Temporal trend in the transfer of Sellafield-derived 14C into different size fractions of the carbonate component of NE Irish Sea sediment

From 1994 onwards, 14C discharges from the Sellafield nuclear fuel reprocessing plant have been made largely to the Northeast Irish Sea. They represent the largest contributor to UK and European populations of the collective dose commitment derived from the entire nuclear industry discharges. Consequently, it is important to understand the long-term fate of 14C in the marine environment. Research undertaken in 2000 suggested that the carbonate component of Northeast Irish Sea sediments would increase in 14C activity as mollusc shells, which have become enriched in Sellafield-derived 14C, are broken down by physical processes including wave action and incorporated into intertidal and sub-tidal sediments. The current study, undertaken in 2011, tested this hypothesis. The results demonstrate significant increases in 14C enrichments found in whole mussel shells compared to those measured in 2000. Additionally, in 2000, there was an enrichment above ambient background within only the largest size fraction (>500 μm) of the intertidal inorganic sediment at Nethertown and Flimby (north of Sellafield). In comparison, the present study has demonstrated 14C enrichments above ambient background in most size fractions at sites up to 40 km north of Sellafield, confirming the hypothesis set out more than a decade ago

Comparison of aggregate and individual participant data approaches to meta-analysis of randomised trials : An observational study

BACKGROUND: It remains unclear when standard systematic reviews and meta-analyses that rely on published aggregate data (AD) can provide robust clinical conclusions. We aimed to compare the results from a large cohort of systematic reviews and meta-analyses based on individual participant data (IPD) with meta-analyses of published AD, to establish when the latter are most likely to be reliable and when the IPD approach might be required. METHODS AND FINDINGS: We used 18 cancer systematic reviews that included IPD meta-analyses: all of those completed and published by the Meta-analysis Group of the MRC Clinical Trials Unit from 1991 to 2010. We extracted or estimated hazard ratios (HRs) and standard errors (SEs) for survival from trial reports and compared these with IPD equivalents at both the trial and meta-analysis level. We also extracted or estimated the number of events. We used paired t tests to assess whether HRs and SEs from published AD differed on average from those from IPD. We assessed agreement, and whether this was associated with trial or meta-analysis characteristics, using the approach of Bland and Altman. The 18 systematic reviews comprised 238 unique trials or trial comparisons, including 37,082 participants. A HR and SE could be generated for 127 trials, representing 53% of the trials and approximately 79% of eligible participants. On average, trial HRs derived from published AD were slightly more in favour of the research interventions than those from IPD (HRAD to HRIPD ratio = 0.95, p = 0.007), but the limits of agreement show that for individual trials, the HRs could deviate substantially. These limits narrowed with an increasing number of participants (p < 0.001) or a greater number (p < 0.001) or proportion (p < 0.001) of events in the AD. On average, meta-analysis HRs from published AD slightly tended to favour the research interventions whether based on fixed-effect (HRAD to HRIPD ratio = 0.97, p = 0.088) or random-effects (HRAD to HRIPD ratio = 0.96, p = 0.044) models, but the limits of agreement show that for individual meta-analyses, agreement was much more variable. These limits tended to narrow with an increasing number (p = 0.077) or proportion of events (p = 0.11) in the AD. However, even when the information size of the AD was large, individual meta-analysis HRs could still differ from their IPD equivalents by a relative 10% in favour of the research intervention to 5% in favour of control. We utilised the results to construct a decision tree for assessing whether an AD meta-analysis includes sufficient information, and when estimates of effects are most likely to be reliable. A lack of power at the meta-analysis level may have prevented us identifying additional factors associated with the reliability of AD meta-analyses, and we cannot be sure that our results are generalisable to all outcomes and effect measures. CONCLUSIONS: In this study we found that HRs from published AD were most likely to agree with those from IPD when the information size was large. Based on these findings, we provide guidance for determining systematically when standard AD meta-analysis will likely generate robust clinical conclusions, and when the IPD approach will add considerable value

Risk factors for death in HIV-infected adult african patients recieving anti-retroviral therapy

Objective: To determine risk factors for death in HIV-infected African patients on anti-retroviral therapy (ART).Design: Retrospective Case-control study.Setting: The MOH-USAID-AMPATH Partnership ambulatory HIV-care clinics in western Kenya.Results: Between November 2001 and December 2005 demographic, clinical and laboratory data from 527 deceased and 1054 living patients receiving ART were compared to determine independent risk factors for death. Median age at ART initiation was 38 versus 36 years for the deceased and living patients respectively (p&lt;0.0148). Mediantime from enrollment at AMPATH to initiation of ART was two weeks for both groups while median time on ART was eight weeks for the deceased and fourty two weeks for the living (p&lt;0.0001). Patients with CD4 cell counts &lt;100/mm3 were more likely to die than those with counts &gt;100/mm3 (HR=1.553. 95% CI (1.156, 2.087), p&lt;0.003). Patientsattending rural clinics had threefold higher risk of dying compared to patients attending clinic at a tertiary referral hospital (p&lt;0.0001). Two years after initiating treatment fifty percent of non-adherent patients were alive compared to 75% of adherent patients. Male gender, WHO Stage and haemoglobin level &lt;10 grams% were associated with time to death while age, marital status, educational level, employment status andweight were not.Conclusion: Profoundly immunosuppressed patients were more likely to die early in the course of treatment. Also, patients receiving care in rural clinics were at greater risk of dying than those receiving care in the tertiary referral hospital

Developing reading-writing connections; the impact of explicit instruction of literary devices on the quality of children's narrative writing

