Investigating and learning lessons from early experiences of implementing ePrescribing systems into NHS hospitals:a questionnaire study

Background: ePrescribing systems have significant potential to improve the safety and efficiency of healthcare, but they need to be carefully selected and implemented to maximise benefits. Implementations in English hospitals are in the early stages and there is a lack of standards guiding the procurement, functional specifications, and expected benefits. We sought to provide an updated overview of the current picture in relation to implementation of ePrescribing systems, explore existing strategies, and identify early lessons learned.Methods: a descriptive questionnaire-based study, which included closed and free text questions and involved both quantitative and qualitative analysis of the data generated.Results: we obtained responses from 85 of 108 NHS staff (78.7% response rate). At least 6% (n = 10) of the 168 English NHS Trusts have already implemented ePrescribing systems, 2% (n = 4) have no plans of implementing, and 34% (n = 55) are planning to implement with intended rapid implementation timelines driven by high expectations surrounding improved safety and efficiency of care. The majority are unclear as to which system to choose, but integration with existing systems and sophisticated decision support functionality are important decisive factors. Participants highlighted the need for increased guidance in relation to implementation strategy, system choice and standards, as well as the need for top-level management support to adequately resource the project. Although some early benefits were reported by hospitals that had already implemented, the hoped for benefits relating to improved efficiency and cost-savings remain elusive due to a lack of system maturity.Conclusions: whilst few have begun implementation, there is considerable interest in ePrescribing systems with ambitious timelines amongst those hospitals that are planning implementations. In order to ensure maximum chances of realising benefits, there is a need for increased guidance in relation to implementation strategy, system choice and standards, as well as increased financial resources to fund local activitie

Unnatural amino acid analogues of membrane-active helical peptides with anti-mycobacterial activity and improved stability

Objectives The emergence of MDR-TB, coupled with shrinking antibiotic pipelines, has increased demands for new antimicrobials with novel mechanisms of action. Antimicrobial peptides have increasingly been explored as promising alternatives to antibiotics, but their inherent poor in vivo stability remains an impediment to their clinical utility. We therefore systematically evaluated unnatural amino acid-modified peptides to design analogues with enhanced anti-mycobacterial activities. Methods Anti-mycobacterial activities were evaluated in vitro and intracellularly against drug-susceptible and MDR isolates of Mycobacterium tuberculosis using MIC, killing efficacy and intracellular growth inhibition studies. Toxicity profiles were assessed against mammalian cells to verify cell selectivity. Anti-mycobacterial mechanisms were investigated using microfluidic live-cell imaging with time-lapse fluorescence microscopy and confocal laser-scanning microscopy. Results Unnatural amino acid incorporation was well tolerated without an appreciable effect on toxicity profiles and secondary conformations of the synthetic peptides. The modified peptides also withstood proteolytic digestion by trypsin. The all D-amino acid peptide, i(llkk)2i (II-D), displayed superior activity against all six mycobacterial strains tested, with a 4-fold increase in selectivity index as compared with the unmodified L-amino acid peptide in broth. II-D effectively reduced the intracellular bacterial burden of both drug-susceptible and MDR clinical isolates of M. tuberculosis after 4 days of treatment. Live-cell imaging studies demonstrated that II-D permeabilizes the mycobacterial membrane, while confocal microscopy revealed that II-D not only permeates the cell membrane, but also accumulates within the cytoplasm. Conclusions Unnatural amino acid modifications not only decreased the susceptibility of peptides to proteases, but also enhanced mycobacterial selectivity

Early star-forming galaxies and the reionization of the Universe

Star forming galaxies represent a valuable tracer of cosmic history. Recent observational progress with Hubble Space Telescope has led to the discovery and study of the earliest-known galaxies corresponding to a period when the Universe was only ~800 million years old. Intense ultraviolet radiation from these early galaxies probably induced a major event in cosmic history: the reionization of intergalactic hydrogen. New techniques are being developed to understand the properties of these most distant galaxies and determine their influence on the evolution of the universe.Comment: Review article appearing in Nature. This posting reflects a submitted version of the review formatted by the authors, in accordance with Nature publication policies. For the official, published version of the review, please see http://www.nature.com/nature/archive/index.htm

Search for Second-Generation Scalar Leptoquarks in ppˉ\bm{p \bar{p}} Collisions at s\sqrt{s}=1.96 TeV

Results on a search for pair production of second generation scalar leptoquark in $p \bar{p}$ collisions at $\sqrt{s}$=1.96 TeV are reported. The data analyzed were collected by the CDF detector during the 2002-2003 Tevatron Run II and correspond to an integrated luminosity of 198 pb$^{-1}$. Leptoquarks (LQ) are sought through their decay into (charged) leptons and quarks, with final state signatures represented by two muons and jets and one muon, large transverse missing energy and jets. We observe no evidence for $LQ$ production and derive 95% C.L. upper limits on the $LQ$ production cross sections as well as lower limits on their mass as a function of $\beta$, where $\beta$ is the branching fraction for $LQ \to \mu q$.Comment: 9 pages (3 author list) 5 figure

Measurement of the B0 anti-B0 oscillation frequency using l- D*+ pairs and lepton flavor tags

The oscillation frequency Delta-md of B0 anti-B0 mixing is measured using the partially reconstructed semileptonic decay anti-B0 -> l- nubar D*+ X. The data sample was collected with the CDF detector at the Fermilab Tevatron collider during 1992 - 1995 by triggering on the existence of two lepton candidates in an event, and corresponds to about 110 pb-1 of pbar p collisions at sqrt(s) = 1.8 TeV. We estimate the proper decay time of the anti-B0 meson from the measured decay length and reconstructed momentum of the l- D*+ system. The charge of the lepton in the final state identifies the flavor of the anti-B0 meson at its decay. The second lepton in the event is used to infer the flavor of the anti-B0 meson at production. We measure the oscillation frequency to be Delta-md = 0.516 +/- 0.099 +0.029 -0.035 ps-1, where the first uncertainty is statistical and the second is systematic.Comment: 30 pages, 7 figures. Submitted to Physical Review

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Expression and trans-specific polymorphism of self-incompatibility RNases in Coffea (Rubiaceae)

Self-incompatibility (SI) is widespread in the angiosperms, but identifying the biochemical components of SI mechanisms has proven to be difficult in most lineages. Coffea (coffee; Rubiaceae) is a genus of old-world tropical understory trees in which the vast majority of diploid species utilize a mechanism of gametophytic self-incompatibility (GSI). The S-RNase GSI system was one of the first SI mechanisms to be biochemically characterized, and likely represents the ancestral Eudicot condition as evidenced by its functional characterization in both asterid (Solanaceae, Plantaginaceae) and rosid (Rosaceae) lineages. The S-RNase GSI mechanism employs the activity of class III RNase T2 proteins to terminate the growth of "self" pollen tubes. Here, we investigate the mechanism of Coffea GSI and specifically examine the potential for homology to S-RNase GSI by sequencing class III RNase T2 genes in populations of 14 African and Madagascan Coffea species and the closely related self-compatible species Psilanthus ebracteolatus. Phylogenetic analyses of these sequences aligned to a diverse sample of plant RNase T2 genes show that the Coffea genome contains at least three class III RNase T2 genes. Patterns of tissue-specific gene expression identify one of these RNase T2 genes as the putative Coffea S-RNase gene. We show that populations of SI Coffea are remarkably polymorphic for putative S-RNase alleles, and exhibit a persistent pattern of trans-specific polymorphism characteristic of all S-RNase genes previously isolated from GSI Eudicot lineages. We thus conclude that Coffea GSI is most likely homologous to the classic Eudicot S-RNase system, which was retained since the divergence of the Rubiaceae lineage from an ancient SI Eudicot ancestor, nearly 90 million years ago.United States National Science Foundation [0849186]; Society of Systematic Biologists; American Society of Plant Taxonomists; Duke University Graduate Schoolinfo:eu-repo/semantics/publishedVersio

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Age-period-cohort analysis for trends in body mass index in Ireland

Background: Obesity is a growing problem worldwide and can often result in a variety of negative health outcomes. In this study we aim to apply partial least squares (PLS) methodology to estimate the separate effects of age, period and cohort on the trends in obesity as measured by body mass index (BMI). Methods. Using PLS we will obtain gender specific linear effects of age, period and cohort on obesity. We also explore and model nonlinear relationships of BMI with age, period and cohort. We analysed the results from 7,796 men and 10,220 women collected through the SLAN (Surveys of Lifestyle, attitudes and Nutrition) in Ireland in the years 1998, 2002 and 2007. Results: PLS analysis revealed a positive period effect over the years. Additionally, men born later tended to have lower BMI (-0.026 kg·m-2 yr-1, 95% CI: -0.030 to -0.024) and older men had in general higher BMI (0.029 kg·m -2 yr-1, 95% CI: 0.026 to 0.033). Similarly for women, those born later had lower BMI (-0.025 kg·m-2 yr-1, 95% CI: -0.029 to -0.022) and older women in general had higher BMI (0.029 kg·m-2 yr-1, 95% CI: 0.025 to 0.033). Nonlinear analyses revealed that BMI has a substantial curvilinear relationship with age, though less so with birth cohort. Conclusion: We notice a generally positive age and period effect but a slightly negative cohort effect. Knowing this, we have a better understanding of the different risk groups which allows for effective public intervention measures to be designed and targeted for these specific population subgroups