Low-dose computed tomography for lung cancer screening in high risk populations: a systematic review and economic evaluation

This is the final version. Available from NIHR Journals Library via the DOI in this record.The dataset associated with this article is located in ORE at: https://doi.org/10.24378/exe.564Background Diagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early. Objectives To estimate the effectiveness and cost-effectiveness of LDCT lung cancer screening in high risk populations. Methods Clinical effectiveness A systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programme (such as chest X-ray (CXR)) was conducted. Bibliographic sources included MEDLINE, Embase, Web of Science and the Cochrane Library. Meta-analyses, including network meta-analyses, were performed. Cost-effectiveness An independent economic model employing discrete event simulation and using a natural history model calibrated to results from a large RCT was developed. There were twelve different population eligibility criteria and four intervention frequencies (single screen, triple screen, annual screening and biennial screening) and a no screening control arm. Results Clinical effectiveness Twelve RCTs were included, four of which currently contribute evidence on mortality. Meta-analysis of these demonstrated that LDCT with up to 9.80 years of follow-up was associated with a non-statistically significant decrease in lung cancer mortality (pooled RR 0.94, 95% CI 0.74 to 1.19). The findings also showed that LDCT screening demonstrated a non-statistically significant increasein all-cause mortality. Given the considerable heterogeneity detected between studies for both outcomes, the results should be treated with caution. Network meta-analysis including six RCTs was performed to assess the relative effectiveness of LDCT, CXR and usual care. The results showed that LDCT was ranked as the best screening strategy in terms of lung cancer mortality reduction. CXR had a 99.7% probability of being the worst intervention with usual care intermediate. Cost-effectiveness Screening programmes are predicted to be more effective than no screening, reduce lung cancer mortality and result in more lung cancer diagnoses. Screening programmes also increase costs. Screening for lung cancer is unlikely to be cost-effective at a threshold of £20,000/QALY, but may be cost-effective at a threshold of £30,000/QALY. The incremental cost-effectiveness ratio for a single screen in smokers aged 60–75 years with at least a 3% risk of lung cancer is £28,169 per QALY. Sensitivity and scenario analyses were conducted. Screening was only cost-effective at a threshold of £20,000/QALY in a minority of analyses. Limitations Clinical effectiveness The largest of the included RCTs compared LDCT with CXR screening rather than no screening. Cost-effectiveness A representative cost to the NHS of lung cancer has not been recently estimated according to key variables such as stage at diagnosis. Certain costs associated with running a screening programme have not been included. Conclusions LDCT screening may be clinically effective in reducing lung cancer mortality but there is considerable uncertainty. There is evidence that a single round of screening could be considered cost-effective at conventional thresholds, but there is significant uncertainty about the effect on costs and the magnitude of benefits. Future work Effectiveness and cost-effectiveness estimates should be updated with the anticipated results from several ongoing RCTs (particularly NELSON).This report was commissioned by the NIHR Health Technology Assessment Programme as project number 14/151/0

Historical Archaeology in the Iberian Peninsula

UID/HIS/04209/2019 DL 57/2016/CP1453/CT0084authorsversionpublishe

Phenotypic microarrays suggest Escherichia coli ST131 is not a metabolically distinct lineage of extra-intestinal pathogenic E. coli

Extraintestinal pathogenic E. coli (ExPEC) are the major aetiological agent of urinary tract infections (UTIs) in humans. The emergence of the CTX-M producing clone E. coli ST131 represents a major challenge to public health worldwide. A recent study on the metabolic potential of E. coli isolates demonstrated an association between the E. coli ST131 clone and enhanced utilisation of a panel of metabolic substrates. The studies presented here investigated the metabolic potential of ST131 and other major ExPEC ST isolates using 120 API test reagents and found that ST131 isolates demonstrated a lower metabolic activity for 5 of 120 biochemical tests in comparison to non-ST131 ExPEC isolates. Furthermore, comparative phenotypic microarray analysis showed a lack of specific metabolic profile for ST131 isolates countering the suggestion that these bacteria are metabolically fitter and therefore more successful human pathogens

Traditional Taxonomic Groupings Mask Evolutionary History: A Molecular Phylogeny and New Classification of the Chromodorid Nudibranchs

Chromodorid nudibranchs (16 genera, 300+ species) are beautiful, brightly colored sea slugs found primarily in tropical coral reef habitats and subtropical coastal waters. The chromodorids are the most speciose family of opisthobranchs and one of the most diverse heterobranch clades. Chromodorids have the potential to be a model group with which to study diversification, color pattern evolution, are important source organisms in natural products chemistry and represent a stunning and widely compelling example of marine biodiversity. Here, we present the most complete molecular phylogeny of the chromodorid nudibranchs to date, with a broad sample of 244 specimens (142 new), representing 157 (106 new) chromodorid species, four actinocylcid species and four additional dorid species utilizing two mitochondrial markers (16s and COI). We confirmed the monophyly of the Chromodorididae and its sister group relationship with the Actinocyclidae. We were also able to, for the first time, test generic monophyly by including more than one member of all 14 of the non-monotypic chromodorid genera. Every one of these 14 traditional chromodorid genera are either non-monophyletic, or render another genus paraphyletic. Additionally, both the monotypic genera Verconia and Diversidoris are nested within clades. Based on data shown here, there are three individual species and five clades limited to the eastern Pacific and Atlantic Oceans (or just one of these ocean regions), while the majority of chromodorid clades and species are strictly Indo-Pacific in distribution. We present a new classification of the chromodorid nudibranchs. We use molecular data to untangle evolutionary relationships and retain a historical connection to traditional systematics by using generic names attached to type species as clade names

Search for sterile neutrino mixing in the MINOS long-baseline experiment

A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18×1020 protons on target in which neutrinos of energies between ~500¿¿MeV and 120 GeV are produced predominantly as ¿µ, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ¿µ flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles ¿24 and ¿34 are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime t3/m3>2.1×10-12¿¿s/eV at 90% C.L

Post-match recovery in soccer with far-infrared emitting ceramic material or cold-water immersion

We investigated the effects of two common recovery methods; far-infrared emitting ceramic materials (Bioceramic) or cold-water immersion on muscular function and damage after a soccer match. Twenty-five university-level soccer players were randomized into Bioceramic (BIO; n = 8), Cold-water immersion (CWI; n = 9), or Control (CON; n = 8) groups. Heart rate [HR], rating of perceived exertion [RPE], and activity profile through Global Positioning Satellite Systems were measured during the match. Biochemical (thiobarbituric acid reactive species [TBARS], superoxide dismutase [SOD], creatine kinase [CK], lactate dehydrogenase [LDH]), neuromuscular (countermovement [CMJ] and squat jump [SJ], sprints [20-m]), and perceptual markers (delayed-onset muscle soreness [DOMS], and the perceived recovery scale [PRS]) were assessed at pre, post, 24 h, and 48 h postmatch. One-way ANOVA was used to compare anthropometric and match performance data. A two-way ANOVA with post-hoc tests compared the timeline of recovery measures. No significant differences existed between groups for anthropometric or match load measures (P > 0.05). Significant post-match increases were observed in SOD, and decreases in TBARS in all groups (p 0.05). Significant increases in CK, LDH, quadriceps and hamstring DOMS (p 0.05). Despite the expected post-match muscle damage and impaired performance, neither Bioceramic nor CWI interventions improved post-match recovery