Self-exclusion from health care in women at high risk for postpartum depression

Background A significant proportion of women who are vulnerable to postnatal depression refuse to engage in treatment programmes. Little is known about them, other than some general demographic characteristics. In particular, their access to health care and their own and their infants' health outcomes are uncharted. Methods We conducted a nested cohort case-control study, using data from computerized health systems, and general practitioner (GP) and maternity records, to identify the characteristics, health service contacts, and maternal and infant health outcomes for primiparous antenatal clinic attenders at high risk for postnatal depression who either refused (self-exclusion group) or else agreed (take-up group) to receive additional Health Visiting support in pregnancy and the first 2 months postpartum. Results Women excluding themselves from Health Visitor support were younger and less highly educated than women willing to take up the support. They were less likely to attend midwifery, GP and routine Health Visitor appointments, but were more likely to book in late and to attend accident and emergency department (A&E). Their infants had poorer outcome in terms of gestation, birthweight and breastfeeding. Differences between the groups still obtained when age and education were taken into account for midwifery contacts, A&E attendance and gestation;the difference in the initiation of breast feeding was attenuated, but not wholly explained, by age and education. Conclusion A subgroup of psychologically vulnerable childbearing women are at particular risk for poor access to health care and adverse infant outcome. Barriers to take-up of services need to be understood in order better to deliver care.

Low cost brain-computer interface: first results

Brain-Computer Interfacing (BCI) has been previously demonstrated to restore patient communication, meeting with varying degrees of success. Due to the nature of the equipment traditionally used in BCI experimentation (the electroencephalograph) it is mostly conned to clinical and research environments. The required medical safety standards, subsequent cost of equipment and its application/training times are all issues that need to be resolved if BCIs are to be taken out of the lab/clinic and delivered to the home market. The results in this paper demonstrate a system developed with a low cost medical grade EEG amplier unit in conjunction with the open source BCI2000 software suite thus constructing the cheapest per electrode system available, meeting rigorous clinical safety standards. Discussion of the future of this technology and future work concerning this platform are also introduced.

Doll Play narratives about starting school in children of socially anxious mothers, and their relation to subsequent child school-based anxiety

Background: Child social anxiety is common, and predicts later emotional and academic impairment. Offspring of socially anxious mothers are at increased risk. It is important to establish whether individual vulnerability to disorder can be identified in young children. Method: The responses of 4.5 year-old children of mothers with social phobia (N = 62) and non-anxious mothers (N = 60) were compared, two months before school entry, using a Doll Play (DP) procedure focused on the social challenge of starting school. DP responses were examined in relation to teacher reports of anxious-depressed symptoms and social worries at the end of the child’s first school term. The role of earlier child behavioral inhibition and attachment, assessed at 14 months, was also considered. Results: Compared to children of non-anxious mothers, children of mothers with social phobia were significantly more likely to give anxiously negative responses in their school DP (OR = 2.57). In turn, negative DP predicted teacher reported anxious-depressed and social worry problems. There were no effects of infant behavioral inhibition or attachment. Conclusion: Vulnerability in young children at risk of anxiety can be identified using Doll Play narratives.

Data-driven treatment selection for seamless phase II/III trials incorporating early-outcome data

Seamless phase II/III clinical trials are conducted in two stages with treatment selection at the first stage. In the first stage, patients are randomized to a control or one of k > 1 experimental treatments. At the end of this stage, interim data are analysed, and a decision is made concerning which experimental treatment should continue to the second stage. If the primary endpoint is observable only after some period of follow-up, at the interim analysis data may be available on some early outcome on a larger number of patients than those for whom the primary endpoint is available. These early endpoint data can thus be used for treatment selection. For two previously proposed approaches, the power has been shown to be greater for one or other method depending on the true treatment effects and correlations. We propose a new approach that builds on the previously proposed approaches and uses data available at the interim analysis to estimate these parameters and then, on the basis of these estimates, chooses the treatment selection method with the highest probability of correctly selecting the most effective treatment. This method is shown to perform well compared with the two previously described methods for a wide range of true parameter values. In most cases, the performance of the new method is either similar to or, in some cases, better than either of the two previously proposed methods.

Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats

Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model.

