Understanding the abnormal brain activity in epilepsy as a potential predictor of the onset of an epileptic seizure

The Brain Research Institute (BRI) uses various types of indirect measurements, including EEG and fMRI, to understand and assess brain activity and function. As well as the recovery of generic information about brain function, research also focuses on the utilisation of such data and understanding to study the initiation, dynamics, spread and suppression of epileptic seizures. To assist with the future focussing of this aspect of their research, the BRI asked the MISG 2010 participants to examine how the available EEG and fMRI data and current knowledge about epilepsy should be analysed and interpreted to yield an enhanced understanding about brain activity occurring before, at commencement of, during, and after a seizure. Though the deliberations of the study group were wide ranging in terms of the related matters considered and discussed, considerable progress was made with the following three aspects. (1) The science behind brain activity investigations depends crucially on the quality of the analysis and interpretation of, as well as the recovery of information from, EEG and fMRI measurements. A number of specific methodologies were discussed and formalised, including independent component analysis, principal component analysis, profile monitoring and change point analysis (hidden Markov modelling, time series analysis, discontinuity identification). (2) Even though EEG measurements accurately and very sensitively record the onset of an epileptic event or seizure, they are, from the perspective of understanding the internal initiation and localisation, of limited utility. They only record neuronal activity in the cortical (surface layer) neurons of the brain, which is a direct reflection of the type of electrical activity they have been designed to record. Because fMRI records, through the monitoring of blood flow activity, the location of localised brain activity within the brain, the possibility of combining fMRI measurements with EEG, as a joint inversion activity, was discussed and examined in detail. (3) A major goal for the BRI is to improve understanding about ``when'' (at what time) an epileptic seizure actually commenced before it is identified on an eeg recording, ``where'' the source of this initiation is located in the brain, and ``what'' is the initiator. Because of the general agreement in the literature that, in one way or another, epileptic events and seizures represent abnormal synchronisations of localised and/or global brain activity the modelling of synchronisations was examined in some detail. References C. M. Michel, G. Thut, S. Morand, A. Khateb, A. J. Pegna, R. Grave de Peralta, S. Gonzalez, M. Seeck and T. Landis, Electric source imaging of human brain functions, Brain Res. 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Induction of epithelial-mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent

Signals from the tumor microenvironment trigger cancer cells to adopt an invasive phenotype through epithelial-mesenchymal transition (EMT). Relatively little is known regarding key signal transduction pathways that serve as cytosolic bridges between cell surface receptors and nuclear transcription factors to induce EMT. A better understanding of these early EMT events may identify potential targets for the control of metastasis. One rapid intracellular signaling pathway that has not yet been explored during EMT induction is calcium. Here we show that stimuli used to induce EMT produce a transient increase in cytosolic calcium levels in human breast cancer cells. Attenuation of the calcium signal by intracellular calcium chelation significantly reduced epidermal growth factor (EGF)- and hypoxia-induced EMT. Intracellular calcium chelation also inhibited EGF-induced activation of signal transducer and activator of transcription 3 (STAT3), while preserving other signal transduction pathways such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. To identify calcium-permeable channels that may regulate EMT induction in breast cancer cells, we performed a targeted siRNA-based screen. We found that transient receptor potential-melastatin-like 7 (TRPM7) channel expression regulated EGF-induced STAT3 phosphorylation and expression of the EMT marker vimentin. Although intracellular calcium chelation almost completely blocked the induction of many EMT markers, including vimentin, Twist and N-cadherin, the effect of TRPM7 silencing was specific for vimentin protein expression and STAT3 phosphorylation. These results indicate that TRPM7 is a partial regulator of EMT in breast cancer cells, and that other calcium-permeable ion channels are also involved in calcium-dependent EMT induction. In summary, this work establishes an important role for the intracellular calcium signal in the induction of EMT in human breast cancer cells. Manipulation of calcium-signaling pathways controlling EMT induction in cancer cells may therefore be an important therapeutic strategy for preventing metastases.

Calibration and validation of wearable monitors

Background Wearable monitors are increasingly being used to objectively monitor physical activity in research studies within the field of exercise science. Calibration and validation of these devices are vital to obtaining accurate data. This article is aimed primarily at the physical activity measurement specialist, although the end user who is conducting studies with these devices also may benefit from knowing about this topic. Best Practices Initially, wearable physical activity monitors should undergo unit calibration to ensure interinstrument reliability. The next step is to simultaneously collect both raw signal data (e.g., acceleration) from the wearable monitors and rates of energy expenditure, so that algorithms can be developed to convert the direct signals into energy expenditure. This process should use multiple wearable monitors and a large and diverse subject group and should include a wide range of physical activities commonly performed in daily life (from sedentary to vigorous). Future Directions New methods of calibration now use "pattern recognition" approaches to train the algorithms on various activities, and they provide estimates of energy expenditure that are much better than those previously available with the single-regression approach. Once a method of predicting energy expenditure has been established, the next step is to examine its predictive accuracy by cross-validating it in other populations. In this article, we attempt to summarize the best practices for calibration and validation of wearable physical activity monitors. Finally, we conclude with some ideas for future research ideas that will move the field of physical activity measurement forward.

Opportunities and challenges : combining distance and on-campus students in concurrent courses

Through its Electronic Delivery of Gator Engineering (EDGE) program, University of Florida (UF) offers online master’s degrees from participating departments within the UF College of Engineering. Each master’s degree requires 10 courses (3 credit hours each). One interesting and unique aspect of the EDGE pro-gram is that distance learners are registered concurrently in the same courses with traditional on-campus students. This paper examines the specific challenges involved in integrating distance students into on-campus courses, including communication, interaction, access to resources, and equal grading practices.

A survey in mathematics for industry: Two-timing and matched asymptotic expansions for singular perturbation problems

Following the derivation of amplitude equations through a new two-time-scale method [O'Malley, R. E., Jr. & Kirkinis, E (2010) A combined renormalization group-multiple scale method for singularly perturbed problems. Stud. Appl. Math. 124, 383-410], we show that a multi-scale method may often be preferable for solving singularly perturbed problems than the method of matched asymptotic expansions. We illustrate this approach with 10 singularly perturbed ordinary and partial differential equations. © 2011 Cambridge University Press.

Examples illustrating the use of renormalization techniques for singularly perturbed differential equations

With nine examples, we seek to illustrate the utility of the Renormalization Group approach as a unification of other asymptotic and perturbation methods.

Phosphoprotein pathway mapping: Akt/Mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival

Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized therapy. Despite advances in combination chemotherapy, the overall survival for childhood rhabdomyosarcoma remains ∼60%. A critical goal is to identify functionally important protein signaling defects associated with treatment failure for the 40% nonresponder cohort. Here, we show, by phosphoproteomic network analysis of microdissected tumor cells, that interlinked components of the Akt/mammalian target of rapamycin (mTOR) pathway exhibited increased levels of phosphorylation for tumors of patients with short-term survival. Specimens (n = 59) were obtained from the Children's Oncology Group Intergroup Rhabdomyosarcoma Study (IRS) IV, D9502 and D9803, with 12-year follow-up. High phosphorylation levels were associated with poor overall and poor disease-free survival: Akt Ser473 (overall survival P < 0.001, recurrence-free survival P < 0.0009), 4EBP1 Thr37/46 (overall survival P < 0.0110, recurrence-free survival P < 0.0106), eIF4G Ser1108 (overall survival P < 0.0017, recurrence-free survival P < 0.0072), and p70S6 Thr389 (overall survival P < 0.0085, recurrence-free survival P < 0.0296). Moreover, the findings support an altered interrelationship between the insulin receptor substrate (IRS-1) and Akt/mTOR pathway proteins (P < 0.0027) for tumors from patients with poor survival. The functional significance of this pathway was tested using CCI-779 in a mouse xenograft model. CCI-779 suppressed phosphorylation of mTOR downstream proteins and greatly reduced the growth of two different rhabdomyosarcoma (RD embryonal P = 0.00008; Rh30 alveolar P = 0.0002) cell lines compared with controls. These results suggest that phosphoprotein mapping of the Akt/mTOR pathway should be studied further as a means to select patients to receive mTOR/IRS pathway inhibitors before administration of chemotherapy.

Practical visual odometry for car-like vehicles

A method for calculating visual odometry for ground vehicles with car-like kinematic motion constraints similar to Ackerman's steering model is presented. By taking advantage of this non-holonomic driving constraint we show a simple and practical solution to the odometry calculation by clever placement of a single camera. The method has been implemented successfully on a large industrial forklift and a Toyota Prado SUV. Results from our industrial test site is presented demonstrating the applicability of this method as a replacement for wheel encoder-based odometry for these vehicles.

Clinical and economic outcomes of nutrition interventions across the continuum of care

Optimal nutrition across the continuum of care plays a key role in the short- and long-term clinical and economic outcomes of patients. Worldwide, an estimated one-quarter to one-half of patients admitted to hospitals each year are malnourished. Malnutrition can increase healthcare costs by delaying patient recovery and rehabilitation and increasing the risk of medical complications. Nutrition interventions have the potential to provide cost-effective preventive care and treatment measures. However, limited data exist on the economics and impact evaluations of these interventions. In this report, nutrition and health system researchers, clinicians, economists, and policymakers discuss emerging global research on nutrition health economics, the role of nutrition interventions across the continuum of care, and how nutrition can affect healthcare costs in the context of hospital malnutrition.

Inner-ear morphology of the New Zealand Kiwi (Apteryx mantelli) suggests high-frequency specialization

The sensory systems of the New Zealand kiwi appear to be uniquely adapted to occupy a nocturnal ground-dwelling niche. In addition to well-developed tactile and olfactory systems, the auditory system shows specializations of the ear, which are maintained along the central nervous system. Here, we provide a detailed description of the auditory nerve, hair cells, and stereovillar bundle orientation of the hair cells in the North Island brown kiwi. The auditory nerve of the kiwi contained about 8,000 fibers. Using the number of hair cells and innervating nerve fibers to calculate a ratio of average innervation density showed that the afferent innervation ratio in kiwi was denser than in most other birds examined. The average diameters of cochlear afferent axons in kiwi showed the typical gradient across the tonotopic axis. The kiwi basilar papilla showed a clear differentiation of tall and short hair cells. The proportion of short hair cells was higher than in the emu and likely reflects a bias towards higher frequencies represented on the kiwi basilar papilla. The orientation of the stereovillar bundles in the kiwi basilar papilla showed a pattern similar to that in most other birds but was most similar to that of the emu. Overall, many features of the auditory nerve, hair cells, and stereovilli bundle orientation in the kiwi are typical of most birds examined. Some features of the kiwi auditory system do, however, support a high-frequency specialization, specifically the innervation density and generally small size of hair-cell somata, whereas others showed the presumed ancestral condition similar to that found in the emu.

Morphometric analysis of telencephalic structure in a variety of neognath and paleognath bird species reveals regional differences associated with specific behavioral traits

Birds exhibit a huge array of behavior, ecology and physiology, and occupy nearly every environment on earth, ranging from the desert outback of Australia to the tropical rain forests of Panama. Some birds have adopted a fully nocturnal lifestyle, such as the barn owl and kiwi, while others, such as the albatross, spend nearly their entire life flying over the ocean. Each species has evolved unique adaptations over millions of years to function in their respective niche. In order to increase processing power or network efficiency, many of these adaptations require enlargements and/or specializations of the brain as a whole or of specific brain regions. In this study, we examine the relative size and morphology of 9 telencephalic regions in a number of Paleognath and Neognath birds and relate the findings to differences in behavior and sensory ecology. We pay particular attention to those species that have undergone a relative enlargement of the telencephalon to determine whether this relative increase in telencephalic size is homogeneous across different brain regions or whether particular regions have become differentially enlarged. The analysis indicates that changes in the relative size of telencephalic regions are not homogeneous, with every species showing hypertrophy or hypotrophy of at least one of them. The three-dimensional structure of these regions in different species was also variable, in particular that of the mesopallium in kiwi. The findings from this study provide further evidence that the changes in relative brain size in birds reflect a process of mosaic evolution.

Evolution of brain size in the palaeognath lineage, with an emphasis on New Zealand ratites

Brain size in vertebrates varies principally with body size. Although many studies have examined the variation of brain size in birds, there is little information on Palaeognaths, which include the ratite lineage of kiwi, emu, ostrich and extinct moa, as well as the tinamous. Therefore, we set out to determine to what extent the evolution of brain size in Palaeognaths parallels that of other birds, i. e., Neognaths, by analyzing the variation in the relative sizes of the brain and cerebral hemispheres of several species of ratites and tinamous. Our results indicate that the Palaeognaths possess relatively smaller brains and cerebral hemispheres than the Neognaths, with the exception of the kiwi radiation (Apteryx spp.). The external morphology and relatively large size of the brain of Apteryx, as well as the relatively large size of its telencephalon, contrast with other Palaeognaths, including two species of historically sympatric moa, suggesting that unique selective pressures towards increasing brain size accompanied the evolution of kiwi. Indeed, the size of the cerebral hemispheres with respect to total brain size of kiwi is rivaled only by a handful of parrots and songbirds, despite a lack of evidence of any advanced behavioral/ cognitive abilities such as those reported for parrots and crows. In addition, the enlargement in brain and telencephalon size of the kiwi occurs despite the fact that this is a precocial bird. These findings form an exception to, and hence challenge, the current rules that govern changes in relative brain size in birds. Copyright (c) 2007 S. Karger AG, Basel.

MRI of postmortem specimens of endangered species for comparative brain anatomy

Many of the 5,500 threatened species of vertebrates found worldwide are highly protected and generally unavailable for scientific investigation. Here we describe a noninvasive protocol to visualize the structure and size of brain in postmortem specimens. We demonstrate its utility by examining four endangered species of kiwi (Apteryx spp.). Frozen specimens are thawed and imaged using MRI, revealing internal details of brain structure. External brain morphology and an estimate of brain volume can be reliably obtained by creating 3D models. This method has facilitated a comparison of brain structure in the different kiwi species, one of which is on the brink of extinction. This new approach has the potential to extend our knowledge of brain structure to species that have until now been outside the reach of anatomical investigation.

Interpreting discovered patterns in terms of ontology concepts

Semantic Web offers many possibilities for future Web technologies. Therefore, it is a need to search for ways that can bring the huge amount of unstructured documents from current Web to Semantic Web automatically. One big challenge in searching for such ways is how to understand patterns by both humans and machine. To address this issue, we present an innovative model which interprets patterns to high level concepts. These concepts can explain the patterns' meanings in a human understandable way while improving the information filtering performance. The model is evaluated by comparing it against one state-of-the-art benchmark model using standard Reuters dataset. The results show that the proposed model is successful. The significance of this model is three fold. It gives a way to interpret text mining output, provides a technique to find concepts relevant to the whole set of patterns which is an essential feature to understand the topic, and to some extent overcomes information mismatch and overload problems of existing models. This model will be very useful for knowledge based applications.