Electron Microscopy of Endothelial Cell - Biopolymer Interaction

Vascular endothelial cells form a natural antithrombogenic lining on all blood vessels. Replacement or bypass of small diameter blood vessels with artificial polymeric grafts has not been clinically acceptable due to the thrombogenic nature of polymeric material. One approach to improving the patency of vascular prosthetic devices has been the establishment of endothelial monolayers on the blood flow surface using the technique known as seeding. Scanning electron microscopy has been a major tool in evaluating the interaction of endothelial cells with polymeric surfaces resulting in a basic understanding of forces and structures regulating endothelium-polymer interactions. In-vitro and in-vivo studies have established the feasibility of using endothelial cell seeding technology in human clinical trials. This tutorial describes the development of endothelial cell seeding technology and illustrates how scanning electron microscopic evaluations have furthered our understanding of endothelial cell-polymer interactions

FDG-PET Quantification of Lung Inflammation with Image-Derived Blood Input Function in Mice

Dynamic FDG-PET imaging was used to study inflammation in lungs of mice following administration of a virulent strain of Klebsiella (K.) pneumoniae. Net whole-lung FDG influx constant (Ki) was determined in a compartment model using an image-derived blood input function. Methods. K. pneumoniae (~3 x 105 CFU) was intratracheally administered to six mice with 6 other mice serving as controls. Dynamic FDG-PET and X-Ray CT scans were acquired 24 hr after K. pneumoniae administration. The experimental lung time activity curves were fitted to a 3-compartment FDG model to obtain Ki. Following imaging, lungs were excised and immunohistochemistry analysis was done to assess the relative presence of neutrophils and macrophages. Results. Mean Ki for control and K. pneumoniae infected mice were (5.1 ± 1.2) ×10−3 versus (11.4 ± 2.0) ×10−3 min−1, respectively, revealing a 2.24 fold significant increase (P = 0.0003) in the rate of FDG uptake in the infected lung. Immunohistochemistry revealed that cellular lung infiltrate was almost exclusively neutrophils. Parametric Ki maps by Patlak analysis revealed heterogeneous inflammatory foci within infected lungs. Conclusion. The kinetics of FDG uptake in the lungs of mice can be noninvasively quantified by PET with a 3-compartment model approach based on an image-derived input function

Community resilience for a 1.5 °C world

Ten essentials are presented for community resilience initiatives in the context of achieving a 1.5 °C world: enhance adaptability; take account of shocks and stresses; work horizontally across issues; work vertically across social scales; aggressively reduce carbon emissions; build narratives about climate change; engage directly with futures; focus on climate disadvantage; focus on processes and pathways; and encourage transformations for resilience. Together the essentials highlight that resilience initiatives seeking to retain the status quo will be detrimental when they enable societies to cling to unsustainable activities. Instead, climate resilience initiatives need to be viewed more as a process of transformative social change, where learning, power, inequities and relationships matter. Finally, there is an urgent need for researchers to shift focus away from examining the nature of resilience to accelerating learning about fostering resilience in practice

Patient-reported measurement of time to diagnosis in cancer: development of the Cancer Symptom Interval Measure (C-SIM) and randomised controlled trial of method of delivery

Background: The duration between first symptom and a cancer diagnosis is important because, if shortened, may lead to earlier stage diagnosis and improved cancer outcomes. We have previously developed a tool to measure this duration in newly-diagnosed patients. In this two-phase study, we aimed further improve our tool and to conduct a trial comparing levels of anxiety between two modes of delivery: self-completed versus researcher-administered. Methods: In phase 1, ten patients completed the modified tool and participated in cognitive debrief interviews. In phase 2, we undertook a Randomised Controlled Trial (RCT) of the revised tool (Cancer Symptom Interval Measure (C-SIM)) in three hospitals for 11 different cancers. Respondents were invited to provide either exact or estimated dates of first noticing symptoms and presenting them to primary care. The primary outcome was anxiety related to delivery mode, with completeness of recording as a secondary outcome. Dates from a subset of patients were compared with GP records. Results: After analysis of phase 1 interviews, the wording and format were improved. In phase 2, 201 patients were randomised (93 self-complete and 108 researcher-complete). Anxiety scores were significantly lower in the researcher-completed group, with a mean rank of 83.5; compared with the self-completed group, with a mean rank of 104.0 (Mann-Whitney U = 3152, p = 0.007). Completeness of data was significantly better in the researcher-completed group, with no statistically significant difference in time taken to complete the tool between the two groups. When comparing the dates in the patient questionnaires with those in the GP records, there was evidence in the records of a consultation on the same date or within a proscribed time window for 32/37 (86%) consultations; for estimated dates there was evidence for 23/37 consultations (62%). Conclusions: We have developed and tested a tool for collecting patient-reported data relating to appraisal intervals, help-seeking intervals, and diagnostic intervals in the cancer diagnostic pathway for 11 separate cancers, and provided evidence of its acceptability, feasibility and validity. This is a useful tool to use in descriptive and epidemiological studies of cancer diagnostic journeys, and causes less anxiety if administered by a researcher

Technology Estimating: A Process to Determine the Cost and Schedule of Space Technology Research and Development

NASA is investing in new technologies that include 14 primary technology roadmap areas, and aeronautics. Understanding the cost for research and development of these technologies and the time it takes to increase the maturity of the technology is important to the support of the ongoing and future NASA missions. Overall, technology estimating may help provide guidance to technology investment strategies to help improve evaluation of technology affordability, and aid in decision support. The research provides a summary of the framework development of a Technology Estimating process where four technology roadmap areas were selected to be studied. The framework includes definition of terms, discussion for narrowing the focus from 14 NASA Technology Roadmap areas to four, and further refinement to include technologies, TRL range of 2 to 6. Included in this paper is a discussion to address the evaluation of 20 unique technology parameters that were initially identified, evaluated and then subsequently reduced for use in characterizing these technologies. A discussion of data acquisition effort and criteria established for data quality are provided. The findings obtained during the research included gaps identified, and a description of a spreadsheet-based estimating tool initiated as a part of the Technology Estimating process

