Evaluating the Quality of Research into a Single Prognostic Biomarker: A Systematic Review and Meta-analysis of 83 Studies of C-Reactive Protein in Stable Coronary Artery Disease

Background Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease. Methods and Findings We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78–2.17), with substantial heterogeneity (I2 = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39–1.96), I2 = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13–1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57–0.66). Conclusion Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research

Predictors of serum dioxin levels among adolescent boys in Chapaevsk, Russia: A cross-sectional pilot study

BACKGROUND: Toxicological studies and limited human studies have demonstrated associations between exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) and adverse developmental and reproductive health effects. Given that children may be particularly susceptible to reproductive and developmental effects of organochlorines, and the paucity of information available regarding childhood exposures to dioxins in particular, we undertook a pilot study to describe the distribution of, and identify potential predictors of exposure to, dioxin-like compounds and dioxins among adolescent boys in Chapaevsk, Russia. The pilot study was also designed to guide the development of a large prospective cohort study on the relationship of exposure to PCDDs, PCDFs, and PCBs with growth and pubertal development in peri-pubertal Chapaevsk boys. METHODS: 221 boys age 14 to 17 participated in the pilot study. Each of the boys, with his mother, was asked to complete a nurse-administered detailed questionnaire on medical history, diet, and lifestyle. The diet questions were used to measure the current and lifetime consumption of locally grown or raised foods. Blood samples from 30 of these boys were sent to the Centers for Disease Control and Prevention (CDC) for analysis of dioxins, furans and PCBs. RESULTS: The median (25(th), 75(th )percentile) concentrations for total PCDDs, PCDFs and coplanar PCBs were 95.8 pg/g lipids (40.9, 144), 33.9 pg/g lipids (20.4, 61.8), and 120 pg/g lipids (77.6, 157), respectively. For WHO-TEQs, the median (25(th), 75(th )percentile) for total PCDDs, PCDFs, and coplanar PCBs were 0.29 (0.1, 9.14), 7.98 (5.27, 12.3), and 7.39 (4.51, 11.9), respectively. Although TCDD was largely non-detectable, two boys had high TCDD levels (17.9 and 21.7 pg/g lipid). Higher serum levels of sum of dioxin-like compounds and sum of dioxin TEQs were positively associated with increased age, consumption of fish, local meats other than chicken, PCB 118, and inversely with weeks of gestation. CONCLUSION: The total TEQs among Chapaevsk adolescents were higher than most values previously reported in non-occupationally exposed populations of comparable or even older ages. Dietary consumption of local foods, as well as age and weeks of gestation, predicted dioxin exposure in this population

Bioavailability of iodine in the UK-Peak District environment and its human bioaccessibility: an assessment of the causes of historical goitre in this area

Iodine is an essential micronutrient for human health. Its deficiency causes a number of functional and developmental abnormalities such as goitre. The limestone region of Derbyshire, UK was goitre-endemic until it declined from the 1930s and the reason for this has escaped a conclusive explanation. The present study investigates the cause(s) of goitre in the UK-Peak District area through an assessment of iodine in terms of its environmental mobility, bioavailability, uptake into the food chain and human bioaccessibility. The goitre-endemic limestone area is compared with the background millstone grit area of the UK-Peak District. The findings of this study show that ‘total’ environmental iodine is not linked to goitre in the limestone area, but the governing factors include iodine mobility, bioavailability and bioaccessibility. Compared with the millstone grit area, higher soil pH and calcium content of the limestone area restrict iodine mobility in this area, also soil organic carbon in the limestone area is influential in binding the iodine to the soil. Higher calcium content in the limestone area is an important factor in terms of strongly fixing the iodine to the soil. Higher iodine bioaccessibility in the millstone grit than the limestone area suggests that its oral bioaccessibility is restricted in the limestone area. Iodine taken up by plant roots is transported freely into the aerial plant parts in the millstone grit area unlike the limestone area, thus providing higher iodine into the human food chain in the millstone grit area through grazing animals unlike the goitre-prevalent limestone area

Exploring user experience and technology acceptance for a fall prevention system: results from a randomized clinical trial and a living lab

Background: Falls are common in older adults and can result in serious injuries. Due to demographic changes, falls and related healthcare costs are likely to increase over the next years. Participation and motivation of older adults in fall prevention measures remain a challenge. The iStoppFalls project developed an information and communication technology (ICT)-based system for older adults to use at home in order to reduce common fall risk factors such as impaired balance and muscle weakness. The system aims at increasing older adults’ motivation to participate in ICT-based fall prevention measures. This article reports on usability, user-experience and user-acceptance aspects affecting the use of the iStoppFalls system by older adults. Methods: In the course of a 16-week international multicenter study, 153 community-dwelling older adults aged 65+ participated in the iStoppFalls randomized controlled trial, of which half used the system in their home to exercise and assess their risk of falling. During the study, 60 participants completed questionnaires regarding the usability, user experience and user acceptance of the iStoppFalls system. Usability was measured with the System Usability Scale (SUS). For user experience the Physical Activity Enjoyment Scale (PACES) was applied. User acceptance was assessed with the Dynamic Acceptance Model for the Re-evaluation of Technologies (DART). To collect more detailed data on usability, user experience and user acceptance, additional qualitative interviews and observations were conducted with participants. Results: Participants evaluated the usability of the system with an overall score of 62 (Standard Deviation, SD 15.58) out of 100, which suggests good usability. Most users enjoyed the iStoppFalls games and assessments, as shown by the overall PACES score of 31 (SD 8.03). With a score of 0.87 (SD 0.26), user acceptance results showed that participants accepted the iStoppFalls system for use in their own home. Interview data suggested that certain factors such as motivation, complexity or graphical design were different for gender and age. Conclusions: The results suggest that the iStoppFalls system has good usability, user experience and user acceptance. It will be important to take these along with factors such as motivation, gender and age into consideration when designing and further developing ICT-based fall prevention systems

