Variations in vertebral venous vasculature

INTRODUCTION Cadaveric studies have previously documented typical patterns of venous drainage within vertebral bodies (VBs) [1,2,3], comprised primarily of the basivertebral vein, a planar tree like structure at the mid-height of the VB. These studies, however, are limited in the number of samples available, and so have not examined any potential differences in this anatomy in conditions such as scoliosis. MRI is able to create 3D images of soft tissue structures in the spine, including the basivertebral vein without the use of contrast. As a non-invasive imaging technique this opens up the possibility of examining the venous network in multiple VBs within the same subject, in healthy controls as well as in subjects with abnormal anatomy such as adolescent idiopathic scoliosis (AIS). CONCLUSIONS High resolution MRI scans allow in vivo quantification of the vertebral venous system at multiple levels on healthy and scoliotic populations for the first time. The length of the basivertebral vein was seen to have a significant bias to the right hand side of the VB in both healthy and AIS adolescents. The spatial pattern of this vein showed large variations in branching both within and across individuals

A review of image-based simulation applications in high-value manufacturing

Image-Based Simulation (IBSim) is the process by which a digital representation of a real geometry is generated from image data for the purpose of performing a simulation with greater accuracy than with idealised Computer Aided Design (CAD) based simulations. Whilst IBSim originates in the biomedical field, the wider adoption of imaging for non-destructive testing and evaluation (NDT/NDE) within the High-Value Manufacturing (HVM) sector has allowed wider use of IBSim in recent years. IBSim is invaluable in scenarios where there exists a non-negligible variation between the ‘as designed’ and ‘as manufactured’ state of parts. It has also been used for characterisation of geometries too complex to accurately draw with CAD. IBSim simulations are unique to the geometry being imaged, therefore it is possible to perform part-specific virtual testing within batches of manufactured parts. This novel review presents the applications of IBSim within HVM, whereby HVM is the value provided by a manufactured part (or conversely the potential cost should the part fail) rather than the actual cost of manufacturing the part itself. Examples include fibre and aggregate composite materials, additive manufacturing, foams, and interface bonding such as welding. This review is divided into the following sections: Material Characterisation; Characterisation of Manufacturing Techniques; Impact of Deviations from Idealised Design Geometry on Product Design and Performance; Customisation and Personalisation of Products; IBSim in Biomimicry. Finally, conclusions are drawn, and observations made on future trends based on the current state of the literature

In vivo strain measurements in the human buttock during sitting using MR-based digital volume correlation

Advancements in systems for prevention and management of pressure ulcers require a more detailed understanding of the complex response of soft tissues to compressive loads. This study aimed at quantifying the progressive deformation of the buttock based on 3D measurements of soft tissue displacements from MR scans of 10 healthy subjects in a semi-recumbent position. Measurements were obtained using digital volume correlation (DVC) and released as a public dataset. A first parametric optimisation of the global registration step aimed at aligning skeletal elements showed acceptable values of Dice coefficient (around 80%). A second parametric optimisation on the deformable registration method showed errors of and against two simulated fields with magnitude and , respectively, generated with a finite element model of the buttock under sitting loads. Measurements allowed the quantification of the slide of the gluteus maximus away from the ischial tuberosity (IT, average 13.74 mm) that was only qualitatively identified in the literature, highlighting the importance of the ischial bursa in allowing sliding. Spatial evolution of the maximus shear strain on a path from the IT to the seating interface showed a peak of compression in the fat, close to the interface with the muscle. Obtained peak values were above the proposed damage threshold in the literature. Results in the study showed the complexity of the deformation of the soft tissues in the buttock and the need for further investigations aimed at isolating factors such as tissue geometry, duration and extent of load, sitting posture and tissue properties

Protocol for the SAFEST review: the Shock-Absorbing Flooring Effectiveness SysTematic review including older adults and staff in hospitals and care homes.

