Application of Multi-SNP Approaches Bayesian LASSO and AUC-RF to Detect Main Effects of Inflammatory-Gene Variants Associated with Bladder Cancer Risk

The relationship between inflammation and cancer is well established in several tumor types, including bladder cancer. We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC)/EPICURO Study. A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing. We further applied two more comprehensive methods to capture the complexity of bladder cancer genetic susceptibility: Bayesian Threshold LASSO (BTL), a regularized regression method, and AUC-Random Forest, a machine-learning algorithm. Both approaches explore the joint effect of markers. BTL analysis identified a signature of 37 SNPs in 34 genes showing an association with bladder cancer. AUC-RF detected an optimal predictive subset of 56 SNPs. 13 SNPs were identified by both methods in the total population. Using resources from the Texas Bladder Cancer study we were able to replicate 30% of the SNPs assessed. The associations between inflammatory SNPs and bladder cancer were reexamined among non-smokers to eliminate the effect of tobacco, one of the strongest and most prevalent environmental risk factor for this tumor. A 9 SNP-signature was detected by BTL. Here we report, for the first time, a set of SNP in inflammatory genes jointly associated with bladder cancer risk. These results highlight the importance of the complex structure of genetic susceptibility associated with cancer risk.

Three-level main-effects designs exploiting prior information about model uncertainty

To explore the projection efficiency of a design, Tsai, et al [2000. Projective three-level main effects designs robust to model uncertainty. Biometrika 87, 467-475] introduced the Q criterion to compare three-level main-effects designs for quantitative factors that allow the consideration of interactions in addition to main effects. In this paper, we extend their method and focus on the case in which experimenters have some prior knowledge, in advance of running the experiment, about the probabilities of effects being non-negligible. A criterion which incorporates experimenters' prior beliefs about the importance of each effect is introduced to compare orthogonal, or nearly orthogonal, main effects designs with robustness to interactions as a secondary consideration. We show that this criterion, exploiting prior information about model uncertainty, can lead to more appropriate designs reflecting experimenters' prior beliefs. (c) 2006 Elsevier B.V. All rights reserved.

Some new three-level orthogonal main effects plans robust to model uncertainty

In this paper, we list some new orthogonal main effects plans for three-level designs for 4, 5 and 6 factors in IS runs and compare them with designs obtained from the existing L-18 orthogonal array. We show that these new designs have better projection properties and can provide better parameter estimates for a range of possible models. Additionally, we study designs in other smaller run-sizes when there are insufficient resources to perform an 18-run experiment. Plans for three-level designs for 4, 5 and 6 factors in 13 to 17 runs axe given. We show that the best designs here are efficient and deserve strong consideration in many practical situations.

Does Social Support Really Help to Eat a Low-Fat Diet? Main Effects and Gender Differences of Received Social Support within the Health Action Process Approach

BACKGROUND: Most theories of health-behavior change focus exclusively on individual self-regulation without taking social factors, such as social support, into account. This study's first aim was to systematically test the added value of received instrumental and emotional social support within the Health Action Process Approach (HAPA) in the context of dietary change. In the social support literature, gender effects emerge with regard to the effectiveness of social support. Thus, a second aim was the examination of gender differences in the association of social support with dietary behavior. METHODS: Participants were 252 overweight and obese individuals. At baseline and 12 months later, participants completed questionnaires on HAPA variables; diet-specific received social support and low-fat diet. RESULTS: For the prediction of intentions 12 months later, instrumental support was more beneficial for men than for women over and above individual self-regulation. In terms of dietary behavior at T2, a moderate main effect of instrumental support emerged. Moreover, received emotional social support was beneficial for men, but not for women in terms of a low-fat diet 12 months later. CONCLUSIONS: Effects of received instrumental social support found in this study provide new evidence for the added value of integrating social support into the HAPA.

An experimental study of the effects of work stress, work control, and task information on adjustment

The present study was designed to examine the main and interactive effects of task demands, work control, and task information on levels of adjustment. Task demands, work control, and task information were manipulated in an experimental setting where participants completed a letter-sorting activity (N = 128). Indicators of adjustment included measures of positive mood, participants' perceptions of task performance, and task satisfaction. Results of the present study provided some support for the main effects of objective task demands, work control, and task information on levels of adjustment. At the subjective level of analysis, there was some evidence to suggest that work control and task information interacted in their effects on levels of adjustment. There was minimal support for the proposal that work control and task information would buffer the negative effects of task demands on adjustment. There was, however, some evidence to suggest that the stress-buffering role of subjective work control was more marked at high, rather than low, levels of subjective task information.

