Evaluation of a Practice Change to Improve Screening, Identification, and Management of Patients with Prediabetes

Background: The prevalence rate of type 2 diabetes among adults in West Virginia (WV) is 10.85, which ranks fourth in the United States in 2007. Furthermore, WV ranks as second highest state for diabetes related deaths in the nation. Prediabetes increases the risks for development of type 2 diabetes. Studies have supported lifestyle modification education for prediabetic adults in an effort to reduce progression to type 2 diabetes.;Objective: To evaluate the use of an EMR reminder to improve the screening, identifying, and documentation of treatment plans for patient at risk for prediabetes.;Methods: A provider focused education session was offered to heightened awareness about prediabetes and provide instruction on the implementation of a new EMR reminder for prediabetes. An EMR was activated for an eight week intervention period. Data was collected from 100 randomly selected pre- and post- intervention chart audits.;Population: The population for this capstone project focused on adults 25 to70 years old within the Wirt County Health Service Association who meet the criteria for prediabetes by American Diabetes Association (2012) medical standards.;Expected Outcomes: The evaluation of the EMR reminder will improve screening, identifying, and documenting treatment plans based on critical appraisal of current literature

Notions and subnotions in information structure

Three dimensions can be distinguished in a cross-linguistic account of information structure. First, there is the definition of the focus constituent, the part of the linguistic expression which is subject to some focus meaning. Second and third, there are the focus meanings and the array of structural devices that encode them. In a given language, the expression of focus is facilitated as well as constrained by the grammar within which the focus devices operate. The prevalence of focus ambiguity, the structural inability to make focus distinctions, will thus vary across languages, and within a language, across focus meanings

Morally Respectful Listening and its Epistemic Consequences

What does it mean to listen to someone respectfully, that is, insofar as they are due recognition respect? This paper addresses that question and gives the following answer: it is to listen in such a way that you are open to being surprised. A specific interpretation of this openness to surprise is then defended

Contrastive focus and emphasis

The paper puts forward a discourse-semantic account of the notoriously evasive phenomena of contrastivity and emphasis. Based on new evidence from Chadic, it is argued that occurrences of focus that are treated in terms of ‘contrastive focus’, ‘kontrast’ (Vallduví-Vilkuna 1998) or ‘identificational focus’ (É. Kiss 1998) in the literature should not be analyzed in familiar semantic terms as involving the introduction and subsequent exclusion of alternatives. Rather, an adequate analysis must take into account discourse-semantic notions like ‘hearer expectation’ or ‘discourse expectability’ of the focused content in a given discourse situation. The less expected the focus content is judged to be for the hearer, relative to the Common Ground, the more likely a speaker is to mark the focus constituent by means of special grammatical devices, thus giving rise to emphasis

Time-resolved crystallography using the Hadamard transform

YesWe describe a method for performing time-resolved X-ray crystallographic experiments based on the Hadamard transform, in which time resolution is defined by the underlying periodicity of the probe pulse sequence, and signal/noise is greatly improved over that for the fastest pump-probe experiments depending on a single pulse. This approach should be applicable on standard synchrotron beamlines and will enable high-resolution measurements of protein and small-molecule structural dynamics. It is also applicable to other time-resolved measurements where a probe can be encoded, such as pump-probe spectroscopy.Wellcome Trust 4-year PhD program “The Molecular Basis of Biological Mechanisms” 089312/Z/09/Z. This work was also supported by the EPSRC Award “Dynamic Structural Science at the Research Complex at Harwell” EP/I01974X/1 and by BBSRC Award BB/H001905/1

An Assay to Monitor HIV-1 Protease Activity for the Identification of Novel Inhibitors in T-Cells

The emergence of resistant HIV strains, together with the severe side-effects of existing drugs and lack of development of effective anti-HIV vaccines highlight the need for novel antivirals, as well as innovative methods to facilitate their discovery. Here, we have developed an assay in T-cells to monitor the proteolytic activity of the HIV-1 protease (PR). The assay is based on the inducible expression of HIV-1 PR fused within the Gal4 DNA-binding and transactivation domains. The fusion protein binds to the Gal4 responsive element and activates the downstream reporter, enhanced green fluorescent protein (eGFP) gene only in the presence of an effective PR Inhibitor (PI). Thus, in this assay, eGFP acts as a biosensor of PR activity, making it ideal for flow cytometry based screening. Furthermore, the assay was developed using retroviral technology in T-cells, thus providing an ideal environment for the screening of potential novel PIs in a cell-type that represents the natural milieu of HIV infection. Clones with the highest sensitivity, and robust, reliable and reproducible reporter activity, were selected. The assay is easily adaptable to other PR variants, a multiplex platform, as well as to high-throughput plate reader based assays and will greatly facilitate the search for novel peptide and chemical compound based PIs in T-cells

Thriving under Stress: Selective Translation of HIV-1 Structural Protein mRNA during Vpr-Mediated Impairment of eIF4E Translation Activity

Translation is a regulated process and is pivotal to proper cell growth and homeostasis. All retroviruses rely on the host translational machinery for viral protein synthesis and thus may be susceptible to its perturbation in response to stress, co-infection, and/or cell cycle arrest. HIV-1 infection arrests the cell cycle in the G2/M phase, potentially disrupting the regulation of host cell translation. In this study, we present evidence that HIV-1 infection downregulates translation in lymphocytes, attributable to the cell cycle arrest induced by the HIV-1 accessory protein Vpr. The molecular basis of the translation suppression is reduced accumulation of the active form of the translation initiation factor 4E (eIF4E). However, synthesis of viral structural proteins is sustained despite the general suppression of protein production. HIV-1 mRNA translation is sustained due to the distinct composition of the HIV-1 ribonucleoprotein complexes. RNA-coimmunoprecipitation assays determined that the HIV-1 unspliced and singly spliced transcripts are predominantly associated with nuclear cap binding protein 80 (CBP80) in contrast to completely-spliced viral and cellular mRNAs that are associated with eIF4E. The active translation of the nuclear cap binding complex (CBC)-bound viral mRNAs is demonstrated by ribosomal RNA profile analyses. Thus, our findings have uncovered that the maintenance of CBC association is a novel mechanism used by HIV-1 to bypass downregulation of eIF4E activity and sustain viral protein synthesis. We speculate that a subset of CBP80-bound cellular mRNAs contribute to recovery from significant cellular stress, including human retrovirus infection