Predictive gene lists for breast cancer prognosis: a topographic visualisation study

Background: The controversy surrounding the non-uniqueness of predictive gene lists (PGL) of small selected subsets of genes from very large potential candidates as available in DNA microarray experiments is now widely acknowledged 1. Many of these studies have focused on constructing discriminative semi-parametric models and as such are also subject to the issue of random correlations of sparse model selection in high dimensional spaces. In this work we outline a different approach based around an unsupervised patient-specific nonlinear topographic projection in predictive gene lists. Methods: We construct nonlinear topographic projection maps based on inter-patient gene-list relative dissimilarities. The Neuroscale, the Stochastic Neighbor Embedding(SNE) and the Locally Linear Embedding(LLE) techniques have been used to construct two-dimensional projective visualisation plots of 70 dimensional PGLs per patient, classifiers are also constructed to identify the prognosis indicator of each patient using the resulting projections from those visualisation techniques and investigate whether a-posteriori two prognosis groups are separable on the evidence of the gene lists. A literature-proposed predictive gene list for breast cancer is benchmarked against a separate gene list using the above methods. Generalisation ability is investigated by using the mapping capability of Neuroscale to visualise the follow-up study, but based on the projections derived from the original dataset. Results: The results indicate that small subsets of patient-specific PGLs have insufficient prognostic dissimilarity to permit a distinction between two prognosis patients. Uncertainty and diversity across multiple gene expressions prevents unambiguous or even confident patient grouping. Comparative projections across different PGLs provide similar results. Conclusion: The random correlation effect to an arbitrary outcome induced by small subset selection from very high dimensional interrelated gene expression profiles leads to an outcome with associated uncertainty. This continuum and uncertainty precludes any attempts at constructing discriminative classifiers. However a patient's gene expression profile could possibly be used in treatment planning, based on knowledge of other patients' responses. We conclude that many of the patients involved in such medical studies are intrinsically unclassifiable on the basis of provided PGL evidence. This additional category of 'unclassifiable' should be accommodated within medical decision support systems if serious errors and unnecessary adjuvant therapy are to be avoided.

Eye movement analysis in congenital nystagmus:concise parameters estimation

Along with other diseases that can affect binocular vision, reducing the visual quality of a subject, Congenital Nystagmus (CN) is of peculiar interest. CN is an ocular-motor disorder characterized by involuntary, conjugated ocular oscillations and, while identified more than forty years ago, its pathogenesis is still under investigation. This kind of nystagmus is termed congenital (or infantile) since it could be present at birth or it can arise in the first months of life. The majority of CN patients show a considerable decrease of their visual acuity: image fixation on the retina is disturbed by nystagmus continuous oscillations, mainly horizontal. However, the image of a given target can still be stable during short periods in which eye velocity slows down while the target image is placed onto the fovea (called foveation intervals). To quantify the extent of nystagmus, eye movement recordings are routinely employed, allowing physicians to extract and analyze nystagmus main features such as waveform shape, amplitude and frequency. Use of eye movement recording, opportunely processed, allows computing "estimated visual acuity" predictors, which are analytical functions that estimate expected visual acuity using signal features such as foveation time and foveation position variability. Hence, it is fundamental to develop robust and accurate methods to measure both those parameters in order to obtain reliable values from the predictors. In this chapter the current methods to record eye movements in subjects with congenital nystagmus will be discussed and the present techniques to accurately compute foveation time and eye position will be presented. This study aims to disclose new methodologies in congenital nystagmus eye movements analysis, in order to identify nystagmus cycles and to evaluate foveation time, reducing the influence of repositioning saccades and data noise on the critical parameters of the estimation functions. Use of those functions extends the information acquired with typical visual acuity measurement (e.g., Landolt C test) and could be a support for treatment planning or therapy monitoring. © 2010 by Nova Science Publishers, Inc. All rights reserved.

Differential gains from Business Link support and advice:a treatment effects approach

The provision of advisory support to small firms is almost ubiquitous in OECD countries, although it is organised in different ways and is justified on slightly different grounds. In England publicly supported advisory services are provided through the Business Link (BL) network. Here, we consider two questions: what sort of companies receive advisory support from BL; and, what types of firms benefit most from that support? Our analysis is based on a telephone survey of 2000 firms, around half of which had received intensive assistance from BL between April and October 2003. Probit analysis suggests that the probability of receiving assistance was greater among younger businesses, those with larger numbers of directors in the firm, and those with more gender diversity among the firm's leadership team. Our business-growth models suggest that BL intensive assistance was having a positive effect on employment growth in 2003. BL had a positive but insignificant impact on sales growth over the period. Employment growth effects tend to be larger where firms have a management and organisational structure, which is more conducive to absorbing and making use of external advice. The analysis suggests that BL might increase its impact through targeting these larger, more export-orientated, businesses. Employment growth effects differ little, however, depending on either the ethnic or the gender diversity of the leadership team.

Ambulatory EEG monitoring in the diagnosis and treatment of epilepsy and related disorders

Ambulatory EEG recording enables patients with epilepsy and related disorders to be monitored in an unrestricted environment for prolonged periods. Attacks can therefore be recorded and EEG changes at the time can aid diagnosis. The relevant Iiterature is reviewed and a study made of' 250 clinical investigations. A study was also made of the artefacts,encountered during ambulatory recording. Three quarters of referrals were for distinguishing between epileptic and non-epileptic attacks. Over 60% of patients showed no abnormality during attacks. In comparison with the basic EEG the ambulatory EEG provided about ten times as much information. A preliminary follow-up study showed that results, of ambulatory monitoring agreed with the final diagnosis in 8 of 12 patients studied. Of 10 patients referred, for monitoring the occurrence of absence seizures, 8 showed abnormality during the baslcJ EEG .and 10 during the ambulatory EEG. Other patients. were referred: for sleep recording and to clarify the seizure type. An investigation into once daily (OD) versus twice daily administration of sodium valproate in patients with absence seizures showed that an OD regime was equally as effective as a BD regime. Circadian variations in spike and wave activity in patients on and off treatment were also examined. There was significant agreement between subjects on the time of occurrence of abnormality during sleep only, This pattern was not ,affected with treatment nor was there any difference in the daily pattern of occurrence of abnormality between the two regimes. Overall findings suggested that ambulatory monitoring was a valuable tool in the diagnosis and treatment of epilepsy which with careful planning and patient selection could be used in any EEG department and would benefit a:wide range of patients.