Laboratory evaluation of erythromycin in a general hospital

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Angular dependent planar metamagnetism in the hexagonal compounds TbPtIn and TmAgGe

Detailed magnetization measurements, M(T,H,theta), were performed on single crystals of TbPtIn and TmAgGe (both members of the hexagonal Fe_2P/ZrNiAl structure type), for the magnetic field H applied perpendicular to the crystallographic c axis. These data allowed us to identify, for each compound, the easy-axes for the magnetization, which coincided with high symmetry directions ([120] for TbPtIn and [110] for TmAgGe). For fixed orientations of the field along each of the two six-fold symmetry axes, a number of magnetically ordered phases is being revealed by M(H,T) measurements below T_N. Moreover, T ~ 2 K, M(H)|_theta measurements for both compounds (with H applied parallel to the basal plane), as well as T = 20 K data for TbPtIn, reveal five metamagnetic transitions with simple angular dependencies: H_{ci,j} ~ 1/cos(theta +/- phi), where phi = 0^0 or 60^0. The high field magnetization state varies with theta like 2/3*mu_{sat}(R^{3+})*cos(theta), and corresponds to a crystal field limited saturated paramagnetic, CL-SPM, state. Analysis of these data allowed us to model the angular dependence of the locally saturated magnetizations M_{sat} and critical fields H_c with a three coplanar Ising-like model, in which the magnetic moments are assumed to be parallel to three adjacent easy axes. Furthermore, net distributions of moments were inferred based on the measured data and the proposed model

Confirmation of co-denitrification in grazed grassland

peer-reviewedPasture-based livestock systems are often associated with losses of reactive forms of nitrogen (N) to the environment. Research has focused on losses to air and water due to the health, economic and environmental impacts of reactive N. Di-nitrogen (N2) emissions are still poorly characterized, both in terms of the processes involved and their magnitude, due to financial and methodological constraints. Relatively few studies have focused on quantifying N2 losses in vivo and fewer still have examined the relative contribution of the different N2 emission processes, particularly in grazed pastures. We used a combination of a high 15N isotopic enrichment of applied N with a high precision of determination of 15N isotopic enrichment by isotope-ratio mass spectrometry to measure N2 emissions in the field. We report that 55.8 g N m−2 (95%, CI 38 to 77 g m−2) was emitted as N2 by the process of co-denitrification in pastoral soils over 123 days following urine deposition (100 g N m−2), compared to only 1.1 g N m−2 (0.4 to 2.8 g m−2) from denitrification. This study provides strong evidence for co-denitrification as a major N2 production pathway, which has significant implications for understanding the N budgets of pastoral ecosystems.The authors are grateful for the funding that was provided through the Research Stimulus Fund Program administered by the Department of Agriculture & Food under the National Development Plan 2007–2013 RSF 07536. The first author is grateful for the funding provided by Teagasc through the Walsh Fellowship Scheme

A rapid allele-specific assay for HLA-A*32:01 to identify patients at risk for vancomycin-induced Drug Reaction with Eosinophilia and systemic symptoms

Human leukocyte antigen (HLA) alleles have been implicated as risk factors for immune-mediated adverse drug reactions. We recently reported a strong association between HLA-A*32:01 and vancomycin-induced drug reaction with eosinophilia and systemic symptoms (DRESS). Identification of individuals with the risk allele prior to or shortly after the initiation of vancomycin therapy is of great clinical importance to prevent morbidity and mortality, improve drug safety and antibiotic treatment options. A prerequisite to the success of a pharmacogenetic screening tests is the development of simple, robust, cost-effective single HLA allele test that can be implemented in routine diagnostic laboratories. In this study, we developed a simple, real-time allele-specific PCR for typing the HLA-A*32:01 allele. Four-hundred and fifty-eight DNA samples including thirty HLA-A*32:01-positive samples were typed by allele-specific PCR. Compared to ASHI accredited sequence-based high-resolution, full allelic HLA typing, this assay demonstrates 100% accuracy, sensitivity of 100% (95% CI: 88.43% to 100%) and specificity of 100% (95% CI: 99.14% to 100%). The lowest limit of detection of this assay using the Power Up SYBR Green is 10 ng of template DNA. The assay demonstrates a sensitivity and specificity to differentiate HLA-A*32:01 allele from closely related non-HLA-A*32 alleles and may be used in clinical settings to identify individuals with the risk allele prior or during the course of vancomycin therapy

Network development in biological gels: role in lymphatic vessel development

In this paper, we present a model that explains the prepatterning of lymphatic vessel morphology in collagen gels. This model is derived using the theory of two phase rubber material due to Flory and coworkers and it consists of two coupled fourth order partial differential equations describing the evolution of the collagen volume fraction, and the evolution of the proton concentration in a collagen implant; as described in experiments of Boardman and Swartz (Circ. Res. 92, 801–808, 2003). Using linear stability analysis, we find that above a critical level of proton concentration, spatial patterns form due to small perturbations in the initially uniform steady state. Using a long wavelength reduction, we can reduce the two coupled partial differential equations to one fourth order equation that is very similar to the Cahn–Hilliard equation; however, it has more complex nonlinearities and degeneracies. We present the results of numerical simulations and discuss the biological implications of our model

Complete Avulsion of the Extensor Mechanism of a Finger with Simultaneous Dislocation of the Proximal Interphalangeal Joint

We report a rare case of open dislocation of the proximal interphalangeal (PIP) joint, associated with simultaneous avulsion of the central band and distal insertion of the extensor mechanism, rapture of the proximal volar plate, and rapture of the ulnar collateral ligament of the PIP joint

Plasma Metabolomics Implicate Modified Transfer RNAs and Altered Bioenergetics in the Outcome of Pulmonary Arterial Hypertension.

BACKGROUND: -Pulmonary arterial hypertension (PAH) is a heterogeneous disorder with high mortality. METHODS: -We conducted a comprehensive study of plasma metabolites using ultra-performance liquid chromatography mass-spectrometry to (1) identify patients at high risk of early death, (2) identify patients who respond well to treatment and (3) provide novel molecular insights into disease pathogenesis. RESULTS: -53 circulating metabolites distinguished well-phenotyped patients with idiopathic or heritable PAH (n=365) from healthy controls (n=121) following correction for multiple testing (p<7.3e-5) and confounding factors, including drug therapy, renal and hepatic impairment. A subset of 20/53 metabolites also discriminated PAH patients from disease controls (symptomatic patients without pulmonary hypertension, n=139). 62 metabolites were prognostic in PAH, with 36/62 independent of established prognostic markers. Increased levels of tRNA-specific modified nucleosides (N2,N2-dimethylguanosine, N1-methylinosine), TCA cycle intermediates (malate, fumarate), glutamate, fatty acid acylcarnitines, tryptophan and polyamine metabolites and decreased levels of steroids, sphingomyelins and phosphatidylcholines distinguished patients from controls. The largest differences correlated with increased risk of death and correction of several metabolites over time was associated with a better outcome. Patients who responded to calcium channel blocker therapy had metabolic profiles similar to healthy controls. CONCLUSIONS: -Metabolic profiles in PAH are strongly related to survival and should be considered part of the deep phenotypic characterisation of this disease. Our results support the investigation of targeted therapeutic strategies that seek to address the alterations in translational regulation and energy metabolism that characterize these patients

HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms

Background Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS) which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy which impacts future treatment choices. Variations in human leukocyte antigen (HLA) class I in particular have been associated with serious T-cell mediated adverse drug reactions which has led to preventive screening strategies for some drugs. Objective To determine if variation in the HLA region is associated with vancomycin-induced DRESS. Methods Probable vancomycin DRESS cases were matched 1:2 with tolerant controls based on sex, race, and age using BioVU, Vanderbilt’s deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by conditional logistic regression. An extended sample set from BioVU was utilized to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele. Results Twenty-three individuals met inclusion criteria for vancomycin-associated DRESS. 19/23 (82.6%) cases carried HLA-A*32:01 compared to 0/46 (0%) of the matched vancomycin tolerant controls (p=1x10-8) and 6.3% of the BioVU population (n=54,249) (p=2x10-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01 positive group indicated that 19.2% developed DRESS and did so within four weeks. Conclusions HLA-A*32:01 is strongly associated with vancomycin DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug and preserve future treatment options with co-administered antibiotics

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter