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This is a copy of the slides presented at the meeting but not formally written up for the volume.
As in vivo cellular imaging becomes the necessary norm for understanding cancer and other diseases, new non-toxic nanoprobes are going to be required to replace the high quality cadmium based nanoprobes in use today. We are developing less toxic probes based on two types of luminescent ceramic nanoparticles: naturally occurring fluorescent (NOF) mimics and Ln-based ceramic oxide materials. The NOF minerals of interest and that have demonstrated initial luminosity of sufficient brightness for use in cellular studies that include sphalerite, scheelite, manganoan and perovskite nanoparticles. For Ln-based materials we have shown that Ln-doped zincite will also luminesce enough to allow for quantification in cellular activity. Once formed, these probes are functionalized such that they can be delivered to desired cellular targets. Probe derivatization has focused on surface capping with functionalized poly(ethyleneglycol) molecules/lipids to yield water soluble NCs and polyarginine-based transporters for transmembrane delivery. The probes are being evaluated for their luminescent properties, as well as their non-toxicity and ability to report on cell-signaling events with various cell lines using multi-spectral, confocal microscopy, and other techniques. Preliminary interdisciplinary studies have validated the basic approaches for the synthesis of NOF nanoprobes and the bio-delivery and imaging of nanoparticles. Work to optimize the design, delivery, and imaging of these new nanoprobes is expected to achieve the NIH directed goal of increasing in the sensitivity and specificity of molecular probes for imaging. Details of the synthesis, functionalization and biological imaging using these probes will be presented. This work partially supported by the United States Department of Energy under contract number DE-AC04-94AL85000. Sandia is a multi-program laboratory operated by Sandia Corporation, a Lockheed-Martin Company, for the United States Department of Energy and by the National Institutes of health through the NIH Roadmap for Medical Research, Grant #1 R21 EB005365-01. Information on this RFA (Innovation in Molecular Imaging Probes) can be found at http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-021.html.
Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology.
We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders’ perspectives, and provide recommendations to guide future studies using this methodology.
The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff.
Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes.
Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.
Introduction: Oxygen is commonly administered to prehospital patients presenting with acute myocardial infarction (AMI). We conducted a systematic review to determine if oxygen administration, in AMI, impacts patient outcomes. Methods: We conducted a systematic search using MeSH terms and keywords in Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Central, clinicaltrials.gov and ISRCTN for relevant randomized controlled trials and observational studies comparing oxygen administration and no oxygen administration. The outcomes of interest were: mortality (≤30 days, in-hospital, and intermediate 2-11 months), infarct size, and major adverse cardiac events (MACE). Risk of Bias assessments were performed and GRADE methodology was employed to assess quality and overall confidence in the effect estimate. A meta-analysis was performed using RevMan 5 software. Results: Our search yielded 1192 citations of which 48 studies were reviewed as full texts and a total of 8 studies were included in the analysis. All evidence was considered low or very low quality. Five studies reported on mortality finding low quality evidence of no benefit or harm. Low quality evidence demonstrated no benefit or harm from supplemental oxygen administration. Similarly, no benefit or harm was found in MACE or infarct size (very low quality). Normoxia was defined as oxygen saturation measured via pulse oximetry at ≥90% in one recent study and ≥94% in another. Conclusion: We found low and very low quality evidence that the administration of supplemental oxygen to normoxic patients experiencing AMI, provides no clear harm nor benefit for mortality or MACE. The evidence on infarct size was inconsistent and warrants further prospective examination.
Introduction: Emergency Department (ED) consultations are often necessary for safe and effective patient care. Delays in throughput related to ED consultations can increase a patient's ED length of stay (LOS) and contribute to ED crowding. This review aimed to characterize and evaluate interventions to improve consultation metrics. Methods: Eight primary literature databases and the grey literature were comprehensively searched. Comparative studies of interventions to improve ED consultation metrics were included. Unique citations were screened for relevance and the full-texts of relevant articles were reviewed by two independent reviewers. Data on study characteristics and outcomes were extracted in duplicate onto standardized forms. Disagreements were resolved through consensus. Categorical variables are reported as proportions. Continuous variables are reported as the median of the means and total range. Results: After screening 2632 unique citations and 19 from the grey literature items, 24 studies were included. Seventeen interventions targeted specific conditions or speciality services, while the remainder targeted all ED presentations. Interventions fell into three broad categories: strategies to expedite patient care, including clinical pathways (42%); interventions to improve consultant responsiveness (33%); and addition of a specialized care team to the ED (25%). Overall, eight studies reported on the overall proportion of consults in the ED, of which six reported an increase in the consultation proportion (median: +0.6%, range: −11.3% to +49.6%). Six studies reported the proportion of consulted patients who were admitted, of which four reported an increase (median: +1.1%, range: −5.9% to +3.5%). On the other hand, six of seven studies reporting on time from request to consult arrival reported a decrease (median: −25 minutes, range: −66 to +3.8 minutes). Similarly, overall ED LOS was reported to be lower in 17/19 studies reporting this metric (median: −47.6 minutes, range: −600 minutes to +59 minutes). Conclusion: A variety of strategies have been employed to improve ED consultation processes and outcomes. Neither the proportion of consulted patients in the ED nor the proportion of admissions were improved; however, interventions appeared successful at improving consultant arrival times and overall ED LOS. Improvements in consultation processes may be an effective strategy to improve ED throughput and thereby reduce ED crowding.
Introduction: While consultation is a common and important aspect of emergency department (ED) care, a previous systematic review identified significant utilization and process variation across ED's. The aim of this review update was to examine the proportion of the patients undergoing consultation in the ED among recent studies. Methods: Eight primary literature databases and the grey literature were searched. Studies published from 2007 to 2018 focusing on all-comers to the ED and reporting a consultation-related outcome were included. Disease- and specialty-specific studies were not eligible. Two independent reviewers screened studies for relevance, inclusion, quality assessment, and data extraction. Disagreements were resolved through consensus. Means, medians and interquartile ranges are reported. Wilcoxon-rank sum test and one-way ANOVA were used to identify differences between groups, as appropriate. Results: A total of 2632 unique citations and 49 studies from the grey literature were screened, of which 29 primary studies were included. Fifteen studies reported on the proportion of ED patients undergoing consultation, involving EDs in the Middle East (n = 4), North America (n = 4), Asia (n = 4), and Europe (n = 3). Overall, the proportion of patients receiving consultation ranged from 7% to 78% (median: 26%; IQR: 20%, 38%). There were no differences in the proportions of consulted patients based on country of origin. Ten studies were conducted prior to 2013, while five studies recruited patients during and after 2013. The mean proportion of consulted patients was lower for post-2012 studies compared to pre-2012 studies (mean: 18% vs. 36%; p = 0.0048). The proportion of consulted patients admitted to hospital ranged considerably between the 14 reporting studies (median: 56%; IQR: 49%, 76%). No differences in the proportion of admitted patients undergoing a consult were identified based on country of origin or year of recruitment for the study. Conclusion: Although consultation utilization appears to be decreasing overall, there is considerable practice variation in EDs around the world. These differences may result from variation in patient acuity, case-load, staffing levels, institutional and health-system organization, and medical training and future research should explore reasons for these differences.
Children with congenital heart disease are at high risk for malnutrition. Standardisation of feeding protocols has shown promise in decreasing some of this risk. With little standardisation between institutions’ feeding protocols and no understanding of protocol adherence, it is important to analyse the efficacy of individual aspects of the protocols.
Adherence to and deviation from a feeding protocol in high-risk congenital heart disease patients between December 2015 and March 2017 were analysed. Associations between adherence to and deviation from the protocol and clinical outcomes were also assessed. The primary outcome was change in weight-for-age z score between time intervals.
Increased adherence to and decreased deviation from individual instructions of a feeding protocol improves patients change in weight-for-age z score between birth and hospital discharge (p = 0.031). Secondary outcomes such as markers of clinical severity and nutritional delivery were not statistically different between groups with high or low adherence or deviation rates.
High-risk feeding protocol adherence and fewer deviations are associated with weight gain independent of their influence on nutritional delivery and caloric intake. Future studies assessing the efficacy of feeding protocols should include the measures of adherence and deviations that are not merely limited to caloric delivery and illness severity.
Introduction: Opioids are routinely administered for analgesia to prehospital patients experiencing chest discomfort from acute myocardial infarction (AMI). We conducted a systematic review to determine if opioid administration impacts patient outcomes. Methods: We conducted a systematic search using MeSH terms and keywords in Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Central and Clinicaltrials.gov for relevant randomized controlled trials and observational studies comparing opioid administration in AMI patients from 1990 to 2017. The outcomes of interest were: all-cause short-term mortality (≤30 days), major adverse cardiac events (MACE), platelet activity and aggregation, immediate adverse events, infarct size, and analgesia. Included studies were hand searched for additional citations. Risk of Bias assessments were performed and GRADE methodology was employed to assess quality and overall confidence in the effect estimate. Results: Our search yielded 3001 citations of which 19 studies were reviewed as full texts and a total of 9 studies were included in the analysis. The studies predominantly reported on morphine as the opioid. Five studies reported on mortality (≤30 days), seven on MACE, four on platelet activity and aggregation, two on immediate adverse events, two on infarct size and none on analgesic effect. We found low quality evidence suggesting no benefit or harm in terms of mortality or MACE. However, low quality evidence indicates that opioids increase infarct size. Low-quality evidence also shows reduced serum P2Y12 (eg: clopidogrel and ticagrelor) active metabolite levels and increased platelet reactivity in the first several hours post administration following an increase in vomiting. Conclusion: We find low and very low quality evidence that the administration of opioids in STEMI may be adversely related to vomiting and some surrogate outcomes including increased infarct size, reduced serum P2Y12 levels, and increased platelet activity. We found no clear benefit or harm on patient-oriented clinical outcomes including mortality.