The effects of work control and job demands on employee adjustment and work performance

The present study examined the effects of work control and job demands on employee adjustment and work performance using a multidimensional measure of work control (assessing levels of task control, decision control and work scheduling control). It was proposed that the negative effects of job demands and employee adjustment would be moderated by high levels of task control. It was also proposed that there would be evidence of main effects of both job demands and work control (particularly task-related levels of control) on employee adjustment. To test these predictions, a study of 135 university employees holding administrative positions was undertaken. Methodological improvements over previous research included the use of both self-reported adjustment measures and supervisor ratings of work performance as outcome variables, and the assessment of the predictor and outcome measures at different points in time (self-reported adjustment was assessed at both Times 1 and 2). The results revealed some support for the proposal that the effects of job demands would be buffered by high levels of task control, but not more peripheral aspects of work control. There were also significant main effects of task control on job satisfaction.

A comparative study of the effects of UV- and gamma-radiation on copolymers of acrylonitrile/butadiene

The radiolysis of nitrile rubbers with different acrylonitrile/butadiene composition and the homopolymers, poly(butadiene) (PBD) and poly(acrylonitrile) (PAN) has been investigated and compared with the photolysis of the same polymers. A significantly different mechanism of degradation was found for the two types of radiation. The results obtained by ESR, FTIR and measurements of soluble fractions of irradiated samples, indicated that the acrylonitrile units of the nitrile rubbers are more sensitive units to gamma-radiation, with the effects of irradiation increasing with the acrylonitrile content. The reactions observed were consumption of double bonds, crosslinking, and cyclization with the formation of conjugated double bonds. No chain-scission reactions were detected. In contrast to gamma-irradiation, the effects of photolysis were centred at the butadiene units, and increases in the acrylonitrile content resulted in a proportional decrease in the sensitivity of the copolymers. Crosslinking and chain scission were identified as the main effects of photolysis of NBR rubbers. (C) 1999 Society of Chemical Industry.

Effects of bromazepam in frontal theta activity on the performance of a sensorimotor integration task: A quantitative electroencephalography study

Our objective is to verify the modulatory effects of bromazepam on EEG theta absolute power when subjects were submitted to a visuomotor task (i.e., car driver task). Sample was composed of 14 students (9 males and 5 females), right handed, with ages varying between 23 and 42 years (mean = 32.5 +/- 9.5), absence of mental or physical impairments, no psychoactive or psychotropic substance use and no neuromuscular disorders (screened by a clinical examination). The results showed an interaction between condition and electrodes (p=0.034) in favor of F8 electrode compared with F7 in both experimental conditions (t-test; p=0.001). Additionally, main effects were observed for condition (p=0.001), period (p=0.001) and electrodes (p=0.031) in favor of F4 electrode compared with F3. In conclusion, Br 6 mg of bromazepam may interfere in sensorimotor processes in the task performance in an unpredictable scenario allowing that certain visuospatial factors were predominant. Therefore, the results may reflect that bromazepam effects influence the performance of the involved areas because of the acquisition and integration of sensory stimuli processes until the development of a motor behavior based on the same stimuli. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Reduced gray matter volume in ventral prefrontal cortex but not amygdala in bipolar disorder: Significant effects of gender and trait anxiety

Neuroimaging studies in bipolar disorder report gray matter volume (GMV) abnormalities in neural regions implicated in emotion regulation. This includes a reduction in ventral/orbital medial prefrontal cortex (OMPFC) GMV and, inconsistently, increases in amygdala GMV. We aimed to examine OMPFC and amygdala GMV in bipolar disorder type 1 patients (BPI) versus healthy control participants (HC), and the potential confounding effects of gender, clinical and illness history variables and psychotropic medication upon any group differences that were demonstrated in OMPFC and amygdala GMV Images were acquired from 27 BPI (17 euthymic, 10 depressed) and 28 age- and gender-matched HC in a 3T Siemens scanner. Data were analyzed with SPM5 using voxel-based morphometry (VBM) to assess main effects of diagnostic group and gender upon whole brain (WB) GMV. Post-hoc analyses were subsequently performed using SPSS to examine the extent to which clinical and illness history variables and psychotropic medication contributed to GMV abnormalities in BPI in a priori and non-a priori regions has demonstrated by the above VBM analyses. BPI showed reduced GMV in bilateral posteromedial rectal gyrus (PMRG), but no abnormalities in amygdala GMV. BPI also showed reduced GMV in two non-a priori regions: left parahippocampal gyrus and left putamen. For left PMRG GMV, there was a significant group by gender by trait anxiety interaction. GMV was significantly reduced in male low-trait anxiety BPI versus male low-trait anxiety HC, and in high-versus low-trait anxiety male BPI. Our results show that in BPI there were significant effects of gender and trait-anxiety, with male BPI and those high in trait-anxiety showing reduced left PMRG GMV. PMRG is part of medial prefrontal network implicated in visceromotor and emotion regulation. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Effects of emotional valence and three-dimensionality of visual stimuli on brain activation: an fMRI study

BACKGROUND: Examining changes in brain activation linked with emotion-inducing stimuli is essential to the study of emotions. Due to the ecological potential of techniques such as virtual reality (VR), inspection of whether brain activation in response to emotional stimuli can be modulated by the three-dimensional (3D) properties of the images is important. OBJECTIVE: The current study sought to test whether the activation of brain areas involved in the emotional processing of scenarios of different valences can be modulated by 3D. Therefore, the focus was made on the interaction effect between emotion-inducing stimuli of different emotional valences (pleasant, unpleasant and neutral valences) and visualization types (2D, 3D). However, main effects were also analyzed.METHODS: The effect of emotional valence and visualization types and their interaction were analyzed through a 3x2 repeated measures ANOVA. Post-hoc t-tests were performed under a ROI-analysis approach. RESULTS: The results show increased brain activation for the 3D affective-inducing stimuli in comparison with the same stimuli in 2D scenarios, mostly in cortical and subcortical regions that are related to emotional processing, in addition to visual processing regions. CONCLUSIONS: This study has the potential of clarify brain mechanisms involved in the processing of emotional stimuli (scenarios’ valence) and their interaction with three-dimensionality.

The separate and combined effects of MHC genotype, parasite clone, and host gender on the course of malaria in mice.

BACKGROUND: The link between host MHC (major histocompatibility complex) genotype and malaria is largely based on correlative data with little or no experimental control of potential confounding factors. We used an experimental mouse model to test for main effects of MHC-haplotypes, MHC heterozygosity, and MHC x parasite clone interactions. We experimentally infected MHC-congenic mice (F2 segregants, homo- and heterozygotes, males and females) with one of two clones of Plasmodium chabaudi and recorded disease progression. RESULTS: We found that MHC haplotype and parasite clone each have a significant influence on the course of the disease, but there was no significant host genotype by parasite genotype interaction. We found no evidence for overdominance nor any other sort of heterozygote advantage or disadvantage. CONCLUSION: When tested under experimental conditions, variation in the MHC can significantly influence the course of malaria. However, MHC heterozygote advantage through overdominance or dominance of resistance cannot be assumed in the case of single-strain infections. Future studies might focus on the interaction between MHC heterozygosity and multiple-clone infections.

Immediate Effects of Neurodynamic Sliding versus Muscle Stretching on Hamstring Flexibility in Subjects with Short Hamstring Syndrome.

Background. Hamstring injuries continue to affect active individuals and although inadequate muscle extensibility remains a commonly accepted factor, little is known about the most effective method to improve flexibility. Purpose. To determine if an isolated neurodynamic sciatic sliding technique would improve hamstring flexibility to a greater degree than stretching or a placebo intervention in asymptomatic subjects with short hamstring syndrome (SHS). Study Design. Randomized double-blinded controlled trial. Methods. One hundred and twenty subjects with SHS were randomized to 1 of 3 groups: neurodynamic sliding, hamstring stretching, and placebo control. Each subject's dominant leg was measured for straight leg raise (SLR) range of motion (ROM) before and after interventions. Data were analyzed with a 3 × 2 mixed model ANOVA followed by simple main effects analyses. Results. At the end of the study, more ROM was observed in the Neurodynamic and Stretching groups compared to the Control group and more ROM in the Neurodynamic group compared to Stretching group. Conclusion. Findings suggest that a neurodynamic sliding technique will increase hamstring flexibility to a greater degree than static hamstring stretching in healthy subjects with SHS. Clinical Relevance. The use of neurodynamic sliding techniques to improve hamstring flexibility in sports may lead to a decreased incidence in injuries; however, this needs to be formally tested.

Clinical and hormonal effects of the new angiotensin II receptor antagonist LRB081.

