Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR) for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy

Structural MRI Covariance Patterns Associated with Normal Aging and Neuropsychological Functioning

Structural magnetic resonance imaging (MRI) studies have shown dramatic age-associated changes in grey and white matter volume, but typically use univariate analyses that do not explicitly test the interrelationship among brain regions. The current study used a multivariate approach to identify covariance patterns of grey and white matter tissue density to distinguish older from younger adults. A second aim was to examine whether the expression of the age-associated covariance topographies is related to performance on cognitive tests affected by normal aging. Eighty-four young (mean age=24.0) and 29 older (mean age=73.1) participants were scanned with a 1.5T MRI machine and assessed with a cognitive battery. Images were spatially normalized and segmented to produce grey and white matter density maps. A multivariate technique, based on the subprofile scaling model, was used to capture sources of between- and within-group variation to produce a linear combination of principal components that represented a "pattern" or "network" that best discriminated between the two age groups. Univariate analyses were also conducted with statistical parametric maps. Grey and white matter covariance patterns were identified that reliably discriminated between the groups with greater than 0.90 sensitivity and specificity. The identified patterns were similar for the univariate and multivariate techniques, and involved widespread regions of the cortex and subcortex. Age and the expression of both patterns were significantly associated with performance on tests of attention, language, memory, and executive functioning. The results suggest that identifiable networks of grey and white matter regions systematically decline with age and that pattern expression is linked to age-related cognitive decline

SNS programming environment user's guide

The computing environment is briefly described for the Supercomputing Network Subsystem (SNS) of the Central Scientific Computing Complex of NASA Langley. The major SNS computers are a CRAY-2, a CRAY Y-MP, a CONVEX C-210, and a CONVEX C-220. The software is described that is common to all of these computers, including: the UNIX operating system, computer graphics, networking utilities, mass storage, and mathematical libraries. Also described is file management, validation, SNS configuration, documentation, and customer services

How to Block Cartel Formation and Price-Fixing

Abstract written by the AEI-Brookings Joint Center: Allowing foreign buyers of goods produced by international cartels to pursue civil antitrust damages in U.S. courts would better deter cartel formation and price-fixing than do sanctions currently imposed by global criminal and civil justice systems.Technology and Industry, Regulatory Reform, Other Topics

Plastron induced drag reduction and increased slip on a superhydrophobic sphere

On low contact angle hysteresis superhydrophobic surfaces, droplets of water roll easily. It is intuitively appealing, but less obvious, that when such material is immersed in water, the liquid will flow more easily across its surface. In recent experiments it has been demonstrated that superhydrophobic surfaces with the same high contact angle and low contact angle hysteresis may not, in fact, have the same drag reducing properties. A key performance parameter is whether the surface is able to retain a layer of air (i.e. a plastron) when fully immersed. In this report, we consider an analytical model of Stokes flow (i.e. low Reynolds number, Re, creeping flow) across a surface retaining a continuous layer of air. The system is based on a compound droplet model consisting of a solid sphere encased in a sheathing layer of air and is the extreme limit of a solid sphere with a superhydrophobic surface. We demonstrate that an optimum thickness of air exists at which the drag on this compound object is minimized and that the level of drag reduction can approach 20 to 30%. Physically, drag reduction is caused by the ability of the external flow to transfer momentum across the water-air interface generating an internal circulation of air within the plastron

The Influence of Physical Activity on Monocyte Phenotype on Circulating Platelet-Monocyte Complexes in Overweight/Obese Persons

Elevated platelet-monocyte complexes (PMC) promote atherosclerosis and are associated with cardiovascular disease. It is unknown whether consistent physical activity (PA) decreases circulating PMCs. Additionally, no one has determined the monocyte phenotype most associated with PMCs. Purposes: 1) to examine the influence of PA on PMCs and their association with inflammatory /prothrombotic markers such as C-reactive protein (CRP), L-selectin (LS), platelet factor 4 (PF4), von Willebrand Factor (vWF), and hemoglobin A1C (HbA1c) and 2) to determine the monocyte phenotype most likely to form PMCs. Methods: Thirty-one overweight/obese subjects (44±5yr, BMI 34.2±5 kg×m2) were divided into two groups: sedentary (SED, n=17) and physically active (PA, n=14) based on physical activity logs. SED participated in \u3c 1 h of formal exercise while PA participated in moderate-high intensity exercise at least 3 h per week. Flow cytometry was used to identify PMCs on the monocyte phenotypes: classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14+CD16++). Platelets were identified using the marker CD42a. Results: Percentage of circulating PMCs and median fluorescence intensity of CD42a (MedFI; marker of platelet density per monocyte) were not different between groups; however, monocyte phenotype significantly impacted PMC percentage and MedFI where the lower the CD16 expression, the greater the adhesion of platelets. Classical monocytes (CD16-) had the highest % of PMC, etc. (Fig 1). HbA1c was greater (p=0.031) and LS (p=0.019) was lower in SED compared to PA (Fig. 2). There were no significant associations between any blood marker and PMC percentage, but PF4 was correlated with percent of CD16 -(r= -0.482, p=0.031) and CD16+(r= 0.473, p=0.035) monocytes. Conclusions: The absence of a separation between groups in VO2max may partially explain the lack of a difference in PMCs between groups. Regarding our second aim, classical monocytes appear to be more involved in PMC formation than do CD16+ monocytes with CD16++ having the lowest percentage of cells with platelets adhered (PMC). This observation may be due to the shedding of adhesion molecules from platelets and monocytes during activation from classical (CD16-) to a more inflammatory state (ie. CD16+)

High resolution (3 Tesla) MRI-guided conformal brachytherapy for cervical cancer: consequences of different high-risk CTV sizes

Purpose: To evaluate conventional brachytherapy (BT) plans using dose-volume parameters and high resolution (3 Tesla) MRI datasets, and to quantify dosimetric benefits and limitations when MRI-guided, conformal BT (MRIG-CBT) plans are generated. Material and methods: Fifty-five clinical high-dose-rate BT plans from 14 cervical cancer patients were retrospectively studied. All conventional plans were created using MRI with titanium tandem-and-ovoid applicator (T&O) for delivery. For each conventional plan, a MRIG-CBT plan was retrospectively generated using hybrid inverse optimization. Three categories of high risk (HR)-CTV were considered based on volume: non-bulky (\u3c 20 cc), low-bulky (\u3e 20 cc and \u3c 40 cc) and bulky (≥ 40 cc). Dose-volume metrics of D90 of HR-CTV and D2cc and D0.1cc of rectum, bladder, and sigmoid colon were analyzed. Results: Tumor coverage (HR-CTV D90) of the conventional plans was considerably affected by the HR-CTV size. Sixteen percent of the plans covered HR-CTV D90 with the prescription dose within 5%. At least one OAR had D2cc values over the GEC-ESTRO recommended limits in 52.7% of the conventional plans. MRIG-CBT plans showed improved target coverage for HR-CTV D90 of 98 and 97% of the prescribed dose for non-bulky and low-bulky tumors, respectively. No MRIG-CBT plans surpassed the D2cc limits of any OAR. Only small improvements (D90 of 80%) were found for large targets (\u3e 40 cc) when using T&O applicator approach. Conclusions: MRIG-CBT plans displayed considerable improvement for tumor coverage and OAR sparing over conventional treatment. When the HR-CTV volume exceeded 40 cc, its improvements were diminished when using a conventional intracavitary applicator

Hypertension in infancy: diagnosis, management and outcome

Abstract Advances in the ability to identify, evaluate, and care for infants with hypertension, coupled with advances in the practice of Neonatology, have led to an increased awareness of hypertension in modern neonatal intensive care units. This review will present updated data on blood pressure values in neonates, with a focus on the changes that occur over the first days and weeks of life in both term and preterm infants. Optimal blood pressure measurement techniques as well as the differential diagnosis of hypertension in the neonate and older infants will be discussed. Recommendations for the optimal immediate and long-term evaluation and treatment, including potential treatment parameters, will be presented. We will also review additional information on outcome that has become available over the past decade