Comparing families of dynamic causal models

Mathematical models of scientific data can be formally compared using Bayesian model evidence. Previous applications in the biological sciences have mainly focussed on model selection in which one first selects the model with the highest evidence and then makes inferences based on the parameters of that model. This “best model” approach is very useful but can become brittle if there are a large number of models to compare, and if different subjects use different models. To overcome this shortcoming we propose the combination of two further approaches: (i) family level inference and (ii) Bayesian model averaging within families. Family level inference removes uncertainty about aspects of model structure other than the characteristic of interest. For example: What are the inputs to the system? Is processing serial or parallel? Is it linear or nonlinear? Is it mediated by a single, crucial connection? We apply Bayesian model averaging within families to provide inferences about parameters that are independent of further assumptions about model structure. We illustrate the methods using Dynamic Causal Models of brain imaging data

The presence of serum anti-Ascaris lumbricoides IgE antibodies and of Trichuris trichiura infection are risk factors for wheezing and/or atopy in preschool-aged Brazilian children

<p>Abstract</p> <p>Background</p> <p>The elucidation of factors that trigger the development of transient wheezing in early childhood may be an important step toward understanding the pathogenesis of asthma and other allergic diseases later in life. Transient wheezing has been mainly attributed to viral infections, although sensitisation to aeroallergens and food allergens may occur at an early age. In developing countries, intestinal helminthic infections have also been associated with allergy or atopy-related disorders.</p> <p>Objective</p> <p>The aim of this study was to explore the association of <it>Trichuris trichiura </it>and <it>Ascaris lumbricoides </it>infections with wheezing and atopy in early childhood.</p> <p>Study design</p> <p>A cross-sectional study using a Portuguese-language ISAAC phase I questionnaire, adapted for preschool-aged children, nested in a cohort study of childhood diarrhoea, was conducted on 682 children. Two faecal samples per child were examined for the presence of intestinal helminthic infection. IgE antibodies against three allergenic preparations <it>(Dermatophagoides pteronyssinus, Blomia tropicalis </it>and common child food), as well as against <it>A. lumbricoides </it>antigens, were measured in a sub-sample of these children, whose parents allowed the procedure. Atopy was defined by the presence of levels of serum IgE antibodies ≥0.35 kU/L against at least one of the three tested allergenic preparations.</p> <p>Results</p> <p>Active <it>T. trichiura </it>infection but not <it>A. lumbricoides </it>infection was positively associated with wheezing in the total studied children population [adjusted OR = 2.60; CI = 1.54;4.38] and in the atopic children sub-population [adjusted OR = 3.07; CI = 1.00;9.43]. The association with atopy was also positive and statistically significant only in the brute analysis [OR = 2.13; CI = 1.03;4.40]. Anti-<it>A. lumbricoides </it>IgE antibodies, but not current <it>A. lumbricoides </it>infection, were positively associated with wheezing in atopic children [adjusted OR = 2.01; CI = 1.00;4.50] and in non-atopic children [adjusted OR = 3.07; CI = 1.13;8.35] and it was also associated with atopy [adjusted OR = 7.29; CI = 3.90; 13.4]. On the other hands, reports of wheezing were not significantly associated with atopy.</p> <p>Conclusions</p> <p>These data corroborate previous studies showing that wheezing is predominantly associated with infection in early childhood and shows that anti-<it>A. lumbricoides </it>IgE antibodies, but not active <it>Ascaris </it>infections, are associated with wheezing and atopy. Additionally, the data demonstrate that <it>T. trichiura </it>infection may play a role in the pathogenesis of atopic wheezing in early childhood.</p

Chronic virus infections supress atopy but not asthma in a set of children from a large latin american city: a cross-section study

<p>Abstract</p> <p>Background</p> <p>The prevalence of allergic diseases has increased over recent decades in affluent countries, but remains low in rural populations and some non-affluent countries. An explanation for these trends is that increased exposure to infections may provide protection against the development of allergy. In this work we investigated the association between exposure to viral infections in children living in urban Brazil and the prevalence of atopy and asthma.</p> <p>Methods</p> <p>School age children living in poor neighborhoods in the city of Salvador were studied. Data on asthma symptoms and relevant risk factors were obtained by questionnaire. Skin prick tests (SPTs) were performed to seven aeroallergens, and specific IgE was measured to four of these. Viral infections were determined by the presence of specific IgG in serum to Herpes simplex (HSV), Herpes zoster (HZV), Epstein-Barr (EBV), and Hepatitis A (HAV) viruses.</p> <p>Results</p> <p>A total of 644 (49.7%) children had at least one allergen-specific IgE> 0.35 kU/L and 489 (37.7%) had specific IgE> 0.70 kU/L. A total of 391 (30.2%) children were skin test positive (SPT+), and 295 (22.8%) children were asthmatic. The seroprevalence of viral infections was 88.9% for EBV, 55.4% for HSV, 45.5% for VZV and 17.5% for HAV. Negative associations were observed between SPT+ and HSV (OR = 0.64, CI = 0.51, 0.82) and EBV (OR = 0.63, CI = 0.44, 0.89) infections, but no associations were seen between viral infections and the presence of allergen-specific IgE or asthma.</p> <p>Conclusion</p> <p>These data do not support previous data showing a protective effect of HAV against atopy, but did show inverse associations between SPT+ (but not specific IgE+) and infections with HSV and EBV. These findings suggest that different viral infections may protect against SPT+ in different settings and may indicate an immunoregulatory role of such infections on immediate hypersensitivity responses. The data provide no support for a protective effect of viral infections against asthma in this population.</p

Proteinuria Is Associated with Quality of Life and Depression in Adults with Primary Glomerulopathy and Preserved Renal Function

BACKGROUND: There is no information about HRQoL, depression and associated factors in adult with nephrotic syndrome-associated glomerulopathy. METHODOLOGY/PRINCIPAL FINDINGS: Patients with primary glomerulopathy where compared with age and sex-matched hemodialysis patients and healthy subjects. Laboratory data, medical history, comorbid conditions were collected to evaluate factors associated with HRQoL (SF-36) and Depression (Hamilton Depression Rating Scale-HAMD). Glomerulopathy patients had low HRQoL in all eight SF-36 domains and two composite scores (physical and mental) in comparison with healthy subjects. HAMD score also was elevated and there was high depression prevalence. Overall, these data were comparable between glomerulopathy and hemodialysis patients. Using multiple regression analysis, factors associated with low HRQoL physical composite score were: last 24 h-urine protein excretion (-0.183, 95%CI -0.223 to -0.710 for each gram of proteinuria, p = 0.01) and cyclosporine use (-15.315, 95%CI -25.913 to -2.717, p = 0.03). Low HRQoL mental composite score was associated with last 24 h-urine protein excretion (-0.157, 95%CI -0.278 to -0.310 for each gram of proteinuria, p = 0.03) and HMAD score was independently associated with age (0.155, 95%CI 0.318 to 0.988 for each year, p = 0.04), female sex (4.788, 95%CI 1.005 to 8.620, 0 = 0.03), disease duration (0.074, 95%CI 0.021 to 0.128 for each month, p = 0.01) and last 24 h-urine protein excretion (0.050, 95%CI 0.018 to 0.085 for each gram of proteinuria, p = 0.02). CONCLUSIONS/SIGNIFICANCE: Nephrotic-syndrome associated glomerulopathy patients have low HRQoL and high prevalence of depression symptoms, comparable with those of hemodialysis patients. Last 24 h-protein excretion rate is independently associated with physical and mental HRQoL domains in addition to depression

The genetic mating system of a sea spider with male-biased sexual size dimorphism: evidence for paternity skew despite random mating success

Male-biased size dimorphism is usually expected to evolve in taxa with intense male–male competition for mates, and it is hence associated with high variances in male mating success. Most species of pycnogonid sea spiders exhibit female-biased size dimorphism, and are notable among arthropods for having exclusive male parental care of embryos. Relatively little, however, is known about their natural history, breeding ecology, and mating systems. Here we first show that Ammothella biunguiculata, a small intertidal sea spider, exhibits male-biased size dimorphism. Moreover, we combine genetic parentage analysis with quantitative measures of sexual selection to show that male body size does not appear to be under directional selection. Simulations of random mating revealed that mate acquisition in this species is largely driven by chance factors, although actual paternity success is likely non-randomly distributed. Finally, the opportunity for sexual selection (Is), an indirect metric for the potential strength of sexual selection, in A. biunguiculata males was less than half of that estimated in a sea spider with female-biased size dimorphism, suggesting the direction of size dimorphism may not be a reliable predictor of the intensity of sexual selection in this group. We highlight the suitability of pycnogonids as model systems for addressing questions relating parental investment and sexual selection, as well as the current lack of basic information on their natural history and breeding ecology

Fin Spine Bone Resorption in Atlantic Bluefin Tuna, Thunnus thynnus, and Comparison between Wild and Captive-Reared Specimens

Bone resorption in the first spine of the first dorsal fin of Atlantic bluefin tuna (ABFT) has long been considered for age estimation studies. In the present paper spine bone resorpion was assessed in wild (aged 1 to 13 years) and captive-reared (aged 2 to 11 years) ABFT sampled from the Mediterranean Sea. Total surface (TS), solid surface (SS) and reabsorbed surface (RS) were measured in spine transverse sections in order to obtain proportions of SS and RS. The spine section surface was found to be isometrically correlated to the fish fork length by a power equation. The fraction of solid spine bone progressively decreased according to a logarithmic equation correlating SS/TS to both fish size and age. The values ranged from 57% in the smallest examined individuals to 37% in the largest specimens. This phenomenon was further enhanced in captive-reared ABFT where SS/TS was 22% in the largest measured specimen. The difference between the fraction of SS of wild and captive-reared ABFT was highly significant. In each year class from 1- to 7-year-old wild specimens, the fraction of spine reabsorbed surface was significantly higher in specimens collected from March to May than in those sampled during the rest of the year. In 4-year-old fish the normal SS increase during the summer did not occur, possibly coinciding with their first sexual maturity. According to the correlations between SS/TS and age, the rate of spine bone resorption was significantly higher, even almost double, in captive-reared specimens. This could be attributed to the wider context of systemic dysfunctions occurring in reared ABFT, and may be related to a number of factors, including nutritional deficiencies, alteration of endocrine profile, cortisol-induced stress, and loss of spine functions during locomotion in rearing conditions.Versión del editor4,411