Emergency presentation of cancer and short-term mortality

Background:The short-term survival following a cancer diagnosis in England is lower than that in comparable countries, with the difference in excess mortality primarily occurring in the months immediately after diagnosis. We assess the impact of emergency presentation (EP) on the excess mortality in England over the course of the year following diagnosis. Methods:All colorectal and cervical cancers presenting in England and all breast, lung, and prostate cancers in the East of England in 2006-2008 are included. The variation in the likelihood of EP with age, stage, sex, co-morbidity, and income deprivation is modelled. The excess mortality over 0-1, 1-3, 3-6, and 6-12 months after diagnosis and its dependence on these case-mix factors and presentation route is then examined. Results:More advanced stage and older age are predictive of EP, as to a lesser extent are co-morbidity, higher income deprivation, and female sex. In the first month after diagnosis, we observe case-mix-adjusted excess mortality rate ratios of 7.5 (cervical), 5.9 (colorectal), 11.7 (breast ), 4.0 (lung), and 20.8 (prostate) for EP compared with non-EP. Conclusion:Individuals who present as an emergency experience high short-term mortality in all cancer types examined compared with non-EPs. This is partly a case-mix effect but EP remains predictive of short-term mortality even when age, stage, and co-morbidity are accounted for

The Open AUC Project

Progress in analytical ultracentrifugation (AUC) has been hindered by obstructions to hardware innovation and by software incompatibility. In this paper, we announce and outline the Open AUC Project. The goals of the Open AUC Project are to stimulate AUC innovation by improving instrumentation, detectors, acquisition and analysis software, and collaborative tools. These improvements are needed for the next generation of AUC-based research. The Open AUC Project combines on-going work from several different groups. A new base instrument is described, one that is designed from the ground up to be an analytical ultracentrifuge. This machine offers an open architecture, hardware standards, and application programming interfaces for detector developers. All software will use the GNU Public License to assure that intellectual property is available in open source format. The Open AUC strategy facilitates collaborations, encourages sharing, and eliminates the chronic impediments that have plagued AUC innovation for the last 20 years. This ultracentrifuge will be equipped with multiple and interchangeable optical tracks so that state-of-the-art electronics and improved detectors will be available for a variety of optical systems. The instrument will be complemented by a new rotor, enhanced data acquisition and analysis software, as well as collaboration software. Described here are the instrument, the modular software components, and a standardized database that will encourage and ease integration of data analysis and interpretation software

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36

DNA repair, genome stability and cancer: a historical perspective

The multistep process of cancer progresses over many years. The prevention of mutations by DNA repair pathways led to an early appreciation of a role for repair in cancer avoidance. However, the broader role of the DNA damage response (DDR) emerged more slowly. In this Timeline article, we reflect on how our understanding of the steps leading to cancer developed, focusing on the role of the DDR. We also consider how our current knowledge can be exploited for cancer therapy

Resource use and direct medical costs of acute respiratory illness in the UK based on linked primary and secondary care records from 2001 to 2009

BackgroundPrevious studies have shown that influenza is associated with a substantial healthcare burden in the United Kingdom (UK), but more studies are needed to evaluate the resource use and direct medical costs of influenza in primary care and secondary care.MethodsA retrospective observational database study in the UK to describe the primary care and directly-associated secondary care resource use, and direct medical costs of acute respiratory illness (ARI), according to age, and risk status (NCT Number: 01521416). Patients with influenza, ARI or influenza-related respiratory infections during 9 consecutive pre-pandemic influenza peak seasons were identified by READ codes in the linked Clinical Practice Research Datalink (CPRD) and Hospital Episodes Statistics (HES) dataset. The study period was from 21st January 2001 to 31st March 2009.ResultsA total of 156,193 patients had ≥1 general practitioner (GP) episode of ARI, and a total of 82,204 patients received ≥1 GP prescription, at a mean of 2.5 (standard deviation [SD]: 3.0) prescriptions per patient. The total cost of GP consultations and prescriptions equated to £462,827 per year per 100,000 patients. The yearly cost of prescribed medication for ARI was £319,732, at an estimated cost of £11,596,350 per year extrapolated to the UK, with 40% attributable to antibiotics. The mean cost of hospital admissions equated to a yearly cost of £981,808 per 100,000 patients. The total mean direct medical cost of ARI over 9 influenza seasons was £21,343,445 (SD: £10,441,364), at £136.65 (SD: £66.85) per case.ConclusionsExtrapolating to the UK population, for pre-pandemic influenza seasons from 2001 to 2009, the direct medical cost of ARI equated to £86 million each year. More studies are needed to assess the costs of influenza disease to help guide public health decision-making for seasonal influenza in the UK

Molecular Variation at the SLC6A3 Locus Predicts Lifetime Risk of PTSD in the Detroit Neighborhood Health Study

Recent work suggests that the 9-repeat (9R) allele located in the 3′UTR VNTR of the SLC6A3 gene increases risk of posttraumatic stress disorder (PTSD). However, no study reporting this association to date has been based on population-based samples. Furthermore, no study of which we are aware has assessed the joint action of genetic and DNA methylation variation at SLC6A3 on risk of PTSD. In this study, we assessed whether molecular variation at SLC6A3 locus influences risk of PTSD. Participants (n = 320; 62 cases/258 controls) were drawn from an urban, community-based sample of predominantly African American Detroit adult residents, and included those who had completed a baseline telephone survey, had provided blood specimens, and had a homozygous genotype for either the 9R or 10R allele or a heterozygous 9R/10R genotype. The influence of DNA methylation variation in the SLC6A3 promoter locus was also assessed in a subset of participants with available methylation data (n = 83; 16 cases/67 controls). In the full analytic sample, 9R allele carriers had almost double the risk of lifetime PTSD compared to 10R/10R genotype carriers (OR = 1.98, 95% CI = 1.02–3.86), controlling for age, sex, race, socioeconomic status, number of traumas, smoking, and lifetime depression. In the subsample of participants with available methylation data, a significant (p = 0.008) interaction was observed whereby 9R allele carriers showed an increased risk of lifetime PTSD only in conjunction with high methylation in the SLC6A3 promoter locus, controlling for the same covariates. Our results confirm previous reports supporting a role for the 9R allele in increasing susceptibility to PTSD. They further extend these findings by providing preliminary evidence that a “double hit” model, including both a putatively reduced-function allele and high methylation in the promoter region, may more accurately capture molecular risk of PTSD at the SLC6A3 locus

Increased Litterfall in Tropical Forests Boosts the Transfer of Soil CO2 to the Atmosphere

Aboveground litter production in forests is likely to increase as a consequence of elevated atmospheric carbon dioxide (CO2) concentrations, rising temperatures, and shifting rainfall patterns. As litterfall represents a major flux of carbon from vegetation to soil, changes in litter inputs are likely to have wide-reaching consequences for soil carbon dynamics. Such disturbances to the carbon balance may be particularly important in the tropics because tropical forests store almost 30% of the global soil carbon, making them a critical component of the global carbon cycle; nevertheless, the effects of increasing aboveground litter production on belowground carbon dynamics are poorly understood. We used long-term, large-scale monthly litter removal and addition treatments in a lowland tropical forest to assess the consequences of increased litterfall on belowground CO2 production. Over the second to the fifth year of treatments, litter addition increased soil respiration more than litter removal decreased it; soil respiration was on average 20% lower in the litter removal and 43% higher in the litter addition treatment compared to the controls but litter addition did not change microbial biomass. We predicted a 9% increase in soil respiration in the litter addition plots, based on the 20% decrease in the litter removal plots and an 11% reduction due to lower fine root biomass in the litter addition plots. The 43% measured increase in soil respiration was therefore 34% higher than predicted and it is possible that this ‘extra’ CO2 was a result of priming effects, i.e. stimulation of the decomposition of older soil organic matter by the addition of fresh organic matter. Our results show that increases in aboveground litter production as a result of global change have the potential to cause considerable losses of soil carbon to the atmosphere in tropical forests

The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and ‘hard-to-reach’ patients

Background Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. Methods/design A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60–75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led ‘lung health check’ hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. Discussion If effective at improving informed uptake of screening and reducing bias in participation, this invitation strategy could be adopted by local screening pilots or a national programme. Trial registration This study was registered with the ISRCTN (International Standard Registered Clinical/soCial sTudy Number : ISRCTN21774741) on the 23rd September 2015 and the NIH ClinicalTrials.gov database (NCT0255810) on the 22nd September 2015

Light and Heavy Fractions of Soil Organic Matter in Response to Climate Warming and Increased Precipitation in a Temperate Steppe

Soil is one of the most important carbon (C) and nitrogen (N) pools and plays a crucial role in ecosystem C and N cycling. Climate change profoundly affects soil C and N storage via changing C and N inputs and outputs. However, the influences of climate warming and changing precipitation regime on labile and recalcitrant fractions of soil organic C and N remain unclear. Here, we investigated soil labile and recalcitrant C and N under 6 years' treatments of experimental warming and increased precipitation in a temperate steppe in Northern China. We measured soil light fraction C (LFC) and N (LFN), microbial biomass C (MBC) and N (MBN), dissolved organic C (DOC) and heavy fraction C (HFC) and N (HFN). The results showed that increased precipitation significantly stimulated soil LFC and LFN by 16.1% and 18.5%, respectively, and increased LFC∶HFC ratio and LFN∶HFN ratio, suggesting that increased precipitation transferred more soil organic carbon into the quick-decayed carbon pool. Experimental warming reduced soil labile C (LFC, MBC, and DOC). In contrast, soil heavy fraction C and N, and total C and N were not significantly impacted by increased precipitation or warming. Soil labile C significantly correlated with gross ecosystem productivity, ecosystem respiration and soil respiration, but not with soil moisture and temperature, suggesting that biotic processes rather than abiotic factors determine variations in soil labile C. Our results indicate that certain soil carbon fraction is sensitive to climate change in the temperate steppe, which may in turn impact ecosystem carbon fluxes in response and feedback to climate change

Several Distinct Polycomb Complexes Regulate and Co-Localize on the INK4a Tumor Suppressor Locus

Misexpression of Polycomb repressive complex 1 (PRC1) components in human cells profoundly influences the onset of cellular senescence by modulating transcription of the INK4a tumor suppressor gene. Using tandem affinity purification, we find that CBX7 and CBX8, two Polycomb (Pc) homologs that repress INK4a, both participate in PRC1-like complexes with at least two Posterior sex combs (Psc) proteins, MEL18 and BMI1. Each complex contains a single representative of the Pc and Psc families. In primary human fibroblasts, CBX7, CBX8, MEL18 and BMI1 are present at the INK4a locus and shRNA-mediated knockdown of any one of these components results in de-repression of INK4a and proliferative arrest. Sequential chromatin immunoprecipitation (ChIP) reveals that CBX7 and CBX8 bind simultaneously to the same region of chromatin and knockdown of one of the Pc or Psc proteins results in release of the other, suggesting that the binding of PRC1 complexes is interdependent. Our findings provide the first evidence that a single gene can be regulated by several distinct PRC1 complexes and raise important questions about their configuration and relative functions