We have studied a series of laminated thin films by x-ray diffraction to correlate their structural and magnetic properties. Previous works have shown that the signal-to-noise characteristics of laminated magnetic films with non-magnetic interlayers can exceed that of single layer magnetic films. In the case where the magnetic layer is known to have low signal-to-noise performance, the signal has been observed to increase as the number of layers whereas the noise increases as the square root of the number of layers. This yields a net improvement of the signal-to-noise ratio, making the overall film more attractive as a magnetic recording medium. In this paper, we investigate films which are laminated layers of magnetic CoPtCr and non-magnetic Cr. The films were deposited with sputtering parameters that generally give low noise characteristics in single layer films. Up to four layers of CoPtCr films were made with Cr spacer layers of 2 nm. We observe some improvement in signal-to-noise characteristics and reduction in coercivity. X-ray diffraction analysis shows that the crystallographic c-axis, which corresponds to the magnetic easy axis, becomes more preferentially oriented perpendicular to the film plane with each additional layer. This change in preferred orientation is consistent with the reduced in-plane coercivity of the film. In the double CoPtCr layer with one Cr spacer layer experiment, we see that as the Cr spacer layer is increased from 0.5 to 8 nm, the c-axis of the CoPtCr again becomes more preferentially oriented out of the film plane, resulting in decreased in-plane coercivity. The media signal-to-noise improves once the Cr spacer layer is beyond 2 nm, consistent with previous observations.
Susceptibility of a system to colonization by a weed is in part a function of environmental resource availability. Doveweed [Murdannia nudiflora (L.) Brenan] can establish in a variety of environments; however, it is found mostly in wet or low-lying areas with reduced interspecies competition. Four studies evaluated the effect of mowing height, interspecies competition, and nitrogen, light, and soil moisture availability on M. nudiflora establishment and growth. A field study evaluated the effect of mowing height on M. nudiflora establishment. In comparison with unmowed plots, mowing at 2 and 4 cm reduced spread 46% and 30%, respectively, at 9 wk after planting. Effect of mowing height and nitrogen fertilization on ‘Tifway’ bermudagrass (Cynodon dactylon Burtt-Davy×C. transvaalensis L. Pers.) and M. nudiflora interspecies competition was evaluated in a greenhouse trial. Murdannia nudiflora coverage was 62% greater in flats maintained at 2.6 cm than flats maintained at 1.3 cm. Supplemental application of 49 kg N ha−1 mo−1 increased M. nudiflora coverage 75% in comparison with 24.5 kg N ha−1 mo−1. A difference in M. nudiflora coverage could not be detected between flats receiving 0 and 24.5 kg N ha−1 mo−1, suggesting moderate nitrogen fertilization does not encourage M. nudiflora colonization. Effect of light availability on M. nudiflora growth and development was evaluated in a greenhouse study. Growth in a 30%, 50%, or 70% reduced light environment (RLE) did not affect shoot growth on a dry weight basis in comparison with plants grown under full irradiance; however, internode length was 28% longer in a 30% RLE and 39% longer in a 50% and 70% RLE. Effect of soil moisture on M. nudiflora growth and development was evaluated in a greenhouse study. Plants maintained at 50%, 75%, and 100% field capacity (FC) increased biomass>200% compared with plants maintained at 12.5% or 25% FC.
