Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

The geodiamolide H, derived from Brazilian sponge Geodia corticostylifera, regulates actin cytoskeleton, migration and invasion of breast cancer cells cultured in three-dimensional environment

We are investigating effects of the depsipeptide geodiamolide H, isolated from the Brazilian sponge Geodia corticostylifera, on cancer cell lines grown in 3D environment. As shown previously geodiamolide H disrupts actin cytoskeleton in both sea urchin eggs and breast cancer cell monolayers. We used a normal mammary epithelial cell line MCF 10A that in 3D assay results formation of polarized spheroids. We also used cell lines derived from breast tumors with different degrees of differentiation: MCF7 positive for estrogen receptor and the Hs578T, negative for hormone receptors. Cells were placed on top of Matrigel. Spheroids obtained from these cultures were treated with geodiamolide H. Control and treated samples were analyzed by light and confocal microscopy. Geodiamolide H dramatically affected the poorly differentiated and aggressive Hs578T cell line. The peptide reverted HsS78T malignant phenotype to polarized spheroid-like structures. MCF7 cells treated by geodiamolide H exhibited polarization compared to controls. Geodiamolide H induced striking phenotypic modifications in Hs578T cell line and disruption of actin cytoskeleton. We investigated effects of geodiamolide H on migration and invasion of Hs578T cells. Time-lapse microscopy showed that the peptide inhibited migration of these cells in a dose-dependent manner. Furthermore invasion assays revealed that geodiamolide H induced a 30% decrease on invasive behavior of Hs578T cells. Our results suggest that geodiamolide H inhibits migration and invasion of Hs578T cells probably through modifications in actin cytoskeleton. The fact that normal cell lines were not affected by treatment with geodiamolide H stimulates new studies towards therapeutic use for this peptide.

One-dimensional trapped atoms: critical coupling parameter and critical number of particles

In this paper we consider the case of a Bose gas in low dimension in order to illustrate the applicability of a method that allows us to construct analytical relations, valid for a broad range of coupling parameters, for a function which asymptotic expansions are known. The method is well suitable to investigate the problem of stability of a collection of Bose particles trapped in one- dimensional configuration for the case where the scattering length presents a negative value. The eigenvalues for this interacting quantum one-dimensional many particle system become negative when the interactions overcome the trapping energy and, in this case, the system becomes unstable. Here we calculate the critical coupling parameter and apply for the case of Lithium atoms obtaining the critical number of particles for the limit of stability.

Paper dimensional stability in sheet-fed offset printing : Papperets dimensionsstabilitet i en arkoffsetpress

In offset printing, dampening solution is used to create a good balance in the process. If too much water is transferred to the paper, the sheet can change its size between the printing units, due to water absorption, and cause a problem with the colour register. This phenomenon is usually referred to as fanout. In this degree project, an investigation was made to see if the paper dimensions changed through its way in the sheet-fed printing process. The instrument Luchs Register Measuring Systems (Lynx) was used, and a method for measuring if the paper changed its dimensions with this instrument, was developed. Paper qualities with three different grammages were used, 90, 130 and 250 gsm. This investigation showed that all paper qualities changed their size with widening in the gripper edge in the range of 10 - 70 µm and in the trailing edge the increase was 10 - 130 µm. The elongations of the papers were in the range of 10- 300 µm. The papers with lowest grammage changed more than the heavier. To see if the print had been affected of the widening and elongation, print quality parameters like relative contrast, dot gain and mottle were correlated with the Lynx data from the sheets. The group of papers that gave correlations were in 130 gsm. The sheets had visual doubling and the combined standard deviation from the Lynx marks K3, K5 and K21 correlated with dot gain. When the variations increased so did the dot gain and this indicates that the doubling was due to the widening. There was also a correlation between the standard deviation from K3 and Mottle. The sheets widened with an average of 30 µm in the gripper edge and since there probably were doubling due to widening it also affected the Mottle values. What the widening depends on is hard to tell. Since widening was so small, it could be due to water absorption, papers being ironed out or maybe the sheets have been flattened out. It probably needs a more detailed investigation to find out what causes the widening. Further investigations about how print quality is affected by the register accuracy of a printing machine should include a print form with measuring areas close to the Lynx marks. The measuring areas should contain fine hairlines, negative text printed with at least two colours and some pictures to evaluate together with standard measuring should give a good knowledge about the subject.

Public policies impacts on Latin American labor structures, preparing for integration

One of the Main Subjects to Be Discussed, in Order to Adjust Latin American Economies to a Regional Integration Network, as Imposed By Mercosul or Other Economic Common Markets, is Related to the Employment and Other Labor Markets Public Policies. the Question to Be Posed Is: Having in Mind the Characteristics of Different Labor Markets and Labor Forces, What are the Impacts of Governmental Measures Presented in the Diverse Economic Conditions of Those Countries. Having in Mind These Impacts, This Paper Aims to Examine the Requisites to Adjust the Labor Structure Standards of Latin American Countries and What Would Be the Reforms to Be Performed By These Countries in Order to Prepare These Markets and Labor Forces to Adapt to Regional Integration Networks Represented By Mercosul, Alca or Other Common Markets. There are Evaluated the Impacts of the Globalization Process, Economic Stabilization and Reform Policies Undertaken By Some Selected Latin American Countries Since the Eighties on the Labor Structure Standards, Considering the Specific Adjustment Measures to Cope With the Negative Effects of These Policies. Next, Some Cases of Europe Union (Eu) Countries Measures to Prepare to Integration is Examined, in Order to Provide Some Elements to Better Understand the Possibilities to Handle With the Extensive Changes in External Conditions. in Sequence Some Statistical Indicatives of the Impacts of These Measures on the Occupational Structuring are Analyzed For a Group of Selected Latin American and Eu Countries.

Five-dimensional f(R) braneworld models

After incorporating f(R) gravity into the general braneworld sum rules scope, it is shown that some particular class of warped five-dimensional nonlinear braneworld models, which may be interesting for the hierarchy problem solution, still require a negative tension brane. For other classes of warp factors (suitable and not suitable for approaching the hierarchy problem) any negative brane tension in the compactification scheme is not necessary. In this vein, it is argued that, in the bulk f(R) gravity context, some types of warp factors may be useful for approaching the hierarchy problem and for evading the necessity of a negative brane tension in the compactification scheme.

A mass-transportation approach to a one dimensional fluid mechanics model with nonlocal velocity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Assessment of Donana National Park contamination in Procambarus clarkii: Integration of conventional biomarkers and proteomic approaches

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Toward the Application of Three-Dimensional Approach to Few-body Atomic Bound States

The first step toward the application of an effective non partial wave (PW) numerical approach to few-body atomic bound states has been taken. The two-body transition amplitude which appears in the kernel of three-dimensional Faddeev-Yakubovsky integral equations is calculated as function of two-body Jacobi momentum vectors, i.e. as a function of the magnitude of initial and final momentum vectors and the angle between them. For numerical calculation the realistic interatomic interactions HFDHE2, HFD-B, LM2M2 and TTY are used. The angular and momentum dependence of the fully off-shell transition amplitude is studied at negative energies. It has been numerically shown that, similar to the nuclear case, the transition amplitude exhibits a characteristic angular behavior in the vicinity of He-4 dimer pole.

SMALLEST UNIVERSE OF NEGATIVE CURVATURE

The smallest known three-dimensional closed manifold of curvature k = -1 was discovered a few years ago by Weeks. This kind of manifold is constructed from a hyperbolic polyhedron with faces pair-wise identified. Here it is used as the comoving spatial section of a Friedmann cosmological model, in the spirit of Ellis and Schreiber's idea of small universes. Its nontrivial global topology has the effect of producing multiple images of single cosmic sources, and this is the basis of an attempt to solve a famous controversy about the redshifts of quasars.

Numerical study of low-cost alternative orbits around the Moon

In this paper, we have investigated a region of direct stable orbits around the Moon, whose stability is related to the H2 Family of periodic orbits and to the quasi-periodic orbits that oscillate around them. The stability criteria adopted was that the path did not escape from the Moon during an integration period of 1000 days (remaining with negative two-body Moon-probe orbital energy during this period). Considering the three-dimensional four-body Sun-Earth-Moon-probe problem, we investigated the evolution of the size of the stability region, taking into account the eccentricity of the Earth's orbit, the eccentricity and inclination of the Moon's orbit, and the solar radiation pressure on the probe. We also investigated the evolution of the region's size and its location by varying the inclination of the probe's initial osculating orbit relative to the Moon's orbital plane between 0 degrees and 180 degrees. The size of the stability region diminishes; nevertheless, it remains significant for 0 <= i <= 25 degrees and 35 degrees <= i <= 45 degrees. The orbits of this region could be useful for missions by space vehicles that must remain in orbit around the Moon for periods of up to 1000 days, requiring low maintenance costs. (c) 2005 COSPAR. Published by Elsevier Ltd. All rights reserved.

Suppression of Anderson localization of light in one-dimensional disordered photonic superlattices

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

One-dimensional analytical model for oxide thin film growth on Ti metal layers during laser heating in air

This paper presents the theoretical and experimental results for oxide thin film growth on titanium films previously deposited over glass substrate. Ti films of thickness 0.1 μm were heated by Nd:YAG laser pulses in air. The oxide tracks were created by moving the samples with a constant speed of 2 mm/s, under the laser action. The micro-topographic analysis of the tracks was performed by a microprofiler. The results taken along a straight line perpendicular to the track axis revealed a Gaussian profile that closely matches the laser's spatial mode profile, indicating the effectiveness of the surface temperature gradient on the film's growth process. The sample's micro-Raman spectra showed two strong bands at 447 and 612 cm -1 associated with the TiO 2 structure. This is a strong indication that thermo-oxidation reactions took place at the Ti film surface that reached an estimated temperature of 1160 K just due to the action of the first pulse. The results obtained from the numerical integration of the analytical equation which describes the oxidation rate (Wagner equation) are in agreement with the experimental data for film thickness in the high laser intensity region. This shows the partial accuracy of the one-dimensional model adopted for describing the film growth rate. © 2001 Elsevier Science B.V.

Economic Survey of Latin America and the Caribbean 2010-2011: Internacional integration and macroeconomic policy challenges amid global economic turmoil

Includes bibliography

Active labor market programs for the integration of youths and immigrants into the labor market: the Nordic experience

Incluye Bibliografía