A National Dialogue on Health Information Technology and Privacy

Increasingly, government leaders recognize that solving the complex problems facing America today will require more than simply keeping citizens informed. Meeting challenges like rising health care costs, climate change and energy independence requires increased level of collaboration. Traditionally, government agencies have operated in silos -- separated not only from citizens, but from each other, as well. Nevertheless, some have begun to reach across and outside of government to access the collective brainpower of organizations, stakeholders and individuals.The National Dialogue on Health Information Technology and Privacy was one such initiative. It was conceived by leaders in government who sought to demonstrate that it is not only possible, but beneficial and economical, to engage openly and broadly on an issue that is both national in scope and deeply relevant to the everyday lives of citizens. The results of this first-of-its-kind online event are captured in this report, together with important lessons learned along the way.This report served as a call to action. On his first full day in office, President Obama put government on notice that this new, more collaborative model can no longer be confined to the efforts of early adopters. He called upon every executive department and agency to "harness new technology" and make government "transparent, participatory, and collaborative." Government is quickly transitioning to a new generation of managers and leaders, for whom online collaboration is not a new frontier but a fact of everyday life. We owe it to them -- and the citizens we serve -- to recognize and embrace the myriad tools available to fulfill the promise of good government in the 21st Century.Key FindingsThe Panel recommended that the Administration give stakeholders the opportunity to further participate in the discussion of heath IT and privacy through broader outreach and by helping the public to understand the value of a person-centered view of healthcare information technology

Spatio-temporal and neighborhood characteristics of two dengue outbreaks in two arid cities of Mexico.

Little is currently known about the spatial-temporal dynamics of dengue epidemics in arid areas. This study assesses dengue outbreaks that occurred in two arid cities of Mexico, Hermosillo and Navojoa, located in northern state of Sonora. Laboratory confirmed dengue cases from Hermosillo (N=2730) and Navojoa (N=493) were geocoded by residence and assigned neighborhood-level characteristics from the 2010 Mexican census. Kernel density and Space-time cluster analysis was performed to detect high density areas and space-time clusters of dengue. Ordinary Least Square regression was used to assess the changing socioeconomic characteristics of cases over the course of the outbreaks. Both cities exhibited contiguous patterns of space-time clustering. Initial areas of dissemination were characterized in both cities by high population density, high percentage of occupied houses, and lack of healthcare. Future research and control efforts in these regions should consider these space-time and socioeconomic patterns.National Institutes of Health - NIAID [R01-AI091843]12 month embargo; Available online 3 January 2017.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Application of Multiplexed Kinase Inhibitor Beads to Study Kinome Adaptations in Drug-Resistant Leukemia

<div><p>Protein kinases play key roles in oncogenic signaling and are a major focus in the development of targeted cancer therapies. Imatinib, a BCR-Abl tyrosine kinase inhibitor, is a successful front-line treatment for chronic myelogenous leukemia (CML). However, resistance to imatinib may be acquired by BCR-Abl mutations or hyperactivation of Src family kinases such as Lyn. We have used <u>m</u>ultiplexed kinase <u>i</u>nhibitor <u>b</u>eads (MIBs) and quantitative mass spectrometry (MS) to compare kinase expression and activity in an imatinib-resistant (MYL-R) and -sensitive (MYL) cell model of CML. Using MIB/MS, expression and activity changes of over 150 kinases were quantitatively measured from various protein kinase families. Statistical analysis of experimental replicates assigned significance to 35 of these kinases, referred to as the MYL-R kinome profile. MIB/MS and immunoblotting confirmed the over-expression and activation of Lyn in MYL-R cells and identified additional kinases with increased (MEK, ERK, IKKα, PKCβ, NEK9) or decreased (Abl, Kit, JNK, ATM, Yes) abundance or activity. Inhibiting Lyn with dasatinib or by shRNA-mediated knockdown reduced the phosphorylation of MEK and IKKα. Because MYL-R cells showed elevated NF-κB signaling relative to MYL cells, as demonstrated by increased IκBα and IL-6 mRNA expression, we tested the effects of an IKK inhibitor (BAY 65-1942). MIB/MS and immunoblotting revealed that BAY 65-1942 increased MEK/ERK signaling and that this increase was prevented by co-treatment with a MEK inhibitor (AZD6244). Furthermore, the combined inhibition of MEK and IKKα resulted in reduced IL-6 mRNA expression, synergistic loss of cell viability and increased apoptosis. Thus, MIB/MS analysis identified MEK and IKKα as important downstream targets of Lyn, suggesting that co-targeting these kinases may provide a unique strategy to inhibit Lyn-dependent imatinib-resistant CML. These results demonstrate the utility of MIB/MS as a tool to identify dysregulated kinases and to interrogate kinome dynamics as cells respond to targeted kinase inhibition.</p></div

Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse

The functional and molecular similarities and distinctions between human and murine astrocytes are poorly understood. Here we report the development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains, and to maintain these cells in serum-free cultures. We found that human astrocytes have similar abilities to murine astrocytes in promoting neuronal survival, inducing functional synapse formation, and engulfing synaptosomes. In contrast to existing observations in mice, we found that mature human astrocytes respond robustly to glutamate. We next performed RNA-sequencing of healthy human astrocytes along with astrocytes from epileptic and tumor foci, and compared these to human neurons, oligodendrocytes, microglia, and endothelial cells. With these profiles, we identified novel human-specific astrocyte genes, and discovered a transcriptome-wide transformation between astrocyte precursor cells and mature post-mitotic astrocytes. These data represent some of the first cell type-specific molecular profiles of the healthy and diseased human brain

Targeted inhibition of kinases detected by MIB/MS leads to induction of apoptosis.

<p>(<b>A</b>) MYL-R cells were treated for 48 hours with AZD6244 (AZD, 5 µM), BAY 65-1942 (BAY, 10 µM), AZD (5 µM) plus BAY (10 µM), or dasatinib (1 nM) and cell viability was assessed by MTS assay. <i>Error bars</i>, SE (N = 3). (<b>B</b>) MYL-R cells were treated for 24 hours with AZD (5 µM), BAY (10 µM), AZD (5 µM) plus BAY (10 µM), or dasatinib (1 nM) and caspase 3/7 activity was assessed by fluorometric assay. <i>Error bars</i>, SE (N = 2). (<b>C</b>) MYL-R cells were treated for 48 hours with AZD (5 µM), BAY (10 µM), AZD (5 µM) plus BAY (10 µM), or dasatinib (1 nM) and cell lysates were analyzed by immunoblot using the antibodies indicated. Data are representative of two separate experiments.</p