OBJECTIVES/SPECIFIC AIMS: Our primary objective was to understand the relationship between incident or recent stressful events and adherence to HIV care in the context of other person, environment, and HIV-specific stressors in a sample of Black women living with HIV (WLWH). METHODS/STUDY POPULATION: Thirty in-depth interviews were conducted with Black women living with HIV who receive care at an academic HIV primary care clinic in the Southern region of the United States to elicit stressful events influencing adherence to HIV care. Semi-structured interview guides were used to facilitate discussion regarding stressful events and adherence to HIV care. Interviews were audiotaped and transcribed verbatim. Transcripts were independently coded using a theme-based approach by two experienced coders, findings were compared, and discrepancies were resolved by discussion. RESULTS/ANTICIPATED RESULTS: Participants described frequently experiencing incident stressful events including death or serious illness of a close friend or family member, and relationship, financial, and employment difficulties. Furthermore, participants reported experiencing traumatic events such as sexual and physical abuse during childhood and adolescents. While experiencing traumatic events such as sexual and physical abuse during childhood and adolescence may be distressing, these events did not influence adherence to HIV care. However, incident stressful events as defined above did influence adherence to HIV care for some participants, but not for others. For participants who reported that stressful events did not influence adherence to HIV care, factors such as personal motivation, access to social support, and adaptive coping strategies facilitated their engagement in care. DISCUSSION/SIGNIFICANCE OF IMPACT: Experiencing stressful events, incident or traumatic, is common among Black WLWH and have the potential to negatively influence adherence to HIV care. Thus, Interventions aimed at identifying and addressing stress, social support, and coping are essential to improve adherence to HIV care behaviors.
The Single Ventricle Reconstruction trial randomised neonates with hypoplastic left heart syndrome to a systemic-to-pulmonary-artery shunt strategy. Patients received care according to usual institutional practice. We analysed practice variation at the Stage II surgery to attempt to identify areas for decreased variation and process control improvement.
Prospectively collected data were available in the Single Ventricle Reconstruction public-use database. Practice variation across 14 centres was described for 397 patients who underwent Stage II surgery. Data are centre-level specific and reported as interquartile ranges across all centres, unless otherwise specified.
Preoperative Stage II median age and weight across centres were 5.4 months (interquartile range 4.9–5.7) and 5.7 kg (5.5–6.1), with 70% performed electively. Most patients had pre-Stage-II cardiac catheterisation (98.5–100%). Digoxin was used by 11/14 centres in 25% of patients (23–31%), and 81% had some oral feeds (68–84%). The majority of the centres (86%) performed a bidirectional Glenn versus hemi-Fontan. Median cardiopulmonary bypass time was 96 minutes (75–113). In aggregate, 26% of patients had deep hypothermic circulatory arrest >10 minutes. In 13/14 centres using deep hypothermic circulatory arrest, 12.5% of patients exceeded 10 minutes (8–32%). Seven centres extubated 5% of patients (2–40) in the operating room. Postoperatively, ICU length of stay was 4.8 days (4.0–5.3) and total length of stay was 7.5 days (6–10).
In the Single Ventricle Reconstruction Trial, practice varied widely among centres for nearly all perioperative factors surrounding Stage II. Further analysis may facilitate establishing best practices by identifying the impact of practice variation.
Gary P. Baker, Research Associate at the University of East Anglia, and a Researcher at the University of Groningen in the Netherlands.,
Craig L. Lambert, Lecturer in Maritime History at the University of Southampton.,
David Simpkin, Teacher of History at Birkenhead Sixth-Form College.,
J. J. N. Palmer
Given the contribution Andrew Ayton has made to the study of late medieval military history we hope he is not surprised by the production of a Festschrift in his honour. All the editors of this volume were supervised by Andrew for their doctoral studies, and all no doubt thrashed out the general outlines to their theses in one of the infamous ‘Ayton’ meetings that regularly ran into the late evening. Andrew's enthusiasm for his subject was infectious and it is to his credit that many of his former students have gone on to publish contributions on late medieval military and naval history. The papers featured in the present volume highlight the important international impact Andrew's work has had on his students and academic colleagues.
Andrew, a native of Dorset, is in his own words ‘a country dweller at heart’ but has spent much of his working life in the big city. He studied as an undergraduate at the University of Hull in the early 1980s, during which time he undertook several modules taught by Professor John Palmer. John's module on the Hundred Years’ War in particular seems to have kindled Andrew's interest in medieval military history and military communities; it certainly began a fruitful association between two like-minded scholars which was to span some three decades until John's retirement in 2002. Andrew often visited John's home to discuss their latest research and he will be pleased to know he is remembered with some affection by John's children.
After graduating, Andrew spent a brief spell in a ‘real’ job, before returning to Hull to study for his Ph.D. under John Palmer – ‘The Warhorse and Military Service under Edward III’ – and from 1985 to 1987 Andrew was employed, alongside Virginia Davis, on John's Domesday Project. This was a role for which Andrew was particularly well equipped. He had taken John Palmer's special subject on the Domesday Book as an undergraduate, which had provided him with the essential background plus the basic computing skills – in particular related to databases – needed for the research: rare qualifications in the mid-1980s. This period, of course, included the 900th anniversary of Domesday Book, which for Andrew and Virginia entailed a frenetic year, giving lectures and demonstrations around the UK while trying to keep to a research schedule and do some work on their own account.