Brain stimulation treatments in epilepsy: Basic mechanisms and clinical advances

Drug-resistant epilepsy, characterized by ongoing seizures despite appropriate trials of anti-seizure medications, affects approximately one-third of people with epilepsy. Brain stimulation has recently become available as an alternative treatment option to reduce symptomatic seizures in short and long-term follow-up studies. Several questions remain on how to optimally develop patient-specific treatments and manage therapy over the long term. This review aims to discuss the clinical use and mechanisms of action of Responsive Neural Stimulation and Deep Brain Stimulation in the treatment of epilepsy and highlight recent advances that may both improve outcomes and present new challenges. Finally, a rational approach to device selection is presented based on current mechanistic understanding, clinical evidence, and device features

‘I just don’t ever use that word’: investigating stakeholders’ understanding of heritage

Understanding the value of heritage sites for diverse stakeholders requires both paying attention to the fields of power in which the sites operate and applying methodologies that are open to user-defined paradigms of value. In the U.S., official discourse often frames the value of heritage sites associated the deep Native American past as archaeological sites, an interpretation that is consistent with settler colonial ideologies. This narrative generally obfuscates connections between the heritage of the sites and contemporary peoples, and it effaces the history of colonialism and dispossession. A study of stakeholder-defined heritage at two contested sites in the central Midwest revealed both congruencies and conflicts among diverse constituencies’ articulations of the sites’ value. At Mounds State Park a proposed dam and reservoir ‘Mounds Lake’ project would inundate a large portion of the site. At Strawtown Koteewi, Native American tribes have made repatriation claims under the federal Native American Graves Protection and Repatriation Act (NAGPRA).The study also problematised the term ‘cultural heritage’ as it is understood and used by the different constituencies, particularly for culturally and historically affiliated Native Americans. It also highlighted the positions of the constituencies within the broader fields of power implicated in these contested sites

Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model

OBJECTIVE: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model. METHODS: We performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes. RESULTS: We found that the spike-suppressive effects of high-frequency neurostimulation are highly dependent on the stimulation amplitude and location, with higher amplitude stimulation being significantly more effective. Epileptiform spiking activity was significantly reduced with ipsilateral 250 μA stimulation of the CA1 and CA3 hippocampal regions with 21.5% and 22.2% reductions, respectively. In contrast, we found that spiking frequency and amplitude significantly increased with stimulation of the ventral hippocampal commissure. We further found spatial differences with broader effects from CA1 versus CA3 stimulation. SIGNIFICANCE: These findings demonstrate that the effects of therapeutic neurostimulation in an acute hippocampal seizure model are highly dependent on the location of stimulation and stimulus amplitude. We provide a platform to optimize the anti-seizure effects of neurostimulation, and demonstrate that an exploration of the large electrical parameter and location space can improve current modalities for treating epilepsy. PLAIN LANGUAGE SUMMARY: In this study, we tested how electrical pulses in the brain can help control seizures in mice. We found that the electrode\u27s placement and the stimulation amplitude had a large effect on outcomes. Some brain regions, notably nearby CA1 and CA3, responded positively with reduced seizure-like activities, while others showed increased activity. These findings emphasize that choosing the right spot for the electrode and adjusting the strength of electrical pulses are both crucial when considering neurostimulation treatments for epilepsy

OPTN/SRTR 2018 Annual Data Report: Heart

The new adult heart allocation policy was approved in 2016 and implemented in October 2018, so its effect was not yet evident in 2018 data. However, the more granular data being collected are anticipated to allow for improved analyses. In 2018, new listings continued to increase; 3883 new adult and 685 new pediatric candidates were added. In 2018, 3440 heart transplants were performed, an increase of 167 over 2017; 473 transplants occurred in pediatric recipients and 2967 in adult recipients. Short‐term and long‐term posttransplant mortality improved. Overall 1‐year survival for adults who underwent heart transplant in 2011‐2013 was 90.3%, 3‐year survival was 84.7%, and 5‐year survival was 79.6%. Mortality rates for pediatric recipients were 4.5% at 6 months and in 5.9% at 1 year posttransplant, 12.5% at 3 years for transplants in 2014‐2015, 14.8% at 5 years for transplants in 2012‐2013, and 29.8% at 10 years for transplants performed in 2008‐2009.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153233/1/ajt15676.pd

