Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort

INTRODUCTION: Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in breast cancer. At least four polymorphisms in the VEGF gene have been associated with changes in VEGF expression levels: -2578C/A, -1154G/A and -634G/C are all located in the promoter region; and +936C/T is located in the 3'-untranslated region. METHOD: We examined the association between these four VEGF polymorphisms and risk for breast cancer among postmenopausal women in CPS-II (Cancer Prevention Study II) Nutrition Cohort. This cohort was established in 1992 and participants were invited to provide a blood sample between 1998 and 2001. Included in this analysis were 501 postmenopausal women who provided a blood sample and were diagnosed with breast cancer between 1992 and 2001 (cases). Control individuals were 504 cancer-free postmenopausal women matched to the cases with respect to age, race/ethnicity, and date of blood collection (controls). RESULTS: We found no association between any of the polymorphisms examined and overall breast cancer risk. However, associations were markedly different in separate analyses of invasive cancer (n = 380) and in situ cancer (n = 107). The -2578C and -1154G alleles, which are both hypothesized to increase expression of VEGF, were associated with increased risk for invasive breast cancer (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.00–2.14 for -2578 CC versus AA; OR 1.64, 95% CI 1.02–2.64 for -1154 GG versus AA) but they were not associated with risk for in situ cancer. The +936C allele, which is also hypothesized to increase VEGF expression, was not clearly associated with invasive breast cancer (OR 1.21, 95% CI 0.88–1.67 for +936 CC versus TT/CT), but it was associated with reduced risk for in situ cancer (OR 0.59, 95% CI 0.37–0.93 for CC versus TT/CT). The -634 C/G polymorphism was not associated with either invasive or in situ cancer. CONCLUSION: Our findings provide limited support for the hypothesis that the -2578C and -1154G VEGF alleles are associated with increased risk for invasive but not in situ breast cancer in postmenopausal women

All different or all the same? Exploring the diversity of professional practices in Portuguese school psychology

"Published online: 29 March 2016"Studies have generally characterized school psychologists as a relative homogenous population. Understanding the differences in professional practices and related variables is important for the development of the profession. Using a sample of 446 Portuguese school psychologists, this study used cluster analysis to identify distinct profiles of professional activity, based on practitioners’ time distribution among different target audiences (i.e.,students, parents, teachers, school board members, school non-professional staff, and other professionals within the school community). Three distinct profiles emerged from the data: a group highly oriented to work with students, a group that distributes time almost equitably between adults and students, and a group that concentrates attention and professional expertise on adults. Practice setting variables, such as school-psychologists-to-student ratio, schoolpsychologists-to-school ratio, number of referrals per year, and school community level of demand for different activities, were found to be significantly related to cluster membership. No personal- or professional-background-related variables differentiated the three groups. The main implications of these findings are discussed in light of recent literature regarding the models of service delivery for school psychologists

Current tidal power technologies and their suitability for applications in coastal and marine areas

A considerable body of research is currently being performed to quantify available tidal energy resources and to develop efficient devices with which to harness them. This work is naturally focussed on maximising power generation from the most promising sites, and a review of the literature suggests that the potential for smaller scale, local tidal power generation from shallow near-shore sites has not yet been investigated. If such generation is feasible, it could have the potential to provide sustainable electricity for nearby coastal homes and communities as part of a distributed generation strategy, and would benefit from easier installation and maintenance, lower cabling and infrastructure requirements and reduced capital costs when compared with larger scale projects. This article reviews tidal barrages and lagoons, tidal turbines, oscillating hydrofoils and tidal kites to assess their suitability for small-scale electricity generation in shallow waters. This is achieved by discussing the power density, scalability, durability, maintainability, economic potential and environmental impacts of each concept. The performance of each technology in each criterion is scored against axial-flow turbines, allowing for them to be ranked according to their overall suitability. The review suggests that tidal kites and range devices are not suitable for small-scale shallow water applications due to depth and size requirements respectively. Cross-flow turbines appear to be the most suitable technology, as they have high power densities and a maximum size that is not constrained by water depth

Standardized ultrasound evaluation of carotid stenosis for clinical trials: University of Washington Ultrasound Reading Center

