Exploring the knowledge contained in neuroimages: Statistical discriminant analysis and automatic segmentation of the most significant changes

Objective: The aim of this article is to propose an integrated framework for extracting and describing patterns of disorders from medical images using a combination of linear discriminant analysis and active contour models. Methods: A multivariate statistical methodology was first used to identify the most discriminating hyperplane separating two groups of images (from healthy controls and patients with schizophrenia) contained in the input data. After this, the present work makes explicit the differences found by the multivariate statistical method by subtracting the discriminant models of controls and patients, weighted by the pooled variance between the two groups. A variational level-set technique was used to segment clusters of these differences. We obtain a label of each anatomical change using the Talairach atlas. Results: In this work all the data was analysed simultaneously rather than assuming a priori regions of interest. As a consequence of this, by using active contour models, we were able to obtain regions of interest that were emergent from the data. The results were evaluated using, as gold standard, well-known facts about the neuroanatomical changes related to schizophrenia. Most of the items in the gold standard was covered in our result set. Conclusions: We argue that such investigation provides a suitable framework for characterising the high complexity of magnetic resonance images in schizophrenia as the results obtained indicate a high sensitivity rate with respect to the gold standard. (C) 2010 Elsevier B.V. All rights reserved.

Therapeutic evaluation of free and liposome-loaded furazolidone in experimental visceral leishmaniasis

Drug delivery systems are promising pharmaceutical formulations used to improve the therapeutic index of drugs. In this study, we developed a liposomal formulation of furazolidone that targets Leishmania (Leishmania) chagasi amastigotes in a hamster model. Using laser scanning confocal microscopy, it was demonstrated that the liposomal drug co-localised with L. (L.) chagasi amastigotes within macrophages. Liposomal furazolidone administered intraperitoneally at 0.5 mg/kg for 12 consecutive days reduced spleen (74%) and liver (32%) parasite burden at a 100-fold lower dose than the free drug. Free furazolidone (50 mg/kg) also effectively reduced spleen (82.5%) and liver (85%) parasites; its in vitro activity against promastigotes and intracellular amastigotes demonstrated a high degree of parasite selectivity. Thus, furazolidone, both in the free and liposome-loaded formulation, is an effective inhibitor of L. (L.) chagasi, representing a possible cost-effective drug candidate for the treatment of visceral leishmaniasis. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

In Vitro Phototoxicity of Liposomes and Nanocapsules Containing Chloroaluminum Phthalocyanine on Human Melanoma Cell Line

In this study, the photodynamic action of liposomes (LP) and nanocapsules (NC) containing Chloroaluminum phthalocyanine (CIAIPc), on the human melanoma cell (WM 1552C), was assessed. The light source was setup at 672 nm, which corresponds to the maximum absorption wavelength of the CIAIPc. Both colloidal carriers presented size in nanometric scale as well as negative zeta potential. The cellular damage was light dose dependent ranging from 30% of cell death at 70 mJ.cm(-2) to 90% of death at 700 mJ.cm(-2). However, the photocytotoxic effect of LP at 70 mJ.cm(-2) was slightly more efficient to induce cellular death than NC formulation. At 140 mJ.cm(-2), and 700 mJ.cm(-2) both nanocarriers were equally efficient to induce cellular damage. Therefore, in the present work, the maximum phototoxic effect was obtained with 700 mJ.cm(-2) of light dose, in combination with 0.29 mu g.mL(-1) of CIAIPc encapsulated into LP and NC. The cells were also positive to annexin V, after the PDT treatment with LP and NC, showing that one of the mechanisms of cellular death involved is apoptosis. In summary, the potential of LP and NC as a drug delivery system, in Photodynamic Therapy (PDT) against melanoma, has been confirmed using a lower concentration of the photosensitizer and lower light doses than that applied in current protocols. This is an innovative proposal to treat melanoma cell lines that until now have not received the benefit of the PDT protocol for treatment.

