectional descriptive qualitative study involving online semi-structured interviews.ParticipantsWe recruited physiotherapists in Canada who self-identified as having clinically treated one or more adults living with Long COVID in the past year.Data collectionUsing an interview guide, we inquired about physiotherapists’ knowledge of Long COVID, assessment and treatment experiences, perspectives on physiotherapists’ roles, contextual and implementation factors influencing rehabilitative outcomes, and their recommendations for Long COVID rehabilitation. Interviews were audio-recorded, transcribed verbatim and analysed using a group-based thematic analytical approach. We administered a demographic questionnaire to describe sample characteristics.Results13 physiotherapists from five provinces participated; most were women (n=8; 62%) and practised in urban settings (n=11; 85%). Participants reported variable amounts of knowledge of existing guidelines and experiences working with adults living with Long COVID in the past year. Physiotherapists characterised their experiences working with adults living with Long COVID as a dynamic process involving: (1) a disruption to the profession (encountering a new patient population and pivoting to new models of care delivery), followed by (2) a cyclical process of learning curves and evolving roles of physiotherapists working with persons living with Long COVID (navigating uncertainty, keeping up with rapidly emerging evidence, trial and error, adapting mindset and rehabilitative approaches and growing prominence of roles as advocate and collaborator). Participants recommended the need for education and training, active and open-minded listening with patients, interdisciplinary models of care, and organisational- and system-level improvements to foster access to care.ConclusionsPhysiotherapists’ experiences involved a disruption to the profession followed by a dynamic process of learning curves and evolving roles in Long COVID rehabilitation. Not all participants demonstrated an in-depth understanding of existing Long COVID rehabilitation guidelines. Results may help inform physiotherapy education in Long COVID rehabilitation.

We study through numerical simulation the optimal hydrodynamic interactions and basic vorticity control mechanisms for two fish-like bodies swimming in tandem. We show that for a fish swimming in the wake of an upstream fish, using independent pitch control of its caudal fin, in addition to optimized body motion, results in reduction of the energy needed for self-propulsion by more than 50 %, providing a quasi-propulsive efficiency of 90 %, up from 60 % without independent caudal fin control. Such high efficiency is found over a narrow parametric range and is possible only when the caudal fin is allowed to pitch independently from the motion of the main body. We identify the vorticity control mechanisms employed by the body and tail to achieve this remarkable performance through thrust augmentation and destructive interference with the upstream fish-generated vortices. A high sensitivity of the propulsive performance to small variations in caudal fin parameters is found, underlying the importance of accurate flow sensing and feedback control. We further demonstrate that using lateral line-like flow measurements to drive an unscented Kalman filter, the near-field vortices can be localized within 1 % of the body length, and be used with a phase-lock controller to drive the body and tail undulation of a self-propelled fish, moving within the wake of an upstream fish, to stably reach the optimal gait and fully achieve maximum energy extraction.

Background Diabetes-related end stage renal disease (DM-ESRD) is a devastating consequence of the type 2 diabetes epidemic, both of which disproportionately affect Indigenous peoples. Projecting case numbers and costs into future decades would help to predict resource requirements, and simulating hypothetical interventions could guide the choice of best practices to mitigate current trends. Methods An agent based model (ABM) was built to forecast First Nations and non-First Nations cases of DM-ESRD in Saskatchewan from 1980 to 2025 and to simulate two hypothetical interventions. The model was parameterized with data from the Canadian Institute for Health Information, Saskatchewan Health Administrative Databases, the Canadian Organ Replacement Register, published studies and expert judgement. Input parameters without data sources were estimated through model calibration. The model incorporated key patient characteristics, stages of diabetes and chronic kidney disease, renal replacement therapies, the kidney transplant assessment and waiting list processes, costs associated with treatment options, and death. We used this model to simulate two interventions: 1) No new cases of diabetes after 2005 and 2) Pre-emptive renal transplants carried out on all diabetic persons with new ESRD. Results There was a close match between empirical data and model output. Going forward, both incidence and prevalence cases of DM-ESRD approximately doubled from 2010 to 2025, with 250–300 new cases per year and almost 1300 people requiring RRT by 2025. Prevalent cases of First Nations people with DM-ESRD increased from 19% to 27% of total DM-ESRD numbers from 1990 to 2025. The trend in yearly costs paralleled the prevalent DM-ESRD case count. For Scenario 1, despite eliminating diabetes incident cases after 2005, prevalent cases of DM-ESRD continued to rise until 2019 before slowly declining. When all DM-ESRD incident cases received a pre-emptive renal transplant (scenario 2), a substantial increase in DM-ESRD prevalence occurred reflecting higher survival, but total costs decreased reflecting the economic advantage of renal transplantation. Conclusions This ABM can forecast numbers and costs of DM-ESRD in Saskatchewan and be modified for application in other jurisdictions. This can aid in resource planning and be used by policy makers to evaluate different interventions in a safe and economical manner.

