2014 Epilepsy Benchmarks Area III: Improve Treatment Options for Controlling Seizures and Epilepsy-Related Conditions Without Side Effects

The Epilepsy Benchmark goals in Area III focus on making progress in understanding and controlling seizures and related conditions as well as on developing biomarkers and new therapies that will reduce seizures and improve outcomes for individuals with epilepsy. Area III emphasizes a need to better understand the ways in which seizures start, propagate, and terminate and whether those network processes are common or unique in different forms of epilepsy. The application of that knowledge to improved seizure prediction and detection will also play a role in improving patient outcomes. Animal models of treatment-resistant epilepsy that are aligned with etiologies and clinical features of human epilepsies are especially encouraged as necessary tools to understand mechanisms and test potential therapies. Antiseizure therapies that target (either alone or in combination) novel or multiple seizure mechanisms are prioritized in this section of the Benchmarks. Area III goals also highlight validation of biomarkers of treatment response and safety risk, effective self-management, and patient-centered outcome measures as important areas of emphasis for the next five to ten years

Controversies in epilepsy: Debates held during the Fourth International Workshop on Seizure Prediction

Debates on six controversial topics were held during the Fourth International Workshop on Seizure Prediction (IWSP4) convened in Kansas City, KS, USA, July 4–7, 2009. The topics were (1) Ictogenesis: Focus versus Network? (2) Spikes and Seizures: Step-relatives or Siblings? (3) Ictogenesis: A Result of Hyposynchrony? (4) Can Focal Seizures Be Caused by Excessive Inhibition? (5) Do High-Frequency Oscillations Provide Relevant Independent Information? (6) Phase Synchronization: Is It Worthwhile as Measured? This article, written by the IWSP4 organizing committee and the debaters, summarizes the arguments presented during the debates

Microstructure and thermal stability of Fe, Ti and Ag implanted Yttria-stabilized zirconia

Yttria-stabilized zirconia (YSZ) was implanted with 15 keV Fe or Ti ions up to a dose of 8×1016 at cm−2. The resulting “dopant” concentrations exceeded the concentrations corresponding to the equilibrium solid solubility of Fe2O3 or TiO2 in YSZ. During oxidation in air at 400° C, the Fe and Ti concentration in the outermost surface layer increased even further until a surface layer was formed of mainly Fe2O3 and TiO2, as shown by XPS and ISS measurements. From the time dependence of the Fe and Ti depth profiles during anneal treatments, diffusion coefficients were calculated. From those values it was estimated that the maximum temperature at which the Fe- and Ti-implanted layers can be operated without changes in the dopant concentration profiles was 700 and 800° C, respectively. The high-dose implanted layer was completely amorphous even after annealing up to 1100° C, as shown by scanning transmission electron microscopy. Preliminary measurements on 50 keV Ag implanted YSZ indicate that in this case the amorphous layer recrystallizes into fine grained cubic YSZ at a temperature of about 1000° C. The average grain diameter was estimated at 20 nm, whereas the original grain size of YSZ before implantation was 400 nm. This result implies that the grain size in the surface of a ceramic material can be decreased by ion beam amorphisation and subsequent recrystallisation at elevated temperatures

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography

OBJECTIVE: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. METHODS: Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. RESULTS: Eighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0-376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording. SIGNIFICANCE: About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions

High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland

Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (θsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/θ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role

Life cycle assessment of the environmental performance of conventional and organic methods of open field pepper cultivation

Summarization: As the scale of the organic cultivation sector keeps increasing, there is growing demand for reliable data on organic agriculture and its effect on the environment. Conventional agriculture uses chemical fertilizers and pesticides, whilst organic cultivation mainly relies on crop rotation and organic fertilizers. The aim of this work is to quantify and compare the environmental sustainability of typical conventional and organic pepper cultivation systems. Methods: Two open field pepper cultivations, both located in the Anthemountas basin, Northern Greece, are selected as case studies. Life cycle assessment (LCA) is used to quantify the overall environmental footprint and identify particular environmental weaknesses (i.e. unsustainable practices) of each cultivation system. Results are analysed at both midpoint and endpoint levels in order to obtain a comprehensive overview of the environmental sustainability of each system. Attributional LCA (ALCA) is employed to identify emissions associated with the life cycles of the two systems. Results are presented for problem-oriented (midpoint) and damage-oriented (endpoint) approaches, using ReCiPe impact assessment. Results and discussion: At midpoint level, conventional cultivation exhibits about threefold higher environmental impact on freshwater eutrophication, than organic cultivation. This arises from the extensive use of nitrogen and phosphorus-based fertilizers, with consequent direct emissions to the environment. The remaining impact categories are mainly affected by irrigation, with associated indirect emissions linked to electricity production. At endpoint level, the main hotspots identified for conventional cultivation are irrigation and fertilizing, due to intensive use of chemical fertilizers and (to a lesser degree) pesticides. For organic pepper cultivation, the main environmental hotspots are irrigation, machinery use, and manure loading and spreading processes. Of these, the highest score for irrigation derives from the heavy electricity consumption required for groundwater pumping associated with the fossil-fuel-dependent Greek electricity mix. Conclusions: Organic and conventional cultivation systems have similar total environmental impacts per unit of product, with organic cultivation achieving lower environmental impacts in ‘freshwater eutrophication’, ‘climate change’, ‘terrestrial acidification’ and ‘marine eutrophication’ categories. Conventional cultivation has a significantly greater effect on the freshwater eutrophication impact category, due to phosphate emissions arising from application of chemical fertilizers.Presented on: International Journal of Life Cycle Assessmen

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Multigroup Ethnic Identity Measure (MEIM) Expansion: Measuring Racial, Religious, and National Aspects of Sense of Ethnic Identity Within the United Kingdom

These studies examined the degree to which racial, religious, and national aspects of individuals' sense of ethnic identity stand as interrelated, yet distinct, constructs. Results of exploratory factor analyses in Study 1 (n = 272) revealed that a three-factor model specifying racial, religious, and national identities yielded optimal fit to correlational data from an expanded, 36-item version of the Multigroup Ethnic Identity Measure (MEIM; Roberts et al., 1999), although results left room for improvement in model fit. Subsequently, results of confirmatory factor analyses in Study 2 (n = 291) revealed that, after taking covariance among the items into account, a six-factor model specifying exploration and commitment dimensions within each of the racial, religious, and national identity constructs provided optimal fit. Implications for the utility of Goffman's (1963b) interactionist role theory and Erikson's (1968) ego psychology for understanding the full complexity of felt ethnic identity are discussed