Injuries in youth football and the relationship to player maturation: an analysis of time-loss injuries during four seasons in an English elite male football academy

A better insight into injuries in elite youth football may inform prevention strategies. The purpose of this prospective cohort study was to investigate the frequency, incidence and pattern of time-loss injuries in an elite male football academy, exploring injuries in relation to age and maturation status. Across four consecutive playing seasons, playing exposure and injuries to all academy players (U’9 to U’21) were recorded by club medical staff. Maturation status at the time of injury was also calculated for players competing in U’13 to U’16 aged squads. Time-loss injury occurrence and maturation status at time of injury were the main outcome measures. A total of 603 time-loss injuries were recorded, from 190 different players. Playing exposure was 229,317 hours resulting in an overall injury rate of 2.4 p/1000h, ranging from 0.7 p/1000h (U’11) to 4.8 p/1000h (u’21). Most injuries were traumatic in mechanism (73%). The most common injury location was the thigh (23%) and the most common injury type was muscle injury (29%) combining to provide the most common injury diagnosis; thigh muscle injury (17%). In U’13-U’16 players, a higher number of injuries to early-maturing players were observed in U’13-U’14 players, whilst more injuries to U’15-U’16 players occurred when classed as ‘on-time’ in maturity status. Maturation status did not statistically relate to injury pattern, however knee bone (not-fracture) injuries peaked in U’13 players whilst hip/groin muscle injuries peaked in U’15 players

Vector meson dominance and the rho meson

We discuss the properties of vector mesons, in particular the rho^0, in the context of the Hidden Local Symmetry (HLS) model. This provides a unified framework to study several aspects of the low energy QCD sector. Firstly, we show that in the HLS model the physical photon is massless, without requiring off field diagonalization. We then demonstrate the equivalence of HLS and the two existing representations of vector meson dominance, VMD1 and VMD2, at both tree level and one loop order. Finally the S matrix pole position is shown to provide a model and process independent means of specifying the rho mass and width, in contrast to the real axis prescription currently used in the Particle Data Group tables.Comment: 18 pages, REVTE

A robust system for RNA interference in the chicken using a modified microRNA operon

AbstractRNA interference (RNAi) provides an effective method to silence gene expression and investigate gene function. However, RNAi tools for the chicken embryo have largely been adapted from vectors designed for mammalian cells. Here we present plasmid and retroviral RNAi vectors specifically designed for optimal gene silencing in chicken cells. The vectors use a chicken U6 promoter to express RNAs modelled on microRNA30, which are embedded within chicken microRNA operon sequences to ensure optimal Drosha and Dicer processing of transcripts. The chicken U6 promoter works significantly better than promoters of mammalian origin and in combination with a microRNA operon expression cassette (MOEC), achieves up to 90% silencing of target genes. By using a MOEC, we show that it is also possible to simultaneously silence two genes with a single vector. The vectors express either RFP or GFP markers, allowing simple in vivo tracking of vector delivery. Using these plasmids, we demonstrate effective silencing of Pax3, Pax6, Nkx2.1, Nkx2.2, Notch1 and Shh in discrete regions of the chicken embryonic nervous system. The efficiency and ease of use of this RNAi system paves the way for large-scale genetic screens in the chicken embryo

Scaling Peak Oxygen Consumption for Body Size and Composition in People With a Fontan Circulation

This is the final version. Available on open access from Wiley via the DOI in this recordBACKGROUND: Peak oxygen consumption (peak ̇ VO2) is traditionally divided (“ratio- scaled”) by body mass (BM) for clinical interpretation. Yet, it is unknown whether ratio- scaling to BM can produce a valid size- independent expression of peak VO2 in people with a Fontan circulation. Furthermore, people with a Fontan circulation have deficits in lean mass, and it is unexplored whether using different measures of body composition may improve scaling validity. The objective was to assess the validity of different scaling denominators (BM, stature, body surface area, fat- free mass, lean mass, and appendicular lean mass using ratio and allometric scaling). ̇ METHODS AND RESULTS: Eighty- nine participants (age: 23.3±6.7 years; 53% female) with a Fontan circulation had their cardiorespiratory fitness and body composition measured by cardiopulmonary exercise testing and dual- energy x- ray absorptiometry. Ratio and allometric (log- linear regression) scaling was performed and Pearson correlations assessed scaling validity. Scaling denominators BM (r=−0.25, P=0.02), stature (r=0.46, P<0.001), and body surface area (0.23, P=0.03) were significantly correlated with their respective ratio- scaled expressions of peak ̇ VO2, but fat- free mass, lean mass, or appendicular Downloaded from http://ahajournals.org by on December 14, 2022 lean mass were not (r≤0.11; R2=1%). Allometrically expressed peak denominator (r=≤0.23; R2=≤4%). ̇ ̇ VO2 resulted in no significant correlation with any scaling CONCLUSIONS: The traditional and accepted method of ratio- scaling to BM is invalid because it fails to create a size- independent expression of peak VO2 in people with a Fontan circulation. However, ratio- scaling to measures of body composition (fat- free mass, lean mass, and appendicular lean mass) and allometric techniques can produce size- independent expressions of peak ̇ VO2 in people with a Fontan circulation.Canon Medical Systems UK Ltd.University of ExeterMedical Research Future Fun