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Hox genes are critical regulators of skeletal development and Hox9-13 paralogs, specifically, are necessary for appendicular development along the proximal to distal axis. Loss of function of both Hoxa11 and Hoxd11 results in severe malformation of the forelimb zeugopod. In the radius and ulna of these mutants, chondrocyte development is perturbed, growth plates are not established, and skeletal growth and maturation fails. In compound mutants in which one of the four Hox11 alleles remains wild-type, establishment of a growth plate is preserved and embryos develop normally through newborn stages, however, skeletal phenotypes become evident postnatally. During postnatal development, the radial and ulnar growth rate slows compared to wild-type controls and terminal bone length is reduced. Growth plate height is decreased in mutants and premature growth plate senescence occurs along with abnormally high levels of chondrocyte proliferation in the reserve and proliferative zones. Compound mutants additionally develop an abnormal curvature of the radius, which causes significant distortion of the carpal elements. The progressive bowing of the radius appears to result from physical constraint caused by the disproportionately slower growth of the ulna than the radius. Collectively, these data are consistent with premature depletion of forelimb zeugopod progenitor cells in the growth plate of Hox11 compound mutants, and demonstrate a continued function for Hox genes in postnatal bone growth and patterning.

Purpose. The outcome of recanalization in patients with chronic symptomatic intracranial vertebral artery (ICVA) total occlusion is poor. This paper reports the technical feasibility and long-term outcome of ICVA stenting in patients with chronic symptomatic total occlusion. Methods. Retrospective review of our prospectively maintained intracranial intervention database to identify patients with symptomatic total occlusion of ICVA with revascularization attempted >1 month after index ischemic event. Results. Eight patients (mean age 58 years) were identified. One had stroke and 7 had recurrent transient ischemic attacks. Four had bilateral ICVA total occlusion and 4 had unilateral ICVA total occlusion with severe stenosis contralaterally. Seven of 8 patients underwent endovascular recanalization, which was achieved in 6. Periprocedural complications included cerebellum hemorrhage, arterial dissection, perforation, and subacute in-stent thrombosis which occurred in 3 patients. One patient died of cerebellum hemorrhage. The other patients improved clinically after endovascular therapy. Conclusions. Stent-supported recanalization of ICVA total occlusion is technically feasible, and may become a viable treatment option in selected patients.

Background: Thoracoabdominal periprocedural occlusion/reperfusion injury of the spinal cord (SCII/R) can lead to devastating paraplegia, underscoring the critical need for effective interventions. However, our knowledge of optimal medical strategies and their efficacy remains limited. Preclinical investigations have shown promise in harnessing adult stem cells, including pluripotent and multipotent stem cells such as mesenchymal stem cells (MSCs), to address SCII/R by enhancing neuro-inflammation, axonal growth, and myelination. Particularly, growth factors derived from adipose tissue-derived MSCs (ADSCs) have been proposed to facilitate recovery. Despite advancements, achieving complete recovery remains a formidable challenge. Therefore, gaining a more profound insight into the role of ADSCs in alleviating SCII/R-induced paraplegia, including optimizing the delivery systems for therapies, is imperative. Materials and methods: In this study, we assessed the impact of subpial allogeneic rat adipose tissue-derived MSCs (rADSCs) transplantation on paraplegia using a rat SCII/R model induced by ephemeral aortic occlusion, known as the Taira-Marsala model. rADSCs were isolated from adipose tissue of male Sprague-Dawley rats, cultured, characterized, and cryopreserved. One week following the induction of paraplegia, rADSCs (n = 6) or physiological saline (n = 6) were transplanted. Hind limb motor function was evaluated before treatment and at 3-, 7-, and 14-days post-treatment using the Basso-Beattie-Bresnahan scoring system. Results: The rADSC-treated group demonstrated a significant improvement in hind limb motor function compared to the saline-treated group (p

Spinal cord injury (SCI) has limited treatment options for regaining function. Adipose-derived stem cells (ADSCs) show promise owing to their ability to differentiate into multiple cell types, promote nerve cell survival, and modulate inflammation. This review explores ADSC therapy for SCI, focusing on its potential for improving function, preclinical and early clinical trial progress, challenges, and future directions.Preclinical studies have demonstrated ADSC transplantation's effectiveness in promoting functional recovery, reducing cavity formation, and enhancing nerve regrowth and myelin repair. To improve ADSC efficacy, strategies including genetic modification and combination with rehabilitation are being explored. Early clinical trials have shown safety and feasibility, with some suggesting motor and sensory function improvements.Challenges remain for clinical translation, including optimizing cell survival and delivery, determining dosing, addressing tumor formation risks, and establishing standardized protocols. Future research should focus on overcoming these challenges and exploring the potential for combining ADSC therapy with other treatments, including rehabilitation and medication.

