Decrease in Propagation of Interictal Epileptiform Activity After Introduction of Levetiracetam Visualized with Electric Source Imaging

Different neuroimaging techniques (fMRI, spectroscopy, PET) are being used to evaluate candidate drugs in pharmacological development. In patients with epilepsy fast propagation of the epileptiform activity between different brain areas occurs. Electric Source Imaging (ESI), in contrast to the aforementioned techniques, has a millisecond time resolution, allowing visualization of this fast propagation. The purpose of the current project was to use ESI to investigate whether introduction of an antiepileptic drug (levetiracetam, LEV) would change the propagation patterns of the interictal epileptiform activity. Thirty patients with epilepsy were subject to an EEG recording before (pre-LEV) and after (in-LEV) introduction of LEV. Interictal spikes with similar topographic distribution were averaged within each subject, and a distributed source model was used to localize the EEG sources of the epileptiform activity. The temporal development of the activity within 20 regions of interest (ROIs) was determined, and source propagation between different regions was compared between the pre-LEV and in-LEV recordings. Patients with epileptic seizures showed propagation in 22/24 identified spike types in the pre-LEV recordings. In the in-LEV recordings only 7/15 spike types showed propagation, and six of these seven propagating spikes were recorded in patients with poor effect of treatment. Also in patients without seizures LEV tended to suppress propagation. We conclude that the observed suppression of source propagation can be considered as an indicator of effective antiepileptic treatment. ESI might thus become a useful tool in the early clinical evaluation of new candidate drugs in pharmacological developmen

Source localisation of epileptiform activity in epilepsy of temporal lobe origin

In patients with drug resistant partial epilepsy, who are under consideration for epilepsy surgery, interictal and ictal EEG recorded with extracranial electrodes plays an important role in the localisation of the seizure onset area. During the past years, methods have been developed, which can be used to estimate the location of the source of epileptiform activity in the brain from extracranial EEG data. In the present thesis, the location of the source of interictal epileptiform activity is determined by use of two different concepts, dipole analysis and LORETA (Low Resolution Electromagnetic Tomography). Localisation of the source of ictal epileptiform activity is made by analysing the frequency content of the seizure activity, with subsequent dipole localisation of the dominant frequency. Dipole reconstruction of the source of interictal spikes, shown to be emanating from the mesiotemporal area, gives quite specific results, with an anterior temporal dipole location, and an oblique posterior, slightly elevated dipole orientation. Dipole reconstruction of frequency analysed ictal activity, in seizures of mesiotemporal origin, gives dipole results, which are quite similar to the results obtained for mesiotemporal interictal epileptiform activity. The characteristic dipole locations and orientations, whether obtained from interictal analysis in the time domain, or from ictal analysis in the frequency domain, thus give an indication of epilepsy of mesolimbic origin. Dipole results deviating markedly from this characteristic pattern, indicate an epileptogenic region outside mesolimbic structures. LORETA analysis of the extracranial fields of temporal lobe interictal spikes identified with intracranial electrodes, consistently shows activation of the temporal area corresponding to the intracranial spikes, even when the extracranial signal to noise-ratio is very unfavourable. Dipole and LORETA analysis of extracranially recorded interictal data, as well as dipole analysis of frequency analysed extracranially recorded ictal data, are useful supplementary methods for localising the epileptogenic region in patients under consideration for epilepsy surger

Ictal EEG source imaging in presurgical evaluation: high agreement between analysis methods

AbstractPurposeTo determine the agreement between five different methods of ictal EEG source imaging, and to assess their accuracy in presurgical evaluation of patients with focal epilepsy. It was hypothesized that high agreement between methods was associated with higher localization-accuracy.MethodsEEGs were recorded with a 64-electrode array. Thirty-eight seizures from 22 patients were analyzed using five different methods phase mapping, dipole fitting, CLARA, cortical-CLARA and minimum norm. Localization accuracy was determined at sub-lobar level. Reference standard was the final decision of the multidisciplinary epilepsy surgery team, and, for the operated patients, outcome one year after surgery.ResultsAgreement between all methods was obtained in 13 patients (59%) and between all but one methods in additional six patients (27%). There was a trend for minimum norm being less accurate than phase mapping, but none of the comparisons reached significance. Source imaging in cases with agreement between all methods was not more accurate than in the other cases. Ictal source imaging achieved an accuracy of 73% (for operated patients: 86%).ConclusionThere was good agreement between different methods of ictal source imaging. However, good inter-method agreement did not necessarily imply accurate source localization, since all methods faced the limitations of the inverse solution

