The identification of informative genes from multiple datasets with increasing complexity

Background In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes. Results In this paper, we identify the most appropriate model complexity using cross-validation and independent test set validation for predicting gene expression in three published datasets related to myogenesis and muscle differentiation. Furthermore, we demonstrate that models trained on simpler datasets can be used to identify interactions among genes and select the most informative. We also show that these models can explain the myogenesis-related genes (genes of interest) significantly better than others (P < 0.004) since the improvement in their rankings is much more pronounced. Finally, after further evaluating our results on synthetic datasets, we show that our approach outperforms a concordance method by Lai et al. in identifying informative genes from multiple datasets with increasing complexity whilst additionally modelling the interaction between genes. Conclusions We show that Bayesian networks derived from simpler controlled systems have better performance than those trained on datasets from more complex biological systems. Further, we present that highly predictive and consistent genes, from the pool of differentially expressed genes, across independent datasets are more likely to be fundamentally involved in the biological process under study. We conclude that networks trained on simpler controlled systems, such as in vitro experiments, can be used to model and capture interactions among genes in more complex datasets, such as in vivo experiments, where these interactions would otherwise be concealed by a multitude of other ongoing events

Sensitivity of Local Dynamic Stability of Over-Ground Walking to Balance Impairment Due to Galvanic Vestibular Stimulation

Impaired balance control during gait can be detected by local dynamic stability measures. For clinical applications, the use of a treadmill may be limiting. Therefore, the aim of this study was to test sensitivity of these stability measures collected during short episodes of over-ground walking by comparing normal to impaired balance control. Galvanic vestibular stimulation (GVS) was used to impair balance control in 12 healthy adults, while walking up and down a 10 m hallway. Trunk kinematics, collected by an inertial sensor, were divided into episodes of one stroll along the hallway. Local dynamic stability was quantified using short-term Lyapunov exponents (λs), and subjected to a bootstrap analysis to determine the effects of number of episodes analysed on precision and sensitivity of the measure. λs increased from 0.50 ± 0.06 to 0.56 ± 0.08 (p = 0.0045) when walking with GVS. With increasing number of episodes, coefficients of variation decreased from 10 ± 1.3% to 5 ± 0.7% and the number of p values >0.05 from 42 to 3.5%, indicating that both precision of estimates of λs and sensitivity to the effect of GVS increased. λs calculated over multiple episodes of over-ground walking appears to be a suitable measure to calculate local dynamic stability on group level

Differences in the haematological profile of healthy 70 year old men and women: normal ranges with confirmatory factor analysis

<p>Abstract</p> <p>Background</p> <p>Reference ranges are available for different blood cell counts. These ranges treat each cell type independently and do not consider possible correlations between cell types.</p> <p>Methods</p> <p>Participants were identified from the Community Health Index as survivors of the 1947 Scottish Mental Survey, all born in 1936, who were resident in Lothian (potential n = 3,810) and invited to participate in the study. Those who consented were invited to attend a Clinical Research Facility where, amongst other assessments, blood was taken for full blood count. First we described cell count data and bivariate correlations. Next we performed principal components analysis to identify common factors. Finally we performed confirmatory factor analysis to evaluate suitable models explaining relationships between cell counts in men and women.</p> <p>Results</p> <p>We examined blood cell counts in 1027 community-resident people with mean age 69.5 (range 67.6-71.3) years. We determined normal ranges for each cell type using Q-Q plots which showed that these ranges were significantly different between men and women for all cell types except basophils. We identified three principal components explaining around 60% of total variance of cell counts. Varimax rotation indicated that these could be considered as erythropoietic, leukopoietic and thrombopoietic factors. We showed that these factors were distinct for men and women by confirmatory factor analysis: in men neutrophil count was part of a 'thrombopoietic' trait whereas for women it was part of a 'leukopoietic' trait.</p> <p>Conclusions</p> <p>First, normal ranges for haematological indices should be sex-specific; at present this only pertains to those associated with erythrocytes. Second, differences between individuals across a range of blood cell counts can be explained to a considerable extent by three major components, but these components are not the same in men and women.</p

Patient-reported treatment burden of chronic immune thrombocytopenia therapies

<p>Abstract</p> <p>Background</p> <p>Chronic immune thrombocytopenia (ITP) is a debilitating autoimmune disorder that causes a reduction in blood platelets and increased risk of bleeding. ITP is currently managed with various pharmacologic therapies and splenectomy.</p> <p>This study was conducted to assess patient perceived and reported treatment side effects, as well as the perceived burden or bother, and need to reduce or stop treatment, associated with these side effects among adult patients with chronic ITP.</p> <p>Methods</p> <p>A Web-enabled survey was administered to members of a US-based ITP patient support group. Patients reported demographic and clinical characteristics, ITP treatments' side effects for treatments received since diagnosed, level of bother (or distress), and need to reduce or stop treatment, associated with side effects. Current and past exposure was assessed for five specific treatment types: corticosteroids (CS), intravenous immunoglobulin (IVIg), anti-D immunoglobulin (anti-D), rituximab (RT), and splenectomy (SPL), as well as for other patient-referenced therapies (captured as "other").</p> <p>Results</p> <p>The survey was completed by 589 patients; 78% female, 89% white, mean age 48 years (SD = 14.71), and 68% reported a typical low platelet count of < 50,000/μL. Current or past treatment with CS was reported by 92% (n = 542) of patients, 56% (n = 322) for IVIg, 36% (n = 209) for anti-D, 36% (n = 213) for RT, and 39% (n = 227) for SPL. A substantial proportion of CS-treated patients reported side effects (98%, <it>P </it>< 0.05), were highly bothered by their side effects (53.1%, <it>P </it>< 0.05), and reported the need to stop or reduce treatment due to side effects (37.8%, <it>P </it>< 0.05). Among patients reporting side effects of treatment, significant associations were noted for the number of side effects, aggregate bother of reported side effects, and the need to stop or reduce treatment (all <it>P </it>< 0.05).</p> <p>Conclusions</p> <p>Current ITP treatments, particularly corticosteroids, are associated with multiple bothersome side effects that may lead to patients stopping or reducing therapy. Open, informed and complete communication between clinician and patient regarding both the benefits and the side effects of ITP treatment may better prepare patients for their prescribed regimens.</p

