HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology

-ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the as

HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma

CONTEXT: ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA. OBJECTIVES: To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making. DESIGN: The College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology convened an expert panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA. RESULTS: The panel is proposing 11 recommendations with strong agreement from the open-comment participants. RECOMMENDATIONS: The panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and a HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance. CONCLUSIONS: This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results

Estimation of shrub biomass by airborne LiDAR data in small forest stands

The presence of shrub vegetation is very significant in Mediterranean ecosystems. However, the difficulty involved in shrub management and the lack of information about behavior of this vegetation means that these areas are often left out of spatial planning projects. Airborne LiDAR (Light Detection And Ranging) has been used successfully in forestry to estimate dendrometric and dasometric variables that allow to characterize forest structure. In contrast, little research has focused on shrub vegetation. The objective of this study was to estimate dry biomass of shrub vegetation in 83 stands of radius 0.5 m using variables derived from LiDAR data. Dominant species was Quercus coccifera, one of the most characteristic species of the Mediterranean forests. Density of LiDAR data in the analyzed stands varied from 2 points/m(2) to 16 points/m(2), being the average 8 points/m(2) and the standard deviation 4.5 points/m(2). Under these conditions, predictions of biomass were performed calculating the mean height, the maximum height and the percentile values 80th, 90th, and 95th derived from LiDAR in concentric areas whose radius varied from 0.50 m to 3.5 m from the center of the stand. The maximum R(2) and the minimum RMSE for dry biomass estimations were obtained when the percentile 95th of LiDAR data was calculated in an area of radius 1.5 m, being 0.48 and 1.45 kg, respectively. For this radius, it was found that for the stands (n = 39) where the DTM is calculated with high accuracy (RMSE lower than 0.20 m) and with a high density of LiDAR data (more than 8 points/m(2)) the R(2) value was 0.73. These results show the possibility of estimating shrub biomass in small areas when the density of LiDAR data is high and errors associated to the DTM are low. These results would allow us to improve the knowledge about shrub behavior avoiding the cost of field measurements and clear cutting actions. (C) 2011 Elsevier B.V. All rights reserved.Estornell Cremades, J.; Ruiz Fernández, LÁ.; Velázquez Martí, B.; Fernández Sarriá, A. (2011). Estimation of shrub biomass by airborne LiDAR data in small forest stands. Forest Ecology and Management. 262(9):1697-1703. doi:10.1016/j.foreco.2011.07.026S16971703262

Effects of rapid urbanisation on the urban thermal environment between 1990 and 2011 in Dhaka Megacity, Bangladesh

This study investigates the influence of land-use/land-cover (LULC) change on land surface temperature (LST) in Dhaka Megacity, Bangladesh during a period of rapid urbanisation. LST was derived from Landsat 5 TM scenes captured in 1990, 2000 and 2011 and compared to contemporaneous LULC maps. We compared index-based and linear spectral mixture analysis (LSMA) techniques for modelling LST. LSMA derived biophysical parameters corresponded more strongly to LST than those produced using index-based parameters. Results indicated that vegetation and water surfaces had relatively stable LST but it increased by around 2 °C when these surfaces were converted to built-up areas with extensive impervious surfaces. Knowledge of the expected change in LST when one land-cover is converted to another can inform land planners of the potential impact of future changes and urges the development of better management strategies

Isolated Optic Perineuritis as the Presenting Sign of Sarcoidosis

A 35-year-old healthy African-American woman presented with a 4-month history of gradual loss of vision in the right eye from an optic neuropathy. MRI of the orbits with gadolinium showed isolated thickening and enhancement of the right optic nerve sheath. Chest x-ray and CT-scan of the chest were performed and showed bilateral hilar and mediastinal lymphadenopathy. This was suggestive of sarcoidosis, and the diagnosis was confirmed with histopathology. The patient promptly recovered vision with high-dose corticosteroids; the thickening of the optic nerve sheath also regressed. Isolated optic nerve sheath thickening from sarcoidosis is rare and may mimic compressive optic neuropathies such as optic nerve sheath meningiomas. A systemic evaluation for systemic inflammatory etiologies should be considered in such cases.kbdopticperineuriti

Non-local impact ionization in silicon devices

\u3cp\u3eIn small bipolar and MOS transistors, the electrons gain much less energy than according to the maximum electric field. This is due to nonlocal electron heating and the small width of the E-field peak. The simplified energy balance equation with the energy relaxation length lambda \u3csub\u3ee\u3c/sub\u3e as parameter gives the electron temperature for a given electric field distribution. From a series of MBE (molecular beam epitaxy)-grown bipolar transistors and scaled submicron MOS transistors, lambda \u3csub\u3ee\u3c/sub\u3e=650 AA was found. With the calculated temperature distribution and known empirical models for the impact ionization, avalanche (substrate) currents are accurately predicted. This procedure can easily be implemented, as postprocessing, in existing device simulators with hardly any extra computation time. It extends in a consistent way the validity range of these simulators to future device generations.\u3c/p\u3

Termination of CD40L co-stimulation promotes human B cell differentiation into antibody-secreting cells

Human naïve B cells are notoriously difficult to differentiate into antibody-secreting cells (ASCs) in vitro while maintaining sufficient cell numbers to evaluate the differentiation process. B cells require T follicular helper (TFH ) cell-derived signals like CD40L and IL-21 during germinal center (GC) responses to undergo differentiation into ASCs. Cognate interactions between B and TFH cells are transient; after TFH contact, B cells cycle between GC light and dark zones where TFH contact is present and absent, respectively. Here, we elucidated that the efficacy of naïve B cells in ACS differentiation is dramatically enhanced by the release of CD40L stimulation. Multiparameter phospho-flow and transcription factor (TF)-flow cytometry revealed that termination of CD40L stimulation downmodulates NF-κB and STAT3 signaling. Furthermore, the termination of CD40 signaling downmodulates C-MYC, while promoting ASC TFs BLIMP1 and XBP-1s. Reduced levels of C-MYC in the differentiating B cells are later associated with crucial downmodulation of the B cell signature TF PAX5 specifically upon the termination of CD40 signaling, resulting in the differentiation of BLIMP1 high expressing cells into ASCs. The data presented here are the first steps to provide further insights how the transient nature of CD40 signaling is in fact needed for efficient human naïve B cell differentiation to ASCs