The potential impact of climate change on Australia's soil organic carbon resources

BACKGROUND: Soil organic carbon (SOC) represents a significant pool of carbon within the biosphere. Climatic shifts in temperature and precipitation have a major influence on the decomposition and amount of SOC stored within an ecosystem and that released into the atmosphere. We have linked net primary production (NPP) algorithms, which include the impact of enhanced atmospheric CO(2 )on plant growth, to the SOCRATES terrestrial carbon model to estimate changes in SOC for the Australia continent between the years 1990 and 2100 in response to climate changes generated by the CSIRO Mark 2 Global Circulation Model (GCM). RESULTS: We estimate organic carbon storage in the topsoil (0–10 cm) of the Australian continent in 1990 to be 8.1 Gt. This equates to 19 and 34 Gt in the top 30 and 100 cm of soil, respectively. By the year 2100, under a low emissions scenario, topsoil organic carbon stores of the continent will have increased by 0.6% (49 Mt C). Under a high emissions scenario, the Australian continent becomes a source of CO(2 )with a net reduction of 6.4% (518 Mt) in topsoil carbon, when compared to no climate change. This is partially offset by the predicted increase in NPP of 20.3% CONCLUSION: Climate change impacts must be studied holistically, requiring integration of climate, plant, ecosystem and soil sciences. The SOCRATES terrestrial carbon cycling model provides realistic estimates of changes in SOC storage in response to climate change over the next century, and confirms the need for greater consideration of soils in assessing the full impact of climate change and the development of quantifiable mitigation strategies

Key issues in recruitment to randomised controlled trials with very different interventions: a qualitative investigation of recruitment to the SPARE trial (CRUK/07/011)

<p>Abstract</p> <p>Background</p> <p>Recruitment to randomised controlled trials (RCTs) with very different treatment arms is often difficult. The ProtecT (Prostate testing for cancer and Treatment) study successfully used qualitative research methods to improve recruitment and these methods were replicated in five other RCTs facing recruitment difficulties. A similar qualitative recruitment investigation was undertaken in the SPARE (Selective bladder Preservation Against Radical Excision) feasibility study to explore reasons for low recruitment and attempt to improve recruitment rates by implementing changes suggested by qualitative findings.</p> <p>Methods</p> <p>In Phase I of the investigation, reasons for low levels of recruitment were explored through content analysis of RCT documents, thematic analysis of interviews with trial staff and recruiters, and conversation analysis of audio-recordings of recruitment appointments. Findings were presented to the trial management group and a plan of action was agreed. In Phase II, changes to design and conduct were implemented, with training and feedback provided for recruitment staff.</p> <p>Results</p> <p>Five key challenges to trial recruitment were identified in Phase I: (a) Investigators and recruiters had considerable difficulty articulating the trial design in simple terms; (b) The recruitment pathway was complicated, involving staff across different specialties/centres and communication often broke down; (c) Recruiters inadvertently used 'loaded' terminology such as 'gold standard' in study information, leading to unbalanced presentation; (d) Fewer eligible patients were identified than had been anticipated; (e) Strong treatment preferences were expressed by potential participants and trial staff in some centres. In Phase II, study information (patient information sheet and flowchart) was simplified, the recruitment pathway was focused around lead recruiters, and training sessions and 'tips' were provided for recruiters. Issues of patient eligibility were insurmountable, however, and the independent Trial Steering Committee advised closure of the SPARE trial in February 2010.</p> <p>Conclusions</p> <p>The qualitative investigation identified the key aspects of trial design and conduct that were hindering recruitment, and a plan of action that was acceptable to trial investigators and recruiters was implemented. Qualitative investigations can thus be used to elucidate challenges to recruitment in trials with very different treatment arms, but require sufficient time to be undertaken successfully.</p> <p>Trial Registration</p> <p>CRUK/07/011; <a href="http://www.controlled-trials.com/ISRCTN61126465">ISRCTN61126465</a></p

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

A decision analytical cost analysis of offering ECV in a UK district general hospital

OBJECTIVE: To determine the care pathways and implications of offering mothers the choice of external cephalic version (ECV) at term for singleton babies who present with an uncomplicated breech pregnancy versus assisted breech delivery or elective caesarean. DESIGN: A prospective observational audit to construct a decision analysis of uncomplicated full term breech presentations. SETTING: The North Staffordshire NHS Trust. SUBJECTS: All women (n = 176) who presented at full term with a breech baby without complications during July 1995 and June 1997. MAIN OUTCOME MEASURES: The study determined to compare the outcome in terms of the costs and cost consequences for the care pathways that resulted from whether a women chose to accept the offer of ECV or not. All the associated events were then mapped for the two possible pathways. The costs were considered only within the hospital setting, from the perspective of the health care provider up to the point of delivery. RESULTS: The additional costs for ECV, assisted breech delivery and elective caesarean over and above a normal birth were £186.70, £425.36 and £1,955.22 respectively. The total expected cost of the respective care pathways for "ECV accepted" and "ECV not accepted" (including the probability of adverse events) were £1,452 and £1,828 respectively, that is the cost of delivery through the ECV care pathways is less costly than the non ECV delivery care pathway. CONCLUSIONS: Implementing an ECV service may yield cost savings in secondary care over and above the traditional delivery methods for breech birth of assisted delivery or caesarean section. The scale of these expected cost savings are in the range of £248 to £376 per patient. This converts to a total expected cost saving of between £43,616 and £44,544 for the patient cohort considered in this study

A novel transcriptional signature identifies T-cell infiltration in high-risk paediatric cancer

Background: Molecular profiling of the tumour immune microenvironment (TIME) has enabled the rational choice of immunotherapies in some adult cancers. In contrast, the TIME of paediatric cancers is relatively unexplored. We speculated that a more refined appreciation of the TIME in childhood cancers, rather than a reliance on commonly used biomarkers such as tumour mutation burden (TMB), neoantigen load and PD-L1 expression, is an essential prerequisite for improved immunotherapies in childhood solid cancers. Methods: We combined immunohistochemistry (IHC) with RNA sequencing and whole-genome sequencing across a diverse spectrum of high-risk paediatric cancers to develop an alternative, expression-based signature associated with CD8+ T-cell infiltration of the TIME. Furthermore, we explored transcriptional features of immune archetypes and T-cell receptor sequencing diversity, assessed the relationship between CD8+ and CD4+ abundance by IHC and deconvolution predictions and assessed the common adult biomarkers such as neoantigen load and TMB. Results: A novel 15-gene immune signature, Immune Paediatric Signature Score (IPASS), was identified. Using this signature, we estimate up to 31% of high-risk cancers harbour infiltrating T-cells. In addition, we showed that PD-L1 protein expression is poorly correlated with PD-L1 RNA expression and TMB and neoantigen load are not predictive of T-cell infiltration in paediatrics. Furthermore, deconvolution algorithms are only weakly correlated with IHC measurements of T-cells. Conclusions: Our data provides new insights into the variable immune-suppressive mechanisms dampening responses in paediatric solid cancers. Effective immune-based interventions in high-risk paediatric cancer will require individualised analysis of the TIME

Cost-effectiveness of external cephalic version for term breech presentation

<p>Abstract</p> <p>Background</p> <p>External cephalic version (ECV) is recommended by the American College of Obstetricians and Gynecologists to convert a breech fetus to vertex position and reduce the need for cesarean delivery. The goal of this study was to determine the incremental cost-effectiveness ratio, from society's perspective, of ECV compared to scheduled cesarean for term breech presentation.</p> <p>Methods</p> <p>A computer-based decision model (TreeAge Pro 2008, Tree Age Software, Inc.) was developed for a hypothetical base case parturient presenting with a term singleton breech fetus with no contraindications for vaginal delivery. The model incorporated actual hospital costs (e.g., $8,023 for cesarean and$5,581 for vaginal delivery), utilities to quantify health-related quality of life, and probabilities based on analysis of published literature of successful ECV trial, spontaneous reversion, mode of delivery, and need for unanticipated emergency cesarean delivery. The primary endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted year of life gained. A threshold of $50,000 per quality-adjusted life-years (QALY) was used to determine cost-effectiveness.</p> <p>Results</p> <p>The incremental cost-effectiveness of ECV, assuming a baseline 58$7,900/QALY. If the estimated probability of successful ECV is less than 32%, then ECV costs more to society and has poorer QALYs for the patient. However, as the probability of successful ECV was between 32% and 63%, ECV cost more than cesarean delivery but with greater associated QALY such that the cost-effectiveness ratio was less than $50,000/QALY. If the probability of successful ECV was greater than 63%, the computer modeling indicated that a trial of ECV is less costly and with better QALYs than a scheduled cesarean. The cost-effectiveness of a trial of ECV is most sensitive to its probability of success, and not to the probabilities of a cesarean after ECV, spontaneous reversion to breech, successful second ECV trial, or adverse outcome from emergency cesarean.</p> <p>Conclusions</p> <p>From society's perspective, ECV trial is cost-effective when compared to a scheduled cesarean for breech presentation provided the probability of successful ECV is > 32%. Improved algorithms are needed to more precisely estimate the likelihood that a patient will have a successful ECV.</p