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Spatiotemporal Bayesian inference dipole analysis for MEG neuroimaging data.

Recently, we described a Bayesian inference approach to the MEG/EEG inverse problem that used numerical techniques to estimate the full posterior probability distributions of likely solutions upon which all inferences were based [Schmidt, D.M., George, J.S., Wood, C.C., 1999. Bayesian inference applied to the electromagnetic inverse problem. Human Brain Mapping 7, 195; Schmidt, D.M., George, J.S., Ranken, D.M., Wood, C.C., 2001. Spatial-temporal bayesian inference for MEG/EEG. In: Nenonen, J., Ilmoniemi, R. J., Katila, T. (Eds.), Biomag 2000: 12th International Conference on Biomagnetism. Espoo, Norway, p. 671]. Schmidt et al. (1999) focused on the analysis of data at a single point in time employing an extended region source model. They subsequently extended their work to a spatiotemporal Bayesian inference analysis of the full spatiotemporal MEG/EEG data set. Here, we formulate spatiotemporal Bayesian inference analysis using a multi-dipole model of neural activity. This approach is faster than the extended region model, does not require use of the subject's anatomical information, does not require prior determination of the number of dipoles, and yields quantitative probabilistic inferences. In addition, we have incorporated the ability to handle much more complex and realistic estimates of the background noise, which may be represented as a sum of Kronecker products of temporal and spatial noise covariance components. This reduces the effects of undermodeling noise. In order to reduce the rigidity of the multi-dipole formulation which commonly causes problems due to multiple local minima, we treat the given covariance of the background as uncertain and marginalize over it in the analysis. Markov Chain Monte Carlo (MCMC) was used to sample the many possible likely solutions. The spatiotemporal Bayesian dipole analysis is demonstrated using simulated and empirical whole-head MEG data.

Algorithms↗

Serotype distribution of invasive group B streptococcal isolates in Maryland: implications for vaccine formulation. Maryland Emerging Infections Program.

Invasive group B streptococcal (GBS) infection is a major health problem among infants and adults. The formulation of GBS vaccines depends on knowledge of the GBS serotype distribution. Serotype V GBS infection appears to have recently emerged, suggesting that the serotype distribution changes over time. GBS isolates from 210 pediatric patients, 23 pregnant women, and 314 nonpregnant adults with invasive infection in Maryland were studied. The predominant serotypes from infants with early-onset disease were as follows: serotype III, 38% of isolates; serotype Ia, 36%; serotype V, 13%; and serotype II, 11%. Although the majority (60%) of isolates among infants with late-onset infection were serotype III, serotype Ia (23%) was also common. The predominant serotype among isolates from nonpregnant adult patients was serotype V, accounting for 29% of the isolates. The serotype distribution differs between pediatric patients and adults and is changing over time. The inclusion of a relatively small number of serotypes in a GBS vaccine could provide protection against the vast majority of isolates.

Adult↗

A multi-objective evolutionary approach to the protein structure prediction problem.

The protein structure prediction (PSP) problem is concerned with the prediction of the folded, native, tertiary structure of a protein given its sequence of amino acids. It is a challenging and computationally open problem, as proven by the numerous methodological attempts and the research effort applied to it in the last few years. The potential energy functions used in the literature to evaluate the conformation of a protein are based on the calculations of two different interaction energies: local (bond atoms) and non-local (non-bond atoms). In this paper, we show experimentally that those types of interactions are in conflict, and do so by using the potential energy function Chemistry at HARvard Macromolecular Mechanics. A multi-objective formulation of the PSP problem is introduced and its applicability studied. We use a multi-objective evolutionary algorithm as a search procedure for exploring the conformational space of the PSP problem.

Algorithms↗

Phase retrieval, error reduction algorithm, and Fienup variants: a view from convex optimization.

The phase retrieval problem is of paramount importance in various areas of applied physics and engineering. The state of the art for solving this problem in two dimensions relies heavily on the pioneering work of Gerchberg, Saxton, and Fienup. Despite the widespread use of the algorithms proposed by these three researchers, current mathematical theory cannot explain their remarkable success. Nevertheless, great insight can be gained into the behavior, the shortcomings, and the performance of these algorithms from their possible counterparts in convex optimization theory. An important step in this direction was made two decades ago when the error reduction algorithm was identified as a nonconvex alternating projection algorithm. Our purpose is to formulate the phase retrieval problem with mathematical care and to establish new connections between well-established numerical phase retrieval schemes and classical convex optimization methods. Specifically, it is shown that Fienup's basic input-output algorithm corresponds to Dykstra's algorithm and that Fienup's hybrid input-output algorithm can be viewed as an instance of the Douglas-Rachford algorithm. We provide a theoretical framework to better understand and, potentially, to improve existing phase recovery algorithms.

