Sirolimus-eluting stent treatment at high-volume centers confers lower mortality at 6-month follow-up: results from the prospective multicenter German Cypher Registry

BACKGROUND: Studies continue to identify percutaneous coronary intervention procedural volume both at the institutional level and at the operator level as being strongly correlated with outcome. High-volume centers have been defined as those that perform >400 percutaneous coronary intervention procedures per year. The relationship between drug-eluting stent procedural volume and outcome is unknown. We investigated this relationship in the German Cypher Registry. METHODS AND RESULTS: The present analysis included 8201 patients treated with sirolimus-eluting stents between April 2002 and September 2005 in 51 centers. Centers that recruited >400 sirolimus-eluting stent patients in this time period were considered high-volume centers; those with 150 to 400 patients were considered intermediate-volume centers; and those with <150 patients were designated as low-volume centers. The primary end point was all death, myocardial infarction, and target-vessel revascularization at 6 months. This end point occurred in 11.3%, 12.1%, and 9.0% of patients in the low-, intermediate-, and high-volume center groups, respectively (P=0.0001). There was no difference between groups in the rate of target-vessel revascularization (P=0.2) or cerebrovascular accidents (P=0.5). The difference in death/myocardial infarction remained significant after adjustment for baseline factors (odds ratio 1.85, 95% confidence interval 1.31 to 2.59, P<0.001 for low-volume centers; odds ratio 1.69, 95% confidence interval 1.29 to 2.21, P<0.001 for intermediate-volume centers). Patient and lesion selection, procedural features, and postprocedural medications differed significantly between groups. CONCLUSIONS: The volume of sirolimus-eluting stent procedures performed on an institutional level was inversely related to death and myocardial infarction but not to target-vessel revascularization at 6-month follow-up. Safety issues are better considered in high-volume centers. These findings have important public health policy implications.

The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up

BACKGROUND: The role of adjuvant dose-intensive chemotherapy and its efficacy according to baseline features has not yet been established. PATIENTS AND METHODS: Three hundred and forty-four patients were randomized to receive seven courses of standard-dose chemotherapy (SD-CT) or three cycles of dose-intensive epirubicin and cyclophosphamide (epirubicin 200 mg/m(2) plus cyclophosphamide 4 mg/m(2) with filgrastim and progenitor cell support). All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). This paper updates the results and explores patterns of recurrence according to predicting baseline features. RESULTS: At 8.3-years median follow-up, patients assigned DI-EC had a significantly better DFS compared with those assigned SD-CT [8-year DFS percent 47% and 37%, respectively, hazard ratio (HR) 0.76; 95% confidence interval 0.58-1.00; P = 0.05]. Only patients with estrogen receptor (ER)-positive disease benefited from the DI-EC (HR 0.61; 95% confidence interval 0.39, 0.95; P = 0.03). CONCLUSIONS: After prolonged follow-up, DI-EC significantly improved DFS, but the effect was observed only in patients with ER-positive disease, leading to the hypothesis that efficacy of DI-EC may relate to its endocrine effects. Further studies designed to confirm the importance of endocrine responsiveness in patients treated with dose-intensive chemotherapy are encouraged.

Algorithms For Automatic And Robust Registration Of 3D Head Scans

wo methods for registering laser-scans of human heads and transforming them to a new semantically consistent topology defined by a user-provided template mesh are described. Both algorithms are stated within the Iterative Closest Point framework. The first method is based on finding landmark correspondences by iteratively registering the vicinity of a landmark with a re-weighted error function. Thin-plate spline interpolation is then used to deform the template mesh and finally the scan is resampled in the topology of the deformed template. The second algorithm employs a morphable shape model, which can be computed from a database of laser-scans using the first algorithm. It directly optimizes pose and shape of the morphable model. The use of the algorithm with PCA mixture models, where the shape is split up into regions each described by an individual subspace, is addressed. Mixture models require either blending or regularization strategies, both of which are described in detail. For both algorithms, strategies for filling in missing geometry for incomplete laser-scans are described. While an interpolation-based approach can be used to fill in small or smooth regions, the model-driven algorithm is capable of fitting a plausible complete head mesh to arbitrarily small geometry, which is known as "shape completion". The importance of regularization in the case of extreme shape completion is shown.

Robust Denoising using Feature and Color Information

We propose a method that robustly combines color and feature buffers to denoise Monte Carlo renderings. On one hand, feature buffers, such as per pixel normals, textures, or depth, are effective in determining denoising filters because features are highly correlated with rendered images. Filters based solely on features, however, are prone to blurring image details that are not well represented by the features. On the other hand, color buffers represent all details, but they may be less effective to determine filters because they are contaminated by the noise that is supposed to be removed. We propose to obtain filters using a combination of color and feature buffers in an NL-means and cross-bilateral filtering framework. We determine a robust weighting of colors and features using a SURE-based error estimate. We show significant improvements in subjective and quantitative errors compared to the previous state-of-the-art. We also demonstrate adaptive sampling and space-time filtering for animations.

