Purification of coagulation factor VIII using chromatographic methods. Direct chromatography of plasma in anion exchange resins

Coagulation factor VIII (FVIII) concentrates are used in the treatment of patients with Hemophilia A. Human FVIII was purified directly from plasma using anion exchange chromatography followed by gel filtration. Three Q-Sepharose resins were tested, resulting in 40% recovery of FVIII activity using Q-Sepharose XL resin, about 80% using Q-Sepharose Fast Flow and 70% using the Q-Sepharose Big Beads. The vitamin K-dependent coagulation factors co-eluted with FVIII from the anion exchange columns. In the second step of purification, when Sepharose 6FF was used, 70% of FVIII activity was recovered free from vitamin K-dependent factors.

A note on the local power of the LR, Wald, score and gradient tests

This paper examines the local power of the likelihood ratio, Wald, score and gradient tests under the presence of a scalar parameter, phi say, that is orthogonal to the remaining parameters. We show that some of the coefficients that define the local powers remain unchanged regardless of whether phi is known or needs to be estimated, where as the others can be written as the sum of two terms, the first of which being the corresponding term obtained as if phi were known, and the second, an additional term yielded by the fact that phi is unknown. The contribution of each set of parameters on the local powers of the tests can then be examined. Various implications of our main result are stated and discussed. Several examples are presented for illustrative purposes

CONTEXT TREE SELECTION AND LINGUISTIC RHYTHM RETRIEVAL FROM WRITTEN TEXTS

The starting point of this article is the question "How to retrieve fingerprints of rhythm in written texts?" We address this problem in the case of Brazilian and European Portuguese. These two dialects of Modern Portuguese share the same lexicon and most of the sentences they produce are superficially identical. Yet they are conjectured, on linguistic grounds, to implement different rhythms. We show that this linguistic question can be formulated as a problem of model selection in the class of variable length Markov chains. To carry on this approach, we compare texts from European and Brazilian Portuguese. These texts are previously encoded according to some basic rhythmic features of the sentences which can be automatically retrieved. This is an entirely new approach from the linguistic point of view. Our statistical contribution is the introduction of the smallest maximizer criterion which is a constant free procedure for model selection. As a by-product, this provides a solution for the problem of optimal choice of the penalty constant when using the BIC to select a variable length Markov chain. Besides proving the consistency of the smallest maximizer criterion when the sample size diverges, we also make a simulation study comparing our approach with both the standard BIC selection and the Peres-Shields order estimation. Applied to the linguistic sample constituted for our case study, the smallest maximizer criterion assigns different context-tree models to the two dialects of Portuguese. The features of the selected models are compatible with current conjectures discussed in the linguistic literature.

Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents

OBJECTIVES: The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. METHOD: The animals were assigned to control (control, n = 10) and monosodium glutamate (monosodium glutamate, n = 13) groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. RESULTS: Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%), an increased area under the curve of total insulin secretion during glucose overload (39.3%), and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times), bradycardic responses (>4 times), and vagal (similar to 38%) and sympathetic effects (similar to 36%) were reduced as compared to the control group. CONCLUSION: Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.

Latent residual analysis in binary regression with skewed link

Model diagnostics is an integral part of model determination and an important part of the model diagnostics is residual analysis. We adapt and implement residuals considered in the literature for the probit, logistic and skew-probit links under binary regression. New latent residuals for the skew-probit link are proposed here. We have detected the presence of outliers using the residuals proposed here for different models in a simulated dataset and a real medical dataset.

The polysurvival model with long-term survivors

Long-term survival models have historically been considered for analyzing time-to-event data with long-term survivors fraction. However, situations in which a fraction (1 - p) of systems is subject to failure from independent competing causes of failure, while the remaining proportion p is cured or has not presented the event of interest during the time period of the study, have not been fully considered in the literature. In order to accommodate such situations, we present in this paper a new long-term survival model. Maximum likelihood estimation procedure is discussed as well as interval estimation and hypothesis tests. A real dataset illustrates the methodology.

Regular and moderate exercise before experimental sepsis reduces the risk of lung and distal organ injury

de Araujo CC, Silva JD, Samary CS, Guimaraes IH, Marques PS, Oliveira GP, do Carmo LGRR, Goldenberg RC, Bakker-Abreu I, Diaz BL, Rocha NN, Capelozzi VL, Pelosi P, Rocco PRM. Regular and moderate exercise before experimental sepsis reduces the risk of lung and distal organ injury. J Appl Physiol 112: 1206-1214, 2012. First published January 19, 2012; doi:10.1152/japplphysiol.01061.2011.-Physical activity modulates inflammation and immune response in both normal and pathologic conditions. We investigated whether regular and moderate exercise before the induction of experimental sepsis reduces the risk of lung and distal organ injury and survival. One hundred twenty-four BALB/c mice were randomly assigned to two groups: sedentary (S) and trained (T). Animals in T group ran on a motorized treadmill, at moderate intensity, 5% grade, 30 min/day, 3 times a week for 8 wk. Cardiac adaptation to exercise was evaluated using echocardiography. Systolic volume and left ventricular mass were increased in T compared with S group. Both T and S groups were further randomized either to sepsis induced by cecal ligation and puncture surgery (CLP) or sham operation (control). After 24 h, lung mechanics and histology, the degree of cell apoptosis in lung, heart, kidney, liver, and small intestine villi, and interleukin (IL)-6, KC (IL-8 murine functional homolog), IL-1 beta, IL-10, and number of cells in bronchoalveolar lavage (BALF) and peritoneal lavage (PLF) fluids as well as plasma were measured. In CLP, T compared with S groups showed: 1) improvement in survival; 2) reduced lung static elastance, alveolar collapse, collagen and elastic fiber content, number of neutrophils in BALF, PLF, and plasma, as well as lung and distal organ cell apoptosis; and 3) increased IL-10 in BALF and plasma, with reduced IL-6, KC, and IL-1 beta in PLF. In conclusion, regular and moderate exercise before the induction of sepsis reduced the risk of lung and distal organ damage, thus increasing survival.

Structure and electronic properties of hydrated mesityl oxide: a sequential quantum mechanics/molecular mechanics approach

The hydration of mesityl oxide (MOx) was investigated through a sequential quantum mechanics/molecular mechanics approach. Emphasis was placed on the analysis of the role played by water in the MOx syn-anti equilibrium and the electronic absorption spectrum. Results for the structure of the MOx-water solution, free energy of solvation and polarization effects are also reported. Our main conclusion was that in gas-phase and in low-polarity solvents, the MOx exists dominantly in syn-form and in aqueous solution in anti-form. This conclusion was supported by Gibbs free energy calculations in gas phase and in-water by quantum mechanical calculations with polarizable continuum model and thermodynamic perturbation theory in Monte Carlo simulations using a polarized MOx model. The consideration of the in-water polarization of the MOx is very important to correctly describe the solute-solvent electrostatic interaction. Our best estimate for the shift of the pi-pi* transition energy of MOx, when it changes from gas-phase to water solvent, shows a red-shift of -2,520 +/- 90 cm(-1), which is only 110 cm(-1) (0.014 eV) below the experimental extrapolation of -2,410 +/- 90 cm(-1). This red-shift of around -2,500 cm(-1) can be divided in two distinct and opposite contributions. One contribution is related to the syn -> anti conformational change leading to a blue-shift of similar to 1,700 cm(-1). Other contribution is the solvent effect on the electronic structure of the MOx leading to a red-shift of around -4,200 cm(-1). Additionally, this red-shift caused by the solvent effect on the electronic structure can by composed by approximately 60 % due to the electrostatic bulk effect, 10 % due to the explicit inclusion of the hydrogen-bonded water molecules and 30 % due to the explicit inclusion of the nearest water molecules.

Radiologic findings of osteoarticular infection in paracoccidioidomycosis

To report the radiological abnormalities of osteoarticular involvement in paracoccidioidomycosis (PCM). After institutional board approval, the medical records and conventional radiology findings of 19 patients with osseous PCM were retrospectively reviewed. Number, distribution, and lesion characteristics were evaluated in consensus by two experienced musculoskeletal radiologists. The mean age of patients was 16.1 years (range 4-49 years), 11 male and eight female. MSK involvement was the only or the primary presentation of the disease in eight of 19 patients (42.1%). In total, 51 focal bone lesions were detected, being 41 in long bones. In long bones lesions, 19 of 41 (46.4%) were metaphyseal, 12 of 41 (29.3%) meta-epiphyseal, and 12 of 41 (29.3%) diaphyseal. The most common presentation was a geographic osteolytic bone lesion (62.7%), without marginal sclerosis (82.4%) and without periosteal reaction (90.2%). Articular involvement was present in six of 19 patients (31.6%), being two cases of primary arthritis. All encountered bone lesions were osteolytic. Metaphyseal or meta-epiphyseal osteomyelitis of a long bone was the most prevalent osteoarticular manifestation of paracoccidioidomycosis. PCM osteoarticular involvement could be solitary or multifocal, occurs almost exclusively in the acute/subacute clinical form, and it is more common in children and in juvenile patients. Axial skeleton involvement, arthritis, or a disseminated osseous pattern of infection may occasionally occur in this fungal disease.

Influence of the initial condition in equilibrium last-passage percolation models

In this paper we consider an equilibrium last-passage percolation model on an environment given by a compound two-dimensional Poisson process. We prove an L-2-formula relating the initial measure with the last-passage percolation time. This formula turns out to be a useful tool to analyze the fluctuations of the last-passage times along non-characteristic directions.

Mortalidade pós-neonatal no território brasileiro: uma revisão da literatura

O presente trabalho trata-se de revisão sistemática, referente ao período de 2004 a 2009, sobre o tema mortalidade pós-neonatal. Teve o objetivo de identificar como se colocam na literatura, as causas da morte e a relação com as condições socioeconômicas. Foram selecionados 27 artigos, 74,4% publicados em periódicos da área da Saúde Pública e 66,7%, de desenho do tipo ecológico. Quase a totalidade versava sobre grupos de causas e seus componentes (66,7%), seguidos pelo terço restante, sobre a identificação dos fatores determinantes dos óbitos. A região Sudeste produziu mais de 37% dos estudos. Na maioria dos municípios e estados brasileiros, a redução superou 50% no final da década de 1990. Dentre os grupos de causas de óbitos, predominou o grupamento diarreia-pneumonia, seguido pelas malformações congênitas. As condições de vida segundo indicadores socioeconômicos - moradia, saneamento básico, educação e acesso à saúde - foram determinantes para os maiores índices de mortalidade pós-neonatal por causas passíveis de redução.