INTRODUCTION: Falls in hospitals and care homes are a major issue of international concern. Inpatient falls are the most commonly reported safety incident in the UK's National Health Service (NHS), costing the NHS £630 million a year. Injurious falls are particularly life-limiting and costly. There is a growing body of evidence on shock-absorbing flooring for fall-related injury prevention; however, no systematic review exists to inform practice. METHODS AND ANALYSIS: We will systematically identify, appraise and summarise studies investigating the clinical and cost-effectiveness, and experiences of shock-absorbing flooring in hospitals and care homes. Our search will build on an extensive search conducted by a scoping review (inception to May 2016). We will search electronic databases (AgeLine, CINAHL, MEDLINE, NHS Economic Evaluation Database, Scopus and Web of Science; May 2016-present), trial registries and grey literature. We will conduct backward and forward citation searches of included studies, and liaise with study researchers. We will evaluate the influence of floors on fall-related injuries, falls and staff work-related injuries through randomised and non-randomised studies, consider economic and qualitative evidence, and implementation factors. We will consider risk of bias, assess heterogeneity and explore potential effect modifiers via subgroup analyses and sensitivity analyses. Where appropriate we will combine studies through meta-analysis. We will use the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach to evaluate the quality of evidence and present the results using summary of findings tables, and adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. ETHICS AND DISSEMINATION: We will follow the ethical principles of systematic review conduct, by attending to publication ethics, transparency and rigour. Our dissemination plan includes peer-reviewed publication, presentations, press release, stakeholder symposium, patient video and targeted knowledge-to-action reports. This review will inform decision-making around falls management in care settings and identify important directions for future research. PROSPERO REGISTRATION NUMBER: CRD42019118834

The SAFEST review: a mixed methods systematic review of shock-absorbing flooring for fall-related injury prevention.

BACKGROUND: Shock-absorbing flooring may minimise impact forces incurred from falls to reduce fall-related injuries; however, synthesized evidence is required to inform decision-making in hospitals and care homes. METHODS: This is a Health Technology Assessment mixed methods systematic review of flooring interventions targeting older adults and staff in care settings. Our search incorporated the findings from a previous scoping review, MEDLINE, AgeLine, and Scopus (to September 2019) and other sources. Two independent reviewers selected, assessed, and extracted data from studies. We assessed risk of bias using Cochrane and Joanna Briggs Institute tools, undertook meta-analyses, and meta-aggregation. RESULTS: 20 of 22 included studies assessed our outcomes (3 Randomised Controlled Trials (RCTs); 7 observational; 5 qualitative; 5 economic), on novel floors (N = 12), sports floors (N = 5), carpet (N = 5), and wooden sub-floors (N = 1). Quantitative data related to 11,857 patient falls (9 studies), and 163 staff injuries (1 study). One care home-based RCT found a novel underlay produced similar injurious falls rates (high-quality evidence) and falls rates (moderate-quality evidence) to a plywood underlay with vinyl overlay and concrete sub-floors. Very low-quality evidence suggested that shock-absorbing flooring may reduce injuries in hospitals (Rate Ratio 0.55, 95% CI 0.36 to 0.84, 2 studies; 27.1% vs. 42.4%; Risk Ratio (RR) = 0.64, 95% CI 0.44 to 0.93, 2 studies) and care homes (26.4% vs. 33.0%; RR 0.80, 95% CI 0.70 to 0.91, 3 studies), without increasing falls. Economic evidence indicated that if injuries are fewer and falls not increased, then shock-absorbing flooring would be a dominant strategy. Fracture outcomes were imprecise; however, hip fractures reduced from 30 in 1000 falls on concrete to 18 in 1000 falls on wooden sub-floors (OR 0.59, 95% CI 0.45 to 0.78; one study; very low-quality evidence). Staff found moving wheeled equipment harder on shock-absorbing floors leading to workplace adaptations. Very low-quality evidence suggests staff injuries were no less frequent on rigid floors. CONCLUSION: Evidence favouring shock-absorbing flooring is uncertain and of very low quality. Robust research following a core outcome set is required, with attention to wider staff workplace implications. TRIAL REGISTRATION: PROSPERO CRD42019118834

Predicting forefoot-orthosis interactions in rheumatoid arthritis using computational modelling

Foot orthoses are prescribed to reduce forefoot plantar pressures and pain in people with rheumatoid arthritis. Computational modelling can assess how the orthoses affect internal tissue stresses, but previous studies have focused on a single healthy individual. This study aimed to ascertain whether simplified forefoot models would produce differing biomechanical predictions at the orthotic interface between people with rheumatoid arthritis of varying severity, and in comparison to a healthy control. The forefoot models were developed from magnetic resonance data of 13 participants with rheumatoid arthritis and one healthy individual. Measurements of bony morphology and soft tissue thickness were taken to assess deformity. These were compared to model predictions (99th% shear strain and plantar pressure, max. pressure gradient, volume of soft tissue over 10% shear strain), alongside clinical data including body mass index and Leeds Foot Impact Scale–Impairment/Footwear score (LFIS-IF). The predicted pressure and shear strain for the healthy participant fell at the lower end of the rheumatoid models’ range. Medial first metatarsal head curvature moderately correlated to all model predicted outcomes (0.529 < r < 0.574, 0.040 < p < 0.063). BMI strongly correlated to all model predictions except pressure gradients (0.600 < r < 0.652, p < 0.05). There were no apparent relationships between model predictions and instances of bursae, erosion and synovial hypertrophy or LFIS-IF score. The forefoot models produced differing biomechanical predictions between a healthy individual and participants with rheumatoid arthritis, and between individuals with rheumatoid arthritis. Models capable of predicting subject specific biomechanical orthotic interactions could be used in the future to inform more personalised devices to protect skin and soft tissue health. While the model results did not clearly correlate with all clinical measures, there was a wide range in model predictions and morphological measures across the participants. Thus, the need for assessment of foot orthoses across a population, rather than for one individual, is clear

