Decision-making regarding place of birth in high-risk pregnancy: a qualitative study

Introduction: Women consider factors including safety and the psychological impact of their chosen location when deciding whether to give birth in hospital or at home. The same is true for women with high-risk pregnancies who may plan homebirths against medical advice. This study investigated women’s decision-making during high-risk pregnancies. Half the participants were planning hospital births and half were planning homebirths. Methods: A qualitative study using semi-structured interviews set in a hospital maternity department in the UK. Twenty-six participants with high-risk pregnancies, at least 32 weeks pregnant. Results were analysed using systematic thematic analysis. Results: Three themes emerged: perceptions of birth at home and hospital; beliefs about how birth should be; and the decision process. Both groups were concerned about safety but they expressed different concerns. Women drew psychological comfort from their chosen birth location. Women planning homebirths displayed faith in the natural birth process and stressed the quality of the birth experience. Women planning hospital births believed the access to medical care outweighed their misgivings about the physical environment. Discussion: Although women from both groups expressed similar concerns about safety they reached different decisions about how these should be addressed regarding birth location. These differences may be related to beliefs about the birth process. Commitment to their decisions may have helped reduce cognitive stress

The genetics of colored sequence synesthesia: Evidence of linkage to chromosome 16q and genetic heterogeneity for the condition

Synesthesia is a perceptual condition in which normal sensory stimulation can trigger anomalous sensory experiences. For example, synesthetes may experience colors in response to sounds, tastes in response to words, or smells in response to touch. We here focus on colored sequence synesthesia, in which color experiences are triggered by learned ordinal sequences such as letters, numbers, weekdays and months. Although synesthesia has been noted in the scientific literature for over a century, it is understood only at the level of the phenomenology, and not at the molecular and neural levels. We have performed a linkage analysis to identify the first genetic loci responsible for the increased neural crosstalk underlying colored sequence synesthesia. Our analysis has identified a 23 MB region on chromosome 16 as a putative locus for the trait. Our data provide the first step in understanding neural crosstalk from its molecular basis to its behavioral consequences, opening a new inroad into the understanding of the multisensory brain

Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy

Metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and mitochondrial biogenesis in subpopulations of CD4+ and CD8+ T cells from 18 virologically-suppressed HIV-positive individuals on combination antiretroviral therapy (cART; median CD4+ cell count: 728 cells/μl) and 13 HIV seronegative controls. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production were also analysed in total CD4+ and CD8+ T cells. Among HIV+/cART individuals, expression of glucose transporter (Glut1) and mitochondrial density were highest within central memory and naïve CD4+ T cells, and lowest among effector memory and transitional memory T cells, with similar trends in HIV-negative controls. Compared to HIV-negative controls, there was a trend towards higher percentage of circulating CD4+Glut1+ T cells in HIV+/cART participants. There were no significant differences in mitochondrial dynamics between subject groups. Glut1 expression was positively correlated with mitochondrial density and MMP in total CD4+ T cells, while MMP was also positively correlated with ROS production in both CD4+ and CD8+ T cells. Our study characterizes specific metabolic features of CD4+ and CD8+ T cells in HIV-negative and HIV+/cART individuals and will invite future studies to explore the immunometabolic consequences of HIV infection

Gene expression profile of cervical tissue compared to exfoliated cells: Impact on biomarker discovery

BACKGROUND: Exfoliated cervical cells are used in cytology-based cancer screening and may also be a source for molecular biomarkers indicative of neoplastic changes in the underlying tissue. However, because of keratinization and terminal differentiation it is not clear that these cells have an mRNA profile representative of cervical tissue, and that the profile can distinguish the lesions targeted for early detection. RESULTS: We used whole genome microarrays (25,353 unique genes) to compare the transcription profiles from seven samples of normal exfoliated cells and one cervical tissue. We detected 10,158 genes in exfoliated cells, 14,544 in the tissue and 7320 genes in both samples. For both sample types the genes grouped into the same major gene ontology (GO) categories in the same order, with exfoliated cells, having on average 20% fewer genes in each category. We also compared microarray results of samples from women with cervical intraepithelial neoplasia grade 3 (CIN3, n = 15) to those from age and race matched women without significant abnormalities (CIN1, CIN0; n = 15). We used three microarray-adapted statistical packages to identify differential gene expression. The six genes identified in common were two to four fold upregulated in CIN3 samples. One of these genes, the ubiquitin-conjugating enzyme E2 variant 1, participates in the degradation of p53 through interaction with the oncogenic HPV E6 protein. CONCLUSION: The findings encourage further exploration of gene expression using exfoliated cells to identify and validate applicable biomarkers. We conclude that the gene expression profile of exfoliated cervical cells partially represents that of tissue and is complex enough to provide potential differentiation between disease and non-disease

Characterization of the Mouse Epidermal Growth Factor Promoter and 5′-Flanking Region: ROLE FOR AN ATYPICAL TATA SEQUENCE