Chronic wounds represent a significant global burden, afflicting millions with debilitating complications. Despite standard care, impaired healing persists due to factors like persistent inflammation and impaired tissue regeneration. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer an innovative regenerative medicine approach, delivering stem cell-derived therapeutic cargo in engineered nanoscale delivery systems. This review examines pioneering bioengineering strategies to engineer MSC-EVs into precision nanotherapeutics for chronic wounds. Emerging technologies like CRISPR gene editing, microfluidic manufacturing, and biomimetic delivery systems are highlighted for their potential to enhance MSC-EV targeting, optimize therapeutic cargo enrichment, and ensure consistent clinical-grade production. However, key hurdles remain, including batch variability, rigorous safety assessment for potential tumorigenicity, immunogenicity, and biodistribution profiling. Crucially, collaborative frameworks harmonizing regulatory science with bioengineering and patient advocacy hold the key to expediting global clinical translation. By overcoming these challenges, engineered MSC-EVs could catalyze a new era of off-the-shelf regenerative therapies, restoring hope and healing for millions afflicted by non-healing wounds.

Abstract Introduction Cenegermin is approved for treatment of neurotrophic keratopathy (NK) and has been studied in patients with stage 2 or 3 NK. This study evaluated the efficacy and safety of cenegermin in adults with stage 1 NK. Methods This was a phase IV, multicenter, prospective, open-label, uncontrolled trial. Adults with stage 1 NK (Mackie criteria) and decreased corneal sensitivity (≤ 4 cm) received 1 drop of cenegermin 20 mcg/ml in the affected eye(s) 6 times/day for 8 weeks with a 24-week follow-up. Results Of 37 patients, corneal epithelial healing was observed in 84.8% (95% confidence interval [CI] 68.1–94.9%; P

Introduction: The environmentally acquired aerobic spore-forming (EAS-Fs) bacteria that are ubiquitous in nature (e.g., soil) are transient colonisers of the mammalian gastro-intestinal tract. Without regular exposure, their numbers quickly diminish. These species of bacteria have been suggested to be essential to the normal functioning of metabolic and immunogenic health. The modern Western lifestyle restricts exposure to these EAS-Fs, possibly explaining part of the pathogenesis of many Western diseases. To date, the only animal studies that address specific microbiome modelling are based around germ-free animals. We have designed a new animal model that specifically restricts exposure to environmental sources of bacteria. Methodology: A new protocol, termed Super Clean, which involves housing mice in autoclaved individually ventilated cages (IVCs), with autoclaved food/water and strict ascetic handling practice was first experimentally validated. The quantification of EAS-Fs was assessed by heat-treating faecal samples and measuring colony-forming units (CFUs). This was then compared to mice in standard conditions. Mice were housed in their respective groups from birth until 18 months. Stool samples were taken throughout the experiment to assess for abundance in transiently acquired environmental bacteria. Clinical, biochemical, histological, and gene expression markers were analysed for diabetes, hypercholesterolaemia, obesity, inflammatory bowel disease, and non-alcoholic fatty liver disease (the “diseases of the West”). Results: Our results show that stringent adherence to the Super Clean protocol produces a significantly decreased abundance of aerobic spore-forming Bacillota after 21 days. This microbiomic shift was correlated with significantly increased levels of obesity and impaired glucose metabolism. There was no evidence of colitis, liver disease or hypercholesterolaemia. Conclusions: This new murine model successfully isolates EAS-Fs and has potential utility for future research, allowing for an investigation into the clinical impact of living in relative hygienic conditions.

Introduction: Ageing tends to have a degenerative effect on the skin and emollient use may help maintain skin integrity in older people. In the hospital setting, skin conditions can sometimes be misinterpreted as minor and therefore regular emollient prescriptions are often incomplete or inaccurate.1 We undertook a quality improvement project to evaluate the prescribing of regular emollients in care of the elderly inpatients. Materials and methods: Baseline data were collected using electronic health records for patients in six care of the elderly wards at Northwick Park hospital. We undertook two Plan Do Study Act (PDSA) cycles to improve the accuracy and reduce the delay in regular emollient prescriptions on admission. Our interventions included posters clearly displayed in Accident and Emergency and on acute medical wards and discussions with pharmacists to alert admitting doctors when regular emollients were not prescribed appropriately over 3 months. Results and discussion: In the first PDSA cycle 156 patients were identified, out of which 46 were on regular emollients. The proportion of timely prescriptions was 26% with a mean delay of 11.5 days. In the second cycle 150 patients were identified, out of which 30 were on regular emollients. Following our interventions, the proportion of timely prescriptions rose to 30% and the mean delay time improved to 6.6 days. Conclusion: Our interventions resulted in increased timely prescriptions of regular emollients and reduced prescription delay time in care of the elderly inpatients. This project highlights the need to continue to raise awareness regarding the suboptimal emollient prescribing in elderly patients on admission and hence further cycles to sustain the improvements seen are planned.

