Design and construction of an actively frequency-switchable RF coil for field-dependent Magnetisation Transfer Contrast MRI with fast field-cycling

Copyright © 2010 Elsevier Inc. All rights reserved.Peer reviewedPostprin

Development and initial validation of the Bedside Paediatric Early Warning System score

Abstract Introduction Adverse outcomes following clinical deterioration in children admitted to hospital wards is frequently preventable. Identification of children for referral to critical care experts remains problematic. Our objective was to develop and validate a simple bedside score to quantify severity of illness in hospitalized children. Methods A case-control design was used to evaluate 11 candidate items and identify a pragmatic score for routine bedside use. Case-patients were urgently admitted to the intensive care unit (ICU). Control-patients had no 'code blue', ICU admission or care restrictions. Validation was performed using two prospectively collected datasets. Results Data from 60 case and 120 control-patients was obtained. Four out of eleven candidate-items were removed. The seven-item Bedside Paediatric Early Warning System (PEWS) score ranges from 0–26. The mean maximum scores were 10.1 in case-patients and 3.4 in control-patients. The area under the receiver operating characteristics curve was 0.91, compared with 0.84 for the retrospective nurse-rating of patient risk for near or actual cardiopulmonary arrest. At a score of 8 the sensitivity and specificity were 82% and 93%, respectively. The score increased over 24 hours preceding urgent paediatric intensive care unit (PICU) admission (P < 0.0001). In 436 urgent consultations, the Bedside PEWS score was higher in patients admitted to the ICU than patients who were not admitted (P < 0.0001). Conclusions We developed and performed the initial validation of the Bedside PEWS score. This 7-item score can quantify severity of illness in hospitalized children and identify critically ill children with at least one hours notice. Prospective validation in other populations is required before clinical application

Antigen depot is not required for alum adjuvanticity

Alum adjuvants have been in continuous clinical use for more than 80 yr. While the prevailing theory has been that depot formation and the associated slow release of antigen and/or inflammation are responsible for alum enhancement of antigen presentation and subsequent T- and B-cell responses, this has never been formally proven. To examine antigen persistence, we used the chimeric fluorescent protein EαGFP, which allows assessment of antigen presentation in situ, using the Y-Ae antibody. We demonstrate that alum and/or CpG adjuvants induced similar uptake of antigen, and in all cases, GFP signal did not persist beyond 24 h in draining lymph node antigen-presenting cells. Antigen presentation was first detectable on B cells within 6–12 h of antigen administration, followed by conventional dendritic cells (DCs) at 12–24 h, then finally plasmacytoid DCs at 48 h or later. Again, alum and/or CpG adjuvants did not have an effect on the magnitude or sequence of this response; furthermore, they induced similar antigen-specific T-cell activation in vivo. Notably, removal of the injection site and associated alum depot, as early as 2 h after administration, had no appreciable effect on antigen-specific T- and B-cell responses. This study clearly rules out a role for depot formation in alum adjuvant activity

Multicentre validation of the bedside paediatric early warning system score: a severity of illness score to detect evolving critical illness in hospitalised children

Abstract Introduction The timely provision of critical care to hospitalised patients at risk for cardiopulmonary arrest is contingent upon identification and referral by frontline providers. Current approaches require improvement. In a single-centre study, we developed the Bedside Paediatric Early Warning System (Bedside PEWS) score to identify patients at risk. The objective of this study was to validate the Bedside PEWS score in a large patient population at multiple hospitals. Methods We performed an international, multicentre, case-control study of children admitted to hospital inpatient units with no limitations on care. Case patients had experienced a clinical deterioration event involving either an immediate call to a resuscitation team or urgent admission to a paediatric intensive care unit. Control patients had no events. The scores ranged from 0 to 26 and were assessed in the 24 hours prior to the clinical deterioration event. Score performance was assessed using the area under the receiver operating characteristic (AUCROC) curve by comparison with the retrospective rating of nurses and the temporal progression of scores in case patients. Results A total of 2,074 patients were evaluated at 4 participating hospitals. The median (interquartile range) maximum Bedside PEWS scores for the 12 hours ending 1 hour before the clinical deterioration event were 8 (5 to 12) in case patients and 2 (1 to 4) in control patients (P < 0.0001). The AUCROC curve (95% confidence interval) was 0.87 (0.85 to 0.89). In case patients, mean scores were 5.3 at 20 to 24 hours and 8.4 at 0 to 4 hours before the event (P < 0.0001). The AUCROC curve (95% CI) of the retrospective nurse ratings was 0.83 (0.81 to 0.86). This was significantly lower than that of the Bedside PEWS score (P < 0.0001). Conclusions The Bedside PEWS score identified children at risk for cardiopulmonary arrest. Scores were elevated and continued to increase in the 24 hours before the clinical deterioration event. Prospective clinical evaluation is needed to determine whether this score will improve the quality of care and patient outcomes

Systematic review of the clinical effectiveness and cost-effectiveness and economic modelling of minimal incision total hip replacement approaches in the management of arthritic disease of the hip

Objectives: To assess the clinical effectiveness and cost-effectiveness of minimal incision approaches to total hip replacement (THR) for arthritis of the hip. Data sources: Major electronic databases were searched from 1966 to 2007. Relevant websites were also examined and experts in the field were consulted. Review methods: Studies of minimal (one or two) incision THR compared with standard THR were assessed for inclusion in the review of clinical effectiveness. A systematic review of economic evaluations comparing a minimal incision approach to standard THR was also performed and the estimates from the systematic review of clinical effectiveness were incorporated into an economic model. Utilities data were sourced to estimate quality-adjusted life-years (QALYs). Due to lack of data, no economic analysis was conducted for the two mini-incision surgical method. Results: Nine randomised controlled trials (RCTs), 17 non-randomised comparative studies, six case series and one registry were found to be useful for the comparison of single mini-incision THR with standard THR. One RCT compared two mini-incision THR with standard THR, and two RCTs, five non-randomised comparative studies and two case series compared two mini-incision with single mini-incision THR. The RCTs were of moderate quality. Most had fewer than 200 patients and had a follow-up period of less than 1 year. The single mini-incision THR may have some perioperative advantages, e.g. blood loss [weighted mean difference (WMD) –57.71 ml, p £30,000) if recovery was 1.5 weeks faster. A threshold analysis around risk of revision showed, using the same cost per QALY threshold, mini-incision THR would have to have no more than a 7.5% increase in revisions compared with standard THR for it to be no longer considered cost-effective (one more revision for every 200 procedures performed). Further sensitivity analysis involved relaxing assumptions of equal long-term outcomes where possible. and broadly similar results to the base-case analysis were found in this and further sensitivity analyses. Conclusions: Compared with standard THR, minimal incision THR has small perioperative advantages in terms of blood loss and operation time. It may offer a shorter hospital stay and quicker recovery. It appears to have a similar procedure cost to standard THR, but evidence on its longer term performance is very limited. Further long-term follow-up data on costs and outcomes including analysis of subgroups of interest to the NHS would strengthen the current economic evaluation.The Health Services Research Unit and the Health Economics Research Unit are both core funded by the Chief Scientist Office of the Scottish Government Health Directorates.Peer reviewedPublisher PD

The FENIKS Survey: Spectroscopic Confirmation of Massive Quiescent Galaxies at z ~ 3-5