A Systematic Review of the Effectiveness of Acceptance and Commitment Therapy (ACT) for Body Image Dissatisfaction and Weight Self-Stigma in Adults

© 2018, The Author(s). Body image dissatisfaction (BID) and weight self-stigma are prevalent and associated with physical and psychological ill-health. Acceptance and Commitment Therapy (ACT) is increasingly employed for both, yet little is known about its effectiveness. Searches of 12 databases identified six studies using online, face-to-face or self-help ACT interventions for BID or weight self-stigma, of varying duration and intensity. Their effectiveness and quality were evaluated. Two reported improved BID, three improved weight self-stigma, and one reported no impact on weight self-stigma. Methodological issues (small sample sizes, lack of allocation concealment, attention control and long-term follow up) impacted the validity of findings. Due to the small number of studies and poor study quality, the effectiveness of ACT for BID and weight self-stigma remains unclear. Nonetheless findings suggest psychological flexibility may facilitate reduction in BID and weight self-stigma and indicate that brief online as well as lengthy face-to-face delivery may be useful. Suggestions for further research are made

CRPV Genomes with Synonymous Codon Optimizations in the CRPV E7 Gene Show Phenotypic Differences in Growth and Altered Immunity upon E7 Vaccination

Papillomaviruses use rare codons relative to their hosts. Recent studies have demonstrated that synonymous codon changes in viral genes can lead to increased protein production when the codons are matched to those of cells in which the protein is being expressed. We theorized that the immunogenicity of the virus would be enhanced by matching codons of selected viral genes to those of the host. We report here that synonymous codon changes in the E7 oncogene are tolerated in the context of the cottontail rabbit papillomavirus (CRPV) genome. Papilloma growth rates differ depending upon the changes made indicating that synonymous codons are not necessarily neutral. Immunization with wild type E7 DNA yielded significant protection from subsequent challenge by both wild type and codon-modified genomes. The reduction in growth was most dramatic with the genome containing the greatest number of synonymous codon changes

The South, the suburbs, and the Vatican too: explaining partisan change among Catholics

This paper explains changes in partisanship among Catholics in the last quarter of the 20th Century using a theory of partisan change centered on the contexts in which Catholics lived. Catholics were part of the post-New Deal Democratic coalition, but they have become a swing demographic group. We argue that these changes in partisanship are best explained by changes in elite messages that are filtered through an individual’s social network. Those Catholics who lived or moved into the increasingly Republican suburbs and South were the Catholics who were most likely to adopt a non-Democratic partisan identity. Changes in context better explain Catholic partisanship than party abortion policy post Roe v. Wade or ideological sorting. We demonstrate evidence in support of our argument using the ANES cumulative file from 1972 through 2000

Molecular targeted therapies in head and neck cancer - An update of recent developements -

Targeted therapies have made their way into clinical practice during the past decade. They have caused a major impact on the survival of cancer patients in many areas of clinical oncology and hematology. Indeed, in some hematologic malignancies, such as chronic myelogenous leukemia or non-Hodgkin's lymphomas, biologicals and antibodies specifically designed to target tumour-specific proteins have revolutionized treatment standards. In solid tumours, new drugs targeting EGF- or VEGF- receptors are now approved and are entering clinical practise for treatment of colon, lung, kidney and other cancers, either alone or in combination with conventional treatment approaches

Dietary Re-education, Exercise Program, Performance and Body Indexes Associated with Risk Factors in Overweight/Obese Women

This study observed the effect of a dietary re-education plus regular physical activity on body composition, risk factors and physical test performance of sedentary overweight/obese women and to correlate these variables one with each other. Fifty women (36 ± 10 yrs; 31 ± 6 body mass index (BMI, kg/m2)) volunteered for the study. Body compositions were obtained by anthropometry and bioimpedance and some body indexes were established. One-repetition maximum (1-RM) and treadmill VO2max tests were carried out and blood samples were obtained for lipid, glucose and uric acid analyses before (T1) and after two months of intervention (T2). Diet was established by indirect calorimetry. Body fat, glucose, uric acid, total cholesterol, HDL-cholesterol and systolic blood pressure were significantly reduced. The 1-RM and VO2max tests were significantly increased. Neck circumference (NC) was correlated with body composition, back muscle 1-MR, HDL and LDL cholesterol, total cholesterol/HDL ratio, uric acid, and resting energy expenditure. BMI was found to be significantly correlated with waist/hip ratio, circumference sum, and body fat percentage by anthropometry and bioimpedance. Body fat percentage determined by bioimpedance and anthropometry was significantly correlated with arm fat area and arm fat area corrected respectively, and both with BMI at T1 and T2. This study suggests that a dietary reeducation plus physical activity around 200 min/week improved body composition and the health of these women. Many anthropometry measurements have correspondence to risk factors and NC could be a simple approach to reflect these results, without other more complex techniques