Estimation of fiber diameters in the spinal dorsal columns from clinical data

Lack of human morphometric data regarding the largest nerve fibers in the dorsal columns (DCs) of the spinal cord has lead to the estimation of the diameters of these fibers from clinical data retrieved from patients with a new spinal cord stimulation (SCS) system. These patients indicated the perception threshold of stimulation induced paresthesia in various body segments, while the stimulation amplitude was increased. The fiber diameters were calculated with a computer model, developed to calculate the effects of SCS on spinal nerve fibers. This computer model consists of two parts: (1) a three-dimensional (3-D) volume conductor model of a spinal cord segment in which the potential distribution due to electrical stimulation is calculated and (2) an electrical equivalent cable model of myelinated nerve fiber, which uses the calculated potential field to determine the threshold stimulus needed for activation. It is shown that the largest fibers in the medial DCs are significantly smaller than the largest fibers in the lateral parts. This finding is in accordance with the fiber distribution in cat, derived from the corresponding propagation velocities. Moreover, it is shown that the mediolateral increase in fiber diameter is mainly confined to the lateral parts of the DCs. Implementation of this mediolateral fiber diameter distribution of the DCs in the computer model enables the prediction of the recruitment order of dermatomal paresthesias following increasing electrical stimulation amplitud

MDMA Decreases Gluatamic Acid Decarboxylase (GAD) 67-Immunoreactive Neurons in the Hippocampus and Increases Seizure Susceptibility: Role for Glutamate

3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37–58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30 days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures

LibQual+ Morris Library Presentation

Results from a survey of the SIUC campus community about their satisfaction with Morris Library

Performance of Landscape Plants from Northern Japan in the North Central United States

In 1984 and 1985, 21 landscape plant introductions from northern Japan were distributed for testing in the NC-7 Regional Ornamental Plant Trials. Seventeen of these introductions were evaluated for 10 years at six to ten sites representing a cross-section of growing conditions in the north central United States. For these 17 introductions, first-year survival averaged 60%; however, by year 10, fewer than 20% of the original 425 plants were alive. Based on these evaluations, the populations could be divided into four groups. One population of Rosa rugosa was adapted to most trial sites; two populations (Alnus hirsuta and Lonicera chrysantha) were adapted to some sites; three populations were of poorly adapted dieback shrubs, and the remaining II populations included a diverse set of trees and shrubs unadapted to any, or nearly any, trial site. Temperature and moisture data from Japan and from trial sites were used to examine relationships between plant adaptation and climate. Statistically significant, multiple-regression models were calculated to describe the functional relationships between temperature and moisture conditions and plant adaptation at the various trial sites. Our models predict that plants from northern Japan are best adapted to sites in the northeastern United States where moisture surpluses exceed those typically found in the north central United States. These models also suggest criteria to evaluate sites throughout northeastern Asia for future exploration

Mechanisms and controlling characteristics of the catalytic oxidation of methane

Methane dissociation and oxygen activation have been found to be structure sensitive on different single crystal palladium surfaces. Geometrically restricted surfaces on Pd single crystal and polycrystalline surfaces using tetrachloroethylene and pentamethylcyclopentasiloxane have been formed and compared with surface structures formed using dichloromethane and chlorine. The adsorption and activation of O{sub 2}, CO, and H{sub 2}O on clean Pd surfaces and those containing the surface ensembles have also been investigated. To interpret high-resolution angle-resolved x-ray photoelectron spectra (HR AR-XPS), a new self-modeling method of resolving HR-XPS spectra was developed and applied to the experimental spectra. The effects of electron-accepting Cl, O{sub 2}, and H{sub 2}O adsobated on Cs/MoS{sub 2} were determined

Instances and connectors : issues for a second generation process language

This work is supported by UK EPSRC grants GR/L34433 and GR/L32699Over the past decade a variety of process languages have been defined, used and evaluated. It is now possible to consider second generation languages based on this experience. Rather than develop a second generation wish list this position paper explores two issues: instances and connectors. Instances relate to the relationship between a process model as a description and the, possibly multiple, enacting instances which are created from it. Connectors refers to the issue of concurrency control and achieving a higher level of abstraction in how parts of a model interact. We believe that these issues are key to developing systems which can effectively support business processes, and that they have not received sufficient attention within the process modelling community. Through exploring these issues we also illustrate our approach to designing a second generation process language.Postprin

Accelerating Drug Development Using Biomarkers: A Case Study with Sitagliptin, A Novel DPP4 Inhibitor for Type 2 Diabetes

The leveraged use of biomarkers presents an opportunity in understanding target engagement and disease impact while accelerating drug development. For effective integration in drug development, it is essential for biomarkers to aid in the elucidation of mechanisms of action and disease progression. The recent years have witnessed significant progress in biomarker selection, validation, and qualification, while enabling surrogate and clinical endpoint qualification and application. Biomarkers play a central role in target validation for novel mechanisms. They also play a central role in the learning/confirming paradigm, particularly when utilized in concert with pharmacokinetic/pharmacodynamic modeling. Clearly, these attributes make biomarker integration attractive for scientific and regulatory applications to new drug development. In this review, applications of proximal, or target engagement, and distal, or disease-related, biomarkers are highlighted using the example of the recent development of sitagliptin for type 2 diabetes, wherein elucidation of target engagement and disease-related biomarkers significantly accelerated sitagliptin drug development. Importantly, use of biomarkers as tools facilitated design of clinical efficacy trials while streamlining dose focus and optimization, the net impact of which reduced overall cycle time to filing as compared to the industry average

CAVASS: A Computer-Assisted Visualization and Analysis Software System

The Medical Image Processing Group at the University of Pennsylvania has been developing (and distributing with source code) medical image analysis and visualization software systems for a long period of time. Our most recent system, 3DVIEWNIX, was first released in 1993. Since that time, a number of significant advancements have taken place with regard to computer platforms and operating systems, networking capability, the rise of parallel processing standards, and the development of open-source toolkits. The development of CAVASS by our group is the next generation of 3DVIEWNIX. CAVASS will be freely available and open source, and it is integrated with toolkits such as Insight Toolkit and Visualization Toolkit. CAVASS runs on Windows, Unix, Linux, and Mac but shares a single code base. Rather than requiring expensive multiprocessor systems, it seamlessly provides for parallel processing via inexpensive clusters of work stations for more time-consuming algorithms. Most importantly, CAVASS is directed at the visualization, processing, and analysis of 3-dimensional and higher-dimensional medical imagery, so support for digital imaging and communication in medicine data and the efficient implementation of algorithms is given paramount importance

The CardioMetabolic Health Alliance Working Toward a New Care Model for the Metabolic Syndrome

AbstractThe Cardiometabolic Think Tank was convened on June 20, 2014, in Washington, DC, as a “call to action” activity focused on defining new patient care models and approaches to address contemporary issues of cardiometabolic risk and disease. Individual experts representing >20 professional organizations participated in this roundtable discussion. The Think Tank consensus was that the metabolic syndrome (MetS) is a complex pathophysiological state comprised of a cluster of clinically measured and typically unmeasured risk factors, is progressive in its course, and is associated with serious and extensive comorbidity, but tends to be clinically under-recognized. The ideal patient care model for MetS must accurately identify those at risk before MetS develops and must recognize subtypes and stages of MetS to more effectively direct prevention and therapies. This new MetS care model introduces both affirmed and emerging concepts that will require consensus development, validation, and optimization in the future