Assessing Conservation Values: Biodiversity and Endemicity in Tropical Land Use Systems

Despite an increasing amount of data on the effects of tropical land use on continental forest fauna and flora, it is debatable whether the choice of the indicator variables allows for a proper evaluation of the role of modified habitats in mitigating the global biodiversity crisis. While many single-taxon studies have highlighted that species with narrow geographic ranges especially suffer from habitat modification, there is no multi-taxa study available which consistently focuses on geographic range composition of the studied indicator groups. We compiled geographic range data for 180 bird, 119 butterfly, 204 tree and 219 understorey plant species sampled along a gradient of habitat modification ranging from near-primary forest through young secondary forest and agroforestry systems to annual crops in the southwestern lowlands of Cameroon. We found very similar patterns of declining species richness with increasing habitat modification between taxon-specific groups of similar geographic range categories. At the 8 km2 spatial level, estimated richness of endemic species declined in all groups by 21% (birds) to 91% (trees) from forests to annual crops, while estimated richness of widespread species increased by +101% (trees) to +275% (understorey plants), or remained stable (- 2%, butterflies). Even traditional agroforestry systems lost estimated endemic species richness by - 18% (birds) to - 90% (understorey plants). Endemic species richness of one taxon explained between 37% and 57% of others (positive correlations) and taxon-specific richness in widespread species explained up to 76% of variation in richness of endemic species (negative correlations). The key implication of this study is that the range size aspect is fundamental in assessments of conservation value via species inventory data from modified habitats. The study also suggests that even ecologically friendly agricultural matrices may be of much lower value for tropical conservation than indicated by mere biodiversity value

Ab Initio Identification of Novel Regulatory Elements in the Genome of Trypanosoma brucei by Bayesian Inference on Sequence Segmentation

Background: The rapid increase in the availability of genome information has created considerable demand for both comparative and ab initio predictive bioinformatic analyses. The biology laid bare in the genomes of many organisms is often novel, presenting new challenges for bioinformatic interrogation. A paradigm for this is the collected genomes of the kinetoplastid parasites, a group which includes Trypanosoma brucei the causative agent of human African trypanosomiasis. These genomes, though outwardly simple in organisation and gene content, have historically challenged many theories for gene expression regulation in eukaryotes. Methodology/Principle Findings: Here we utilise a Bayesian approach to identify local changes in nucleotide composition in the genome of T. brucei. We show that there are several elements which are found at the starts and ends of multicopy gene arrays and that there are compositional elements that are common to all intergenic regions. We also show that there is a composition-inversion element that occurs at the position of the trans-splice site. Conclusions/Significance: The nature of the elements discovered reinforces the hypothesis that context dependant RN

Carbon sequestration potential and physicochemical properties differ between wildfire charcoals and slow-pyrolysis biochars

Pyrogenic carbon (PyC), produced naturally (wildfire charcoal) and anthropogenically (biochar), is extensively studied due to its importance in several disciplines, including global climate dynamics, agronomy and paleosciences. Charcoal and biochar are commonly used as analogues for each other to infer respective carbon sequestration potentials, production conditions, and environmental roles and fates. The direct comparability of corresponding natural and anthropogenic PyC, however, has never been tested. Here we compared key physicochemical properties (elemental composition, δ13C and PAHs signatures, chemical recalcitrance, density and porosity) and carbon sequestration potentials of PyC materials formed from two identical feedstocks (pine forest floor and wood) under wildfire charring- and slow-pyrolysis conditions. Wildfire charcoals were formed under higher maximum temperatures and oxygen availabilities, but much shorter heating durations than slow-pyrolysis biochars, resulting in differing physicochemical properties. These differences are particularly relevant regarding their respective roles as carbon sinks, as even the wildfire charcoals formed at the highest temperatures had lower carbon sequestration potentials than most slow-pyrolysis biochars. Our results challenge the common notion that natural charcoal and biochar are well suited as proxies for each other, and suggest that biochar’s environmental residence time may be underestimated when based on natural charcoal as a proxy, and vice versa

Higher Level Phylogeny and the First Divergence Time Estimation of Heteroptera (Insecta: Hemiptera) Based on Multiple Genes

