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The Lancet COVID-19 Commission Task Force for Public Health Measures to Suppress the Pandemic was launched to identify critical points for consideration by governments on public health interventions to control coronavirus disease 2019 (COVID-19). Drawing on our review of published studies of data analytics and modelling, evidence synthesis and contextualisation, and behavioural science evidence and theory on public health interventions from a range of sources, we outline evidence for a range of institutional measures and behaviour-change measures. We cite examples of measures adopted by a range of countries, but especially jurisdictions that have, thus far, achieved low numbers of COVID-19 deaths and limited community transmission of severe acute respiratory syndrome coronavirus 2. Finally, we highlight gaps in knowledge where research should be undertaken. As countries consider long-term measures, there is an opportunity to learn, improve the response and prepare for future pandemics. [ABSTRACT FROM AUTHOR]

Transcripts originating from the transcriptional read through of two adjacent, similarly oriented genes have been identified in normal and neoplastic tissues, but their functional role and the mechanisms that regulate their expression are mostly unknown. Here, we investigated whether the expression of read-through transcripts previously identified in the non-involved lung tissue of lung adenocarcinoma patients was genetically regulated. Data on genome-wide single nucleotide variant genotypes and expression levels of 10 read-through transcripts in 201 samples of lung tissue were combined to identify expression quantitative trait loci (eQTLs). Then, to identify genes whose expression levels correlated with the 10 read-through transcripts, we used whole transcriptome profiles available for 154 patients. For 8 read-though transcripts, we identified 60 eQTLs (false discovery rate <0.05), including 17 cis -eQTLs and 43 trans -eQTLs. These eQTLs did not maintain their behavior on the 'parental' genes involved in the read-through transcriptional event. The expression levels of 7 read-through transcripts were found to correlate with the expression of other genes: CHIA–PIFO and CTSC–RAB38 correlated with CHIA and RAB38 , respectively, while 5 other read-through transcripts correlated with 43 unique non-parental transcripts; thus offering indications about the molecular processes in which these chimeric transcripts may be involved. We confirmed 9 eQTLs (for 4 transcripts) in the non-involved lung tissue from an independent series of 188 lung adenocarcinoma patients. Therefore, this study indicates that the expression of four read-through transcripts in normal lung tissue is under germline genetic regulation, and that this regulation is independent of that of the genes involved in the read-through event. [ABSTRACT FROM AUTHOR]

Asbestos exposure is the main etiology of malignant mesothelioma, but there are conflicting data on whether the intensity of exposure modulates the development of this disease. This study considered 594 patients with malignant mesothelioma for whom count data on asbestos bodies and fibers (per gram of wet lung tissue) were available. The relationships between age at diagnosis (a time-to-event outcome variable) and these two measures of internal asbestos exposure, along with other possible modulating factors (sex, tumor location, histological subtype and childhood exposure), were assessed on multivariable Cox proportional hazard models, stratifying by decade of birth year. For both measures of asbestos in lung tissue, younger age at diagnosis was associated with higher internal measures of exposure to asbestos. Stratified Cox analyses showed that for each doubling in asbestos body count patients were 1.07 times more likely to be diagnosed at a younger age [hazard ratio (HR) = 1.07; 95% confidence interval (CI), 1.04–1.09; P = 2.2 × 10−7] and for each doubling in asbestos fiber count patients were 1.13 times more likely to be diagnosed at a younger age (HR = 1.13; 95% CI, 1.09–1.17; P = 8.6 × 10−11). None of the other variables considered were associated with age at diagnosis. Our finding that tumors become clinically apparent at a younger age in heavily exposed subjects suggests that asbestos is involved not only in the malignant mesothelioma tumor initiation but, somehow, also in the progression of the disease. [ABSTRACT FROM AUTHOR]

Chromosomal locus 15q25, implicated in lung cancer risk and nicotine dependence, shows extensive linkage disequilibrium that complicates identification of causal variation. Cholinergic receptor nicotinic α5 (CHRNA5) has been identified as a lung cancer risk factor. We identified by sequence analysis three haplotypes (delTTC, insATC, and insTGG) in the 5′ promoter region and three at the 3′-untranslated region of CHRNA5. Linkage disequilibrium analysis of the 5′ variants showed that the insTGG haplotype is associated with three tightly linked risk alleles (nicotine dependence, lung cancer, and chronic obstructive pulmonary disease). The three CHRNA5 promoter haplotypes were statistically significantly associated with lung CHRNA5 transcript levels, determined by real-time polymerase chain reaction. In nontumor lung parenchyma from 68 patients who underwent lung lobectomy, the delTTC haplotype was associated with the highest CHRNA5 transcript levels (relative quantification units = 1.82), whereas the insTGG haplotype was associated with the lowest (0.88 units, Pdiff < .001, Welch t test; all statistical tests were two-sided). Luciferase reporter assays in human lung cancer cell lines A549, H460, H520, and H596 also showed that the 5′ region haplotypes were statistically significantly associated with changes in CHRNA5 promoter activity, whereas the 3′-untranslated region variants were not. [ABSTRACT FROM PUBLISHER]