Innate immunity is the first line to defend against pathogenic microorganisms, and Toll-like receptor (TLR)-mediated inflammatory responses are an essential component of innate immunity. However, the regulatory mechanisms of TLRs in innate immunity remain unperfected. We found that the expression of E3 ligase Ring finger protein 99 (RNF99) decreased significantly in peripheral blood monocytes from patients infected with Gram negative bacteria (G-) and macrophages stimulated by TLRs ligands, indicating the role of RNF99. We also demonstrated for the first time, the protective role of RNF99 against LPS-induced septic shock and dextran sodium sulfate (DSS)-induced colitis using RNF99 knockout mice (RNF99–/–) and bone marrow-transplanted mice. In vitro experiments revealed that RNF99 deficiency significantly promoted TLR-mediated inflammatory cytokine expression and activated the NF-κB and MAPK pathways in macrophages. Mechanistically, in both macrophages and HEK293 cell line with TLR4 stably transfection, RNF99 interacted with and degraded TAK1-binding protein (TAB) 2, a regulatory protein of the kinase TAK1, via the lysine (K)48-linked ubiquitin-proteasomal pathway on lysine 611 of TAB2, which further regulated the TLR-mediated inflammatory response. Overall, these findings indicated the physiological significance of RNF99 in macrophages in regulating TLR-mediated inflammatory reactions. It provided new insight into TLRs signal transduction, and offered a novel approach for preventing bacterial infections, endotoxin shock, and other inflammatory ills.

A towed underwater vehicle equipped with a bio-inspired artificial lateral line (ALL) was constructed and tested with the goal of active detection and correction of the vehicle's yaw angle. Preliminary experiments demonstrate that a low number of sensors are sufficient to enable the discrimination between different orientations, and that a basic proportional controller is capable of keeping the vehicle aligned with the direction of flow. We propose that a model based controller could be developed to improve system response. Toward this, we derive a vehicle model based on a first-order 3D Rankine Source Panel Method, which is shown to be competent in estimating the pressure field in the region of interest during motion at constant angles, and during execution of dynamic maneuvers. To solve the inverse problem of estimating the vehicle orientation given specific pressure measurements, an Unscented Kalman Filter is developed around the model. It is shown to provide a close estimation of the vehicle state using experimentally collected pressure measurements. This demonstrates that an artificial lateral line is a promising technology for dynamically mediating the angle of a body relative to the oncoming flow.

Dental topography is a powerful tool for investigating the relationship between diet and tooth shape in mammals. Here, we test whether dental topographic metrics (DTMs) can accurately predict diet in marsupials based on 81 lower molars from 43 extant species in 12 families (representing six of the seven extant orders), and compare them to DTMs of primates with similar diets. Specific DTMs tested included Dirichlet normal energy (DNE) and variants (ariaDNE, convex DNE, and ariaDNE CV), orientation patch count rotated (OPCR), and Relief Index (RFI). We also investigate the use of the ratio of trigonid to talonid height (TriTaHI) as an additional DTM. Highest dietary classification accuracy using a leave-one-out quadratic discriminant function analysis for marsupials was reached when ariaDNE, RFI, molar size, and TriTaHI of lower second and third molars were combined, resulting in 69.2% dietary accuracy. In contrast, the primate sample of lower second molars reached the highest classification accuracy of 80.4% when only ariaDNE, RFI, and molar size were used. Notably, 3D meshes from epoxy casts showed consistently higher OPCR and ariaDNE CV values than meshes from original specimens. When using a cross-validated approach, using the primate sample to predict marsupial diets and vice versa, only ariaDNE, RFI, and molar size were needed to obtain the maximum classification accuracy (69.7% when classifying primates using the marsupial training set; and 61.8% vice versa). The comparative dataset of this study will be very useful for studies aiming to reconstruct the diets of fossil mammals that lack phylogenetically close extant analogues.