Assessing the performance of maternity care in Europe: A critical exploration of tools and indicators

Background: This paper critically reviews published tools and indicators currently used to measure maternity care performance within Europe, focusing particularly on whether and how current approaches enable systematic appraisal of processes of minimal (or non-) intervention in support of physiological or "normal birth". The work formed part of COST Actions IS0907: "Childbirth Cultures, Concerns, and Consequences: Creating a dynamic EU framework for optimal maternity care" (2011-2014) and IS1405: Building Intrapartum Research Through Health - an interdisciplinary whole system approach to understanding and contextualising physiological labour and birth (BIRTH) (2014-). The Actions included the sharing of country experiences with the aim of promoting salutogenic approaches to maternity care. Methods: A structured literature search was conducted of material published between 2005 and 2013, incorporating research databases, published documents in english in peer-reviewed international journals and indicator databases which measured aspects of health care at a national and pan-national level. Given its emergence from two COST Actions the work, inevitably, focused on Europe, but findings may be relevant to other countries and regions. Results: A total of 388 indicators were identified, as well as seven tools specifically designed for capturing aspects of maternity care. Intrapartum care was the most frequently measured feature, through the application of process and outcome indicators. Postnatal and neonatal care of mother and baby were the least appraised areas. An over-riding focus on the quantification of technical intervention and adverse or undesirable outcomes was identified. Vaginal birth (no instruments) was occasionally cited as an indicator; besides this measurement few of the 388 indicators were found to be assessing non-intervention or "good" or positive outcomes more generally. Conclusions: The tools and indicators identified largely enable measurement of technical interventions and undesirable health (or pathological medical) outcomes. A physiological birth generally necessitates few, or no, interventions, yet most of the indicators presently applied fail to capture (a) this phenomenon, and (b) the relationship between different forms and processes of care, mode of birth and good or positive outcomes. A need was identified for indicators which capture non-intervention, reflecting the reality that most births are low-risk, requiring few, if any, technical medical procedures

t10c12 Conjugated Linoleic Acid Suppresses HER2 Protein and Enhances Apoptosis in SKBr3 Breast Cancer Cells: Possible Role of COX2

BACKGROUND: HER2-targeted therapy with the monoclonal antibody trastuzumab (Herceptin) has improved disease-free survival for women diagnosed with HER2-positive breast cancers; however, treatment resistance and disease progression are not uncommon. Current data suggest that resistance to treatment in HER2 cancers may be a consequence of NF-kappaB overexpression and increased COX2-derived prostaglandin E2 (PGE(2)). Conjugated linoleic acid (CLA) has been shown to have anti-tumor properties and to inhibit NF-kappaB activity and COX2. METHODS: In this study, HER2-overexpressing SKBr3 breast cancer cells were treated with t10c12 CLA. Protein expression of the HER2 receptor, nuclear NF-kappaB p65, and total and phosphorylated IkappaB were examined by western blot and immunofluorescence. PGE(2) levels were determined by ELISA. Proliferation was measured by metabolism of 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and apoptosis was measured by FITC-conjugated Annexin V staining and flow cytometry. RESULTS/CONCLUSIONS: We observed a significant decrease in HER2 protein expression on western blot following treatment with 40 and 80 microM t10c12 CLA (p<0.01 and 0.001, respectively) and loss of HER2 protein in cells using immunoflourescence that was most pronounced at 80 microM. Protein levels of nuclear NF-kappaB p65 were also significantly reduced at the 80 microM dose. This was accompanied by a significant decrease in PGE(2) levels (p = 0.05). Pretreatment with t10c12 CLA significantly enhanced TNFalpha-induced apoptosis and the anti-proliferative action of trastuzumab (p = 0.05 and 0.001, respectively). These data add to previous reports of an anti-tumor effect of t10c12 CLA and suggest an effect on the HER2 oncogene that may be through CLA mediated downregulation of COX2-derived PGE(2)

Population Genomics of Parallel Adaptation in Threespine Stickleback using Sequenced RAD Tags

Next-generation sequencing technology provides novel opportunities for gathering genome-scale sequence data in natural populations, laying the empirical foundation for the evolving field of population genomics. Here we conducted a genome scan of nucleotide diversity and differentiation in natural populations of threespine stickleback (Gasterosteus aculeatus). We used Illumina-sequenced RAD tags to identify and type over 45,000 single nucleotide polymorphisms (SNPs) in each of 100 individuals from two oceanic and three freshwater populations. Overall estimates of genetic diversity and differentiation among populations confirm the biogeographic hypothesis that large panmictic oceanic populations have repeatedly given rise to phenotypically divergent freshwater populations. Genomic regions exhibiting signatures of both balancing and divergent selection were remarkably consistent across multiple, independently derived populations, indicating that replicate parallel phenotypic evolution in stickleback may be occurring through extensive, parallel genetic evolution at a genome-wide scale. Some of these genomic regions co-localize with previously identified QTL for stickleback phenotypic variation identified using laboratory mapping crosses. In addition, we have identified several novel regions showing parallel differentiation across independent populations. Annotation of these regions revealed numerous genes that are candidates for stickleback phenotypic evolution and will form the basis of future genetic analyses in this and other organisms. This study represents the first high-density SNP–based genome scan of genetic diversity and differentiation for populations of threespine stickleback in the wild. These data illustrate the complementary nature of laboratory crosses and population genomic scans by confirming the adaptive significance of previously identified genomic regions, elucidating the particular evolutionary and demographic history of such regions in natural populations, and identifying new genomic regions and candidate genes of evolutionary significance

Drug Resistance in Eukaryotic Microorganisms

Eukaryotic microbial pathogens are major contributors to illness and death globally. Although much of their impact can be controlled by drug therapy as with prokaryotic microorganisms, the emergence of drug resistance has threatened these treatment efforts. Here, we discuss the challenges posed by eukaryotic microbial pathogens and how these are similar to, or differ from, the challenges of prokaryotic antibiotic resistance. The therapies used for several major eukaryotic microorganisms are then detailed, and the mechanisms that they have evolved to overcome these therapies are described. The rapid emergence of resistance and the restricted pipeline of new drug therapies pose considerable risks to global health and are particularly acute in the developing world. Nonetheless, we detail how the integration of new technology, biological understanding, epidemiology and evolutionary analysis can help sustain existing therapies, anticipate the emergence of resistance or optimize the deployment of new therapies