Factors associated with crisis pregnancies in Ireland: Findings from three nationally representative sexual health surveys

Background: Findings on the demographic and sexual health characteristics associated with the experience of a crisis pregnancy is important to inform the public health policy of a country, including Ireland. Findings from other jurisdictions have suggested that certain demographic groups are at risk for unintended pregnancies and the disparity between the groups have been growing in recent years. Ireland is a country which experienced much economic and societal change in the first decade of the 21st century, changes which are likely to have affected demographic variables pertaining to sexual health. The current study had two aims: to investigate changes in the socioeconomic characteristics associated with crisis pregnancies over a seven year period [2003 to 2010], and to investigate the recent [2010] socioeconomic risk factors associated with crisis pregnancies in Ireland. Methods: The study compared the results from 18-45 year old women using data from three broadly similar nationally representative Irish sexual health surveys carried out in 2003, 2004-2006 and 2010. Chi square analysis compared of the socioeconomic characteristics across the seven year period and found that a higher proportion of women with two or more children and women for whom religion was not important reported a crisis pregnancy in 2010 compared with earlier years. A logistic regression then investigated the sexual health history and socioeconomic factors associated with the experience of a recent crisis pregnancy using the most recent 2010 data. Results: Receipt of sex education and contraception use at first sex significantly predicted the experiencing of a recent crisis pregnancy. Younger women and those with a lower level of education were more likely to report having experienced a recent crisis pregnancy. Conclusion: Similar demographic groups are at risk for experiencing a crisis pregnancy in Ireland compared with international research, yet the disparities between demographic groups who have experienced a crisis pregnancy appear to be decreasing rather than increasing over a seven year period. Recommendations are made with regard to the provision of continued sex education throughout the lifespan, particularly for those women who are at an increased risk of experiencing a crisis pregnancy

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

High Expression Levels of Total IGF-1R and Sensitivity of NSCLC Cells In Vitro to an Anti-IGF-1R Antibody (R1507)

© 2009 Gong et al

Self-esteem in adolescent patients with attention-deficit/hyperactivity disorder during open-label atomoxetine treatment: psychometric evaluation of the Rosenberg Self-Esteem Scale and clinical findings

To report on (1) psychometric properties of the Rosenberg Self-Esteem Scale (SES) studied in adolescents with ADHD, (2) correlations of SES with ADHD scale scores, and (3) change in patient-reported self-esteem with atomoxetine treatment. ADHD patients (12–17 years), treated in an open-label study for 24 weeks. Secondary analyses on ADHD symptoms (assessed with ADHD-RS, CGI, GIPD scales) and self-esteem (SES) were performed. One hundred and fifty-nine patients were treated. A dichotomous structure of the SES could be confirmed. Reliability and internal consistency were moderate to excellent. Highest coefficients were found for the correlation between SES and GIPD scores. Self-esteem significantly increased over time, accompanied by an improvement of ADHD symptoms and related perceived difficulties. The Rosenberg SES was shown to be internally consistent, reliable, and sensitive to treatment-related changes of self-esteem. According to these findings, self-esteem may be an important individual patient outcome beyond the core symptoms of ADHD

Predictors of long-term outcome following high-dose chemotherapy in high-risk primary breast cancer

We report on a predictive model of long-term outcome in 114 high-risk breast cancer patients treated with high-dose chemotherapy between 1989 and 1994. Paraffin-blocks from 90 of the 114 primaries were assessed for the presence of five risk factors: grade, mitotic index, protein expression of p53, HER2/neu, and oestrogen/progesterone receptor status; we could analyse the effect of risk factors in 84 of these 90 tumours. Seven-year relapse-free and overall survival was 58% (95% confidence interval 44–74%) and 82% (95% confidence interval 71–94%) vs 33% (95% confidence interval 21–52%) and 41% (95% confidence interval 28–60%) for patients whose primary tumours displayed ⩾3 risk factors vs patients with ⩽2 risk factors. For the entire group of 168 high-risk breast cancer patients, inflammatory stage IIIB disease and involved post-mastectomy margins were associated with decreased relapse-free survival and overall survival; patients treated with non-doxorubicin containing standard adjuvant therapy experienced worse overall survival (RR, 2.08; 95% confidence interval 1.04 to 4.16; P=0.04), while adjuvant tamoxifen improved overall survival (RR, 0.65; 95% confidence interval 0.41–1.01; P=0.054). Future trial designs and patient selection for studies specific for high-risk breast cancer patients should include appropriate prognostic models. Validation of such models could come from recently completed randomised, prospective trials