Aerosol retrieval experiments in the ESA Aerosol_cci project

Within the ESA Climate Change Initiative (CCI) project Aerosol_cci (2010–2013), algorithms for the production of long-term total column aerosol optical depth (AOD) datasets from European Earth Observation sensors are developed. Starting with eight existing pre-cursor algorithms three analysis steps are conducted to improve and qualify the algorithms: (1) a series of experiments applied to one month of global data to understand several major sensitivities to assumptions needed due to the ill-posed nature of the underlying inversion problem, (2) a round robin exercise of "best" versions of each of these algorithms (defined using the step 1 outcome) applied to four months of global data to identify mature algorithms, and (3) a comprehensive validation exercise applied to one complete year of global data produced by the algorithms selected as mature based on the round robin exercise. The algorithms tested included four using AATSR, three using MERIS and one using PARASOL. This paper summarizes the first step. Three experiments were conducted to assess the potential impact of major assumptions in the various aerosol retrieval algorithms. In the first experiment a common set of four aerosol components was used to provide all algorithms with the same assumptions. The second experiment introduced an aerosol property climatology, derived from a combination of model and sun photometer observations, as a priori information in the retrievals on the occurrence of the common aerosol components. The third experiment assessed the impact of using a common nadir cloud mask for AATSR and MERIS algorithms in order to characterize the sensitivity to remaining cloud contamination in the retrievals against the baseline dataset versions. The impact of the algorithm changes was assessed for one month (September 2008) of data: qualitatively by inspection of monthly mean AOD maps and quantitatively by comparing daily gridded satellite data against daily averaged AERONET sun photometer observations for the different versions of each algorithm globally (land and coastal) and for three regions with different aerosol regimes. The analysis allowed for an assessment of sensitivities of all algorithms, which helped define the best algorithm versions for the subsequent round robin exercise; all algorithms (except for MERIS) showed some, in parts significant, improvement. In particular, using common aerosol components and partly also a priori aerosol-type climatology is beneficial. On the other hand the use of an AATSR-based common cloud mask meant a clear improvement (though with significant reduction of coverage) for the MERIS standard product, but not for the algorithms using AATSR. It is noted that all these observations are mostly consistent for all five analyses (global land, global coastal, three regional), which can be understood well, since the set of aerosol components defined in Sect. 3.1 was explicitly designed to cover different global aerosol regimes (with low and high absorption fine mode, sea salt and dust).

Evidence for interplay between genes and maternal stress in utero: monoamine oxidase A polymorphism moderates effects of life events during pregnancy on infant negative emotionality at 5 weeks

The low activity variant of the monoamine oxidase A (MAOA) functional promoter polymorphism, MAOA-LPR, in interaction with adverse environments (G × E) is associated with child and adult antisocial behaviour disorders. MAOA is expressed during foetal development so in utero G × E may influence early neurodevelopment. We tested the hypothesis that MAOA G × E during pregnancy predicts infant negative emotionality soon after birth. In an epidemiological longitudinal study starting in pregnancy, using a two stage stratified design, we ascertained MAOA-LPR status (low vs. high activity variants) from the saliva of 209 infants (104 boys and 105 girls), and examined predictions to observed infant negative emotionality at 5 weeks post-partum from life events during pregnancy. In analyses weighted to provide estimates for the general population, and including possible confounders for life events, there was an MAOA status by life events interaction (P = 0.017). There was also an interaction between MAOA status and neighbourhood deprivation (P = 0.028). Both interactions arose from a greater effect of increasing life events on negative emotionality in the MAOA-LPR low activity, compared with MAOA-LPR high activity infants. The study provides the first evidence of moderation by MAOA-LPR of the effect of the social environment in pregnancy on negative emotionality in infancy, an early risk for the development of child and adult antisocial behaviour disorders.

Evidence for interplay between genes and parenting on infant temperament in the first year of life: monoamine oxidase A polymorphism moderates effects of maternal sensitivity on infant anger proneness

Background The low expression polymorphism of the MAOA gene in interaction with adverse environments (G × E) is associated with antisocial behaviour disorders. These have their origins in early life, but it is not known whether MAOA G × E occurs in infants. We therefore examined whether MAOA G × E predicts infant anger proneness, a temperamental dimension associated with later antisocial behaviour disorders. In contrast to previous studies, we examined MAOA G × E prospectively using an observational measure of a key aspect of the infant environment, maternal sensitivity, at a specified developmental time point. Methods In a stratified epidemiological cohort recruited during pregnancy, we ascertained MAOA status (low vs. high expression alleles) from the saliva of 193 infants, and examined specific predictions to maternal report of infant temperament at 14 months from maternal sensitivity assessed at 29 weeks of age. Results Analyses, weighted to provide general population estimates, indicated a robust interaction between MAOA status and maternal sensitivity in the prediction of infant anger proneness (p = .003) which became stronger once possible confounders for maternal sensitivity were included in the model (p = .0001). The interaction terms were similar in males (p = .010) and females (p = .016), but the effects were different as a consequence of an additional sex of infant by maternal sensitivity interaction. Conclusions This prospective study provides the first evidence of moderation by the MAOA gene of effects of parenting on infant anger proneness, an important early risk for the development of disruptive and aggressive behaviour disorders.

