Materials-based approach for interrogating human prostate cancer cell adhesion and migratory potential using a fluoroalkylsilica culture surface

OPCT-1 is a heterogeneous prostate cancer cell line derived from primary (rather than metastatic) disease which contains epithelial, mesenchymal, and CD44 high/CD24 low cancer stem cell (CSC) subpopulations and from which we have previously generated and characterized stable mesenchymal (P4B6B) and epithelial (P5B3) cell subpopulations. In this contribution, we explore the effect of tissue culture surface chemistry (standard tissue culture plastic (TCP) and a fluoroalkylsilica (FS) culture surface with inherently low surface energy) on the phenotype and adherent capacity of mesenchymal and epithelial cell populations. We demonstrate that OPCT-1 cells adherent to FS surfaces comprise both epithelial- and mesenchymal-like populations; a mesenchymal subpopulation derived from OPCT1 (P4B6B) poorly adheres to FS and formed spheroids, whereas an epithelial subpopulation derived from OPCT1 (P5B3) forms an adherent monolayer. In contrast, P4B6B cells do adhere to FS when cocultured with P5B3 cells. Taken together, these findings demonstrate that EMT/cell differentiation status dictates cell adhesive capacity and provide a novel insight into the relationship between epithelial and mesenchymal cell populations in metastasis. Importantly, the differences in adherence capacity between P4B6B and P5B3 are not apparent using standard TCP-based culture, thereby highlighting the value of using alternative culture surfaces for studying cell surface interaction/adhesion phenomena and interrogating mechanisms involved in adhesion and detachment of metastatic tumor cells

The potential role of cost-utility analysis in the decision to implement major system change in acute stroke services in metropolitan areas in England

BACKGROUND: The economic implications of major system change are an important component of the decision to implement health service reconfigurations. Little is known about how best to report the results of economic evaluations of major system change to inform decision-makers. Reconfiguration of acute stroke care in two metropolitan areas in England, namely London and Greater Manchester (GM), was used to analyse the economic implications of two different implementation strategies for major system change. METHODS: A decision analytic model was used to calculate difference-in-differences in costs and outcomes before and after the implementation of two major system change strategies in stroke care in London and GM. Values in the model were based on patient level data from Hospital Episode Statistics, linked mortality data from the Office of National Statistics and data from two national stroke audits. Results were presented as net monetary benefit (NMB) and using Programme Budgeting and Marginal Analysis (PBMA) to assess the costs and benefits of a hypothetical typical region in England with approximately 4000 strokes a year. RESULTS: In London, after 90 days, there were nine fewer deaths per 1000 patients compared to the rest of England (95% CI -24 to 6) at an additional cost of £770,027 per 1000 stroke patients admitted. There were two additional deaths (95% CI -19 to 23) in GM, with a total costs saving of £156,118 per 1000 patients compared to the rest of England. At a £30,000 willingness to pay the NMB was higher in London and GM than the rest of England over the same time period. The results of the PBMA suggest that a GM style reconfiguration could result in a total greater health benefit to a region. Implementation costs were £136 per patient in London and £75 in GM. CONCLUSIONS: The implementation of major system change in acute stroke care may result in a net health benefit to a region, even one functioning within a fixed budget. The choice of what model of stroke reconfiguration to implement may depend on the relative importance of clinical versus cost outcomes

Isolation of a wide range of minerals from a thermally treated plant: Equisetum arvense, a Mare’s tale

Silica is the second most abundant biomineral being exceeded in nature only by biogenic CaCO3. Many land plants (such as rice, cereals, cucumber, etc.) deposit silica in significant amounts to reinforce their tissues and as a systematic response to pathogen attack. One of the most ancient species of living vascular plants, Equisetum arvense is also able to take up and accumulate silica in all parts of the plant. Numerous methods have been developed for elimination of the organic material and/or metal ions present in plant material to isolate biogenic silica. However, depending on the chemical and/or physical treatment applied to branch or stem from Equisetum arvense; other mineral forms such glass-type materials (i.e. CaSiO3), salts (i.e. KCl) or luminescent materials can also be isolated from the plant material. In the current contribution, we show the chemical and/or thermal routes that lead to the formation of a number of different mineral types in addition to biogenic silica

Characterisation of LV myocardial exercise function by 2-D strain deformation imaging in elite adolescent footballers

