Cost-utility of transcatheter aortic valve implantation for inoperable patients with severe aortic stenosis treated by medical management: a UK cost-utility analysis based on patient-level data from the ADVANCE study.

OBJECTIVE: To use patient-level data from the ADVANCE study to evaluate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared to medical management (MM) in patients with severe aortic stenosis from the perspective of the UK NHS. METHODS: A published decision-analytic model was adapted to include information on TAVI from the ADVANCE study. Patient-level data informed the choice as well as the form of mathematical functions that were used to model all-cause mortality, health-related quality of life and hospitalisations. TAVI-related resource use protocols were based on the ADVANCE study. MM was modelled on publicly available information from the PARTNER-B study. The outcome measures were incremental cost-effectiveness ratios (ICERs) estimated at a range of time horizons with benefits expressed as quality-adjusted life-years (QALY). Extensive sensitivity/subgroup analyses were undertaken to explore the impact of uncertainty in key clinical areas. RESULTS: Using a 5-year time horizon, the ICER for the comparison of all ADVANCE to all PARTNER-B patients was £13 943 per QALY gained. For the subset of ADVANCE patients classified as high risk (Logistic EuroSCORE >20%) the ICER was £17 718 per QALY gained). The ICER was below £30 000 per QALY gained in all sensitivity analyses relating to choice of MM data source and alternative modelling approaches for key parameters. When the time horizon was extended to 10 years, all ICERs generated in all analyses were below £20 000 per QALY gained. CONCLUSION: TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis

Investigating bacteriophages targeting the opportunistic pathogen Acinetobacter baumannii

The multi-drug resistance of the opportunistic pathogen Acinetobacter baumannii is of growing concern, with many clinical isolates proving to be resistant to last resort as well as front line antibiotic treatments. The use of bacteriophages is an attractive alternative to controlling and treating this emerging nosocomial pathogen. In this study, we have investigated bacteriophages collected from hospital wastewater in Thailand and we have explored their activity against clinical isolates of A. baumannii. Bacteriophage vB_AbaM_PhT2 showed 28% host range against 150 multidrug resistant (MDR) isolates and whole genome sequencing did not detect any known virulence factors or antibiotic resistance genes. Purified vB_AbaM_PhT2 samples had endotoxin levels below those recommended for preclinical trials and were not shown to be directly cytotoxic to human cell lines in vitro. The treatment of human brain and bladder cell lines grown in the presence of A. baumannii with this bacteriophage released significantly less lactate dehydrogenase compared to samples with no bacteriophage treatment, indicating that vB_AbaM_PhT2 can protect from A. baumannii induced cellular damage. Our results have also indicated that there is synergy between this bacteriophage and the end line antibiotic colistin. We therefore propose bacteriophage vB_AbaM_PhT2 as a good candidate for future research and for its potential development into a surface antimicrobial for use in hospitals. View Full-Tex

Scenicness assessment of onshore wind sites with geotagged photographs and impacts on approval and cost-efficiency

Funding Information: We gratefully acknowledge the contributions of D. Schlund, who carried out some of the wind analysis whilst a Student Assistant at KIT, as well as C. Moutard, on whose Master’s Thesis at DTU this article builds (Assessing the ‘acceptable’ onshore wind potential in the UK, 2019, https://findit.dtu.dk/en/catalog/2451029061). M. D’Andrea, K. Paidis and T. Jaenicke supported the preparation of early versions of the manuscript whilst Student Assistants at DTU. I.M. gratefully acknowledges financial support from Kraks Fond, Copenhagen ([email protected]). T.P. and H.S.M. are grateful for support from The Alan Turing Institute under the EPSRC grant EP/N510129/1 (including awards TU/B/000006 and TU/B/000008).Peer reviewedPostprin

Human Placental Arterial Distensibility, Birth Weight, and Body Size Are Positively Related to Fetal Homocysteine Concentration

