The search for stable prognostic models in multiple imputed data sets

<p>Abstract</p> <p>Background</p> <p>In prognostic studies model instability and missing data can be troubling factors. Proposed methods for handling these situations are bootstrapping (B) and Multiple imputation (MI). The authors examined the influence of these methods on model composition.</p> <p>Methods</p> <p>Models were constructed using a cohort of 587 patients consulting between January 2001 and January 2003 with a shoulder problem in general practice in the Netherlands (the Dutch Shoulder Study). Outcome measures were persistent shoulder disability and persistent shoulder pain. Potential predictors included socio-demographic variables, characteristics of the pain problem, physical activity and psychosocial factors. Model composition and performance (calibration and discrimination) were assessed for models using a complete case analysis, MI, bootstrapping or both MI and bootstrapping.</p> <p>Results</p> <p>Results showed that model composition varied between models as a result of how missing data was handled and that bootstrapping provided additional information on the stability of the selected prognostic model.</p> <p>Conclusion</p> <p>In prognostic modeling missing data needs to be handled by MI and bootstrap model selection is advised in order to provide information on model stability.</p

Heart-type Fatty acid-binding protein in Acute Myocardial infarction Evaluation (FAME): Background and design of a diagnostic study in primary care

<p>Abstract</p> <p>Background</p> <p>Currently used biomarkers for cardiac ischemia are elevated in blood plasma after a delay of several hours and therefore unable to detect acute coronary syndrome (ACS) in a very early stage. General practitioners (GPs), however, are often confronted with patients suspected of ACS within hours after onset of complaints. This ongoing study aims to evaluate the added diagnostic value beyond clinical assessment for a rapid bedside test for heart-type fatty-acid binding protein (H-FABP), a biomarker that is detectable as soon as one hour after onset of ischemia.</p> <p>Methods</p> <p>Participating GPs perform a blinded H-FABP rapid bedside test (Cardiodetect^®) in patients with symptoms suggestive of ACS such as chest pain or discomfort at rest. All patients, whether referred to hospital or not, undergo electrocardiography (ECG) and venapunction for a plasma troponin test within 12–36 hours after onset of complaints. A final diagnosis will be established by an expert panel consisting of two cardiologists and one general practitioner (blinded to the H-FABP test result), using all available patient information, also including signs and symptoms. The added diagnostic value of the H-FABP test beyond history taking and physical examination will be determined with receiver operating characteristic curves derived from multivariate regression analysis.</p> <p>Conclusion</p> <p>Reasons for presenting the design of our study include the prevention of publication bias and unacknowledged alterations in the study aim, design or data-analysis. To our knowledge this study is the first to assess the diagnostic value of H-FABP <it>outside </it>a hospital-setting. Several previous hospital-based studies showed the potential value of H-FABP in diagnosing ACS. Up to now however it is unclear whether these results are equally promising when the test is used in primary care. The first results are expected in the end of 2008.</p

DODO: an efficient orthologous genes assignment tool based on domain architectures. Domain based ortholog detection

<p>Abstract</p> <p>Background</p> <p>Orthologs are genes derived from the same ancestor gene loci after speciation events. Orthologous proteins usually have similar sequences and perform comparable biological functions. Therefore, ortholog identification is useful in annotations of newly sequenced genomes. With rapidly increasing number of sequenced genomes, constructing or updating ortholog relationship between all genomes requires lots of effort and computation time. In addition, elucidating ortholog relationships between distantly related genomes is challenging because of the lower sequence similarity. Therefore, an efficient ortholog detection method that can deal with large number of distantly related genomes is desired.</p> <p>Results</p> <p>An efficient ortholog detection pipeline DODO (DOmain based Detection of Orthologs) is created on the basis of domain architectures in this study. Supported by domain composition, which usually directly related with protein function, DODO could facilitate orthologs detection across distantly related genomes. DODO works in two main steps. Starting from domain information, it first assigns protein groups according to their domain architectures and further identifies orthologs within those groups with much reduced complexity. Here DODO is shown to detect orthologs between two genomes in considerably shorter period of time than traditional methods of reciprocal best hits and it is more significant when analyzed a large number of genomes. The output results of DODO are highly comparable with other known ortholog databases.</p> <p>Conclusions</p> <p>DODO provides a new efficient pipeline for detection of orthologs in a large number of genomes. In addition, a database established with DODO is also easier to maintain and could be updated relatively effortlessly. The pipeline of DODO could be downloaded from <url>http://140.109.42.19:16080/dodo_web/home.htm</url></p

Tree diversity and species identity effects on soil fungi, protists and animals are context dependent

Plant species richness and the presence of certain influential species (sampling effect) drive the stability and functionality of ecosystems as well as primary production and biomass of consumers. However, little is known about these floristic effects on richness and community composition of soil biota in forest habitats owing to methodological constraints. We developed a DNA metabarcoding approach to identify the major eukaryote groups directly from soil with roughly species-level resolution. Using this method, we examined the effects of tree diversity and individual tree species on soil microbial biomass and taxonomic richness of soil biota in two experimental study systems in Finland and Estonia and accounted for edaphic variables and spatial autocorrelation. Our analyses revealed that the effects of tree diversity and individual species on soil biota are largely context dependent. Multiple regression and structural equation modelling suggested that biomass, soil pH, nutrients and tree species directly affect richness of different taxonomic groups. The community composition of most soil organisms was strongly correlated due to similar response to environmental predictors rather than causal relationships. On a local scale, soil resources and tree species have stronger effect on diversity of soil biota than tree species richness per se

