Effects of Prenatal Social Stress and Maternal Dietary Fatty Acid Ratio on Infant Temperament: Does Race Matter?

Background: Infant temperament predicts a range of developmental and behavioral outcomes throughout childhood. Both maternal fatty acid intake and psychosocial stress exposures during pregnancy may influence infant temperament. Furthermore, maternal race may modify prenatal diet and stress effects. The goals of this study are to examine the joint effects of prenatal diet and stress and the modifying effects of race on infant behavior. Methods: Analyses included N=255 mother-infant dyads, primarily minorities (21% Blacks; 42% Hispanics), enrolled in an urban pregnancy cohort. Maternal prenatal stress was indexed by a negative life events (NLEs) score on the Crisis in Family Systems-Revised survey. Prenatal total daily intakes of polyunsaturated fatty acids (PUFAs) (n3, n6) were estimated from a food frequency questionnaire; n3:n6 ratios were calculated. Mothers completed the Infant Behavior Questionnaire-Revised (IBQ-R), a measure of infant temperament, when the children were 6 months old. Three commonly used dimensions were derived: Orienting & Regulation, Extraversion, and Negative Affectivity. Associations among prenatal stress, maternal n3:n6 ratio, and race/ethnicity on infant temperament, controlling for maternal education and age and child sex, were examined. Results: Among Blacks, prenatal stress effects on infant Orienting & Regulation scores were modified by maternal n3:n6 ratios (p=0.03): As NLEs increased, lower n3:n6 ratios predicted lower infant Orienting & Regulation scores, whereas higher n3:n6 ratios attenuated the effect of prenatal stress. There were no main or interaction effects predicting Extraversion or Negative Affectivity. Conclusions: An optimal PUFA ratio may protect the fetus from stress effects on infant behavior, particularly among Blacks. These findings may have implications for later neurodevelopment and social functioning predicted by early temperamental characteristics

The Feasibility of Societal Cost Equivalence between Robotic Hysterectomy and Alternate Hysterectomy Methods for Endometrial Cancer

Objectives. We assess whether it is feasible for robotic hysterectomy for endometrial cancer to be less expensive to society than traditional laparoscopic hysterectomy or abdominal hysterectomy. Methods. We performed a retrospective cohort analysis of patient characteristics, operative times, complications, and hospital charges from all (n = 234) endometrial cancer patients who underwent hysterectomy in 2009 at our hospital. Per patient costs of each hysterectomy method were examined from the societal perspective. Sensitivity analysis and Monte Carlo simulation were performed using a cost-minimization model. Results. 40 (17.1%) of hysterectomies for endometrial cancer were robotic, 91 (38.9%), were abdominal, and 103 (44.0%) were laparoscopic. 96.3% of the variation in operative cost between patients was predicted by operative time (R = 0.963, P < 0.01). Mean operative time for robotic hysterectomy was significantly longer than other methods (P < 0.01). Abdominal hysterectomy was consistently the most expensive while the traditional laparoscopic approach was consistently least expensive. The threshold in operative time that makes robotic hysterectomy cost equivalent to the abdominal approach is within the range of our experience. Conclusion. It is feasible for robotic hysterectomy to be less expensive than abdominal hysterectomy, but unlikely for robotic hysterectomy to be less expensive than traditional laparoscopy

Parents, children and the porous boundaries of the sexual family in law and popular culture

This article focuses on a perceived ideological overlap between popular cultural and judicial treatments of sex and conjugality that contributes to a discursive construction of parenthood and parenting. The author perceives that in both legal and popular cultural texts, there is a sense in which notions of ‘natural’ childhood are discursively constituted as being put at risk by those who reproduce outside of dominant sexual norms, and that signs of normative sexuality (typically in the form of heterosexual coupling) may be treated as a sign of safety. These ideas are rooted in ancient associations between fertility, sexuality and femininity that can also be traced in the historical development of the English language. With the help of commentators such as Martha Fineman, the article situates parents and children within a discourse of family which prioritises conjugality, with consequences for the ways in which the internal and external boundaries of families are delineated

Ontologies relevant to behaviour change interventions: a method for their development.