Superconducting qubit network with controllable nearest neighbor coupling

We investigate the design and functionality of a network of loop-shaped charge qubits with switchable nearest-neighbour coupling. The qubit coupling is achieved by placing large Josephson junctions (JJs) at the intersections of the qubit loops and selectively applying bias currents. The network is scalable and makes it possible to perform a universal set of quantum gates. The coupling scheme allows gate operation at the charge degeneracy point of each qubit, and also applies to charge-phase qubits. Additional JJs included in the qubit loops for qubit readout can also be employed for qubit coupling

ESTIMATING THE EU BIOGAS POTENTIAL FROM MANURE AND CROP RESIDUES – A SPATIAL ANALYSIS

Anaerobic fermentation of agricultural wastes such as crop residues and animal manure, producing biogas, is an example of an advanced biofuel that can contribute to the EU target of a minimum 10% of transport fuels from renewable sources in 2020. Producing biogas from residues has received increasing attention following the debate on the impact conventional biofuel production has on food prices, poverty and land-use change. The EU, as well as major producers of biogas such as Germany and Italy, are currently revising their policy framework to incentivize the sourcing of biogas substrates from waste streams.Given these developments it is important to improve our understanding of how large the potential is for producing biogas and biomethane from agricultural wastes in the EU, how that potential is distributed across member states, and what the main limitations to this potential are. Previous studies on the potential for producing biogas from agricultural wastes in the EU, however, have either been local cases studies that account for a host of detailed economic and technical constraints, an approach that is almost impossible to scale up to the EU level, or top-down assessments of gross substrate potentials that do not account for any of the technical and economic limitations specific to biogas production.In this report we present a spatially explicit approach for estimating the availability of agricultural wastes - crop residues and animal manure - across the EU, which also allows for an analysis of how key economic and technical constraints such as minimum viable plant size, maximum collection distances for substrates, and substrate composition affects the total potential for biogas production.Our main results from this analysis can be summarized as follows:* Total annually available biogas substrates from agricultural wastes in the EU28 amounts to roughly 80 million tonnes of crop residues (dry matter) and 110 million tonnes (dry matter) of animal manure.* In our base case scenario, three quarters of the manure and a fifth of the crop residues are technically and economically exploitable for biogas production, yielding a total biogas potential from agricultural wastes of almost 700 PJ (HHV) per year.* Animal production and arable farming are spatially highly segregated in some parts of the EU28. This leads to some areas having considerable surpluses of either dry, carbon-rich crop residues or nitrogen-rich manures which cannot be fully utilized due to technical constraints on dry matter content and carbon-to-nitrogen ratios. There are, however, potential ways to relax these constraints, for example using dry fermentation technology or adding wet, carbon-rich co-substrates, such as energy crops.* If we assume a larger minimum viable biogas plant size of 8 MW, typical if the biogas is to be upgraded to vehicle fuel quality, the potential decreases by about a quarter. However, the base case potential can still be reached or even surpassed under this constraint if one allows for a somewhat increased collection radius for substrates or if the constraint on maximum dry matter content is relaxed

ESTIMATING THE EU BIOGAS POTENTIAL FROM MANURE AND CROP RESIDUES – A SPATIAL ANALYSIS

Anaerobic fermentation of agricultural wastes such as crop residues and animal manure, producing biogas, is an example of an advanced biofuel that can contribute to the EU target of a minimum 10% of transport fuels from renewable sources in 2020. Producing biogas from residues has received increasing attention following the debate on the impact conventional biofuel production has on food prices, poverty and land-use change. The EU, as well as major producers of biogas such as Germany and Italy, are currently revising their policy framework to incentivize the sourcing of biogas substrates from waste streams. Given these developments it is important to improve our understanding of how large the potential is for producing biogas and biomethane from agricultural wastes in the EU, how that potential is distributed across member states, and what the main limitations to this potential are. Previous studies on the potential for producing biogas from agricultural wastes in the EU, however, have either been local cases studies that account for a host of detailed economic and technical constraints, an approach that is almost impossible to scale up to the EU level, or top-down assessments of gross substrate potentials that do not account for any of the technical and economic limitations specific to biogas production. In this report we present a spatially explicit approach for estimating the availability of agricultural wastes - crop residues and animal manure - across the EU, which also allows for an analysis of how key economic and technical constraints such as minimum viable plant size, maximum collection distances for substrates, and substrate composition affects the total potential for biogas production. Our main results from this analysis can be summarized as follows: * Total annually available biogas substrates from agricultural wastes in the EU28 amounts to roughly 80 million tonnes of crop residues (dry matter) and 110 million tonnes (dry matter) of animal manure. * In our base case scenario, three quarters of the manure and a fifth of the crop residues are technically and economically exploitable for biogas production, yielding a total biogas potential from agricultural wastes of almost 700 PJ (HHV) per year. * Animal production and arable farming are spatially highly segregated in some parts of the EU28. This leads to some areas having considerable surpluses of either dry, carbon-rich crop residues or nitrogen-rich manures which cannot be fully utilized due to technical constraints on dry matter content and carbon-to-nitrogen ratios. There are, however, potential ways to relax these constraints, for example using dry fermentation technology or adding wet, carbon-rich co-substrates, such as energy crops. * If we assume a larger minimum viable biogas plant size of 8 MW, typical if the biogas is to be upgraded to vehicle fuel quality, the potential decreases by about a quarter. However, the base case potential can still be reached or even surpassed under this constraint if one allows for a somewhat increased collection radius for substrates or if the constraint on maximum dry matter content is relaxed

Incidence of hyperthyroidism in Stockholm, Sweden, 2003-2005

Objectives: To investigate the incidence of hyperthyroidism in Stockholm County in those patients who were diagnosed with hyperthyroidism for the First time during the years 2003-2005. Design: All new cases of hyperthyroidism >= 18 years of age were prospectively registered to calculate the total incidence of hyperthyroidism, as well as the incidence of the subgroups: Graves' disease (GD), toxic multinodular goitre and solitary toxic adenoma (STA). Eight specialized units/hospitals in Stockholm County participated in the registration. The participating physicians were all specialists in medical endocrinology. oncology, nuclear medicine or surgery. Results: Duringa 3-year period, 1431 new patients of hyperthyroidism were diagnosed in a well-defined adult population (>18 years of age) of in average 1 457 036 inhabitants. This corresponds to a mean annual incidence of hyperthyroidism of 32.7/100 000. The incidence of GD was 24.5/100 000 per year. toxic nodular goitre was 3.3/100 000 per year and STA was 4.9/100 000 per year. Conclusions: The total incidence of hyperthyroidism in Stockholm County was found to be 32.7/100 000 per year. of which 75% had GD. There were a higher percentage of smokers among the patients with hyperthyroidism compared with the overall population in Stockholm, but no difference in the frequency of smoking between patients with GD and toxic nodular goitre

Long-Term Outcome of Graves' Disease : A Gender Perspective

Introduction: In gender-skewed conditions such as Graves' disease (GD), the outcome naturally becomes dominated by the majority. This may lead to gender-biased misunderstandings regarding treatment outcomes. This especially holds true when complications, such as depression, are unevenly distributed. We have, therefore, studied the long-term outcome of GD from a gender perspective.Materials and Methods: A cohort of 1186 patients with GD was included in a follow-up 6-10 years after inclusion. Choice of treatment, the feeling of recovery, long-term treatment, comorbidity, and quality of life were investigated with questionnaires. All results were studied sex-divided.Results: We included 973 women and 213 men. There was no difference between men and women in the choice of treatment. At follow-up, women scored significantly worse in the general questionnaire 36-item Short-Form Health Status (SF-36) domain bodily pain and in the thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) domains depression, impaired sex life, and cosmetic complaints, all p < 0.05. Women were twice as likely (29.5%) to be treated with levothyroxine after successful treatment with antithyroid drugs (ATD) compared with men (14.9%, p < 0.05).Conclusion: After treatment for GD, women were more affected by depression, impaired sex life, cosmetic issues, and bodily pain despite successful cure of hyperthyroidism. The prevalence of hypothyroidism was also doubled in women. Whether these observed gender differences reflect a worse outcome of GD in women or a natural consequence of a higher prevalence of these symptoms and autoimmunity in the female population is difficult to disentangle. Nevertheless, several years after GD, women reveal more persistent symptoms