1973: Abilene Christian College Bible Lectures - Full Text

JESUS Being the Abilene Christian College Annual Bible Lectures 1973 Published by ABILENE CHRISTIAN COLLEGE BOOK STORE ACC Station Abilene, Texas 7960

1970: Abilene Christian College Bible Lectures - Full Text

THE APOSTLES’ DOCTRINE Being the Abilene Christian College Annual Bible Lectures 1970 Published by ABILENE CHRISTIAN COLLEGE BOOK STORE ACC Station Abilene, Texas 7960

Probing Nucleation Mechanism of Self-Catalyzed InN Nanostructures

The nucleation and evolution of InN nanowires in a self-catalyzed growth process have been investigated to probe the microscopic growth mechanism of the self-catalysis and a model is proposed for high pressure growth window at ~760 Torr. In the initial stage of the growth, amorphous InNx microparticles of cone shape in liquid phase form with assistance of an InNx wetting layer on the substrate. InN crystallites form inside the cone and serve as the seeds for one-dimensional growth along the favorable [0001] orientation, resulting in single-crystalline InN nanowire bundles protruding out from the cones. An amorphous InNx sheath around the faucet tip serves as the interface between growing InN nanowires and the incoming vapors of indium and nitrogen and supports continuous growth of InN nanowires in a similar way to the oxide sheath in the oxide-assisted growth of other semiconductor nanowires. Other InN 1D nanostructures, such as belts and tubes, can be obtained by varying the InN crystallites nucleation and initiation process

Identification of a small molecule yeast TORC1 inhibitor with a flow cytometry-based multiplex screen

TOR (target of rapamycin) is a serine/threonine kinase, evolutionarily conserved from yeast to human, which functions as a fundamental controller of cell growth. The moderate clinical benefit of rapamycin in mTOR-based therapy of many cancers favors the development of new TOR inhibitors. Here we report a high throughput flow cytometry multiplexed screen using five GFPtagged yeast clones that represent the readouts of four branches of the TORC1 signaling pathway in budding yeast. Each GFP-tagged clone was differentially color-coded and the GFP signal of each clone was measured simultaneously by flow cytometry, which allows rapid prioritization of compounds that likely act through direct modulation of TORC1 or proximal signaling components. A total of 255 compounds were confirmed in dose-response analysis to alter GFP expression in one or more clones. To validate the concept of the high throughput screen, we have characterized CID 3528206, a small molecule most likely to act on TORC1 as it alters GFP expression in all five GFP clones in an analogous manner to rapamycin. We have shown that CID 3528206 inhibited yeast cell growth, and that CID 3528206 inhibited TORC1 activity both in vitro and in vivo with EC50s of 150 nM and 3.9 μM, respectively. The results of microarray analysis and yeast GFP collection screen further support the notion that CID 3528206 and rapamycin modulate similar cellular pathways. Together, these results indicate that the HTS has identified a potentially useful small molecule for further development of TOR inhibitors

Measurement of w-InN/h-BN Heterojunction Band Offsets by X-Ray Photoemission Spectroscopy

X-ray photoelectron spectroscopy has been used to measure the valence band offset (VBO) of the w-InN/h-BN heterojunction. We find that it is a type-II heterojunction with the VBO being −0.30 ± 0.09 eV and the corresponding conduction band offset (CBO) being 4.99 ± 0.09 eV. The accurate determination of VBO and CBO is important for designing the w-InN/h-BN-based electronic devices

Leveraging analytics to produce compelling and profitable film content

Producing compelling film content profitably is a top priority to the long-term prosperity of the film industry. Advances in digital technologies, increasing availabilities of granular big data, rapid diffusion of analytic techniques, and intensified competition from user generated content and original content produced by Subscription Video on Demand (SVOD) platforms have created unparalleled needs and opportunities for film producers to leverage analytics in content production. Built upon the theories of value creation and film production, this article proposes a conceptual framework of key analytic techniques that film producers may engage throughout the production process, such as script analytics, talent analytics, and audience analytics. The article further synthesizes the state-of-the-art research on and applications of these analytics, discuss the prospect of leveraging analytics in film production, and suggest fruitful avenues for future research with important managerial implications