The renin-angiotensin system is a major contributor to the pathophysiology of cardiovascular diseases such as congestive heart failure and hypertension. Antagonizing angiotensin (Ang) II at the receptor site may produce fewer side effects than inhibition of the promiscuous converting enzyme. The present study was designed to assess in healthy human subjects the effect of LRB081, a new orally active AT1-receptor antagonist, on the pressor action of exogenous Ang II. At the same time, plasma hormones and drug levels were monitored. At 1-week intervals and in a double-blind randomized fashion, 8 male volunteers received three doses of LRB081 (10, 40, and 80 mg) and placebo. Blood pressure (BP) was measured at a finger by photoplethysmograph. The peak BP response to intravenous injection of a standard dose of Ang II was determined before and for < or = 24 h after administration of an oral dose of LRB081 or placebo. After drug administration, the blood BP response to Ang II was expressed in percent of the response before drug administration. At the same time, plasma renin activity (PRA), Ang II, aldosterone, catecholamine (radioassays), and drug levels (by high-performance liquid chromatography) were monitored. After LRB081 administration, a dose dependent inhibition of the BP response to Ang II was observed. Maximal inhibition of the systolic BP response was 54 +/- 3 (mean +/- SEM), 63 +/- 2, and 93 +/- 1% with 10, 40, and 80 mg LRB081, respectively. The time to peak was 3 h for 6 subjects and 4 and 6 h for 2 others. Preliminary plasma half-life (t1/2) was calculated at 2 h. With the highest dose, the inhibition remained significant for 24 h (31 +/- 5%, p < 0.05). Maximal BP-blocking effect and maximal plasma drug level coincided, suggesting that the unmetabolized LRB081 is responsible for the antagonistic effect. PRA and Ang II increased dose dependently after LRB081 intake. Aldosterone, epinephrine, and norepinephrine concentrations remained unchanged. No clinically significant adverse reaction was observed during the study. LRB081 is a well-tolerated, orally active, potent, and long-acting Ang II receptor antagonist. Unlike in the case of losartan, no active metabolite of LRB081 has been shown to be responsible for the main effects.

Auction theory, sequential local service privatization, and the effects of geographical scale economies on effective competition

A sequential weakly efficient two-auction game with entry costs, interdependence between objects, two potential bidders and IPV assumption is presented here in order to give some theoretical predictions on the effects of geographical scale economies on local service privatization performance. It is shown that the first object seller takes profit of this interdependence. The interdependence externality rises effective competition for the first object, expressed as the probability of having more than one final bidder. Besides, if there is more than one final bidder in the first auction, seller extracts the entire bidder¿s expected future surplus differential between having won the first auction and having lost. Consequences for second object seller are less clear, reflecting the contradictory nature of the two main effects of object interdependence. On the one hand, first auction winner becomes ¿stronger¿, so that expected payments rise in a competitive environment. On the other hand, first auction loser becomes relatively ¿weaker¿, hence (probably) reducing effective competition for the second object. Additionally, some contributions to static auction theory with entry cost and asymmetric bidders are presented in the appendix

The ecological significance of arbuscular mycorrhizal fungal effects on clonal reproduction in plants

The population ecology of clonal plants depends on the number and distribution of ramets formed during growth. Variation in clonal reproduction has previously been explained by variation in effects of abiotic resource heterogeneity and by plant genotypic variation. Different co-occurring species of the mutualistic arbuscular mycorrhizal fungi (AMF) have been shown to differentially alter growth traits of Prunella vulgaris which we hypothesize would lead to changes in clonal reproduction. Two experiments were carried out to test whether different co-occurring mycorrhizal fungi significantly influence clonal reproduction of P. vulgaris whether this effect also occurs when P. vulgaris is growing in an artificial plant community and how the effects compare with plant genotype effects on clonal growth of P. vulgaris. In the first experiment the number of ramets of P. vulgaris growing in a plant community of simulated calcareous grassland was significantly affected by inoculation with different mycorrhizal fungi. The number of ramets produced by P. vulgaris differed by a factor of up to 1.8 with different mycorrhizal fungi. The fungal effects on the number of new ramets were independent of their effects on the biomass of P. vulgaris. In a second experiment 17 different genotypes of P. vulgaris were inoculated with different mycorrhizal fungi. There were significant main effects of genotypes and mycorrhizal fungi on clonal reproduction of P. vulgaris. The effect of different mycorrhizal fungi contributed more than the effect of plant genotype to variation in size and ramet production. However mean stolon length and spacer length which determine the spatial arrangement of ramets were only significantly affected by plant genotype. There were no mycorrhizal fungal X plant genotype interactions on clonal growth of P. vulgaris indicating that there is no obvious evidence that selection pressures would favor further coevolution between P. vulgaris and mycorrhizal fungal species. In natural communities plants can be colonized by several different AMF at the same time. The effect of the mixed AMF treatment on the growth and clonal reproduction of P. vulgaris could not be predicted from the responses of the plants to the single AMF To what extent however the patterns of colonization by different AMF differ among plants in a natural community is unknown. Since the effects of AMF on growth and clonal reproduction occur on a population of P. vulgaris in a microcosm plant community and because the effects are also as great as those caused by plant genotypic variation we conclude that the effects are strong enough to potentially affect population size and variation of clonal plants in communities.