Lung cancer is a major health problem. CT lung screening can reduce lung cancer mortality through early diagnosis by at least 20%. Screening high-risk individuals is most effective. Retrospective ...analyses suggest that identifying individuals for screening by accurate prediction models is more efficient than using categorical age-smoking criteria, such as the US Preventive Services Task Force (USPSTF) criteria. This study prospectively compared the effectiveness of the USPSTF2013 and PLCOm2012 model eligibility criteria.
In this prospective cohort study, participants from the International Lung Screening Trial (ILST), aged 55–80 years, who were current or former smokers (ie, had ≥30 pack-years smoking history or ≤15 quit-years since last permanently quitting), and who met USPSTF2013 criteria or a PLCOm2012 risk threshold of at least 1·51% within 6 years of screening, were recruited from nine screening sites in Canada, Australia, Hong Kong, and the UK. After enrolment, patients were assessed with the USPSTF2013 criteria and the PLCOm2012 risk model with a threshold of at least 1·70% at 6 years. Data were collected locally and centralised. Main outcomes were the comparison of lung cancer detection rates and cumulative life expectancies in patients with lung cancer between USPSTF2013 criteria and the PLCOm2012 model. In this Article, we present data from an interim analysis. To estimate the incidence of lung cancers in individuals who were USPSTF2013-negative and had PLCOm2012 of less than 1·51% at 6 years, ever-smokers in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) who met these criteria and their lung cancer incidence were applied to the ILST sample size for the mean follow-up occurring in the ILST. This trial is registered at ClinicalTrials.gov, NCT02871856. Study enrolment is almost complete.
Between June 17, 2015, and Dec 29, 2020, 5819 participants from the International Lung Screening Trial (ILST) were enrolled on the basis of meeting USPSTF2013 criteria or the PLCOm2012 risk threshold of at least 1·51% at 6 years. The same number of individuals was selected for the PLCOm2012 model as for the USPSTF2013 criteria (4540 78% of 5819). After a mean follow-up of 2·3 years (SD 1·0), 135 lung cancers occurred in 4540 USPSTF2013-positive participants and 162 in 4540 participants included in the PLCOm2012 of at least 1·70% at 6 years group (cancer sensitivity difference 15·8%, 95% CI 10·7–22·1%; absolute odds ratio 4·00, 95% CI 1·89–9·44; p<0·0001). Compared to USPSTF2013-positive individuals, PLCOm2012-selected participants were older (mean age 65·7 years SD 5·9 vs 63·3 years 5·7; p<0·0001), had more comorbidities (median 2 IQR 1–3 vs 1 1–2; p<0·0001), and shorter life expectancy (13·9 years 95% CI 12·8–14·9 vs 14·8 13·6–16·0 years). Model-based difference in cumulative life expectancies for those diagnosed with lung cancer were higher in those who had PLCOm2012 risk of at least 1·70% at 6 years than individuals who were USPSTF2013-positive (2248·6 years 95% CI 2089·6–2425·9 vs 2000·7 years 1841·2–2160·3; difference 247·9 years, p=0·015).
PLCOm2012 appears to be more efficient than the USPSTF2013 criteria for selecting individuals to enrol into lung cancer screening programmes and should be used for identifying high-risk individuals who benefit from the inclusion in these programmes.
Terry Fox Research Institute, The UBC-VGH Hospital Foundation and the BC Cancer Foundation, the Alberta Cancer Foundation, the Australian National Health and Medical Research Council, Cancer Research UK and a consortium of funders, and the Roy Castle Lung Cancer Foundation for the UK Lung Screen Uptake Trial.
Background: Lung cancer is a substantial public health problem in western countries. Previous studies have examined different screening strategies for lung cancer but there have been no published ...systematic reviews. Methods: A systematic review of controlled trials was conducted to determine whether screening for lung cancer using regular sputum examinations or chest radiography or computed tomography (CT) reduces lung cancer mortality. The primary outcome was lung cancer mortality; secondary outcomes were lung cancer survival and all cause mortality. Results: One non-randomised controlled trial and six randomised controlled trials with a total of 245 610 subjects were included in the review. In all studies the control group received some type of screening. More frequent screening with chest radiography was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, 95% CI 1.00 to 1.23). A non-statistically significant trend to reduced mortality from lung cancer was observed when screening with chest radiography and sputum cytological examination was compared with chest radiography alone (RR 0.88, 95% CI 0.74 to 1.03). Several of the included studies had potential methodological weaknesses. Controlled studies of spiral CT scanning have not been reported. Conclusions: The current evidence does not support screening for lung cancer with chest radiography or sputum cytological examination. Frequent chest radiography might be harmful. Further methodologically rigorous trials are required before any new screening methods are introduced into clinical practice.
ABSTRACT There is an overwhelming evidence that white dwarfs host planetary systems; revealed by the presence, disruption, and accretion of planetary bodies. A lower limit on the frequency of white ...dwarfs that host planetary material has been estimated to be ≃ 25–50 per cent; inferred from the ongoing or recent accretion of metals on to both hydrogen-atmosphere and warm helium-atmosphere white dwarfs. Now with the unbiased sample of white dwarfs observed by the Dark Energy Spectroscopic Instrument (DESI) survey in their Early Data Release (EDR), we have determined the frequency of metal enrichment around cool-helium atmosphere white dwarfs as 21 ± 3 per cent using a sample of 234 systems. This value is in good agreement with values determined from previous studies. With the current samples we cannot distinguish whether the frequency of planetary accretion varies with system age or host-star mass, but the DESI data release 1 will contain roughly an order of magnitude more white dwarfs than DESI EDR and will allow these parameters to be investigated.