The purpose of this collaborative schools-university study was to investigate how the explicit instruction of literary devices during designated literacy sessions could improve the quality of children's narrative writing. A guiding question for the study was: Can children's writing can be enhanced by teachers drawing attention to the literary devices used by professional writers or “mentor authors”? The study was conducted with 18 teachers, working as research partners in nine elementary schools over one school year. The research group explored ways of developing children as reflective authors, able to draft and redraft writing in response to peer and teacher feedback. Daily literacy sessions were complemented by weekly writing workshops where students engaged in authorial activity and experienced writers' perspectives and readers' demands (Harwayne, 1992; May, 2004). Methods for data collection included video recording of peer-peer and teacher-led group discussions and audio recording of teacher-child conferences. Samples of children's narrative writing were collected and a comparison was made between the quality of their independent writing at the beginning and end of the research period. The research group documented the importance of peer-peer and teacher-student discourse in the development of children's metalanguage and awareness of audience. The study suggests that reading, discussing, and evaluating mentor texts can have a positive impact on the quality of children's independent writing

Controlling the Production of Acid Catalyzed Products of Furfural Hydrogenation by Pd/TiO2

We demonstrate a modified sol-immobilization procedure using (MeOH)x/(H2O)1-x solvent mixtures to prepare Pd/TiO2 catalysts that are able to reduce the formation of acid catalyzed products, e. g. ethers, for the hydrogenation of furfural. Transmission electron microscopy found a significant increase in polyvinyl alcohol (PVA) deposition at the metal-support interface and temperature programmed reduction found a reduced uptake of hydrogen, compared to an established Pd/TiO2 preparation. We propose that the additional PVA hinders hydrogen spillover onto the TiO2 support and limits the formation of Brønsted acid sites, required to produce ethers. Elsewhere, the new preparation route was able to successfully anchor colloidal Pd to the TiO2 surface, without the need for acidification. This work demonstrates the potential for minimizing process steps as well as optimizing catalyst selectivity – both important objectives for sustainable chemistry

Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis

BACKGROUND: There is a need to synthesise the results of numerous randomised controlled trials evaluating the addition of therapies to androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer (mHSPC). This systematic review aims to assess the effects of adding abiraterone acetate plus prednisone/prednisolone (AAP) to ADT. METHODS: Using our framework for adaptive meta-analysis (FAME), we started the review process before trials had been reported and worked collaboratively with trial investigators to anticipate when eligible trial results would emerge. Thus, we could determine the earliest opportunity for reliable meta-analysis and take account of unavailable trials in interpreting results. We searched multiple sources for trials comparing AAP plus ADT versus ADT in men with mHSPC. We obtained results for the primary outcome of overall survival (OS), secondary outcomes of clinical/radiological progression-free survival (PFS) and grade III-IV and grade V toxicity direct from trial teams. Hazard ratios (HRs) for the effects of AAP plus ADT on OS and PFS, Peto Odds Ratios (Peto ORs) for the effects on acute toxicity and interaction HRs for the effects on OS by patient subgroups were combined across trials using fixed-effect meta-analysis. FINDINGS: We identified three eligible trials, one of which was still recruiting (PEACE-1 (NCT01957436)). Results from the two remaining trials (LATITUDE (NCT01715285) and STAMPEDE (NCT00268476)), representing 82% of all men randomised to AAP plus ADT versus ADT (without docetaxel in either arm), showed a highly significant 38% reduction in the risk of death with AAP plus ADT (HR = 0.62, 95% confidence interval [CI] = 0.53-0.71, p = 0.55 × 10(-10)), that translates into a 14% absolute improvement in 3-year OS. Despite differences in PFS definitions across trials, we also observed a consistent and highly significant 55% reduction in the risk of clinical/radiological PFS (HR = 0.45, 95% CI = 0.40-0.51, p = 0.66 × 10(-36)) with the addition of AAP, that translates to a 28% absolute improvement at 3 years. There was no evidence of a difference in the OS benefit by Gleason sum score, performance status or nodal status, but the size of the benefit may vary by age. There were more grade III-IV acute cardiac, vascular and hepatic toxicities with AAP plus ADT but no excess of other toxicities or death. INTERPRETATION: Adding AAP to ADT is a clinically effective treatment option for men with mHSPC, offering an alternative to docetaxel for men who are starting treatment for the first time. Future research will need to address which of these two agents or whether their combination is most effective, and for whom

Bayesian Parameter Estimation for Latent Markov Random Fields and Social Networks

Undirected graphical models are widely used in statistics, physics and machine vision. However Bayesian parameter estimation for undirected models is extremely challenging, since evaluation of the posterior typically involves the calculation of an intractable normalising constant. This problem has received much attention, but very little of this has focussed on the important practical case where the data consists of noisy or incomplete observations of the underlying hidden structure. This paper specifically addresses this problem, comparing two alternative methodologies. In the first of these approaches particle Markov chain Monte Carlo (Andrieu et al., 2010) is used to efficiently explore the parameter space, combined with the exchange algorithm (Murray et al., 2006) for avoiding the calculation of the intractable normalising constant (a proof showing that this combination targets the correct distribution in found in a supplementary appendix online). This approach is compared with approximate Bayesian computation (Pritchard et al., 1999). Applications to estimating the parameters of Ising models and exponential random graphs from noisy data are presented. Each algorithm used in the paper targets an approximation to the true posterior due to the use of MCMC to simulate from the latent graphical model, in lieu of being able to do this exactly in general. The supplementary appendix also describes the nature of the resulting approximation.Comment: 26 pages, 2 figures, accepted in Journal of Computational and Graphical Statistics (http://www.amstat.org/publications/jcgs.cfm

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe