Enhanced 3-epi-25-hydroxyvitamin D3 signal leads to overestimation of its concentration and amplifies interference in 25-hydroxyvitamin D LC-MS/MS assays

Background 3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3) interferes in most liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for 25-hydroxyvitamin D (25OHD). The clinical significance of this is unclear, with concentrations from undetectable to 230 nmol/L reported. Many studies have quantified 3-epi-25OHD3 based on 25OHD3 calibrators or other indirect methods, and we speculated that this contributes to the observed variability in reported 3-epi-25OHD3 concentrations. Methods We compared continuous MS/MS infusions of 3-epi-25OHD3 and 25OHD3 solutions, spiked both analytes into the same serum matrix and analysed patient samples to assess the effect of three different quantitation methods on 3-epi-25OHD3 concentration. Experiments were performed on an LC-MS/MS system using a phenyl column which does not resolve 3-epi-25OHD3, and a modified method utilizing a Zorbax SB-CN column that chromatographically resolves 3-epi-25OHD3 from 25OHD3. Results A greater 3-epi-25OHD3 signal, compared with 25OHD3, was observed during equimolar post-column continuous infusion of analyte solutions, and following analysis of a serum pool spiked with both analytes. 3-epi-25OHD3 signal enhancement was dependent on mobile phase composition. Compared with 3-epi-25OHD3 calibrators, indirect quantitation methods resulted in up to 10 times as many samples having 3-epi-25OHD3 concentrations ≥ 10 nmol/L, and an approximately fourfold increase in the maximum observed 3-epi-25OHD3 concentration to 95 nmol/L. Conclusions Enhanced 3-epi-25OHD3 signal leads to overestimation of its concentrations in the indirect quantitation methods used in many previous studies. The enhanced signal may contribute to greater interference in some 25OHD LC-MS/MS assays than others. We highlight that equimolar responses cannot be assumed in LC-MS/MS systems, even if two molecules are structurally similar

Nontrivial Sha in the Jacobian of an Infinite Family of Curves of Genus 2.

We give an infinite family of curves of genus 2 whose Jacobians have non-trivial members of the Tate-Shafarevich group for descent via Richelot isogeny. We prove this by performing a descent via Richelot isogeny and a complete 2-descent on the isogenous Jacobian. We also give an explicit model of an associated family of surfaces which violate the Hasse principle

The Use of a Laser Doppler Velocimeter in a Standard Flammability Tube

The use of the Laser Doppler Velocimeter, (LDV), to measure the flow associated with the passage of a flame through a standard flammability limit tube (SFLT) was studied. Four major results are presented: (1) it is shown that by using standard ray tracing calculations, the displacement of the LDV volume and the fringe rotation within the experimental error of measurement can be predicted; (2) the flow velocity vector field associated with passage of an upward propagating flame in an SFLT is determined; (3) it is determined that the use of a light interruption technique to track particles is not feasible; and (4) it is shown that a 25 mW laser is adequate for LDV measurements in the Shuttle or Spacelab

Heavy Quark Physics From Lattice QCD

We review the application of lattice QCD to the phenomenology of b- and c-quarks. After a short discussion of the lattice techniques used to evaluate hadronic matrix elements and the corresponding systematic uncertainties, we summarise results for leptonic decay constants, B--Bbar mixing, semileptonic and rare radiative decays. A discussion of the determination of heavy quark effective theory parameters is followed by an explanation of the difficulty in applying lattice methods to exclusive nonleptonic decays.Comment: 52 pages LaTeX with 10 eps files. Requires: hfsprocl.sty (included) plus axodraw.sty, rotating.sty and array.sty. To appear in Heavy Flavours (2nd edition) edited by A J Buras and M Lindner (World Scientific, Singapore). Revised version corrects typo in axis labelling of Fig 1

Effect of a quality improvement programme on leadership, innovation and use of quality improvement methods in general practice

Introduction Market mechanisms and pay-for-performance have failed to deliver continuing improvements in UK clinical care. Leadership and innovation are currently seen as essential to maintain and improve clinical quality but little is known about the relationship between these and the extent to which quality improvement (QI) methods are used in general practice. This study aimed to investigate the effect of quality improvement training on leadership behaviour, culture of innovation and adoption of QI methods in general practice. Method Self-administered postal questionnaires were sent to general practitioner quality leads in one UK county at the beginning (2007) and the end (2010) of a QI programme. The questionnaire consisted of background demographic information, a 12-item scale to assess leadership behaviour, a seven-dimension self-rating scale for innovation culture and questions on current use of quality improvement techniques and the effect of this on practice. We analysed change between the two surveys and the effect of participation in QI training. Results Sixty-three completed questionnaires (62%) were returned in 2007 and 47 (46%) in 2010; 32 practices completed both surveys. Although leadership behaviours were not commonly expressed, many practices reported a positive culture of innovation with significant positive correlation between leadership and innovation (r = 0.57; P < 0.001); apart from clinical audit and significant event analysis, QI methods were not reported as having been adopted by most participating practices. Percentage leadership score changed little over three years (increase 4.0 points, 95%CI -8.9 to 16.9) with little difference between participating and non-participating practices (7.6, -6.4 to 21.6) and no evidence of differential change (-1.5, -17.0 to 14.0). Percentage innovation culture scores showed a similar pattern (time -4.1 points, -15.1 to 6.9, group -1.6, -12.7 to 9.4, differential change 5.3, -7.8 to 18.5). Conclusions Leadership behaviours were infrequently reported, and despite describing a culture of innovation there was low uptake of QI methods beyond clinical and significant event audit even after practices participated in a QI programme. There is evidence that practices may need greater support to enhance leadership competences and develop quality improvement skills to stimulate innovation if improvements in health care are to accelerate

Archaeological Studies for the San Antonio Channel Improvement Project, including Investigations at Guenther\u27s Upper Mill (41BX342)

Under Contract No. DACW63-81-C-0022 to the Department of the Army, Corps of Engineers, Fort Worth District, the Center for Archaeological Research, The University of Texas at San Antonio, in the spring of 1981, conducted historic research and survey in the areas to be affected by the San Antonio Channel Improvement Project. In the summer of 1981, extensive archaeological testing and excavation were done to determine the extent of the structural remains on the sites of Guenther\u27s Upper Mill and the Stribling House. In the spring and summer of 1982, the Center documented the removal and replacement of the mill\u27s west wall. As a result of the investigations, it can now be affirmed that most of the foundation of the east section of the mill is still present beneath the ground. The main foundation walls are made of cut limestone and measure two feet in thickness, except for the west wall which is three feet thick. Of the other buildings at various times related to the mill, only portions of a late (ca. 1910) stone and cement foundation for the Reigler Creamery still remain in the ground. The survey revealed no other cultural resources to be affected by the project

The Brauer-Manin Obstruction and Sha[2].

We discuss the Brauer-Manin obstruction on del Pezzo surfaces of degree 4. We outline a detailed algorithm for computing the obstruction and provide associated programs in magma. This is illustrated with the computation of an example with an irreducible cubic factor in the singular locus of the defining pencil of quadrics (in contrast to previous examples, which had at worst quadratic irreducible factors). We exploit the relationship with the Tate-Shafarevich group to give new types of examples of Sha[2], for families of curves of genus 2 of the form y^2 = f(x), where f(x) is a quintic containing an irreducible cubic factor

Operational Capabilities: The Secret Ingredient

We develop a theoretical definition of operational capabilities, based on the strategic management and operations management literature, and differentiate this construct from the related constructs of resources and operational practices, drawing upon the resourcebased view of the firm as our foundation. We illustrate the key features of operational capabilities using the illustration of a restaurant kitchen. Because the traits of operational capabilities are distinct, they create a barrier to imitation, making them a potential source of competitive advantage. However, operational capabilities are particularly challenging to measure, because they emerge gradually and are tacit, embedded, and manifested differently across firms. In solving this measurement conundrum, we draw upon similar situations experienced by Schein (2004) and Eisenhardt and Martin (2000) in operationalizing organizational culture and dynamic capabilities. A taxonomy of six emergent operational capabilities is developed: operational improvement, operational innovation, operational customization, operational cooperation, operational responsiveness, and operational reconfiguration. A set of measurement scales is developed, in order to measure each of the operational capabilities, and validated using two different datasets. This allows replication of the psychometric properties of the multi-item scales and helps to ensure the validity of the resulting measures