Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast.

An association has been reported between consumption of a high soy diet and a low incidence of breast cancer within populations of Southeast Asia. Phytoestrogens present in soy act as partial estrogen agonists or antagonists and can inhibit breast cancer cell proliferation in vitro. The effect of 14-day dietary soy supplementation with 60 g (45 mg isoflavones) on the normal breast of 84 premenopausal patients was determined. Serum concentrations of the isoflavanoids, genistein, daidzein, and equol, were raised in patients after soy supplementation (P < or = 0.025). Nipple aspirate (NA) levels of genistein and daidzein were higher than paired serum levels, both before (P < 0.001 and P = 0.001, respectively) and after soy supplementation (P < 0.001 and P = 0.049, respectively); however, there was no significant increase in NA isoflavone levels in response to soy. NA levels of apolipoprotein D were significantly lowered and pS2 levels raised in response to soy supplementation (P < or = 0.002), indicative of an estrogenic stimulus. No effect of soy supplementation on breast epithelial cell proliferation, estrogen and progesterone receptor status, apoptosis, mitosis, or Bcl-2 expression was detected. In conclusion, short term dietary soy has a weak estrogenic response on the breast, as measured by nipple aspirate apolipoprotein D and pS2 expression. No antiestrogenic effect of soy on the breast was detected

Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

The Hubbard model within the equations of motion approach

The Hubbard model has a special role in Condensed Matter Theory as it is considered as the simplest Hamiltonian model one can write in order to describe anomalous physical properties of some class of real materials. Unfortunately, this model is not exactly solved except for some limits and therefore one should resort to analytical methods, like the Equations of Motion Approach, or to numerical techniques in order to attain a description of its relevant features in the whole range of physical parameters (interaction, filling and temperature). In this manuscript, the Composite Operator Method, which exploits the above mentioned analytical technique, is presented and systematically applied in order to get information about the behavior of all relevant properties of the model (local, thermodynamic, single- and two- particle ones) in comparison with many other analytical techniques, the above cited known limits and numerical simulations. Within this approach, the Hubbard model is shown to be also capable to describe some anomalous behaviors of the cuprate superconductors.Comment: 232 pages, more than 300 figures, more than 500 reference

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

Gold OAIntroduction: Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. Methods More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer ‘stem’ cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. Results The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. Conclusions With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Challenge clusters facing LCA in environmental decision-making—what we can learn from biofuels

Purpose Bioenergy is increasingly used to help meet greenhouse gas (GHG) and renewable energy targets. However, bioenergy’s sustainability has been questioned, resulting in increasing use of life cycle assessment (LCA). Bioenergy systems are global and complex, and market forces can result in significant changes, relevant to LCA and policy. The goal of this paper is to illustrate the complexities associated with LCA, with particular focus on bioenergy and associated policy development, so that its use can more effectively inform policymakers. Methods The review is based on the results from a series of workshops focused on bioenergy life cycle assessment. Expert submissions were compiled and categorized within the first two workshops. Over 100 issues emerged. Accounting for redundancies and close similarities in the list, this reduced to around 60 challenges, many of which are deeply interrelated. Some of these issues were then explored further at a policyfacing workshop in London, UK. The authors applied a rigorous approach to categorize the challenges identified to be at the intersection of biofuels/bioenergy LCA and policy. Results and discussion The credibility of LCA is core to its use in policy. Even LCAs that comply with ISO standards and policy and regulatory instruments leave a great deal of scope for interpretation and flexibility. Within the bioenergy sector, this has led to frustration and at times a lack of obvious direction. This paper identifies the main challenge clusters: overarching issues, application and practice and value and ethical judgments. Many of these are reflective of the transition from application of LCA to assess individual products or systems to the wider approach that is becoming more common. Uncertainty in impact assessment strongly influences planning and compliance due to challenges in assigning accountability, and communicating the inherent complexity and uncertainty within bioenergy is becoming of greater importance. Conclusions The emergence of LCA in bioenergy governance is particularly significant because other sectors are likely to transition to similar governance models. LCA is being stretched to accommodate complex and broad policy-relevant questions, seeking to incorporate externalities that have major implications for long-term sustainability. As policy increasingly relies on LCA, the strains placed on the methodology are becoming both clearer and impedimentary. The implications for energy policy, and in particular bioenergy, are large

Fulvestrant is an effective and well-tolerated endocrine therapy for postmenopausal women with advanced breast cancer: results from clinical trials

Fulvestrant (‘Faslodex’) is a new type of endocrine treatment – an oestrogen receptor (ER) antagonist that downregulates the ER and has no agonist effects. Early efficacy data from phase I/II trials have demonstrated fulvestrant to be effective and well tolerated. Two randomised phase III trials have compared the efficacy of fulvestrant and the aromatase inhibitor, anastrozole, in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy. Fulvestrant (intramuscular injection 250 mg month−1) was found to be at least as effective as anastrozole (orally 1 mg day−1) for time to progression (5.5 vs 4.1 months, respectively (hazard ratio (HR): 0.95; 95.14% confidence interval (CI), 0.82–1.10; P=0.48)) and objective response 19.2 vs 16.5%, respectively; treatment difference 2.75%; 95.14% CI, −2.27 to 9.05%; P=0.31). More recently, fulvestrant has also been shown to be noninferior to anastrozole in terms of overall survival, with median time to death being 26.4 months in fulvestrant-treated patients and 24.2 months in those treated with anastrozole (HR: 0.97; 95% CI, 0.78–1.21; P=0.82). In a further randomised phase III trial, fulvestrant was compared with tamoxifen as first-line therapy for advanced disease in postmenopausal women. In the overall population, efficacy differences favoured tamoxifen and noninferiority of fulvestrant could not be ruled out. In the prospectively defined subset of patients with ER-positive and/or progesterone receptor-positive disease, there was no statistically significant difference between fulvestrant and tamoxifen. This paper reviews the efficacy and tolerability results from these trials

Reconnecting with nature for sustainability

Calls for humanity to ‘reconnect to nature’ have grown increasingly louder from both scholars and civil society. Yet, there is relatively little coherence about what reconnecting to nature means, why it should happen and how it can be achieved. We present a conceptual framework to organise existing literature and direct future research on human–nature connections. Five types of connections to nature are identified: material, experiential, cognitive, emotional, and philosophical. These various types have been presented as causes, consequences, or treatments of social and environmental problems. From this conceptual base, we discuss how reconnecting people with nature can function as a treatment for the global environmental crisis. Adopting a social–ecological systems perspective, we draw upon the emerging concept of ‘leverage points’—places in complex systems to intervene to generate change—and explore examples of how actions to reconnect people with nature can help transform society towards sustainability