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

Hope, optimism, and other business assets: Why “psychological capital” is so valuable to your company

Entrevista com Fred Luthans,1 coauthor of Psychological Capital: Developing the Human Competitive EdgeInterview with Fred Luthans,1 coauthor of Psychological Capital: Developing the Human Competitive Edg

The Void Abundance with Non-Gaussian Primordial Perturbations

We use a Press-Schechter-like calculation to study how the abundance of voids changes in models with non-Gaussian initial conditions. While a positive skewness increases the cluster abundance, a negative skewness does the same for the void abundance. We determine the dependence of the void abundance on the non-Gaussianity parameter fnl for the local-model bispectrum-which approximates the bispectrum in some multi-field inflation models-and for the equilateral bispectrum, which approximates the bispectrum in e.g. string-inspired DBI models of inflation. We show that the void abundance in large-scale-structure surveys currently being considered should probe values as small as fnl < 10 and fnl^eq < 30, over distance scales ~10 Mpc.Comment: Submitted to JCA

A dynamical model of lipoprotein metabolism

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Social roles and aging from a life-span perspective

Este trabalho investigou os papéis sociais e as tarefas evolutivas desempenhados por adultos. O local escolhido para investigação foi um assentamento de famílias de baixa renda do Distrito Federal criado em 1989. Utilizou-se um questionário contendo 17 questões abertas e 15 questões fechadas, preenchido pela primeira autora durante uma visita domiciliar. Participaram 98 respondentes (73 F e 25 M), sendo 51 entre 50 e 59 anos e 47 a partir de 60 anos. Os resultados apontaram que este grupo é heterogêneo e que seus papéis sociais são influenciados pelas variáveis demográficas (idade, sexo, escolaridade, ocupação, naturalidade e estado civil) e também pelas variáveis relativas à moradia atual. Concluiu-se também que as expectativas sociais, o suporte social e a escolarização são fatores de suma importância para oferecer recursos para a otimização e compensação necessárias a um envelhecimento bem sucedido. __________________________________________________________________________________________________________ ABSTRACTThis study investigated the social roles and developmental tasks of adults. The study took place in a settlement of low-income families, created in The Federal District in 1989. Data were collected through a questionnaire composed of 17 open and 15 closed questions, administered by the first author during a home visit. There were 98 respondents, 73 female and 25 male, being 51 between 50 to 59 years old and 47 elders above the age of 60. The result indicated that this group is heterogeneous and that its social roles are influenced by the demographic variables - age, sex, educational level, work, place of the birth and marital status, as well for the relative variables to current residence. The data allow the conclusion that social expectations, social support and the educational level are important resources for the optimization and necessary compensation to successful aging

Evolution of white matter damage in amyotrophic lateral sclerosis

Objective To characterize disease evolution in amyotrophic lateral sclerosis using an event‐based model designed to extract temporal information from cross‐sectional data. Conventional methods for understanding mechanisms of rapidly progressive neurodegenerative disorders are limited by the subjectivity inherent in the selection of a limited range of measurements, and the need to acquire longitudinal data. Methods The event‐based model characterizes a disease as a series of events, each comprising a significant change in subject state. The model was applied to data from 154 patients and 128 healthy controls selected from five independent diffusion MRI datasets acquired in four different imaging laboratories between 1999 and 2016. The biomarkers modeled were mean fractional anisotropy values of white matter tracts implicated in amyotrophic lateral sclerosis. The cerebral portion of the corticospinal tract was divided into three segments. Results Application of the model to the pooled datasets revealed that the corticospinal tracts were involved before other white matter tracts. Distal corticospinal tract segments were involved earlier than more proximal (i.e., cephalad) segments. In addition, the model revealed early ordering of fractional anisotropy change in the corpus callosum and subsequently in long association fibers. Interpretation These findings represent data‐driven evidence for early involvement of the corticospinal tracts and body of the corpus callosum in keeping with conventional approaches to image analysis, while providing new evidence to inform directional degeneration of the corticospinal tracts. This data‐driven model provides new insight into the dynamics of neuronal damage in amyotrophic lateral sclerosis

From chemical gardens to chemobrionics

Chemical gardens in laboratory chemistries ranging from silicates to polyoxometalates, in applications ranging from corrosion products to the hydration of Portland cement, and in natural settings ranging from hydrothermal vents in the ocean depths to brinicles beneath sea ice. In many chemical-garden experiments, the structure forms as a solid seed of a soluble ionic compound dissolves in a solution containing another reactive ion. In general any alkali silicate solution can be used due to their high solubility at high pH. The cation should not precipitate with the counterion of the metal salt used as seed. A main property of seed chemical-garden experiments is that initially, when the fluid is not moving under buoyancy or osmosis, the delivery of the inner reactant is diffusion controlled. Another experimental technique that isolates one aspect of chemical-garden formation is to produce precipitation membranes between different aqueous solutions by introducing the two solutions on either side of an inert carrier matrix. Chemical gardens may be grown upon injection of solutions into a so-called Hele-Shaw cell, a quasi-two-dimensional reactor consisting in two parallel plates separated by a small gap

A combined first and second order variational approach for image reconstruction

In this paper we study a variational problem in the space of functions of bounded Hessian. Our model constitutes a straightforward higher-order extension of the well known ROF functional (total variation minimisation) to which we add a non-smooth second order regulariser. It combines convex functions of the total variation and the total variation of the first derivatives. In what follows, we prove existence and uniqueness of minimisers of the combined model and present the numerical solution of the corresponding discretised problem by employing the split Bregman method. The paper is furnished with applications of our model to image denoising, deblurring as well as image inpainting. The obtained numerical results are compared with results obtained from total generalised variation (TGV), infimal convolution and Euler's elastica, three other state of the art higher-order models. The numerical discussion confirms that the proposed higher-order model competes with models of its kind in avoiding the creation of undesirable artifacts and blocky-like structures in the reconstructed images -- a known disadvantage of the ROF model -- while being simple and efficiently numerically solvable.Comment: 34 pages, 89 figure

The Plasma Environment of Comets

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138863/1/rog199129s2976.pd