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A chronic subdural haematoma (cSDH) is an encapsulated collection of fluid and blood degradation products in the subdural space. It is increasingly common, affecting older people and those living with frailty. Currently, no guidance exists to define optimal care from onset of symptoms through to recovery. This paper presents the first consensus-built recommendations for best practice in the care of cSDH, co-designed to support each stage of the patient pathway. Guideline development was led by a multidisciplinary Steering Committee with representation from diverse clinical groups, professional associations, patients, and carers. Literature searching to identify relevant evidence was guided by core clinical questions formulated through facilitated discussion with specially convened working groups. A modified Delphi exercise was undertaken to build consensus on draft statements for inclusion in the guideline using survey methodology and an in-person meeting. The proposed guideline was subsequently endorsed by the Society for British Neurological Surgeons, Neuroanaesthesia and Critical Care Society, Association of Anaesthetists, British Association of Neuroscience Nurses, British Geriatric Society, and Centre for Perioperative Care. We identified that high quality evidence was generally lacking in the literature, although randomised controlled trial (RCT) data were available to inform specific recommendations on aspects of surgical technique and use of corticosteroids. The final guideline represents the outcome of synthesising available evidence, consensus-built expert opinion and patient involvement. The guideline comprises 67 recommendations across eight major themes, covering: presentation and diagnosis, neurosurgical triage and shared decision-making, non-operative management, perioperative management (including anticoagulation), timing of surgery, intraoperative and postoperative care, rehabilitation and recovery. We present the first multidisciplinary guideline for the care of patients with cSDH. The recommendations reflect a paradigm shift in the care of cSDH, recognising and formalising the need for multidisciplinary and collaborative clinical management, communication and decision-making delivered effectively across secondary and tertiary care.
The article presents research on the application of computed tomography with an incomplete dataset to the problem of examining the internal structure of walls. The case of incomplete information in computed tomography often occurs in various applications, e.g., when examining large objects or when examining hard-to-reach objects. Algorithms dedicated to this type of problem can be used to detect anomalies (defects, cracks) in the walls, among other artifacts. Situations of this type may occur, for example, in old buildings, where special caution should be exercised. The approach presented in the article consists of a non-standard solution to the problem of reconstructing the internal structure of the tested object. The classical approach involves constructing an appropriate system of equations based on X-rays, the solution of which describes the structure. However, this approach has a drawback: solving such systems of equations is computationally very complex, because the algorithms used, combined with incomplete information, converge very slowly. In this article, we propose a different approach that eliminates this problem. To simulate the structure of the tested object, we use a hybrid algorithm that is a combination of a metaheuristic optimization algorithm (Group Teaching Optimization Algorithm) and a numerical optimization method (Hook-Jeeves method). In order to solve the considered inverse problem, a functional measuring the fit of the model to the measurement data is created. The hybrid algorithm presented in this paper was used to find the minimum of this functional. This paper also shows computational examples illustrating the effectiveness of the algorithms.
Coronaviruses are abundant and diverse RNA viruses with broad vertebrate host ranges. These viruses include agents of human seasonal respiratory illness, such as human coronaviruses OC43 and HKU1; important pathogens of livestock and domestic animals such as swine acute diarrhoea syndrome coronavirus and feline coronavirus; and human pathogens of epidemic potential such as SARS-CoV, MERS-CoV and SARS-CoV-2. Most coronavirus surveillance has been conducted in bat species. However, small terrestrial mammals such as rodents and eulipotyphlans are important hosts of coronaviruses as well. Although fewer studies of rodent and eulipotyphlan coronaviruses exist compared to those of bats, notable diversity of coronaviruses has been reported in the former. No literature synthesis for this area of research has been completed despite (a) growing evidence for a small mammal origin of certain human coronaviruses and (b) global abundance of small mammal species. In this review, we present an overview of the current state of coronavirus research in wild terrestrial small mammals. We conducted a literature search for studies that investigated coronaviruses infecting rodent and eulipotyphlan hosts, which returned 63 studies published up to and including 2024. We describe trends in coronavirus diversity and surveillance for these studies. To further the examination of the interrelatedness of these viruses, we conducted a phylogenetic analysis of coronavirus whole genomes recovered from rodent and eulipotyphlan hosts. We discuss important facets of terrestrial small mammal coronaviruses, including evolutionary aspects and zoonotic spillover risk. Lastly, we present important recommendations and considerations for further surveillance and viral characterization efforts in this field.
