"Y'all come back now, y'hear!?"

Nicht angegeben.This MA thesis is based on a field study that investigated the language attitudes of informants from the Northern and Southern United States towards Southern American English as spoken in Tennessee. A 'verbal guise' speaker evaluation experiment was conducted in which informants were asked to provide judgments on four speakers (two from the South, two from the North, one male and one female each) who all read the same text in the context of a job interview in sales. Results show that the Southern speakers were rated significantly lower in terms of perceived competence (e.g. education, intelligence), but that the Southern female received the highest ratings for social attractiveness. The study thus provides quantitative and qualitative evidence for common stereotypes regarding Southern American English in the U.S

The development of the concept of return-on-investment from large-scale quality improvement programmes in healthcare: an integrative systematic literature review

BACKGROUND: Return on Investment (ROI) is increasingly being used to evaluate financial benefits from healthcare Quality Improvement (QI). ROI is traditionally used to evaluate investment performance in the commercial field. Little is known about ROI in healthcare. The aim of this systematic review was to analyse and develop ROI as a concept and develop a ROI conceptual framework for large-scale healthcare QI programmes. METHODS: We searched Medline, Embase, Global health, PsycInfo, EconLit, NHS EED, Web of Science, Google Scholar using ROI or returns-on-investment concepts (e.g., cost–benefit, cost-effectiveness, value). We combined this terms with healthcare and QI. Included articles discussed at least three organisational QI benefits, including financial or patient benefits. We synthesised the different ways in which ROI or return-on-investment concepts were used and discussed by the QI literature; first the economically focused, then the non-economically focused QI literature. We then integrated these literatures to summarise their combined views. RESULTS: We retrieved 10 428 articles. One hundred and two (102) articles were selected for full text screening. Of these 34 were excluded and 68 included. The included articles were QI economic, effectiveness, process, and impact evaluations as well as reports and conceptual literature. Fifteen of 68 articles were directly focused on QI programme economic outcomes. Of these, only four focused on ROI. ROI related concepts in this group included cost-effectiveness, cost–benefit, ROI, cost-saving, cost-reduction, and cost-avoidance. The remaining articles mainly mentioned efficiency, productivity, value, or benefits. Financial outcomes were not the main goal of QI programmes. We found that the ROI concept in healthcare QI aligned with the concepts of value and benefit, both monetary and non-monetary. CONCLUSION: Our analysis of the reviewed literature indicates that ROI in QI is conceptualised as value or benefit as demonstrated through a combination of significant outcomes for one or more stakeholders in healthcare organisations. As such, organisations at different developmental stages can deduce benefits that are relevant and legitimate as per their contextual needs. TRIAL REGISTRATION: Review registration: PROSPERO; CRD42021236948. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-022-08832-3

Synthesis and biological evaluation of benzochromenopyrimidinones as cholinesterase inhibitors and potent antioxidant, non-hepatotoxic agents for Alzheimer’s disease

We report herein the straightforward two-step synthesis and biological assessment of novel racemic benzochromenopyrimidinones as non-hepatotoxic, acetylcholinesterase inhibitors with antioxidative properties. Among them, compound 3Bb displayed a mixed-type inhibition of human acetylcholinesterase (IC50 = 1.28 ± 0.03 μM), good antioxidant activity, and also proved to be non-hepatotoxic on human HepG2 cell line.JMC thanks Government of Spain for support (SAF2016-65586-R), JJ and OS thank MH CZ- DRO (UHHK 00179906).We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

Discovery of Dual Aβ/Tau Inhibitors and Evaluation of Their Therapeutic Effect on a Drosophila Model of Alzheimer's Disease

Alzheimer's disease (AD), the most common type of dementia, currently represents an extremely challenging and unmet medical need worldwide. Amyloid-β (Aβ) and Tau proteins are prototypical AD hallmarks, as well as validated drug targets. Accumulating evidence now suggests that they synergistically contribute to disease pathogenesis. This could not only help explain negative results from anti-Aβ clinical trials but also indicate that therapies solely directed at one of them may have to be reconsidered. Based on this, herein, we describe the development of a focused library of 2,4-thiazolidinedione (TZD)-based bivalent derivatives as dual Aβ and Tau aggregation inhibitors. The aggregating activity of the 24 synthesized derivatives was tested in intact Escherichia coli cells overexpressing Aβ42 and Tau proteins. We then evaluated their neuronal toxicity and ability to cross the blood−brain barrier (BBB), together with the in vitro interaction with the two isolated proteins. Finally, the most promising (most active, nontoxic, and BBB-permeable) compounds 22 and 23 were tested in vivo, in a Drosophila melanogaster model of AD. The carbazole derivative 22 (20 μM) showed extremely encouraging results, being able to improve both the lifespan and the climbing abilities of Aβ42 expressing flies and generating a better outcome than doxycycline (50 μM). Moreover, 22 proved to be able to decrease Aβ42 aggregates in the brains of the flies. We conclude that bivalent small molecules based on 22 deserve further attention as hits for dual Aβ/Tau aggregation inhibition in A

The First HET Planet: A Companion to HD 37605

We report the first detection of a planetary-mass companion to a star using the High Resolution Spectrograph (HRS) of the Hobby-Eberly Telescope (HET). The HET-HRS now gives routine radial velocity precision of 2-3 m/s for high SNR observations of quiescent stars. The planetary-mass companion to the metal-rich K0V star HD37605 has an orbital period of 54.23 days, an orbital eccentricity of 0.737, and a minimum mass of 2.84 Jupiter masses. The queue-scheduled operation of the Hobby-Eberly Telescope enabled us to discovery of this relatively short-period planet with a total observation time span of just two orbital periods. The ability of queue-scheduled large-aperture telescopes to respond quickly to interesting and important results demonstrates the power of this new approach in searching for extra-solar planets as well as in other ares of research requiring rapid response time critical observations.Comment: 4 Pages, 2 figures. Accepted in Astrophysical Journal Letters, http://austral.as.utexas.edu/planets/hd37605/hd37605.htm

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Historical Sociolinguistic Philology – a New Hybrid Discipline, its Interests, and its Scope

This contribution presents the basic rationale and principles of a new hybrid discipline of historical sociolinguistic philology, or the sociolinguistically informed study of ancient texts, as showcased in the current special issue. It is shown how an interactional model of communication validates and scaffolds the application of synchronic sociocultural linguistic theory and findings to the analysis of ancient texts in order to achieve a more fully contextualized account and interpretation of their meaning from a perspective contemporary to their origination. In fact, it is argued that any study of ancient texts should take the perspective of its producer(s) and addressee(s) into consideration, and that written language use cannot be satisfactorily accounted for without reference to the immediate, on-the-ground-level social context and situation within which it arose