The future burden of lung cancer attributable to current modifiable behaviours: a pooled study of seven Australian cohorts

BACKGROUND: Knowledge of preventable disease and differences in disease burden can inform public health action to improve health and health equity. We quantified the future lung cancer burden preventable by behavioural modifications across Australia. METHODS: We pooled seven Australian cohort studies (n = 367 058) and linked them to national registries to identify lung cancers and deaths. We estimated population attributable fractions and their 95% confidence intervals (CIs) for modifiable risk factors, using risk estimates from the cohort data and risk factor exposure distribution from contemporary national health surveys. RESULTS: During the first 10-year follow-up, there were 2025 incident lung cancers and 20 349 deaths. Stopping current smoking could prevent 53.7% (95% CI, 50.0-57.2%) of lung cancers over 40 years and 18.3% (11.0-25.1%) in 10 years. The smoking-attributable burden is highest in males, those who smoke <20 cigarettes per day, are <75 years of age, unmarried, of lower educational attainment, live in remote areas or are healthy weight. Increasing physical activity and fruit consumption, if causal, could prevent 15.6% (6.9-23.4%) and 7.5% (1.3-13.3%) of the lung cancer burden, respectively. Jointly, the three behaviour modifications could prevent up to 63.0% (58.0-67.5%) of lung cancers in 40 years, and 31.2% (20.9-40.1%) or 43 300 cancers in 10 years. The preventable burden is highest among those with multiple risk factors. CONCLUSIONS: Smoking remains responsible for the highest burden of lung cancer in Australia. The uneven burden distribution distinguishes subgroups that could benefit the most from activities to control the world's deadliest cancer

Mortality from cutaneous melanoma: evidence for contrasting trends between populations

In recent years several reports have been published concerning trends in melanoma mortality in different countries, some of which have indicated that rates are beginning to fall. Many of these reports, however, have been based on small populations and have used different forms of statistical analysis. Our objective was to analyse systematically to what degree the epidemic of melanoma mortality had evolved similarly in different populations and whether there were any divergent trends that might increase our understanding. Instead of using all available data, we focused on countries with a minimum time series of 30 years and a minimum of 100 deaths annually in at least one sex from melanoma. We first inspected sex-specific age-standardized mortality rates and then performed age-period-cohort modelling. We found that the increase in mortality observed after 1950 was more pronounced in the age group 60–79. Statistical modelling showed a general increase in mortality rates in generations born after the turn of the century. Downturns in mortality, essentially in women and starting with generations born just before World War II, were found in Australia (where the earliest decreases were noted), the Nordic countries and the USA. Small decreases in rates in more recent generations were found in the UK and Canada. However, in France, Italy and Czechoslovakia, mortality rates were seen to be still increasing in recent cohorts. Our analysis suggests that populations are at different places on the melanoma mortality epidemic curve. The three trend patterns we observed are in agreement with time differences between populations with respect to the promotion of sun protection and the surveillance of pigmented skin lesions. © 2000 Cancer Research Campaig

A symmoriiform chondrichthyan braincase and the origin of chimaeroid fishes

Chimaeroid fishes (Holocephali) are one of the four principal divisions of modern gnathostomes (jawed vertebrates). Despite only 47 described living species1, chimaeroids are the focus of resurgent interest as potential archives of genomic data2 and for the unique perspective they provide on chondrichthyan and gnathostome ancestral conditions. Chimaeroids are also noteworthy for their highly derived body plan1,3,4. However, like other living groups with distinctive anatomies5, fossils have been of limited use in unravelling their evolutionary origin, as the earliest recognized examples already exhibit many of the specializations present in modern forms6,7. Here we report the results of a computed tomography analysis of Dwykaselachus, an enigmatic chondrichthyan braincase from the ~280 million year old Karoo sediments of South Africa8. Externally, the braincase is that of a symmoriid shark9,10,11,12,13and is by far the most complete uncrushed example yet discovered. Internally, the morphology exhibits otherwise characteristically chimaeroid specializations, including the otic labyrinth arrangement and the brain space configuration relative to exceptionally large orbits. These results have important implications for our view of modern chondrichthyan origins, add robust structure to the phylogeny of early crown group gnathostomes, reveal preconditions that suggest an initial morpho-functional basis for the derived chimaeroid cranium, and shed new light on the chondrichthyan response to the extinction at the end of the Devonian period

Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation

Distinct prion strains often exhibit different incubation periods and patterns of neuropathological lesions. Strain characteristics are generally retained upon intraspecies transmission, but may change on transmission to another species. We investigated the inactivation of two related prions strains: BSE prions from cattle and mouse-passaged BSE prions, termed 301V. Inactivation was manipulated by exposure to sodium dodecyl sulfate (SDS), variations in pH, and different temperatures. Infectivity was measured using transgenic mouse lines that are highly susceptible to either BSE or 301V prions. Bioassays demonstrated that BSE prions are up to 1,000-fold more resistant to inactivation than 301V prions while Western immunoblotting showed that short acidic SDS treatments reduced protease-resistant PrPSc from BSE prions and 301V prions at similar rates. Our findings argue that despite being derived from BSE prions, mouse 301V prions are not necessarily a reliable model for cattle BSE prions. Extending these comparisons to human sporadic Creutzfeldt-Jakob disease and hamster Sc237 prions, we found that BSE prions were 10- and 106-fold more resistant to inactivation, respectively. Our studies contend that any prion inactivation procedures must be validated by bioassay against the prion strain for which they are intended to be used

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission.

Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.This work was supported by the Wellcome Trust Senior Research Fellowships 108070/Z/15/Z to MPW, 215515/Z/19/Z to SGB and 207498/Z/17/Z to IGG; Collaborative award 206298/B/17/Z to IGG; Principal Research Fellowship 210688/Z/18/Z to PJL; Investigator Award 200871/Z/16/Z to KGCS; Addenbrooke’s Charitable Trust (to MPW, SGB, IGG and PJL); the Medical Research Council (CSF MR/P008801/1 to NJM); NHS Blood and Transfusion (WPA15-02 to NJM); National Institute for Health Research (Cambridge Biomedical Research Centre at CUHNFT), to JRB, MET, AC and GD, Academy of Medical Sciences and the Health Foundation (Clinician Scientist Fellowship to MET), Engineering and Physical Sciences Research Council (EP/P031447/1 and EP/N031938/1 to RS),Cancer Research UK (PRECISION Grand Challenge C38317/A24043 award to JY). Components of this work were supported by the COVID-19 Genomics UK Consortium, (COG-UK), which is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institut

Social network types and functional dependency in older adults in Mexico

<p>Abstract</p> <p>Background</p> <p>Social networks play a key role in caring for older adults. A better understanding of the characteristics of different social networks types (TSNs) in a given community provides useful information for designing policies to care for this age group. Therefore this study has three objectives: 1) To derive the TSNs among older adults affiliated with the Mexican Institute of Social Security; 2) To describe the main characteristics of the older adults in each TSN, including the instrumental and economic support they receive and their satisfaction with the network; 3) To determine the association between functional dependency and the type of social network.</p> <p>Methods</p> <p>Secondary data analysis of the 2006 Survey of Autonomy and Dependency (N = 3,348). The TSNs were identified using the structural approach and cluster analysis. The association between functional dependency and the TSNs was evaluated with Poisson regression with robust variance analysis in which socio-demographic characteristics, lifestyle and medical history covariates were included.</p> <p>Results</p> <p>We identified five TSNs: diverse with community participation (12.1%), diverse without community participation (44.3%); widowed (32.0%); nonfriends-restricted (7.6%); nonfamily-restricted (4.0%). Older adults belonging to widowed and restricted networks showed a higher proportion of dependency, negative self-rated health and depression. Older adults with functional dependency more likely belonged to a widowed network (adjusted prevalence ratio 1.5; 95%CI: 1.1-2.1).</p> <p>Conclusion</p> <p>The derived TSNs were similar to those described in developed countries. However, we identified the existence of a diverse network without community participation and a widowed network that have not been previously described. These TSNs and restricted networks represent a potential unmet need of social security affiliates.</p

Influence of Calendar Period on the Association Between BMI and Coronary Heart Disease: A Meta-Analysis of 31 Cohorts

Objective: The association between obesity and coronary heart disease (CHD) may have changed over time, for example due to improved pharmacological treatment of CHD risk factors. This meta-analysis of 31 prospective cohort studies explores the influence of calendar period on CHD risk associated with body mass index (BMI). Design and Methods: The relative risks (RRs) of CHD for a five-BMI-unit increment and BMI categories were pooled by means of random effects models. Meta-regression analysis was used to examine the influence of calendar period (>1985 v 1985) in univariate and multivariate analyses (including mean population age as a covariate). Results: The age, sex, and smoking adjusted RR (95% confidence intervals) of CHD for a five-BMI-unit increment was 1.28(1.22:1.34). For underweight, overweight and obesity, the RRs (compared to normal weight) were 1.11(0.91:1.36), 1.31(1.22:1.41), and 1.78(1.55:2.04), respectively. The univariate analysis indicated 31% (95%CI: 56:0) lower RR of CHD associated with a five-BMI-unit increment and a 51% (95%CI: 78: 14)) lower RR associated with obesity in studies starting after 1985 (n ¼ 15 and 10, respectively) compared to studies starting in or before 1985 (n ¼ 16 and 10). However, in the multivariate analysis, only mean population age was independently associated with the RRs for a five-BMI-unit increment and obesity ( 29(95%CI: 55: 5)) and 31(95%CI: 66:3), respectively) per 10-year increment in mean age). Conclusion: This study provides no consistent evidence for a difference in the association between BMI and CHD by calendar period. The mean population age seems to be the most important factor that modifies the association between the risk of CHD and BMI, in which the RR decreases with increasing age

Preconceptional Folate Supplementation and the Risk of Spontaneous Preterm Birth: A Cohort Study

In an analysis of a cohort of pregnant women, Radek Bukowski and colleagues describe an association between taking folic acid supplements and a reduction in the risk of preterm birth

A Systematically Improved High Quality Genome and Transcriptome of the Human Blood Fluke Schistosoma mansoni

Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq) from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org) and SchistoDB (www.schistodb.net) databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research

An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital

Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients. Two retrospective reviews were performed. Over a 10-year period, 14 cases of PCP were identified: no cases were attributable to failed chemoprophylaxis, drug allergy or intolerance. During a 6-month period, 73 patients received high-dose corticosteroid therapy (⩾25 mg prednisolone or ⩾4 mg dexamethasone daily) for ⩾4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51 (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis compared to patients with haematologic malignancy (3.9 vs 63.6%, P<0.0001). Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or solid tumours who receive corticosteroid therapy are proposed. Successful primary prevention of PCP in this population will require a multifaceted approach targeting the suboptimal prescribing patterns for chemoprophylaxis