Coupling computer-interpretable guidelines with a drug-database through a web-based system – The PRESGUID project

BACKGROUND: Clinical Practice Guidelines (CPGs) available today are not extensively used due to lack of proper integration into clinical settings, knowledge-related information resources, and lack of decision support at the point of care in a particular clinical context. OBJECTIVE: The PRESGUID project (PREScription and GUIDelines) aims to improve the assistance provided by guidelines. The project proposes an online service enabling physicians to consult computerized CPGs linked to drug databases for easier integration into the healthcare process. METHODS: Computable CPGs are structured as decision trees and coded in XML format. Recommendations related to drug classes are tagged with ATC codes. We use a mapping module to enhance computerized guidelines coupling with a drug database, which contains detailed information about each usable specific medication. In this way, therapeutic recommendations are backed up with current and up-to-date information from the database. RESULTS: Two authoritative CPGs, originally diffused as static textual documents, have been implemented to validate the computerization process and to illustrate the usefulness of the resulting automated CPGs and their coupling with a drug database. We discuss the advantages of this approach for practitioners and the implications for both guideline developers and drug database providers. Other CPGs will be implemented and evaluated in real conditions by clinicians working in different health institutions

Quantifying the daily economic impact of extreme space weather due to failure in electricity transmission infrastructure

Extreme space weather due to coronal mass ejections has the potential to cause considerable disruption to the global economy by damaging the transformers required to operate electricity transmission infrastructure. However, expert opinion is split between the potential outcome being one of a temporary regional blackout and of a more prolonged event. The temporary blackout scenario proposed by some is expected to last the length of the disturbance, with normal operations resuming after a couple of days. On the other hand, others have predicted widespread equipment damage with blackout scenarios lasting months. In this paper we explore the potential costs associated with failure in the electricity transmission infrastructure in the U.S. due to extreme space weather, focusing on daily economic loss. This provides insight into the direct and indirect economic consequences of how an extreme space weather event may affect domestic production, as well as other nations, via supply chain linkages. By exploring the sensitivity of the blackout zone, we show that on average the direct economic cost incurred from disruption to electricity represents only 49% of the total potential macroeconomic cost. Therefore, if indirect supply chain costs are not considered when undertaking cost-benefit analysis of space weather forecasting and mitigation investment, the total potential macroeconomic cost is not correctly represented. The paper contributes to our understanding of the economic impact of space weather, as well as making a number of key methodological contributions relevant for future work. Further economic impact assessment of this threat must consider multiday, multiregional event

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Human Embryonic and Fetal Mesenchymal Stem Cells Differentiate toward Three Different Cardiac Lineages in Contrast to Their Adult Counterparts

Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for α-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express α-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role

Preparation and Instability of Nanocrystalline Cuprous Nitride

Low-dimensional cuprous nitride (Cu3N) was synthesized by nitridation (ammonolysis) of cuprous oxide (Cu2O) nanocrystals using either ammonia (NH3) or urea (H2NCONH2) as the nitrogen source. The resulting nanocrystalline Cu3N spontaneously decomposes to nanocrystalline CuO in the presence of both water and oxygen from air at room temperature. Ammonia was produced in 60% chemical yield during Cu3N decomposition, as measured using the colorimetric indophenol method. Because Cu3N decomposition requires H2O and produces substoichiometric amounts of NH3\u3e, we conclude that this reaction proceeds through a complex stoichiometry that involves the concomitant release of both N2 and NH3. This is a thermodynamically unfavorable outcome, strongly indicating that H2O (and thus NH3 production) facilitate the kinetics of the reaction by lowering the energy barrier for Cu3N decomposition. The three different Cu2O, Cu3N, and CuO nanocrystalline phases were characterized by a combination of optical absorption, powder X-ray diffraction, transmission electron microscopy, and electronic density of states obtained from electronic structure calculations on the bulk solids. The relative ease of interconversion between these interesting and inexpensive materials bears possible implications for catalytic and optoelectronic applications

Improving care for people with dementia: development and initial feasibility study for evaluation of life story work in dementia care

