Design, development and evaluation of a novel percutaneous Ascending Thoracic Aortic Graft (ATAG.

MD (Res)There is a huge unmet clinical need for a new, safe and effective minimally invasive treatment for Acute Ascending Aortic Dissection (AAAD) (1). In 2012 AAAD has a mortality rate of 1-2% per hour within the first 24 hours, and even with contemporary surgical techniques, advanced intensive and post operative care, the mortality from AAAD following surgery in most series remains in the unacceptable range of 10-30% at 30 days (2;3). 28% of patients presenting with AAAD are denied life saving surgery often because of age or co-morbidity - medical therapy alone associated with an in hospital mortality rate in excess of 50% (2;4-6). Currently available endovascular stent grafts used in the descending thoracic and abdominal aorta are not adequately designed to be utilised within the ascending aorta. They have a large stowed diameter 22-25 French (F), with a rigid covering of either Dacron or ePTFE, and a stiff inflexible delivery system unlikely to traverse the aortic arch without complication. While the contemporary results of elective surgery for ascending thoracic aortic aneurysm (ATAA) are good, with an elective mortality of <5%, surgical results for AAAD have improved little over the last 20 years, with a 30 day mortality rate between 10-30% (3;7). With the emerging role of endovascular stent grafts in the treatment of thoracic aneurysm and dissection, with shorter hospital stays and improved outcomes I believe now is the time for the development of a percutaneous solution for AAAD. Potential ascending thoracic aortic graft (ATAG) designs must take into account the very close proximity of intimal tear to both the coronary arteries and aortic valve, allowing a 4 good proximal graft seal without compromising coronary flow or aortic valve competence. ATAG should have a low profile, with a thin non porous covering and a flexible delivery sheath with accurate and precise deployment characteristics. Following a literature review and novel anatomical data collection from computerised tomography (CT) and magnetic resonance imaging (MRI) scans of AAAD and ATAA patient cohorts, it seems that 3 embodiments of ATAG should be designed and developed, all sharing advanced core technologies including a laser-cut nitinol stent frame, thin polyurethane (PU) material covering and accurate and precise deployment mechanisms: 1) The “supra-coronary tubular ATAG”, for treating AAAD with an intimal tear in the ascending aorta, no coronary or aortic valve involvement and adequate landing zones above the coronary arteries and before the right brachiocephalic trunk (RBCT). It is likely that this graft will be capable of treating at least a third of all patients with AAAD (8). 2) The “inverted t-shirt ATAG” to proactively protect coronary artery flow and achieve proximal seal within the sinuses in patients with an intimal tear in close association or involving the coronary arteries. 3) The “valved ATAG” to treat patients who have significant aortic regurgitation (AR), to achieve a proximal seal at the annulus when anatomy suggests it would be difficult to achieve with embodiment 1) or 2), and in those patients who have a hugely dilated aortic root, so that the ATAG can seal proximally at a relatively normal annulus size, and seal distally at a normal ascending aorta diameter 5 proximal to the RBCT. This could be the treatment option for the 25-35% of AAAD patients who currently require aortic valve repair or replacement (9). The most complex of the 3 devices above is embodiment 2), the “inverted t-shirt ATAG”, as it must ensure proximal aortic seal within an often dilated sinus, without compromise to aortic valve and proactively protect both coronary arteries with 2 coronary sleeves. Basic proof of concept (PoC) of this embodiment has been demonstrated in vitro within a normal sized aortic glass model, with some important study limitations, nevertheless it does demonstrate that tracking an ATAG branched graft with 2 coronary sleeves is possible over 3 guidewires and deploying accurately within the aortic root under both direct vision and fluoroscopy. Following successful PoC deployment I then specified and had manufactured a 2nd Generation ATAG (2G ATAG), with a laser-cut nitinol frame, longitudinal tie bars, and a novel thin PU graft covering material. The 2G ATAG has been shown to have adequate radial strength when compared to competitor devices, and can be stowed to 28 F for deployment. During ATAG development 2 patents have been filed, and I wrote with Professor Rothman a successful NIHR I4I grant for £743,000 to take ATAG from the current 28 F 2G device, towards the goal of an 18 F device with bench testing, in vitro flow rig and deployment analysis, and in collaboration with the Royal Veterinary College (RVC) into an animal model over the next 3 years (beyond the scope of this thesis). I hope that within this next development cycle ATAG can be iterated into a device that might be ready to embark on a first in man (FIM) trial to offer the AAAD population an effective and less invasive treatment strategy

Bifurcated polarization rotation in bismuth-based piezoelectrics

ABO3 perovskite-type solid solutions display a large variety of structural and physical properties, which can be tuned by chemical composition or external parameters such as temperature, pressure, strain, electric, or magnetic fields. Some solid solutions show remarkably enhanced physical properties including colossal magnetoresistance or giant piezoelectricity. It has been recognized that structural distortions, competing on the local level, are key to understanding and tuning these remarkable properties, yet, it remains a challenge to experimentally observe such local structural details. Here, from neutron pair-distribution analysis, a temperature-dependent 3D atomic-level model of the lead-free piezoelectric perovskite Na0.5Bi0.5TiO3 (NBT) is reported. The statistical analysis of this model shows how local distortions compete, how this competition develops with temperature, and, in particular, how different polar displacements of Bi3+ cations coexist as a bifurcated polarization, highlighting the interest of Bi-based materials in the search for new lead-free piezoelectrics

Socioeconomic inequalities in food outlet access through an online food delivery service in England: A cross-sectional descriptive analysis.

Online food delivery services facilitate 'online' access to food outlets selling food prepared away-from-home. Online food outlet access has not previously been investigated in England or across an entire country. Systematic differences in online food outlet access could exacerbate existing health inequalities, which is a public health concern. However, this is not known. Across postcode districts in England (n = 2118), we identified and described the number of food outlets and unique cuisine types accessible online from the market leader (Just Eat). We investigated associations with area-level deprivation using adjusted negative binomial regression models. We also compared the number of food outlets accessible online with the number physically accessible in the neighbourhood (1600m Euclidean buffers of postcode district geographic centroids) and investigated associations with deprivation using an adjusted general linear model. For each outcome, we predicted means and 95% confidence intervals. In November 2019, 29,232 food outlets were registered to accept orders online. Overall, the median number of food outlets accessible online per postcode district was 63.5 (IQR; 16.0-156.0). For the number of food outlets accessible online as a percentage of the number accessible within the neighbourhood, the median was 63.4% (IQR; 35.6-96.5). Analysis using negative binomial regression showed that online food outlet access was highest in the most deprived postcode districts (n = 106.1; 95% CI: 91.9, 120.3). The number of food outlets accessible online as a percentage of those accessible within the neighbourhood was highest in the least deprived postcode districts (n = 86.2%; 95% CI: 78.6, 93.7). In England, online food outlet access is socioeconomically patterned. Further research is required to understand how online food outlet access is related to using online food delivery services

Revised structural phase diagram of (Ba0.7Ca0.3TiO3)-(BaZr0.2Ti0.8O3)

The temperature-composition phase diagram of barium calcium titanate zirconate (x(Ba0.7Ca0.3TiO3)(1-x)(BaZr0.2Ti0.8O3); BCTZ) has been reinvestigated using high-resolution synchrotron x-ray powder diffraction. Contrary to previous reports of an unusual rhombohedral-tetragonal phase transition in this system, we have observed an intermediate orthorhombic phase, isostructural to that present in the parent phase, BaTiO3, and we identify the previously assigned T-R transition as a T-O transition. We also observe the O-R transition coalescing with the previously observed triple point, forming a phase convergence region. The implication of the orthorhombic phase in reconciling the exceptional piezoelectric properties with the surrounding phase diagram is discussed

Topology and temperature dependence of the diffuse X-ray scattering in Na0.5Bi0.5TiO3 ferroelectric single crystals

The results of high-resolution measurements of the diffuse X-ray scattering produced by a perovskite-based Na0.5Bi0.5TiO3 ferroelectric single crystal between 40 and 620 K are reported. The study was designed as an attempt to resolve numerous controversies regarding the average structure of Na0.5Bi0.5TiO3, such as the mechanism of the phase transitions between the tetragonal, P4bm, and rhombohedral | monoclinic, R3c | Cc, space groups and the correlation between structural changes and macroscopic physical properties. The starting point was to search for any transformations of structural disorder in the temperature range of thermal depoling (420–480 K), where the average structure is known to remain unchanged. The intensity distribution around the {032} pseudocubic reflection was collected using a PILATUS 100K detector at the I16 beamline of the Diamond Light Source (UK). The data revealed previously unknown features of the diffuse scattering, including a system of dual asymmetric L-shaped diffuse scattering streaks. The topology, temperature dependence, and relationship between Bragg and diffuse intensities suggest the presence of complex microstructure in the low-temperature R3c | Cc phase. This microstructure may be formed by the persistence of the higher-temperature P4bm phase, built into a lower-temperature R3c | Cc matrix, accompanied by the related long-range strain fields. Finally, it is shown that a correlation between the temperature dependence of the X-ray scattering features and the temperature regime of thermal depoling is present

Correlates of English local government use of the planning system to regulate hot food takeaway outlets: a cross-sectional analysis

Background: Greater neighbourhood takeaway food outlet access has been associated with increased takeaway food consumption and higher body weight. National planning guidelines in England suggest that urban planning could promote healthier food environments through takeaway food outlet regulation, for example by restricting the proliferation of outlets near schools. It is unknown how geographically widespread this approach is, or local characteristics associated with its use. We aimed to address these knowledge gaps. Methods: We used data from a complete review of planning policy documents adopted by local government areas in England (n = 325), which contained policies for the purpose of takeaway food outlet regulation. This review classified local government area planning policies as having a health (diet or obesity) or non-health focus. We explored geographical clustering of similar planning policies using spatial statistics. We used multinomial logistic regression models to investigate whether the odds of planning policy adoption varied according to local characteristics, for example the proportion of children with excess weight or the current number of takeaway food outlets. Results: We observed clusters of local government areas with similar adopted planning policies in the North East, North West, and Greater London regions of England. In unadjusted logistic regression models, compared to local government areas with the lowest, those with highest proportion of 10–11 year olds with excess weight (OR: 25.31; 95% CI: 6.74, 94.96), and takeaway food outlet number (OR: 54.00; 95% CI: 6.17, 472.41), were more likely to have a health-focused planning policy, than none. In models adjusted for deprivation, relationships for excess weight metrics were attenuated. Compared to local government areas with the lowest, those with the highest takeaway food outlet number remained more likely to have a health-focused planning policy, than none (OR: 16.98; 95% CI: 1.44, 199.04). When local government areas were under Labour political control, predominantly urban, and when they had more geographically proximal and statistically similar areas in the same planning policy status category, they were also more likely to have health-focused planning policies. Conclusions: Planning policies for the purpose of takeaway food outlet regulation with a health focus were more likely in areas with greater numbers of takeaway food outlets and higher proportions of children with excess weight. Other characteristics including Labour political control, greater deprivation and urbanisation, were associated with planning policy adoption, as were the actions of similar and nearby local government areas. Further research should engage with local policymakers to explore the drivers underpinning use of this approach

Percutaneous balloon aortic valvuloplasty in the era of transcatheter aortic valve implantation: a narrative review

The role of percutaneous balloon aortic valvuloplasty (BAV) in the management of severe symptomatic aortic stenosis has come under the spotlight following the development of the transcatheter aortic valve implantation (TAVI) technique. Previous indications for BAV were limited to symptom palliation and as a bridge to definitive therapy for patients undergoing conventional surgical aortic valve replacement (AVR). In the TAVI era, BAV may also be undertaken to assess the ‘therapeutic response’ of a reduction in aortic gradient in borderline patients often with multiple comorbidities, to assess symptomatic improvement prior to consideration of definitive TAVI intervention. This narrative review aims to update the reader on the current indications and practical techniques involved in undertaking a BAV procedure. In addition, a summary of the haemodynamic and clinical outcomes, as well as the frequently encountered procedural complications is presented for BAV procedures conducted during both the pre-TAVI and post-TAVI era