The specific role of relationship life events in the onset of depression during pregnancy and the postpartum

Background The precipitating role of life events in the onset of depression is well-established. The present study sought to examine whether life events hypothesised to be personally salient would be more strongly associated with depression than other life events. In a sample of women making the first transition to parenthood, we hypothesised that negative events related to the partner relationship would be particularly salient and thus more strongly predictive of depression than other events. Methods A community-based sample of 316 first-time mothers stratified by psychosocial risk completed interviews at 32 weeks gestation and 29 weeks postpartum to assess dated occurrence of life events and depression onsets from conception to 29 weeks postpartum. Complete data was available from 273 (86.4%). Cox proportional hazards regression was used to examine risk for onset of depression in the 6 months following a relationship event versus other events, after accounting for past history of depression and other potential confounders. Results 52 women (19.0%) experienced an onset of depression between conception and 6 months postpartum. Both relationship events (Hazard Ratio = 2.1, p = .001) and other life events (Hazard Ratio = 1.3, p = .020) were associated with increased risk for depression onset; however, relationship events showed a significantly greater risk for depression than did other life events (p = .044). Conclusions The results are consistent with the hypothesis that personally salient events are more predictive of depression onset than other events. Further, they indicate the clinical significance of events related to the partner relationship during pregnancy and the postpartum.

Followers are not followed: observed group interactions modulate subsequent social attention

We asked whether previous observations of group interactions modulate subsequent social attention episodes. Participants first completed a learning phase with two conditions. In the ‘leader’ condition one of three identities turned her gaze first, followed by the two other faces. In the ‘follower’ condition, one of the identities turned her gaze after the two other faces had first shifted their gaze. Thus, participants observed that some individuals were consistently ‘leaders’ and others ‘followers’ of others’ attention. In the test phase, the faces of ‘leaders’ and ‘followers’ were presented in a gaze cueing paradigm. Remarkably, the ‘followers’ did not elicit gaze cueing. Our data demonstrate that individuals who do not guide group attention in exploring the environment are ineffective social attention directors in later encounters. Thus, the role played in previous group social attention interactions modulates the relative weight assigned to others’ gaze: we ignore the gaze of group followers.

Detection of the phosphorylation of the estrogen receptor alpha as an outcome of GPR30 activation

Phosphorylation of the serine residues in estrogen receptor (ER) α is important in transcriptional activation. Hence, methods to detect such posttranslational modifi cation events are valuable. We describe, in detail, the analysis of the phosphorylated ERα by electrophoretic separation of proteins and subsequent immuno-blotting techniques. In particular, phosphorylation of the ERα is one possible outcome of activation of the putative membrane estrogen receptor (mER), GPR30. Hence, phosphorylation represents a cross talk event between GPR30 and ERα and may be important in estrogen-regulated physiology.

Additive genetic relationships between scrotal circumference, heifer pregnancy, and stayability in Nellore cattle

Scrotal circumference data from 47,605 Nellore young bulls, measured at around 18 mo of age (SC18), were analyzed simultaneously with 27,924 heifer pregnancy (HP) and 80,831 stayability (STAY) records to estimate their additive genetic relationships. Additionally, the possibility that economically relevant traits measured directly in females could replace SC18 as a selection criterion was verified. Heifer pregnancy was defined as the observation that a heifer conceived and remained pregnant, which was assessed by rectal palpation at 60 d. Females were exposed to sires for the first time at about 14 mo of age (between 11 and 16 mo). Stayability was defined as whether or not a cow calved every year up to 5 yr of age, when the opportunity to breed was provided. A Bayesian linear-threshold-threshold analysis via Gibbs sampler was used to estimate the variance and covariance components of the multitrait model. Heritability estimates were 0.42 +/- 0.01, 0.53 +/- 0.03, and 0.10 +/- 0.01, for SC18, HP, and STAY, respectively. The genetic correlation estimates were 0.29 +/- 0.05, 0.19 +/- 0.05, and 0.64 +/- 0.07 between SC18 and HP, SC18 and STAY, and HP and STAY, respectively. The residual correlation estimate between HP and STAY was -0.08 +/- 0.03. The heritability values indicate the existence of considerable genetic variance for SC18 and HP traits. However, genetic correlations between SC18 and the female reproductive traits analyzed in the present study can only be considered moderate. The small residual correlation between HP and STAY suggests that environmental effects common to both traits are not major. The large heritability estimate for HP and the high genetic correlation between HP and STAY obtained in the present study confirm that EPD for HP can be used to select bulls for the production of precocious, fertile, and long-lived daughters. Moreover, SC18 could be incorporated in multitrait analysis to improve the prediction accuracy for HP genetic merit of young bulls.

