Vitamin D measurement, the debates continue, new analytes have emerged, developments have variable outcomes

The demand for measurement of vitamin D metabolites for clinical diagnosis and to advance our understanding of the role of vitamin D in human health has significantly increased in the last decade. New developments in technologies employed have enabled the separation and quantification of additional metabolites and interferences. Also, developments of immunoassays have changed the landscape. Programmes and materials for assay standardisation, harmonisation and the expansion of the vitamin D external quality assurance scheme (DEQAS) with the provision of target values as measured by a reference measurement procedure have improved standardisation, quality assurance and comparability of measurements. In this article, we describe developments in the measurement of the commonly analysed vitamin D metabolites in clinical and research practice. We describe current analytical approaches, discuss differences between assays, their origin, and how these may be influenced by physiological and experimental conditions. The value of measuring metabolites beyond 25 hydroxyvitamin D (25(OH)D), the marker of vitamin D status, in routine clinical practice is not yet confirmed. Here we provide an overview of the value and application of the measurement of 1,25 dihydroxyvitamin D, 24,25 dihydroxyvitamin D and free 25OHD in the diagnosis of patients with abnormalities in vitamin D metabolism and for research purposes

Reference intervals for serum 24,25-Dihydroxyvitamin D and the ratio with 25-Hydroxyvitamin established using a newly developed LC-MS/MS method

24,25(OH)2D is the product of 25(OH)D catabolism by CYP24A1.The measurement of serum 24,25(OH)2D concentration may serve as an indicator of vitamin D catabolic status and the relative ratio with 25(OH)D can be used to identify patients with inactivating mutations in CYP24A1. We describe a LC-MS/MS method to determine: 1) the relationships between serum 24,25(OH)2D and 25(OH)D; 2) serum reference intervals in healthy individuals; 3) the diagnostic accuracy of 24,25(OH)2D measurement as an indicator for vitamin D status; 4) 24,25(OH)2D cut-off value for clinically significant change between inadequate and sufficient 25(OH)D status. Serum samples of healthy participants (n=1996) from Army recruits and patients (n=294) were analysed. The LC-MS/MS assay satisfied industry standards for method validation. We found a positive, concentration-dependent relationship between serum 24,25(OH)2D and 25(OH)2D concentrations. The 25(OH)D:24,25(OH)2D ratio was significantly higher (p4.2 nmol/L was identified as a diagnostic cut-off for 25(OH)D replete status. One patient sample with an elevated 25(OH)D:24,25(OH)2D ratio of 32 and hypercalcaemia who on genetic testing confirmed to have a biallelic mutation of CYP24A1. Our study demonstrated the feasibility of a combined 24,25(OH)2D and 25(OH)D assessment profile. Our established cut-off value for 24,25(OH)2D and ratio reference ranges can be useful to clinicians in the investigation of patients with an impaired calcium/phosphate metabolism and may point towards the existence of CYP24A1 gene abnormalities

Embryologic and Fetal Development of the Human Eyelid

To review the recent data about eyelid morphogenesis, and outline a timeline for eyelid development from the very early stages during embryonic life till final maturation of the eyelid late in fetal life

Tissue Necrosis Following Diode Laser-assisted Transcanalicular Dacryocystorhinostomy

Advantages of transcanalicular laser-assisted dacryocystorhinostomy (TCDCR) over conventional external and endonasal dacryocystorhinostomy (DCR) have been purported to include decreased operating time, reduced morbidity, enhanced cosmesis, avoidance of general anesthesia, and a shorter recovery time. However, one case of skin necrosis has recently been reported to have occurred following diode laser-assisted TCDCR, and we now report three additional cases that were evaluated by the Ophthalmic Plastic Surgery services at the University of North Carolina and the University of California, San Francisco. Three patients developed full-thickness tissue necrosis over the medial canthus following TCDCR, and two of these patients experienced persistent tissue breakdown at the site following reconstructive repair

Comparative study of healthy older and younger adults shows they have the same skin concentration of vitamin D3 precursor, 7-dehydrocholesterol, and similar response to UVR

Vitamin D3 synthesis in human skin is initiated by solar ultraviolet radiation (UVR) exposure of precursor 7-dehydrocholesterol (7DHC), but influence of age on the early stage of vitamin D3 metabolism is uncertain. We performed a prospective standardised study in healthy ambulant adults aged ≥65 and ≤40 years examining (1) if baseline skin 7DHC concentration differs between younger and older adults and (2) the impact of older age on serum vitamin D3 response to solar simulated UVR. Eleven younger (18–40 years) and 10 older (65–89 years) adults, phototype I–III, received low-dose UVR (95% UVA, 5% UVB, 1.3 SED) to ~35% of the body surface area. Biopsies were taken for 7DHC assay from unexposed skin, skin immediately and 24 h post-UVR, and blood sampled at baseline, 24 h and 7 d post-UVR for vitamin D3 assay. Samples were analysed by HPLC-MS/MS. Baseline skin 7DHC (mean ± SD) was 0.22 ± 0.07 and 0.25 ± 0.08 µg/mg in younger versus older adults (no significant difference). Baseline serum vitamin D3 concentration was 1.5 ± 1.5 and 1.5 ± 1.7 nmol/L in younger versus older adults, respectively, and showed a significant increase in both groups post-UVR (no significant differences between age groups). Thus, skin 7DHC concentration was not a limiting factor for vitamin D3 production in older relative to younger adults. This information assists public health guidance on sun exposure/vitamin D nutrition, with particular relevance to the growing populations of healthy ambulant adults ≥65 years

The Epoch of Disk Settling: Z Approximately Equal to 1 to Now

We present evidence from a sample of 544 galaxies from the DEEP2 Survey for evolution of the internal kinematics of blue galaxies over 0.2 < z < 1.2. DEEP2 provides a large sample of high resolution galaxy spectra and dual-band Hubble imaging from which we measure emission-line kinematics and galaxy inclinations, respectively. Our large sample allows us to overcome scatter intrinsic to galaxy properties, in order to examine trends. At a fixed stellar mass, galaxies systematically decrease in disturbed motions and increase in rotation velocity and potential well depth with time. The most massive galaxies are the most well-ordered at all times, with higher rotation velocities and less disturbed motions compared to less massive galaxies. We quantify disturbed motions with an integrated gas velocity dispersion (sigma(sub g)), which is unlike the typical pressure-supported velocity dispersion measured for early type galaxies and galaxy bulges. Due to finite slit width and seeing, sigma(sub g) integrates over unresolved velocity gradients which can correspond to non-ordered gas kinematics such as small-scale velocity gradients, gas motions due to star-formation, or super-imposed clumps along the line-of-sight. We compile surveys of galaxy kinematics over 1.2 < z < 3.8 and do not find any trends with redshift, likely because these studies are biased toward the most highly star-forming systems. In summary, over the last approx 8 billion years since z = 1.2, blue galaxies evolve from disturbed to ordered systems as they settle to become the rotation-dominated disk galaxies observed in the Universe today, with the most massive galaxies always being the most evolved at any time

Magnetic order in holmium and erbium formate: Parent frameworks for a potential random spin chain paramagnet

This work uses a combination of neutron diffraction and bulk property measurements to establish the low temperature magnetic states in the dense metal-organic frameworks Ho(HCO2)3 and Er(HCO2)3; whose structures feature chains of face-sharing LnO9 polyhedra packed into a triangular lattice. Below 0.7 K Ho(HCO2)3 is found to adopt a state in which the magnetic moment on its ferromagnetic chains vary from neighbouring chains but the sum around each triangle is constant. Er(HCO2)3 is found to be the first lanthanide formate to adopt an ordered magnetic state with antiferromagnetic coupling within its chains near 50 mK. The potential to combine the ferromagnetic and antiferromagnetic coupling within chains associated with Ho and Er cations, respectively, in the same compound has also been explored via the series Ho1-xErx(HCO2)3. Ho0.5Er0.5(HCO2)3 remains paramagnetic to 0.4 K, suggesting it may be a starting point to search for a random spin chain paramagnet

Complete genome sequence of Candidatus Ruthia magnifica

The hydrothermal vent clam Calyptogena magnifica (Bivalvia: Mollusca) is a member of the Vesicomyidae. Species within this family form symbioses with chemosynthetic Gammaproteobacteria. They exist in environments such as hydrothermal vents and cold seeps and have a rudimentary gut and feeding groove, indicating a large dependence on their endosymbionts for nutrition. The C. magnifica symbiont, Candidatus Ruthia magnifica, was the first intracellular sulfur-oxidizing endosymbiont to have its genome sequenced (Newton et al. 2007). Here we expand upon the original report and provide additional details complying with the emerging MIGS/MIMS standards. The complete genome exposed the genetic blueprint of the metabolic capabilities of the symbiont. Genes which were predicted to encode the proteins required for all the metabolic pathways typical of free-living chemoautotrophs were detected in the symbiont genome. These include major pathways including carbon fixation, sulfur oxidation, nitrogen assimilation, as well as amino acid and cofactor/vitamin biosynthesis. This genome sequence is invaluable in the study of these enigmatic associations and provides insights into the origin and evolution of autotrophic endosymbiosis

Gefitinib and <i>EGFR</i> Gene Copy Number Aberrations in Esophageal Cancer

Purpose: The cancer esophagus gefitinib (COG) trial demonstrated improved progression free survival with the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI), gefitinib relative to placebo in advanced esophageal cancer patients with disease progression after chemotherapy. Rapid and durable responses were observed in a minority. We hypothesised that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Patients and Methods: A pre-specified blinded molecular analysis of COG trial tumours was conducted to compare efficacy of gefitinib to placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF and PIK3CA mutation status. EGFR CNG was determined by fluorescent insitu hybridisation (FISH) using pre-specified criteria and EGFR FISH positive defined as high polysomy or amplification. Results: Biomarker data were available for 340 patients. In EGFR FISH positive tumours (20.2%) overall survival was improved with gefitinib compared to placebo (hazard ratio [HR] for death, 0.59; 95% confidence interval [CI], 0.35, 1.00 p=0.05). In EGFR FISH negative tumours there was no difference in overall survival with gefitinib compared to placebo (HR for death, 0.90, 95% CI 0.69, 1.18 p=0.46). EGFR amplification (7.2%) patients gained greatest benefit from gefitinib (HR for death, 0.21; 95% CI 0.07-0.64; p=0.006). There was no difference in overall survival for gefitinib versus placebo for patients with EGFR, KRAS, BRAF and PIK3CA mutations, or for any mutation versus none. Conclusion: EGFR CNG assessed by FISH appears to identify a subgroup of esophageal cancer patients who may benefit from gefitinib as a second line treatment, and suggests that anti-EGFR 3 therapies should be investigated in prospective clinical trials in different settings in EGFR FI SH positive, and in particular EGFR amplified, esophageal cancer

Deep ugrizY imaging and DEEP2/3 spectroscopy: a photometric redshift testbed for LSST and public release of data from the DEEP3 Galaxy Redshift Survey

We present catalogues of calibrated photometry and spectroscopic redshifts in the Extended Groth Strip, intended for studies of photometric redshifts (photo-z’s). The data includes ugriz photometry from Canada–France–Hawaii Telescope Legacy Survey (CFHTLS) and Y-band photometry from the Subaru Suprime camera, as well as spectroscopic redshifts from the DEEP2, DEEP3, and 3D-HST surveys. These catalogues incorporate corrections to produce effectively matched-aperture photometry across all bands, based upon object size information available in the catalogue and Moffat profile point spread function fits. We test this catalogue with a simple machine learning-based photometric redshift algorithm based upon Random Forest regression, and find that the corrected aperture photometry leads to significant improvement in photo-z accuracy compared to the original SEXTRACTOR catalogues from CFHTLS and Subaru. The deep ugrizY photometry and spectroscopic redshifts are well suited for empirical tests of photometric redshift algorithms for LSST. The resulting catalogues are publicly available at http://d-scholarship.pitt.edu/36064/. We include a basic summary of the strategy of the DEEP3 Galaxy Redshift Survey to accompany the recent public release of DEEP3 data