Front Matter

Robert Burns & Friends essays by W. Ormiston Roy Fellows presented to G. Ross Roy edited by Patrick Scott and Kenneth Simpson This volume of essays about the Scottish poet Robert Burns (1759-1796) pays tribute to the distinguished Burns scholar G. Ross Roy. Subjects covered include writers who influenced Burns; aspects of the writing of Burns and that of his friends and contemporaries; and Burns\u27s influence on later writers. The volume also includes essays on Ross Roy\u27s own accomplishments and on the Burns collection he built (now at the University of South Carolina), together with a checklist of his published writings. G. Ross Roy, Distinguished Professor Emeritus of English and Comparative Literature, founded the journal Studies in Scottish Literature in 1963, and as its editor for nearly fifty years he has had a central role in establishing international academic recognition for the field. His own scholarly work includes the standard Letters of Robert Burns (2 vols., Clarendon Press, 1985). His contributions to Scottish literature have earned him honorary doctorates from the Universities of Edinburgh (2002) and Glasgow (2009). The contributors are all former W. Ormiston Roy Visiting Fellows at the University of South Carolina. This book is also available in a print edition (ISBN: 978-1439270974) through the usual on-line vendors. It is not available for direct purchase from the editors or the University of South Carolina

Prelims, Prefatory Note to SSL 37, Preface to Robert Burns & Friends

Prefatory note by Patrick Scott and Tony Jarrells, preface by Patrick Scott and Kenneth Simpso

On the prevalence of bridged macrocyclic pyrroloindolines formed in regiodivergent alkylations of tryptophan.

A Friedel-Crafts alkylation is described that efficiently transforms tryptophan-containing peptides into macrocycles of varying ring connectivity. Factors are surveyed that influence the distribution of regioisomers, with a focus on indole C3-alkylations leading to bridged endo-pyrroloindolines. We probe the stability and stereochemistry of these pyrroloindolines, study their rearrangement to C2-linked indolic macrocycles, and demonstrate a scalable, stereoselective synthesis of this compound class. Placing the macrocyclization in sequence with further template-initiated annulation leads to extraordinary polycyclic products and further demonstrates the potential for this chemistry to drive novel peptidomimetic lead discovery programs

A New Radioligand Binding Assay to Measure the Concentration of Drugs in Rodent Brain Ex Vivo

ABSTRACT We have developed a new radioligand binding assay method to measure the concentration of nonradiolabeled drugs in the brain ex vivo. This new method fuses the concepts of standard competition and saturation binding assays and uses a transformed version of the Cheng-Prusoff equation (Biochem Pharmacol 22: 3099 -3108, 1973) to calculate the drug concentration. After testing the validity of this method, we demonstrated its utility by measuring the brain concentration of sazetidine-A, a newly developed nicotinic receptor ligand, and its elimination rate after a single subcutaneous administration. Our results indicate that sazetidine-A reaches brain concentrations that are known to occupy and desensitize the majority of neuronal nicotinic acetylcholine receptor binding sites. Furthermore, using this method, we estimated the half-life of sazetidine-A in the rat brain to be ϳ65 min. It is important to note that the method described here to measure sazetidine-A in brain should be generalizable to other drugs acting at any receptor that can be reliably measured with a radiolabeled ligand

Thermal Analysis of Fly Ashes Sourced from European Non-Blended Coals

Fly ashes exist as a mixture of major amorphous phases and minor crystalline phases. For commercial applications, such as in concretes and for the production of zeolites, it would be desirable to be able to predict the reactivity of fly ashes. The amorphous phase dominates degradation behaviour, because glasses have a higher potential energy than the equivalent crystal structure and the variation of bond angles and distances in a glass make the bond breakage easier. Despite the large quantities of fly ash produced annually by coal-burning power plants, there have been very few studies investigating the microstructure and composition of the amorphous component. In particular, there has been little research undertaken in measuring the glass transition temperature (Tg), which can be directly correlated to the chemical reactivity of the glass phase. Thirteen European fly ashes were used for the present study. Differential scanning calorimetry (DSC) was employed to determine the presence of transition temperatures and any other thermal events (exotherms or endotherms) in the glassy phase of the fly ashes. Several different but distinct behaviours were evident in the DSC traces with Tg values visible for six of the ashes. The results suggest that thermal analysis has potential as a technique for fly ash characterisation. © 2002 Society of Chemical Industry

Modelling of the Glass Phase in Fly Ashes using Network Connectivity Theory

The amorphous phase of fly ash dominates degradation behaviour because glass has a higher potential energy than the equivalent crystal structure and the variation of bond angles and distances in a glass make the bond breakage easier. It would be advantageous to predict the presence and subsequent degradability of glass on the basis of the solid-state chemistry of the fly ash. To this end, and inorganic polymer model was applied to a selection of European fly ashes to determine the value known as cross-link density (CLD). A cross-link density value of less than two implies that the material is amorphous in nature and the lower the CLD below two, the greater the reactivity and solubility of the glass. Applying this model may facilitate the selection of the most suitable fly ash for a particular recycling application where glass reactivity or dissolution rates are important. To check the applicability of the model to the glass phase of fly ashes, CLD calculations have been performed by removing the contribution to the ash composition from the known crystal phases. The model would be then expected to give a maximum CLD value of two for all the materials. While this approach has been applied successfully to synthetic glasses and glass-ceramics in the past, only very limited applicability has been found with fly ashes. This is believed to be due to the inherent heterogeneity of the glass phase in fly ash. © 2002 Society of Chemical Industry

Safety of paclitaxel-coated balloon angioplasty for femoropopliteal peripheral artery disease

OBJECTIVES: The aim of this study was to assess safety outcomes of femoropopliteal drug-coated balloon (DCB) angioplasty using patient-level data from the Lutonix clinical program. BACKGROUND: A recent systematic review and meta-analysis of heterogenous trials and summary-level data identified increased long-term mortality in patients treated with paclitaxel-coated balloons and stents. METHODS: We evaluated DCB angioplasty (n = 1,093) and uncoated balloon angioplasty (percutaneous transluminal angioplasty [PTA]) (n = 250) outcomes in LEVANT 1 (The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis), LEVANT 2 (Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries), and the LEVANT Japan Clinical Trial. Hazard ratios (HRs) were calculated with Cox proportional hazards modeling. RESULTS: There were no significant differences in mortality rates between DCB angioplasty and PTA. The 5-year HR was 1.01 (95% confidence interval [CI]: 0.68 to 1.52) in the aggregated LEVANT trials. The 2-year HR after DCB angioplasty was 0.99 (95% CI: 0.25 to 3.95) in LEVANT 1, 1.40 (95% CI: 0.62 to 3.14) in LEVANT 2, and 0.32 (95% CI: 0.05 to 1.92) in the LEVANT Japan Clinical Trial. The 5-year HR was 1.60 (95% CI: 0.94 to 2.72) in LEVANT 2. Adverse events and causes of death were balanced, without clustering between DCB angioplasty and PTA. Patients who underwent paclitaxel or nonpaclitaxel reinterventions had higher survival rates than those who did not undergo reinterventions. Baseline covariates predicting mortality included, among others, age (HR: 1.03 per year; p \u3c 0.0001), prior treatment of target lesion (HR: 1.67; p = 0.022), arrhythmia (HR: 1.65; p = 0.031), and diabetes (HR: 1.18; p = 0.047), without differences between the 2 arms. No dose-response relationship was identified when adjusted for key predictors of mortality. CONCLUSIONS: Analyses of patient-level data identified no mortality differences between DCB angioplasty and PTA. Furthermore, the lack of dose-response relationships or clustering of causes of death argues against a causal relationship between paclitaxel and mortality. (LEVANT 1, The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis [LEVANT 1], NCT00930813; Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries [LEVANT 2], NCT01412541; LEVANT 2 Continued Access Registry, NCT01628159; LEVANT Japan Clinical Trial, NCT01816412)

Successful Management of Refractory Type 1 Renal Tubular Acidosis with Amiloride

A 28-year-old female with history of hypothyroidism, Sjögren’s Syndrome, and Systemic Lupus Erythematosus (SLE) presented with complaints of severe generalized weakness, muscle pain, nausea, vomiting, and anorexia. Physical examination was unremarkable. Laboratory test showed hypokalemia at 1.6 mmol/l, nonanion metabolic acidosis with HCO3 of 11 mmol/l, random urine pH of 7.0, and urine anion gap of 8 mmol/l. CT scan of the abdomen revealed bilateral nephrocalcinosis. A diagnosis of type 1 RTA likely secondary to Sjögren’s Syndrome was made. She was started on citric acid potassium citrate with escalating dosages to a maximum dose of 60 mEq daily and potassium chloride over 5 years without significant improvement in serum K+ and HCO3 levels. She had multiple emergency room visits for persistent muscle pain, generalized weakness, and cardiac arrhythmias. Citric acid potassium citrate was then replaced with sodium bicarbonate at 15.5 mEq every 6 hours which was continued for 2 years without significant improvement in her symptoms and electrolytes. Amiloride 5 mg daily was added to her regimen as a potassium sparing treatment with dramatic improvement in her symptoms and electrolyte levels (as shown in the figures). Amiloride was increased to 10 mg daily and potassium supplementation was discontinued without affecting her electrolytes. Her sodium bicarbonate was weaned to 7.7 mEq daily

Validity and Reliability of Scores Obtained on Multiple-Choice Questions: Why Functioning Distractors Matter

Purpose Plausible distractors are important for accurate measurement of knowledge via multiple-choice questions (MCQs). This study demonstrates the impact of higher distractor functioning on validity and reliability of scores obtained on MCQs. Methods Free-response (FR) and MCQ versions of a neurohistology practice exam were given to four cohorts of Year 1 medical students. Consistently non-functioning multiple-choice distractors (<5% selection frequency) were replaced with those developed from incorrect responses on FR version of the items, followed by administration of the revised MCQ version to subsequent two cohorts. Validity was assessed by comparing an index of expected MCQ difficulty with an index of observed MCQ difficulty, while reliability was assessed via Cronbach’s alpha coefficient before and after replacement of consistently non-functioning distractors. Result Pre-intervention, effect size (Cohen’s d) of the difference between mean expected and observed MCQ difficulty indices was noted to be 0.4 – 0.59. Post-intervention, this difference reduced to 0.15 along with an increase in Cronbach’s alpha coefficient of scores obtained on MCQ version of the exam. Conclusion Multiple-choice distractors developed from incorrect responses on free-response version of the items enhance the validity and reliability of scores obtained on MCQs