A Closed-Form, Consistent and Robust Solution to Uncalibrated Photometric Stereo Via Local Diffuse Reflectance Maxima

Images of an object under different illumination are known to provide strong cues about the object surface. A mathematical formalization of how to recover the normal map of such a surface leads to the so-called uncalibrated photometric stereo problem. In the simplest instance, this problem can be reduced to the task of identifying only three parameters: the so-called generalized bas-relief (GBR) ambiguity. The challenge is to find additional general assumptions about the object, that identify these parameters uniquely. Current approaches are not consistent, i.e., they provide different solutions when run multiple times on the same data. To address this limitation, we propose exploiting local diffuse reflectance (LDR) maxima, i.e., points in the scene where the normal vector is parallel to the illumination direction (see Fig. 1). We demonstrate several noteworthy properties of these maxima: a closed-form solution, computational efficiency and GBR consistency. An LDR maximum yields a simple closed-form solution corresponding to a semi-circle in the GBR parameters space (see Fig. 2); because as few as two diffuse maxima in different images identify a unique solution, the identification of the GBR parameters can be achieved very efficiently; finally, the algorithm is consistent as it always returns the same solution given the same data. Our algorithm is also remarkably robust: It can obtain an accurate estimate of the GBR parameters even with extremely high levels of outliers in the detected maxima (up to 80 % of the observations). The method is validated on real data and achieves state-of-the-art results.

Multi-scale micro-structure generation strategy for up-scaling transport in clays

Clays and claystones are used as backfill and barrier materials in the design of waste repositories, because they act as hydraulic barriers and retain contaminants. Transport through such barriers occurs mainly by molecular diffusion. There is thus an interest to relate the diffusion properties of clays to their structural properties. In previous work, we have developed a concept for up-scaling pore-scale molecular diffusion coefficients using a grid-based model for the sample pore structure. Here we present an operational algorithm which can generate such model pore structures of polymineral materials. The obtained pore maps match the rock’s mineralogical components and its macroscopic properties such as porosity, grain and pore size distributions. Representative ensembles of grains in 2D or 3D are created by a lattice Monte Carlo (MC) method, which minimizes the interfacial energy of grains starting from an initial grain distribution. Pores are generated at grain boundaries and/or within grains. The method is general and allows to generate anisotropic structures with grains of approximately predetermined shapes, or with mixtures of different grain types. A specific focus of this study was on the simulation of clay-like materials. The generated clay pore maps were then used to derive upscaled effective diffusion coefficients for non-sorbing tracers using a homogenization technique. The large number of generated maps allowed to check the relations between micro-structural features of clays and their effective transport parameters, as is required to explain and extrapolate experimental diffusion results. As examples, we present a set of 2D and 3D simulations and investigated the effects of nanopores within particles (interlayer pores) and micropores between particles. Archie’s simple power law is followed in systems with only micropores. When nanopores are present, additional parameters are required; the data reveal that effective diffusion coefficients could be described by a sum of two power functions, related to the micro- and nanoporosity. We further used the model to investigate the relationships between particle orientation and effective transport properties of the sample.

Improving follow-up of abnormal cancer screens using electronic health records: trust but verify test result communication.

BACKGROUND: Early detection of colorectal cancer through timely follow-up of positive Fecal Occult Blood Tests (FOBTs) remains a challenge. In our previous work, we found 40% of positive FOBT results eligible for colonoscopy had no documented response by a treating clinician at two weeks despite procedures for electronic result notification. We determined if technical and/or workflow-related aspects of automated communication in the electronic health record could lead to the lack of response. METHODS: Using both qualitative and quantitative methods, we evaluated positive FOBT communication in the electronic health record of a large, urban facility between May 2008 and March 2009. We identified the source of test result communication breakdown, and developed an intervention to fix the problem. Explicit medical record reviews measured timely follow-up (defined as response within 30 days of positive FOBT) pre- and post-intervention. RESULTS: Data from 11 interviews and tracking information from 490 FOBT alerts revealed that the software intended to alert primary care practitioners (PCPs) of positive FOBT results was not configured correctly and over a third of positive FOBTs were not transmitted to PCPs. Upon correction of the technical problem, lack of timely follow-up decreased immediately from 29.9% to 5.4% (p<0.01) and was sustained at month 4 following the intervention. CONCLUSION: Electronic communication of positive FOBT results should be monitored to avoid limiting colorectal cancer screening benefits. Robust quality assurance and oversight systems are needed to achieve this. Our methods may be useful for others seeking to improve follow-up of FOBTs in their systems.

