What are the Characteristics of Sustainability for School Improvement?

A capstone submitted in partial fulfillment of the requirements for the degree of Doctor of Education in the College of Education at Morehead State University by Jason Thomas Radford on March 3, 2015

The Cornell Caltech Atacama Telescope status and technical progress

Five partners have currently joined a Consortium to develop the Cornell Caltech Atacama Telescope (CCAT.) Included are Cornell University, the California Institute of Technology (Caltech), the University of Colorado at Boulder, the United Kingdom as represented by the Astronomy Technology Centre (ATC), and Canada as represented by the Universities of British Columbia and Waterloo. This consortium has continued work toward the design of the telescope and instrumentation, pursued fund raising, and further developed the science case for CCAT. An Engineering Design Phase is being planned for 2009-2011 with construction planned to begin shortly thereafter. CCAT continues as a wide field (20 arc min) FOV telescope operating from a shortest wavelength of 200µ. Testing has continued near the summit of Cerro Chajnantor in the Atacama Region of Chile above 5600 meters altitude and data indicates significantly lower water vapor in the seeing column than measured at the ALMA site on the plateau below. Work over the past two years has included research on manufacturing methods for optical segments, extensive study of mirror alignment sensing and control techniques, additional concepts for major structures, and further development of instrumentation

The Cornell Caltech Atacama Telescope status and technical progress

Five partners have currently joined a Consortium to develop the Cornell Caltech Atacama Telescope (CCAT.) Included are Cornell University, the California Institute of Technology (Caltech), the University of Colorado at Boulder, the United Kingdom as represented by the Astronomy Technology Centre (ATC), and Canada as represented by the Universities of British Columbia and Waterloo. This consortium has continued work toward the design of the telescope and instrumentation, pursued fund raising, and further developed the science case for CCAT. An Engineering Design Phase is being planned for 2009-2011 with construction planned to begin shortly thereafter. CCAT continues as a wide field (20 arc min) FOV telescope operating from a shortest wavelength of 200µ. Testing has continued near the summit of Cerro Chajnantor in the Atacama Region of Chile above 5600 meters altitude and data indicates significantly lower water vapor in the seeing column than measured at the ALMA site on the plateau below. Work over the past two years has included research on manufacturing methods for optical segments, extensive study of mirror alignment sensing and control techniques, additional concepts for major structures, and further development of instrumentation

Interim analysis:Open-label extension study of leniolisib for patients with APDS

Background: Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS; or p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency) is an inborn error of immunity caused by PI3Kδ hyperactivity. Resultant immune deficiency and dysregulation lead to recurrent sinopulmonary infections, herpes viremia, autoimmunity, and lymphoproliferation. Objective: Leniolisib, a selective PI3Kδ inhibitor, demonstrated favorable impact on immune cell subsets and lymphoproliferation over placebo in patients with APDS over 12 weeks. Here, we report results from an interim analysis of an ongoing open-label, single-arm extension study. Methods: Patients with APDS aged 12 years or older who completed NCT02435173 or had previous exposure to PI3Kδ inhibitors were eligible. The primary end point was safety, assessed via investigator-reported adverse events (AEs) and clinical/laboratory evaluations. Secondary and exploratory end points included health-related quality of life, inflammatory markers, frequency of infections, and lymphoproliferation. Results: Between September 2016 and August 2021, 37 patients (median age, 20 years; 42.3% female) were enrolled. Of these 37 patients, 26, 9, and 2 patients had previously received leniolisib, placebo, or other PI3Kδ inhibitors, respectively. At the data cutoff date (December 13, 2021), median leniolisib exposure was 102 weeks. Overall, 32 patients (87%) experienced an AE. Most AEs were grades 1 to 3; none were grade 4. One patient with severe baseline comorbidities experienced a grade 5 AE, determined as unrelated to leniolisib treatment. While on leniolisib, patients had reduced annualized infection rates (P =.004), and reductions in immunoglobulin replacement therapy occurred in 10 of 27 patients. Other observations include reduced lymphadenopathy and splenomegaly, improved cytopenias, and normalized lymphocyte subsets. Conclusions: Leniolisib was well tolerated and maintained durable outcomes with up to 5 years of exposure in 37 patients with APDS. ClinicalTrials.gov identifier: NCT02859727.</p

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker