Clinical and molecular characterization of HER2 amplified-pancreatic cancer

<p>Background: Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.</p> <p>Methods: HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).</p> <p>Results: An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.</p> <p>Conclusions: HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.</p&gt

Lifestyle modification in the prevention and treatment of atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia worldwide and has a significant impact on morbidity and mortality. Additionally, the incidence and prevalence of AF is expected to increase in the United States and worldwide over the next few decades. While the pathophysiology concerning the development of AF is not completely understood, multiple modifiable, as well as non-modifiable risk factors, for AF development have been discovered. The goal of this paper is to provide an overview of the modifiable risk factors that contribute to the development and recurrence of AF, in addition to discussing potential lifestyle changes that may aid in the prevention and treatment of AF

Cellular Imaging Of The Tapetal-like Reflex In Carriers Of RPGR-associated Retinopathy

PURPOSE: To examine the features of the tapetal-like reflex (TLR) in female carriers of RPGR-associated retinopathy by means of adaptive optics scanning light ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography. METHODS: Nine molecularly confirmed RPGR carriers and three healthy controls underwent ocular examination and the following retinal imaging modalities: color photography, near-infrared reflectance, fundus autofluorescence, spectral domain optical coherence tomography, and AOSLO. After identifying TLR areas across all imaging modalities, normalized local contrast of outer retinal bands on spectral domain optical coherence tomography was calculated and AOSLO-acquired photoreceptor mosaic analysis was performed. RESULTS: Seven carriers had TLR areas, which colocalized with increased rod photoreceptor reflectivity on confocal AOSLO and reduced cone photoreceptor densities. Parafoveal TLR areas also exhibited reduced local contrast (i.e., increased reflectivity) of the outer retinal bands on spectral domain optical coherence tomography (inner segment ellipsoid zone and outer segment interdigitation zone). Healthy controls did not show TLR. CONCLUSION: The cellular resolution provided by AOSLO affords the characterization of the photoreceptor mosaic in RPGR carriers with a TLR. Features revealed include reduced cone densities, increased cone inner segment diameters, and increased rod outer segment reflectivity

Rainwater Harvesting and Its Impact on Farming Systems

Landless, small holders and other poors supplement their livelihood and adapt to climate change by grazing, stall feeding with crop residues and fodder cultivated under rainfed and irrigated conditions. Improving productivity by conserving rainfall, ground water recharging, harvesting and recycling of rainwater especially in degraded open access or shared land with community participation was quite successful over a wide range of precipitation and ecological situations. Various types of trenches, bunding, vegetative barriers, gully plugs, ponds, check dams, land slides and mine spoils stabilization etc. retained more soil moisture, seeds, vegetative propagules etc. in situ and prevented soil erosion. It regenerated and enhanced biomass production of grasses, other forages, crop residues and environmental externalities. It reduced socially undesirable seasonal migration of herders by 35-100%, number of goats, dependency on open or common access resources and increased bovine population, stall feeding and milk productivity. Limited irrigation with harvested and recharged rainwater led to farm diversification, more availability of crop residues and better income. Climate change has reduced number of rainy days, increased intensity and frequency of run off producing events and can be converted into still better opportunities of adaptation by rain water harvesting

Mapping Children's Discussions of Evidence in Science to Assess Collaboration and Argumentation

The research reported in this paper concerns the development of children's skills of interpreting and evaluating evidence in science. Previous studies have shown that school teaching often places limited emphasis on the development of these skills, which are necessary for children to engage in scientific debate and decision-making. The research, undertaken in the UK, involved four collaborative decision-making activities to stimulate group discussion, each was carried out with five groups of four children (10-11 years old). The research shows how the children evaluated evidence for possible choices and judged whether their evidence was sufficient to support a particular conclusion or the rejection of alternative conclusions. A mapping technique was developed to analyse the discussions and identify different "levels" of argumentation. The authors conclude that suitable collaborative activities that focus on the discussion of evidence can be developed to exercise children's ability to argue effectively in making decisions

Il monastero benedettino di S. Giorgio in Braida a Verona: nuove prospettive di ricerca sulla rifabbrica romanica (sec. XII)

L’attuale aspetto rinascimentale della chiesa di San Giorgio in Braida è frutto di una serie di interventi promossi dai canonici veneziani di San Giorgio in Alga a partire dalla fine del XV secolo. Il monastero benedettino, tuttavia, fu fondato nella metà dell’XI secolo e completamente ricostruito fra il terzo e il quarto decennio del secolo successivo per volere del vescovo Bernardo. L’articolo ripercorre le vicende storiche dell’istituzione in età medievale e rende nota l’esistenza di alcune parti della compagine romanica tuttora inedite, che permettono d’inserire il cantiere di San Giorgio in Braida nel contesto delle coeve manifestazioni architettoniche veronesi

Vicious walkers, friendly walkers and Young tableaux II: With a wall

We derive new results for the number of star and watermelon configurations of vicious walkers in the presence of an impenetrable wall by showing that these follow from standard results in the theory of Young tableaux, and combinatorial descriptions of symmetric functions. For the problem of $n$-friendly walkers, we derive exact asymptotics for the number of stars and watermelons both in the absence of a wall and in the presence of a wall.Comment: 35 pages, AmS-LaTeX; Definitions of n-friendly walkers clarified; the statement of Theorem 4 and its proof were correcte

Vacuum/Compression Valving (VCV) Using Parrafin-Wax on a Centrifugal Microfluidic CD Platform

This paper introduces novel vacuum/compression valves (VCVs) utilizing paraffin wax. A VCV is implemented by sealing the venting channel/hole with wax plugs (for normally-closed valve), or to be sealed by wax (for normally-open valve), and is activated by localized heating on the CD surface. We demonstrate that the VCV provides the advantages of avoiding unnecessary heating of the sample/reagents in the diagnostic process, allowing for vacuum sealing of the CD, and clear separation of the paraffin wax from the sample/reagents in the microfluidic process. As a proof of concept, the microfluidic processes of liquid flow switching and liquid metering is demonstrated with the VCV. Results show that the VCV lowers the required spinning frequency to perform the microfluidic processes with high accuracy and ease of control.open5