This is the final version. Available on open access from Springer via the DOI in this recordPurpose: Few data exist on the descriptions of LV myocardial mechanics and reserve during dynamic exercise of adolescent athletes. The aim of this study was to describe the LV myocardial and cardiopulmonary changes during exercise using 2-D strain deformation imaging. Methods: Elite adolescent male football players (n = 42) completed simultaneous cardiopulmonary exercise testing (CPET) and exercise echocardiography measurement of LV myocardial deformation by 2-D strain imaging. LV longitudinal and circumferential 2-D strain and strain rates were analyzed at each stage during incremental exercise to a work rate of 150 W. Additionally, exercise LV myocardial deformation and its relation to metabolic exercise parameters were evaluated at each exercise stage and in recovery using repeated measures ANOVA, linear regression and paired t tests. Results: LV peak systolic baseline 2-D strain (longitudinal: − 15.4 ± 2.5%, circumferential: − 22.5 ± 3.1%) increased with each exercise stage, but longitudinal strain plateaued at 50 W (mean strain reserve − 7.8 ± 3.0) and did not significantly increase compared to subsequent exercise stages (P > 0.05), whilst circumferential strain (mean strain reserve − 11.6 ± 3.3) significantly increased (P < 0.05) throughout exercise up to 150 W as the dominant mechanism of exercise LV contractility increase. Regression analyses showed LV myocardial strain increased linearly relative to HR, VO2 and O2 pulse (P < 0.05) for circumferential deformation, but showed attenuation for longitudinal deformation. Conclusion: This study describes LV myocardial deformation dynamics by 2-D strain and provides reference values for LV myocardial strain and strain rate during exercise in adolescent footballers. It found important differences between LV longitudinal and circumferential myocardial mechanics during exercise and introduces a methodology that can be used to quantify LV function and cardiac reserve during exercise in adolescent athletes.National Institute for Health Research (NIHR

High survivability of micrometeorites on Mars: Sites with enhanced availability of limiting nutrients

NASA's strategy in exploring Mars has been to follow the water, because water is essential for life, and it has been found that there are many locations where there was once liquid water on the surface. Now perhaps, to narrow down the search for life on a barren basalt‐dominated surface, there needs to be a refocusing to a strategy of “follow the nutrients.” Here we model the entry of metallic micrometeoroids through the Martian atmosphere, and investigate variations in micrometeorite abundance at an analogue site on the Nullarbor Plain in Australia, to determine where the common limiting nutrients available in these (e.g., P, S, Fe) become concentrated on the surface of Mars. We find that dense micrometeorites are abundant in a range of desert environments, becoming concentrated by aeolian processes into specific sites that would be easily investigated by a robotic rover. Our modeling suggests that micrometeorites are currently far more abundant on the surface of Mars than on Earth, and given the far greater abundance of water and warmer conditions on Earth and thus much more active weather system, this was likely true throughout the history of Mars. Because micrometeorites contain a variety of redox sensitive minerals including FeNi alloys, sulfide and phosphide minerals, and organic compounds, the sites where these become concentrated are far more nutrient rich, and thus more compatible with chemolithotrophic life than most of the Martian surface. Plain Language Summary NASA's exploration program has allowed the scientific community to demonstrate clearly that Mars had a watery past, so the search for life needs to move on to identifying the places where water and nutrients coincided. We have investigated the relative abundance of micrometeorites on Mars compared to the Earth because these contain key nutrients that the earliest life forms on Earth used, and because their contained minerals can be used to investigate past atmospheric chemistry. We suggest that micrometeorites should be far more abundant on the Martian surface than on Earth's, and that wind‐driven modification of sediments is expected to concentrate micrometeorites, and their contained nutrients, in gravel beds and cracks in exposed bedrock

Investigating the Accuracy of Quantitative Echocardiographic-Modified Task Force Criteria for Arrhythmogenic Ventricular Cardiomyopathy in Adolescent Male Elite Athletes

This is the final version. Available on open access from Springer via the DOI in this recordAthlete preparticipation screening focuses on preventing sudden cardiac death (SCD) by detecting diseases such as arrhythmogenic ventricular cardiomyopathy (AVC), which affects primarily the right ventricular myocardium. Diagnosis may be obscured by physiological remodeling of the athlete heart. Healthy athletes may meet the 2010 Task Force Criteria right ventricular outflow tract (RVOT) dimension cut-offs, questioning the suitability of the modified Task Force Criteria (mTFC) in adolescent athletes. In this study, 67 male adolescent footballers undergoing preparticipation screening were reviewed. All athletes underwent a screening for resting ECG and echocardiogram according to the English FA protocol, as well as cardiopulmonary exercise testing, stress ECG, and exercise echocardiography. Athletes' right ventricular outflow tract (RVOT) that met the major AVC diagnostic criteria for dilatation were identified. Of 67 evaluated athletes, 7 had RVOT dilatation that met the major criteria, all in the long axis parasternal view measurement. All had normal right ventricular systolic function, including normal free-wall longitudinal strain (ranging from - 21.5 to - 32.7%). Left ventricular ejection fraction ranged from 52 to 67%, without evidence of structural changes. Resting ECGs and cardiopulmonary exercise tests were normal in all individuals. In a series of healthy athletes meeting the major AVC diagnostic criteria for RVOT dilatation, none had any other pathological changes on a detailed screening including ECG, exercise testing, and echocardiography. This report highlights that current AVC echocardiographic diagnosis criteria have limitations in this population.National Institute for Health Research (NIHR)Medical Research Council (MRC

Strain control of a bandwidth-driven spin reorientation in Ca₃Ru₂O₇

The layered-ruthenate family of materials possess an intricate interplay of structural, electronic and magnetic degrees of freedom that yields a plethora of delicately balanced ground states. This is exemplified by Ca3Ru2O7, which hosts a coupled transition in which the lattice parameters jump, the Fermi surface partially gaps and the spins undergo a 90∘ in-plane reorientation. Here, we show how the transition is driven by a lattice strain that tunes the electronic bandwidth. We apply uniaxial stress to single crystals of Ca3Ru2O7, using neutron and resonant x-ray scattering to simultaneously probe the structural and magnetic responses. These measurements demonstrate that the transition can be driven by externally induced strain, stimulating the development of a theoretical model in which an internal strain is generated self-consistently to lower the electronic energy. We understand the strain to act by modifying tilts and rotations of the RuO6 octahedra, which directly influences the nearest-neighbour hopping. Our results offer a blueprint for uncovering the driving force behind coupled phase transitions, as well as a route to controlling them

UK Head and neck cancer surgical capacity during the second wave of the COVID—19 pandemic: Have we learned the lessons? COVIDSurg collaborative

Objectives The aim of this study was to evaluate the differences in surgical capacity for head and neck cancer in the UK between the first wave (March-June 2020) and the current wave (Jan-Feb 2021) of the COVID-19 pandemic. Design REDcap online-based survey of hospital capacity. Setting UK secondary and tertiary hospitals providing head and neck cancer surgery. Participants One representative per hospital was asked to report the capacity for head and neck cancer surgery in that institution. Main outcome measures The principal measures of interests were new patient referrals, capacity in outpatients, theatres and critical care; therapeutic compromises constituting delay to surgery, de-escalated surgery and therapeutic migration to non-surgical primary modality. Results Data were returned from approximately 95% of UK hospitals with a head and neck cancer surgery specialist service. 50% of UK head and neck cancer patients requiring surgery have significantly compromised treatments during the second wave: 28% delayed, 10% have received radiotherapy-based treatment instead of surgery, and 12% have received de-escalated surgery. Surgical capacity has been more severely constrained in the second wave (58% of pre-pandemic level) compared with the first wave (62%) despite the time to prepare. Conclusions Some hospitals are overwhelmed by COVID-19 and unable to offer essential cancer surgery, but all have neighbouring hospitals in their region retaining good (or even normal) capacity. It is noteworthy that very few patients have been appropriately redirected away from the hospitals most constrained by their burden of COVID-19. The paucity of an effective central or regional strategic response to this evident mismatch between demand and surgical capacity is to the detriment of our head and neck cancer patients

A systematic review of randomised controlled trials on the effectiveness of exercise programs on lumbo pelvic pain among postnatal women

Background: A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. Methods: A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group’s Trials Register, and electronic libraries of authors’institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Results: Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of ‘good’ methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Conclusion: Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment

Histological validation of a type 1 diabetes clinical diagnostic model for classification of diabetes

This is the final version. Available on open access from Wiley via the DOI in this recordAims: Misclassification of diabetes is common due to an overlap in the clinical features of type 1 and type 2 diabetes. Combined diagnostic models incorporating clinical and biomarker information have recently been developed that can aid classification, but they have not been validated using pancreatic pathology. We evaluated a clinical diagnostic model against histologically defined type 1 diabetes. Methods: We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (n = 111) or non-type 1 (n = 42) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin-containing islets along with multiple insulin-deficient islets. We assessed the discriminative performance of previously described type 1 diabetes diagnostic models, based on clinical features (age at diagnosis, BMI) and biomarker data [autoantibodies, type 1 diabetes genetic risk score (T1D-GRS)], and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC-ROC). Results: Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D-GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC-ROC 0.97 vs. 0.95; P = 0.03). Histological classification of type 1 diabetes was concordant with serum C-peptide [median < 17 pmol/l (limit of detection) vs. 1037 pmol/l in non-type 1 diabetes; P < 0.0001]. Conclusions: Our study provides robust histological evidence that a clinical diagnostic model, combining clinical features and biomarkers, could improve diabetes classification. Our study also provides reassurance that a C-peptide-based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible. Parts of this study were presented in abstract form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19–22 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6–8 March 2019.Diabetes UKNational Institutes of Health (NIH)National Institute for Health Research (NIHR)JDRFHelmsley Charitable Trus