M-ficolin in the neonatal period: Associations with need for mechanical ventilation and mortality in premature infants with necrotising enterocolitis

OBJECTIVE: Necrotising enterocolitis (NEC) causes significant mortality in premature infants. The involvement of the innate immune system in the pathogenesis of NEC remains unclear. M-, L- and H-ficolins recognize microorganisms and activate the complement system, but their role in host defense is largely unknown. This study investigated whether ficolin concentrations are associated with NEC. STUDY DESIGN: Case-control study including 30 premature infants with NEC and 60 controls. M-, L- and H-ficolins were measured in cord blood using time-resolved immunofluorometric assays. Multivariate logistic regression was performed. RESULTS: Of the 30 NEC cases (median gestational age, 29.5 weeks), 12 (40%) were operated and 4 (13%) died. No difference regarding ficolin concentration was found when comparing NEC cases versus controls (p>0.05). However, infants who died of NEC had significantly lower M-ficolin cord blood concentrations than NEC survivors (for M-ficolin <300ng/ml; multivariate OR 12.35, CI 1.03-148.59, p=0.048). In the entire study population, M-, L- and H-ficolins were positively correlated with gestational age (p<0.001) and birth weight (p<0.001). Infants with low M-ficolin required significantly more often mechanical ventilation after birth multivariate (OR 10.55, CI 2.01-55.34, p=0.005). CONCLUSIONS: M-, L- and H-ficolins are already present in cord blood and increase with gestational age. Low cord blood concentration of M-ficolin was associated with higher NEC-associated fatality and with increased need for mechanical ventilation. Future studies need to assess whether M-ficolin is involved in multiorgan failure and pulmonary disease.

Hierarchical modeling gave plausible estimates of associations between metabolic syndrome and components of antiretroviral therapy

OBJECTIVE: Hierarchical modeling has been proposed as a solution to the multiple exposure problem. We estimate associations between metabolic syndrome and different components of antiretroviral therapy using both conventional and hierarchical models. STUDY DESIGN AND SETTING: We use discrete time survival analysis to estimate the association between metabolic syndrome and cumulative exposure to 16 antiretrovirals from four drug classes. We fit a hierarchical model where the drug class provides a prior model of the association between metabolic syndrome and exposure to each antiretroviral. RESULTS: One thousand two hundred and eighteen patients were followed for a median of 27 months, with 242 cases of metabolic syndrome (20%) at a rate of 7.5 cases per 100 patient years. Metabolic syndrome was more likely to develop in patients exposed to stavudine, but was less likely to develop in those exposed to atazanavir. The estimate for exposure to atazanavir increased from hazard ratio of 0.06 per 6 months' use in the conventional model to 0.37 in the hierarchical model (or from 0.57 to 0.81 when using spline-based covariate adjustment). CONCLUSION: These results are consistent with trials that show the disadvantage of stavudine and advantage of atazanavir relative to other drugs in their respective classes. The hierarchical model gave more plausible results than the equivalent conventional model.

Depressive symptoms from kindergarten to early school age: longitudinal associations with social skills deficits and peer victimization

BACKGROUND: Depressive symptoms in children are associated with social skills deficits and problems with peers. We propose a model which suggests different mechanisms for the impact of deficits in self-oriented social skills (assertiveness and social participation) and other-oriented social skills (pro-social, cooperative and non-aggressive behaviors) on children's depressive symptoms. We hypothesized that deficits in self-oriented social skills have a direct impact on children's depressive symptoms because these children have non-rewarding interactions with peers, whereas the impact of deficits in other-oriented social skills on depressive symptoms is mediated through negative reactions from peers such as peer victimization. METHOD: 378 kindergarten children (163 girls) participated at two assessments (Age at T1: M = 5.8, T2: M = 7.4). Teachers completed questionnaires on children's social skills at T1. Teacher reports on peer victimization and depressive symptoms were assessed at both assessment points. RESULTS: Our study partially confirmed the suggested conceptual model. Deficits in self-oriented social skills significantly predicted depressive symptoms, whereas deficits in other-oriented social skills were more strongly associated with peer victimization. Longitudinal associations between other-oriented social skills and depressive symptoms were mediated through peer victimization. CONCLUSION: The study emphasizes the role of deficits in self-oriented social skills and peer victimization for the development of internalizing disorders.

Direct and indirect associations between plant species richness and productivity in grasslands: regional differences preclude simple generalization of productivity-biodiversity relationships

Plant species richness of permanent grasslands has often been found to be significantly associated with productivity. Concentrations of nutrients in biomass can give further insight into these productivity- plant species richness relationships, e.g. by reflecting land use or soil characteristics. However, the consistency of such relationships across different regions has rarely been taken into account, which might significantly compromise our potential for generalization. We recorded plant species richness and measured above-ground biomass and concentrations of nutrients in biomass in 295 grasslands in three regions in Germany that differ in soil and climatic conditions. Structural equation modelling revealed that nutrient concentrations were mostly indirectly associated with plant species richness via biomass production. However, negative associations between the concentrations of different nutrients and biomass and plant species richness differed considerably among regions. While in two regions, more than 40% of the variation in plant species richness could be attributed to variation in biomass, K, P, and to some degree also N concentrations, in the third region only 15% of the variation could be explained in this way. Generally, highest plant species richness was recorded in grasslands where N and P were co-limiting plant growth, in contrast to N or K (co-) limitation. But again, this pattern was not recorded in the third region. While for two regions land-use intensity and especially the application of fertilizers are suggested to be the main drivers causing the observed negative associations with productivity, in the third region the little variance accounted for, low species richness and weak relationships implied that former intensive grassland management, ongoing mineralization of peat and fluctuating water levels in fen grasslands have overruled effects of current land-use intensity and productivity. Finally, we conclude that regional replication is of major importance for studies seeking general insights into productivity-diversity relationships.

Associations of Forest Type, Parasitism and Body Condition of Two European Passerines, Fringilla coelebs and Sylvia atricapilla

Human-induced forest modification can alter parasite-host interactions and might change the persistence of host populations. We captured individuals of two widespread European passerines (Fringilla coelebs and Sylvia atricapilla) in southwestern Germany to disentangle the associations of forest types and parasitism by haemosporidian parasites on the body condition of birds. We compared parasite prevalence and parasite intensity, fluctuating asymmetries, leukocyte numbers, and the heterophil to lymphocyte ratio (H/L-ratio) among individuals from beech, mixed-deciduous and spruce forest stands. Based on the biology of bird species, we expected to find fewer infected individuals in beech or mixed-deciduous than in spruce forest stands. We found the highest parasite prevalence and intensity in beech forests for F. coelebs. Although, we found the highest prevalence in spruce forests for S. atricapilla, the highest intensity was detected in beech forests, partially supporting our hypothesis. Other body condition or health status metrics, such as the heterophil to lymphocyte ratio (H/L-ratio), revealed only slight differences between bird populations inhabiting the three different forest types, with the highest values in spruce for F. coelebs and in mixed-deciduous forests for S. atricapilla. A comparison of parasitized versus non-parasitized individuals suggests that parasite infection increased the immune response of a bird, which was detectable as high H/L-ratio. Higher infections with blood parasites for S. atricapilla in spruce forest indicate that this forest type might be a less suitable habitat than beech and mixed-deciduous forests, whereas beech forests seem to be a suboptimal habitat regarding parasitism for F. coelebs.

Suicide assisted by right-to-die associations: a population based cohort study

Background: In Switzerland, assisted suicide is legal but there is concern that vulnerable or disadvantaged groups are more likely to die in this way than other people. We examined socio-economic factors associated with assisted suicide. Methods: We linked the suicides assisted by right-to-die associations during 2003–08 to a census-based longitudinal study of the Swiss population. We used Cox and logistic regression models to examine associations with gender, age, marital status, education, religion, type of household, urbanization, neighbourhood socio-economic position and other variables. Separate analyses were done for younger (25 to 64 years) and older (65 to 94 years) people. Results: Analyses were based on 5 004 403 Swiss residents and 1301 assisted suicides (439 in the younger and 862 in the older group). In 1093 (84.0%) assisted suicides, an underlying cause was recorded; cancer was the most common cause (508, 46.5%). In both age groups, assisted suicide was more likely in women than in men, those living alone compared with those living with others and in those with no religious affiliation compared with Protestants or Catholics. The rate was also higher in more educated people, in urban compared with rural areas and in neighbourhoods of higher socio-economic position. In older people, assisted suicide was more likely in the divorced compared with the married; in younger people, having children was associated with a lower rate. Conclusions: Assisted suicide in Switzerland was associated with female gender and situations that may indicate greater vulnerability such as living alone or being divorced, but also with higher education and higher socio-economic position.

A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control

HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10−12). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation for identifying host factors: (1) association signals are much stronger for HIV-1 sequence variants than VL, reflecting the ‘intermediate phenotype’ nature of viral variation; (2) association testing can be run without any clinical data. The proposed genome-to-genome approach highlights sites of genomic conflict and is a strategy generally applicable to studies of host–pathogen interaction.

Inter- and intraindividual associations between volitional processes and daily smoking during a quit attempt

Background: The Health Action Process Approach (HAPA) assumes that volitional processes are important for effective behavioral change. This study examined the associations of volitional predictors and daily smoking in quitters at the inter- and intraindividual level. Method: Overall, 105 smokers completed daily electronic questionnaires 10 days before and 21 days after a self-set quit date, assessing intentions, self-efficacy, planning, action control and numbers of cigarettes smoked. Findings: Multilevel analyses showed that mean levels of volitional predictors across the 32 days were negatively associated with numbers of cigarettes smoked. Moreover, on days with higher intentions, self-efficacy, planning and action control than usual, less cigarettes were smoked. These effects were stronger after the quit date than before the quit date. Intentions and action control emerged as most powerful predictors at the intraindividual level. Discussion: Findings emphasize the importance of volitional processes at the intraindividual level in the context of quitting smoking.