Heteroptera, or true bugs, are the largest, morphologically diverse and economically important group of insects with incomplete metamorphosis. However, the phylogenetic relationships within Heteroptera are still in dispute and most of the previous studies were based on morphological characters or with single gene (partial or whole 18S rDNA). Besides, so far, divergence time estimates for Heteroptera totally rely on the fossil record, while no studies have been performed on molecular divergence rates. Here, for the first time, we used maximum parsimony (MP), maximum likelihood (ML) and Bayesian inference (BI) with multiple genes (18S rDNA, 28S rDNA, 16S rDNA and COI) to estimate phylogenetic relationships among the infraorders, and meanwhile, the Penalized Likelihood (r8s) and Bayesian (BEAST) molecular dating methods were employed to estimate divergence time of higher taxa of this suborder. Major results of the present study included: Nepomorpha was placed as the most basal clade in all six trees (MP trees, ML trees and Bayesian trees of nuclear gene data and four-gene combined data, respectively) with full support values. The sister-group relationship of Cimicomorpha and Pentatomomorpha was also strongly supported. Nepomorpha originated in early Triassic and the other six infraorders originated in a very short period of time in middle Triassic. Cimicomorpha and Pentatomomorpha underwent a radiation at family level in Cretaceous, paralleling the proliferation of the flowering plants. Our results indicated that the higher-group radiations within hemimetabolous Heteroptera were simultaneously with those of holometabolous Coleoptera and Diptera which took place in the Triassic. While the aquatic habitat was colonized by Nepomorpha already in the Triassic, the Gerromorpha independently adapted to the semi-aquatic habitat in the Early Jurassic

Parasites of non-native freshwater fishes introduced into england and wales suggest enemy release and parasite acquisition

When non-native species are introduced into a new range, their parasites can also be introduced, with these potentially spilling-over into native hosts. However, in general, evidence suggests that a high proportion of their native parasites are lost during introduction and infections by some new parasites from the native range might occur, potentially resulting in parasite spill-back to native species. These processes were investigated here using parasite surveys and literature review on seven non-native freshwater fishes introduced into England and Wales. Comparison of the mean numbers of parasite species and genera per population for each fish species England andWaleswith their native ranges revealed\9 % of the native parasite fauna were present in their populations in England and Wales. There was no evidence suggesting these introduced parasites had spilled over into sympatric native fishes. The non-native fishes did acquire parasites following their introduction, providing potential for parasite spill-back to sympatric fishes, and resulted in non-significant differences in overall mean numbers of parasites per populations between the two ranges. Through this acquisition, the non-native fishes also had mean numbers of parasite species and genera per population that were not significantly different to sympatric native fishes. Thus, the non-native fishes in England and Wales showed evidence of enemy release, acquired new parasites following introduction providing potential for spill-back, but showed no evidence of parasite spill-over

Efficacy of a training intervention on the quality of practitioners' decision support for patients deciding about place of care at the end of life: A randomized control trial: Study protocol

<p>Abstract</p> <p>Background</p> <p>Most people prefer home palliation but die in an institution. Some experience decisional conflict when weighing options regarding place of care. Clinicians can identify patients' decisional needs and provide decision support, yet generally lack skills and confidence in doing so. This study aims to determine whether the quality of clinicians' decision support can be improved with a brief, theory-based, skills-building intervention.</p> <p>Theory</p> <p>The Ottawa Decision Support Framework (ODSF) guides an evidence based, practical approach to assist clinicians in providing high-quality decision support. The ODSF proposes that decisional needs [personal uncertainty, knowledge, values clarity, support, personal characteristics] strongly influence the quality of decisions patients make. Clinicians can improve decision quality by providing decision support to address decisional needs [clarify decisional needs, provide facts and probabilities, clarify values, support/guide deliberation, monitor/facilitate progress].</p> <p>Methods/Design</p> <p>The efficacy of a brief education intervention will be assessed in a two-phase study. In phase one a focused needs assessment will be conducted with key informants. Phase two is a randomized control trial where clinicians will be randomly allocated to an intervention or control group. The intervention, informed by the needs assessment, knowledge transfer best practices and the ODSF, comprises an online tutorial; an interactive skills building workshop; a decision support protocol; performance feedback, and educational outreach. Participants will be assessed: a) at baseline (quality of decision support); b) after the tutorial (knowledge); and c) four weeks after the other interventions (quality of decision support, intention to incorporate decision support into practice and perceived usefulness of intervention components). Between group differences in the primary outcome (quality of decision support scores) will be analyzed using ANOVA.</p> <p>Discussion</p> <p>Few studies have investigated the efficacy of an evidence-based, theory guided intervention aimed at assisting clinicians to strengthen their patient decision support skills. Expanding our understanding of how clinicians can best support palliative patients' decision-making will help to inform best practices in patient-centered palliative care. There is potential transferability of lessons learned to other care situations such as chronic condition management, advance directives and anticipatory care planning. Should the efficacy evaluation reveal clear improvements in the quality of decision support provided by clinicians who received the intervention, a larger scale implementation and effectiveness trial will be considered.</p> <p>Trial registration</p> <p>This study is registered as NCT00614003</p