Methionine demethylation during metabolism generates homocysteine (Hcy) and its remethylation requires folate and cobalamin. Elevated Hcy concentrations are associated with vascular-related complications of pregnancy, including increased vascular stiffness, predictive of clinical vascular disease. Maternal and fetal total Hcy (tHcy) concentrations are positively related, yet the influence of Hcy on fetoplacental vascular function in normal pregnancy has not been examined. We hypothesized that Hcy alters fetoplacental vascular characteristics with influences on fetal growth outcomes. We investigated (1) placental chorionic plate artery distensibility and neonatal blood pressure in relation to umbilical plasma tHcy; (2) relationships between cord venous (CV) and cord arterial (CA) plasma tHcy, folate, and cobalamin concentrations; and (3) tHcy associations with birth weight and anthropometric measurements of body size as indices of fetal growth in normal pregnancies with appropriate weight-for-gestational age newborns. Maternal plasma tHcy, folate, and cobalamin concentrations were consistent with published data. Placental chorionic plate artery distensibility index (β; measure of vessel stiffness) was inversely related to CA tHcy, yet neonatal blood pressure was not significantly affected. CV and CA tHcy concentrations were positively related and CV tHcy negatively related to CV cobalamin but not folate. CV tHcy concentration positively related to birth weight, corrected birth weight per-centile, length, head circumference, and mid-arm circumference of newborns. CV cobalamin was inversely related to fetal growth indices but not to folate concentration. Our study demonstrates a potential relationship between fetal tHcy and placental artery distensibility, placing clinical relevance to cobalamin in influencing Hcy concentration and maintaining low vascular resistance to facilitate nutrient exchange favorable to fetal growth

Observed variability of the North Atlantic current in the Rockall Trough from four years of mooring measurements

The Rockall Trough is one of the main conduits for warm Atlantic Water to the Nordic Seas. Ocean heat anomalies, originating from the eastern subpolar gyre, are known to influence Arctic sea ice extent, marine ecosystems, and continental climate. Knowledge of the transport through this basin has previously been limited to estimates from hydrographic sections which cannot characterise the intra‐annual and multi‐annual variability. As part of the Overturning in the Subpolar North Atlantic Programme (OSNAP), a mooring array was deployed in the Rockall Trough in order to obtain the first continuous measurements of transport. Here, we define the methodology and the errors associated with estimating these transports. Results show a 4‐year mean northward transport of 6.6 Sv (1 Sv = 106 m3/s) by the North Atlantic Current (NAC) in the east and interior of the Rockall Trough (2014‐2018). A mean transport of ‐2.0 Sv (southward) is observed in the west of the basin, which could be part of a recirculation around the Rockall Plateau. The 90‐day low‐pass filtered transport shows large sub‐annual and inter‐annual variability (‐1.6 Sv to 9.1 Sv), mostly resulting from changes in the mid‐basin geostrophic transport. Satellite altimetry reveals the periods of low and high transport are associated with significant changes in the Rockall Trough circulation. There is a detectable seasonal signal, with the greatest transport in spring and autumn

Domains and processes for institutionalizing evidence-informed health policy-making: a critical interpretive synthesis

BACKGROUND: While calls for institutionalization of evidence-informed policy-making (EIP) have become stronger in recent years, there is a paucity of methods that governments and organizational knowledge brokers can use to sustain and integrate EIP as part of mainstream health policy-making. The objective of this paper was to conduct a knowledge synthesis of the published and grey literatures to develop a theoretical framework with the key features of EIP institutionalization. METHODS: We applied a critical interpretive synthesis (CIS) that allowed for a systematic, yet iterative and dynamic analysis of heterogeneous bodies of literature to develop an explanatory framework for EIP institutionalization. We used a "compass" question to create a detailed search strategy and conducted electronic searches to identify papers based on their potential relevance to EIP institutionalization. Papers were screened and extracted independently and in duplicate. A constant comparative method was applied to develop a framework on EIP institutionalization. The CIS was triangulated with the findings of stakeholder dialogues that involved civil servants, policy-makers and researchers. RESULTS: We identified 3001 references, of which 88 papers met our eligibility criteria. This CIS resulted in a definition of EIP institutionalization as the "process and outcome of (re-)creating, maintaining and reinforcing norms, regulations, and standard practices that, based on collective meaning and values, actions as well as endowment of resources, allow evidence to become-over time-a legitimate and taken-for-granted part of health policy-making". The resulting theoretical framework comprised six key domains of EIP institutionalization that capture both structure and agency: (1) governance; (2) standards and routinized processes; (3) partnership, collective action and support; (4) leadership and commitment; (5) resources; and (6) culture. Furthermore, EIP institutionalization is being achieved through five overlapping stages: (i) precipitating events; (ii) de-institutionalization; (iii) semi-institutionalization (comprising theorization and diffusion); (iv) (re)-institutionalization; and (v) renewed de-institutionalization processes. CONCLUSIONS: This CIS advances the theoretical and conceptual discussions on EIP institutionalization, and provides new insights into an evidence-informed framework for initiating, strengthening and/or assessing efforts to institutionalize EIP

Optimisation of methods for bacterial skin microbiome investigation: primer selection and comparison of the 454 versus MiSeq platform

BACKGROUND: The composition of the skin microbiome is predicted to play a role in the development of conditions such as atopic eczema and psoriasis. 16S rRNA gene sequencing allows the investigation of bacterial microbiota. A significant challenge in this field is development of cost effective high throughput methodologies for the robust interrogation of the skin microbiota, where biomass is low. Here we describe validation of methodologies for 16S rRNA (ribosomal ribonucleic acid) gene sequencing from the skin microbiome, using the Illumina MiSeq platform, the selection of primer to amplify regions for sequencing and we compare results with the current standard protocols.. METHODS: DNA was obtained from two low density mock communities of 11 diverse bacterial strains (with and without human DNA supplementation) and from swabs taken from the skin of healthy volunteers. This was amplified using primer pairs covering hypervariable regions of the 16S rRNA gene: primers 63F and 519R (V1-V3); and 347F and 803R (V3-V4). The resultant libraries were indexed for the MiSeq and Roche454 and sequenced. Both data sets were denoised, cleaned of chimeras and analysed using QIIME. RESULTS: There was no significant difference in the diversity indices at the phylum and the genus level observed between the platforms. The capture of diversity using the low density mock community samples demonstrated that the primer pair spanning the V3-V4 hypervariable region had better capture when compared to the primer pair for the V1-V3 region and was robust to spiking with human DNA. The pilot data generated using the V3-V4 region from the skin of healthy volunteers was consistent with these results, even at the genus level (Staphylococcus, Propionibacterium, Corynebacterium, Paracoccus, Micrococcus, Enhydrobacter and Deinococcus identified at similar abundances on both platforms). CONCLUSIONS: The results suggest that the bacterial community diversity captured using the V3-V4 16S rRNA hypervariable region from sequencing using the MiSeq platform is comparable to the Roche454 GS Junior platform. These findings provide evidence that the optimised method can be used in human clinical samples of low bacterial biomass such as the investigation of the skin microbiota. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-017-0927-4) contains supplementary material, which is available to authorized users

Prediction of residual stresses in girth welded pipes using an artificial neural network approach

Management of operating nuclear power plants greatly relies on structural integrity assessments for safety critical pressure vessels and piping components. In the present work, residual stress profiles of girth welded austenitic stainless steel pipes are characterised using an artificial neural network approach. The network has been trained using residual stress data acquired from experimental measurements found in literature. The neural network predictions are validated using experimental measurements undertaken using neutron diffraction and the contour method. The approach can be used to predict through-wall distribution of residual stresses over a wide range of pipe geometries and welding parameters thereby finding potential applications in structural integrity assessment of austenitic stainless steel girth welds