Abstract Background Genetically engineered mouse models (GEMMs) of cancer are powerful tools to study mechanisms of disease progression and therapy response, yet little is known about how these models respond to multimodality therapy used in patients. Radiation therapy (RT) is frequently used to treat localized cancers with curative intent, delay progression of oligometastases, and palliate symptoms of metastatic disease. Methods Here we report the development, testing, and validation of a platform to immobilize and target tumors in mice with stereotactic ablative RT (SART). Xenograft and autochthonous tumor models were treated with hypofractionated ablative doses of radiotherapy. Results We demonstrate that hypofractionated regimens used in clinical practice can be effectively delivered in mouse models. SART alters tumor stroma and the immune environment, improves survival in GEMMs of primary prostate and colorectal cancer, and synergizes with androgen deprivation in prostate cancer. Complete pathologic responses were achieved in xenograft models, but not in GEMMs. Conclusions While SART is capable of fully ablating xenografts, it is unable to completely eradicate disease in GEMMs, arguing that resistance to potentially curative therapy can be modeled in GEMMs.

Background Distal transradial access (dTRA) is an alternative to conventional forearm transradial access (fTRA) for coronary angiography (CAG). Differences in healing of the radial artery (RA) in the forearm have not been evaluated between these 2 access strategies. We sought to compare the mean difference in forearm RA intimal‐medial thickening (IMT) in patients randomized to dTRA versus fTRA. Methods and Results In this single‐center randomized clinical trial, 64 patients undergoing nonemergent CAG were randomized (1:1) to dTRA versus fTRA. Ultra–high‐resolution (55‐MHz) vascular ultrasound of the forearm and distal RA was performed pre‐CAG and at 90 days. The primary end point was the mean change in forearm RA IMT. Secondary end points included procedural characteristics, vascular injury, RA occlusion, and ipsilateral hand pain and function. Baseline demographics and clinical characteristics, mean forearm RA IMT, and procedural specifics were similar between the dTRA and fTRA cohorts. There was no difference in mean change in forearm RA IMT between the 2 cohorts (0.07 versus 0.07 mm; P=0.37). No RA occlusions or signs of major vascular injury were observed at 90 days. Ipsilateral hand pain and function (Borg pain scale score: 12 versus 11; P=0.24; Disabilities of the Arm, Shoulders, and Hand scale score: 6 versus 8; P=0.46) were comparable. Conclusions Following CAG, dTRA was associated with no differences in mean change of forearm RA IMT, hand pain, and function versus fTRA for CAG. Further investigation is warranted to elucidate mechanisms and predictors of RA healing and identify effective strategies to preserving RA integrity for repeated procedures. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04801901.

This article describes the arc of global measles and rubella elimination since 2000 from the perspective of the founding partners of the Measles Initiative. The Measles Initiative was formed in 2001 as a partnership among the American Red Cross, the Centers for Disease Control and Prevention, UNICEF, the United Nations Foundation, and the World Health Organization with the aim to reduce measles deaths in low-income countries. Recognizing rubella as the leading infectious disease cause of congenital abnormalities globally and achievement of measles and rubella elimination in the region of the Americas, the partnership was renamed the Measles and Rubella Initiative (MRI) in 2012. The goals of the MRI were at least a 95% reduction in global measles mortality and elimination of measles and rubella in at least five of the six WHO regions. In January 2023, the membership of the partnership was expanded to include the Bill and Melinda Gates Foundation (BMGF) and Gavi the Vaccine Alliance, and its name changed to the IA2030 Measles and Rubella Partnership. We describe the role the partnership has had in measles partner effectiveness and its impact on measles and rubella disease burden, including how the partnership has strategically adapted to the evolving immunization landscape. We conclude with lessons learned regarding the role global partnerships can play in furthering the impact of disease control programs within the current global immunization environment.

Background Visual perception has been defined as the first step to a football player’s decision-making process and it plays an important role in performance in sport. The skill of focussing to prioritize relevant cues has been also considered crucial in sport. This pilot study aims to explore the visual behaviour and attentional effort of three football players (mean age 19 ± 0 years old) in specific-role positions; Right-winger (RW), Centre-Midfielder (CM) and Left-Back (LB), in the five seconds before receiving the ball from their teammate. Methods Twenty-two male football players performed an 11v11 game, where 24 game sequences (trials) from which 166 fixations were recorded and analysed via the Tobii Pro eye-movement registration glasses and software. The gaze behaviour dependent variables were the mean of fixation duration (FD), time to first fixation (TTF), both measured in milliseconds (ms), and the number of fixations (NF) on eight areas of interest (AOIs). AOIs include teammate with and without the ball, opponent without the ball, space around teammate with and without the ball, space around opponent without the ball, ball and undefined. The mean pupil diameter (PD) correlates to the attentional effort and was measured in millimetres (mm). Results Descriptive statistics showed nonregular search rate data between the participants in FD, TTF, NF on the AOIs. Mean FD on the ball: (CM, 270 ms), (RW, 570 ms), (CM, 380 ms). They also presented differences in the mean PD during play; (CM: 2.90 mm ± 0.26), (RW: 2.74 mm ± 0.30), (LB 2.77mm ± 0.27). Conclusions Albeit the sample size was small, the findings demonstrated a promising way to measure the on-field perceptual-cognitive abilities of football players according to their specific positions, since different playing roles revealed to present distinctive visual and attentional patterns. This could potentially assist in tailoring players ‘visual and focus training.