This article summarises the activities of the International Committee on Taxonomy of Viruses Bacterial Viruses Subcommittee, detailing developments in the classification of bacterial viruses. We provide here an overview of all new, abolished, moved and renamed taxa proposed in 2024, approved by the Executive Committee, and ratified by membership vote in 2025. Through the collective efforts of 74 international contributors of taxonomy proposals in this round, 43 ratified proposals have led to the creation of one new phylum, one class, four orders, 33 families, 14 subfamilies, 194 genera and 995 species. These proposals mark significant progress in refining the taxonomy of bacterial viruses. Key updates include the creation of new orders and families that include existing taxa to better reflect genomic and evolutionary relationships. As sequencing and bioinformatics approaches continue to advance, further expansion and refinements in viral taxonomy can be anticipated in the coming years.
Non-ribosomal peptide synthetases (NRPSs) are complex molecular machineries that synthesize non-proteinaceous peptides in microorganisms. These peptides (NRPs) usually present a wide range of biological activities and are highly regarded as potential anti-cancer and anti-infective agents. Because of their chemical complexity, derivatives of NRPs with tailored pharmacological properties are difficult to synthesize chemically, which has triggered efforts to understand the functional mechanisms of NRPS systems and develop protein engineering strategies aimed at enabling enzymatic synthesis of non-natural NRPs. A fundamental reaction step of NRPS systems is the formation of peptide bonds between amino-acid-like building blocks. This reaction is catalyzed by so-called condensation domains. The structures of several condensation domains and their complexes have been solved by crystallography and electron microscopy, but these structures have failed to provide the key to the design of artificial condensation domains. Here, we use NMR spectroscopy to reveal a complex network of dynamics in the condensation domain of the NRPS responsible for the synthesis of Tomaymycin and reveal how these motions mediate communication between the two substrate binding sites, providing a means to synchronize interactions for efficient catalysis. Our results underline the impact of dynamics, next to structure, on the function of enzymatic units and reinforce the need to consider conformational flexibility in the design of proteins with altered functions.
Adrian Tchaikovsky's new novel Service Model humorously imagines a robot Jeeves coping with the end of civilization.
The increasing complexity and high-dimensional nature of real-world optimization problems necessitate the development of advanced optimization algorithms. Traditional Particle Swarm Optimization (PSO) often faces challenges such as local optima entrapment and slow convergence, limiting its effectiveness in complex tasks. This paper introduces a novel Hybrid Strategy Particle Swarm Optimization (HSPSO) algorithm, which integrates adaptive weight adjustment, reverse learning, Cauchy mutation, and the Hook-Jeeves strategy to enhance both global and local search capabilities. HSPSO is evaluated using CEC-2005 and CEC-2014 benchmark functions, demonstrating superior performance over standard PSO, Dynamic Adaptive Inertia Weight PSO (DAIW-PSO), Hummingbird Flight patterns PSO (HBF-PSO), Butterfly Optimization Algorithm (BOA), Ant Colony Optimization (ACO), and Firefly Algorithm (FA). Experimental results show that HSPSO achieves optimal results in terms of best fitness, average fitness, and stability. Additionally, HSPSO is applied to feature selection for the UCI Arrhythmia dataset, resulting in a high-accuracy classification model that outperforms traditional methods. These findings establish HSPSO as an effective solution for complex optimization and feature selection tasks.
