Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG)

BACKGROUND: We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified. PATIENTS AND METHODS: We evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time. RESULTS: Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%). CONCLUSION: Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.

Effect of echo time pair selection on quantitative analysis for adrenal tumor characterization with in-phase and opposed-phase MR imaging: initial experience

PURPOSE: To determine the effect of two pairs of echo times (TEs) for in-phase (IP) and opposed-phase (OP) 3.0-T magnetic resonance (MR) imaging on (a) quantitative analysis prospectively in a phantom study and (b) diagnostic accuracy retrospectively in a clinical study of adrenal tumors, with use of various reference standards in the clinical study. MATERIALS AND METHODS: A fat-saline phantom was used to perform IP and OP 3.0-T MR imaging for various fat fractions. The institutional review board approved this HIPAA-compliant study, with waiver of informed consent. Single-breath-hold IP and OP 3.0-T MR images in 21 patients (14 women, seven men; mean age, 63 years) with 23 adrenal tumors (16 adenomas, six metastases, one adrenocortical carcinoma) were reviewed. The MR protocol involved two acquisition schemes: In scheme A, the first OP echo (approximately 1.5-msec TE) and the second IP echo (approximately 4.9-msec TE) were acquired. In scheme B, the first IP echo (approximately 2.4-msec TE) and the third OP echo (approximately 5.8-msec TE) were acquired. Quantitative analysis was performed, and analysis of variance was used to test for differences between adenomas and nonadenomas. RESULTS: In the phantom study, scheme B did not enable discrimination among voxels that had small amounts of fat. In the clinical study, no overlap in signal intensity (SI) index values between adenomas and nonadenomas was seen (P < .05) with scheme A. However, with scheme B, no overlap in the adrenal gland SI-to-liver SI ratio between adenomas and nonadenomas was seen (P < .05). With scheme B, no overlap in adrenal gland SI index-to-liver SI index ratio between adenomas and nonadenomas was seen (P < .05). CONCLUSION: This initial experience indicates SI index is the most reliable parameter for characterization of adrenal tumors with 3.0-T MR imaging when obtaining OP echo before IP echo. When acquiring IP echo before OP echo, however, nonadenomas can be mistaken as adenomas with use of the SI index value.

Effect of high order interpolation in the stability and efficiency of the time-integration process in vorticity-velocity CFD algorithms

The numerical solution of the incompressible Navier-Stokes Equations offers an effective alternative to the experimental analysis of Fluid-Structure interaction i.e. dynamical coupling between a fluid and a solid which otherwise is very complex, time consuming and very expensive. To have a method which can accurately model these types of mechanical systems by numerical solutions becomes a great option, since these advantages are even more obvious when considering huge structures like bridges, high rise buildings, or even wind turbine blades with diameters as large as 200 meters. The modeling of such processes, however, involves complex multiphysics problems along with complex geometries. This thesis focuses on a novel vorticity-velocity formulation called the KLE to solve the incompressible Navier-stokes equations for such FSI problems. This scheme allows for the implementation of robust adaptive ODE time integration schemes and thus allows us to tackle the various multiphysics problems as separate modules. The current algorithm for KLE employs a structured or unstructured mesh for spatial discretization and it allows the use of a self-adaptive or fixed time step ODE solver while dealing with unsteady problems. This research deals with the analysis of the effects of the Courant-Friedrichs-Lewy (CFL) condition for KLE when applied to unsteady Stoke’s problem. The objective is to conduct a numerical analysis for stability and, hence, for convergence. Our results confirmthat the time step ∆t is constrained by the CFL-like condition ∆t ≤ const. hα, where h denotes the variable that represents spatial discretization.

The Geology of Lost Creek Canyon with Special Reference to Igneous Activity

This investigation was undertaken primarily as a problem in geologic mapping, coupled with a study of stratigraphy, glaciation, igneous phenomena, and structure. The area is admirably suited to a study of geology and geologic events. Because it is small in extent, the area was studied in some detail during the time which was devoted to field work. The record of igneous activity of past geological ages is re­markably well exposed, since Lost Creek Canyon was carved through the roof of a stock or batholith by the glaciers of the Pleistocene epoch.

The Implementation of Full-time Schools: The Situation in the Federal State of Sao Paulo (Brazil)

During the past years, Brazil has been mentioned internationally as a one of the so-called BRICs (Brazil, Russia, India and China). These countries have been taking increasing space in the economical and political global scenarios in the XXI century. The facts that they possess a vast territory and stand among the highest populated countries increase their relevance within the United Nations. Besides, three of them constitute nuclear powers and two of them belong to the United Nations Security Council. Brazil has significantly participated in forums such as WTO and UNO, representing central political articulation and stability to Latin America and in the structuring and growth of MERCOSUL (Brazil, Argentina, Uruguay, Paraguay and Venezuela). Once again among the ten greatest economies of the world, the country has launched ambitious poverty-fighting programs helping more than 20 million people in the last years, such as the “Bolsa Família” (Familienstipendium) Program or and its complements). Nevertheless, Latin American countries are far from generating structural funds as the “European Social Fund” to assist specific demands of big cities as Sao Paulo and Buenos Aires. The commitments are restricted to commercial areas and bring nothing but slow and scarce advances to education or infra-structure and to the integration of systems related to these areas.

Spanish Supreme Court Rules in Favour of Google Search Engine... and a Flexible Reading of Copyright Statutes?

On 3 April 2012, the Spanish Supreme Court issued a major ruling in favour of the Google search engine, including its ‘cache copy’ service: Sentencia n.172/2012, of 3 April 2012, Supreme Court, Civil Chamber.* The importance of this ruling lies not so much in the circumstances of the case (the Supreme Court was clearly disgusted by the claimant’s ‘maximalist’ petitum to shut down the whole operation of the search engine), but rather on the court going beyond the text of the Copyright Act into the general principles of the law and case law, and especially on the reading of the three-step test (in Art. 40bis TRLPI) in a positive sense so as to include all these principles. After accepting that none of the limitations listed in the Spanish Copyright statute (TRLPI) exempted the unauthorized use of fragments of the contents of a personal website through the Google search engine and cache copy service, the Supreme Court concluded against infringement, based on the grounds that the three-step test (in Art. 40bis TRLPI) is to be read not only in a negative manner but also in a positive sense so as to take into account that intellectual property – as any other kind of property – is limited in nature and must endure any ius usus inocui (harmless uses by third parties) and must abide to the general principles of the law, such as good faith and prohibition of an abusive exercise of rights (Art. 7 Spanish Civil Code).The ruling is a major success in favour of a flexible interpretation and application of the copyright statutes, especially in the scenarios raised by new technologies and market agents, and in favour of using the three-step test as a key tool to allow for it.

Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner

BACKGROUND & AIMS Development of strictures is a major concern for patients with eosinophilic esophagitis (EoE). At diagnosis, EoE can present with an inflammatory phenotype (characterized by whitish exudates, furrows, and edema), a stricturing phenotype (characterized by rings and stenosis), or a combination of these. Little is known about progression of stricture formation; we evaluated stricture development over time in the absence of treatment and investigated risk factors for stricture formation. METHODS We performed a retrospective study using the Swiss EoE Database, collecting data on 200 patients with symptomatic EoE (153 men; mean age at diagnosis, 39 ± 15 years old). Stricture severity was graded based on the degree of difficulty associated with passing of the standard adult endoscope. RESULTS The median delay in diagnosis of EoE was 6 years (interquartile range, 2-12 years). With increasing duration of delay in diagnosis, the prevalence of fibrotic features of EoE, based on endoscopy, increased from 46.5% (diagnostic delay, 0-2 years) to 87.5% (diagnostic delay, >20 years; P = .020). Similarly, the prevalence of esophageal strictures increased with duration of diagnostic delay, from 17.2% (diagnostic delay, 0-2 years) to 70.8% (diagnostic delay, >20 years; P < .001). Diagnostic delay was the only risk factor for strictures at the time of EoE diagnosis (odds ratio = 1.08; 95% confidence interval: 1.040-1.122; P < .001). CONCLUSIONS The prevalence of esophageal strictures correlates with the duration of untreated disease. These findings indicate the need to minimize delay in diagnosis of EoE.

Application of real-time fluorescent PCR for quantitative assessment of Neospora caninum infections in organotypic slice cultures of rat central nervous system tissue

The previously described Nc5-specific PCR test for the diagnosis of Neospora caninum infections was used to develop a quantitative PCR assay which allows the determination of infection intensities within different experimental and diagnostic sample groups. The quantitative PCR was performed by using a dual fluorescent hybridization probe system and the LightCycler Instrument for online detection of amplified DNA. This assay was successfully applied for demonstrating the parasite proliferation kinetics in organotypic slice cultures of rat brain which were infected in vitro with N. caninum tachyzoites. This PCR-based method of parasite quantitation with organotypic brain tissue samples can be regarded as a novel ex vivo approach for exploring different aspects of cerebral N. caninum infection.

Simultaneous detection and discrimination of virulent and benign Dichelobacter nodosus in sheep of flocks affected by foot rot and in clinically healthy flocks by competitive real-time PCR.

Ovine foot rot caused by Dichelobacter nodosus is affecting sheep worldwide. The current diagnostic methods are difficult and cumbersome. Here, we present a competitive real-time PCR based on allelic discrimination of the protease genes aprV2 and aprB2. This method allows direct detection and differentiation of virulent and benign D. nodosus from interdigital skin swabs in a single test. Clinically affected sheep harbored high loads of only virulent strains, whereas healthy sheep had lower loads of predominantly benign strains.

Outcome study of real-time MR-guided cervical periradicular injection therapy in an open 1.0 Tesla MRI system

PURPOSE To evaluate the accuracy, safety, and efficacy of cervical nerve root injection therapy using magnetic resonance guidance in an open 1.0 T MRI system. METHODS Between September 2009 and April 2012, a total of 21 patients (9 men, 12 women; mean age 47.1 ± 11.1 years) underwent MR-guided cervical periradicular injection for cervical radicular pain in an open 1.0 T system. An interactive proton density-weighted turbo spin echo (PDw TSE) sequence was used for real-time guidance of the MR-compatible 20-gauge injection needle. Clinical outcome was evaluated on a verbal numeric rating scale (VNRS) before injection therapy (baseline) and at 1 week and 1, 3, and 6 months during follow-up. RESULTS All procedures were technically successful and there were no major complications. The mean preinterventional VNRS score was 7.42 and exhibited a statistically significant decrease (P < 0.001) at all follow-up time points: 3.86 ± 1.53 at 1 week, 3.21 ± 2.19 at 1 month, 2.58 ± 2.54 at 3 months, and 2.76 ± 2.63 at 6 months. At 6 months, 14.3 % of the patients reported complete resolution of radicular pain and 38.1 % each had either significant (4-8 VNRS score points) or mild (1-3 VNRS score points) relief of pain; 9.5 % experienced no pain relief. CONCLUSION Magnetic resonance fluoroscopy-guided periradicular cervical spine injection is an accurate, safe, and efficacious treatment option for patients with cervical radicular pain. The technique may be a promising alternative to fluoroscopy- or CT-guided injections of the cervical spine, especially in young patients and in patients requiring repeat injections.

A New Approach for Automatic Removal of Movement Artifacts in Near-Infrared Spectroscopy Time Series by Means of Acceleration Data

Abstract: Near-infrared spectroscopy (NIRS) enables the non-invasive measurement of changes in hemodynamics and oxygenation in tissue. Changes in light-coupling due to movement of the subject can cause movement artifacts (MAs) in the recorded signals. Several methods have been developed so far that facilitate the detection and reduction of MAs in the data. However, due to fixed parameter values (e.g., global threshold) none of these methods are perfectly suitable for long-term (i.e., hours) recordings or were not time-effective when applied to large datasets. We aimed to overcome these limitations by automation, i.e., data adaptive thresholding specifically designed for long-term measurements, and by introducing a stable long-term signal reconstruction. Our new technique (“acceleration-based movement artifact reduction algorithm”, AMARA) is based on combining two methods: the “movement artifact reduction algorithm” (MARA, Scholkmann et al. Phys. Meas. 2010, 31, 649–662), and the “accelerometer-based motion artifact removal” (ABAMAR, Virtanen et al. J. Biomed. Opt. 2011, 16, 087005). We describe AMARA in detail and report about successful validation of the algorithm using empirical NIRS data, measured over the prefrontal cortex in adolescents during sleep. In addition, we compared the performance of AMARA to that of MARA and ABAMAR based on validation data.