Background Visual perception has been defined as the first step to a football player’s decision-making process and it plays an important role in performance in sport. The skill of focussing to prioritize relevant cues has been also considered crucial in sport. This pilot study aims to explore the visual behaviour and attentional effort of three football players (mean age 19 ± 0 years old) in specific-role positions; Right-winger (RW), Centre-Midfielder (CM) and Left-Back (LB), in the five seconds before receiving the ball from their teammate. Methods Twenty-two male football players performed an 11v11 game, where 24 game sequences (trials) from which 166 fixations were recorded and analysed via the Tobii Pro eye-movement registration glasses and software. The gaze behaviour dependent variables were the mean of fixation duration (FD), time to first fixation (TTF), both measured in milliseconds (ms), and the number of fixations (NF) on eight areas of interest (AOIs). AOIs include teammate with and without the ball, opponent without the ball, space around teammate with and without the ball, space around opponent without the ball, ball and undefined. The mean pupil diameter (PD) correlates to the attentional effort and was measured in millimetres (mm). Results Descriptive statistics showed nonregular search rate data between the participants in FD, TTF, NF on the AOIs. Mean FD on the ball: (CM, 270 ms), (RW, 570 ms), (CM, 380 ms). They also presented differences in the mean PD during play; (CM: 2.90 mm ± 0.26), (RW: 2.74 mm ± 0.30), (LB 2.77mm ± 0.27). Conclusions Albeit the sample size was small, the findings demonstrated a promising way to measure the on-field perceptual-cognitive abilities of football players according to their specific positions, since different playing roles revealed to present distinctive visual and attentional patterns.

Renewable energy provides a low-carbon alternative to power generation in the UK. However, the resultant supply varies on daily, weekly and seasonal cycles, such that for green energies to be fully exploited new grid-scale energy storage systems must be implemented. Two pilot facilities in Germany and the United States have demonstrated the potential of the Earth as a battery to store compressed air, using off-peak surplus energy. Natural accumulations of salt (halite deposits) in the UK represent a large and untapped natural storage reservoir for compressed air with the ability to provide instantaneous green energy to meet peak demand. To realise the potential of this emerging technology, a detailed knowledge of the relationship between mechanics, chemistry and geological properties is required to optimise cavern design, storage potential and economic feasibility. The variable stresses imposed on the rock matrix by gas storage, combined with the cyclic nature of cavern pressurisation are barriers to deployment that need to be addressed to enable large-scale adoption of schemes. Well-designed field experiments are a lynchpin for advancing research in this area, especially when supported by state-of-the-art characterisation and modelling techniques. The research facility at STFC’s Boulby Underground Laboratory presents the ideal location to tackle these fundamental issues to optimise “Battery Earth”.

Abstract Background The coexistence of calcium pyrophosphate dihydrate crystal deposition (CPP) and synovial chondromatosis (SC) in the temporomandibular joint (TMJ) is rarely reported. CPP disease (CPPD) is complex arthritis synonymous with excessive pyrophosphate production and variable aberrations in mineral and organic phase metabolism of the joint cartilage, leading to local inundated CPP and crystal deposition of partially deciphered predispositions. Meanwhile, SC is a rare benign synovial joint proliferative disease of unclear etiology and has a low risk of malignant transformation. However, SC manifests severe joint disability and dysfunction because of connective tissue metaplasia of the synovial membrane, which forms cartilaginous nodules with or without calcifications or ossifications. These nodules often detach and form intra-articular loose bodies and very rarely within extraarticular spaces. Case presentation We report the case of a 61-year-old man to expand the body of literature on these unusual coexisting arthropathies of the TMJ. The patient presented to our hospital in 2020 with complaints of pain in the right TMJ and trismus for over 6 months. Radiographic assessments of the TMJ provided a preoperative provisional diagnosis of SC. However, the histopathology of the open biopsy revealed tumor-like lesions comprising several deposits of rhomboid and rod-shaped crystals that displayed positive birefringence in polarized light, confirming a coexistence of CPPD. A second-stage operation was performed for the complete removal of the loose bodies and chalk-like lesions including synovectomy. No evidence of recurrence was recorded after a follow-up of nearly 1.5 years. Conclusions Isolated CPPD and SC of the TMJ are prevalent in the literature however, monoarticular coexistence of these diseases is rare, due to the lack of consistency in the diagnostic criteria in clinical practice. Moreover, optimal treatment depends on several considerations. This report delineated the molecular etiopathology and underscored the need for continued deciphering of the causal mechanisms of coexisting CPPD and SC of the TMJ. In addition, the importance of confirmatory testing for accurate diagnosis, and appropriate management of these diseases were discussed.

