Statistical modelling of transcript profiles of differentially regulated genes

Background: The vast quantities of gene expression profiling data produced in microarray studies, and the more precise quantitative PCR, are often not statistically analysed to their full potential. Previous studies have summarised gene expression profiles using simple descriptive statistics, basic analysis of variance (ANOVA) and the clustering of genes based on simple models fitted to their expression profiles over time. We report the novel application of statistical non-linear regression modelling techniques to describe the shapes of expression profiles for the fungus Agaricus bisporus, quantified by PCR, and for E. coli and Rattus norvegicus, using microarray technology. The use of parametric non-linear regression models provides a more precise description of expression profiles, reducing the "noise" of the raw data to produce a clear "signal" given by the fitted curve, and describing each profile with a small number of biologically interpretable parameters. This approach then allows the direct comparison and clustering of the shapes of response patterns between genes and potentially enables a greater exploration and interpretation of the biological processes driving gene expression. Results: Quantitative reverse transcriptase PCR-derived time-course data of genes were modelled. "Splitline" or "broken-stick" regression identified the initial time of gene up-regulation, enabling the classification of genes into those with primary and secondary responses. Five-day profiles were modelled using the biologically-oriented, critical exponential curve, y(t) = A + (B + Ct)Rt + ε. This non-linear regression approach allowed the expression patterns for different genes to be compared in terms of curve shape, time of maximal transcript level and the decline and asymptotic response levels. Three distinct regulatory patterns were identified for the five genes studied. Applying the regression modelling approach to microarray-derived time course data allowed 11% of the Escherichia coli features to be fitted by an exponential function, and 25% of the Rattus norvegicus features could be described by the critical exponential model, all with statistical significance of p < 0.05. Conclusion: The statistical non-linear regression approaches presented in this study provide detailed biologically oriented descriptions of individual gene expression profiles, using biologically variable data to generate a set of defining parameters. These approaches have application to the modelling and greater interpretation of profiles obtained across a wide range of platforms, such as microarrays. Through careful choice of appropriate model forms, such statistical regression approaches allow an improved comparison of gene expression profiles, and may provide an approach for the greater understanding of common regulatory mechanisms between genes

Response execution and inhibitionin children with AD/HD and other disruptive disorders: the role of behavioural activation.

Item does not contain fulltextThis study was aimed at (a) replicating findings of slow and variable response execution and slow response inhibition in Attention Deficit/Hyperactivity Disorder (AD/HD), (b) investigating whether these deficits are specifically related to AD/HD or may also be observed in Oppositional Defiant Disorder (ODD), and children comorbid for AD/HD+ODD, and (c) examining the role of activation level in task performance of children with AD/HD. To meet these aims, the stop paradigm was administered at three levels of activation, using a slow, medium, and fast presentation rate of stimuli, to 4 groups of children: 24 AD/HD children, 21 children with ODD, 27 children with comorbid AD/HD+ODD, and 41 normal controls. As hypothesized, children with AD/HD exhibited a slow response execution process with considerable variability in the speed of responding compared to normal controls. Slow response execution was also observed in the comorbid AD/HD+ODD group but not in the pure ODD group. Larger variability in the speed of responding was common to all disruptive groups compared with controls. In contrast to our hypothesis, no group differences emerged for inhibitory functioning. Finally, the slow event rate condition caused a further deterioration in the speed of the response execution process in both the AD/HD group and ODD group

Speed of inhibition predicts teacher-rated medication response in boys with attention deficit hyperactivity disorder

Item does not contain fulltextThis study aimed at investigating whether one of the key deficits in Attention Deficit Hyperactivity Disorder (ADHD), slow response inhibition, predicted the response to methylphenidate (MPH) treatment. In order to address this issue, we used Stop Signal Reaction Times (SSRTs) measured at baseline in 20 medication-nave boys with ADHD as predictor, and parent and teacher ratings that were collected during a double-blind, placebo-controlled titration trial of MPH in the same group as outcome measures. Parent and teacher ratings were collected on primary scales, measuring ADHD symptoms, and secondary scales, measuring oppositional and disruptive behaviour. Placebo response and ADHD/Oppositional Defiant Disorder symptom severity at baseline were controlled for in the analyses. The SSRT did not predict the MPH response as measured by parent ratings, but it did predict the MPH response as measured by teacher ratings. This effect was specific for the ADHD scales. The slower SSRTs were, the less children benefited from MPH. Moreover, children with longer SSRTs needed higher doses of MPH for optimal symptom relief than children with shorter SSRTs. These findings have implications for clinicians who face the decision of which MPH dose to prescribe.18 p

Response Inhibition in Children With DSM-IV Subtypes of AD/HD and Related Disruptive Disorders: The Role of Reward

Item does not contain fulltextThe current study had four aims: (a) to replicate previous findings of slow response inhibition in Attention Deficit/Hyperactivity Disorder (AD/HD), (b) to explore whether poor response inhibition in children with AD/HD is a core problem or rather a result of an underlying problem related to reward, (c) to investigate the specificity of poor response inhibition and the role of reward in relation to AD/HD, and (d) to study whether findings would be different for three subtypes of AD/HD. In order to address these issues, a stop paradigm was administered under a reward condition and under a nonreward condition to an AD/HD group (n = 24), an Oppositional Defiant Disorder (ODD)/Conduct Disorder (CD) group (n = 21), a comorbid AD/HD + ODD/CD group (n = 27), and a normal control (NC) group (n = 41). Firstly, contrary to prediction, none of the Disruptive Behavior Disorder (DBD) groups differed from the NC group with respect to the speed of the inhibition process. Secondly, it was shown that children with AD/HD and children with comorbid AD/HD + ODD/CD, but not children with ODD/CD alone, slowed down more dramatically in the reward condition than normal controls. This finding was interpreted as a strategy to increase the chance of being rewarded in children with AD/HD and children with comorbid AD/HD + ODD/CD, but not in children with pure ODD/CD. Finally, analysis of AD/HD subtypes did not change the main findings of this study

Motor timing deficits in community and clinical boys with hyperactive behaviour: The effect of methylphenidate on motor timing.

In a previous paper we showed that community children with hyperactive behavior were more inconsistent than controls in the temporal organization of their motor output. In this study we investigated: (1) various aspects of motor timing processes in 13 clinically diagnosed boys with attention deficit hyperactivity disorder (ADHD) who were compared to 11 community boys with hyperactive behavior and to a control group and (2) the effect of methylphenidate on the motor timing processes in the clinical group with ADHD in a double blind, cross-over, medication-placebo design, including 4 weeks of medication. The clinical group with ADHD, like the community group with hyperactivity, showed greater variability in sensorimotor synchronization and in sensorimotor anticipation relative to controls. The clinical group was also impaired in time perception, which was spared in the community group with hyperactivity. The persistent, but not the acute dose, of methylphenidate reduced the variability of sensorimotor synchronization and anticipation, but had no effect on time perception. This study shows that motor timing functions are impaired in both clinical and community children with hyperactivity. It is the first study to show the effectiveness of persistent administration of methylphenidate on deficits in motor timing in ADHD children and extends the use of methylphenidate from the domain of attentional and inhibitory functions to the domain of executive motor timing

Aprotinin reduces cardiac troponin I release and inhibits apoptosis of polymorphonuclear cells during off-pump coronary artery bypass surgery

Objectives: In addition to blood-sparing effects, aprotinin may have cardioprotective and anti-inflammatory effects during cardiopulmonary bypass-assisted cardiac surgery. In this study, the authors examined whether aprotinin had cardioprotective and/or anti-inflammatory effects in patients undergoing off-pump coronary artery bypass grafting. Design: A prospective randomized clinical trial. Setting: University hospital. Participants: Fifty patients were randomized to control (n = 25) or aprotinin treatment (n = 25) groups. Interventions: Aprotinin was given as a loading dose (2 x 10(6) KIU) followed by a continuous infusion at 5 x 10(5) KIU/h until skin closure. Measurements and Main Results: Blood samples for cardiac troponin I; interleukin-6, interleukin-8, and interleukin-10; tumor necrosis factor a; and elastase were taken after anesthesia induction, completion of revascularization, and 6 hours, 12 hours, and 24 hours after revascularization. Blood samples were taken to assess for apoptosis in polymorphonuclear cells. Baseline plasma levels for cardiac troponin I did not differ between groups but were significantly lower in aprotinin-treated patients at the time of revascularization (P = 0.03) and 6 hours (p = 0.004) and 24 hours (p = 0.03) later. Aprotinin significantly reduced apoptosis in polymorphonuclear cells compared with control-treated patients (p = 0.04). There were no differences in plasma cytokine or elastase levels between groups. Conclusions: The authors conclude that aprotinin reduces perioperative cardiac troponin I release and attenuates apoptosis in polymorphonuclear cells but has no significant effects on plasma cytokine levels in patients undergoing off-pump coronary artery bypass graft surgery

Analytical modeling of axial flux PM machines with eccentricities

© 2017 IOS Press and the authors. All rights reserved. In this paper, an analytical quasi three-dimensional method is used to model an axial flux permanent magnet (AFPM) machine with various eccentricities. AFPM machines (AFPMMs) have various advantages but they are sensitive to geometrical imperfections for manufacturing aspect. The main aim of this paper is to propose a general analytical model to analyze the AFPMMs with various types of eccentricities. The radial and tangential magnetic flux densities in the air gap under healthy condition are obtained via combination of Maxwell's equations and Schwarz-Christoffel (SC) mapping firstly. Next, in order to investigate the eccentricities, equations for air gap length and radii are deduced. The back electromotive force (EMF) is calculated and compared with those from healthy condition and finite element (FE) analysis, respectively. The results show that the analytical predictions agree well with the FE results. Moreover, using this method has a significantly less time consuming than the 3D FM simulation process, which is a great advantage of this method. Finally, the analytical model is verified via experimental results

Avian malaria is absent in juvenile colonial herons (Ardeidae) but not Culex pipiens mosquitoes in the Camargue, Southern France

Apicomplexan blood parasites Plasmodium and Haemoproteus (together termed “Avian malaria”) and Leucocytozoon are widespread, diverse vector-transmitted blood parasites of birds, and conditions associated with colonial nesting in herons (Ardeidae) and other waterbirds appear perfect for their transmission. Despite studies in other locations reporting high prevalence of parasites in juvenile herons, juvenile Little Egrets (Egretta garzetta) previously tested in the Camargue, Southern France, had a total absence of malaria parasites. This study tested the hypotheses that this absence was due to insufficient sensitivity of the tests of infection; an absence of infective vectors; or testing birds too early in their lives. Blood was sampled from juveniles of four species shortly before fledging: Little Egret (n = 40), Cattle Egret (Bubulcus ibis; n = 40), Black-crowned Night-Heron (Nycticorax nycticorax, n = 40), and Squacco Heron (Ardeola ralloides; n = 40). Sensitive nested-Polymerase Chain Reaction was used to test for the presence of parasites in both birds and host-seeking female mosquitoes captured around the colonies. No malaria infection was found of in any of the heron species. Four different lineages of Plasmodium were detected in pooled samples of female Culex pipiens mosquitoes, including two in potentially infective mosquitoes. These results confirm that the absence of malaria parasites previously demonstrated in Little Egret is not due to methodological limitations. Although the prevalence of infection in mosquitoes was low, conditions within the colonies were suitable for transmission of Plasmodium. These colonial heron species may have evolved strategies for resisting malaria infection through physiological or behavioral mechanisms

The effect of methylphenidate on three forms of response inhibition in boys with AD/HD

Item does not contain fulltextThe current study was aimed at (a) investigating the effect of three doses methylphenidate (MPH) and placebo on inhibition of a prepotent response, inhibition of an ongoing response, and interference control in Attention Deficit/Hyperactivity Disorder (AD/HD), and (b) studying dose-response relations for the three forms of response inhibition. To meet these aims, the following tasks were selected: two versions of the Stop Paradigm for inhibition of a prepotent response, a Circle Tracing Task and a recently developed Follow Task for inhibition of an ongoing response, and the Stroop Color-Word Test and an Eriksen Flanker Task for interference control. These tasks were administered to 23 boys with AD/HD during four treatment conditions: 5 mg MPH, 10 mg MPH, 20 mg MPH, and placebo. A pseudorandomized, multiple-blind, placebo-controlled, within-subject design was used. As hypothesized, inhibitory control in children with AD/HD improved under MPH compared to placebo. However, this effect was only significant for inhibition of a prepotent response and inhibition of an ongoing response (as measured by the Follow Task), but not for interference control. The relation between treatment condition and response was linear. However, this linear relation was due to improved inhibitory control under MPH compared to placebo, because no effects of MPH dose were observed for any of the response inhibition measures