Opening the 100-Year Window for Time Domain Astronomy

The large-scale surveys such as PTF, CRTS and Pan-STARRS-1 that have emerged within the past 5 years or so employ digital databases and modern analysis tools to accentuate research into Time Domain Astronomy (TDA). Preparations are underway for LSST which, in another 6 years, will usher in the second decade of modern TDA. By that time the Digital Access to a Sky Century @ Harvard (DASCH) project will have made available to the community the full sky Historical TDA database and digitized images for a century (1890--1990) of coverage. We describe the current DASCH development and some initial results, and outline plans for the "production scanning" phase and data distribution which is to begin in 2012. That will open a 100-year window into temporal astrophysics, revealing rare transients and (especially) astrophysical phenomena that vary on time-scales of a decade. It will also provide context and archival comparisons for the deeper modern surveysComment: 6 pages, 3 figures; invited talk at IAUS 28

Methods for the Measurement of Vitamin D Metabolites and Studies on Their Relationships in Health and Disease

The prevalence of vitamin D deficiency in the general population has become a major public health problem. Vitamin D deficiency might have significant consequences not only to bone health but possible to other autoimmune, infectious, cancer and cardiovascular diseases. The explosion of interests in vitamin D had sparked a massive increase in the number of laboratory requests for the measurement of serum 25 hydroxyvitamin D (25(OH)D). This in turn highlighted problems of the methodologies available for measuring vitamin D metabolites. The aim of the study was to develop and fully validate quantitative assays for measuring serum vitamin D metabolites by Liquid Chromatography Tandem Mass Spectrometry (LC/MS-MS). The methods were used to perform analysis on samples collected for vitamin D research studies to establish relationships between the metabolites and determine reference intervals. Using solid phase extraction to remove phospholipids in sample matrix and derivatisation to enhance sensitivity, assays were successfully developed for 25(OH)D3/D2, C3-epi-25(OH)D3/D2, and for the dihydroxyvitamin D 24,25(OH)2D3/D2 and 1,25(OH)2D3/D2. The performance characteristic of the assays satisfied industry standards for method validation. Results showed a high prevalence of C3-epi-25(OH)D3 (87.7%) in paediatric samples that resulted in misclassification of total 25(OH)D status in 10.4% of cases. Serum 25(OH)D showed a significant correlation with 24,25(OH)2D (r2=0.754, p<0.001), but not with 1,25(OH)2D (r2=0.1034). The reference intervals (2.5-97.5 percentile) for 25(OH)D:24,25(OH)2D ratio was established between 7-23. Loess fitting showed an increase in the 25(OH)D:24,25(OH)2D ratio at 25(OH)D <50 nmol/L; evidence of reduced catabolic activity during low vitamin D status. In contrast, when high dose vitamin D3 was supplemented, serum 24,25(OH)2D was found to be grossly elevated to counteract against excessive vitamin D and prevent toxicity. Using the 1,25(OH)2D:24,25(OH)2D/25(OH)D ratio model, this thesis was the first to demonstrate a relationship between the three metabolites, and the association with PTH concentration. This thesis has provided new insights to the vitamin D metabolism that will further our understanding and appreciation of its role in health and pathophysiological conditions. The methods developed have provided an analytical platform for many large scale studies in musculoskeletal research and other areas of science; the publications and citations are a testament to the impact of this research

FGF23 metabolism, a new paradigm for chronic kidney disease

Introduction:  Fibroblast growth factor-23 (FGF23) is a major regulator of phosphate metabolism often elevated in genetic hypophosphataemic disorders and in chronic kidney disease. Recent studies have identified relationships between FGF23 and various markers of iron status including ferritin. New assays measuring the intact form of FGF23 have been released.  Objective:  To determine the relationship between ferritin and C-terminal and intact FGF23 concentrations in blood.  Method:  FGF23 concentrations were measured using the 2nd generation, two-site enzyme-linked immunosorbent assay for either C-terminal or intact FGF23 (Immutopics Inc., Ca, USA). Ferritin was measured on a COBAS 6000 (Roche Diagnostics). Assay accuracy and precision were monitored using kit controls supplied by the manufacturers.  Results:  We observe a weak negative correlation between measurements of C-terminal and intact FGF23 (Pearson’s rho=0.85 p<0.0001). We observed no statistically significant correlation of ferritin concentrations with either FGF23 C-terminal or intact. However high concentrations of ferritin were observed in samples showing low concentrations of C-terminal FGF23 (<140RU/mL) and intact FGF23 (<122pg/mL).  Conclusion:  Although not statistically significant, we observe a negative relationship between concentrations of ferritin and FGF23. High level of C-terminal FGF23 is found in patients with chronic kidney disease, especially in patients with end-stage renal disease usually regarded as a compensatory response to hyperphosphatemia or phosphate overload. We observed a cluster of patients with retention of both C-terminal and intact FGF23 associated with low levels of ferritin suggesting that metabolism and/or excretion of FGF23 in CDK patients might be an iron dependent mechanism