Current trends indicate a growing interest among healthcare specialists and the public in the use of regenerative medicine-based approaches for skin regeneration. The approaches are categorised in either cell-based or cell-free therapies and are reportedly safe and effective. Cell-based therapies include mesenchymal stem cells (MSCs), tissue induced pluripotent stem cells (iPSCs), fibroblast-based products, and blood-derived therapies, such as those employing platelet-rich plasma (PRP) products. Cell-free therapies primarily involve the use of MSC-derived extracellular vesicles/exosomes. MSCs are isolated from various tissues, such as fat, bone marrow, umbilical cord, menstrual blood, and foetal skin, and expanded ex vivo before transplantation. In cell-free therapies, MSC exosomes, MSC-derived cultured media, and MSC-derived extracellular vesicles are collected from MSC-conditioned media or supernatant. In this review, a literature search of the Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus was conducted using several combinations of terms, such as ‘stem’, ‘cell’, ‘aging’, ‘wrinkles’, ‘nasolabial folds’, ‘therapy’, ‘mesenchymal stem cells’, and ‘skin’, to identify relevant articles providing a comprehensive update on the different regenerative medicine-based therapies and their application to skin regeneration. In addition, the regulatory perspectives on the clinical application of some of these therapies in Japan are highlighted.

Hair loss, or alopecia, is associated with several psychosocial and medical comorbidities, and it remains an economic burden to individuals and the society. Alopecia is attributable to varied mechanisms and features a multifactorial predisposition, and the available conventional medical interventions have several limitations. Thus, several therapeutic strategies for alopecia in regenerative medicine are currently being explored, with increasing evidence suggesting that mesenchymal stem cell (MSC) implantation, MSC-derived secretome treatment, and blood-derived platelet-rich plasma therapies are potential treatment options. In this review, we searched the Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus using various combinations of terms, such as “stem cell,” “alopecia,” “hair loss,” “Androgenetic alopecia,” “male-pattern hair loss,” “female-pattern hair loss,” “regenerative hair growth,” “cell therapy,” “mesenchymal stem cells,” “MSC-derived extracellular vesicles,” “MSC-derived exosomes,” and “platelet-rich plasma” and summarized the most promising regenerative treatments for alopecia. Moreover, further opportunities of improving efficacy and innovative strategies for promoting clinical application were discussed.

Abstract Millimetre‐wave frequency‐modulated continuous wave (FMCW) radars are at present widely deployed in the autonomous vehicles. The growing usage of such sensors, as a vital part of a robust future autonomous sensing system, sees the potential for significant increase in mutual interference and adverse effects on sensor operation. Effective target detection in the background of interference requires knowledge of the interference statistics. In the case that such statistics are found to be similar to that of additive white Gaussian noise (AWGN), then classical well‐established detection techniques can be applied. Conversely, if statistics are found to be different, traditional techniques (matched filtering) will not be optimal. Here, a statistical analysis of mutual interference within an FMCW victim radar is presented. The majority of cases show a low correlation between the interference pulses received at the victim radar, with close to a Gaussian distribution. Some specific cases show a high correlation between the interference pulses in the victim radar chirps with a sinusoidal‐like distribution, which degrades the victim radar’s detection performance. The presented analysis is validated by experimental data for various interference cases.

Background: Because heart rate variability (HRV) has been linked to important clinical outcomes in various cardiovascular disease states, we investigated whether preprocedural ultrashort-term HRV (UST-HRV) differs between 1-year survivors and nonsurvivors after transcatheter aortic valve replacement (TAVR). Methods: In our single-center, retrospective, nested pilot study, we analyzed data from patients with severe aortic stenosis undergoing TAVR. All patients had preprocedural UST-HRV measured before the administration of any medications or any intervention. To investigate whether preprocedural HRV is associated with 1-year survival, we performed a logistic regression analysis controlling for Kansas City Cardiomyopathy Questionnaire 12 score. Results: In our parent cohort of 100 patients, 42 patients (28 survivors and 14 nonsurvivors) were included for analysis. Root mean square of successive differences (RMSSD) and standard deviation of NN intervals (SDNN) were lower in patients who survived to 1-year post TAVR compared to nonsurvivors [10 (IQR 8–23) vs 23 (IQR 17–33), P = 0.04 and 10 (IQR 7–16) vs 17 (IQR 11–40), P = 0.03, respectively]. Logistic regression demonstrated a trend in the association of preprocedure RMSSD with 1-year mortality and a 5% higher risk of 1-year mortality with each unit increment in UST-HRV using SDNN (OR 1.05; 95%CI 1.01–1.09, P = 0.02). Conclusion: Our data suggest an inverse relationship between preprocedural UST-HRV and 1-year survival post-TAVR. This finding highlights the potential complexity of HRV regulation in chronic vs acute illness. Prospective studies are needed to validate our findings and to determine whether UST-HRV can be used for risk stratification in patients with severe aortic stenosis.