Prophylactic Melatonin for Delirium in Intensive Care (Pro-MEDIC): Study protocol for a randomised controlled trial

Background: Delirium is an acute state of brain dysfunction characterised by fluctuating inattention and cognitive disturbances, usually due to illness. It occurs commonly in the intensive care unit (ICU), and it is associated with greater morbidity and mortality. It is likely that disturbances of sleep and of the day-night cycle play a significant role. Melatonin is a naturally occurring, safe and cheap hormone that can be administered to improve sleep. The main aim of this trial will be to determine whether prophylactic melatonin administered to critically ill adults, when compared with placebo, decreases the rate of delirium. Methods: This trial will be a multi-centre, randomised, placebo-controlled study conducted in closed ICUs in Australia. Our aim is to enrol 850 adult patients with an expected ICU length of stay (LOS) of 72h or more. Eligible patients for whom there is consent will be randomised to receive melatonin 4mg enterally or placebo in a 1:1 ratio according to a computer-generated randomisation list, stratified by site. The study drug will be indistinguishable from placebo. Patients, doctors, nurses, investigators and statisticians will be blinded. Melatonin or placebo will be administered once per day at 21:00 until ICU discharge or 14days after enrolment, whichever occurs first. Trained staff will assess patients twice daily to determine the presence or absence of delirium using the Confusion Assessment Method for the ICU score. Data will also be collected on demographics, the overall prevalence of delirium, duration and severity of delirium, sleep quality, participation in physiotherapy sessions, ICU and hospital LOS, morbidity and mortality, and healthcare costs. A subgroup of 100 patients will undergo polysomnographic testing to further evaluate the quality of sleep. Discussion: Delirium is a significant issue in ICU because of its frequency and associated poorer outcomes. This trial will be the largest evaluation of melatonin as a prophylactic agent to prevent delirium in the critically ill population. This study will also provide one of the largest series of polysomnographic testing done in ICU. Trial registration: Australian New Zealand Clinical Trial Registry (ANZCTR) number: ACTRN12616000436471. Registered on 20 December 2015

Interactive and Single Effects of Ectomycorrhiza Formation and Bacillus cereus on Metallothionein MT1 Expression and Phytoextraction of Cd and Zn by Willows

Single and joint ectomycorrhizal (+ Hebeloma mesophaeum) and bacterial (+ Bacillus cereus) inoculations of willows (Salix viminalis) were investigated for their potential and mode of action in the promotion of cadmium (Cd) and zinc (Zn) phytoextraction. Dual fungal and bacterial inoculations promoted the biomass production of willows in contaminated soil. Single inoculations either had no effect on the plant growth or inhibited it. All inoculated willows showed increased concentrations of nutritional elements (N, P, K and Zn) and decreased concentrations of Cd in the shoots. The lowest biomass production and concentration of Cd in the willows (+ B. cereus) were combined with the strongest expression of metallothioneins. It seems that biotic stress from bacterial invasion increased the synthesis of these stress proteins, which responded in decreased Cd concentrations. Contents of Cd and Zn in the stems of willows were combination-specific, but were always increased in dual inoculated plants. In conclusion, single inoculations with former mycorrhiza-associated B. cereus strains decreased the phytoextraction efficiency of willows by causing biotic stress. However, their joint inoculation with an ectomycorrhizal fungus is a very promising method for promoting the phytoextraction of Cd and Zn through combined physiological effects on the plant

Persistent Oxytetracycline Exposure Induces an Inflammatory Process That Improves Regenerative Capacity in Zebrafish Larvae

BACKGROUND: The excessive use of antibiotics in aquaculture can adversely affect not only the environment, but also fish themselves. In this regard, there is evidence that some antibiotics can activate the immune system and reduce their effectiveness. None of those studies consider in detail the adverse inflammatory effect that the antibiotic remaining in the water may cause to the fish. In this work, we use the zebrafish to analyze quantitatively the effects of persistent exposure to oxytetracycline, the most common antibiotic used in fish farming. METHODOLOGY: We developed a quantitative assay in which we exposed zebrafish larvae to oxytetracycline for a period of 24 to 96 hrs. In order to determinate if the exposure causes any inflammation reaction, we evaluated neutrophils infiltration and quantified their total number analyzing the Tg(mpx:GFP)(i114) transgenic line by fluorescence stereoscope, microscope and flow cytometry respectively. On the other hand, we characterized the process at a molecular level by analyzing several immune markers (il-1β, il-10, lysC, mpx, cyp1a) at different time points by qPCR. Finally, we evaluated the influence of the inflammation triggered by oxytetracycline on the regeneration capacity in the lateral line. CONCLUSIONS: Our results suggest that after 48 hours of exposure, the oxytetracycline triggered a widespread inflammation process that persisted until 96 hours of exposure. Interestingly, larvae that developed an inflammation process showed an improved regeneration capacity in the mechanosensory system lateral line