Bumps and rings in a two-dimensional neural field: splitting and rotational instabilities

In this paper we consider instabilities of localised solutions in planar neural field firing rate models of Wilson-Cowan or Amari type. Importantly we show that angular perturbations can destabilise spatially localised solutions. For a scalar model with Heaviside firing rate function we calculate symmetric one-bump and ring solutions explicitly and use an Evans function approach to predict the point of instability and the shapes of the dominant growing modes. Our predictions are shown to be in excellent agreement with direct numerical simulations. Moreover, beyond the instability our simulations demonstrate the emergence of multi-bump and labyrinthine patterns. With the addition of spike-frequency adaptation, numerical simulations of the resulting vector model show that it is possible for structures without rotational symmetry, and in particular multi-bumps, to undergo an instability to a rotating wave. We use a general argument, valid for smooth firing rate functions, to establish the conditions necessary to generate such a rotational instability. Numerical continuation of the rotating wave is used to quantify the emergent angular velocity as a bifurcation parameter is varied. Wave stability is found via the numerical evaluation of an associated eigenvalue problem

Evaluation of peak-picking algorithms for protein mass spectrometry

Peak picking is an early key step in MS data analysis. We compare three commonly used approaches to peak picking and discuss their merits by means of statistical analysis. Methods investigated encompass signal-to-noise ratio, continuous wavelet transform, and a correlation-based approach using a Gaussian template. Functionality of the three methods is illustrated and discussed in a practical context using a mass spectral data set created with MALDI-TOF technology. Sensitivity and specificity are investigated using a manually defined reference set of peaks. As an additional criterion, the robustness of the three methods is assessed by a perturbation analysis and illustrated using ROC curves

Obtaining reliable information from minute amounts of RNA using cDNA microarrays

BACKGROUND: High density cDNA microarray technology provides a powerful tool to survey the activity of thousands of genes in normal and diseased cells, which helps us both to understand the molecular basis of the disease and to identify potential targets for therapeutic intervention. The promise of this technology has been hampered by the large amount of biological material required for the experiments (more than 50 μg of total RNA per array). We have modified an amplification procedure that requires only 1 μg of total RNA. Analyses of the results showed that most genes that were detected as expressed or differentially expressed using the regular protocol were also detected using the amplification protocol. In addition, many genes that were undetected or weakly detected using the regular protocol were clearly detected using the amplification protocol. We have carried out a series of confirmation studies by northern blotting, western blotting, and immunohistochemistry assays. RESULTS: Our results showed that most of the new information revealed by the amplification protocol represents real gene activity in the cells. CONCLUSION: We have confirmed a powerful and consistent cDNA microarray procedure that can be used to study minute amounts of biological tissue

Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer

Background: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. Results: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. Conclusion: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer

Mass spectrometry data processing using zero-crossing lines in multi-scale of Gaussian derivative wavelet

Motivation: Peaks are the key information in mass spectrometry (MS) which has been increasingly used to discover diseases-related proteomic patterns. Peak detection is an essential step for MS-based proteomic data analysis. Recently, several peak detection algorithms have been proposed. However, in these algorithms, there are three major deficiencies: (i) because the noise is often removed, the true signal could also be removed; (ii) baseline removal step may get rid of true peaks and create new false peaks; (iii) in peak quantification step, a threshold of signal-to-noise ratio (SNR) is usually used to remove false peaks; however, noise estimations in SNR calculation are often inaccurate in either time or wavelet domain. In this article, we propose new algorithms to solve these problems. First, we use bivariate shrinkage estimator in stationary wavelet domain to avoid removing true peaks in denoising step. Second, without baseline removal, zero-crossing lines in multi-scale of derivative Gaussian wavelets are investigated with mixture of Gaussian to estimate discriminative parameters of peaks. Third, in quantification step, the frequency, SD, height and rank of peaks are used to detect both high and small energy peaks with robustness to noise

The medical licensing examination debate

National licensing examinations are typically large-scale examinations taken early in a career or near the point of graduation, and, importantly, success is required to subsequently be able to practice. They are becoming increasingly popular as a method of quality assurance in the medical workforce, but debate about their contribution to patient safety and the improvement of healthcare outcomes continues. A systematic review of the national licensing examination literature demonstrates that there is disagreement between assessment experts about the strengths and challenges of licensing examinations. This is characterized by a trans-Atlantic divide between the dominance of psychometric reliability assurance in North America and the wider interpretations of validity, to include consequences, in Europe. We conclude that the debate might benefit from refocusing to what a national licensing examination should assess: to achieve a balance between assessing a breadth of skills and the capacity for such skills in practice, and focusing less on reproducibility

Magnon dispersion and thermodynamics in CsNiF_3

We present an accurate transfer matrix renormalization group calculation of the thermodynamics in a quantum spin-1 planar ferromagnetic chain. We also calculate the field dependence of the magnon gap and confirm the accuracy of the magnon dispersion derived earlier through an 1/n expansion. We are thus able to examine the validity of a number of previous calculations and further analyze a wide range of experiments on CsNiF_3 concerning the magnon dispersion, magnetization, susceptibility, and specific heat. Although it is not possible to account for all data with a single set of parameters, the overall qualitative agreement is good and the remaining discrepancies may reflect departure from ideal quasi-one-dimensional model behavior. Finally, we present some indirect evidence to the effect that the popular interpretation of the excess specific heat in terms of sine-Gordon solitons may not be appropriate.Comment: 9 pages 10 figure

The International Landscape of Medical Licensing Examinations: A Typology Derived From a Systematic Review

Background National licensing examinations (NLEs) are large-scale examinations usually taken by medical doctors close to the point of graduation from medical school. Where NLEs are used, success is usually required to obtain a license for full practice. Approaches to national licensing, and the evidence that supports their use, varies significantly across the globe. This paper aims to develop a typology of NLEs, based on candidacy, to explore the implications of different examination types for workforce planning. Methods A systematic review of the published literature and medical licensing body websites, an electronic survey of all medical licensing bodies in highly developed nations, and a survey of medical regulators. Results The evidence gleaned through this systematic review highlights four approaches to NLEs: where graduating medical students wishing to practice in their national jurisdiction must pass a national licensing exam before they are granted a license to practice; where all prospective doctors, whether from the national jurisdiction or international medical graduates, are required to pass a national licensing exam in order to practice within that jurisdiction; where international medical graduates are required to pass a licensing exam if their qualifications are not acknowledged to be comparable with those students from the national jurisdiction; and where there are no NLEs in operation. This typology facilitates comparison across systems and highlights the implications of different licensing systems for workforce planning. Conclusion The issue of national licensing cannot be viewed in isolation from workforce planning; future research on the efficacy of national licensing systems to drive up standards should be integrated with research on the implications of such systems for the mobility of doctors to cross borders

Democratization in a passive dendritic tree : an analytical investigation

One way to achieve amplification of distal synaptic inputs on a dendritic tree is to scale the amplitude and/or duration of the synaptic conductance with its distance from the soma. This is an example of what is often referred to as “dendritic democracy”. Although well studied experimentally, to date this phenomenon has not been thoroughly explored from a mathematical perspective. In this paper we adopt a passive model of a dendritic tree with distributed excitatory synaptic conductances and analyze a number of key measures of democracy. In particular, via moment methods we derive laws for the transport, from synapse to soma, of strength, characteristic time, and dispersion. These laws lead immediately to synaptic scalings that overcome attenuation with distance. We follow this with a Neumann approximation of Green’s representation that readily produces the synaptic scaling that democratizes the peak somatic voltage response. Results are obtained for both idealized geometries and for the more realistic geometry of a rat CA1 pyramidal cell. For each measure of democratization we produce and contrast the synaptic scaling associated with treating the synapse as either a conductance change or a current injection. We find that our respective scalings agree up to a critical distance from the soma and we reveal how this critical distance decreases with decreasing branch radius