Chiral Extrapolation of the Strangeness Changing K pi Form Factor

We perform a chiral extrapolation of lattice data on the scalar K pi form factor and the ratio of the kaon and pion decay constants within Chiral Perturbation Theory to two loops. We determine the value of the scalar form factor at zero momentum transfer, at the Callan-Treiman point and at its soft kaon analog as well as its slope. Results are in good agreement with their determination from experiment using the standard couplings of quarks to the W boson. The slope is however rather large. A study of the convergence of the chiral expansion is also performed.Comment: few minor change

Lattice QCD at the physical point: Simulation and analysis details

We give details of our precise determination of the light quark masses m_{ud}=(m_u+m_d)/2 and m_s in 2+1 flavor QCD, with simulated pion masses down to 120 MeV, at five lattice spacings, and in large volumes. The details concern the action and algorithm employed, the HMC force with HEX smeared clover fermions, the choice of the scale setting procedure and of the input masses. After an overview of the simulation parameters, extensive checks of algorithmic stability, autocorrelation and (practical) ergodicity are reported. To corroborate the good scaling properties of our action, explicit tests of the scaling of hadron masses in N_f=3 QCD are carried out. Details of how we control finite volume effects through dedicated finite volume scaling runs are reported. To check consistency with SU(2) Chiral Perturbation Theory the behavior of M_\pi^2/m_{ud} and F_\pi as a function of m_{ud} is investigated. Details of how we use the RI/MOM procedure with a separate continuum limit of the running of the scalar density R_S(\mu,\mu') are given. This procedure is shown to reproduce the known value of r_0m_s in quenched QCD. Input from dispersion theory is used to split our value of m_{ud} into separate values of m_u and m_d. Finally, our procedure to quantify both systematic and statistical uncertainties is discussed.Comment: 45 page

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange

Massively Parallel Sequencing and Analysis of the Necator americanus Transcriptome

The blood-feeding hookworm Necator americanus infects hundreds of millions of people. To elucidate fundamental molecular biological aspects of this hookworm, the transcriptome of adult Necator americanus was studied using next-generation sequencing and in silico analyses. Contigs (n = 19,997) were assembled from the sequence data; 6,771 of them had known orthologues in the free-living nematode Caenorhabditis elegans, and most encoded proteins with WD40 repeats (10.6%), proteinase inhibitors (7.8%) or calcium-binding EF-hand proteins (6.7%). Bioinformatic analyses inferred that C. elegans homologues are involved mainly in biological pathways linked to ribosome biogenesis (70%), oxidative phosphorylation (63%) and/or proteases (60%). Comparative analyses of the transcriptomes of N. americanus and the canine hookworm, Ancylostoma caninum, revealed qualitative and quantitative differences. Essential molecules were predicted using a combination of orthology mapping and functional data available for C. elegans. Further analyses allowed the prioritization of 18 predicted drug targets which did not have human homologues. These candidate targets were inferred to be linked to mitochondrial metabolism or amino acid synthesis. This investigation provides detailed insights into the transcriptome of the adult stage of N. americanus

A qualitative exploration of workarounds related to the implementation of national electronic health records in early adopter mental health hospitals

AIMS: To investigate the perceptions and reported practices of mental health hospital staff using national hospital electronic health records (EHRs) in order to inform future implementations, particularly in acute mental health settings. METHODS: Thematic analysis of interviews with a wide range of clinical, information technology (IT), managerial and other staff at two early adopter mental health National Health Service (NHS) hospitals in London, UK, implementing national EHRs. RESULTS: We analysed 33 interviews. We first sought out examples of workarounds, such as delayed data entry, entering data in wrong places and individuals using the EHR while logged in as a colleague, then identified possible reasons for the reported workarounds. Our analysis identified four main categories of factors contributing to workarounds (i.e., operational, cultural, organisational and technical). Operational factors included poor system integration with existing workflows and the system not meeting users' perceived needs. Cultural factors involved users' competence with IT and resistance to change. Organisational factors referred to insufficient organisational resources and training, while technical factors included inadequate local technical infrastructure. Many of these factors, such as integrating the EHR system with day-to-day operational processes, staff training and adequate local IT infrastructure, were likely to apply to system implementations in various settings, but we also identified factors that related particularly to implementing EHRs in mental health hospitals, for example: EHR system incompatibility with IT systems used by mental health-related sectors, notably social services; the EHR system lacking specific, mental health functionalities and options; and clinicians feeling unable to use computers while attending to distressed psychiatric patients. CONCLUSIONS: A better conceptual model of reasons for workarounds should help with designing, and supporting the implementation and adoption of, EHRs for use in hospital mental health settings

High-performance liquid chromatography–tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites

Applications of tandem mass spectrometry (MS/MS) techniques coupled with high-performance liquid chromatography (HPLC) in the identification and determination of phase I and phase II drug metabolites are reviewed with an emphasis on recent papers published predominantly within the last 6 years (2002–2007) reporting the employment of atmospheric pressure ionization techniques as the most promising approach for a sensitive detection, positive identification and quantitation of metabolites in complex biological matrices. This review is devoted to in vitro and in vivo drug biotransformation in humans and animals. The first step preceding an HPLC-MS bioanalysis consists in the choice of suitable sample preparation procedures (biomatrix sampling, homogenization, internal standard addition, deproteination, centrifugation, extraction). The subsequent step is the right optimization of chromatographic conditions providing the required separation selectivity, analysis time and also good compatibility with the MS detection. This is usually not accessible without the employment of the parent drug and synthesized or isolated chemical standards of expected phase I and sometimes also phase II metabolites. The incorporation of additional detectors (photodiode-array UV, fluorescence, polarimetric and others) between the HPLC and MS instruments can result in valuable analytical information supplementing MS results. The relation among the structural changes caused by metabolic reactions and corresponding shifts in the retention behavior in reversed-phase systems is discussed as supporting information for identification of the metabolite. The first and basic step in the interpretation of mass spectra is always the molecular weight (MW) determination based on the presence of protonated molecules [M+H]+ and sometimes adducts with ammonium or alkali-metal ions, observed in the positive-ion full-scan mass spectra. The MW determination can be confirmed by the [M-H]- ion for metabolites providing a signal in negative-ion mass spectra. MS/MS is a worthy tool for further structural characterization because of the occurrence of characteristic fragment ions, either MSn analysis for studying the fragmentation patterns using trap-based analyzers or high mass accuracy measurements for elemental composition determination using time of flight based or Fourier transform mass analyzers. The correlation between typical functional groups found in phase I and phase II drug metabolites and corresponding neutral losses is generalized and illustrated for selected examples. The choice of a suitable ionization technique and polarity mode in relation to the metabolite structure is discussed as well

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes