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Postnatal depression and anxiety have been shown to increase the risk of disturbances in mother-child interaction and child development. Research into mechanisms has focused on genetics and maternal behavior; maternal cognitions have received little attention. Our aim was to experimentally determine if worry and rumination in mothers with generalized anxiety disorder (GAD) and major depressive disorder (MDD), diagnosed in the postnatal 6 months, interfered with maternal responsiveness to their 10-month old infants. Mothers (N = 253: GAD n = 90; MDD n = 57; control n = 106) and their infants were randomized to either a worry/rumination prime (WRP) or a neutral prime (NP); mother-infant interactions were assessed before and after priming. Type of priming was a significant predictor of maternal cognitions, with WRP resulting in more negative thoughts, higher thought recurrence and more self-focus relative to NP across the entire sample. Interaction effects between group and priming were significant for two parenting variables: Compared with controls, WRP had a more negative impact on maternal responsiveness to infant vocalization for GAD, and to a lesser extent for MDD; WRP led to decreased maternal vocalization for GAD. Also, mothers with GAD used stronger control after the NP than WRP, as well as compared with other groups, and overall post-priming, their children exhibited lower emotional tone and more withdrawal. Across the entire sample, WRP was associated with increased child vocalization relative to NP. This study demonstrated that disturbances in maternal cognitions, in the context of postnatal anxiety and to a lesser degree depression, play a significant role in mother-child interaction.

Following the replication of the association of the human leucocyte antigen (HLA) allele, HLA-B*07, with Alzheimer's disease (AD) in the cohort of the Oxford Project to Investigate Memory and Ageing (OPTIMA) in a previous study, we examined whether that association could be due to linkage disequilibrium with MICA or MICB alleles. We found a possible association of MICA*00801 heterozygotes with AD in subjects positive for the ε4 allele of apolipoprotein E. This finding was supported by Hardy-Weinberg analysis, by stratified association analysis and by interaction analysis, but did not survive correction for multiple testing. In any case, these results do not explain our previously reported association of HLA-B*07 with AD. © 2009 John Wiley and Sons A/S.

Neuroinflammation contributes to the pathogenesis of sporadic Alzheimer's disease (AD). Variations in genes relevant to inflammation may be candidate genes for AD risk. Whole-genome association studies have identified relevant new and known genes. Their combined effects do not explain 100% of the risk, genetic interactions may contribute. We investigated whether genes involved in inflammation, i.e. PPAR-α, interleukins (IL) IL1α, IL-1β, IL-6, and IL-10 may interact to increase AD risk. Methods: The Epistasis Project identifies interactions that affect the risk of AD. Genotyping of single nucleotide polymorphisms (SNPs) in PPARA, IL1A, IL1B, IL6 and IL10 was performed. Possible associations were analyzed by fitting logistic regression models with AD as outcome, controlling for centre, age, sex and presence of apolipoprotein ε4 allele (APOEε4). Adjusted synergy factors were derived from interaction terms (p

Objectives: To estimate the prevalence of and identify risk factors for lipodystrophy syndrome (LS) and body fat abnormality in a population of HIV-infected children and adolescents. Design: Cross-sectional observational study. Methods: HIV-infected subjects aged 2-18 years were recruited from 15 HIV centers in Belgium Italy, and Poland between January 2007 and December 2008. Standardized assessments by the patient's long-term clinician were performed to establish the presence of abnormality. Risk factors were explored in logistic regression models for fat abnormality outcomes and LS (abnormality plus dyslipidemia). Results: Among 426 subjects (70% white), median age was 12.2 years (interquartile range: 9.0-15.0 years) and median duration of antiretroviral therapy was 5.2 years (interquartile range: 2.2-8.8 years). Prevalence was 57% (n = 235) for LS and 42% (n =176) for fat abnormality; 90 subjects with abnormality were affected in ≥3 locations. Lipoatrophy occurred in 28% (n =117) of subjects and lipohypertrophy in 27% (n = 115), most commonly in the face and trunk, respectively. In multivariable analysis, white ethnicity, body mass index, ritonavir/lopinavir, and nonnucleoside reverse transcriptase inhibitors were each associated with an increased risk of LS (P

