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.
Arbuscular mycorrhizal (AM) fungi associate with the roots of many plant species, enhancing their hosts access to soil nutrients whilst obtaining their carbon supply directly as photosynthates. AM ...fungi often face competition for plant carbon from other organisms. The mechanisms by which plants prioritise carbon allocation to mutualistic AM fungi over parasitic symbionts remain poorly understood. Here, we show that host potato plants (Solanum tuberosum cv. Désirée) selectively allocate carbon resources to tissues interacting with AM fungi rather than those interacting with phytophagous parasites (the nematode Globodera pallida). We found that plants reduce the supply of hexoses but maintain the flow of plant-derived fatty acids to AM fungi when concurrently interacting with parasites. Transcriptomic analysis suggest that plants prioritise carbon transfer to AM fungi by maintaining expression of fatty acid biosynthesis and transportation pathways, whilst decreasing the expression of mycorrhizal-induced hexose transporters. We also report similar findings from a different plant host species (Medicago truncatula) and phytophagous pest (the aphid Myzus persicae). These findings suggest a general mechanism of plant-driven resource allocation in scenarios involving multiple symbionts.
Summary Background While the size and clinical appearance are known risk factors for malignant transformation of potentially malignant oral the importance of site, grade of dysplasia and exposure to ...environmental carcinogens remains controversial. We aim to report the clinical determinants of malignant progression in a series of patients with histopathologically graded oral epithelial dysplasia (OED). Methods We recruited patients with a histopathological diagnosis of OED to a longitudinal observational study in a tertiary oral dysplasia clinic. Clinical, histopathological and risk factor data were recorded at baseline. One of three clinical endpoints were determined: malignant transformation, progression of dysplasia grade, remission/stable dysplasia grade. Results Ninety-one patients meeting the criteria gave consent for inclusion to the cohort, with outcomes reported after a median follow up of 48 months. An estimated 22% (SE 6%) of patients underwent malignant transformation within 5 years, with significant predictors being: non-smoking status ( χ2 = 15.1, p = 0.001), site ( χ2 = 15.3, p = 0.002), non-homogeneous appearance ( χ2 = 8.2, p = 0.004), size of lesion >200 mm2 ( χ2 = 4.7, p = 0.03) and, of borderline significance, high grade ( χ2 = 5.8, p = 0.06). Gender, age, number of lesions and alcohol history did not predict for malignant transformation. Conclusions Although a number of these clinical determinants have previously been associated with higher malignant transformation in OED, the high-risk nature of lesions in non-smokers is of particular note and requires a greater emphasis and recognition amongst clinicians dealing with OED. It suggests that those non-smokers with OED, have an inherited or acquired predisposition and should be treated more aggressively; these should form the focus for further investigation.
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.
Using a model-based approach, we estimated the probability that an individual, with a specified combination of risk factors, would develop lung cancer within a 5-year period. Data from 579 lung ...cancer cases and 1157 age- and sex-matched population-based controls were available for this analysis. Significant risk factors were fitted into multivariate conditional logistic regression models. The final multivariate model was combined with age-standardised lung cancer incidence data to calculate absolute risk estimates. Combinations of lifestyle risk factors were modelled to create risk profiles. For example, a 77-year-old male non-smoker, with a family history of lung cancer (early onset) and occupational exposure to asbestos has an absolute risk of 3.17% (95% CI, 1.67-5.95). Choosing a 2.5% cutoff to trigger increased surveillance, gave a sensitivity of 0.62 and specificity of 0.70, while a 6.0% cutoff gave a sensitivity of 0.34 and specificity of 0.90. A 10-fold cross validation produced an AUC statistic of 0.70, indicating good discrimination.If independent validation studies confirm these results, the LLP risk models' application as the first stage in an early detection strategy is a logical evolution in patient care.
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.
Bioenergy with carbon capture and storage (BECCS) is a negative emissions technology that is a largely untested but prominent feature of ambitious climate change mitigation scenarios. This strategy ...involves capturing carbon dioxide (CO
2
) from stationary bioenergy facilities and sequestering it in suitable geological formations, effectively removing CO
2
from the atmosphere. Many factors potentially limit BECCS deployment including obstacles to building pipeline networks that move large quantities of liquefied CO
2
over long distances. Here, we examine the BECCS opportunity that exists in regions overlapping storage basins. Under current conditions, the equivalent of 22.9 GtCO
2
y
−1
of net primary production (NPP), a measure of biomass growth, overlies highly prospective CO
2
storage basins, representing a sustainably harvestable total of approximately 7.6 GtCO
2
y
−1
. Most land overlying basins is either forested or linked to food production. If only marginal agricultural lands, those inconsistently under agricultural production, are used to source biomass, the scale of the available resource is approximately 1 GtCO
2
y
−1
. If transportation of biomass or CO
2
is constrained, and if BECCS is not developed on forests or prime croplands, then BECCS deployments will be limited to a small, but meaningful fraction (~10%) of the levels typical in cost-optimized model trajectories that stabilize warming at 2 °C or less above pre-industrial temperatures. Marginal agricultural lands over storage basins can be an entry point for maturing the engineering technologies and financial markets needed for BECCS.
Histologic grading of intracranial astrocytomas is affected by sampling error and substantial inter- and intraobserver variability. We proposed that incorporating MR imaging into grading will predict ...patient survival more accurately than histopathology alone.
Patients with a new diagnosis of World Health Organization grades II-IV astrocytoma or mixed oligoastrocytoma diagnosed between September 2007 and December 2010 were identified. Two hundred forty-five patients met the inclusion criteria. Preoperative MRIs were independently reviewed by 2 readers blinded to the histologic grade, and an MR imaging grade was given. The MR imaging and histopathologic grades were compared with patient survival.
Patients with grade II or III astrocytomas on histology but evidence of necrosis on MR imaging (consistent with a grade IV tumor) had significantly worse survival than patients with the same histology but no evidence of necrosis on MR imaging (P = .002 for grade II histology and P = .029 for grade III). Their survival was not significantly different from that in patients with grade IV tumors on histology (P = .164 and P = .385, respectively); this outcome suggests that all or most are likely to have truly been grade IV tumors. MR imaging evidence of necrosis was less frequent in grade II and III oligoastrocytomas, preventing adequate subgroup analysis.
MR imaging can improve grading of intracranial astrocytomas by identifying patients suspected of being undergraded by histology, with high interobserver agreement. This finding has the potential to optimize patient management, for example, by encouraging more aggressive treatment earlier in the patient's course.
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