Zinc Supplement Modifies Auditory Brainstem Responses in Patients with Tinnitus

Introduction: Zinc is an essential element for human homeostasis being clearly related to almost all metabolic pathways. It is found in some neural circuitries, probably acting as a modulator of glutamatergic excitatory synapsis. In the auditory system its presence has been demonstrated within the cochlea and cochlear nuclei. Tinnitus symptoms are correlated to zinc physiology, and it has been postulated that the oligoelement could be used as an alternative treatment for this clinical situation. Aim: This study has evaluated the brainstem responses (ABR) in patients who suffer from chronic idiophatic tinnitus, before and after being treated with zinc. Neural transmissions in the brainstem auditory structures were also compared in both conditions. Materials and Methods: Forty-one patients (22 with tinnitus and 19 controls, groups I and II, respectively) were included in the study and submitted to anamnesis, otorhinolaryngologic examinations, biochemical evaluation and audiological tests. Group I patients received an specific zinc formulation for 90 days. ABR tests were performed at the beginning of the study and at the end of the zinc treatment. Results: First ABR tests showed no differences between the groups, but on the second evaluation there was a significant prolongation of the wave V latency and an enlargement of wave V amplitude shown in group I. Conclusion: Treatment with systemic zinc could change some aspects of auditory neurotransmission in the brainstem.

Efficacy of Marigold Extract-Loaded Formulations Against UV-induced Oxidative Stress

The present study investigated the potential use of topical formulations containing marigold extract (ME) (Calendula officinalis extract) against ultraviolet (UV) B irradiation-induced skin damage. The physical and functional stabilities, as well as the skin penetration capacity, of the different topical formulations developed were evaluated. In addition, the in vivo capacity to prevent/treat the UVB irradiation-induced skin damage, in hairless mice, of the formulation with better skin penetration capacity was investigated. All of the formulations were physically and functionally stable. The gel formulation [Formulation 3 (F3)] was the most effective for the topical delivery of ME, which was detected as 0.21 mu g/cm(2) of narcissin and as 0.07 mu g/cm(2) of the rutin in the viable epidermis. This formulation was able to maintain glutathione reduced levels close to those of nonirradiated animals, but did not affect the gelatinase-9 and myeloperoxidase activities increased by exposure to UVB irradiation. In addition, F3 reduced the histological skin changes induced by UVB irradiation that appear as modifications of collagen fibrils. Therefore, the photoprotective effect in hairless mice achieved with the topical application of ME in gel formulation is most likely associated with a possible improvement in the collagen synthesis in the subepidermal connective tissue. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2182-2193, 2011

Interchangeability among therapeutics equivalents of lamotrigine in the treatment of refractory epilepsy patients: risks and benefits

Introduction. Epilepsy is a condition characterized by signs and symptoms of neurological disorder. Lamotrigine has been widely used, mainly due to their greater tolerability and lower rate of drug interactions with other antiepileptic drugs however the newest antiepileptic drugs have high cost to patient. In Brazil there are three different sort of pharmaceutical equivalents (reference, generic and similar), and the Brazilian health care authorities offers to users the possibility to receive them free of charge. Moreover these pharmaceutical equivalents can change during the treatment of epilepsy because this authorities buy the cheapest by public tender two or three times a year. Aim. To evaluate the clinical and laboratory findings related to the most frequently used therapeutic equivalents of lamotrigine (reference drugs and similar products). Patients and methods. Two similar formulations (A and B) and one reference (C) were tested in nine epileptic refractory patients. The study was divided into three periods of 42 days, one for each formulation, and medical data about the frequency of seizures, the occurrence of side effects and measurement of plasma concentrations of lamotrigine were collected. Results. The average number of seizures/week and plasma concentration of lamotrigine for formulations A, B and C were not statistically significant differences. Three patients during the use of the formulation C presented mild and transitory side effects. Conclusion. Similar or reference drugs showed satisfactory results, however the interchangeability among the formulations raise the difficulty for the management of seizures in refractory epilepsy.

Photoinitiator content in restorative composites: Influence on degree of conversion, reaction kinetics, volumetric shrinkage and polymerization stress

Purpose: To determine the influence of rate of polymerization, degree of conversion and volumetric shrinkage on stress development by varying the amount of photoinitiators in a model composite. Methods: Volumetric shrinkage (with a mercury dilatometer), degree of conversion, maximum rate of reaction (RP(max)) (with differential scanning calorimetry) and polymerization stress (with a controlled compliance device) were evaluated. Bis-GMA/TEGDMA (equal mass ratios) were mixed with a tertiary amine (EDMAB) and camphorqpinone, respectively, in three concentrations (wt%): high= 0.8/1.6; intermediate= 0.4/0.8 and low= 0.2/0.4. 80 wt% filler was added. Composites were photoactivated (400 mW/cm(2) x 40 seconds; radiant exposure=16J/cm(2)). A fourth experimental group was included in which the low concentration formulation was exposed for 80 seconds (32 J/cm(2)). Results: For the same radiant exposure, conversion, RP(max) and stress increased with photoinitiator concentration (P< 0.001). When the low concentration group exposed to 32 J/cm(2) was compared with the high and intermediate groups (exposed to 16 J/cm(2)), RPmax Still increased with the photoinitiator concentration between all levels (P< 0.001) but conversion and stress did not vary (P> 0.05). Shrinkage did not vary regardless of the photoinitiator concentration or radiant exposure. For the photoinitiator concentrations used in this study. Polymerization stress was influenced by conversion but not by rate of reaction. (Am J Dent 2009;22:206-210).

Influence of BisGMA, TEGDMA, and BisEMA contents on viscosity, conversion, and flexural strength of experimental resins and composites

Different monomer structures lead to different physical and mechanical properties for both the monomers and the polymers. The objective of this study was to determine the influence of the bisphenylglycidyl dimethacrylate (BisGMA) concentration (33, 50 or 66 mol%) and the co-monomer content [triethylene glycol dimethacrylate (TEGDMA), ethoxylated bisphenol-A dimethacrylate (BisEMA), or both in equal parts] on viscosity (eta), degree of conversion (DC), and flexural strength (FS). eta was measured using a viscometer, DC was obtained by Fourier transfer Raman (FT-Raman) spectroscopy, and FS was determined by three-point bending. At 50 and 66% BisGMA, increases in eta were observed following the partial and total substitution of TEGDMA by BisEMA. For 33% BisGMA, eta increased significantly only when no TEGDMA was present. The DC was influenced by BisGMA content and co-monomer type. Mixtures containing 66% BisGMA showed a lower DC compared with mixtures containing other concentrations of BisGMA. The BisEMA mixtures had a lower DC compared with the TEGDMA mixtures. The FS was influenced by co-monomer content only. BisEMA mixtures presented a statistically lower FS, followed by TEGDMA + BisEMA mixtures, and then by TEGDMA mixtures. Partial or total replacement of TEGDMA by BisEMA increased eta, which was associated with the observed decreases in DC and FS. Although the BisGMA content influenced the DC, it did not affect the FS results.

Can increasing the viscosity of formulations be used to reduce the human skin penetration of the sunscreen oxybenzone?

The effect of adding thickening agents on the penetration of a sunscreen benzophenone-3 through epidermal and a high-density polyethylene membrane was studied using both very thick (infinite dose) and thin tin use) applications. Contradictory results were obtained. Thickening agents retard skin penetration, in a manner consistent with a diffusional resistance in the formulation, when applied as an infinite dose. In contrast, when applied as in thin (in use) doses, thickening agents promote penetration, most likely through greater stratum corneum diffusivity arising from an enhanced hydration by the thicker formulations. The two key implications from this work are (i) a recognition of the danger in the potential extrapolation of infinite dosing to in use situations, and (ii) to recognize that thicker formulations may sometimes enhance the penetration of other topical agents when applied in use.

Complex natural resonances of conducting planar objects buried in a dielectric half-space

A scheme is presented to incorporate a mixed potential integral equation (MPIE) using Michalski's formulation C with the method of moments (MoM) for analyzing the scattering of a plane wave from conducting planar objects buried in a dielectric half-space. The robust complex image method with a two-level approximation is used for the calculation of the Green's functions for the half-space. To further speed up the computation, an interpolation technique for filling the matrix is employed. While the induced current distributions on the object's surface are obtained in the frequency domain, the corresponding time domain responses are calculated via the inverse fast Fourier transform (FFT), The complex natural resonances of targets are then extracted from the late time response using the generalized pencil-of-function (GPOF) method. We investigate the pole trajectories as we vary the distance between strips and the depth and orientation of single, buried strips, The variation from the pole position of a single strip in a homogeneous dielectric medium was only a few percent for most of these parameter variations.

Solution techniques for transport problems involving steep concentration gradients: application to noncatalytic fluid solid reactions

Some efficient solution techniques for solving models of noncatalytic gas-solid and fluid-solid reactions are presented. These models include those with non-constant diffusivities for which the formulation reduces to that of a convection-diffusion problem. A singular perturbation problem results for such models in the presence of a large Thiele modulus, for which the classical numerical methods can present difficulties. For the convection-diffusion like case, the time-dependent partial differential equations are transformed by a semi-discrete Petrov-Galerkin finite element method into a system of ordinary differential equations of the initial-value type that can be readily solved. In the presence of a constant diffusivity, in slab geometry the convection-like terms are absent, and the combination of a fitted mesh finite difference method with a predictor-corrector method is used to solve the problem. Both the methods are found to converge, and general reaction rate forms can be treated. These methods are simple and highly efficient for arbitrary particle geometry and parameters, including a large Thiele modulus. (C) 2001 Elsevier Science Ltd. All rights reserved.

A new diffusion and flow theory for activated carbon from low pressure to capillary condensation range

In this paper, we develop a theory for diffusion and flow of pure sub-critical adsorbates in microporous activated carbon over a wide range of pressure, ranging from very low to high pressure, where capillary condensation is occurring. This theory does not require any fitting parameter. The only information needed for the prediction is the complete pore size distribution of activated carbon. The various interesting behaviors of permeability versus loading are observed such as the maximum permeability at high loading (occurred at about 0.8-0.9 relative pressure). The theory is tested with diffusion and flow of benzene through a commercial activated carbon, and the agreement is found to be very good in the light that there is no fitting parameter in the model. (C) 2001 Elsevier Science B.V. All rights reserved.

Nucleation, growth and breakage phenomena in agitated wet granulation processes: a review

Wet agglomeration processes have traditionally been considered an empirical art, with great difficulties in predicting and explaining observed behaviour. Industry has faced a range of problems including large recycle ratios, poor product quality control, surging and even the total failure of scale up from laboratory to full scale production. However, in recent years there has been a rapid advancement in our understanding of the fundamental processes that control granulation behaviour and product properties. This review critically evaluates the current understanding of the three key areas of wet granulation processes: wetting and nucleation, consolidation and growth, and breakage and attrition. Particular emphasis is placed on the fact that there now exist theoretical models which predict or explain the majority of experimentally observed behaviour. Provided that the correct material properties and operating parameters are known, it is now possible to make useful predictions about how a material will granulate. The challenge that now faces us is to transfer these theoretical developments into industrial practice. Standard, reliable methods need to be developed to measure the formulation properties that control granulation behaviour, such as contact angle and dynamic yield strength. There also needs to be a better understanding of the flow patterns, mixing behaviour and impact velocities in different types of granulation equipment. (C) 2001 Elsevier Science B.V. All rights reserved.

A semi-analytical solution for vibration of rectangular plates with abrupt thickness variation

A semi-analytical analysis of free vibration of plates with cross-sectional discontinuities due to abrupt changes in thickness is presented. A basic square element divided into suitable subdomains dependent upon the positions of these abrupt changes is used as the basic building element, Admissible functions that satisfy the essential or geometric boundary conditions are used to define the transverse deflection of each subdomain. Continuities in the displacement, slope, moment and higher derivatives between adjacent subdomains are enforced at the interconnecting edges. The resulting global energy functional from the proper assembly of the coupled strain and kinetic energy contributions of each subdomain is then minimized via the Ritz procedure to extract the frequencies and mode shapes. Contour plots of a range of new mode shapes are presented for the enhancement of understanding the dynamic behavior of this class of plates, (C) 2001 Elsevier Science Ltd, All rights reserved.

Knowledge and markets

An economy is a coordinated system of distributed knowledge. Economic evolution occurs as knowledge grows and the structure of the system changes. This paper is about the role of markets in this process. Traditionally, the theory of markets has not been a central feature of evolutionary economics. This seems to be due to the orthodox view of markets as information-processing mechanisms for finding equilibria. But in economic evolution markets are actually knowledge-structuring mechanisms. What then is the relation between knowledge, information, markets and mechanisms? I argue that an evolutionary theory of markets, in the manner of Loasby (1999), requires a clear formulation of these relations. I suggest that a conception of knowledge and markets in terms of a graphical theory of complex systems furnishes precisely this.