Journal Article↗

Classification of problems, clinical findings and treatment goals in patients with low back pain using the ICIDH-2 beta-2.

PURPOSE: This study aimed to explore problems, clinical findings and treatment goals presented by patients with low back pain and their physiotherapists, and to which extent this information could be classified according to the ICIDH-2 Beta-2. METHOD: An explorative field trial of 12 physiotherapists and 28 patients with low back pain in outpatient practices. RESULTS: Pain and impairments related to muscles, joints and structures of the lower back, pelvis and hips were most often presented. Functioning related to daily activities and participation in society was often described in the treatment goals, but vaguely formulated. Most of the problems and clinical findings could be classified according to the ICIDH-2 Beta-2. However, several treatment goals could not be classified. CONCLUSIONS: There was a lack of specification in several of the detailed codes of the Body, Function and Structure Dimension, particularly regarding classification of pain and muscle functions. The main limitation concerned the detailed version of the Body Function and Structure Dimension, which provided no additional precision compared with the short version when classifying pain and other impairments. However, the ICIDH-2 offers a tool to enhance the precision of clinical findings and the possibilities for performing a multidimensional evaluation of functioning related to patients with low back pain.

Adult↗

Improving the accuracy of the boundary element method by the use of second-order interpolation functions.

The boundary element method (BEM) is a widely used method to solve biomedical electromagnetic volume conduction problems. The commonly used formulation of this method uses constant interpolation functions for the potential and flat triangular surface elements. Linear interpolation for the potential on a flat triangular mesh turned out to yield a better accuracy. In this paper, we introduce quadratic interpolation functions for the potential and quadratically curved surface elements, resulting from second-order spatial interpolation. Theoretically, this results in an accuracy that is inversely proportional to the third power of element size. The method is tested on a four concentric sphere geometry, representative for electroencephalogram modeling, and compared to previous solutions of this problem in literature. In addition, a cylindrical test configuration is used. We conclude that the use of quadratic interpolation functions for the potential and of quadratically curved surface elements in BEM results in a significant increase in accuracy and in some cases even a reduction of the computation time with the same number of nodes involved in the calculations.

Algorithms↗

[Ethical observations concerning the limitations of medical duty to treat in severely handicapped neonates].

The author places the new treatment options of neonatal intensive care units into the framework of modern medicine in general. Paradoxical situations emerge. In one section of the hospital, premature newborn babies are treated in the intensive-care unit, and in another section others are selected for abortion. A late interruption is often an early labour and delivery. The right to live for every person is formulated in the text. The problems concerning viability and perspectives for life of premature or handicapped newborn babies makes it impossible to formulate a list of situations in which the duty to treat can be disregarded. The only treatment limit is complete brain-death. The parents of the child are the ones most affected by its disabilities; therefore, they must be included in the process of decision-making. There is no right for a healthy child, but a right of the child for acceptance and appropriate care by parents and a stable society.

Child Advocacy↗

In vitro disintegration and dissolution and in vivo bioequivalence of two alendronate once-weekly formulations.

Bioequivalence of two tablet formulations of 70 mg alendronate (CAS 121268-17-5) was assessed in a single-dose, open-label, randomised, fasted state crossover trial, with a washout period of 21 days, in 80 healthy subjects. Urine samples were collected up to +36 h post dosing and the concentrations of alendronic acid were assessed using a high-performance liquid chromatographic method with pre-derivatization and fluorescence detection (HPLC/FL) method. The 90 % confidence intervals (90 % CI) obtained for Ae0-36 (cumulative urinary excretion) and Rmax (maximum rate of urinary excretion) were 98.67-118.99 % and 102.22-122.46 %, respectively. The intra-subject coefficient of variation was between 32-35 % for both parameters. No relevant tolerability problems were detected. Both formulations can be considered bioequivalent. In vitro testing was performed to confirm the adequacy of the quality control conditions and no significant differences were detected neither in the disintegration test nor in the dissolution tests conducted in HCl 0.1 N and H2O and thus in these conditions the lack of statistically significant differences in vitro was accompanied by in vivo bioequivalence.

Adult↗

Problem-based case study to enhance critical thinking in student nurses.

The use of traditional teaching methods, for example the lecture method, does not stimulate critical thinking in student nurses. This problem can be solved by the utilisation of problem-based case study in the classroom/clinical setting. The purpose of this study is to describe guidelines for the implementation of problem-based case study in a clinical setting among first year, comprehensive course students at the Northern Province College of Nursing: Sovenga campus. The research design of this study was qualitative, explorative, descriptive and contextual and was conducted in the following phases: Phase 1: The development and implementation of a program for problem-based case study in the clinical setting; Phase II: The experiences of student nurses who were exposed to problem-based case study in the clinical setting; Phase III: The perceptions of tutors regarding the implementation of problem-based case study in the clinical setting (focus group), and; ase IV: Guidelines for the implementation of problem-based case study. The data from Phases I, II and III were used to formulate guidelines for the implementation of problem-based case study. The sample group consisted of all 69 first year student nurses at the Northern Province College of Nursing: Sovenga campus and ten tutors teaching clinical courses at the same campus. The Tesch (1990) approach is used for data analysis. Nine guidelines for the implementation of a problem-based case study approach were formulated and recommendations for development of an instrument to measure critical thinking in nursing were recommended.

Curriculum↗

Some boundary problems in electrical impedance tomography.

Accurate mathematical modelling is important in the development of iterative image reconstruction algorithms for electrical impedance tomography (EIT). In such schemes the forward problem of calculating the electric potential from Neumann boundary data is solved many times. One aspect of this problem which has received some attention is the mathematical modelling of the electrodes used in the technique. In this paper we describe an integral equation formulation of a boundary value problem associated with this tissue and we indicate some of the ways in which this formulation can be used to obtain numerical and analytic results.

Algorithms↗

Prioritizing global conservation efforts.

One of the most pressing issues facing the global conservation community is how to distribute limited resources between regions identified as priorities for biodiversity conservation. Approaches such as biodiversity hotspots, endemic bird areas and ecoregions are used by international organizations to prioritize conservation efforts globally. Although identifying priority regions is an important first step in solving this problem, it does not indicate how limited resources should be allocated between regions. Here we formulate how to allocate optimally conservation resources between regions identified as priorities for conservation--the 'conservation resource allocation problem'. Stochastic dynamic programming is used to find the optimal schedule of resource allocation for small problems but is intractable for large problems owing to the "curse of dimensionality". We identify two easy-to-use and easy-to-interpret heuristics that closely approximate the optimal solution. We also show the importance of both correctly formulating the problem and using information on how investment returns change through time. Our conservation resource allocation approach can be applied at any spatial scale. We demonstrate the approach with an example of optimal resource allocation among five priority regions in Wallacea and Sundaland, the transition zone between Asia and Australasia.

Algorithms↗

Which prophylactic aspirin?

Low doses of aspirin are now a standard part of the management of patients with thromboembolic disease. One risk of taking even low doses is bleeding from the gut, and various aspirin formulations are marketed with claims that they reduce this problem. In this article we review the formulations available and consider their relative safety.

Aspirin↗

Idiographic formulations, symbols, narratives, context and meaning.

To locate the place of idiographic, narrative formulations in a psychiatric nosology and to address the problems stemming from the absence of such formulations in ICD-10 and DSM-IV, the author begins with a review of the stated goals of DSM-IV: that it should serve clinical, research, educational and information-management purposes. He argues that there is a conflict between the clinical and research goals of both manuals and that, with their emphasis on categorical diagnoses, criteria sets and statistical reliability, they serve the purposes of the biomedically oriented researcher better than those of the clinician. The latter is focused on the individual patient and tends in his diagnostic assessment toward a narrative fleshing out of the particulars of the patient's life and personality. Clinicians do not work with tight criteria sets but rather with a prototypal or ideal-type approach, and they emphasize individual histories, psychodynamic formulations and other kinds of idiographic accounts. If a psychiatric nosology is to serve as a clinically useful instrument, it will have to allow for such formulations. The author then offers a description and definition of idiographic, narrative formulations, along with remarks on the conceptual background to this approach. He concludes by highlighting the work of the workgroup of the World Psychiatric Association in developing a section of their International Guidelines for Diagnostic Assessment entitled 'Idiographic (personalised) Diagnostic Formulation'.

Diagnostic and Statistical Manual of Mental Disord↗

[Ischio-vertebral dysplasia (a dangerous syndrome for the spinal cord)].

PURPOSE OF STUDY: A previously unreported condition is defined, diagnostic features identified, and clinical course and treatment modalities presented. MATERIAL AND METHODS: This is a retrospective study of 11 patients with ischio-vertebral dysplasia (IVD), accomplished by record and radiographic review. RESULTS: 11 patients were included in the study group, age at presentation from 1 day to 33 yrs. Follow-up ranged from 5-30 yrs. Involvement of 3 successive generations (grandmother, mother and daughter) with similar findings was present in 1 family. Common features of IVD include: peculiar facies incomplete ossification of the ischial ramus, and a dysplasic scoliosis with a significant kyphotic element, constituting a rotatory dislocation. 2 patients followed from birth demonstrated the natural history of the condition, beginning without spinal deformity, and progressing to significant deformity. The spinal deformity was manageable surgically. The scoliosis ranged from 10 degrees to 235 degrees, and the kyphosis from 0 degrees to 200 degrees (the 10 and 0 being at day 1 of age). 6 patients incurred neurological sequelae, either spontaneously or associated with surgical treatment. 2 patients died, 1 due to cardiopulmonary failure at age 33; the 2nd was an infant with severe neurologic and cardiopulmonary complications due to the spinal deformity. Multiple surgical approaches to the problems were employed. Analysis of results permitted formulation of a logical and successful approach to the problem. Pre-op mean kyphosis = 112 degrees, post-op at maximum follow-up = 67 degrees. Deformity stabilization and neurologic normalcy was produced in every patient operated but 1. DISCUSSION: The characteristics of the syndrome are clear, as is the progressive nature of the deformity. The very high risk of neurologic involvement is emphasized. Before age 10, circumferencial fusion prevents progression and neurologic deterioration. Older patients require gradual correction by skeletal traction, followed by anterior concave strut stabilization and posterior fusion (with or without instrumentation). Extreme care is necessary for protection of the particularly vulnerable neurologic structures. Early stabilization and correction is recommended for prevention of the deterioration of cardiopulmonary function.

Abnormalities, Multiple↗

A neural network approach to breast cancer diagnosis as a constraint satisfaction problem.

A constraint satisfaction neural network (CSNN) approach is proposed for breast cancer diagnosis using mammographic and patient history findings. Initially, the diagnostic decision to biopsy was formulated as a constraint satisfaction problem. Then, an associative memory type neural network was applied to solve the problem. The proposed network has a flexible, nonhierarchical architecture that allows it to operate not only as a predictive tool but also as an analysis tool for knowledge discovery of association rules. The CSNN was developed and evaluated using a database of 500 nonpalpable breast lesions with definitive histopathological diagnosis. The CSNN diagnostic performance was evaluated using receiver operating characteristic analysis (ROC). The results of the study showed that the CSNN ROC area index was 0.84+/-0.02. The CSNN predictive performance is competitive with that achieved by experienced radiologists and backpropagation artificial neural networks (BP-ANNs) presented before. Furthermore, the study illustrates how CSNN can be used as a knowledge discovery tool overcoming some of the well-known limitations of BP-ANNs.

Age Factors↗

[The formulation aspects of drug liberation].

Author raised problems and showed through research data some simple possibilities to achieve controlled release drug liberation. The dosage form developed during drug formulation work may influence the biological effects exerted by the active ingredients and therefore may alter the therapeutic efficacy, too. The dosage from itself includes all the chemical properties of active ingredients (salt-, ester form, polar-apolar material etc.), the physical state (crystal, amorphous, polymorphous, particle size, surface area, solvated state etc.), the value of stability and the parameters of auxiliary materials and manufacturing processes. The aim of formulation -among others-is to achieve the optimal liberation and bioavailability of drugs. The article reviews the possibilities through examples (theophylline, nitrofurantoin, phenacetin, antacids) how to make production prescriptions with high reproducibility used for the preparation of prolonged action systems with controlled release drug liberation.

Antacids↗

Bayesian parallel imaging with edge-preserving priors.

Existing parallel MRI methods are limited by a fundamental trade-off in that suppressing noise introduces aliasing artifacts. Bayesian methods with an appropriately chosen image prior offer a promising alternative; however, previous methods with spatial priors assume that intensities vary smoothly over the entire image, resulting in blurred edges. Here we introduce an edge-preserving prior (EPP) that instead assumes that intensities are piecewise smooth, and propose a new approach to efficiently compute its Bayesian estimate. The estimation task is formulated as an optimization problem that requires a nonconvex objective function to be minimized in a space with thousands of dimensions. As a result, traditional continuous minimization methods cannot be applied. This optimization task is closely related to some problems in the field of computer vision for which discrete optimization methods have been developed in the last few years. We adapt these algorithms, which are based on graph cuts, to address our optimization problem. The results of several parallel imaging experiments on brain and torso regions performed under challenging conditions with high acceleration factors are shown and compared with the results of conventional sensitivity encoding (SENSE) methods. An empirical analysis indicates that the proposed method visually improves overall quality compared to conventional methods.

Algorithms↗

Optimal choice of prognostic variables with an application to cardiac monitoring using M-mode echocardiography.

This paper provides a methodology for the optimal choice of a subset from a large number of interrelated diagnostic variables. We use predetermined abnormal ranges for each measurement and code subjects as abnormal or normal on this basis. We present a procedure to determine the smallest subset of measurements that identifies any subject abnormal on at least one measurement. We formulate and solve the problem using integer programming. We then apply this methodology to study the use of M-mode echocardiography to determine potentially cardiotoxic side effects of chemotherapy and compare its performance to several multivariate methods. Extensions and modifications are discussed.

Child↗