Repetitive N-WASP–Binding Elements of the Enterohemorrhagic Escherichia coli Effector EspFU Synergistically Activate Actin Assembly

Enterohemorrhagic Escherichia coli (EHEC) generate F-actin–rich adhesion pedestals by delivering effector proteins into mammalian cells. These effectors include the translocated receptor Tir, along with EspFU, a protein that associates indirectly with Tir and contains multiple peptide repeats that stimulate actin polymerization. In vitro, the EspFU repeat region is capable of binding and activating recombinant derivatives of N-WASP, a host actin nucleation-promoting factor. In spite of the identification of these important bacterial and host factors, the underlying mechanisms of how EHEC so potently exploits the native actin assembly machinery have not been clearly defined. Here we show that Tir and EspFU are sufficient for actin pedestal formation in cultured cells. Experimental clustering of Tir-EspFU fusion proteins indicates that the central role of the cytoplasmic portion of Tir is to promote clustering of the repeat region of EspFU. Whereas clustering of a single EspFU repeat is sufficient to bind N-WASP and generate pedestals on cultured cells, multi-repeat EspFU derivatives promote actin assembly more efficiently. Moreover, the EspFU repeats activate a protein complex containing N-WASP and the actin-binding protein WIP in a synergistic fashion in vitro, further suggesting that the repeats cooperate to stimulate actin polymerization in vivo. One explanation for repeat synergy is that simultaneous engagement of multiple N-WASP molecules can enhance its ability to interact with the actin nucleating Arp2/3 complex. These findings define the minimal set of bacterial effectors required for pedestal formation and the elements within those effectors that contribute to actin assembly via N-WASP-Arp2/3–mediated signaling pathways

Small Non-coding RNAs Govern Mammary Gland Tumorigenesis

Small non-coding RNAs include siRNA, miRNA, piRNA and snoRNA. The involvement of miRNAs in the regulation of mammary gland tumorigenesis has been widely studied while the role for other small non-coding RNAs remains unclear. Here we summarize the involvement of miRNA in breast cancer onset and progression through regulating the cell cycle and cellular proliferation. The regulation of breast cancer stem cells and tumor regeneration by miRNA is reviewed. In addition, the emerging evidence demonstrating the involvement of piRNA and snoRNA in breast cancer is briefly described

Fibrotic Myofibroblasts Manifest Genome-Wide Derangements of Translational Control

Background: As a group, fibroproliferative disorders of the lung, liver, kidney, heart, vasculature and integument are common, progressive and refractory to therapy. They can emerge following toxic insults, but are frequently idiopathic. Their enigmatic propensity to resist therapy and progress to organ failure has focused attention on the myofibroblast–the primary effector of the fibroproliferative response. We have recently shown that aberrant beta 1 integrin signaling in fibrotic fibroblasts results in defective PTEN function, unrestrained Akt signaling and subsequent activation of the translation initiation machinery. How this pathological integrin signaling alters the gene expression pathway has not been elucidated. Results: Using a systems approach to study this question in a prototype fibrotic disease, Idiopathic Pulmonary Fibrosis (IPF); here we show organized changes in the gene expression pathway of primary lung myofibroblasts that persist for up to 9 sub-cultivations in vitro. When comparing IPF and control myofibroblasts in a 3-dimensional type I collagen matrix, more genes differed at the level of ribosome recruitment than at the level of transcript abundance, indicating pathological translational control as a major characteristic of IPF myofibroblasts. To determine the effect of matrix state on translational control, myofibroblasts were permitted to contract the matrix. Ribosome recruitment in control myofibroblasts was relatively stable. In contrast, IPF cells manifested large alterations in the ribosome recruitment pattern. Pathological studies suggest an epithelial origin for IPF myofibroblasts through the epithelial to mesenchymal transition (EMT). In accord wit