In many cooperatively breeding mammals, an unrelated dominant pair monopolizes reproduction in the social group while subordinates help to raise their offspring. In Kalahari meerkats (Suricata ...suricatta), dominant males are usually immigrants while dominant females are natal animals that have not left the group where they were born. However, in around 20% of cases, a natal male acquires and holds the dominant position – despite being closely related to the dominant female. Natal dominant males seldom mate within their group (either with the dominant female or with subordinate females) and the benefits they accrue from acquiring and maintaining the dominant position are not obvious. Here, we describe the circumstances in which natal males acquire dominance and explore the possible benefits they gain by comparing the life history, growth and behavioural differences between natal dominants, natal subordinates and immigrant dominants in wild groups. We show that natal dominant males do not appear to obtain any survival, nutritional or reproductive benefits from their status while they remain in the natal group. However, after dispersing from their natal group, they have a higher chance of acquiring dominant status in another breeding group, suggesting that acquiring dominance in their natal group has deferred direct fitness benefits for male meerkats.
Socially dominant individuals in cooperative breeders monopolize reproduction – but the position may hold alternate benefits which are less well understood. Here, we show that the existence of natal dominant males in meerkat groups may be explained by long‐term benefits: natal male dominants are usually closely related to group females and do not benefit directly from the position, but have improved chances of taking dominant breeding positions elsewhere when they emigrate from their natal group.
Nitric oxide (NO) is a free radical that functions as a cell signaling molecule but at high concentrations can be toxic. It
is formed from arginine, which is consumed by the mouse blastocyst, but its ...effect on early embryo development has been little
studied. In this study, the role of NO in mouse preimplantation development has been examined in terms of developmental rate
and oxidative metabolism. Zygotes were cultured in one of four media; potassium simplex optimization medium (KSOM), KSOM with
amino acids (KSOMaa), KSOM without glutamine (KSOM-glut), or KSOM with 0.5 mM arginine (KSOMarg) ± l -NAME (a specific inhibitor of NO production). End points were Day 4 blastocyst rates, cell counts determined using bis benzimide and oxygen consumption. In KSOM and KSOM-glut, the blastocyst rate was decreased by 1 mM l -NAME from 50.2% ± 3.1% and 37.4% ± 4.5% to 6% ± 3% and 0%, respectively. In KSOMaa, cavitation rates were unaltered but the
blastocysts contained fewer cells ( P < 0.001). Blastocysts cultured in KSOM and KSOM-glut consumed significantly more oxygen than those cultured in KSOMaa ( P < 0.001 and P < 0.05, respectively). However, the addition of 0.1 mM or 1 mM l -NAME to KSOMaa significantly increased the amount of oxygen consumed ( P < 0.05 and P < 0.001, respectively). The data suggest a physiological role for NO in mouse preimplantation metabolism and development.
One possibility is that NO may limit oxygen consumption at the blastocyst stage at the level of mitochondrial cytochrome c
oxidase.
White dwarfs with emission lines from gaseous debris discs are among the rarest examples of planetary remnant hosts, but at the same time they are key objects for studying the final evolutionary ...stage of planetary systems. Making use of the large number of white dwarfs identified in Gaia DR2, we are conducting a survey of planetary remnants and here we present the first results of our search: six white dwarfs with gaseous debris discs. This first publication focuses on the main observational properties of these objects and highlights their most unique features. Three systems in particular stand out: WDJ084602.47+570328.64 displays an exceptionally strong infrared excess which defies the standard model of a geometrically-thin, optically-thick dusty debris disc; WDJ213350.72+242805.93 is the hottest gaseous debris disc host known with Teff=29282 K; and WDJ052914.32-340108.11, in which we identify a record number of 51 emission lines from five elements. These discoveries shed light on the underlying diversity in gaseous debris disc systems and bring the total number of these objects to 21. With these numbers we can now start looking at the properties of these systems as a class of objects rather than on a case-by-case basis.
Leishmaniasis is endemic in southern Europe, and in other European countries cases are diagnosed in travellers who have visited affected areas both within the continent and beyond. Prompt and ...accurate diagnosis poses a challenge in clinical practice in Europe. Different methods exist for identification of the infecting Leishmania species. Sixteen clinical laboratories in 10 European countries, plus Israel and Turkey, conducted a study to assess their genotyping performance. DNA from 21 promastigote cultures of 13 species was analysed blindly by the routinely used typing method. Five different molecular targets were used, which were analysed with PCR-based methods. Different levels of identification were achieved, and either the Leishmania subgenus, species complex, or actual species were reported. The overall error rate of strains placed in the wrong complex or species was 8.5%. Various reasons for incorrect typing were identified. The study shows there is considerable room for improvement and standardisation of Leishmania typing. The use of well validated standard operating procedures is recommended, covering testing, interpretation, and reporting guidelines. Application of the internal transcribed spacer 1 of the rDNA array should be restricted to Old World samples, while the heat-shock protein 70 gene and the mini-exon can be applied globally.
PDF
