Comparative analytical performance of multiple plasma Aβ42 and Aβ40 assays and their ability to predict positron emission tomography amyloid positivity

INTRODUCTION: This report details the approach taken to providing a dataset allowing for analyses on the performance of recently developed assays of amyloid beta (Aβ) peptides in plasma and the extent to which they improve the prediction of amyloid positivity. METHODS: Alzheimer's Disease Neuroimaging Initiative plasma samples with corresponding amyloid positron emission tomography (PET) data were run on six plasma Aβ assays. Statistical tests were performed to determine whether the plasma Aβ measures significantly improved the area under the receiver operating characteristic curve for predicting amyloid PET status compared to age and apolipoprotein E (APOE) genotype. RESULTS: The age and APOE genotype model predicted amyloid status with an area under the curve (AUC) of 0.75. Three assays improved AUCs to 0.81, 0.81, and 0.84 (P < .05, uncorrected for multiple comparisons). DISCUSSION: Measurement of Aβ in plasma contributes to addressing the amyloid component of the ATN (amyloid/tau/neurodegeneration) framework and could be a first step before or in place of a PET or cerebrospinal fluid screening study. HIGHLIGHTS: The Foundation of the National Institutes of Health Biomarkers Consortium evaluated six plasma amyloid beta (Aβ) assays using Alzheimer's Disease Neuroimaging Initiative samples. Three assays improved prediction of amyloid status over age and apolipoprotein E (APOE) genotype. Plasma Aβ42/40 predicted amyloid positron emission tomography status better than Aβ42 or Aβ40 alone

Protecting Synaptic Function from Acute Oxidative Stress: A Novel Role for Big K+ (BK) Channels and Resveratrol-Like Compounds

Oxidative stress causes neural damage and inhibits essential cellular processes, such as synaptic transmission. Despite this knowledge, currently available pharmaceutical agents cannot effectively protect neural cells from acute oxidative stress elicited by strokes, heart attacks, and traumatic brain injuries in a real life clinical setting. Our lab has developed an electrophysiology protocol to identify novel drugs that protect an essential cellular process (neurotransmission) from acute oxidative stress-induced damage. Through this doctoral dissertation, we have identified three new drugs, including a Big K+ (BK) K+ channel blocker (iberiotoxin), resveratrol, and a custom made resveratrol-like compound (fly2) that protect synaptic function from oxidative stress-induced insults. Further developing these drugs as neuroprotective agents may prove transformative in protecting the human brain from acute oxidative stress elicited by strokes, heart attacks, and traumatic brain injuries. Inhibiting the protein kinase G (PKG) pathway protects neurotransmission from acute oxidative stress. This dissertation has expanded upon these findings by determining that the PKG pathway and BK K+ channels function through independent biochemical pathways to protect neurotransmission from acute oxidative stress. Taken together, this dissertation has identified two classes of compounds that protect neurotransmission from acute oxidative stress, including resveratrol-like compounds (resveratrol, fly2) and a BK K + channel inhibitor (iberiotoxin). Further developing these drugs in clinical trials may finally lead to the development of an effective neuroprotective agent

The efficacy of gun controls

Guns are used in the commission of many violent crimes and gun controls are the legislative attempt to reduce crimes by reducing access to guns. Crime has a significantly negative effect on the economic productivity of high crime areas and diminishes human capital. This study measures the efficacy of gun controls in reducing firearm homicide rates for years 2007-2011 using state level data. An index created by the Brady Campaign is used to reflect the totality of gun control legislation in each state. Evidence is found that not only are gun controls ineffective in reducing the firearm homicide rate, but may actually increase it. Due to possible endogeneity, future research should verify these results with instrumental variables

The efficacy of gun controls

Thesis (M.A., Economics) -- California State University, Sacramento, 2013.Guns are used in the commission of many violent crimes and gun controls are the legislative attempt to reduce crimes by reducing access to guns. Crime has a significantly negative effect on the economic productivity of high crime areas and diminishes human capital. This study measures the efficacy of gun controls in reducing firearm homicide rates for years 2007-2011 using state level data. An index created by the Brady Campaign is used to reflect the totality of gun control legislation in each state. Evidence is found that not only are gun controls ineffective in reducing the firearm homicide rate, but may actually increase it. Due to possible endogeneity, future research should verify these results with instrumental variables.Economic

Ptolemy versus Copernicus

If, as Thomas Kuhn suggested in The Structure of Scientific Revolutions, Copernicus was not superior to Ptolemy, why was Ptolemy rejected? Was Copernican theory more elegant? Frank Tipler shows that Tycho Brahe compared their predictions with his own observations. The winner, on balance, was Copernicus. </jats:p

Information vs. Automation and Implications for Dynamic Pricing

Essential resources, like electricity and water, can experience rapidly changing demand or supply while the other side of the market is unchanged. Short-run price variation could efficiently allocate resources at these critical times but only if consumers exhibit short-run demand elasticity. The question for firms in these markets has always been how to enable this response. Randomized control trials are increasingly used to test dynamic pricing and technologies that can assist in response by providing information and/or automated response. However, the trials typically do not randomize short-run prices. This paper illustrates how demand from a randomly assigned control group can be used to test the effectiveness of different technologies in increasing short-term price elasticity. To do so, we use a nonparametric control function approach that eliminates the bias inherent in estimating short-term price response using only household random assignment. We find that only automation technology leads to the short-term price elasticity needed to justify real-time pricing. This paper was accepted by Matthew Shum, marketing. </jats:p