Background: Improving dementia care quality is an urgent priority nationally and internationally. Life story work (LSW) is an intervention that aims to improve individual outcomes and care for people with dementia and their carers. LSW gathers information and artefacts about the person, their history and interests, and produces a tangible output: the ‘life story’. Objective: To establish whether or not full evaluation of LSW was feasible. Design: Mixed-methods feasibility study. Methods: In-depth interviews and focus groups explored experiences of LSW and best practice with people with dementia, family members and dementia care staff. A systematic review explored best practice and theories of change for LSW. These stages helped to identify the outcomes and resources to explore in the feasibility study. A representative sample survey of health and social care dementia care providers in England established LSW practice in different settings. A survey of a self-selected sample of family members of people with dementia explored how LSW is experienced. Two small outcome studies (stepped-wedge study in six care homes and pre-test post-test study in inpatient specialist dementia care wards) explored the feasibility of full evaluation of LSW in these settings. Settings: Survey: generalist and specialist care homes; NHS dementia care settings; and community dementia services. Feasibility study: care homes and NHS inpatient dementia care wards. Participants: NHS and social care services, people with dementia, family carers, care home staff and NHS staff. Interventions: LSW. Main outcome measures: Spread of LSW and good practice, quality of life (QoL) for the person with dementia and carers, relationships between people with dementia and family carers, staff attitudes about dementia, staff burnout, resource use and costs. Review methods: Narrative review and synthesis, following Centre for Review and Dissemination guidelines. Results: Good practice in LSW is identifiable, as are theories of change about how it might affect given outcomes. Indicators of best practice were produced. LSW is spreading but practice and use vary between care settings and are not always in line with identified good practice. Two different models of LSW are evident; these are likely to be appropriate at different stages of the dementia journey. The feasibility study showed some positive changes in staff attitudes towards dementia and, for some people with dementia, improvements in QoL. These may be attributable to LSW but these potential benefits require full evaluation. The feasibility work established the likely costs of LSW and highlighted the challenges of future evaluation in care homes and inpatient dementia care settings. Limitations: There was insufficient evidence in the literature to allow estimation of outcome size. We did not carry out planned Markov chain modelling to inform decisions about carrying out future evaluation because of the dearth of outcome data in the literature; low levels of data return for people with dementia in the hospital settings; lack of detected effect for most people with dementia; and questions about implementation in the research settings. Conclusions: LSW is used across different health and social care settings in England, but in different ways, not all of which reflect ‘good practice’. This large, complex study identified a wide range of challenges for future research, but also the possibility that LSW may help to improve care staff attitudes towards dementia and QoL for some people with dementia. Future work: Full evaluation of LSW as an intervention to improve staff attitudes and care is feasible with researchers based in or very close to care settings to ensure high-quality data collection. Funding: The National Institute for Health Research Health Services and Delivery Research programme. Keywords

Quantitative cardiovascular magnetic resonance for molecular imaging

Cardiovascular magnetic resonance (CMR) molecular imaging aims to identify and map the expression of important biomarkers on a cellular scale utilizing contrast agents that are specifically targeted to the biochemical signatures of disease and are capable of generating sufficient image contrast. In some cases, the contrast agents may be designed to carry a drug payload or to be sensitive to important physiological factors, such as pH, temperature or oxygenation. In this review, examples will be presented that utilize a number of different molecular imaging quantification techniques, including measuring signal changes, calculating the area of contrast enhancement, mapping relaxation time changes or direct detection of contrast agents through multi-nuclear imaging or spectroscopy. The clinical application of CMR molecular imaging could offer far reaching benefits to patient populations, including early detection of therapeutic response, localizing ruptured atherosclerotic plaques, stratifying patients based on biochemical disease markers, tissue-specific drug delivery, confirmation and quantification of end-organ drug uptake, and noninvasive monitoring of disease recurrence. Eventually, such agents may play a leading role in reducing the human burden of cardiovascular disease, by providing early diagnosis, noninvasive monitoring and effective therapy with reduced side effects

Measurement of the cross-section for b-jets produced in association with a Z boson at root s=7 TeV with the ATLAS detector ATLAS Collaboration

A measurement is presented of the inclusive cross-section for b-jet production in association with a Z boson in pp collisions at a centre-of-mass energy of root s = 7 TeV. The analysis uses the data sample collected by the ATLAS experiment in 2010, corresponding to an integrated luminosity of approximately 36 pb(-1). The event selection requires a Z boson decaying into high P-T electrons or muons, and at least one b-jet, identified by its displaced vertex, with transverse momentum p(T) > 25 GeV and rapidity vertical bar y vertical bar < 2.1. After subtraction of background processes, the yield is extracted from the vertex mass distribution of the candidate b-jets. The ratio of this cross-section to the inclusive Z cross-section (the average number of b-jets per Z event) is also measured. Both results are found to be in good agreement with perturbative QCD predictions at next-to-leading order