As a step toward delineating mechanisms that regulate its activity, we have characterized the mouse epidermal growth factor (EGF) promoter. Primer extension and S1 nuclease analyses identified prominent (+1/+2) and minor (+28) transcription start sites, with the dominant +1/+2 site located 33 bases downstream from a TTTAAA sequence. A restriction fragment that spanned these start sites and contained 390 base pairs of 5'-flanking sequence directed transcription from the +1/+2 site in vitro in the presence of HeLa cell nuclear extracts. Additionally, it promoted expression of a coupled luciferase reporter gene in transfected cell lines. The inclusion of additional 5'-flanking sequence either stimulated or inhibited luciferase expression depending on the cell line. Approximately 2 kilobases of EGF 5'-flanking sequence was determined and found to contain several motifs with partial homology to steroid hormone response elements. Despite this fact and evidence that EGF expression might be regulated by androgens in vivo, EGF promoter-luciferase constructs were not steroid-responsive in cells cotransfected with steroid receptor expression vectors. An oligonucleotide containing the aforementioned TTTAAA sequence specifically bound TATA-binding protein and TFIIA in gel shift assays, and an EGF promoter-luciferase construct in which the core TA dinucleotide was mutated to CG was not active in transfected cells. These data suggest that the TTTAAA sequence functions as an atypical TATA box

Analysis of and workarounds for element reversal for a finite element-based algorithm for warping triangular and tetrahedral meshes

We consider an algorithm called FEMWARP for warping triangular and tetrahedral finite element meshes that computes the warping using the finite element method itself. The algorithm takes as input a two- or three-dimensional domain defined by a boundary mesh (segments in one dimension or triangles in two dimensions) that has a volume mesh (triangles in two dimensions or tetrahedra in three dimensions) in its interior. It also takes as input a prescribed movement of the boundary mesh. It computes as output updated positions of the vertices of the volume mesh. The first step of the algorithm is to determine from the initial mesh a set of local weights for each interior vertex that describes each interior vertex in terms of the positions of its neighbors. These weights are computed using a finite element stiffness matrix. After a boundary transformation is applied, a linear system of equations based upon the weights is solved to determine the final positions of the interior vertices. The FEMWARP algorithm has been considered in the previous literature (e.g., in a 2001 paper by Baker). FEMWARP has been succesful in computing deformed meshes for certain applications. However, sometimes FEMWARP reverses elements; this is our main concern in this paper. We analyze the causes for this undesirable behavior and propose several techniques to make the method more robust against reversals. The most successful of the proposed methods includes combining FEMWARP with an optimization-based untangler.Comment: Revision of earlier version of paper. Submitted for publication in BIT Numerical Mathematics on 27 April 2010. Accepted for publication on 7 September 2010. Published online on 9 October 2010. The final publication is available at http://www.springerlink.co

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer

PMCID: PMC3446380This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Reversible linkage of two distinct small molecule inhibitors of myc generates a dimeric inhibitor with improved potency that is active in myc over-expressing cancer cell lines

We describe the successful application of a novel approach for generating dimeric Myc inhibitors by modifying and reversibly linking two previously described small molecules.We synthesized two directed libraries of monomers, each comprised of a ligand, a connector, and a bioorthogonal linker element, to identify the optimal dimer configuration required to inhibit Myc. We identified combinations of monomers, termed self-assembling dimeric inhibitors, which displayed synergistic inhibition of Myc-dependent cell growth. We confirmed that these dimeric inhibitors directly bind to Myc blocking its interaction with Max and affect transcription of MYC dependent genes. Control combinations that are unable to form a dimer do not show any synergistic effects in these assays. Collectively, these data validate our new approach to generate more potent and selective inhibitors of Myc by self-assembly from smaller, lower affinity components. This approach provides an opportunity for developing novel therapeutics against Myc and other challenging protein:protein interaction (PPI) target classes. © 2015 Wanner et al

The edge of the periphery: situating the ≠Khomani San of the Southern Kalahari in the political economy of Southern Africa

This is an Accepted Manuscript of an article published by Taylor & Francis in African Identities on 14/04/16, available online: http://www.tandfonline.com/10.1080/14725843.2016.1154813In this article, we situate the Southern Kalahari San within the political economy of Southern Africa and within the world system. Here we draw on and critique modernization theory as a model of explanation for the lack of development found locally. In the Southern Kalahari, the ≠Khomani San won a massive land claim that should have empowered and enabled local development. Yet they remain largely impoverished, while seeking out a meaningful life on the edge of the capitalist world system. Within states, contradictions remain as local diversity continues to be reproduced and modernity itself is reproduced as local diversity. The research is premised on empirical fieldwork conducted in the Southern Kalahari in 2013 and supported by a series of earlier field research over the previous five years. The San of the Southern Kalahari are not resisting modernity but drawing on aspects of it selectively for their own vision of meaningful development