Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial.
The pilot UK Lung Cancer Screening (UKLS) is a randomised ...controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction.
247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569).
The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction.
ISRCTN 78513845.
Atom probe tomography and transmission electron microscopy (TEM) have been used to determine the location and distribution of carbon and alloying elements associated with the complex structural ...changes that occur at the atomic and nanoscale in 4340 steel after quenching to martensite and tempering at 325, 450 or 575°C. Tempering at 325°C resulted in carbide formation without partitioning of chromium, manganese, molybdenum, aluminum, nickel or phosphorus, but with early-stage silicon rejection from the carbide. TEM verified the presence of cementite and the Bagaryatsky orientation relationship with the tempered martensite matrix and detected complex precipitate structures. Tempering at 450 or 575°C developed concentrations of all alloying elements at ferrite–cementite interfaces: chromium, manganese and molybdenum partitioned into the cementite, and silicon, aluminum, nickel and phosphorus were clearly rejected from the cementite. These results provide direct evidence for staged cementite growth, where early-stage growth likely occurs under paraequilibrium conditions, followed by initial silicon redistribution and subsequent alloying element redistribution during late-stage growth. Tempering at 575°C induced spheroidization of the cementite, loss of the Bagaryatsky orientation relationship, and phosphorus concentrations at Cottrell atmospheres within the cementite and at ferrite–cementite interfaces, correlating with early observations of the retardation of spheroidization by phosphorus.
High densities of the corallivorous crown-of-thorns starfish (CoTS;
Acanthaster
sp.) have occurred throughout the Indo-Pacific often resulting in widespread coral loss. Whilst CoTS have previously ...been recorded at Barrow and the Montebello Islands, in the Pilbara offshore bioregion of northwestern Australia, their densities were relatively low. Outbreak densities of CoTS have been described as the level at which the rate of coral consumption by the starfish is equal to or greater than rate at which the coral grows. In 2014, we recorded densities as high as 320 ± 58 CoTS ha
−1
in the region which is well above recognised outbreak densities. Whilst there is little terrestrial runoff and agriculture in the Pilbara region, both temperature and chlorophyll-α levels appear to be sufficient to allow a high degree of CoTS larval success in most years. The region was subjected to anomalously high water temperatures during the summers of 2010–2011 and particularly 2012–2013 which resulted in the mortality of almost 70% of live coral. We hypothesise that the high densities of CoTS observed are a result of CoTS responding to a reduced food supply and aggregating around the remaining live coral resulting in outbreak densities rather than a significant increase in the number of CoTS in the area. The small amount of remaining live coral is concentrated in a few areas and this, combined with high densities of CoTS in these areas, suggest that CoTS represent a significant threat to the recovery of the coral communities of the region.
Glassy carbon is a technologically important material with isotropic properties that is nongraphitizing up to ∼3000 °C and displays complete or "superelastic" recovery from large compression. The ...pressure limit of these properties is not yet known. Here we use experiments and modeling to show permanent densification, and preferred orientation occurs in glassy carbon loaded to 45 GPa and above, where 45 GPa represents the limit to the superelastic and nongraphitizing properties of the material. The changes are explained by a transformation from its sp^{2} rich starting structure to a sp^{3} rich phase that reverts to fully sp^{2} bonded oriented graphite during pressure release.
Results from simulations performed for the Atmospheric Chemistry and Climate Modeling Intercomparison Project (ACCMIP) are analysed to examine how OH and methane lifetime may change from present day ...to the future, under different climate and emissions scenarios. Present day (2000) mean tropospheric chemical lifetime derived from the ACCMIP multi-model mean is 9.8+/-1.6 yr (9.3+/-0.9 yr when only including selected models), lower than a recent observationally-based estimate, but with a similar range to previous multi-model estimates. Future model projections are based on the four Representative Concentration Pathways (RCPs), and the results also exhibit a large range. Decreases in global methane lifetime of 4.5 +/- 9.1% are simulated for the scenario with lowest radiative forcing by 2100 (RCP 2.6), while increases of 8.5+/-10.4% are simulated for the scenario with highest radiative forcing (RCP 8.5). In this scenario, the key driver of the evolution of OH and methane lifetime is methane itself, since its concentration more than doubles by 2100 and it consumes much of the OH that exists in the troposphere. Stratospheric ozone recovery, which drives tropospheric OH decreases through photolysis modifications, also plays a partial role. In the other scenarios, where methane changes are less drastic, the interplay between various competing drivers leads to smaller and more diverse OH and methane lifetime responses, which are difficult to attribute. For all scenarios, regional OH changes are even more variable, with the most robust feature being the large decreases over the remote oceans in RCP8.5. Through a regression analysis, we suggest that differences in emissions of non-methane volatile organic compounds and in the simulation of photolysis rates may be the main factors causing the differences in simulated present day OH and methane lifetime. Diversity in predicted changes between present day and future OH was found to be associated more strongly with differences in modelled temperature and stratospheric ozone changes. Finally, through perturbation experiments we calculated an OH feedback factor (F) of 1.24 from present day conditions (1.50 from 2100 RCP8.5 conditions) and a climate feedback on methane lifetime of 0.33+-0.13 yr/K, on average. Models that did not include interactive stratospheric ozone effects on photolysis showed a stronger sensitivity to climate, as they did not account for negative effects of climate-driven stratospheric ozone recovery on tropospheric OH, which would have partly offset the overall OH/methane lifetime response to climate change.
