Does response to vagus nerve stimulation for drug-resistant epilepsy differ in patients with and without Lennox–Gastaut syndrome?

Introduction: Literature on outcomes of patients with Lennox–Gastaut syndrome (LGS) receiving adjunctive vagus nerve stimulation (VNS) lacks information on seizure types and the time course of therapeutic effects. We have therefore performed what is to our knowledge the largest and most in-depth analysis of the effectiveness of VNS in LGS patients paying special attention to the impact of VNS Therapy on individual seizure types. Methods: The VNS Therapy Outcomes Registry includes over 7000 patients. A propensity score matching method was employed to match patients with LGS to non-LGS patients with drug-resistant epilepsy (DRE). Overall seizure frequencies were assessed prior to implantation and at 3-, 6-, 12-, 18-, and 24-month follow-ups to derive the main study outcomes: response rates and time to first response.Results: A total of 564 LGS patients with sufficient data were identified in the registry and matched 2:1 to 1128 non-LGS patients. Responder rates at 24 months were 57.5% in the LGS group and 61.5% in the non-LGS group. Median seizure frequency reduction at 24 months was 64.3% versus 66.7% in the LGS versus non-LGS group, respectively. In both groups, VNS was most effective at reducing focal aware seizures, “other” seizures, generalized-onset non-motor seizures, and drop attacks with relative reduction rates for these seizure types at 24 months exceeding 90% in both groups. Time-to-first response did not differ between the groups; however, there was a significantly higher proportion of patients who regressed from bilateral tonic–clonic (BTC) seizure response in the LGS group versus the non-LGS group at 24 months: 22.4% versus 6.7%; p =.015. Conclusions: Although limited by its retrospective design, the study shows that the effectiveness of VNS is comparable in DRE patients with and without LGS; however, LGS patients may be more prone to fluctuating control of BTCs.</p

The nontoxic natural compound Curcumin exerts anti-proliferative, anti-migratory, and anti-invasive properties against malignant gliomas

Background: New drugs are constantly sought after to improve the survival of patients with malignant gliomas. The ideal substance would selectively target tumor cells without eliciting toxic side effects. Here, we report on the anti-proliferative, anti-migratory, and anti-invasive properties of the natural, nontoxic compound Curcumin observed in five human glioblastoma (GBM) cell lines in vitro. Methods: We used monolayer wound healing assays, modified Boyden chamber trans-well assays, and cell growth assays to quantify cell migration, invasion, and proliferation in the absence or presence of Curcumin at various concentrations. Levels of the transcription factor phospho-STAT3, a potential target of Curcumin, were determined by sandwich-ELISA. Subsequent effects on transcription of genes regulating the cell cycle were analyzed by quantitative real-time PCR. Effects on apoptosis were determined by caspase assays. Results: Curcumin potently inhibited GBM cell proliferation as well as migration and invasion in all cell lines contingent on dose. Simultaneously, levels of the biologically active phospho-STAT3 were decreased and correlated with reduced transcription of the cell cycle regulating gene c-Myc and proliferation marking Ki-67, pointing to a potential mechanism by which Curcumin slows tumor growth. Conclusions: Curcumin is part of the diet of millions of people every day and is without known toxic side effects. Our data show that Curcumin bears anti-proliferative, anti-migratory, and anti-invasive properties against GBM cells in vitro. These results warrant further in vivo analyses and indicate a potential role of Curcumin in the treatment of malignant gliomas

Low-Frequency Oscillations Code Speech during Verbal Working Memory

Item does not contain fulltextThe way the human brain represents speech in memory is still unknown. An obvious characteristic of speech is its evolvement over time. During speech processing, neural oscillations are modulated by the temporal properties of the acoustic speech signal, but also acquired knowledge on the temporal structure of language influences speech perception-related brain activity. This suggests that speech could be represented in the temporal domain, a form of representation that the brain also uses to encode autobiographic memories. Empirical evidence for such a memory code is lacking. We investigated the nature of speech memory representations using direct cortical recordings in the left perisylvian cortex during delayed sentence reproduction in female and male patients undergoing awake tumor surgery. Our results reveal that the brain endogenously represents speech in the temporal domain. Temporal pattern similarity analyses revealed that the phase of frontotemporal low-frequency oscillations, primarily in the beta range, represents sentence identity in working memory. The positive relationship between beta power during working memory and task performance suggests that working memory representations benefit from increased phase separation.SIGNIFICANCE STATEMENT Memory is an endogenous source of information based on experience. While neural oscillations encode autobiographic memories in the temporal domain, little is known on their contribution to memory representations of human speech. Our electrocortical recordings in participants who maintain sentences in memory identify the phase of left frontotemporal beta oscillations as the most prominent information carrier of sentence identity. These observations provide evidence for a theoretical model on speech memory representations and explain why interfering with beta oscillations in the left inferior frontal cortex diminishes verbal working memory capacity. The lack of sentence identity coding at the syllabic rate suggests that sentences are represented in memory in a more abstract form compared with speech coding during speech perception and production

Розвиток закордонної релігійної періодики УАПЦ в екзилі на прикладі часопису «Життя і Церква» (The Development of Foreign Religious Periodicals of Ukrainian Autocephalous Orthodox Church in Exile on the Example of the Magazine Life and Church)

Тези присвячені історії української православної церкви закордоном. У центрі уваги – внутрішнє життя церкви, яке репрезентувалося на шпальтах релігійної періодики. На прикладі такого видання як «Життя і церква», з’ясовано інформаційне наповнення публікацій на сторінках подібних журналів. Різноплановий характер поданих у них відомостей є важливим джерелом до вивчення історії українського релігійного життя в діаспорі, особливостей церковного повсякдення. Вони також виступають ключем до розуміння методів збереження національної ідентичності та релігійної самобутності в чужому соціокультурному середовищі. (The author presents the history of the Ukrainian Orthodox Church abroad. The main attention is focused on the internal life of the church, that is represented on the pages of religious periodicals. Using the magazine Life and Church as an example, the author of the research illustrates the typicality of the content of such kind of a publication. Versatile character of the content is an important source to study the history of the Ukrainian religious life in the Diaspora, as well as the features of everyday life in church. They also act as a key to understanding the methods of preserving national and religious identity in another sociocultural environment.

Dynamik als Leitprinzip zur Revitalisierung des Leipziger Auensystems

10 Thesen zur Revitalisierung der Leipziger Aue, eine Vision, ein konkreter Maßnahmenkatalog mit Karte zu Dynamisierungsoptionen und ein Ausblick mit Realisierungsvorschläge

Seasonal variation of the mesospheric inversion layer, thunderstorms and mesospheric ozone over India

Temperature and ozone volume mixing ratio profiles obtained from the Halogen Occultation Experiment (HALOE) aboard the Upper Atmospheric Research Satellite (UARS) over India and over the open ocean to the south during the period 1991-2001 are analyzed to study the characteristic features of the Mesospheric Inversion Layer (MIL) at 70 to 85 km altitude and its relation with the ozone mixing ratio at this altitude. We have also analyzed both the number of lightning flashes measured by the Optical Transient Detector (OTD) onboard the MicroLab-1 satellite for the period April 1995 - March 2000 and ground-based thunderstorm data collected from 78 widespread Indian observatories for the same period to show that the MIL amplitude and thunderstorm activity are correlated. All the data sets examined exhibit a semiannual variation. The seasonal variation of MIL amplitude and the frequency of occurrence of the temperature inversion indicate a fairly good correlation with the seasonal variation of thunderstorms and the average ozone volume mixing ratio across the inversion layer. The observed correlation between local thunderstorm activity, MIL amplitude and mesospheric ozone volume mixing ratio are explained by the generation, upward propagation and mesospheric absorption of gravity waves produced by thunderstorms.Comment: 45 pages, 10 figures, 2 tables, PDF format, version published in Journal of Geophysical Research-Atmospher

Long-term outcome and patterns of failure in patients with advanced head and neck cancer

<p>Abstract</p> <p>Purpose</p> <p>To access the long-time outcome and patterns of failure in patients with advanced head and neck squamous cell carcinoma (HNSCC).</p> <p>Methods and materials</p> <p>Between 1992 and 2005 127 patients (median age 55 years, UICC stage III n = 6, stage IV n = 121) with primarily inoperable, advanced HNSCC were treated with definite platinum-based radiochemotherapy (median dose 66.4 Gy). Analysed end-points were overall survival (OS), disease-free survival (DFS), loco-regional progression-free survival (LPFS), development of distant metastases (DM), prognostic factors and causes of death.</p> <p>Results</p> <p>The mean follow-up time was 34 months (range, 3-156 months), the 3-, 5- and 10-year OS rates were 39%, 28% and 14%, respectively. The median OS was 23 months. Forty-seven patients achieved a complete remission and 78 patients a partial remission. The median LPFS was 17 months, the 3-, 5- and 10-year LPFS rates were 41%, 33% and 30%, respectively. The LPFS was dependent on the nodal stage (p = 0.029). The median DFS was 11 months (range, 2-156 months), the 3-, 5- and 10-year DFS rates were 30%, 24% and 22%, respectively. Prognostic factors in univariate analyses were alcohol abuse (n = 102, p = 0.015), complete remission (n = 47, p < 0.001), local recurrence (n = 71, p < 0.001), development of DM (n = 45, p < 0.001; median OS 16 months) and borderline significance in nodal stage N2 versus N3 (p = 0.06). Median OS was 26 months with lung metastases (n = 17). Nodal stage was a predictive factor for the development of DM (p = 0.025). Cause of death was most commonly tumor progression.</p> <p>Conclusions</p> <p>In stage IV HNSCC long-term survival is rare and DM is a significant predictor for mortality. If patients developed DM, lung metastases had the most favourable prognosis, so intensified palliative treatment might be justified in DM limited to the lungs.</p

The Molecular Genetic Architecture of Self-Employment

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg2/σP2= 25%, h2= 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10-5were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases

The Molecular Genetic Architecture of Self-Employment

Peer reviewe

Chemical Milling Increasing Efficiency at Wyman Gordon Company

Chemical Milling is a finishing process that removes oxide scale and alpha-case from forged titanium parts. To increase efficiency of chemical milling at Wyman-Gordon Company, we analyzed previous projects, assessed the etch quality of their chemical milling bath, and evaluated means of process control and potential areas of cost and raw material savings. Via our experimentation we determined that the ideal concentration of HF is 8% for all temperatures 90 degrees Fahrenheit to 120 degrees Fahrenheit to effectively etch a titanium part