Background: Behaviour and behaviour change are integral to many aspects of wellbeing and sustainability. However, reporting behaviour change interventions accurately and synthesising evidence about effective interventions is hindered by lacking a shared, scientific terminology to describe intervention characteristics. Ontologies are standardised frameworks that provide controlled vocabularies to help unify and connect scientific fields. To date, there is no published guidance on the specific methods required to develop ontologies relevant to behaviour change. We report the creation and refinement of a method for developing ontologies that make up the Behaviour Change Intervention Ontology (BCIO). Aims: (1) To describe the development method of the BCIO and explain its rationale; (2) To provide guidance on implementing the activities within the development method. Method and results: The method for developing ontologies relevant to behaviour change interventions was constructed by considering principles of good practice in ontology development and identifying key activities required to follow those principles. The method's details were refined through application to developing two ontologies. The resulting ontology development method involved: (1) defining the ontology's scope; (2) identifying key entities; (3) refining the ontology through an iterative process of literature annotation, discussion and revision; (4) expert stakeholder review; (5) testing inter-rater reliability; (6) specifying relationships between entities, and; (7) disseminating and maintaining the ontology. Guidance is provided for conducting relevant activities for each step.  Conclusions: We have developed a detailed method for creating ontologies relevant to behaviour change interventions, together with practical guidance for each step, reflecting principles of good practice in ontology development. The most novel aspects of the method are the use of formal mechanisms for literature annotation and expert stakeholder review to develop and improve the ontology content. We suggest the mnemonic SELAR3, representing the method's first six steps as Scope, Entities, Literature Annotation, Review, Reliability, Relationships

Development of an Intervention Setting Ontology for behaviour change: Specifying where interventions take place.

Background: Contextual factors such as an intervention's setting are key to understanding how interventions to change behaviour have their effects and patterns of generalisation across contexts. The intervention's setting is not consistently reported in published reports of evaluations. Using ontologies to specify and classify intervention setting characteristics enables clear and reproducible reporting, thus aiding replication, implementation and evidence synthesis. This paper reports the development of a Setting Ontology for behaviour change interventions as part of a Behaviour Change Intervention Ontology, currently being developed in the Wellcome Trust funded Human Behaviour-Change Project. Methods: The Intervention Setting Ontology was developed following methods for ontology development used in the Human Behaviour-Change Project: 1) Defining the ontology's scope, 2) Identifying key entities by reviewing existing classification systems (top-down) and 100 published behaviour change intervention reports (bottom-up), 3) Refining the preliminary ontology by literature annotation of 100 reports, 4) Stakeholder reviewing by 23 behavioural science and public health experts to refine the ontology, 5) Assessing inter-rater reliability of using the ontology by two annotators familiar with the ontology and two annotators unfamiliar with it, 6) Specifying ontological relationships between setting entities and 7) Making the Intervention Setting Ontology machine-readable using Web Ontology Language (OWL) and publishing online. Re sults: The Intervention Setting Ontology consists of 72 entities structured hierarchically with two upper-level classes: Physical setting including Geographic location, Attribute of location (including Area social and economic condition, Population and resource density sub-levels) and Intervention site (including Facility, Transportation and Outdoor environment sub-levels), as well as Social setting. Inter-rater reliability was found to be 0.73 (good) for those familiar with the ontology and 0.61 (acceptable) for those unfamiliar with it. Conclusion: The Intervention Setting Ontology can be used to code information from diverse sources, annotate the setting characteristics of existing intervention evaluation reports and guide future reporting

KDM4B is a master regulator of the estrogen receptor signalling cascade

The importance of the estrogen receptor (ER) in breast cancer (BCa) development makes it a prominent target for therapy. Current treatments, however, have limited effectiveness, and hence the definition of new therapeutic targets is vital. The ER is a member of the nuclear hormone receptor superfamily of transcription factors that requires co-regulator proteins for complete regulation. Emerging evidence has implicated a small number of histone methyltransferase (HMT) and histone demethylase (HDM) enzymes as regulators of ER signalling, including the histone H3 lysine 9 tri-/di-methyl HDM enzyme KDM4B. Two recent independent reports have demonstrated that KDM4B is required for ER-mediated transcription and depletion of the enzyme attenuates BCa growth in vitro and in vivo. Here we show that KDM4B has an overarching regulatory role in the ER signalling cascade by controlling expression of the ER and FOXA1 genes, two critical components for maintenance of the estrogen-dependent phenotype. KDM4B interacts with the transcription factor GATA-3 in BCa cell lines and directly co-activates GATA-3 activity in reporter-based experiments. Moreover, we reveal that KDM4B recruitment and demethylation of repressive H3K9me3 marks within upstream regulatory regions of the ER gene permits binding of GATA-3 to drive receptor expression. Ultimately, our findings confirm the importance of KDM4B within the ER signalling cascade and as a potential therapeutic target for BCa treatment

X-ray and Multiwavelength Insights into the Nature of Weak Emission-Line Quasars at Low Redshift

(Abridged) We report on the X-ray and multiwavelength properties of 11 radio-quiet quasars with weak or no emission lines identified by the Sloan Digital Sky Survey (SDSS) with redshift z=0.4-2.5. The distribution of relative X-ray brightness for our low-redshift weak-line quasar (WLQ) candidates is significantly different from that of typical radio-quiet quasars, having an excess of X-ray weak sources, but it is consistent with that of high-redshift WLQs. The X-ray weak sources generally show similar UV emission-line properties to those of the X-ray weak quasar PHL 1811; they may belong to the notable class of PHL 1811 analogs. The average X-ray spectrum of these sources is somewhat harder than that of typical radio-quiet quasars. Several other low-redshift WLQ candidates have normal ratios of X-ray-to-optical/UV flux, and their average X-ray spectral properties are also similar to those of typical radio-quiet quasars. The X-ray weak and X-ray normal WLQ candidates may belong to the same subset of quasars having high-ionization "shielding gas" covering most of the wind-dominated broad emission-line region, but be viewed at different inclinations. The mid-infrared-to-X-ray spectral energy distributions (SEDs) of these sources are generally consistent with those of typical SDSS quasars, showing that they are not likely to be BL Lac objects with relativistically boosted continua and diluted emission lines. However, one source in our X-ray observed sample is remarkably strong in X-rays, indicating that a small fraction of low-redshift WLQ candidates may actually be BL Lacs residing in the radio-faint tail of the BL Lac population. We also investigate universal selection criteria for WLQs over a wide range of redshift, finding that it is not possible to select WLQ candidates in a fully consistent way using different prominent emission lines as a function of redshift.Comment: ApJ in press; 26 pages, 11 figures and 7 tables. The full Table 3 is available upon reques

Heritability and reliability of automatically segmented human hippocampal formation subregions

The human hippocampal formation can be divided into a set of cytoarchitecturally and functionally distinct subregions, involved in different aspects of memory formation. Neuroanatomical disruptions within these subregions are associated with several debilitating brain disorders including Alzheimer's disease, major depression, schizophrenia, and bipolar disorder. Multi-center brain imaging consortia, such as the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, are interested in studying disease effects on these subregions, and in the genetic factors that affect them. For large-scale studies, automated extraction and subsequent genomic association studies of these hippocampal subregion measures may provide additional insight. Here, we evaluated the test-retest reliability and transplatform reliability (1.5 T versus 3 T) of the subregion segmentation module in the FreeSurfer software package using three independent cohorts of healthy adults, one young (Queensland Twins Imaging Study, N=39), another elderly (Alzheimer's Disease Neuroimaging Initiative, ADNI-2, N=163) and another mixed cohort of healthy and depressed participants (Max Planck Institute, MPIP, N=598). We also investigated agreement between the most recent version of this algorithm (v6.0) and an older version (v5.3), again using the ADNI-2 and MPIP cohorts in addition to a sample from the Netherlands Study for Depression and Anxiety (NESDA) (N=221). Finally, we estimated the heritability (h(2)) of the segmented subregion volumes using the full sample of young, healthy QTIM twins (N=728). Test-retest reliability was high for all twelve subregions in the 3 T ADNI-2 sample (intraclass correlation coefficient (ICC)=0.70-0.97) and moderate-to-high in the 4 TQTIM sample (ICC=0.5-0.89). Transplatform reliability was strong for eleven of the twelve subregions (ICC=0.66-0.96); however, the hippocampal fissure was not consistently reconstructed across 1.5 T and 3 T field strengths (ICC=0.47-0.57). Between-version agreement was moderate for the hippocampal tail, subiculum and presubiculum (ICC=0.78-0.84; Dice Similarity Coefficient (DSC)=0.55-0.70), and poor for all other subregions (ICC=0.34-0.81; DSC=0.28-0.51). All hippocampal subregion volumes were highly heritable (h(2)=0.67-0.91). Our findings indicate that eleven of the twelve human hippocampal subregions segmented using FreeSurfer version 6.0 may serve as reliable and informative quantitative phenotypes for future multi-site imaging genetics initiatives such as those of the ENIGMA consortium. (C) 2016 The Authors. Published by Elsevier Inc

The Feasibility of Societal Cost Equivalence between Robotic Hysterectomy and Alternate Hysterectomy Methods for Endometrial Cancer

Objectives. We assess whether it is feasible for robotic hysterectomy for endometrial cancer to be less expensive to society than traditional laparoscopic hysterectomy or abdominal hysterectomy.Methods. We performed a retrospective cohort analysis of patient characteristics, operative times, complications, and hospital charges from all (n = 234) endometrial cancer patients who underwent hysterectomy in 2009 at our hospital. Per patient costs of each hysterectomy method were examined from the societal perspective. Sensitivity analysis and Monte Carlo simulation were performed using a cost-minimization model. Results. 40 (17.1%) of hysterectomies for endometrial cancer were robotic, 91 (38.9%), were abdominal, and 103 (44.0%) were laparoscopic. 96.3% of the variation in operative cost between patients was predicted by operative time (R = 0.963, P &lt; 0.01). Mean operative time for robotic hysterectomy was significantly longer than other methods (P &lt; 0.01). Abdominal hysterectomy was consistently the most expensive while the traditional laparoscopic approach was consistently least expensive. The threshold in operative time that makes robotic hysterectomy cost equivalent to the abdominal approach is within the range of our experience. Conclusion. It is feasible for robotic hysterectomy to be less expensive than abdominal hysterectomy, but unlikely for robotic hysterectomy to be less expensive than traditional laparoscopy