BackgroundAlthough low back pain (LBP) beliefs have been well investigated in mainstream healthcare discipline students, the beliefs within sports-related study students, such as Sport and Exercise Science (SES), Sports Therapy (ST), and Sport Performance and Coaching (SPC) programmes have yet to be explored. This study aims to understand any differences in the beliefs and fear associated with movement in students enrolled in four undergraduate study programmes-physiotherapy (PT), ST, SES, and SPC.Method136 undergraduate students completed an online survey. All participants completed the Tampa Scale of Kinesiophobia (TSK) and Back Beliefs Questionnaire (BBQ). Two sets of two-way between-subjects Analysis of Variance (ANOVA) were conducted for each outcome of TSK and BBQ, with the independent variables of the study programme, study year (1st, 2nd, 3rd), and their interaction.ResultsThere was a significant interaction between study programme and year for TSK (F(6, 124) = 4.90, P < 0.001) and BBQ (F(6, 124) = 8.18, P < 0.001). Post-hoc analysis revealed that both PT and ST students had lower TSK and higher BBQ scores than SES and SPC students particularly in the 3rd year.ConclusionsThe beliefs of clinicians and trainers managing LBP are known to transfer to patients, and more negative beliefs have been associated with greater disability. This is the first study to understand the beliefs about back pain in various sports study programmes, which is timely, given that the management of injured athletes typically involves a multidisciplinary team.

Rheumatoid arthritis (RA) is a highly prevalent, chronic, and progressive autoimmune disorder primarily affecting joints and muscles. The associated inflammation, pain, and motor restriction negatively impact patient quality of life (QOL) and can even contribute to premature mortality. Further, conventional treatments such as antiinflammatory drugs are only symptomatic. Substantial progress has been made on elucidating the etiopathology of overt RA, in particular the contributions of innate and adaptive immune system dysfunction to chronic inflammation. Although the precise mechanisms underlying onset and progression remain elusive, the discovery of new drug targets, early diagnosis, and new targeted treatments have greatly improved the prognosis and QOL of patients with RA. However, a sizable proportion of patients develop severe adverse effects, exhibit poor responses, or cannot tolerate long-term use of these drugs, necessitating more effective and safer therapeutic alternatives. Mounting preclinical and clinical evidence suggests that the transplantation of multipotent adult stem cells such as mesenchymal stromal/stem cells is a safe and effective treatment strategy for controlling chronic inflammation and promoting tissue regeneration in patients with intractable diseases, including RA. This review describes the current status of MSC-based therapies for RA as well as the opportunities and challenges to broader clinical application.

Abstract Mutual interference in automotive radar is expected to become a major issue owing to the rapid increase in the number of vehicles on the road equipped with radar. The phenomenology of interference in frequency modulated continuous wave radar is presented. Interference is empirically analysed at every signal processing stage in the victim radar by means of experimentally verified simulation modelling. Knowledge of how interference manifests in different domains provides a useful tool to develop algorithms for interference detection, mitigation and/or avoidance. The receiver's filter response is analysed to minimise the interference duration and increase the effectiveness of time‐domain mitigation techniques. A innovative method of interference parameter extraction by using spectrograms is also introduced.

Abstract Objective Compared to other stem cells, the multipotency of human adipose-derived mesenchymal stem cells (ASCs) is limited. Effective approaches that trigger or enhance lineage-specific transdifferentiation are highly envisaged in the improvement of ASCs-based cell therapies. Using Immunofluorescence assays and the secretion of cardiac troponin T (cTnT) protein, we studied the impact of two substrates: Hydroxyapatite (HAp)-coated nonwoven polyethylene (PET)/polypropylene (PP) fabric and glass surfaces, representing 3 dimensional (D) and 2 D environments respectively, on the induction of cardiomyocytes – a non-mesodermal cell type from ASCs for 1–5 weeks. Results ASCs were successfully isolated from human adipose tissue under cGMP conditions. Within 1–3 weeks, expression of cTnT in the induced 3D cultures was overall significantly higher (P

Adiabatic Compressed Air Energy Storage (ACAES) is regarded as a promising, grid scale, medium-to-long duration energy storage technology. In ACAES, the air storage may be isochoric (constant volume) or isobaric (constant pressure). Isochoric storage, wherein the internal pressure cycles between an upper and lower limit as the system charges and discharges is mechanically simpler, however, it leads to undesirable thermodynamic consequences which are detrimental to the ACAES overall performance. Isobaric storage can be a valuable alternative: the storage volume varies to offset the pressure and temperature changes that would otherwise occur as air mass enters or leaves the high-pressure storage. In this paper we develop a thermodynamic model based on expected ACAES and existing CAES system features to compare the effects of isochoric and isobaric storage. Importantly, off-design compressor performance due to the sliding storage pressure is included by using a second degree polynomial fit for the isentropic compressor efficiency. For our modelled systems, the isobaric system round-trip efficiency (RTE) reaches 61.5%. The isochoric system achieves 57.8% even when no compressor off-design performance decrease is taken into account. This fact is associated to inherent losses due to throttling and mixing of heat stored at different temperatures. In our base-case scenario where the isentropic compressor efficiency varies between 55% and 85%, the isochoric system RTE is approximately 10% lower than the isobaric. These results indicate that isobaric storage for CAES is worth further development. We suggest that subsequent work investigate the exergy flows as well as the scalability challenges with isobaric storage mechanisms.

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

Rationale & Objective: Social support in older adults with chronic kidney disease (CKD) is a potentially modifiable factor that may affect important clinical outcomes such as health-related quality of life, cognitive function, and frailty. However, limited data about the effects of social support in older patients with non–dialysis-dependent CKD exist. Our objective was to evaluate the association of social support with health-related quality of life, cognitive function, and frailty in older adults with CKD. Study Design: Cross-sectional analysis of a prospective cohort study. Setting & Population: 1,851 participants older than 65 years with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Exposure: Social support (Lubben Social Network Scale [LSNS]). Outcomes(s): Health-related quality of life (Kidney Disease Quality of Life-36), cognitive function (Modified Mini-Mental State Examination, Trail Making Test A & B, and Buschke Selective Reminder Tests), and frailty (modified Fried frailty criteria). Analytic Approach: Multivariable, linear, and logistic regression to determine the association between social support and health-related quality of life, cognitive function, and frailty. Results: Low social support, defined as LSNS score

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

Introduction Sex hormone binding globulin (SHBG) levels are reported to be inversely associated with diabetes risk. It is unknown whether diabetes prevention interventions increase SHBG and whether resultant changes in SHBG affect diabetes risk. The purpose of this analysis was to determine whether intensive lifestyle intervention (ILS) or metformin changed circulating SHBG and if resultant changes influenced diabetes risk in the Diabetes Prevention Program (DPP).Research design and methods This is a secondary analysis from the DPP (1996–2001), a randomized trial of ILS or metformin versus placebo on diabetes risk over a mean follow-up of 3.2 years. The DPP was conducted across 27 academic study centers in the USA. Men, premenopausal and postmenopausal women without hormone use in the DPP were evaluated. The DPP included overweight/obese persons with elevated fasting glucose and impaired glucose tolerance. Main outcomes measures were changes in SHBG levels at 1 year and risk of diabetes over 3 years.Results ILS resulted in significantly higher increases (postmenopausal women: p

Whether as teachers listening to students, as designers ‘pitching’ designs to clients, or critics writing about historical spaces, we use speech and gesture to describe interiors. We assume that the interior does not speak on it’s own, but must be spoken for. How do designers, curators, and guides talk interiors into existence? How, more generally should we speak of the interior? This paper will explore this issue through reflection on three encounters between space, speech and gesture in the form of guided tours of historic interiors. It will frame these questions with four contexts: firstly, the evolution of the historical concept of the guide; secondly, the idea of the interior as portraiture; thirdly, the evolution, particularly in the twentieth century, of performance (particularly theatrical performance) and finally, the distinction between the interior as image, and the interior as inhabitation.

Abstract Introduction This study sought to determine whether 10 years of assignment to intensive lifestyle intervention (ILI) relative to diabetes support and education leads to better cognition. We examine intervention effects overall and among clinical subgroups, and report correlations between computer‐administered and interviewer‐administered cognitive batteries. Methods The Action for Health in Diabetes (Look AHEAD) was a 16‐site randomized controlled trial with overweight/obese individuals (aged 45–76) who had type 2 diabetes. The NIH Toolbox Cognition Battery tests developed to measure cognition across the lifespan were used to evaluate cognition. Results were compared with standard paper‐and‐pencil tests. The Toolbox and paper‐and‐pencil tests were administered an average of 10.9 years after randomization to 1002 participants. Results Toolbox measures significantly correlated with interviewer‐administered measures, with the strongest correlations between the Toolbox Fluid Cognition Composite and Trails B (r = −0.64, P .05 for all). Subgroup analyses identified different intervention effects within baseline body mass index groups for Picture Sequence Memory (P = .01), within baseline cardiovascular disease groups for Picture Vocabulary (P = .01) and Fluid Cognition Composite (P = .02) measures, and within baseline age groups for Picture Vocabulary (P = .02). Discussion Correlations between Toolbox and interviewer‐administered outcomes provide a measure of internal validity. Findings suggest no overall effect of the intervention on cognition and that an ILI resulting in weight loss may have negative implications for cognition in individuals aged ≥60, with previous history of cardiovascular disease, and those with body mass index ≥40.

Abstract There remains a need to identify novel pro-resolution drugs for treatment of inflammatory disease. To date, there are no neutrophil-specific anti-inflammatory treatments in clinical use, perhaps due to our lack of understanding of how drugs access this complex cell type. Here we present the first comprehensive description and expression of both major classes of drug transporters, SLC and ABC, in resting human blood neutrophils. Moreover, we have studied the expression of these carriers in the tractable model system, the zebrafish (Danio rerio), additionally examining the evolutionary relationship between drug transporters in zebrafish and humans. We anticipate that this will be a valuable resource to the field of inflammation biology and will be an important asset in future anti-inflammatory drug design.

Introduction Choosing Wisely, an international effort to reduce low value care worldwide, considers communication between clinicians and patients during routine clinical encounters a key mechanism for change. In Australia, Choosing Wisely has developed a 5 Questions resource to facilitate better conversations. The primary aim of this study is to evaluate the impact of the Choosing Wisely Australia 5 Questions resource and a video designed to prepare patients for question-asking and participation in shared decision-making on (a) self-efficacy to ask questions and participate in shared decision-making, (b) intention to participate in shared decision-making and (c) a range of secondary outcomes. The secondary aim of this study is to determine whether participants’ health literacy modifies the effects of the interventions.Methods and analysis We will use 2×2×2 between-subjects factorial design (preparation video: yes, no × Choosing Wisely 5 Questions resource: yes, no × health literacy: adequate, inadequate). Participants will be recruited by an online market research company, presented with a hypothetical non-specific low back pain scenario, and randomised to study groups stratified by health literacy. Quantitative primary and secondary outcome data will be analysed as intention-to-treat using appropriate regression models (ie, linear regression for continuous outcomes, logistic regression for dichotomous categorical outcomes).Ethics and dissemination Ethical approval for this study was obtained from the University of Sydney Human Research Ethics Committee (protocol number: 2018/965). The results from this work will be disseminated through peer-reviewed international journals, conferences and updates with collaborating public health bodies. Resources developed for this study will be made available to patients and clinicians following trial completion.Trial registration number This trial has been registered with the Australia New Zealand Clinical Trials Registry (trial number: 376477) and the stage is Pre-results.

The protozoan parasite Leishmania possesses a single flagellum, which is remodelled during the parasite's life cycle from a long motile flagellum in promastigote forms in the sand fly to a short immotile flagellum in amastigotes residing in mammalian phagocytes. This study examined the protein composition and in vivo function of the promastigote flagellum. Protein mass spectrometry and label free protein enrichment testing of isolated flagella and deflagellated cell bodies defined a flagellar proteome for L. mexicana promastigote forms (available via ProteomeXchange with identifier PXD011057). This information was used to generate a CRISPR-Cas9 knockout library of 100 mutants to screen for flagellar defects. This first large-scale knockout screen in a Leishmania sp. identified 56 mutants with altered swimming speed (52 reduced and 4 increased) and defined distinct mutant categories (faster swimmers, slower swimmers, slow uncoordinated swimmers and paralysed cells, including aflagellate promastigotes and cells with curled flagella and disruptions of the paraflagellar rod). Each mutant was tagged with a unique 17-nt barcode, providing a simple barcode sequencing (bar-seq) method for measuring the relative fitness of L. mexicana mutants in vivo. In mixed infections of the permissive sand fly vector Lutzomyia longipalpis, paralysed promastigotes and uncoordinated swimmers were severely diminished in the fly after defecation of the bloodmeal. Subsequent examination of flies infected with a single paralysed mutant lacking the central pair protein PF16 or an uncoordinated swimmer lacking the axonemal protein MBO2 showed that these promastigotes did not reach anterior regions of the fly alimentary tract. These data show that L. mexicana need directional motility for successful colonisation of sand flies.

Streptococcus pneumoniae displays increased resistance to antibiotic therapy following biofilm formation. A genome-wide search revealed that SP 0320 and SP 0675 (respectively annotated as 5-keto-D-gluconate-5-reductase and glucose dehydrogenase) contain the highest degree of homology to CsgA of Myxococcus xanthus, a signaling factor that promotes cell aggregation and biofilm formation. Single and double SP 0320 and SP 0675 knockout mutants were created in strain BS72; however, no differences were observed in the biofilm-forming phenotypes of mutants compared to the wild type strain. Using the chinchilla model of otitis media and invasive disease, all three mutants exhibited greatly increased virulence compared to the wild type strain (increased pus formation, tympanic membrane rupture, mortality rates). The SP 0320 gene is located in an operon with SP 0317, SP 0318 and SP 0319, which we bioinformatically annotated as being part of the Entner-Doudoroff pathway. Deletion of SP 0317 also resulted in increased mortality in chinchillas; however, mutations in SP 0318 and SP 0319 did not alter the virulence of bacteria compared to the wild type strain. Complementing the SP 0317, SP 0320 and SP 0675 mutant strains reversed the virulence phenotype. We prepared recombinant SP 0317, SP 0318, SP 0320 and SP 0675 proteins and confirmed their functions. These data reveal that disruption of genes involved in the degradation of ketogluconate, the Entner-Doudoroff pathway, and glucose dehydrogenase significantly increase the virulence of bacteria in vivo; two hypothetical models involving virulence triggered by reduced in carbon-flux through the glycolytic pathways are presented.

This paper presents an experimental study of the propagation of mm-wave/low-THz signals in the frequency ranges of 79 and 300 GHz through fire. Radar performance was investigated in various real scenarios, including fire with strong flame, dense smoke and water vapour. A stereo video camera and a LIDAR were used as a comparison with other common types of sensors. The ability of radars to enable the visibility of objects in fire environments was proven. In all scenarios, the radar signal attenuation was measured, and in the case of steam was compared with theoretical calculations. The analysis of the experimental results allows us to conclude that there are good prospects for millimetre wave and Low Terahertz radar in the field of firefighting imaging equipment.