Disease modifying therapy for multiple system atrophy – Parkinsonian Type

BACKGROUND: Multiple System Atrophy –Parkinsonian Type (MSA-P) is a rare, rapidly progressive neurodegenerative disease without any current treatment. Recent research has increased the understanding of brain iron accumulation and its association with neurodegenerative synucleinopathies, like MSA-P. Because of this improved understanding of the disease process, there is potential for new therapies that could benefit patients with MSA-P. Unfortunately, many attempts at finding a new and effective treatments for MSA-P have been unsuccessful. Two drugs that have shown potential in neurodegenerative synucleinopathies associated with brain iron accumulation are iron chelators (Deferiprone) and tyrosine kinase inhibitors (Nilotinib.) METHODS: The proposed study is a multicenter, double blind, randomized control study of Nilotinib and Deferiprone for the treatment of MSA-P. There will be two treatment arms; Nilotinib and a placebo group vs. Nilotinib and Deferiprone. There will be a 24 week treatment phase, followed by a 24 week wash-out phase. All patients will have a baseline evaluation including: a full neurological exam with rating scales (UMSARS, UPDRS, SCOPA, and MOCA) to assess motor and non-motor symptoms of MSA-P. Lab and imaging data will include CBC, CMP, serum iron panel, CSF iron panel and brain SWI-MR scans. Neurological exams and rating scales will be assessed every four weeks while imaging and laboratory data will be assessed at baseline (week 0) at the end of the intervention phase (week 24) and at the end of the follow-up phase (week 48). CONCLUSIONS: Deferiprone and Nilotinib when used together will have a synergistic impact on the symptoms of MSA-P and will be more effective when used together versus when they are used individually. SIGNIFICANCE: Patients with MSA-P have shortened life expectancy as well as severely diminished quality of life due to rapidly progressive neurodegeneration. This trial aims to implementing evidence based treatment for MSA-P that could potentially improve life expectancy as well as quality of life in this patient population

It’s All about That Base: Persuading Learners of Spanish as a Second Language That Verb Acquisition Is the Essence of Communication

The intended result of a series of Spanish courses is the ability to speak fluidly, if not extensively, in Spanish. The quickest way to speak quickly is to learn some set phrases. As a result of strategies that involve this learning tool, perhaps 75% of Americans can parrot “¿Dónde está el baño?” and “Dos cervezas, por favor.” However, a disappointingly high percentage of people who can say those things cannot say anything that would be useful outside a restaurant. Working backwards from my curricular goal of creating verbal facility in my students, I start by expressing the threshold concept that verb-conjugation skills matter more than a broad vocabulary when it comes to speaking clearly and smoothly in Spanish. I tell my students that you can point at objects you want to buy or eat, but there are many verbs that one would not be willing to act out before strangers in order to be understood

Reinforcement by Error Analysis of Multiple: Threshold Concepts in Advanced Spanish Composition

This year, I taught a course in advanced Spanish grammar, Spanish 302. This course provided me with an opportunity to build on a procedure I developed and refined in the Backwards by Design writing instruction workshops in 2012 and 2013 for emphasizing one of the threshold concepts in basic Spanish, noun-adjective agreement. This year’s enhanced procedure, which could not be implemented easily at the 100 level, is proving to serve as a gateway to greater understanding on the part of my students of their individual strengths and weaknesses

Folate-PEG-Histidine for Use in Detection, Capture, and Analysis of FR+ Cells

Folate receptor alpha is a membrane-bound protein displaying high affinity for folic acid. This receptor serves as a receptor-mediated transport system of folic acid into cancer and cells associated with inflammation (e.g., macrophages). Folate is a basic component of cell metabolism in both the synthesis of DNA and proteins, which is hypothesized to be necessary for maintaining adequate processes during increased metabolic demand. Interestingly, most normal cells in the body have little or no high affinity folate receptor alpha. Based on these attributes, folate based drug delivery, imaging systems, and diagnostic systems are in several stages of development worldwide. To the best of our knowledge, this is the first time a folate 5-His conjugate has been used in this fashion. In this project, analytical analysis of a folate polyethylene glycol (PEG) 5-histidine conjugate was undertaken. This conjugate is capable of binding to nitrilotriacetic acid (NTA) nickel in the classic 6-histidine (his) capture systems including NTA-Ni magnetic beads and Nano composites. The resulting compound was successfully synthesized and proven with the diode array detector during liquid chromatography separation with a maximal absorption at 280 nm with a shoulder peak at 363 nm at 15.277 minutes. This peak was isolated and then directly injected into the electrospray ionization ion trap mass spectrometer (Agilent technologies) which produced a doubly charged and triply charged anions at m/z’s of 665.0 and 443.7 respectively, which fall within the expected range for the protonated Folate-PEG-5-His molecule

Enhancing Athletic Programs\u27 Recruitment Success: A Strategic Planning Model of Recruiting

A critical yet understudied element in recruiting success is understanding an athletic program’s strengths and weaknesses relative to influential college choice factors. The purpose of this study is to provide practitioners and researchers with a new approach to assess an athletic program’s recruiting process, improve its effectiveness and efficiency, and close the gap between what student-athletes desire in an athletic program and what the program offers. To achieve that end, collegiate football players (N = 66) at a NCAA FBS school were surveyed using a scale consolidated from past college choice factor scholarship. Exploratory factor analysis using principle-component analysis and Varimax rotation was then used to assess the underlying factor structure of the proposed scale and the commonalities among the 48 scale items. From the results, a strategic recruiting model was created that categorizes college choice factors into a four-quadrant matrix consisting of Urgency, Strength, Support, and Concern components

Linearity testing of LED transmitter and corresponding voltage to current op-amp configuration [abstract]

Abstract only availableThe LM7171 operational amplifier is made for high electrostatic discharge and fast signal performance. In a configuration using the diode in the transmitter and a resistor on the negative op-amp terminal, the op amp will convert the voltage measurement to a current value, which will then be sent linearly via the HFBR-1414MZ optical transmitter over optical fiber. First, the transmitter and receiver pair will be tested for linearity using a variable current source. Should data confirm linearity, the voltage to current op amp configuration will be tested. This paper presents the results of these tests. This project is sponsored by Los Alamos National Laboratory.Los Alamos National Laborator

A Process for Engagement with Threshold Concepts in Spanish Composition

Numerous practices and assignments discussed at the 2012 Backwards by Design Curriculum Workshop appeal to me as sources of creativity in the classroom. Some will suit courses I teach in the future. For this year, I faced an issue: I am working with students whose classroom vocabulary is equivalent to that of a three-year-old, because I am teaching first-year Spanish. The most applicable idea, one that energized me greatly, was the identification of threshold concepts. Working backward from that identification, I sought ways to implement practices that would, I hoped, bring those concepts permanently into my students’ approach to writing in Spanis

L'application de la Grande Loi de la Paix (Kaianerekowa) de la Haudenosaunee dans la pratique de la médiation à Kahnawake

La tradition juridique iroquoise, ou de la Confédération iroquoise - autrement connue sous l‟appellation Haudenosaunee ou Gens du Longhouse - est non seulement ancienne, mais aussi organique et viable. Les rappels de son existence et de son contenu nous entourent et nous pénètrent. Son application, toutefois, exige notre volonté et notre participation, ainsi que celles des communautés autochtones dont les ancêtres l‟ont développée il y a plusieurs siècles. Ceci représente un défi constant pour la communauté mohawk de Kahnawake où la marche du temps a mené, malgré la présence notable et indépendante des Mohawks avant et pendant les premiers siècles d‟interaction avec les Européens, à une intégration juridique de la mentalité coloniale. L‟on pourrait même douter de l‟existence de leur ordre juridique, la Kaianerekowa. La réalité néanmoins est toute autre et cet ordre est complet, sophistiqué et applicable; il s‟ouvre ainsi, nécessairement, à la possibilité de critique et d‟amélioration progressive. La médiation illustre bien ces dynamiques, parce qu‟elle en fait partie depuis un temps immémorial. Aujourd‟hui, Kahnawake cherche à développer son identité juridique ainsi que ses relations avec le monde extérieur. La Kaianerekowa représente une alternative concrète viable pour les communautés locales ou globales. La médiation demeure une application pratique et efficace de cet ordre juridique pour cette communauté, comme pour d‟autres, chacune avec des adaptations particulières. Nous argumenterons pour la reconnaissance pleine et entière de la Kaianerekowa comme ordre juridique et de la médiation comme forme juridique potentiellement dominante à Kahnawake.The Iroquois Legal Tradition, or that of the Iroquois Confederation otherwise known as the Haudenosaunee or the People of the Longhouse, is not only ancient but also organic and currently viable. The reminders of its existence and of its content surround us and traverse us. Its application, however, requires our will and our participation as well as that of Indigenous communities of which the ancestors themselves developed it many centuries ago. This presents a constant challenge for the Mohawk community of Kahnawake where the march of time led, despite the notable independent Mohawk presence before and during the first centuries of interaction with the Europeans, to a legal integration of the colonial mentality. This could even lead one to doubt of the existence of their legal order, the Kaianerekowa. Reality, however, is otherwise and this order is complete, sophisticated and applicable; it is thus open necessarily to the possibility of critique and progressive improvement. The mediation exemplifies these dynamics, because it has been a part of them since before one can say. Today, Kahnawake seeks to develop its legal identity as well as its relations with the outside world. The Kaianerekowa presents itself as a concrete and viable alternative for local and global communities. The mediation remains a practical and efficient application of this legal order for this community, as for others and each with its own particular adaptation. We will argue for the full and entire recognition of the Kaianerekowa as a legal order and of mediation as a legal form potentially dominant in Kahnawake