Technical pre-analytical effects on the clinical biochemistry of Atlantic salmon (Salmo salar L.)

Clinical biochemistry has long been utilized in human and veterinary medicine as a vital diagnostic tool, but despite occasional studies showing its usefulness in monitoring health status in Atlantic salmon (Salmo salar L.), it has not yet been widely utilized within the aquaculture industry. This is due, in part, to a lack of an agreed protocol for collection and processing of blood prior to analysis. Moreover, while the analytical phase of clinical biochemistry is well controlled, there is a growing understanding that technical pre-analytical variables can influence analyte concentrations or activities. In addition, post-analytical interpretation of treatment effects is variable in the literature, thus making the true effect of sample treatment hard to evaluate. Therefore, a number of pre-analytical treatments have been investigated to examine their effect on analyte concentrations and activities. In addition, reference ranges for salmon plasma biochemical analytes have been established to inform veterinary practitioners and the aquaculture industry of the importance of clinical biochemistry in health and disease monitoring. Furthermore, a standardized protocol for blood collection has been proposed

Managing complexity in a distributed digital library

As the capabilities of distributed digital libraries increase, managing organizational and software complexity becomes a key issue. How can collections and indexes be updated without impacting queries currently in progress? How can the system handle several user-interface clients for the same collections? Computer science professors and lectors from the University of Waikato have developed a software structure that successfully manages this complexity in the New Zealand Digital Library. This digital library has been a success in managing organizational and software complexity. The researchers' primary goal has been to minimize the effort required to keep the system operational and yet continue to expand its offerings

Alternative Data Reduction Procedures for UVES: Wavelength Calibration and Spectrum Addition

This paper addresses alternative procedures to the ESO supplied pipeline procedures for the reduction of UVES spectra of two quasar spectra to determine the value of the fundamental constant mu = Mp/Me at early times in the universe. The procedures utilize intermediate product images and spectra produced by the pipeline with alternative wavelength calibration and spectrum addition methods. Spectroscopic studies that require extreme wavelength precision need customized wavelength calibration procedures beyond that usually supplied by the standard data reduction pipelines. An example of such studies is the measurement of the values of the fundamental constants at early times in the universe. This article describes a wavelength calibration procedure for the UV-Visual Echelle Spectrometer on the Very Large Telescope, however, it can be extended to other spectrometers as well. The procedure described here provides relative wavelength precision of better than 3E-7 for the long-slit Thorium-Argon calibration lamp exposures. The gain in precision over the pipeline wavelength calibration is almost entirely due to a more exclusive selection of Th/Ar calibration lines.Comment: Accepted for publication in New Astronom

An Observational Determination of the Proton to Electron Mass Ratio in the Early Universe

In an effort to resolve the discrepancy between two measurements of the fundamental constant mu, the proton to electron mass ratio, at early times in the universe we reanalyze the same data used in the earlier studies. Our analysis of the molecular hydrogen absorption lines in archival VLT/UVES spectra of the damped Lyman alpha systems in the QSOs Q0347-383 and Q0405-443 yields a combined measurement of a (Delta mu)/mu value of (-7 +/- 8) x 10^{-6}, consistent with no change in the value of mu over a time span of 11.5 gigayears. Here we define (Delta mu) as (mu_z - mu_0) where mu_z is the value of mu at a redshift of z and mu_0 is the present day value. Our null result is consistent with the recent measurements of King et al. 2009, (Delta mu)/u = (2.6 +/- 3.0) x 10^{-6}, and inconsistent with the positive detection of a change in mu by Reinhold et al. 2006. Both of the previous studies and this study are based on the same data but with differing analysis methods. Improvements in the wavelength calibration over the UVES pipeline calibration is a key element in both of the null results. This leads to the conclusion that the fundamental constant mu is unchanged to an accuracy of 10^{-5} over the last 80% of the age of the universe, well into the matter dominated epoch. This limit provides constraints on models of dark energy that invoke rolling scalar fields and also limits the parameter space of Super Symmetric or string theory models of physics. New instruments, both planned and under construction, will provide opportunities to greatly improve the accuracy of these measurements.Comment: Accepted for publication in the Astrophysical Journa

Diatom Proteomics Reveals Unique Acclimation Strategies to Mitigate Fe Limitation

Phytoplankton growth rates are limited by the supply of iron (Fe) in approximately one third of the open ocean, with major implications for carbon dioxide sequestration and carbon (C) biogeochemistry. To date, understanding how alteration of Fe supply changes phytoplankton physiology has focused on traditional metrics such as growth rate, elemental composition, and biophysical measurements such as photosynthetic competence (Fv/Fm). Researchers have subsequently employed transcriptomics to probe relationships between changes in Fe supply and phytoplankton physiology. Recently, studies have investigated longer-term (i.e. following acclimation) responses of phytoplankton to various Fe conditions. In the present study, the coastal diatom, Thalassiosira pseudonana, was acclimated (10 generations) to either low or high Fe conditions, i.e. Fe-limiting and Fe-replete. Quantitative proteomics and a newly developed proteomic profiling technique that identifies low abundance proteins were employed to examine the full complement of expressed proteins and consequently the metabolic pathways utilized by the diatom under the two Fe conditions. A total of 1850 proteins were confidently identified, nearly tripling previous identifications made from differential expression in diatoms. Given sufficient time to acclimate to Fe limitation, T. pseudonana up-regulates proteins involved in pathways associated with intracellular protein recycling, thereby decreasing dependence on extracellular nitrogen (N), C and Fe. The relative increase in the abundance of photorespiration and pentose phosphate pathway proteins reveal novel metabolic shifts, which create substrates that could support other well-established physiological responses, such as heavily silicified frustules observed for Fe-limited diatoms. Here, we discovered that proteins and hence pathways observed to be down-regulated in short-term Fe starvation studies are constitutively expressed when T. pseudonana is acclimated (i.e., nitrate and nitrite transporters, Photosystem II and Photosystem I complexes). Acclimation of the diatom to the desired Fe conditions and the comprehensive proteomic approach provides a more robust interpretation of this dynamic proteome than previous studies.This work was supported by National Science Foundation grants OCE1233014 (BLN) and the Office of Polar Programs Postdoctoral Fellowship grant 0444148 (BLN). DRG was supported by National Institutes of Health 5P30ES007033-10. AH and MTM were supported by Natural Sciences and Engineering Research Council of Canada. RFS and PWB were supported by the New Zealand Royal Society Marsden Fund and the Ministry of Science. This work is supported in part by the University of Washington's Proteomics Computer Resource Centre (UWPR95794). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Blocking neutrophil integrin activation prevents ischemia-reperfusion injury.

Neutrophil recruitment, mediated by β2 integrins, combats pyogenic infections but also plays a key role in ischemia-reperfusion injury and other inflammatory disorders. Talin induces allosteric rearrangements in integrins that increase affinity for ligands (activation). Talin also links integrins to actin and other proteins that enable formation of adhesions. Structural studies have identified a talin1 mutant (L325R) that perturbs activation without impairing talin's capacity to link integrins to actin and other proteins. Here, we found that mice engineered to express only talin1(L325R) in myeloid cells were protected from renal ischemia-reperfusion injury. Dissection of neutrophil function in vitro and in vivo revealed that talin1(L325R) neutrophils had markedly impaired chemokine-induced, β2 integrin-mediated arrest, spreading, and migration. Surprisingly, talin1(L325R) neutrophils exhibited normal selectin-induced, β2 integrin-mediated slow rolling, in sharp contrast to the defective slow rolling of neutrophils lacking talin1 or expressing a talin1 mutant (W359A) that blocks talin interaction with integrins. These studies reveal the importance of talin-mediated activation of integrins for renal ischemia-reperfusion injury. They further show that neutrophil arrest requires talin recruitment to and activation of integrins. However, although neutrophil slow rolling requires talin recruitment to integrins, talin-mediated integrin activation is dispensable

Temporal-spatial modeling of electron density enhancement due to successive lightning strokes

We report results on the temporal-spatial modeling of electron density enhancement due to successive lightning strokes. Stroke rates based on World-Wide Lightning Location Network measurements are used as input to an axisymmetric Finite Difference Time Domain model that describes the effect of lightning electromagnetic pulses (EMP) on the ionosphere. Each successive EMP pulse interacts with a modified background ionosphere due to the previous pulses, resulting in a nonlinear electron density perturbation over time that eventually reaches a limiting value. The qualitative ionospheric response to successive EMPs is presented in 2-D, axisymmetric space. Results from this study show that the nonlinear electron density perturbations due to successive lightning strokes must be taken into account and varies with altitude. The limiting maximum electron density is reached earlier in time for higher altitudes, and the most significant effect occurs at 88 km. The limiting modeled electron density profile in the 83–91 km altitude range does not depend on the initial electron density

Timing of the first vancomycin maintenance dose in an acute hospital setting - room for improvement?

Introduction Intravenous vancomycin therapy typically starts with a loading dose followed by a maintenance dose 12 to 24 hours later. In the acute hospital setting, this often results in doses being administered in the middle of the night, which is impractical for both patients and staff. This audit examined current practice and developed new guidelines to support greater flexibility in the timing of the first maintenance dose. Methods Data recording forms used by pharmacists to support the therapeutic drug monitoring of vancomycin were collected from two hospital sites over six weeks. Forms containing at least two vancomycin concentrations were selected and the time of administration of the first maintenance dose was recorded. Individual vancomycin pharmacokinetic parameter estimates were obtained using MAP Bayesian analysis then used to predict vancomycin concentrations 6, 8, 10, 12 and 14 hours after a banded loading dose and 20 mg/kg (capped at 3000 mg). Predicted concentrations were compared with a target range of 10 – 20 mg/L. Results Data were obtained from 49 patients with a mean (SD) age of 63.1 (16.7) years and weight 80.1 (27.6) kg. In all patients, creatinine clearance estimates were >40 mL/min and, according to current practice guidelines, all patients required 12 hourly maintenance dosing. The time recorded for the administration of the first maintenance dose was between 11 pm and 7 am in 30 (61%) of these patients. In 14 patients (29%), the first maintenance dose was administered >12 hours after loading. The target range was achieved with banded doses (20 mg/kg) in 65% (71%) of concentrations at 6 hours, 74% (84%) at 8 hours, 57% (67%) at 10 hours, 53% (55%) at 12 hours and 39% (43%) at 14 hours. Conclusions This audit has shown that current practice results in a high proportion of vancomycin maintenance doses being administered at impractical times. Allowing a more flexible time window of 6-12 hours after the loading dose for administration of the first vancomycin maintenance dose could help to alleviate this problem and reduce the risk of early subtherapeutic vancomycin trough concentrations