Factors contributing to the yield strength of polycrystalline nickel-based superalloys

Nickel-based superalloys are the material of choice for use in the hottest regions of gas turbine engines due to their inimitable mechanical properties, in particular, high temperature strength. As we become increasingly aware of the environmental consequences of air travel, manufacturers are striving to improve engine efficiency. This may be achieved by increasing the operating temperature of the engine, however, the limiting factor to achieve this is the material used. In order to successfully design new alloys for use in such high temperature applications, a full understanding of the strengthening mechanisms is required. If this were possible, alloy properties such as composition and microstructure could be optimized to the specific mechanisms known to be occurring. However, this is a complex task, as many underlying mechanisms contribute to the superior high temperature strength of these materials, and the extent of each individual mechanism is contentious. The aim of this work was to gain a full understanding of the effect of microstructure on the yield strength of polycrystalline Ni-based superalloys, and the effect on and extent of each of the underlying strengthening mechanisms. To this end, model polycrystalline Ni-based superalloys were studied, based on the quinary Ni-Cr-Al-Ti-Mo system. The series contained 6 alloys with varying Mo content from 0 to 5 at.%, and, as typical of polycrystalline Ni-based superalloys, all had microstructures containing ordered γ′ precipitates within the disordered γ matrix phase. These alloys were fully characterized using electron microscopy techniques in addition to neutron diffraction, to determine experimentally properties such as phase composition, particle size distribution, γ′ volume fraction and grain size. Results were found to differ to commonly accepted wisdom in the literature. Accepted models from the literature for each of the underlying strengthening mechanisms were used to predict the contribution of each mechanism to the overall yield strength of the alloys in this model series. These results were compared to experimental data to determine the efficacy of the models. Microstructural and compositional data from the literature for a number of commercial polycrystalline alloys were also used as input for the models to determine their effectiveness at this more complex level. The results obtained indicate that our currently accepted understanding of yield strength modeling in Ni-based superalloys is insufficient and does not successfully incorporate all of the strengthening mechanisms that are occurring concurrently in these materials. To gain further understanding of the deformation processes that give rise to the overall yield strength of these materials, in situ neutron diffraction experiments were carried out to quantify the degree of load partitioning between grain orientations and between the γ and γ′ phases. It was concluded that both intergranular and interphase load partitioning occur during loading, amid complex interaction between phase strength and coherency.Funding was provided by the EPSRC/Rolls-Royce Strategic Partnership under EP/M005607/1 and EP/H022309/1

Cluster randomised trial of a tailored intervention to improve the management of overweight and obesity in primary care in England. Implement Sci.

Abstract Background: Tailoring is a frequent component of approaches for implementing clinical practice guidelines, although evidence on how to maximise the effectiveness of tailoring is limited. In England, overweight and obesity are common, and national guidelines have been produced by the National Institute for Health and Care Excellence. However, the guidelines are not routinely followed in primary care. Methods: A tailored implementation intervention was developed following an analysis of the determinants of practice influencing the implementation of the guidelines on obesity and the selection of strategies to address the determinants. General practices in the East Midlands of England were invited to take part in a cluster randomised controlled trial of the intervention. The primary outcome measure was the proportion of overweight or obese patients offered a weight loss intervention. Secondary outcomes were the proportions of patients with (1) a BMI or waist circumference recorded, (2) record of lifestyle assessment, (3) referred to weight loss services, and (4) any change in weight during the study period. We also assessed the mean weight change over the study period. Follow-up was for 9 months after the intervention. A process evaluation was undertaken, involving interviews of samples of participating health professionals. Results: There were 16 general practices in the control group, and 12 in the intervention group. At follow-up, 15. 08 % in the control group and 13.19 % in the intervention group had been offered a weight loss intervention, odds ratio (OR) 1.16, 95 % confidence interval (CI) (0.72, 1.89). BMI/waist circumference measurement 42. 71 % control, 39.56 % intervention, OR 1.15 (CI 0.89, 1.48), referral to weight loss services 5.10 % control, 3.67 % intervention, OR 1.45 (CI 0.81, 2.63), weight management in the practice 9.59 % control, 8.73 % intervention, OR 1.09 (CI 0.55, 2.15), lifestyle assessment 23.05 % control, 23.86 % intervention, OR 0.98 (CI 0.76, 1.26), weight loss of at least 1 kg 42.22 % control, 41.65 % intervention, OR 0.98 (CI 0.87, 1.09). Health professionals reported the interventions as increasing their confidence in managing obesity and providing them with practical resources