<p>Abstract</p> <p>Introduction</p> <p>Serial monitoring of patients participating in clinical trials of carotid artery therapy requires noninvasive precision methods that are inexpensive, safe and widely available. Noninvasive ultrasonic duplex Doppler velocimetry provides a precision method that can be used for recruitment qualification, pre-treatment classification and post treatment surveillance for remodeling and restenosis. The University of Washington Ultrasound Reading Center (UWURC) provides a uniform examination protocol and interpretation of duplex Doppler velocity measurements.</p> <p>Methods</p> <p>Doppler waveforms from 6 locations along the common carotid and internal carotid artery path to the brain plus the external carotid and vertebral arteries on each side using a Doppler examination angle of 60 degrees are evaluated. The UWURC verifies all measurements against the images and waveforms for the database, which includes pre-procedure, post-procedure and annual follow-up examinations. Doppler angle alignment errors greater than 3 degrees and Doppler velocity measurement errors greater than 0.05 m/s are corrected.</p> <p>Results</p> <p>Angle adjusted Doppler velocity measurements produce higher values when higher Doppler examination angles are used. The definition of peak systolic velocity varies between examiners when spectral broadening due to turbulence is present. Examples of measurements are shown.</p> <p>Discussion</p> <p>Although ultrasonic duplex Doppler methods are widely used in carotid artery diagnosis, there is disagreement about how the examinations should be performed and how the results should be validated. In clinical trails, a centralized reading center can unify the methods. Because the goals of research examinations are different from those of clinical examinations, screening and diagnostic clinical examinations may require fewer velocity measurements.</p

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

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

Non-Functional Parathyroid Carcinoma: A Review of the Literature and Report of a Case Requiring Extensive Surgery

Parathyroid carcinoma is a rare malignancy, and only accounts for 0.5–2% of cases of primary hyperparathyroidism. Less than 10% of parathyroid carcinomas are non-functional, and as such, they have been rarely reported in the literature. Importantly, margin status at resection is related to prognosis, and only a handful of case reports of non-functional carcinoma note this important parameter. Here we report the first case of non-functional parathyroid carcinoma with negative margins, and review the literature on this rare entity. Whether functional or non-functional, parathyroid carcinoma can often be difficult to differentiate from benign parathyroid adenoma. While diagnosis has been based on clinical and histological criteria, recent data concerning the molecular underpinnings of parathyroid carcinoma may allow for improved accuracy in distinguishing benign and malignant parathyroid tumors

Role of genetic polymorphisms in tumour angiogenesis

Angiogenesis plays a crucial role in the development, growth and spread of solid tumours. Pro- and anti-angiogenic factors are abnormally expressed in tumours, influencing tumour angiogenesis, growth and progression. Polymorphisms in genes encoding angiogenic factors or their receptors may alter protein expression and/or activity. This article reviews the literature to determine the possible role of angiogenesis-related polymorphisms in cancer. Further research studies in this potentially crucial area of tumour biology are proposed

Tamoxifen mechanically deactivates hepatic stellate cells via the G protein-coupled estrogen receptor

Tamoxifen has been used for many years to target estrogen receptor signalling in breast cancer cells. Tamoxifen is also an agonist of the G protein-coupled estrogen receptor (GPER), a GPCR ubiquitously expressed in tissues that mediates the acute response to estrogens. Here we report that tamoxifen promotes mechanical quiescence in hepatic stellate cells (HSCs), stromal fibroblast-like cells whose activation triggers and perpetuates liver fibrosis in hepatocellular carcinomas. This mechanical deactivation is mediated by the GPER/RhoA/myosin axis and induces YAP deactivation. We report that tamoxifen decreases the levels of hypoxia-inducible factor-1 alpha (HIF-1α) and the synthesis of extracellular matrix proteins through a mechanical mechanism that involves actomyosin-dependent contractility and mechanosensing of tissue stiffness. Our results implicate GPER-mediated estrogen signalling in the mechanosensory-driven activation of HSCs and put forward estrogenic signalling as an option for mechanical reprogramming of myofibroblast-like cells in the tumour microenvironment. Tamoxifen, with half a century of safe clinical use, might lead this strategy of drug repositioning.Peer reviewe