35 research outputs found
On the Chopping Block: Examining the Fairness of Observational Data of Teacher Effectiveness
Since the No Child Left Behind legislation, the assessment of teacher effectiveness (TE) for accountability purposes has been at the forefront of educational policy. Prominent among both already-existing and newly developed measures is the Classroom Assessment Scoring System (CLASS; Pianta, La Paro, & Hamre, 2008). The CLASS is used currently in over 40 states across the country (Teachstone, 2013; Office of Head Start, 2014) to make high-stakes decisions for teachers, including compensation, promotion, and termination. For this reason, it is important that measures like the CLASS are evaluated by research. Our research hypothesizes that if measures like the CLASS can be reliably used for high-stakes outcomes, then scores for individual teachers should remain stable over time, and particularly so within units of thematically related lessons. We used a single-subject design, reflective of the real-world uses of TE scores, to assess score stability for two kindergarten teachers purposively selected from a larger database. Stability ranges were created around mean scores and then visually examined. Significant variability was found between lessons for both teachers, particularly in the instructional support domain of the CLASS. We conclude that single observations are likely not sufficient to reliably evaluate teachers’ instructional effectiveness. Further research should investigate: (1) if similar variability is found with a larger number of teachers when observed for longer periods of time; (2) if this instability is found when using other TE measures; (3) the factors that contribute to observed instability; and (4) the number of teacher observations needed to obtain accurate views of teachers’ effectiveness patterns
Regulation of IGF-I Signaling in Retinal Endothelial Cells by Hyperglycemia
PURPOSE. To investigate the role of hyperglycemia in regulating the proliferative response of retinal endothelial cells (RECs) to insulin-like growth factor (IGF)-I. METHODS. The regulation of IGF-I signaling by glucose concentration was assessed by biochemical analysis of primary RECs grown in media containing normal (5 mM) and high (25 mM) glucose. Cell counting was used to asses the proliferative response to IGF-I. RESULTS. Glucose (25 mM) enhanced the proliferative response of RECs to IGF-I. Phosphorylation of the adaptor protein She (Src homology 2 domain containing) transforming protein 1) was increased in RECs grown in high glucose. For She to be phosphorylated, it must be recruited to the cytoplasmic domain of the transmembrane protein SHPS-1 (SHP substrate-1). She recruitment to SHPS-1 was increased when RECs were grown in high glucose. The difference in She recruitment to SHPS-1 was attributable to a difference in SHPS-1 phosphorylation that is required for She recruitment. This, in turn, was attributable to an increase in SHPS-1 association with integrin-associated protein (IAP), which is necessary for SHPS-1 phosphorylation. The difference in response under the two different glucose conditions appeared to be attributable to changes in the activation of the integrin αVβ3, since blocking αVβ3 in high glucose inhibited the response to IGF-I, whereas addition of the active region of vitronectin to RECs grown in normal glucose enhanced their response. CONCLUSIONS. This study demonstrates that hyperglycemic conditions enhance the response of RECs to IGF-I by increasing the association of IAP with SHPS-1 permitting the formation of the SHPS-1-Shc signaling complex, which is required for the proliferative response to IGF-I
Identification of Compounds That Inhibit IGF-I Signaling in Hyperglycemia
Increased responsiveness of vascular cells to the growth factor IGF-I has been implicated in complications associated with diabetes. Here we describe the development of an assay and screening of a library of compounds for their ability to accelerate cleavage of the transmembrane protein integrin-associated protein (IAP) thereby disrupting the association between IAP and SHPS-1 which we have shown as critical for the enhanced response of vascular cells to IGF-I. The cell-based ELISA utilizes an antibody that specifically detects cleaved, but not intact, IAP. Of the 1040 compounds tested, 14 were considered active by virtue of their ability to stimulate an increase in antibody-binding indicative of IAP cleavage. In experiments with smooth muscle and retinal endothelial cell cultures in hyperglycemic conditions, each active compound was shown to accelerate the cleavage of IAP, and this was associated with a decrease in IAP association with SHPS-1 as determined by coimmunoprecipitation of the proteins from cell lysates. As a consequence of the acceleration in IAP cleavage, the compounds were shown to inhibit IGF-I-stimulated phosphorylation of key signaling molecules including Shc and ERK1/2, and this in turn was associated with a decrease in IGF-I-stimulated cell proliferation. Identification of these compounds that utilize this mechanism has the potential to yield novel therapeutic approaches for the prevention and treatment of vascular complications associated with diabetes
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017
This work was produced as part of the activities of FAPESP Research,\ud
Disseminations and Innovation Center for Neuromathematics (grant\ud
2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud
FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud
supported by a CNPq fellowship (grant 306251/2014-0)
Whole-house mechanical ventilation in a mixed-humid climate
As building codes and green building programs require tighter home construction, the need for outdoor air ventilation to improve indoor air quality increases. Major improvements in building envelopes and duct systems have led to decreases in heating and cooling loads causing fewer HVAC system run-time hours, and increasing the probability for air stagnation within homes with poor outdoor air ventilation. ASHRAE Standard 62.2 quantifies the amount of whole-house ventilation required based on the number of occupants and the square footage of conditioned space, but leaves the design of the ventilation system up to the mechanical engineer or HVAC contractor. In 2010, ASHRAE began requiring flow testing for confirmation of outdoor air ventilation rates, yet few municipalities and green building programs have adopted the new standard.
Builders in mixed-humid climates are forced to balance the need for outdoor air ventilation with the upfront costs for mechanical ventilation systems, and the potential for increased humidity loads and energy costs associated with mechanical ventilation strategies. One common solution employed in the southeastern United States involves a central fan integrated supply (CFIS) ventilation system controlled with an air-cycler for minimum run-time to meet ASHRAE Standard 62.2. While this system has been tested and proven to meet design ventilation rates, those tests were often conducted on homes constructed by well trained builders receiving strong oversight from building scientists and the design ventilation rates were not always ASHRAE compliant.
The following report analyzes whether the CFIS ventilation system with air-cycler controller provides ventilation meeting ASHRAE Standard 62.2 when employed by builders with minimal training and support.MSCommittee Chair: Roper, Kathy; Committee Member: Gentry, Russell; Committee Member: Porter, Ric
Program in Flux: New Priorities and Implementation Challenges for 287(g)
Slightly more than 2.1 million unauthorized immigrant youth and young adults could be eligible to apply for legal status under the DREAM Act legislation pending in Congress, though perhaps fewer than 40 percent would obtain legal status because of barriers limiting their ability to take advantage of the legislation's educational and military service routes to legalization. This MPI analysis offers the most recent and detailed estimates of potential DREAM Act beneficiaries age, education levels, gender, state of residence and likelihood of gaining legalization