Aims/hypothesis Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in ...Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. Methods Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat. Results During fenofibrate run-in, plasma creatinine increased by 10.0 μmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 μmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min⁻¹ 1.73 m⁻² annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min⁻¹ 1.73 m⁻², p = 0.065) than on placebo (6.9 ml min⁻¹ 1.73 m⁻², p < 0.001), sparing 5.0 ml min⁻¹ 1.73 m⁻² (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% 95% CI 9-18; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48). Conclusions/interpretation Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited. Trial registration ISRCTN64783481 Funding The study was funded by grants from Laboratoires Fournier SA (Dijon, France; now part of Abbott Pharmaceuticals) and the National Health and Medical Research Council, Australia
The UK Lung Screen (UKLS) is a randomised controlled trial of the use of low-dose multidetector CT for lung cancer screening. It completed the Health Technology Appraisal (HTA)-funded feasibility ...stage in October 2009 and the pilot UKLS will be initiated in early 2011. The pilot will randomise 4000 subjects to either low-dose CT screening or no screening. The full study, due to start in September 2012, if progression criteria are met, will randomise a further 28,000 subjects from seven centres in the UK. Subjects will be selected if they have sufficient risk of developing lung cancer according to the Liverpool Lung Project risk model. The UKLS employs the 'Wald Single Screen Design', which was modelled in the UKLS feasibility study. This paper describes the modelling of nodule management in UKLS by using volumetric analysis with a single initial screen design and follow-up period of 10 years. This modelling has resulted in the development and adoption of the UKLS care pathway, which will be implemented in the planned CT screening trial in the UK.
Perspectives on Quenching and Tempering 4340 Steel Clarke, A. J.; Klemm-Toole, J.; Clarke, K. D. ...
Metallurgical and materials transactions. A, Physical metallurgy and materials science,
10/2020, Letnik:
51, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Steels are ubiquitous due to their affordability and the landscape of useful properties that can be generated for engineering applications. But to further expand the performance envelope, one must be ...able to understand and control microstructure development by alloying and processing. Here we use multiscale, advanced characterization to better understand the structural and chemical evolution of AISI 4340 steel after quenching and tempering (Q&T), including the role of quench rate and short-time, isothermal tempering below 573 K (300 °C), with an emphasis on carbide formation. We compare the microstructure and/or property changes produced by conventional tempering to those produced by higher temperature, short-time “rapid” tempering. We underscore that no single characterization technique can fully capture the subtle microstructure changes like carbon redistribution, transition carbide and/or cementite formation, and retained austenite decomposition that occur during Q&T. Only the use of multiple techniques begins to unravel these complexities. After controlled fast or slow quenching,
η
transition carbides clearly exist in the microstructure, likely associated with autotempering of this high martensite start temperature (
M
s
) steel. Isothermal tempering below 598 K (325 °C) results in the relief of carbon supersaturation in the martensite, primarily by the formation of
η
transition carbides that exhibit a range of carbon levels, seemingly without substitutional element partitioning between the carbide and matrix phases. Hägg transition carbide is present between 300 °C and 325 °C. After conventional tempering at or above 598 K (325 °C) for 2 h, cementite is predominant, but small amounts of cementite are also present in other conditions, even after quenching. Previous work has indicated that silicon (Si) and substitutional elements partition between the cementite, which initially forms under paraequilibrium conditions, and the matrix. Phosphorous (P) may also be preferentially located at cementite/matrix interfaces after high temperature tempering. Slower quench rates result in greater amounts of retained austenite compared to those after fast quenching, which we attribute to increased austenite stability resulting from “autopartitioning”. Rapid, high temperature tempering is also found to diminish tempered martensite embrittlement (TME) believed to be associated with the extent of austenite decomposition, resulting in mechanical properties not attainable by conventional tempering, which may have important implications with respect to industrial heat treatment processes like induction tempering. Controlling the amount and stability of retained austenite is not only relevant to the properties of Q&T steels, but also next-generation advanced high strength steels (AHSS) with austenite/martensite mixtures.
Perspectives on Quenching and Tempering 4340 Steel Clarke, A. J.; Klemm-Toole, J.; Clarke, K. D. ...
Metallurgical and materials transactions. A, Physical metallurgy and materials science,
10/2020, Letnik:
51, Številka:
10
Journal Article
The immune system of preterm infants is immature, placing them at increased risk for serious immune-related complications. Human milk provides a variety of immune protective and immune maturation ...factors that are beneficial to the preterm infant's poorly developed immune system. The most studied immune components in human milk include antimicrobial proteins, maternal leukocytes, immunoglobulins, cytokines and chemokines, oligosaccharides, gangliosides, nucleotides, and long-chain polyunsaturated fatty acids. There is growing evidence that these components contribute to the lower incidence of immune-related conditions in the preterm infant. Therefore, provision of these components in human milk, donor milk, or formula may provide immunologic benefits.
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