Rapid post-glacial bedrock weathering in coastal Norway

Quantifying bedrock weathering rates under diverse climate conditions is essential to understanding timescales of landscape evolution. Yet, weathering rates are often difficult to constrain, and associating a weathered landform to a specific formative environment can be complicated by overprinting of successive processes and temporally varying climate. In this study, we investigate three sites between 59°N and 69°N along the Norwegian coast that display grussic saprolite, tafoni, and linear weathering grooves on diverse lithologies. These weathering phenomena have been invoked as examples of geomorphic archives predating Quaternary glaciations and consequently as indicators of minimal glacial erosion. Here we apply cosmogenic nuclide chronometry to assess the recent erosional history. Our results demonstrate that all three sites experienced sufficient erosion to remove most cosmogenic nuclides formed prior to the Last Glacial Maximum. This finding is inconsistent with preservation of surficial (<1–2 m) weathered landforms under non-erosive ice during the last glacial period, while simultaneously demonstrating that post-glacial weathering and erosion rates can be locally rapid (4–10 cm kyr−1) in cold temperate to subarctic coastal locations

Plasma long-chain omega-3 fatty acid status and risk of recurrent early spontaneous preterm birth: a prospective observational study

Introduction A 2018 Cochrane review found that omega-3 supplementation in pregnancy was associated with a risk reduction of early preterm birth of 0.58; prompting calls for universal supplementation. Recent analysis suggests the benefit may be confined to women with a low baseline omega-3 fatty acid status, however the contemporary UK pregnant omega-3 fatty acid status is largely unknown. This is particularly pertinent for women with a previous preterm birth, in whom a small relative risk reduction would have a larger reduction of absolute risk. This study aimed to assess the omega-3 fatty acid status of a UK pregnant population and determine the association between the long-chain omega-3 fatty acids and recurrent spontaneous early preterm birth. Material and methods A total of 283 high-risk women with previous early preterm birth were recruited to the prospective obstervational study in Liverpool, UK. Additionally, 96 pregnant women with previous term births and birth ≥39⁺⁰ weeks in the index pregnancy provided a low-risk population sample. Within the high-risk group we assessed the odds ratio of recurrent early preterm birth compared to birth at ≥37⁺⁰ weeks gestation according to plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) at 15-22 weeks gestation.  RESULTS: Our participants had low EPA+DHA; 62% (143/229) of women with previous preterm birth and 69% (68/96) of the population sample had levels within the lowest two quintiles of a previously published pregnancy cohort. We found no association between long-chain omega-3 status and recurrent early preterm birth (n=51). The crude odds ratio of a recurrent event was 0.91 (95% CI 0.38 to 2.15, p=0.83) for women in the lowest, compared to the highest three quintiles of EPA+DHA. Conclusions In the majority of our participants levels of long-chain omega-3 were low; within the range that may benefit from supplementation. However, levels showed no association with risk of recurrent early spontaneous preterm birth. This could be because our population levels were too low to show benefit in being omega-3 'replete'; or else omega-3 levels may be of lesser importance in recurrent early preterm birth.Laura Goodfellow, Angharad Care, Jane Harrold, Andrew Sharp, Jelena Ivandic, Borna Poljak ... et al

Cluster randomised trial of a tailored intervention to improve the management of overweight and obesity in primary care in England

