BackgroundLung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial.MethodsThe 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.Results247 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 mm3 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 mm3 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).ConclusionsThe 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.Trial registrationISRCTN 78513845.
This Letter reports the first scientific results from the observation of antineutrinos emitted by fission products of ^{235}U at the High Flux Isotope Reactor. PROSPECT, the Precision Reactor ...Oscillation and Spectrum Experiment, consists of a segmented 4 ton ^{6}Li-doped liquid scintillator detector covering a baseline range of 7-9 m from the reactor and operating under less than 1 m water equivalent overburden. Data collected during 33 live days of reactor operation at a nominal power of 85 MW yield a detection of 25 461±283 (stat) inverse beta decays. Observation of reactor antineutrinos can be achieved in PROSPECT at 5σ statistical significance within 2 h of on-surface reactor-on data taking. A reactor model independent analysis of the inverse beta decay prompt energy spectrum as a function of baseline constrains significant portions of the previously allowed sterile neutrino oscillation parameter space at 95% confidence level and disfavors the best fit of the reactor antineutrino anomaly at 2.2σ confidence level.
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This Letter reports one of the most precise measurements to date of the antineutrino spectrum from a purely 235U-fueled reactor, made with the final dataset from the PROSPECT-I detector at the High ...Flux Isotope Reactor. By extracting information from previously unused detector segments, this analysis effectively doubles the statistics of the previous PROSPECT measurement. Further, the reconstructed energy spectrum is unfolded into antineutrino energy and compared with both the Huber-Mueller model and a spectrum from a commercial reactor burning multiple fuel isotopes. A local excess over the model is observed in the 5–7 MeV energy region. Comparison of the PROSPECT results with those from commercial reactors provides new constraints on the origin of this excess, disfavoring at 2.0 and 3.7 standard deviations the hypotheses that antineutrinos from 235U are solely responsible and noncontributors to the excess observed at commercial reactors, respectively.
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This Letter reports the first measurement of the 235U $\bar{ν}$e energy spectrum by PROSPECT, the Precision Reactor Oscillation and Spectrum experiment, operating 7.9 m from the 85 MWth highly ...enriched uranium (HEU) High Flux Isotope Reactor. With a surface-based, segmented detector, PROSPECT has observed 31678±304(stat) $\bar{ν}$e-induced inverse beta decays, the largest sample from HEU fission to date, 99% of which are attributed to 235U. Despite broad agreement, comparison of the Huber 235U model to the measured spectrum produces a χ2/ndf=51.4/31, driven primarily by deviations in two localized energy regions. The measured 235U spectrum shape is consistent with a deviation relative to prediction equal in size to that observed at low-enriched uranium power reactors in the $\bar{ν}$e energy region of 5–7 MeV.
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Personality can be thought of as a set of characteristics that influence people's thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes ...in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17,375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ≈ 2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P=2.8 × 10(-8) and 3.1 × 10(-8)) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P=4.9 × 10(-8)). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.
Objective The objective of the study was to compare and contrast the effects of developmental hypoxia vs undernutrition on fetal growth, cardiovascular morphology, and function. Study Design On day ...15 of gestation, Wistar dams were divided into control, hypoxic (10% O2 ), or undernourished (35% reduction in food intake) pregnancy. On day 20, fetal thoraces were fixed, and the fetal heart and aorta underwent quantitative histological analysis. In a separate group, fetal aortic vascular reactivity was determined via wire myography. Results Both hypoxic and undernourished pregnancy was associated with asymmetric fetal growth restriction. Pregnancy complicated by hypoxia promoted fetal aortic thickening without changes in cardiac volumes when expressed as a percentage of total heart volume. In contrast, maternal undernutrition affected fetal cardiac morphology without changes in aortic structure. Fetal aortic vascular reactivity was also differentially affected by hypoxia or undernutrition. Conclusion Developmental hypoxia or undernutrition in late gestation has differential effects on fetal cardiovascular morphology and function.
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