A cardiovascular mathematical model of graded head-up tilt

A lumped parameter model of the cardiovascular system has been developed and optimized using experimental data obtained from 13 healthy subjects during graded head-up tilt (HUT) from the supine position to [Formula: see text]. The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, nonlinear pressure volume relationship of the lower body compartment, arterial and cardiopulmonary baroreceptors, as well as autoregulatory mechanisms. A number of important features, including the separate effects of arterial and cardiopulmonary baroreflexes, and autoregulation in the lower body, as well as diastolic ventricular interaction through the pericardium have been included and tested for their significance. Furthermore, the individual effect of parameter associated with heart failure, including LV and RV contractility, baseline systemic vascular resistance, pulmonary vascular resistance, total blood volume, LV diastolic stiffness and reflex gain on HUT response have also been investigated. Our fitted model compares favorably with our experimental measurements and published literature at a range of tilt angles, in terms of both global and regional hemodynamic variables. Compared to the normal condition, a simulated congestive heart failure condition produced a blunted response to HUT with regards to the percentage changes in cardiac output, stroke volume, end diastolic volume and effector response (i.e., heart contractility, venous unstressed volume, systemic vascular resistance and heart rate) with progressive tilting.

Effectiveness of integrated care including therapeutic assertive community treatment in severe schizophrenia spectrum and bipolar I disorders: the 24-month follow-up ACCESS II study

OBJECTIVE The ACCESS treatment model offers assertive community treatment embedded in an integrated care program to patients with psychoses. Compared to standard care and within a controlled study, it proved to be more effective in terms of service disengagement and illness outcomes in patients with schizophrenia spectrum disorders over 12 months. ACCESS was implemented into clinical routine and its effectiveness assessed over 24 months in severe schizophrenia spectrum disorders and bipolar I disorder with psychotic features (DSM-IV) in a cohort study. METHOD All 115 patients treated in ACCESS (from May 2007 to October 2009) were included in the ACCESS II study. The primary outcome was rate of service disengagement. Secondary outcomes were change of psychopathology, severity of illness, psychosocial functioning, quality of life, satisfaction with care, medication nonadherence, length of hospital stay, and rates of involuntary hospitalization. RESULTS Only 4 patients (3.4%) disengaged with the service. Another 11 (9.6%) left because they moved outside the catchment area. Patients received a mean of 1.6 outpatient contacts per week. Involuntary admissions decreased from 34.8% in the 2 previous years to 7.8% during ACCESS (P < .001). Mixed models repeated-measures analyses revealed significant improvements among all patients in psychopathology (effect size d = 0.64, P < .001), illness severity (d = 0.84, P = .03), functioning level (d = 0.65, P < .001), quality of life (d = 0.50, P < .001), and client satisfaction (d = 0.11, P < .001). At 24 months, 78.3% were fully adherent to medication, compared to 25.2% at baseline (P = .002). CONCLUSIONS ACCESS was successfully implemented in clinical routine and maintained excellent rates of service engagement and other outcomes in patients with schizophrenia spectrum disorders or bipolar I disorder with psychotic features over 24 months. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01888627.

Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology and treatment

Mast cells (MCs) are well known for their neoplastic transformation in solitary and multiple cutaneous mast cell tumours (MCTs), as well as visceral and systemic mastocytosis. Dogs have a unique risk of developing cutaneous MCTs, and they account for 7% to 21% of all canine skin tumours. The aetiology of canine MCTs is unknown but is probably multifactorial. This article reviews up-to-date knowledge on the pathogenesis, the clinical presentation, the clinical prognostic factors, the diagnostic workup including clinical staging, cytological findings, histological findings and the various grading systems which have been evaluated based on morphology, the assessment of proliferation markers and other factors such as vessel density. Furthermore, detailed information about current treatment protocols for canine cutaneous MCTs is provided.

There is more than "more is up": Hand and foot responses reverse the vertical association of number magnitudes

Recent research in cognitive sciences shows a growing interest in spatial-numerical associations. The horizontal SNARC (spatial-numerical association of response codes) effect is defined by faster left-sided responses to small numbers and faster right-sided responses to large numbers in a parity judgment task. In this study we investigated whether there is also a SNARC effect for upper and lower responses. The grounded cognition approach suggests that the universal experience of "more is up" serves as a robust frame of reference for vertical number representation. In line with this view, lower hand responses to small numbers were faster than to large numbers (Experiment 1). Interestingly, the vertical SNARC effect reversed when the lower responses were given by foot instead of the hand (Experiments 2, 3, and 4). We found faster upper (hand) responses to small numbers and faster lower (foot) responses to large numbers. Additional experiments showed that spatial factors cannot account for the reversal of the vertical SNARC effect (Experiments 4 and 5). Our results question the view of "more is up" as a robust frame of reference for spatial-numerical associations. We discuss our results within a hierarchical framework of numerical cognition and point to a possible link between effectors and number representation.

Abacavir induced T cell reactivity from drug naïve individuals shares features of allo-immune responses.

Abacavir hypersensitivity is a severe hypersensitivity reaction which occurs exclusively in carriers of the HLA-B*57∶01 allele. In vitro culture of PBMC with abacavir results in the outgrowth of abacavir-reacting CD8+ T cells, which release IFNγ and are cytotoxic. How this immune response is induced and what is recognized by these T cells is still a matter of debate. We analyzed the conditions required to develop an abacavir-dependent T cell response in vitro. The abacavir reactivity was independent of co-stimulatory signals, as neither DC maturation nor release of inflammatory cytokines were observed upon abacavir exposure. Abacavir induced T cells arose in the absence of professional APC and stemmed from naïve and memory compartments. These features are reminiscent of allo-reactivity. Screening for allo-reactivity revealed that about 5% of generated T cell clones (n = 136) from three donors were allo-reactive exclusively to the related HLA-B*58∶01. The addition of peptides which can bind to the HLA-B*57∶01-abacavir complex and to HLA-B*58∶01 during the induction phase increased the proportion of HLA-B*58∶01 allo-reactive T cell clones from 5% to 42%. In conclusion, abacavir can alter the HLA-B*57∶01-peptide complex in a way that mimics an allo-allele ('altered self-allele') and create the potential for robust T cell responses.

The Challenge of Prenatal Diagnostic Work-Up of Maternally Inherited X-Linked Opitz G/BBB: Case Report and Literature Review

Background. Prenatal diagnosis of Optiz G/BBB syndrome (OS) is challenging because the characteristic clinical features, such as facial and genitourinary anomalies, may be subtle at sonography and rather unspecific. Furthermore, molecular testing of the disease gene is not routinely performed, unless a specific diagnosis is suggested. Method. Both familial and ultrasound data were used to achieve the diagnosis of X-linked OS (XLOS), which was confirmed by molecular testing of MID1 gene (Xp22.3) at birth. Results. Sequencing of MID1 gene disclosed the nucleotide change c.1285 +1 G>T, previously associated with XLOS. Conclusions. This case illustrates current challenges of the prenatal diagnostic work-up of XLOS and exemplifies how clinical investigation, including family history, and accurate US foetal investigations can lead to the correct diagnosis.

Lagrangian back-tracing results for Kohnen station; output of time dependent numerical experiment with a 3D nested Antarctic ice sheet model

A nested ice flow model was developed for eastern Dronning Maud Land to assist with the dating and interpretation of the EDML deep ice core. The model consists of a high-resolution higher-order ice dynamic flow model that was nested into a comprehensive 3-D thermomechanical model of the whole Antarctic ice sheet. As the drill site is on a flank position the calculations specifically take into account the effects of horizontal advection as deeper ice in the core originated from higher inland. First the regional velocity field and ice sheet geometry is obtained from a forward experiment over the last 8 glacial cycles. The result is subsequently employed in a Lagrangian backtracing algorithm to provide particle paths back to their time and place of deposition. The procedure directly yields the depth-age distribution, surface conditions at particle origin, and a suite of relevant parameters such as initial annual layer thickness. This paper discusses the method and the main results of the experiment, including the ice core chronology, the non-climatic corrections needed to extract the climatic part of the signal, and the thinning function. The focus is on the upper 89% of the ice core (appr. 170 kyears) as the dating below that is increasingly less robust owing to the unknown value of the geothermal heat flux. It is found that the temperature biases resulting from variations of surface elevation are up to half of the magnitude of the climatic changes themselves.

Isotopic-geochemical features of spontaneous gases from mud volcanoes in Eastern Georgia

Isotopic-geochemical study revealed presence of mantle He (3He/4He up to 223x10**-8) in gases from mud volcanoes of Eastern Georgia. This fact confirms that the Middle Kura basin fill encloses an intrusive body previously distinguished from geophysical data. Wide variations of carbon isotopic composition d13C in CH4 and CO2 and chemical composition of gas and water at temporally constant 3He/4He ratio indicate their relation with crustal processes. Unusual direct correlations of 3He/4He ratio with concentrations of He and CH4 and 40Ar/36Ar ratio can be explained by generation of gas in the Cenozoic sequence of the Middle Kura basin.