Background: Tailoring is a frequent component of approaches for implementing clinical practice guidelines, although evidence on how to maximise the effectiveness of tailoring is limited. In England, overweight and obesity are common, and national guidelines have been produced by the National Institute for Health and Care Excellence. However, the guidelines are not routinely followed in primary care. Methods: A tailored implementation intervention was developed following an analysis of the determinants of practice influencing the implementation of the guidelines on obesity and the selection of strategies to address the determinants. General practices in the East Midlands of England were invited to take part in a cluster randomised controlled trial of the intervention. The primary outcome measure was the proportion of overweight or obese patients offered a weight loss intervention. Secondary outcomes were the proportions of patients with (1) a BMI or waist circumference recorded, (2) record of lifestyle assessment, (3) referred to weight loss services, and (4) any change in weight during the study period. We also assessed the mean weight change over the study period. Follow-up was for 9 months after the intervention. A process evaluation was undertaken, involving interviews of samples of participating health professionals. Results: There were 16 general practices in the control group, and 12 in the intervention group. At follow-up, 15. 08 % in the control group and 13.19 % in the intervention group had been offered a weight loss intervention, odds ratio (OR) 1.16, 95 % confidence interval (CI) (0.72, 1.89). BMI/waist circumference measurement 42.71 % control, 39.56 % intervention, OR 1.15 (CI 0.89, 1.48), referral to weight loss services 5.10 % control, 3.67 % intervention, OR 1.45 (CI 0.81, 2.63), weight management in the practice 9.59 % control, 8.73 % intervention, OR 1.09 (CI 0.55, 2.15), lifestyle assessment 23.05 % control, 23.86 % intervention, OR 0.98 (CI 0.76, 1.26), weight loss of at least 1 kg 42.22 % control, 41.65 % intervention, OR 0.98 (CI 0.87, 1.09). Health professionals reported the interventions as increasing their confidence in managing obesity and providing them with practical resources. Conclusions: The tailored intervention did not improve the implementation of the guidelines on obesity, despite systematic approaches to the identification of the determinants of practice. The methods of tailoring require further development to ensure that interventions target those determinants that most influence implementation

Combined point of care nucleic acid and antibody testing for SARS-CoV-2 following emergence of D614G Spike Variant

Rapid COVID-19 diagnosis in hospital is essential, though complicated by 30-50% of nose/throat swabs being negative by SARS-CoV-2 nucleic acid amplification testing (NAAT). Furthermore, the D614G spike mutant now dominates the pandemic and it is unclear how serological tests designed to detect anti-Spike antibodies perform against this variant. We assess the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease due to either wild type or the D614G spike mutant SARS-CoV-2. The overall detection rate for COVID-19 is 79.2% (95CI 57.8-92.9%) by rapid NAAT alone. Combined point of care antibody test and rapid NAAT is not impacted by D614G and results in very high sensitivity for COVID-19 diagnosis with very high specificity

Heat inactivation of clinical COVID-19 samples on an industrial scale for low risk and efficient high-throughput qRT-PCR diagnostic testing.

We report the development of a large scale process for heat inactivation of clinical COVID-19 samples prior to laboratory processing for detection of SARS-CoV-2 by RT-qPCR. With more than 266 million confirmed cases, over 5.26 million deaths already recorded at the time of writing, COVID-19 continues to spread in many parts of the world. Consequently, mass testing for SARS-CoV-2 will remain at the forefront of the COVID-19 response and prevention for the near future. Due to biosafety considerations the standard testing process requires a significant amount of manual handling of patient samples within calibrated microbiological safety cabinets. This makes the process expensive, effects operator ergonomics and restricts testing to higher containment level laboratories. We have successfully modified the process by using industrial catering ovens for bulk heat inactivation of oropharyngeal/nasopharyngeal swab samples within their secondary containment packaging before processing in the lab to enable all subsequent activities to be performed in the open laboratory. As part of a validation process, we tested greater than 1200 clinical COVID-19 samples and showed less than 1 Cq loss in RT-qPCR test sensitivity. We also demonstrate the bulk heat inactivation protocol inactivates a murine surrogate of human SARS-CoV-2. Using bulk heat inactivation, the assay is no longer reliant on containment level 2 facilities and practices, which reduces cost, improves operator safety and ergonomics and makes the process scalable. In addition, heating as the sole method of virus inactivation is ideally suited to streamlined and more rapid workflows such as 'direct to PCR' assays that do not involve RNA extraction or chemical neutralisation methods

Effective control of SARS-CoV-2 transmission between healthcare workers during a period of diminished community prevalence of COVID-19

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to near-zero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK ‘lockdown’. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent ‘hubs’ of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant