Patient-specific modellling of cortical spreading depression applied to migraine studies.

254 p.-La migraña es un trastorno neurológico muy común. Un tercio de los pacientes que sufren migraña experimentan lo que se denomina aura, una serie de alteraciones sensoriales que preceden al típico dolor de cabeza unilateral. Diversos estudios apuntan a la existencia de una correlación entre el aura visual y la depresión cortical propagada (DCP), una onda de despolarización que tiene su origen en el córtex visual para propagarse, a continuación, por todo el córtex hacia las zonas periféricas. La complejidad y la elevada especificidad de las características del córtex cerebral sugieren que la geometría podría tener un impacto significativo en la propagación de la DCP. En esta tesis hemos combinado dos modelos existentes: un modelo neurológico pormenorizado para el componente electrofisiológico de la DCP y un modelo de reacción-difusión que tiene en consideración la difusión del potasio, el impulsor de la propagación de la DCP. Durante el proceso, hemos integrado dos aspectos de la DCP que tienen lugar en diferentes escalas de tiempo: la dinámica electrofisiológica seguiría un patrón temporal del orden de milisegundos, mientras que la dinámica del potasio extracelular que acciona las funciones de propagación de la DCP se mediría en una escala de minutos. Como resultado, obtendremos un modelo multiescalar EDP-EDO. Asimismo, hemos incorporado los datos específicos del paciente en el modelo DCP: (i) la geometría cerebral específica de un paciente obtenida a través de resonancia magnética, y (ii) los tensores de conductividad personalizados obtenidos a través de diffusion tensor images. A fin de estudiar el papel que desempeña la geometría en la propagación de la DCP, hemos definido las cantidades de interés (CdI) relacionadas con la geometría y las que dependen de la DCP y las hemos evaluado en dos casos prácticos. Si bien la geometría no parece tener un impacto significativo en la propagación de la DCP, algunas CdI han resultado ser unas candidatas muy prometedoras para facilitar la clasificación de individuos sanos y pacientes con migraña. Finalmente, para justificar la carencia de datos experimentales para la validación y selección de los parámetros del modelo, hemos aplicado diversas técnicas de cuantificación de la incertidumbre al modelo DCP y hemos analizado el impacto de las diversas elecciones de parámetros en el resultado del modelo.Migraine is a common neurological disorder and one-third of migraine patients suffer from migraine aura, a perceptual disturbance preceding the typically unilateral headache. Cortical spreading depression (CSD), a depolarisation wave that originates in the visual cortex and propagates across the cortex to the peripheral areas, has been suggested as a correlate of visual aura by several studies. The complex and highly individual-specific characteristics of the brain cortex suggest that the geometry might have a significant impact on CSD propagation. In this thesis, we combine two existing models, a detailed neurological model for the electrophysiological component of CSD and a reaction-diffusion model accounting for the potassium diffusion, the driving force of CSD propagation. In the process, we integrate two aspects of CSD that occur at different time scales: the electrophysiological dynamics features a temporal scale in the order of milliseconds, while the extracellular potassium dynamics that triggers CSD propagation features is on the scale of minutes. As a result we obtain a multi-scale PDE-ODE model. In addition, we incorporate patient-specific data in the CSD model: (i) a patient-specific brain geometry obtained from magnetic resonance imaging, and (ii) personalised conductivity tensors derived from diffusion tensor imaging data. To study the role of the geometry in CSD propagation, we define geometric and CSD-dependent quantities of interest (QoI) that we evaluate in two case studies. Even though the geometry does not seem to have a major impact on the CSD propagation, some QoI are promising candidates to aid in the classification of healthy individuals and migraine patients. Finally, to account for the lack of experimental data for validation and selection of the model parameters, we apply different techniques of uncertainty quantification to the CSD model and analyse the impact of various parameter choices on the model outcom

Voluntary Clawback Adoption and the Use of Financial Measures in CFO Bonus Plans

Firms trade-off CFOs’ fiduciary duties against their decision-making duties when designing CFO bonus plans. Decreasing bonus incentives tied to financial measures benefits CFOs’ fiduciary responsibilities at the expense of motivating their decision making duties. As prior research indicates that clawbacks increase personal misreporting costs through the loss of previously awarded compensation, we examine whether clawbacks allow firms to increase incentives in CFO bonus contracts. Based on a sample of U.S. firms between 2007 and 2013, we find that clawbacks are associated with greater CFO bonus incentives. We also find the increase in incentives to be more pronounced for CFOs relative to other executives. Our results are moderated by firms’ susceptibility to misreporting. The relation between clawbacks and incentives is weaker when firms experienced internal control deficiencies, have larger abnormal accruals, when CFOs are more vulnerable to pressure from CEOs, and when audit committees have less financial expertise and prestige

Multisensory Integration Sites Identified by Perception of Spatial Wavelet Filtered Visual Speech Gesture Information

Perception of speech is improved when presentation of the audio signal is accompanied by concordant visual speech gesture information. This enhancement is most prevalent when the audio signal is degraded. One potential means by which the brain affords perceptual enhancement is thought to be through the integration of concordant information from multiple sensory channels in a common site of convergence, multisensory integration (MSI) sites. Some studies have identified potential sites in the superior temporal gyrus/sulcus (STG/S) that are responsive to multisensory information from the auditory speech signal and visual speech movement. One limitation of these studies is that they do not control for activity resulting from attentional modulation cued by such things as visual information signaling the onsets and offsets of the acoustic speech signal, as well as activity resulting from MSI of properties of the auditory speech signal with aspects of gross visual motion that are not specific to place of articulation information. This fMRI experiment uses spatial wavelet bandpass filtered Japanese sentences presented with background multispeaker audio noise to discern brain activity reflecting MSI induced by auditory and visual correspondence of place of articulation information that controls for activity resulting from the above-mentioned factors. The experiment consists of a low-frequency (LF) filtered condition containing gross visual motion of the lips, jaw, and head without specific place of articulation information, a midfrequency (MF) filtered condition containing place of articulation information, and an unfiltered (UF) condition. Sites of MSI selectively induced by auditory and visual correspondence of place of articulation information were determined by the presence of activity for both the MF and UF conditions relative to the LF condition. Based on these criteria, sites of MSI were found predominantly in the left middle temporal gyrus (MTG), and the left STG/S (including the auditory cortex). By controlling for additional factors that could also induce greater activity resulting from visual motion information, this study identifies potential MSI sites that we believe are involved with improved speech perception intelligibility

Innovative stored plant products in Germany and the potential threat by native and invasive pest insects: Presentation

Climate change, economic-political developments as well as new trends in diet and in bio-economy considerably influence the assortment of cultivated plants in Germany and thereby, determine the plant products which have to be stored after harvest. In the light of the International Year of Pulses 2016 and also, as a result of the European Soya Declaration, the acreage cultivated with new plants such as pulses, stress tolerant wheat varieties and also oil seed rape expanded worldwide. Due to increasing stocks of novel commodities, the emergence of economically important insects infesting stored products and the possible risk caused by native and invasive pest species have to be generally considered during storage. In this overall context, we studied the capacity of various stored-product pest insects to infest two important pulses. In laboratory tests different varieties of soy and lupine have been offered as whole seeds, grist and flour to selected moth and beetle species common in Germany. Over 14 weeks we examined the developmental time from egg to eclosion as well as the number of adults in the F1 generation compared to control insects reared on their standard feeding substrate. First findings under laboratory conditions (20-25 °C, 65-70 % RH) indicate that these innovative stored products, and in particular its simply processed plant products are highly susceptible to moths (i.a. Ephestia elutella, Plodia interpunctella) and to a much lesser extent also to some beetle species (i.a. Callosobruchus chinensis, Tribolium confusum), but the usally recommended optimal storage conditions (T = 16 °C, RH = 65%) can prevent a loss of volume and quality.Climate change, economic-political developments as well as new trends in diet and in bio-economy considerably influence the assortment of cultivated plants in Germany and thereby, determine the plant products which have to be stored after harvest. In the light of the International Year of Pulses 2016 and also, as a result of the European Soya Declaration, the acreage cultivated with new plants such as pulses, stress tolerant wheat varieties and also oil seed rape expanded worldwide. Due to increasing stocks of novel commodities, the emergence of economically important insects infesting stored products and the possible risk caused by native and invasive pest species have to be generally considered during storage. In this overall context, we studied the capacity of various stored-product pest insects to infest two important pulses. In laboratory tests different varieties of soy and lupine have been offered as whole seeds, grist and flour to selected moth and beetle species common in Germany. Over 14 weeks we examined the developmental time from egg to eclosion as well as the number of adults in the F1 generation compared to control insects reared on their standard feeding substrate. First findings under laboratory conditions (20-25 °C, 65-70 % RH) indicate that these innovative stored products, and in particular its simply processed plant products are highly susceptible to moths (i.a. Ephestia elutella, Plodia interpunctella) and to a much lesser extent also to some beetle species (i.a. Callosobruchus chinensis, Tribolium confusum), but the usally recommended optimal storage conditions (T = 16 °C, RH = 65%) can prevent a loss of volume and quality

Geometry shapes propagation: Assessing the presence and absence of cortical symmetries through a computational model of cortical spreading depression

Cortical spreading depression (CSD), a depolarization wave which originates in the visual cortex and travels toward the frontal lobe, has been suggested to be one neural correlate of aura migraine. To the date, little is known about the mechanisms which can trigger or stop aura migraine. Here, to shed some light on this problem and, under the hypothesis that CSD might mediate aura migraine, we aim to study different aspects favoring or disfavoring the propagation of CSD. In particular, by using a computational neuronal model distributed throughout a realistic cortical mesh, we study the role that the geometry has in shaping CSD. Our results are two-fold: first, we found significant differences in the propagation traveling patterns of CSD, both intra and inter-hemispherically, revealing important asymmetries in the propagation profile. Second, we developed methods able to identify brain regions featuring a peculiar behavior during CSD propagation. Our study reveals dynamical aspects of CSD, which, if applied to subject-specific cortical geometry, might shed some light on how to differentiate between healthy subjects and those suffering migraine

Clinical correlates of mathematical modeling of cortical spreading depression: Single‐cases study

Introduction: Considerable connections between migraine with aura and cortical spreading depression (CSD), a depolarization wave originating in the visual cortex and traveling toward the frontal lobe, lead to the hypothesis that CSD is underlying migraine aura. The highly individual and complex characteristics of the brain cor‐ tex suggest that the geometry might impact the propagation of cortical spreading depression. Methods: In a single‐case study, we simulated the CSD propagation for five migraine with aura patients, matching their symptoms during a migraine attack to the CSD wavefront propagation. This CSD wavefront was simulated on a patient‐specific tri‐ angulated cortical mesh obtained from individual MRI imaging and personalized dif‐ fusivity tensors derived locally from diffusion tensor imaging data. Results: The CSD wave propagation was simulated on both hemispheres, despite in all but one patient the symptoms were attributable to one hemisphere. The CSD wave diffused with a large wavefront toward somatosensory and prefrontal regions, devoted to pain processing. Discussion: This case‐control study suggests that the cortical geometry may con‐ tribute to the modality of CSD evolution and partly to clinical expression of aura symptoms. The simulated CSD is a large and diffuse phenomenon, possibly capa‐ ble to activate trigeminal nociceptors and to involve cortical areas devoted to pain processing

Isolation of the Two Monoferric Human Transferrins by Preparative Isoelectric Focussing

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