The Many Faces of Appalachia

This volume of the Proceedings of the 7th Annual Appalachian Studies Conference, held in 1985 at Unicoi State Park in Helen, Georgia, offers a look at diversity and Appalachian identity

Faces of NPS: Lt. Col. Sam Gray

Faces of NPS features Interviews spotlighting the students, faculty, staff and alumni of our Nation’s premier defense education and research institution.Lt. Col. Sam Gray is the Marine Corps Service Liaison to the Office of the Secretary of Defense Strategic Capabilities Office (SCO) where he identifies SCO technologies being developed that will support the Marine Corps and Force Design 2030

What’s in a Name? Exploring the Nomenclature of Science Communication in the UK [version 2]

This study, via a consideration of the literature, and a limited survey of active science communicators, presents concise and workable definitions for science outreach, public engagement, widening participation, and knowledge exchange, in a UK context. Sixty-six per cent of participants agreed that their definitions of outreach, public engagement, and widening participation aligned with those of their colleagues, whilst 64% felt that their personal definitions matched those of their institute. However, closer inspection of the open-ended questions found the respondents often differed in the use of the nomenclature. In particular, the respondents found it difficult to define knowledge exchange in this context. It is hoped that this initial study will form the foundation of future work in this area, and that it will help to further develop the debate regarding the need for a consistent nomenclature across science communication

An ANGPTL4-ceramide-protein kinase Cζ axis mediates chronic glucocorticoid exposure-induced hepatic steatosis and hypertriglyceridemia in mice.

Chronic or excess glucocorticoid exposure causes lipid disorders such as hypertriglyceridemia and hepatic steatosis. Angptl4 (angiopoietin-like 4), a primary target gene of the glucocorticoid receptor in hepatocytes and adipocytes, is required for hypertriglyceridemia and hepatic steatosis induced by the synthetic glucocorticoid dexamethasone. Angptl4 has also been shown to be required for dexamethasone-induced hepatic ceramide production. Here, we further examined the role of ceramide-mediated signaling in hepatic dyslipidemia caused by chronic glucocorticoid exposure. Using a stable isotope-labeling technique, we found that dexamethasone treatment induced the rate of hepatic de novo lipogenesis and triglyceride synthesis. These dexamethasone responses were compromised in Angptl4-null mice (Angptl4-/-). Treating mice with myriocin, an inhibitor of the rate-controlling enzyme of de novo ceramide synthesis, serine palmitoyltransferase long-chain base subunit 1 (SPTLC1)/SPTLC2, decreased dexamethasone-induced plasma and liver triglyceride levels in WT but not Angptl4-/- mice. We noted similar results in mice infected with adeno-associated virus-expressing small hairpin RNAs targeting Sptlc2. Protein phosphatase 2 phosphatase activator (PP2A) and protein kinase Cζ (PKCζ) are two known downstream effectors of ceramides. We found here that mice treated with an inhibitor of PKCζ, 2-acetyl-1,3-cyclopentanedione (ACPD), had lower levels of dexamethasone-induced triglyceride accumulation in plasma and liver. However, small hairpin RNA-mediated targeting of the catalytic PP2A subunit (Ppp2ca) had no effect on dexamethasone responses on plasma and liver triglyceride levels. Overall, our results indicate that chronic dexamethasone treatment induces an ANGPTL4-ceramide-PKCζ axis that activates hepatic de novo lipogenesis and triglyceride synthesis, resulting in lipid disorders

Drug screening to identify compounds to act as co-therapies for the treatment of Burkholderia species

Burkholderia pseudomallei is a soil-dwelling organism present throughout the tropics. It is the causative agent of melioidosis, a disease that is believed to kill 89,000 people per year. It is naturally resistant to many antibiotics, requiring at least two weeks of intravenous treatment with ceftazidime, imipenem or meropenem followed by 6 months of orally delivered co-trimoxazole. This places a large treatment burden on the predominantly middle-income nations where the majority of disease occurs. We have established a high-throughput assay for compounds that could be used as a co-therapy to potentiate the effect of ceftazidime, using the related non-pathogenic bacterium Burkholderia thailandensis as a surrogate. Optimization of the assay gave a Z' factor of 0.68. We screened a library of 61,250 compounds and identified 29 compounds with a pIC50 (-log10(IC50)) greater than five. Detailed investigation allowed us to down select to six "best in class" compounds, which included the licensed drug chloroxine. Co-treatment of B. thailandensis with ceftazidime and chloroxine reduced culturable cell numbers by two orders of magnitude over 48 hours, compared to treatment with ceftazidime alone. Hit expansion around chloroxine was performed using commercially available compounds. Minor modifications to the structure abolished activity, suggesting that chloroxine likely acts against a specific target. Finally, an initial study demonstrates the utility of chloroxine to act as a co-therapy to potentiate the effect of ceftazidime against B. pseudomallei. This approach successfully identified potential co-therapies for a recalcitrant Gram-negative bacterial species. Our assay could be used more widely to aid in chemotherapy to treat infections caused by these bacteria

Elective orthopaedic cancellations due to the COVID-19 pandemic: where are we now, and where are we heading?

Aims The primary aim is to estimate the current and potential number of patients on NHS England orthopaedic elective waiting lists by November 2020. The secondary aims are to model recovery strategies; review the deficit of hip and knee arthroplasty from National Joint Registry (NJR) data; and assess the cost of returning to pre-COVID-19 waiting list numbers. Methods A model of referral, waiting list, and eventual surgery was created and calibrated using historical data from NHS England (April 2017 to March 2020) and was used to investigate the possible consequences of unmet demand resulting from fewer patients entering the treatment pathway and recovery strategies. NJR data were used to estimate the deficit of hip and knee arthroplasty by August 2020 and NHS tariff costs were used to calculate the financial burden. Results By November 2020, the elective waiting list in England is predicted to be between 885,286 and 1,028,733. If reduced hospital capacity is factored into the model, returning to full capacity by November, the waiting list could be as large as 1.4 million. With a 30% increase in productivity, it would take 20 months if there was no hidden burden of unreferred patients, and 48 months if there was a hidden burden, to return to pre-COVID-19 waiting list numbers. By August 2020, the estimated deficits of hip and knee arthroplasties from NJR data were 18,298 (44.8%) and 16,567 (38.6%), respectively, compared to the same time period in 2019. The cost to clear this black log would be £198,811,335. Conclusion There will be up to 1.4 million patients on elective orthopaedic waiting lists in England by November 2020, approximate three-times the pre-COVID-19 average. There are various strategies for recovery to return to pre-COVID-19 waiting list numbers reliant on increasing capacity, but these have substantial cost implications. Cite this article: Bone Jt Open 2021;2(2):103–110

Understanding the National Student Survey: investigations in languages, linguistics and area studies

This report is a summary of interviews and focus groups with around 100 students and 50 members of academic staff in departments of languages, linguistics or area studies at nine universities in the UK. In recent years, concerns have been expressed about the ambiguity of some of the statements which students are asked to respond to in the National Student Survey (NSS). This project set out to get a better understanding of how students and staff understand the questions. The interviews and focus groups were carried out by members of academic staff at the nine institutions who each then wrote an individual report of their findings. This summary is designed to enable wider distribution of these findings without identifying individual staff, institutions `or departments

Evaluation of the i3 Scale-up of Reading Recovery | Year One Report, 2011-12

Reading Recovery (RR) is a short-term early intervention designed to help the lowest-achieving readers in first grade reach average levels of classroom performance in literacy. Students identified to receive Reading Recovery meet individually with a specially trained Reading Recovery (RR) teacher every school day for 30-minute lessons over a period of 12 to 20 weeks. The purpose of these lessons is to support rapid acceleration of each child's literacy learning. In 2010, The Ohio State University received a Scaling Up What Works grant from the U.S. Department of Education's Investing in Innovation (i3) Fund to expand the use of Reading Recovery across the country. The award was intended to fund the scale-up of Reading Recovery by training 3,675 new RR Teachers in U.S. schools, thereby expanding capacity to allow service to an additional 88,200 students.The Consortium for Policy Research in Education (CPRE) was contracted to conduct an independent evaluation of the i3 scale up of Reading Recovery over the course of five years. The evaluation includes parallel rigorous experimental and quasi-experimental designs for estimating program impacts, coupled with a large-scale mixed-methods study of program implementation under the i3 scale-up. This report presents findings through the second year of the evaluation. The primary goals of this evaluation were: a) to assess the success of the scale-up in meeting the i3 grant's expansion goals; b) to document the implementation of scale-up and fidelity to program standards; and, c) to provide experimental evidence of the impacts of Reading Recovery on student learning under this scale-up effort