Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

Ultrathin 2 nm gold as ideal impedance-matched absorber for infrared light

Thermal detectors are a cornerstone of infrared (IR) and terahertz (THz) technology due to their broad spectral range. These detectors call for suitable broad spectral absorbers with minimalthermal mass. Often this is realized by plasmonic absorbers, which ensure a high absorptivity butonly for a narrow spectral band. Alternativly, a common approach is based on impedance-matching the sheet resistance of a thin metallic film to half the free-space impedance. Thereby, it is possible to achieve a wavelength-independent absorptivity of up to 50 %, depending on the dielectric properties of the underlying substrate. However, existing absorber films typicallyrequire a thickness of the order of tens of nanometers, such as titanium nitride (14 nm), whichcan significantly deteriorate the response of a thermal transducers. Here, we present the application of ultrathin gold (2 nm) on top of a 1.2 nm copper oxide seed layer as an effective IR absorber. An almost wavelength-independent and long-time stable absorptivity of 47(3) %, ranging from 2 $\mu$m to 20 $\mu$m, could be obtained and is further discussed. The presented gold thin-film represents analmost ideal impedance-matched IR absorber that allows a significant improvement of state-of-the-art thermal detector technology

Patient-physician interaction in general practice and health inequalities in a multidisciplinary study: design, methods and feasibility in the French INTERMEDE study

<p>Abstract</p> <p>Background</p> <p>The way in which patients and their doctors interact is a potentially important factor in optimal communication during consultations as well as treatment, compliance and follow-up care. The aim of this multidisciplinary study is to use both qualitative and quantitative methods to explore the 'black box' that is the interaction between the two parties during a general practice consultation, and to identify factors therein that may contribute to producing health inequalities. This paper outlines the original multidisciplinary methodology used, and the feasibility of this type of study.</p> <p>Methods and design</p> <p>The study design combines methodologies on two separate samples in two phases. Firstly, a qualitative phase collected ethnographical and sociological data during consultation, followed by in-depth interviews with both patients and doctors independently. Secondly, a quantitative phase on a different sample of patients and physicians collected data via several questionnaires given to patients and doctors consisting of specific 'mirrored' questions asked post-consultation, as well as collecting information on patient and physician characteristics.</p> <p>Discussion</p> <p>The design and methodology used in this study were both successfully implemented, and readily accepted by doctors and patients alike. This type of multidisciplinary study shows great potential in providing further knowledge into the role of patient/physician interaction and its influence on maintaining or producing health inequalities. The next challenge in this study will be implementing the multidisciplinary approach during the data analysis.</p

Paradoxical embolism following thromboaspiration of an arteriovenous fistula thrombosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Paradoxical embolism is an increasingly reported cause of arterial embolism. Several embolic sources have been described, but thrombosis of an arteriovenous fistula as a paradoxical emboligenic source has not, to the best of our knowledge, been reported.</p> <p>Case presentation</p> <p>A 50-year-old Caucasian woman received a renal graft for primary hyperoxaluria. After transplantation, she was maintained on daily hemodialysis. Thrombosis of her arteriovenous fistula occurred two weeks post-transplantation and was treated by thromboaspiration, which was partially successful. During a hemodialysis session immediately following thromboaspiration, she developed a coma with tetraplegia requiring intensive cardiorespiratory resuscitation. Brain magnetic resonance imaging revealed various hyperdense areas in the vertebrobasilar territory resulting from bilateral occlusion of posterior cerebral arteries. Transesophageal echocardiographic examination showed a patent foramen ovale, while pulse echography of the arteriovenous fistula revealed the persistence of extensive clots that were probably the embolic source. A paradoxical embolus through a patent foramen ovale was suggested because of the proximity of the neurological event to the thrombectomy procedure.</p> <p>Conclusions</p> <p>The risk of paradoxical embolism in a hemodialyzed patient with a patent foramen ovale deserves consideration and requires careful evaluation in situations of arteriovenous fistula thrombosis.</p

Wavelet Cycle Spinning Denoising of NDE Ultrasonic Signals Using a Random Selection of Shifts

Wavelets are a powerful tool for signal and image denoising. Most of the denoising applications in different fields were based on the thresholding of the discrete wavelet transform (DWT) coefficients. Nevertheless, DWT transform is not a time or shift invariant transform and results depend on the selected shift. Improvements on the denoising performance can be obtained using the stationary wavelet transform (SWT) (also called shift-invariant or undecimated wavelet transform). Denoising using SWT has previously shown a robust and usually better performance than denoising using DWT but with a higher computational cost. In this paper, wavelet shrinkage schemes are applied for reducing noise in synthetic and experimental non-destructive evaluation ultrasonic A-scans, using DWT and a cycle-spinning implementation of SWT. A new denoising procedure, which we call random partial cycle spinning (RPCS), is presented. It is based on a cycle-spinning over a limited number of shifts that are selected in a random way. Wavelet denoising based on DWT, SWT and RPCS have been applied to the same sets of ultrasonic A-scans and their performances in terms of SNR are compared. In all cases three well known threshold selection rules (Universal, Minimax and Sure), with decomposition level dependent selection, have been used. It is shown that the new procedure provides a good robust denoising performance, without the DWT fluctuating performance, and close to SWT but with a much lower computational cost.This work was partially supported by Spanish MCI Project DPI2011-22438San Emeterio Prieto, JL.; Rodríguez-Hernández, MA. (2015). Wavelet Cycle Spinning Denoising of NDE Ultrasonic Signals Using a Random Selection of Shifts. 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NDT & E Int. 35, 567–572 (2002)Pardo, E., San Emeterio, J.L.: Noise reduction in ultrasonic NDT using undecimated wavelet transforms. Ultrasonics 44, e1063–e1067 (2006)Kechida, A., Drai, R., Guessoum, A.: Texture analysis for flaw detection in ultrasonic images. J. Nondestruct. Eval. 31, 108–116 (2012). doi: 10.1007/s10921-011-0126-4Rucka, M., Wilde, K.: Experimental study on ultrasonic monitoring of splitting failure in reinforced concrete. J. Nondestruct. Eval. 32, 372–383 (2013). doi: 10.1007/s10921-013-0191-yHosseini, S.M.H., Duczek, S., Gabbert, U.: Damage localization in plates using mode conversion characteristics of ultrasonic guided waves. J. Nondestruct. Eval. 33, 152–165 (2014). doi: 10.1007/s10921-013-0211-yMohammed, M.S., Ki-Seong, K.: Shift-invariant wavelet packet for signal de-noising in ultrasonic testing. Insight 54, 366–370 (2012)San Emeterio, J.L., Rodriguez-Hernandez, M.A.: Wavelet denoising of ultrasonic A-scans by random partial cycle spinning. 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Non-compartment model to compartment model pharmacokinetics transformation meta-analysis – a multivariate nonlinear mixed model

Background To fulfill the model based drug development, the very first step is usually a model establishment from published literatures. Pharmacokinetics model is the central piece of model based drug development. This paper proposed an important approach to transform published non-compartment model pharmacokinetics (PK) parameters into compartment model PK parameters. This meta-analysis was performed with a multivariate nonlinear mixed model. A conditional first-order linearization approach was developed for statistical estimation and inference. Results Using MDZ as an example, we showed that this approach successfully transformed 6 non-compartment model PK parameters from 10 publications into 5 compartment model PK parameters. In simulation studies, we showed that this multivariate nonlinear mixed model had little relative bias (<1%) in estimating compartment model PK parameters if all non-compartment PK parameters were reported in every study. If there missing non-compartment PK parameters existed in some published literatures, the relative bias of compartment model PK parameter was still small (<3%). The 95% coverage probabilities of these PK parameter estimates were above 85%. Conclusions This non-compartment model PK parameter transformation into compartment model meta-analysis approach possesses valid statistical inference. It can be routinely used for model based drug development

Validation of Results from Knowledge Discovery: Mass Density as a Predictor of Breast Cancer

The purpose of our study is to identify and quantify the association between high breast mass density and breast malignancy using inductive logic programming (ILP) and conditional probabilities, and validate this association in an independent dataset. We ran our ILP algorithm on 62,219 mammographic abnormalities. We set the Aleph ILP system to generate 10,000 rules per malignant finding with a recall >5% and precision >25%. Aleph reported the best rule for each malignant finding. A total of 80 unique rules were learned. A radiologist reviewed all rules and identified potentially interesting rules. High breast mass density appeared in 24% of the learned rules. We confirmed each interesting rule by calculating the probability of malignancy given each mammographic descriptor. High mass density was the fifth highest ranked predictor. To validate the association between mass density and malignancy in an independent dataset, we collected data from 180 consecutive breast biopsies performed between 2005 and 2007. We created a logistic model with benign or malignant outcome as the dependent variable while controlling for potentially confounding factors. We calculated odds ratios based on dichomotized variables. In our logistic regression model, the independent predictors high breast mass density (OR 6.6, CI 2.5–17.6), irregular mass shape (OR 10.0, CI 3.4–29.5), spiculated mass margin (OR 20.4, CI 1.9–222.8), and subject age (β = 0.09, p < 0.0001) significantly predicted malignancy. Both ILP and conditional probabilities show that high breast mass density is an important adjunct predictor of malignancy, and this association is confirmed in an independent data set of prospectively collected mammographic findings

CdSe Ring- and Tribulus-Shaped Nanocrystals: Controlled Synthesis, Growth Mechanism, and Photoluminescence Properties

With air-stable and generic reagents, CdSe nanocrystals with tunable morphologies were prepared by controlling the temperature in the solution reaction route. Thereinto, the lower reaction temperature facilitates the anisotropic growth of crystals to obtain high-yield CdSe ring- and tribulus-shaped nanocrystals with many branches on their surfaces. The photoluminescence properties are sensitive to the nature of particle and its surface. The products synthesized at room temperature, whose surfaces have many branches, show higher blue shift and narrower emission linewidths (FWHM) of photoluminescence than that of samples prepared at higher temperature, whose surfaces have no branches. Microstructural studies revealed that the products formed through self-assembly of primary crystallites. Nanorings formed through the nonlinear attachment of primary crystallites, and the branches on the surfaces grew by linear attachment at room temperature. And the structure of tribulus-shaped nanoparticle was realized via two steps of aggregation, i.e., random and linear oriented aggregation. Along with the elevation of temperature, the branches on nanocrystal surfaces shortened gradually because of the weakened linear attachment

Oral diagnosis and treatment planning: Part 6. Preventive and treatment planning for periodontal disease

A high level of sustained personal plaque control is fundamental for successful treatment outcomes in patients with active periodontal disease and, hence, oral hygiene instructions are the cornerstone of periodontal treatment planning. Other risk factors for periodontal disease also should be identified and modified where possible. Many restorative dental treatments in particular require the establishment of healthy periodontal tissues for their clinical success. Failure by patients to control dental plaque because of inappropriate designs and materials for restorations and prostheses will result in the long-term failure of the restorations and the loss of supporting tissues. Periodontal treatment planning considerations are also very relevant to endodontic, orthodontic and osseointegrated dental implant conditions and proposed therapies.E. Corbet and R. Smale