Shock-absorbing flooring for fall-related injury prevention in older adults and staff in hospitals and care homes: the SAFEST systematic review.

BACKGROUND: Injurious falls in hospitals and care homes are a life-limiting and costly international issue. Shock-absorbing flooring may offer part of the solution; however, evidence is required to inform decision-making. OBJECTIVES: The objectives were to assess the clinical effectiveness and cost-effectiveness of shock-absorbing flooring for fall-related injury prevention among older adults in care settings. REVIEW METHODS: A systematic review was conducted of experimental, observational, qualitative and economic studies evaluating flooring in care settings targeting older adults and/or staff. Studies identified by a scoping review (inception to May 2016) were screened, and the search of MEDLINE, AgeLine and Scopus (to September 2019) was updated, alongside other sources. Two independent reviewers assessed risk of bias in duplicate (using Cochrane's Risk of Bias 2.0 tool, the Risk Of Bias In Non-randomized Studies - of Interventions tool, or the Joanna Briggs Institute's qualitative tool). RESULTS: Of the 22 included studies, 20 assessed the outcomes (three randomised controlled trials; and seven observational, five qualitative and five economic studies) on novel floors (n = 12), sports floors (n = 5), carpet (n = 5) and wooden subfloors (n = 1). Quantitative data related to 11,857 patient/resident falls (nine studies) and 163 staff injuries (one study). Qualitative studies included patients/residents (n = 20), visitors (n = 8) and staff (n = 119). Hospital-based randomised controlled trial data were too imprecise; however, very low-quality evidence indicated that novel/sports flooring reduced injurious falls from three per 1000 patients per day on vinyl with concrete subfloors to two per 1000 patients per day (rate ratio 0.55, 95% confidence interval 0.36 to 0.84; two studies), without increasing falls rates (two studies). One care home-based randomised controlled trial found that a novel underlay produces similar injurious falls rates (high-quality evidence) and falls rates (moderate-quality evidence) to those of a plywood underlay with vinyl overlays and concrete subfloors. Very low-quality data demonstrated that, compared with rigid floors, novel/sports flooring reduced the number of falls resulting in injury in care homes (26.4% vs. 33.0%; risk ratio 0.80, 95% confidence interval 0.70 to 0.91; three studies) and hospitals (27.1% vs. 42.4%; risk ratio 0.64, 95% confidence interval 0.44 to 0.93; two studies). Fracture and head injury outcomes were imprecise; however, hip fractures reduced from 30 per 1000 falls on concrete to 18 per 1000 falls on wooden subfloors in care homes (odds ratio 0.59, 95% confidence interval 0.45 to 0.78; one study; very low-quality evidence). Four low-quality economic studies concluded that shock-absorbing flooring reduced costs and improved outcomes (three studies), or increased costs and improved outcomes (one study). One, more robust, study estimated that shock-absorbing flooring resulted in fewer quality-adjusted life-years and lower costs, if the number of falls increased on shock-absorbing floors, but that shock-absorbing flooring would be a dominant economic strategy if the number of falls remained the same. Staff found moving wheeled equipment more difficult on shock-absorbing floors, leading to workplace adaptations. Staff injuries were observed; however, very low-quality evidence suggests that these are no less frequent on rigid floors. LIMITATIONS: Evidence favouring shock-absorbing flooring is of very low quality; thus, much uncertainty remains. CONCLUSIONS: Robust evidence is lacking in hospitals and indicates that one novel floor may not be effective in care homes. Very low-quality evidence indicates that shock-absorbing floors may be beneficial; however, wider workplace implications need to be addressed. Work is required to establish a core outcome set, and future research needs to more comprehensively deal with confounding and the paucity of hospital-based studies, and better plan for workplace adaptations in the study design. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019118834. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 5. See the NIHR Journals Library website for further project information

Thermoneutrality improves skeletal impairment in adult Prader-Willi syndrome mice

International audienc

Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination

Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529