Use of Online Food Delivery Services to Order Food Prepared Away-From-Home and Associated Sociodemographic Characteristics: A Cross-Sectional, Multi-Country Analysis

Online food delivery services like Just Eat and Grubhub facilitate online ordering and home delivery of food prepared away-from-home. It is poorly understood how these services are used and by whom. This study investigated the prevalence of online food delivery service use and sociodemographic characteristics of customers, in and across Australia, Canada, Mexico, the UK, and the USA. We analyzed online survey data (n = 19,378) from the International Food Policy Study, conducted in 2018. We identified respondents who reported any online food delivery service use in the past 7 days and calculated the frequency of use and number of meals ordered. We investigated whether odds of any online food delivery service use in the past 7 days differed by sociodemographic characteristics using adjusted logistic regression. Overall, 15% of respondents (n = 2929) reported online food delivery service use, with the greatest prevalence amongst respondents in Mexico (n = 839 (26%)). Online food delivery services had most frequently been used once and the median number of meals purchased through this mode of order was two. Odds of any online food delivery service use were lower per additional year of age (OR: 0.95; 95% CI: 0.94, 0.95) and greater for respondents who were male (OR: 1.50; 95% CI: 1.35, 1.66), that identified with an ethnic minority (OR: 1.57; 95% CI: 1.38, 1.78), were highly educated (OR: 1.66; 95% CI: 1.46, 1.90), or living with children (OR: 2.71; 95% CI: 2.44, 3.01). Further research is required to explore how online food delivery services may influence diet and health

External validation of the Hospital Frailty Risk Score in France

BACKGROUND: The Hospital Frailty Risk Score (HFRS) has made it possible internationally to identify subgroups of patients with characteristics of frailty from routinely collected hospital data. OBJECTIVE: To externally validate the HFRS in France. DESIGN: A retrospective analysis of the French medical information database. SETTING: 743 hospitals in Metropolitan France. SUBJECTS: All patients aged 75 years or older hospitalised as an emergency in 2017 (n = 1,042,234). METHODS: The HFRS was calculated for each patient based on the index stay and hospitalisations over the preceding 2 years. Main outcome measures were 30-day in-patient mortality, length of stay (LOS) >10 days and 30-day readmissions. Mixed logistic regression models were used to investigate the association between outcomes and HFRS score. RESULTS: Patients with high HFRS risk were associated with increased risk of mortality and prolonged LOS (adjusted odds ratio [aOR] = 1.38 [1.35-1.42] and 3.27 [3.22-3.32], c-statistics = 0.676 and 0.684, respectively), while it appeared less predictive of readmissions (aOR = 1.00 [0.98-1.02], c-statistic = 0.600). Model calibration was excellent. Restricting the score to data prior to index admission reduced discrimination of HFRS substantially. CONCLUSIONS: HFRS can be used in France to determine risks of 30-day in-patient mortality and prolonged LOS, but not 30-day readmissions. Trial registration: Reference ID on clinicaltrials.gov: ID: NCT03905629

Relationship between the structure and optical properties of lithium tantalate at the zero-birefringence point

The structure of lithium tantalate powders has been investigated using neutron diffraction between room temperature and 445 K, which includes the zero-birefringence point. As the temperature increases, the displacement of the Ta atom from the centre of the O octahedra and the tilt of the octahedra both decrease linearly in the range investigated. The measured structures form the basis of a range of density functional theory calculations utilizing the WIEN2 k code, with a focus on calculating the optical properties. These calculations are sensitive to the small structural changes measured in this temperature range; the calculated birefringence changes are consistent with the changes measured experimentally. Further, by investigating the effect of each atom in isolation, it can be shown that the birefringence of lithium tantalate mainly depends on the Ta displacement and the octahedral tilt, with the linear change in these as a function of temperature producing the change in birefringence with temperature, which results in it becoming zero-birefringent. This work demonstrates the unique material insights that can be obtained by combining density functional calculations with precise structural studies