Can Zipf's law be adapted to normalize microarrays?

BACKGROUND: Normalization is the process of removing non-biological sources of variation between array experiments. Recent investigations of data in gene expression databases for varying organisms and tissues have shown that the majority of expressed genes exhibit a power-law distribution with an exponent close to -1 (i.e. obey Zipf's law). Based on the observation that our single channel and two channel microarray data sets also followed a power-law distribution, we were motivated to develop a normalization method based on this law, and examine how it compares with existing published techniques. A computationally simple and intuitively appealing technique based on this observation is presented. RESULTS: Using pairwise comparisons using MA plots (log ratio vs. log intensity), we compared this novel method to previously published normalization techniques, namely global normalization to the mean, the quantile method, and a variation on the loess normalization method designed specifically for boutique microarrays. Results indicated that, for single channel microarrays, the quantile method was superior with regard to eliminating intensity-dependent effects (banana curves), but Zipf's law normalization does minimize this effect by rotating the data distribution such that the maximal number of data points lie on the zero of the log ratio axis. For two channel boutique microarrays, the Zipf's law normalizations performed as well as, or better than existing techniques. CONCLUSION: Zipf's law normalization is a useful tool where the Quantile method cannot be applied, as is the case with microarrays containing functionally specific gene sets (boutique arrays)

Dynamic imaging of coherent sources reveals different network connectivity underlying the generation and perpetuation of epileptic seizures

The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone) and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS), an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity) between coherent sources was investigated using the renormalized partial directed coherence (RPDC) method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis

Investigation of Magnetoelectric Sensor Requirements for Deep Brain Stimulation Electrode Localization and Rotational Orientation Detection

Correct position and orientation of a directional deep brain stimulation (DBS) electrode in the patient's brain must be known to fully exploit its benefit in guiding stimulation programming. Magnetoelectric (ME) sensors can play a critical role here. The aim of this study was to determine the minimum required limit of detection (LOD) of a ME sensor that can be used for this application by measuring the magnetic field induced by DBS. For this experiment, a commercial DBS system was integrated into a head phantom and placed inside of a state-of-the-art Superconducting Quantum Interference Device (SQUID)-based magnetoencephalography system. Measurements were performed and analyzed with digital signal processing. Investigations have shown that the minimum required detection limit depends on various factors such as: measurement distance to electrode, bandwidth of magnetic sensor, stimulation amplitude, stimulation pulse width, and measurement duration. For a sensor that detects only a single DBS frequency (stimulation frequency or its harmonics), a LOD of at least 0.04 pT/Hz0.5 is required for 3 mA stimulation amplitude and 60 μμs pulse width. This LOD value increases by an order of magnitude to 0.4 pT/Hz0.5 for a 1 kHz, and by approximately two orders to 3 pT/Hz0.5 for a 10 kHz sensor bandwidth. By averaging, the LOD can be reduced by at least another 2 orders of magnitude with a measurement duration of a few minutes

Влияние волнистости S-образных пружин на точностные характеристики часов

Экспериментальным путем установлено отрицательное влияние волнистости S-образных пружин на точностные характеристики наручных часов. Предложен способ оперативного контроля этого дефекта пружин

Mapping of subthalamic nucleus using microelectrode recordings during deep brain stimulation

Alongside stereotactic magnetic resonance imaging, microelectrode recording (MER) is frequently used during the deep brain stimulation (DBS) surgery for optimal target localization. The aim of this study is to optimize subthalamic nucleus (STN) mapping using MER analytical patterns. 16 patients underwent bilateral STN-DBS. MER was performed simultaneously for 5 microelectrodes in a setting of Ben's-gun pattern in awake patients. Using spikes and background activity several different parameters and their spectral estimates in various frequency bands including low frequency (2-7 Hz), Alpha (8-12 Hz), Beta (sub-divided as Low_Beta (13-20 Hz) and High_Beta (21-30 Hz)) and Gamma (31 to 49 Hz) were computed. The optimal STN lead placement with the most optimal clinical effect/ side-effect ratio accorded to the maximum spike rate in 85% of the implantation. Mean amplitude of background activity in the low beta frequency range was corresponding to right depth in 85% and right location in 94% of the implantation respectively. MER can be used for STN mapping and intraoperative decisions for the implantation of DBS electrode leads with a high accuracy. Spiking and background activity in the beta range are the most promising independent parameters for the delimitation of the proper anatomical site

Associative Stimulation of the Supraorbital Nerve Fails to Induce Timing-Specific Plasticity in the Human Blink Reflex

BACKGROUND: Associative high-frequency electrical stimulation (HFS) of the supraorbital nerve in five healthy individuals induced long-term potentiation (LTP)-like or depression (LTD)-like changes in the human blink reflex circuit according to the rules of spike timing-dependent plasticity (Mao and Evinger, 2001). HFS given at the onset of the R2 component of the blink reflex (HFS(LTP)) produced a lasting facilitation of the R2, whereas HFS given shortly before R2 (HFS(LTD)) caused a lasting suppression of the R2. In patients with benign essential blepharospasm (BEB), a focal dystonia affecting the orbicularis oculi muscles, HFS(LTP) induced excessive LTP-like associative plasticity relative to healthy controls, which was normalized after botulinum toxin (BTX) injections (Quartarone et al, 2006). METHODOLOGY/PRINCIPAL FINDINGS: We used HFS conditioning of the supraorbital nerve to study homeostatic metaplasticity of the blink reflex circuit in healthy subjects and dystonic patients. On separate days, we tested the conditioning effects on the R2 response and paired-pulse R2 inhibition after (i) HFS(LTP), (ii) HFS(LTP) followed by HFS(LTP), and (iii) HFS(LTP) followed by HFS(LTD). Controls also received (iv) HFS(LTD) alone and (v) a non-intervention protocol. In BEB patients, HFS(LTP) followed by HFS(LTD) was given before and after BTX treatment. We were not able to replicate the bidirectional timing-dependent effects of HFS(LTP) and HFS(LTD) alone. All HFS protocols produced a non-specific reduction of the R2 response and a relative decrease in paired-pulse inhibition. These R2 changes also occurred in controls when no HFS was applied. There was also no trace of a homeostatic response pattern in BEB patients before or after BTX treatment. CONCLUSION/SIGNIFICANCE: Our data challenge the efficacy of associative HFS to produce bidirectional plasticity in the human blink reflex circuit. The non-specific decrease of the R2 response might indicate habituation of the blink reflex following repeated electrical supraorbital stimulation. The increase of inhibition after paired pulse stimulation might reflect homeostatic behaviour to prevent further down regulation of the R2 response to preserve the protection of this adverse-effects reflex

Moderate Frequency Resistance and Balance Training Do Not Improve Freezing of Gait in Parkinson's Disease: A Pilot Study

Background and Aim: Individuals with Parkinson's disease (PD) and Freezing of Gait (FOG) have impaired postural control, which relate to the severity of FOG. The aim of this study was to analyze whether a moderate frequency resistance (RT) and balance training (BT), respectively, are effective to diminish FOG.Methods: This post-hoc sub-analysis of a randomized controlled training intervention study of PD patients with and without FOG reports about results from FOG patients. Twelve FOG patients performed RT and 8 BT (training 2x/week, 7 weeks). Testing was performed prior and post intervention. FOG was assessed with the FOG Questionnaire (FOGQ) and with the FOG score of a FOG provoking walking course. Balance performance was evaluated with the Fullerton Advanced Balance (FAB) scale. Tests were conducted by raters blinded to group allocation and assessment time point (only FOG score and FAB scale).Results: For the FOGQ and FOG score, no significant differences were found within and between the two training groups (p > 0.05) and effect sizes for the improvements were small (r < 0.1). Groups did not significantly improve in the FAB scale. FOG score changes and FAB scale changes within the RT group showed a trend toward significant negative correlation (Rho = −0.553, p = 0.098).Conclusions: Moderate frequency RT and BT was not effective in reducing FOG in this pilot study. The trend toward negative correlation between changes in FOG score and FAB scale suggests an interaction between balance (improvement) and FOG (improvement). Future studies should include larger samples and high frequency interventions to investigate the role of training balance performance to reduce the severity of FOG

Mapping the EQ-5D index by UPDRS and PDQ-8 in patients with Parkinson’s disease

Background: Clinical studies employ the Unified Parkinson’s Disease Rating Scale (UPDRS) to measure the severity of Parkinson’s disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates. Methods: Linear and fractional polynomial regression analyses were performed with data from a study of Parkinson’s disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson’s disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R2, the root mean square error (RMS), the Bayesian information criterion, and Pregibon’s link test. Three independent data sets validated the models. Results: The regression analyses resulted in a single best prediction model (R2: 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R2 of 0.60 and 0.67. The independent data confirmed the prediction models. Conclusion: The best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use