Bartonella are emerging bacterial zoonotic pathogens. Utilization of clotted blood samples for surveillance of these bacteria in wildlife has begun to supersede the use of tissues; however, the efficacy of these samples has not been fully investigated. Our objective was to compare the efficacy of spleen and blood samples for DNA extraction and direct detection of Bartonella spp. via qPCR. In addition, we present a protocol for improved DNA extraction from clotted, pelleted (i.e., centrifuged) blood samples obtained from wild small mammals. DNA concentrations from kit-extracted blood clot samples were low and A260/A280 absorbance ratios indicated high impurity. Kit-based DNA extraction of spleen samples was efficient and produced ample DNA concentrations of good quality. We developed an in-house extraction method for the blood clots which resulted in apposite DNA quality when compared to spleen samples extracted via MagMAX DNA Ultra 2.0 kit. We detected Bartonella in 9/30 (30.0%) kit-extracted spleen DNA samples and 11/30 (36.7%) in-house-extracted blood clot samples using PCR. Our results suggest that kit-based methods may be less suitable for DNA extraction from blood clots, and that blood clot samples may be superior to tissues for Bartonella detection.
Echinococcus multilocularis, a cestode with zoonotic potential, is now known to have a high prevalence in wild canid definitive hosts of southern Ontario. The distribution of E. multilocularis across this region in red foxes (Vulpes vulpes) and coyotes (Canis latrans) is widespread yet heterogenous. In contrast, confirmed diagnoses of E. multilocularis in wild free-ranging intermediate hosts within Ontario are currently limited to a single eastern chipmunk (Tamias striatus). These findings prompted ongoing surveillance efforts in intermediate host species, primarily rodents. Our report describes the results of passive surveillance through wildlife carcass submissions to the Canadian Wildlife Health Cooperative (CWHC) and targeted active sampling of small mammal species from 2018 to 2023; a second and third eastern chipmunk were found to be infected with E. multilocularis. However, these were the only occurrences from surveillance efforts which collectively totaled 510 rodents and other small mammals. Continued surveillance for E. multilocularis in intermediate hosts is of high importance in light of the recent emergence of this parasite in Ontario.
To accurately characterize the mesoscopic properties of NEPE (Nitrate Ester Plasticized Polyether) propellant, the mechanical contraction method was used to construct a representative volume element (RVE) model. Based on this model, the macroscopic mechanical response of NEPE propellant at a strain rate of 0.0047575 s-1 was simulated and calculated, and the parameters of the cohesive zone model (CZM) were inversely optimized using the Hooke-Jeeves algorithm by comparing the simulation results with the results of the uniaxial tensile test of NEPE propellants. Additionally, the macroscopic mechanical behavior of NEPE composite solid propellants at strain rates of 0.00023776 s-1 and 0.023776 s-1 was also predicted. The mesoscopic damage evolution process of NEPE propellants was investigated by the established model. The study results indicate that the predicted curves are relatively consistent with the basic features and change trends of the test curves. Therefore, the established model can effectively simulate the mesoscopic damage process of NEPE composite solid propellants and their macroscopic mechanical properties.
One Health is an integrated approach that aims to balance and optimize the interconnectedness of the health of humans, animals, and ecosystems. Using this transdisciplinary approach, experts from across Canada led the formation of the Wildlife Emerging Pathogens Initiative (Wild EPI) to undertake research and surveillance programs evaluating the potential risks of emerging pathogens at the human-animal interface. Wild EPI is dedicated to implementing the One Health approach to enhance our understanding of the epidemiology and burden of zoonotic infections among humans and other animal hosts.
Globally, back pain is the leading cause of years of disability. In the United Kingdom, over 20 million people live with musculoskeletal (MSK) pain, with low back pain being one of the most common causes. National strategies promote self-management and the use of digital technologies to empower populations. To evaluate the uptake and impact of providing the SelfSTart approach (STarT Back and SelfBACK App) when delivered by a First Contact Physiotherapist (FCP) to people presenting with low back pain in primary care. Patients presenting with a new episode of low back pain underwent routine assessment and completion of a STarT Back questionnaire. Patients with low/medium scores were offered the SelfBACK App. A control population was provided by the MIDAS-GP study. Patient Experience, outcome measures, healthcare utilisation and retention were captured through the app and clinical systems (EMIS). Interviews with five FCPs explored the experiences of using the SelfSTart approach. SelfSTarT was taken up by almost half (48%) of those to whom it was offered. Compared to MIDAS-GP, users were more likely to be younger, male, in work, and with higher health literacy. SelfSTarT users reported significant improved experiences relating to receiving an agreed care plan and receiving sufficient information. There were no significant differences in treatments offered. FCPs were positive about the app and felt it had value but wanted feedback on patient progress. They recognised that a digital solution would not be suitable for all. This approach offers an opportunity to empower and support self-management, using robustly evaluated digital technology.
Vγ9Vδ2 T cells play critical roles in microbial immunity by detecting target cells exposed to pathogen-derived phosphoantigens (P-Ags). Target cell expression of BTN3A1, the "P-Ag sensor," and BTN2A1, a direct ligand for T cell receptor (TCR) Vγ9, is essential for this process; however, the molecular mechanisms involved are unclear. Here, we characterize BTN2A1 interactions with Vγ9Vδ2 TCR and BTN3A1. Nuclear magnetic resonance (NMR), modeling, and mutagenesis establish a BTN2A1-immunoglobulin V (IgV)/BTN3A1-IgV structural model compatible with their cell-surface association in cis. However, TCR and BTN3A1-IgV binding to BTN2A1-IgV is mutually exclusive, owing to binding site proximity and overlap. Moreover, mutagenesis indicates that the BTN2A1-IgV/BTN3A1-IgV interaction is non-essential for recognition but instead identifies a molecular surface on BTN3A1-IgV essential to P-Ag sensing. These results establish a critical role for BTN3A-IgV in P-Ag sensing, in mediating direct or indirect interactions with the γδ-TCR. They support a composite-ligand model whereby intracellular P-Ag detection coordinates weak extracellular germline TCR/BTN2A1 and clonotypically influenced TCR/BTN3A-mediated interactions to initiate Vγ9Vδ2 TCR triggering.
Major burns are associated with multiple risk factors for thrombosis such as decreased mobilization and systemic inflammation. It is unclear if these factors are offset by the inherent lower thrombosis risk in the paediatric patient. As such there is no consensus on thromboprophylaxis for paediatric burns patients, in contrast to this being a mainstay of treatment in the adult population. This retrospective cohort study examines the incidence of, and risk factors for, thrombotic events in major paediatric burns with a view to establish guidelines for prevention. Review of major paediatric burns, defined as % total body surface area (%TBSA) ≥30%, at the Adelaide Women's and Children's Hospital (WCH) over a 16-year period. Coding data and the local burns database were used to identify participants with subsequent review of case files. Of the cohort (n = 23), six cases (26%) were complicated by thrombotic events. These patients had the most extensive burns averaging 68.5% TBSA, longer PICU admissions and associated interventions. These data points were more than doubled in the cohort diagnosed with a thrombus. Of the six events, five were secondary to central venous catheters (CVC) and one deep venous thrombosis (DVT) to the left calf. The incidence of thrombotic events in our study was significant albeit in a small population. There is a strong association between large %TBSA and thrombus, with clots mostly forming around CVCs. While further research is required, this study demonstrates screening and targeted thromboprophylaxis may be required for major paediatric burns.
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from wildlife has raised concerns about spillover from humans to animals, the establishment of novel wildlife reservoirs, and the potential for future outbreaks caused by variants of wildlife origin. Norway rats (Rattus norvegicus) are abundant in urban areas and live in close proximity to humans, providing the opportunity for spillover of SARS-CoV-2. Evidence of SARS-CoV-2 infection and exposure has been reported in Norway rats. We investigated SARS-CoV-2 infection and exposure in Norway rats from Southern Ontario, Canada. From October 2019 to June 2021, 224 rats were submitted by collaborating pest control companies. The majority of samples were collected in Windsor (79.9%; n = 179), Hamilton (13.8%; n = 31), and the Greater Toronto Area (5.8%; n = 13). Overall, 50.0% (n = 112) were female and most rats were sexually mature (55.8%; n = 125). Notably, 202 samples were collected prior to the emergence of variants of concern (VOC) and 22 were collected while the Alpha variant (B.1.1.7) was the predominant circulating VOC in humans. Nasal turbinate (n = 164) and small intestinal (n = 213) tissue samples were analyzed for SARS-CoV-2 RNA by RT-PCR. Thoracic cavity fluid samples (n = 213) were tested for neutralizing antibodies using a surrogate virus neutralization test (sVNT) (GenScript cPass); confirmatory plaque reduction neutralization test (PRNT) was conducted on presumptive positive samples. We did not detect SARS-CoV-2 RNA in any samples tested. Two out of eleven samples positive on sVNT had neutralizing antibodies confirmed positive by PRNT (1 : 40 and 1 : 320 PRNT70); both were collected prior to the emergence of VOC. It is imperative that efforts to control and monitor SARS-CoV-2 include surveillance of rats and other relevant wildlife species as novel variants continue to emerge.
Tuberous breast is a complex congenital breast anomaly that can be challenging to correct surgically. The authors conducted a systematic review with pooled analysis of data, with the aim of determining the effectiveness and complications related to operative management of the deformity. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were adopted in performing this systematic review. A simplified classification system for tuberous breast deformity was developed to accurately compare data and guide analysis. The review identified 38 studies, reporting a total of 897 patients undergoing tuberous breast surgery. The mean age of patients was 24 years (range 13-53 years). Mean follow-up was 39 months. A combination of tissue rearrangement and implant augmentation was the most common technique (73% of patients) followed by fat transfer alone (9%). Breast implants were employed in 83% of patients. The mean implanted volume per breast was 263 cc. Fat grafting was performed in 13% of patients and mean volume of fat grafted per breast was 185 cc. An overall complication rate of 20% was reported. Subjective assessment of patient satisfaction was 99%, and the mean score on BREAST-Q for satisfaction with clinical outcome was 86.7. Future studies should focus on robust study designs including randomized and cohort studies, use of patient-reported outcome measures, and long-term follow-up. The surgical techniques to correct tuberous breast deformity are safe, effective, and have a high satisfaction rate. Fat transfer has the capacity to provide promising results in treating tuberous breast deformity.
Few interventions are proven to reduce total health care costs, and addressing cost-related nonadherence has the potential to do so. To determine the effect of eliminating out-of-pocket medication fees on total health care costs. This secondary analysis of a multicenter randomized clinical trial using a prespecified outcome took place across 9 primary care sites in Ontario, Canada (6 in Toronto and 3 in rural areas), where health care services are generally publicly funded. Adult patients (≥18 years old) reporting cost-related nonadherence to medicines in the past 12 months were recruited between June 1, 2016, and April 28, 2017, and followed up until April 28, 2020. Data analysis was completed in 2021. Access to a comprehensive list of 128 medicines commonly prescribed in ambulatory care with no out-of-pocket costs for 3 years vs usual medicine access. Total publicly funded health care costs over 3 years, including costs of hospitalizations. Health care costs were determined using administrative data from Ontario's single-payer health care system, and all costs are reported in Canadian dollars with adjustments for inflation. A total of 747 participants from 9 primary care sites were included in the analysis (mean [SD] age, 51 [14] years; 421 [56.4%] female). Free medicine distribution was associated with a lower median total health care spending over 3 years of $1641 (95% CI, $454-$2792; P = .006). Mean total spending was $4465 (95% CI, -$944 to $9874) lower over the 3-year period. In this secondary analysis of a randomized clinical trial, eliminating out-of-pocket medication expenses for patients with cost-related nonadherence in primary care was associated with lower health care spending over 3 years. These findings suggest that eliminating out-of-pocket medication costs for patients could reduce overall costs of health care. ClinicalTrials.gov Identifier: NCT02744963.
In recent times, many different types of systems have been based on fractional derivatives. Thanks to this type of derivatives, it is possible to model certain phenomena in a more precise and desirable way. This article presents a system consisting of a two-dimensional fractional differential equation with the Riemann-Liouville derivative with a numerical algorithm for its solution. The presented algorithm uses the alternating direction implicit method (ADIM). Further, the algorithm for solving the inverse problem consisting of the determination of unknown parameters of the model is also described. For this purpose, the objective function was minimized using the ant algorithm and the Hooke-Jeeves method. Inverse problems with fractional derivatives are important in many engineering applications, such as modeling the phenomenon of anomalous diffusion, designing electrical circuits with a supercapacitor, and application of fractional-order control theory. This paper presents a numerical example illustrating the effectiveness and accuracy of the described methods. The introduction of the example made possible a comparison of the methods of searching for the minimum of the objective function. The presented algorithms can be used as a tool for parameter training in artificial neural networks.