Background Although mother-to-child transmission (MTCT) rates are at an all-time low in Western Europe, potentially preventable transmissions continue to occur. Duration of antenatal combination antiretroviral therapy (ART) is strongly associated with MTCT risk. Methods Data on pregnant HIV-infected women enrolled in the Western and Central European sites of the European Collaborative Study between January 2000 and July 2009 were analysed. The proportion of women receiving no antenatal ART or 1–13 days of treatment was investigated, and associated factors explored using logistic regression models. Results Of 2,148 women, 142 (7%) received no antenatal ART, decreasing from 8% in 2000–2003 to 5% in 2004– 2009 (χ2=8.73; PConclusions Over the last 10 years, around one in 11 women in this study received insufficient antenatal ART, accounting for 40% of MTCTs. One-half of these women were diagnosed before conception, suggesting disengagement from care.

BACKGROUND: The effectiveness of prenatal treatment to prevent serious neurological sequelae (SNSD) of congenital toxoplasmosis is not known. METHODS AND FINDINGS: Congenital toxoplasmosis was prospectively identified by universal prenatal or neonatal screening in 14 European centres and children were followed for a median of 4 years. We evaluated determinants of postnatal death or SNSD defined by one or more of functional neurological abnormalities, severe bilateral visual impairment, or pregnancy termination for confirmed congenital toxoplasmosis. Two-thirds of the cohort received prenatal treatment (189/293; 65%). 23/293 (8%) fetuses developed SNSD of which nine were pregnancy terminations. Prenatal treatment reduced the risk of SNSD. The odds ratio for prenatal treatment, adjusted for gestational age at maternal seroconversion, was 0.24 (95% Bayesian credible intervals 0.07-0.71). This effect was robust to most sensitivity analyses. The number of infected fetuses needed to be treated to prevent one case of SNSD was three (95% Bayesian credible intervals 2-15) after maternal seroconversion at 10 weeks, and 18 (9-75) at 30 weeks of gestation. Pyrimethamine-sulphonamide treatment did not reduce SNSD compared with spiramycin alone (adjusted odds ratio 0.78, 0.21-2.95). The proportion of live-born infants with intracranial lesions detected postnatally who developed SNSD was 31.0% (17.0%-38.1%). CONCLUSION: The finding that prenatal treatment reduced the risk of SNSD in infected fetuses should be interpreted with caution because of the low number of SNSD cases and uncertainty about the timing of maternal seroconversion. As these are observational data, policy decisions about screening require further evidence from a randomized trial of prenatal screening and from cost-effectiveness analyses that take into account the incidence and prevalence of maternal infection. Please see later in the article for the Editors' Summary.

Earlier literature suggested there may be a seasonal rhythm of onset of Hodgkin's disease. This issue has been re-examined using population-based prospectively-collected data with high ascertainment levels, The Data Collection Study (DCS) of the Leukaemia Research Fund (LRF) Centre for Clinical Epidemiology (University of Leeds) generated the information used, which was based on a population of 13.5 million - about one quarter of England and Wales - over 10 years. The RYE histopathological classification was employed. The findings show that in patients with nodular sclerosing histopathology there was a highly significant circannual rhythm with a low amplitude (extent of seasonal variation) and a peas in March. A significant, but different, rhythm with a high amplitude and a peal; in August was found in lymphocyte predominant Hodgkin's disease, However, this finding is less certain, due to smaller numbers and a lower significance level. The main conclusion is that there is a highly significant seasonality in nodular sclerosing Hodgkin's disease. The findings provide further evidence that nodular sclerosing and lymphocyte predominant may be two different diseases. The differing seasonality rhythms may provide aetiological clues.

