Minimal residual disease monitoring in multiple myeloma: a comparison between allelic-specific oligonucleotide real-time quantitative polymerase chain reaction and flow cytometry.

BACKGROUND AND OBJECTIVES: Minimal residual disease (MRD) studies are useful in multiple myeloma (MM). However, the definition of the best technique and clinical utility are still unresolved issues. The aim of this study was to analyze and compare the clinical utility of MRD studies in MM with two different techniques: allelic-specific oligonucleotide real-time quantitative PCR (ASO-RQ-PCR), and flow cytometry (FCM). DESIGN AND METHODS: Bone marrow samples from 32 MM patients who had achieved complete response after transplantation were evaluated by ASO-RQ-PCR, using TaqMan technology, and multiparametric FCM. RESULTS: ASO-RQ-PCR was only applicable in 75% of patients for a variety of technical reasons, while FCM was applicable in up to 90%. Therefore, simultaneous PCR/FCM analysis was possible in only 24 patients. The number of residual tumor cells identified by both techniques was very similar (mean=0.29%, range=0.001-1.61%, correlation coefficient=0.861). However, RQ-PCR was able to detect residual myelomatous cells in 17 patients while FCM only did so in 11; thus, 6 cases were FCM negative but PCR positive, all of them displaying a very low number of clonal cells (median=0.014%, range=0.001-0.11). Using an MRD threshold of 0.01% (10(-4)) two risk groups with significantly different progression-free survival could be identified by either PCR (34 vs. 15m, p=0.04) or FCM (27 vs. 10m, p=0.05). INTERPRETATION AND CONCLUSIONS: Although MRD evaluation by ASO-RQ-PCR is slightly more sensitive and specific than FCM, it is applicable in a lower proportion of MM patients and is more time-consuming, while both techniques provide similar prognostic information.

Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR.

The hypervariable regions of immunoglobulin heavy-chain (IgH) rearrangements provide a specific tumor marker in multiple myeloma (MM). Recently, real-time PCR assays have been developed in order to quantify the number of tumor cells after treatment. However, these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (MM) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells. Our group has recently described a 60% incidence of incomplete DJH rearrangements in MM patients, with no or very low rates of SH. In this study, we compare the efficiency of a real-time PCR approach for the analysis of both complete and incomplete IgH rearrangements in eight MM patients using only three JH consensus probes. We were able to design an allele-specific oligonucleotide for both the complete and incomplete rearrangement in all patients. DJH rearrangements fulfilled the criteria of effectiveness for real-time PCR in all samples (ie no unspecific amplification, detection of less than 10 tumor cells within 10(5) polyclonal background and correlation coefficients of standard curves higher than 0.98). By contrast, only three out of eight VDJH rearrangements fulfilled these criteria. Further analyses showed that the remaining five VDJH rearrangements carried three or more somatic mutations in the probe and primer sites, leading to a dramatic decrease in the melting temperature. These results support the use of incomplete DJH rearrangements instead of complete somatically mutated VDJH rearrangements for investigation of minimal residual disease in multiple myeloma.

Geometric properties of 2-dimensional minimal surfaces in a sub-Riemannian manifold which models the Visual Cortex

In this paper we study the notion of degree forsubmanifolds embedded in an equiregular sub-Riemannian manifold and we provide the definition of their associated area functional. In this setting we prove that the Hausdorff dimension of a submanifold coincides with its degree, as stated by Gromov. Using these general definitions we compute the first variation for surfaces embedded in low dimensional manifolds and we obtain the partial differential equation associated to minimal surfaces. These minimal surfaces have several applications in the neurogeometry of the visual cortex.

Caracterização da economia solidária à luz do ambiente isonômico de Guerreiro Ramos: um estudo no Grupo Mulheres Decididas a Vencer

The Solidary Economy is an area that has shown unusual traits to what is preached in the traditional economic organizations, even organizations that have very similar principles, as some cooperatives. This trait is approaching the concept of isonomy proposed by Ramos (1989). Given this context, and the notion that the isonomy is like a ideal type, the objective this work was to evidence particulars of isonomic environment the in economic and solidarity experiences, taking as an empirical research area the Grupo de Mulheres Decididas a Vencer, considered a solidary economic enterprise. For this, we used the descriptive-exploratory research of qualitative nature, where the object of such research is the know enterprise, therefore, also characterized as a case study, which were taken as research subjects six associates, they being the most active in the enterprise. From the five categories that characterize isonomy - minimum standards prescribing, self-gratifying activity, activities undertaken as a vocation, wide system of making decision and primaries interpersonal relations - and from the traits of a solidary economic enterprise the data analysis was built, through content analysis, specifically the categorial analysis. Given this context and reality in which it is Grupo de Mulheres Decididas a Vencer, with minimal rules and procedures for conducting activities, comparing them to a therapy, women choosing to insert in that environment, faced with a democratic space and unfettered bureaucracy in professional interpersonal relationships, in others words, an organizational space where they were shown signs of substantive rationality was possible to conclude that the Group will share experiences and characteristics of isonomy. This disclosure meets the multidimensional social that presupposes Paraecomomic Paradigm, enabling man to enter in different social environments of the economy in order to search for self-actualization

Belief and Bounded Rationality

Predictive accounts of belief ascription, either following the principle of charity or Dennett's intentional stance, have proved popular recently. However, such accounts require us first to treat agents as perfectly rational agents and then revise this assumption as appropriate. I argue that such downwards revision is no easy task and that several proposed accounts are not satisfactory. I propose a way of characterising agent's belief states which shares Dennett's approach but avoids treating agents as perfectly rational, and develop a formal account in terms of fan models.

Regular homomorphisms of minimal sets

The classification of minimal sets is a central theme in abstract topological dynamics. Recently this work has been strengthened and extended by consideration of homomorphisms. Background material is presented in Chapter I. Given a flow on a compact Hausdorff space, the action extends naturally to the space of closed subsets, taken with the Hausdorff topology. These hyperspaces are discussed and used to give a new characterization of almost periodic homomorphisms. Regular minimal sets may be described as minimal subsets of enveloping semigroups. Regular homomorphisms are defined in Chapter II by extending this notion to homomorphisms with minimal range. Several characterizations are obtained. In Chapter III, some additional results on homomorphisms are obtained by relativizing enveloping semigroup notions. In Veech's paper on point distal flows, hyperspaces are used to associate an almost one-to-one homomorphism with a given homomorphism of metric minimal sets. In Chapter IV, a non-metric generalization of this construction is studied in detail using the new notion of a highly proximal homomorphism. An abstract characterization is obtained, involving only the abstract properties of homomorphisms. A strengthened version of the Veech Structure Theorem for point distal flows is proved. In Chapter V, the work in the earlier chapters is applied to the study of homomorphisms for which the almost periodic elements of the associated hyperspace are all finite. In the metric case, this is equivalent to having at least one fiber finite. Strong results are obtained by first assuming regularity, and then assuming that the relative proximal relation is closed as well.

Preservation through Access: Minimal Processing at the Heinz History Center

Presentation from the MARAC conference in Roanoke, VA on October 7–10, 2015. S8 - Minimal Processing and Preservation: Friends or Foes?

Motion compensation with minimal residue dispersion matching criteria

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Tecnoloigia, 2016.

Emotional Theory of Rationality

In recent decades, it has been definitely established the existence of a close relationship between the emotional phenomena and rational processes, but we still do not have a unified definition, or effective models to describe any of them well. To advance our understanding of the mechanisms governing the behavior of living beings we must integrate multiple theories, experiments and models from both fields. In this paper we propose a new theoretical framework that allows integrating and understanding, from a functional point of view, the emotion-cognition duality. Our reasoning, based on evolutionary principles, add to the definition and understanding of emotion, justifying its origin, explaining its mission and dynamics, and linking it to higher cognitive processes, mainly with attention, cognition, decision-making and consciousness. According to our theory, emotions are the mechanism for brain function optimization, besides being the contingency and stimuli prioritization system. As a result of this approach, we have developed a dynamic systems-level model capable of providing plausible explanations for some psychological and behavioral phenomena, and establish a new framework for scientific definition of some fundamental psychological terms.

Caracterização da economia solidária à luz do ambiente isonômico de Guerreiro Ramos: um estudo no Grupo Mulheres Decididas a Vencer

The Solidary Economy is an area that has shown unusual traits to what is preached in the traditional economic organizations, even organizations that have very similar principles, as some cooperatives. This trait is approaching the concept of isonomy proposed by Ramos (1989). Given this context, and the notion that the isonomy is like a ideal type, the objective this work was to evidence particulars of isonomic environment the in economic and solidarity experiences, taking as an empirical research area the Grupo de Mulheres Decididas a Vencer, considered a solidary economic enterprise. For this, we used the descriptive-exploratory research of qualitative nature, where the object of such research is the know enterprise, therefore, also characterized as a case study, which were taken as research subjects six associates, they being the most active in the enterprise. From the five categories that characterize isonomy - minimum standards prescribing, self-gratifying activity, activities undertaken as a vocation, wide system of making decision and primaries interpersonal relations - and from the traits of a solidary economic enterprise the data analysis was built, through content analysis, specifically the categorial analysis. Given this context and reality in which it is Grupo de Mulheres Decididas a Vencer, with minimal rules and procedures for conducting activities, comparing them to a therapy, women choosing to insert in that environment, faced with a democratic space and unfettered bureaucracy in professional interpersonal relationships, in others words, an organizational space where they were shown signs of substantive rationality was possible to conclude that the Group will share experiences and characteristics of isonomy. This disclosure meets the multidimensional social that presupposes Paraecomomic Paradigm, enabling man to enter in different social environments of the economy in order to search for self-actualization

Unpacking insanity defence standards: an experimental study of rationality and control tests in criminal law

The present study investigated the impact of different legal standards on mock juror decisions concerning whether a defendant was guilty or not guilty by reason of insanity. Undergraduate students (N = 477) read a simulated case summary involving a murder case and were asked to make an insanity determination. The cases differed in terms of the condition of the defendant (rationality deficit or control deficit) and the legal standard given to the jurors to make the determination (Model Penal Code, McNaughten or McNaughten plus a separate control determination). The effects of these variables on the insanity determination were investigated. Jurors also completed questionnaires measuring individualism and hierarchy attitudes and perceptions of facts in the case. Results indicate that under current insanity standards jurors do not distinguish between defendants with rationality deficits and defendants with control deficits regardless of whether the legal standard requires them to do so. Even defendants who lacked control were found guilty at equal rates under a legal standard excusing rationality deficits only and a legal standard excluding control and rationality deficits. This was improved by adding a control test as a partial defence, to be determined after a rationality determination. Implications for the insanity defence in the Criminal Justice System are discussed.

Nested Sampling and its Applications in Stable Compressive Covariance Estimation and Phase Retrieval with Near-Minimal Measurements

Compressed covariance sensing using quadratic samplers is gaining increasing interest in recent literature. Covariance matrix often plays the role of a sufficient statistic in many signal and information processing tasks. However, owing to the large dimension of the data, it may become necessary to obtain a compressed sketch of the high dimensional covariance matrix to reduce the associated storage and communication costs. Nested sampling has been proposed in the past as an efficient sub-Nyquist sampling strategy that enables perfect reconstruction of the autocorrelation sequence of Wide-Sense Stationary (WSS) signals, as though it was sampled at the Nyquist rate. The key idea behind nested sampling is to exploit properties of the difference set that naturally arises in quadratic measurement model associated with covariance compression. In this thesis, we will focus on developing novel versions of nested sampling for low rank Toeplitz covariance estimation, and phase retrieval, where the latter problem finds many applications in high resolution optical imaging, X-ray crystallography and molecular imaging. The problem of low rank compressive Toeplitz covariance estimation is first shown to be fundamentally related to that of line spectrum recovery. In absence if noise, this connection can be exploited to develop a particular kind of sampler called the Generalized Nested Sampler (GNS), that can achieve optimal compression rates. In presence of bounded noise, we develop a regularization-free algorithm that provably leads to stable recovery of the high dimensional Toeplitz matrix from its order-wise minimal sketch acquired using a GNS. Contrary to existing TV-norm and nuclear norm based reconstruction algorithms, our technique does not use any tuning parameters, which can be of great practical value. The idea of nested sampling idea also finds a surprising use in the problem of phase retrieval, which has been of great interest in recent times for its convex formulation via PhaseLift, By using another modified version of nested sampling, namely the Partial Nested Fourier Sampler (PNFS), we show that with probability one, it is possible to achieve a certain conjectured lower bound on the necessary measurement size. Moreover, for sparse data, an l1 minimization based algorithm is proposed that can lead to stable phase retrieval using order-wise minimal number of measurements.