The measured ages of massive, quiescent galaxies at $z\sim 3-4$ imply that massive galaxies quench as early as $z\sim 6$. While the number of spectroscopic confirmations of quiescent galaxies at $z < 3$ has increased over the years, there are only a handful at $z > 3.5$. We report spectroscopic redshifts of one secure ($z=3.757$) and two tentative ($z = 3.336$, $z=4.673$) massive ($\log(M_\ast/M_\odot) > 10.3$) quiescent galaxies with 11 hours of Keck/MOSFIRE $K$-band observations. Our candidates were selected from the FENIKS survey, which uses deep Gemini/Flamingos-2 $K_b$ $K_r$ imaging optimized for increased sensitivity to the characteristic red colors of galaxies at $z > 3$ with strong Balmer/4000 \AA\ breaks. The rest-frame $UVJ$ and $(ugi)_s$ colors of 3/4 quiescent candidates are consistent with $1-2$ Gyr old stellar populations. This places these galaxies as the oldest objects at these redshifts, and challenges the notion that quiescent galaxies at $z > 3$ are all recently-quenched, "post-starburst'' galaxies. Our spectroscopy shows that the other quiescent-galaxy candidate is a broad-line AGN ($z = 3.594$) with strong, redshifted $H\beta$+[O III] emission with a velocity offset $>1000$ km/s, indicative of a powerful outflow. The star-formation history of our highest redshift candidate suggests that its progenitor was already in place by $z \sim 7-11$, reaching $\sim$ 10$^{11} M_{\odot}$ by $z \simeq 10$. These observations reveal the limit of what is possible with deep near-infrared photometry and targeted spectroscopy from the ground and demonstrate that secure spectroscopic confirmation of quiescent galaxies at $z > 4$ is only feasible with JWST.Comment: 20 pages, 11 figures, submitted to Ap

Effect of a pediatric early warning system on all-cause mortality in Hospitalized pediatric patients: The epoch randomized clinical trial

IMPORTANCE: There is limited evidence that the use of severity of illness scores in pediatric patients can facilitate timely admission to the intensive care unit or improve patient outcomes. OBJECTIVE: To determine the effect of the Bedside Paediatric Early Warning System (BedsidePEWS) on all-cause hospital mortality and late admission to the intensive care unit (ICU), cardiac arrest, and ICU resource use. DESIGN, SETTING, AND PARTICIPANTS: A multicenter cluster randomized trial of 21 hospitals located in 7 countries (Belgium, Canada, England, Ireland, Italy, New Zealand, and the Netherlands) that provided inpatient pediatric care for infants (gestational age ≥37 weeks) to teenagers (aged ≤18 years). Participating hospitals had continuous physician staffing and subspecialized pediatric services. Patient enrollment began on February 28, 2011, and ended on June 21, 2015. Follow-up ended on July 19, 2015. INTERVENTIONS: The BedsidePEWS intervention (10 hospitals) was compared with usual care (no severity of illness score; 11 hospitals). MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause hospital mortality. The secondary outcome was a significant clinical deterioration event, which was defined as a composite outcome reflecting late ICU admission. Regression analyses accounted for hospital-level clustering and baseline rates. RESULTS: Among 144539 patient discharges at 21 randomized hospitals, there were 559 443 patient-days and 144539 patients (100%) completed the trial. All-cause hospital mortality was 1.93 per 1000 patient discharges at hospitals with BedsidePEWS and 1.56 per 1000 patient discharges at hospitals with usual care (adjusted between-group rate difference, 0.01 [95% CI, -0.80 to 0.81 per 1000 patient discharges]; adjusted odds ratio, 1.01 [95% CI, 0.61 to 1.69]; P =.96). Significant clinical deterioration events occurred during 0.50 per 1000 patient-days at hospitals with BedsidePEWS vs 0.84 per 1000 patient-days at hospitals with usual care (adjusted between-group rate difference, -0.34 [95% CI, -0.73 to 0.05 per 1000 patient-days]; adjusted rate ratio, 0.77 [95% CI, 0.61 to 0.97]; P =.03). CONCLUSIONS AND RELEVANCE: Implementation of the Bedside Paediatric Early Warning System compared with usual care did not significantly decrease all-cause mortality among hospitalized pediatric patients. These findings do not support the use of this system to reduce mortality

A Cell-Free Microtiter Plate Screen for Improved [FeFe] Hydrogenases

, a potential renewable fuel. Attempts to exploit these catalysts in engineered systems have been hindered by the biotechnologically inconvenient properties of the natural enzymes, including their extreme oxygen sensitivity. Directed evolution has been used to improve the characteristics of a range of natural catalysts, but has been largely unsuccessful for [FeFe] hydrogenases because of a lack of convenient screening platforms. [FeFe] hydrogenase HydA1 with a specific activity ∼4 times that of the wild-type enzyme. cell extracts, which allows unhindered access to the protein maturation and assay environment