Despite recent discoveries in the genetics of sporadic Alzheimer's disease, there remains substantial "hidden heritability." It is thought that some of this missing heritability may be because of gene-gene, i.e., epistatic, interactions. We examined potential epistasis between 110 candidate polymorphisms in 1757 cases of Alzheimer's disease and 6294 control subjects of the Epistasis Project, divided between a discovery and a replication dataset. We found an epistatic interaction, between rs7483 in GSTM3 and rs1111875 in the HHEX/IDE/KIF11 gene cluster, with a closely similar, significant result in both datasets. The synergy factor (SF) in the combined dataset was 1.79, 95% confidence interval [CI], 1.35-2.36; p = 0.00004. Consistent interaction was also found in 7 out of the 8 additional subsets that we examined post hoc: i.e., it was shown in both North Europe and North Spain, in both men and women, in both those with and without the epsilon 4 allele of apolipoprotein E, and in people older than 75 years (SF, 2.27; 95% CI, 1.60-3.20; p < 0.00001), but not in those younger than 75 years (SF, 1.06; 95% CI, 0.59-1.91; p = 0.84). The association with Alzheimer's disease was purely epistatic with neither polymorphism showing an independent effect: odds ratio, 1.0; p >= 0.7. Indeed, each factor was associated with protection in the absence of the other factor, but with risk in its presence. In conclusion, this epistatic interaction showed a high degree of consistency when stratifying by sex, the epsilon 4 allele of apolipoprotein E genotype, and geographic region. (C) 2013 Elsevier Inc. All rights reserved.

We are most grateful to the Moulton Charitable Foundation for a grant to fund the Epistasis Project, to all those who have provided support for the individual clinical studies and to the Alzheimer’s Research Trust. GKW was partly funded by the NIHR Biomedical Research Centre Programme, Oxford., Kölsch, H., Lehmann, D.J., Ibrahim-Verbaas, C.A., Combarros, O., Van Duijn, C.M., Hammond, N., Belbin, O., Cortina-Borja, M., Lehmann, M.G., Aulchenko, Y.S., Schuur, M., Breteler, M., Wilcock, G.K., Brown, K., Kehoe, P.G., Barber, R., Coto, E., Alvarez, V., Deloukas, P., Mateo, I., Maier, W., Morgan, K., Warden, D.R., Smith, A.D., Heun, R.

Neuroinflammation contributes to the pathogenesis of sporadic Alzheimer's disease (AD). Variations in genes relevant to inflammation may be candidate genes for AD risk. Whole-genome association studies have identified relevant new and known genes. Their combined effects do not explain 100% of the risk, genetic interactions may contribute. We investigated whether genes involved in inflammation, i.e. PPAR-α, interleukins (IL) IL1α, IL-1β, IL-6, and IL-10 may interact to increase AD risk. Methods: The Epistasis Project identifies interactions that affect the risk of AD. Genotyping of single nucleotide polymorphisms (SNPs) in PPARA, IL1A, IL1B, IL6 and IL10 was performed. Possible associations were analyzed by fitting logistic regression models with AD as outcome, controlling for centre, age, sex and presence of apolipoprotein ε4 allele (APOEε4). Adjusted synergy factors were derived from interaction terms (p

Background Total lymphocyte count has been proposed as an alternative to the percentage of CD4+ T-cells to indicate when antiretroviral therapy should be started in children with HIV in resource-poor settings. We aimed to assess thresholds of total lymphocyte count at which antiretroviral therapy should be considered, and compared monitoring of total lymphocyte count with monitoring of CD4-cell percentage. Methods Longitudinal data on 3917 children with HIV infection were pooled from observational and randomised studies in Europe and the USA. The 12-month risks of death and AIDS by most recent total lymphocyte count and age were estimated by parametric survival models, based on measurements before antiretroviral therapy or during zidovudine monotherapy. Risks were derived and compared at thresholds of total lymphocyte count and CD4-cell percentage for starting antiretroviral therapy recommended in WHO 2003 guidelines. Findings Total lymphocyte count was a powerful predictor of the risk of disease progression despite a weak correlation with CD4-cell percentage (r=0.08-0.19 dependent on age). For children older than 2 years, the 12-month risk of death and AIDS increased sharply at values less than 1500-2000 cells per mu L, with little trend at higher values. Younger children had higher risks and total lymphocyte count was less prognostic. Mortality risk was substantially higher at thresholds of total lymphocyte count recommended by WHO than at corresponding thresholds of CD4-cell percentage. When the markers were compared at the threshold values at which mortality risks were about equal, total lymphocyte count was as effective as CD4-cell percentage for identifying children before death, but resulted in an earlier start of antiretroviral therapy. Interpretation In this population, total lymphocyte count was a strong predictor of short-term disease progression, being only marginally less predictive than CD4-cell percentage. Confirmatory studies in resource-poor settings are needed to identify the most cost-effective markers to guide initiation of antiretroviral therapy.