uPA is upregulated by high dose celecoxib in women at increased risk of developing breast cancer

<p>Abstract</p> <p>Background</p> <p>While increased urokinase-type plasminogen activator (uPA) expression in breast cancer tissue is directly associated with poor prognosis, recent evidence suggests that uPA overexpression may suppress tumor growth and prolong survival. Celecoxib has been shown to have antiangiogenic and antiproliferative properties. We sought to determine if uPA, PA inhibitor (PAI)-1 and prostaglandin (PG)E₂expression in nipple aspirate fluid (NAF) and uPA and PGE₂expression in plasma were altered by celecoxib dose and concentration in women at increased breast cancer risk.</p> <p>Methods</p> <p>NAF and plasma samples were collected in women at increased breast cancer risk before and 2 weeks after taking celecoxib 200 or 400 mg twice daily (bid). uPA, PAI-1 and PGE₂were measured before and after intervention.</p> <p>Results</p> <p>Celecoxib concentrations trended higher in women taking 400 mg (median 1025.0 ng/mL) compared to 200 mg bid (median 227.3 ng/mL), and in post- (534.6 ng/mL) compared to premenopausal (227.3 ng/mL) women. In postmenopausal women treated with the higher (400 mg bid) celecoxib dose, uPA concentrations increased, while PAI-1 and PGE₂decreased. In women taking the higher dose, both PAI-1 (r = -.97, p = .0048) and PGE₂(r = -.69, p = .019) in NAF and uPA in plasma (r = .45, p = .023) were correlated with celecoxib concentrations.</p> <p>Conclusion</p> <p>Celecoxib concentrations after treatment correlate inversely with the change in PAI-1 and PGE₂in the breast and directly with the change in uPA in the circulation. uPA upregulation, in concert with PAI-1 and PGE₂downregulation, may have a cancer preventive effect.</p

Regression analysis for peak designation in pulsatile pressure signals

Following recent studies, the automatic analysis of intracranial pressure (ICP) pulses appears to be a promising tool for forecasting critical intracranial and cerebrovascular pathophysiological variations during the management of many disorders. A pulse analysis framework has been recently developed to automatically extract morphological features of ICP pulses. The algorithm is able to enhance the quality of ICP signals, to segment ICP pulses, and to designate the locations of the three ICP sub-peaks in a pulse. This paper extends this algorithm by utilizing machine learning techniques to replace Gaussian priors used in the peak designation process with more versatile regression models. The experimental evaluations are conducted on a database of ICP signals built from 700 h of recordings from 64 neurosurgical patients. A comparative analysis of different state-of-the-art regression analysis methods is conducted and the best approach is then compared to the original pulse analysis algorithm. The results demonstrate a significant improvement in terms of accuracy in favor of our regression-based recognition framework. It reaches an average peak designation accuracy of 99% using a kernel spectral regression against 93% for the original algorithm

Regional differences in the pattern of airway remodeling following chronic allergen exposure in mice

BACKGROUND: Airway remodeling present in the large airways in asthma or asthma models has been associated with airway dysfunction in humans and mice. It is not clear if airways distal to the large conducting airways have similar degrees of airway remodeling following chronic allergen exposure in mice. Our objective was to test the hypothesis that airway remodeling is heterogeneous by optimizing a morphometric technique for distal airways and applying this to mice following chronic exposure to allergen or saline. METHODS: In this study, BALB/c mice were chronically exposed to intranasal allergen or saline. Lung sections were stained for smooth muscle, collagen, and fibronectin content. Airway morphometric analysis of small (0–50000 μm(2)), medium (50000 μm(2)–175000 μm(2)) and large (>175000 μm(2)) airways was based on quantifying the area of positive stain in several defined sub-epithelial regions of interest. Optimization of this technique was based on calculating sample sizes required to detect differences between allergen and saline exposed animals. RESULTS: Following chronic allergen exposure BALB/c mice demonstrate sustained airway hyperresponsiveness. BALB/c mice demonstrate an allergen-induced increase in smooth muscle content throughout all generations of airways, whereas changes in subepithelial collagen and fibronectin content are absent from distal airways. CONCLUSION: We demonstrate for the first time, a systematic objective analysis of allergen induced airway remodeling throughout the tracheobronchial tree in mice. Following chronic allergen exposure, at the time of sustained airway dysfunction, BALB/c mice demonstrate regional differences in the pattern of remodeling. Therefore results obtained from limited regions of lung should not be considered representative of the entire airway tree

How does gender influence the recognition of cardiovascular risk and adherence to self-care recommendations? : a study in polish primary care

Background: Studies have shown a correlation between gender and an ability to change lifestyle to reduce the risk of disease. However, the results of these studies are ambiguous, especially where a healthy lifestyle is concerned. Additionally, health behaviors are strongly modified by culture and the environment. Psychological factors also substantially affect engagement with disease-related lifestyle interventions. This study aimed to examine whether there are differences between men and women in the frequency of health care behavior for the purpose of reducing cardiovascular risk (CVR), as well as cognitive appraisal of this type of risk. We also aimed to identify the psychological predictors of engaging in recommended behavior for reducing the risk of cardiovascular disease after providing information about this risk in men and women. Methods: A total of 134 consecutive eligible patients in a family practice entered a longitudinal study. At initial consultation, the individual’s CVR and associated health burden was examined, and preventive measures were recommended by the physician. Self-care behavior, cognitive appraisal of risk, and coping styles were then assessed using psychological questionnaires. Six months after the initial data collection, the frequency of subjects’ self-care behavior was examined. Results: We found an increase in health care behavior after providing information regarding the rate of CVR in both sexes; this increase was greater for women than for men. Women followed self-care guidelines more often than men, particularly for preventive measures and dietary advice. Women were more inclined to recognize their CVR as a challenge. Coping style, cognitive appraisal, age, level of health behaviors at baseline and CVR values accounted for 48% of the variance in adherence to self-care guidelines in women and it was 52% in men. In women, total risk of CVD values were most important, while in men, cognitive appraisal of harm/loss was most important. Conclusions: Different predictors of acquisition of health behavior are encountered in men and women. Our results suggest that gender-adjusted motivation models influencing the recognition process need to be considered to optimize compliance in patients with CVR

Spectral Parameters for Scattering Amplitudes in N=4 Super Yang-Mills Theory

49 pages, 20 figures; v2: typos fixedPlanar N=4 Super Yang-Mills theory appears to be a quantum integrable four-dimensional conformal theory. This has been used to find equations believed to describe its exact spectrum of anomalous dimensions. Integrability seemingly also extends to the planar space-time scattering amplitudes of the N=4 model, which show strong signs of Yangian invariance. However, in contradistinction to the spectral problem, this has not yet led to equations determining the exact amplitudes. We propose that the missing element is the spectral parameter, ubiquitous in integrable models. We show that it may indeed be included into recent on-shell approaches to scattering amplitude integrands, providing a natural deformation of the latter. Under some constraints, Yangian symmetry is preserved. Finally we speculate that the spectral parameter might also be the regulator of choice for controlling the infrared divergences appearing when integrating the integrands in exactly four dimensions.Peer reviewe

What About Interaction Geography to Evaluate Physical Learning Spaces?

This paper reviews and explores how interaction geography, a new approach to visualize people’s interaction over space and time, extends current approaches to evaluate physical learning spaces. This chapter begins by reviewing representations produced using interaction geography to study visitor engagement and learning in a museum. In particular, this review illustrates Mondrian Transcription, a method to map people’s movement and conversation over space and time, and the Interaction Geography Slicer (IGS), a dynamic visualisation tool that supports new forms of interaction and multi-modal analysis. Subsequently, this chapter explores how interaction geography may advance the evaluation of physical learning spaces by providing dynamic information visualisation methods that support more expansive views of learning and the evaluation of the alignment between space and pedagogy. This chapter concludes by outlining significant limitations and next steps to expand interaction geography to evaluate physical learning spaces

Fluid gels: a new feedstock for high viscosity jetting

Suspensions of gel particles which are pourable or spoonable at room temperature can be created by shearing a gelling biopolymer through its gelation (thermal or ion mediated) rather than allowing quiescent cooling – thus the term ‘fluid gel’ may be used to describe the resulting material. As agar gelation is thermoreversible this type of fluid gel is able to be heated again to melt agar gel particles to varying degrees then re-form a network quiescently upon cooling, whose strength depends on the temperature of re-heating, determining the amount of agar solubilised and subsequently able to partake in re-gelation. Using this principle, for the first time fluid gels have been applied to a high viscosity 3D printing process wherein the printing temperature (at the nozzle) is controllable. This allows the use of ambient temperature feedstocks and by altering the nozzle temperature, the internal nature (presence or absence of gel particles) and gel strength of printed droplets differs. If the nozzle prints at different temperatures for each layer a structure with modulated texture could be created

Integration of Data Mining Classification Techniques and Ensemble Learning for Predicting the Type of Breast Cancer Recurrence

Conservative surgery plus radiotherapy is an alternative to radical mastectomy in the early stages of breast cancer, presenting equivalent survival rates. Data mining facilitates to manage the data and provide the useful medical progression and treatment of cancerous conditions as these methods can help to reduce the number of false positive and false negative decisions. Various machine learning techniques can be used to support the doctors in effective and accurate decision making. In this paper, various classifiers have been tested for the prediction of type of breast cancer recurrence and the results show that neural networks outperform others