Hybrid copula mixed models for combining case-control and cohort studies in meta-analysis of diagnostic tests

Copula mixed models for trivariate (or bivariate) meta-analysis of diagnostic test accuracy studies accounting (or not) for disease prevalence have been proposed in the biostatistics literature to synthesize information. However, many systematic reviews often include case-control and cohort studies, so one can either focus on the bivariate meta-analysis of the case-control studies or the trivariate meta-analysis of the cohort studies, as only the latter contains information on disease prevalence. In order to remedy this situation of wasting data we propose a hybrid copula mixed model via a combination of the bivariate and trivariate copula mixed model for the data from the case-control studies and cohort studies, respectively. Hence, this hybrid model can account for study design and also due to its generality can deal with dependence in the joint tails. We apply the proposed hybrid copula mixed model to a review of the performance of contemporary diagnostic imaging modalities for detecting metastases in patients with melanoma

Association of Over-The-Counter Pharmaceutical Sales with Influenza-Like-Illnesses to Patient Volume in an Urgent Care Setting

We studied the association between OTC pharmaceutical sales and volume of patients with influenza-like-illnesses (ILI) at an urgent care center over one year. OTC pharmaceutical sales explain 36% of the variance in the patient volume, and each standard deviation increase is associated with 4.7 more patient visits to the urgent care center (p<0.0001). Cross-correlation function analysis demonstrated that OTC pharmaceutical sales are significantly associated with patient volume during non-flu season (p<0.0001), but only the sales of cough and cold (p<0.0001) and thermometer (p<0.0001) categories were significant during flu season with a lag of two and one days, respectively. Our study is the first study to demonstrate and measure the relationship between OTC pharmaceutical sales and urgent care center patient volume, and presents strong evidence that OTC sales predict urgent care center patient volume year round. © 2013 Liu et al

Toward the optimal strategy for sustained weight loss in overweight cancer survivors: a systematic review of the literature

Purpose: To gain more insight into the optimal strategy to achieve weight loss and weight loss maintenance in overweight and obese cancer survivors after completion of initial treatment, this systematic review aimed to provide an overview of the literature on intervention effects on weight, to describe intervention components used in effective interventions, to identify and synthesize behaviour change techniques (BCTs) and to assess the frequency with which these BCTs were used in effective interventions. / Methods: Six databases were searched for original research articles describing weight changes in adult overweight cancer survivors after participation in a lifestyle intervention initiated after completion of initial treatment. Two researchers independently screened the retrieved papers and extracted BCTs using the BCT Taxonomy version 1. / Results: Thirty-two papers describing 27 interventions were included. Interventions that were evaluated with a robust study design (n = 8) generally showed <5% weight loss and did not evaluate effects at ≥12 months after intervention completion. Effective interventions promoted both diet and physical activity and used the BCTs ‘goal setting (behaviour)’, ‘action planning’, ‘social support (unspecified)’ and ‘instruction on how to perform the behaviour’. / Conclusions: The results of this first review on intervention components of effective interventions could be used to inform intervention development and showed a need for future publications to report long-term effects, a detailed intervention description and an extensive process evaluation. / Implications for cancer survivors: This study contributed to increasing knowledge on the optimal strategy to achieve weight loss, which is recommended for overweight cancer survivors to improve health outcomes

Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules

Background: Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties.&lt;p&gt;&lt;/p&gt; Methods: An in vitro multi-species biofilm containing &lt;i&gt;S. mitis, F. nucleatum, P. Gingivalis&lt;/i&gt; and &lt;i&gt;A. Actinomycetemcomitans&lt;/i&gt; was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level.&lt;p&gt;&lt;/p&gt; Results: CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA.&lt;p&gt;&lt;/p&gt; Conclusions: CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.&lt;p&gt;&lt;/p&gt

Heterologous expression screens in Nicotiana benthamiana identify a candidate effector of the wheat Yellow Rust Pathogen that associates with processing bodies

Rust fungal pathogens of wheat (Triticum spp.) affect crop yields worldwide. The molecular mechanisms underlying the virulence of these pathogens remain elusive, due to the limited availability of suitable molecular genetic research tools. Notably, the inability to perform high-throughput analyses of candidate virulence proteins (also known as effectors) impairs progress. We previously established a pipeline for the fast-forward screens of rust fungal candidate effectors in the model plant Nicotiana benthamiana. This pipeline involves selecting candidate effectors in silico and performing cell biology and protein-protein interaction assays in planta to gain insight into the putative functions of candidate effectors. In this study, we used this pipeline to identify and characterize sixteen candidate effectors from the wheat yellow rust fungal pathogen Puccinia striiformis f sp tritici. Nine candidate effectors targeted a specific plant subcellular compartment or protein complex, providing valuable information on their putative functions in plant cells. One candidate effector, PST02549, accumulated in processing bodies (P-bodies), protein complexes involved in mRNA decapping, degradation, and storage. PST02549 also associates with the P-body-resident ENHANCER OF mRNA DECAPPING PROTEIN 4 (EDC4) from N. benthamiana and wheat. We propose that P-bodies are a novel plant cell compartment targeted by pathogen effectors

Candidiasis : predisposing factors, prevention, diagnosis and alternative treatment

Candidiasis is the most common opportunistic yeast infection. Candida species and other microorganisms are involved in this complicated fungal infection, but Candida albicans continues to be the most prevalent. In the past two decades, it has been observed an abnormal overgrowth in the gastrointestinal, urinary and respiratory tracts, not only in immunocompromised patients, but also related to nosocomial infections and even in healthy individuals. There is a widely variety of causal factors that contribute to yeast infection which means that candidiasis is a good example of a multifactorial syndrome. Due to rapid increase in the incidence in these infections, this is the subject of numerous studies. Recently, the focus of attention is the treatment and, above all, the prevention of those complications. The diagnosis of candidiasis could become quite complicated. Prevention is the most effective “treatment,” much more than eradication of the yeast with antifungal agents. There are several aspects to consider in the daily routine that can provide a strength protection. However, a therapeutic approach is necessary when the infection is established, and therefore, other alternatives should be explored. This review provides an overview on predisposition factors, prevention and diagnosis of candidiasis, highlighting alternative approaches for candidiasis treatment.The authors are grateful to Foundation for Science and Technology (FCT, Portugal) for N. Martins grant (SFRH/BD/87658/2012), L. Barros researcher contract under "Programa Compromisso com Ciencia-2008'' and financial support to the research center CIMO (strategic project PEst-OE/AGR/UI0690/2011)

A novel 3D imaging system for strawberry phenotyping

Accurate and quantitative phenotypic data in plant breeding programmes is vital in breeding to assess the performance of genotypes and to make selections. Traditional strawberry phenotyping relies on the human eye to assess most external fruit quality attributes, which is time-consuming and subjective. 3D imaging is a promising high-throughput technique that allows multiple external fruit quality attributes to be measured simultaneously. A low cost multi-view stereo (MVS) imaging system was developed, which captured data from 360° around a target strawberry fruit. A 3D point cloud of the sample was derived and analysed with custom-developed software to estimate berry height, length, width, volume, calyx size, colour and achene number. Analysis of these traits in 100 fruits showed good concordance with manual assessment methods. This study demonstrates the feasibility of an MVS based 3D imaging system for the rapid and quantitative phenotyping of seven agronomically important external strawberry traits. With further improvement, this method could be applied in strawberry breeding programmes as a cost effective phenotyping technique

A Variant of TNFR2-Fc Fusion Protein Exhibits Improved Efficacy in Treating Experimental Rheumatoid Arthritis

Etanercept, a TNF receptor 2-Fc fusion protein, is currently being used for the treatment of rheumatoid arthritis (RA). However, 25% to 38% of patients show no response which is suspected to be partially due to insufficient affinity of this protein to TNFα. By using computational protein design, we found that residue W89 and E92 of TNFR2 were critical for ligand binding. Among several mutants tested, W89Y/E92N displayed 1.49-fold higher neutralizing activity to TNFα, as compared to that of Etanercept. Surface plasmon resonance (SPR) based binding assay revealed that the equilibrium dissociation constant of W89Y/E92N to TNFα was 3.65-fold higher than that of Etanercept. In a rat model of collagen-induced arthritis (CIA), W89Y/E92N showed a significantly better ability than Etanercept in reducing paw swelling and improvement of arthritic joint histopathologically. These data demonstrate that W89Y/E92N is potentially a better candidate with improved efficacy in treating RA and other autoimmune diseases

Set optimization - a rather short introduction

Recent developments in set optimization are surveyed and extended including various set relations as well as fundamental constructions of a convex analysis for set- and vector-valued functions, and duality for set optimization problems. Extensive sections with bibliographical comments summarize the state of the art. Applications to vector optimization and financial risk measures are discussed along with algorithmic approaches to set optimization problems

Tune Deafness: Processing Melodic Errors Outside of Conscious Awareness as Reflected by Components of the Auditory ERP

Tune deafness (TD) is a central auditory processing disorder characterized by the inability to discriminate pitch, reproduce melodies or to recognize deviations in melodic structure, in spite of normal hearing. The cause of the disorder is unknown. To identify a pathophysiological marker, we ascertained a group of severely affected TD patients using the Distorted Tunes Test, an ecologically valid task with a longstanding history, and used electrophysiological methods to characterize the brain's responses to correct and incorrect melodic sequences. As expected, we identified a neural correlate of patients' unawareness of melodic distortions: deviant notes modulated long-latency auditory evoked potentials and elicited a mismatch negativity in controls but not in affected subjects. However a robust P300 was elicited by deviant notes, suggesting that, as in blindsight, TD subjects process stimuli that they cannot consciously perceive. Given the high heritability of TD, these patients may make it possible to use genetic methods to study cellular and molecular mechanisms underlying conscious awareness