Morpho-physical Recording of Bovine Conceptus (Bos indicus) and Placenta from Days 20 to 70 of Pregnancy

The study is based on 141 pregnant Bos indicus cows, from days 20 to 70 post-insemination. First, special attention was given to the macroscopically observable phenomena of attachment of the conceptus to the uterus, i.e. the implantation, from about days 20 to 30 post-insemination up to day 70, and placentome development by growth, vascularization and increase in the number of cotyledons opposite to the endometrial caruncles. Secondly, as for the conceptuses, semiquantitative, statistical analyses were performed of the lengths of chorio-allantois, amnion and yolk sac; and the different parts of the centre and two extremes of the yolk sacs were also analysed. Thirdly, the embryos/foetuses corresponding to their membranes were measured by their greatest length and by weight, and described by the appearance of external developmental phenomena during the investigated period like neurulation, somites, branchial arcs, brain vesicles, limb buds, C-form, pigmented eye and facial grooves. In conclusion, all the data collected in this study from days 20 to 70 of bovine pregnancy were compared extensively with corresponding data of the literature. This resulted in an `embryo/foetal age-scale`, which has extended the data in the literature by covering the first 8 to 70 days of pregnancy. This age-scale of early bovine intrauterine development provides model for studies, even when using slaughtered cows without distinct knowledge of insemination or fertilization time, through macroscopic techniques. This distinctly facilitates research into the cow, which is now being widely used as `an experimental animal` for testing new techniques of reproduction like in vitro fertilization, embryo transfer and cloning.

Macrophage migration inhibitory factor is up-regulated in human first-trimester placenta stimulated by soluble antigen of Toxoplasma gondii, resulting in increased monocyte adhesion on villous explants

Considering the potential role of macrophage migration inhibitory factor (MIF) in the inflammation process in placenta when infected by pathogens, we investigated the production of this cytokine in chorionic villous explants obtained from human first-trimester placentas stimulated with soluble antigen from Toxoplasma gondii (STAg). Parallel cultures were performed with villous explants stimulated with STAB, interferon-gamma (IFN-gamma), or STAB plus IFN-gamma. To assess the role of placental MIF on monocyte adhesiveness to human trophoblast, explants were co-cultured with human myelomonocytic THP-1 cells in the presence or absence of supernatant from cultures treated with STAB (SPN), SPN plus anti-MIF antibodies, or recombinant MIF. A significantly higher concentration of MIF was produced and secreted by villous explants treated with STAB or STAB plus IFN-gamma after 24-hour culture. Addition of SPN or recombinant MIF was able to increase THP-1 adhesion, which was inhibited after treatment with anti-MIF antibodies. This phenomenon was associated with intercellular adhesion molecule expression by villous explants. Considering that the processes leading to vertical dissemination of T. gondii remain widely unknown, our results demonstrate that MIF production by human first-trimester placenta is up-regulated by parasite antigen and may play an essential role as an autocrine/paracrine mediator in placental infection by T. gondii.

Effects of long-term diabetes on the structure and cell proliferation of the myometrium in the early pregnancy of mice

P>It is known that the development of diabetic complications in human pregnancy is directly related to the severity and the duration of this pathology. In this study, we developed a model of long-term type 1 diabetes to investigate its effects on the cytoarchitecture, extracellular matrix and cell proliferation during the first adaptation phase of the myometrium for pregnancy. A single dose of alloxan was used to induce diabetes in mice prior to pregnancy. To identify the temporal effects of diabetes the mice were divided into two groups: Group D1 (females that became pregnant 90-100 days after alloxan); Group D2 (females that became pregnant 100-110 days after alloxan). Uterine samples were collected after 168 h of pregnancy and processed for light and electron microscopy. In both groups the histomorphometric evaluation showed that diabetes promoted narrowing of the myometrial muscle layers which was correlated with decreased cell proliferation demonstrated by PCNA immunodetection. In D1, diabetes increased the distance between muscle layers and promoted oedema. Contrarily, in D2 the distance between muscle layers decreased and, instead of oedema, there was a markedly deposition of collagen in the myometrium. Ultrastructural analysis showed that diabetes affects the organization of the smooth muscle cells and their myofilaments. Consistently, the immunoreaction for smooth muscle alpha-actin revealed clear disorganization of the contractile apparatus in both diabetic groups. In conclusion, the present model demonstrated that long-term diabetes promotes significant alterations in the myometrium in a time-sensitive manner. Together, these alterations indicate that diabetes impairs the first phenotypic adaptation phase of the pregnant myometrium.