Transfusion Rates in Emergency General Surgery: High but Modifiable

Background: Transfusion of red blood cells (RBC) increases morbidity and mortality, and emergency general surgery (EGS) cases have increased risk for transfusion and complication given case complexity and patient acuity. Transfusion reduction strategies and blood-conservation technology have been developed to decrease transfusions. This study explores whether transfusion rates in EGS have decreased as these new strategies have been implemented. Methods: This is a retrospective review of the American College of Surgeons\u27 National Surgical Quality Improvement Program (ACS NSQIP) data from three academic medical centers. Operations performed by general surgeons on adults (aged ≥18 years) were selected. Data were analyzed from two periods: 2011-2013 and 2014-2016. Cases were grouped by the first four digits of the primary procedure Current Procedural Terminology code. Transfusion was defined as any RBC transfusion during or within 72 hours following the operation. Composite morbidity was defined as any NSQIP complication within 30 days following the operation. Results: Overall general surgery transfusion rates decreased from 6.4% to 4.8% from period 1 to period 2 (emergent: 16.6%–11.5%; non-emergent 4.9%–3.7%; Fisher’s exact p values \u3c 0.001). Among patients transfused, the number of units received decreased slightly (median 2 U (IQR 2–3) to median 2 U (IQR 1–3), Mann-Whitney U test p = 0.005). Morbidity decreased (overall: 13.8%–12.3%, p = 0.001; emergent: 26.3%–20.6%, p \u3c 0.001) while mortality did not change. Discussion: Rates of RBC transfusion decreased in both emergent and non-emergent cases. Efforts to reduce transfusion may have been successful in the EGS population. Morbidity improved over the time periods while mortality was unchanged. Level of Evidence: Level III

Bayesian penalised likelihood reconstruction (Q.Clear) of 18F-fluciclovine PET for imaging of recurrent prostate cancer: semi-quantitative and clinical evaluation

Objective: 18F-Fluciclovine (FACBC) is an amino acid PET radiotracer approved for recurrent prostate cancer imaging. We investigate the use of Bayesian penalised likelihood (BPL) reconstruction for 18F-fluciclovine PET. Methods: 15 18F-fluciclovine scans were reconstructed using ordered subset expectation maximisation (OSEM), OSEM + point spread function (PSF) modelling and BPL using β-values 100–600. Lesion maximum standardised uptake value (SUVmax), organ SUVmean and standard deviation were measured. Deidentified reconstructions (OSEM, PSF, BPL using β200–600) from 10 cases were visually analysed by two readers who indicated their most and least preferred reconstructions, and scored overall image quality, noise level, background marrow image quality and lesion conspicuity. Results: Comparing BPL to OSEM, there were significant increments in lesion SUVmax and signal-to-background up to β400, with highest gain in β100 reconstructions (mean ΔSUVmax 3.9, p < 0.0001). Organ noise levels increased on PSF, β100 and β200 reconstructions. Across BPL reconstructions, there was incremental reduction in organ noise with increasing β, statistically significant beyond β300–500 (organ-dependent). Comparing with OSEM and PSF, lesion signal-to-noise was significantly increased in BPL reconstructions where β ≥ 300 and ≥ 200 respectively. On visual analysis, β 300 had the first and second highest scores for image quality, β500 and β600 equal highest scores for marrow image quality and least noise, PSF and β 200 had first and second highest scores for lesion conspicuity. For overall preference, one reader preferred β 300 in 9/10 cases and the other preferred β 200 in all cases. Conclusion: BPL reconstruction of 18F-fluciclovine PET images improves signal-to-noise ratio, affirmed by overall reader preferences. On balance, β300 is suggested for 18F-fluciclovine whole body PET image reconstruction using BPL. Advances in knowledge: The optimum β is different to that previously published for 18F-fluorodeoxyglucose, and has practical implications for a relatively new tracer in an environment with modern reconstruction technologies

Rapid flow-based synthesis of post-translationally modified peptides and proteins : a case study on MYC's transactivation domain

Protein–protein interactions of c-Myc (MYC) are often regulated by post-translational modifications (PTMs), such as phosphorylation, and crosstalk thereof. Studying these interactions requires proteins with unique PTM patterns, which are challenging to obtain by recombinant methods. Standard peptide synthesis and native chemical ligation can produce such modified proteins, but are time-consuming and therefore typically limited to the study of individual PTMs. Herein, we report the development of flow-based methods for the rapid synthesis of phosphorylated MYC sequences (up to 84 AA), and demonstrate the versatility of this approach for the incorporation of other PTMs (Nε-methylation, sulfation, acetylation, glycosylation) and combinations thereof. Peptides containing up to seven PTMs and phosphorylation at up to five sites were successfully prepared and isolated in high yield and purity. We further produced ten PTM-decorated analogues of the MYC Transactivation Domain (TAD) to screen for binding to the tumor suppressor protein, Bin1, using heteronuclear NMR and native mass spectrometry. We determined the effects of phosphorylation and glycosylation on the strength of the MYC:Bin1 interaction, and reveal an influence of MYC sequence length on binding. Our platform for the rapid synthesis of MYC sequences up to 84 AA with distinct PTM patterns thus enables the systematic study of PTM function at a molecular level, and offers a convenient way for expedited screening of constructs

Comprehensive multimodality characterization of hemodynamically significant and non-significant coronary lesions using invasive and noninvasive measures

Background There is limited knowledge about morphological molecular-imaging-derived parameters to further characterize hemodynamically relevant coronary lesions. Objective The aim of this study was to describe and differentiate specific parameters between hemodynamically significant and non-significant coronary lesions using various invasive and non-invasive measures. Methods This clinical study analyzed patients with symptoms suggestive of coronary artery disease (CAD) who underwent native T1-weighted CMR and gadofosveset-enhanced CMR as well as invasive coronary angiography. OCT of the culprit vessel to determine the plaque type was performed in a subset of patients. Functional relevance of all lesions was examined using quantitative flow reserve (QFR-angiography). Hemodynamically significant lesions were defined as lesions with a QFR <0.8. Signal intensity (contrast-to-noise ratios; CNRs) on native T1-weighted CMR and gadofosveset-enhanced CMR was defined as a measure for intraplaque hemorrhage and endothelial permeability, respectively. Results Overall 29 coronary segments from 14 patients were examined. Segments containing lesions with a QFR 0.8; n = 19) (5.32 (4.47–7.02) vs. 2.42 (1.04–5.11); p = 0.042). No differences in signal enhancement were seen on native T1-weighted CMR (2.2 (0.68–6.75) vs. 2.09 (0.91–6.57), p = 0.412). 66.7% (4 out of 6) of all vulnerable plaque and 33.3% (2 out of 6) of all non-vulnerable plaque (fibroatheroma) as assessed by OCT were hemodynamically significant lesions. Conclusion The findings of this pilot study suggest that signal enhancement on albumin-binding probe-enhanced CMR but not on T1-weighted CMR is associated with hemodynamically relevant coronary lesion

Engaging Undergraduates in Science Research: Not Just About Faculty Willingness.

Despite the many benefits of involving undergraduates in research and the growing number of undergraduate research programs, few scholars have investigated the factors that affect faculty members' decisions to involve undergraduates in their research projects. We investigated the individual factors and institutional contexts that predict faculty members' likelihood of engaging undergraduates in their research project(s). Using data from the Higher Education Research Institute's 2007-2008 Faculty Survey, we employ hierarchical generalized linear modeling to analyze data from 4,832 science, technology, engineering, and mathematics (STEM) faculty across 194 institutions to examine how organizational citizenship behavior theory and social exchange theory relate to mentoring students in research. Key findings show that faculty who work in the life sciences and those who receive government funding for their research are more likely to involve undergraduates in their research project(s). In addition, faculty at liberal arts or historically Black colleges are significantly more likely to involve undergraduate students in research. Implications for advancing undergraduate research opportunities are discussed

The EGS Grading Scale For Skin And Soft Tissue Infections Is Predictive Of Poor Outcomes : A Multicenter Validation Study

Introduction: Over the last five years, the American Association for the Surgery of Trauma (AAST) has developed grading scales for Emergency General Surgery (EGS) diseases. In a prior validation study using diverticulitis, the grading scales were predictive of complications and length of stay. As EGS encompasses diverse diseases, the purpose of this study was to validate the grading scale concept against a different disease process with a higher associated mortality. We hypothesized that the grading scale would be predictive of complications, length of stay and mortality in skin and soft tissue infections (STI). Methods: This multi-institutional trial encompassed 12 centers. Data collected included demographic variables, disease characteristics and outcomes such as mortality, overall complications, hospital and ICU length of stay. The EGS scale for STI was used to grade each infection and two surgeons graded each case to evaluate inter-rater reliability. Results: 1170 patients were included in this study. Inter-rater reliability was moderate (kappa coefficient 0.472-0.642, with 64-76% agreement). Higher grades (IV and V) corresponded to significantly higher LRINEC scores when compared with lower EGS grades. Patients with grade IV and V STI had significantly increased odds of all complications, as well as ICU and overall length of stay. These associations remained significant in logistic regression controlling for age, gender, comorbidities, mental status and hospital-level volume. Grade V disease was significantly associated with mortality as well. Conclusion: This validation effort demonstrates that Grade IV and V STI are significantly predictive of complications, hospital length of stay and mortality. Though predictive ability does not improve linearly with STI grade, this is consistent with the clinical disease process, in which lower grades represent cellulitis and abscess and higher grades are invasive infections. This second validation study confirms the EGS grading scale as predictive, and easily used, in disparate disease processes

A multi-decade record of high quality fCO2 data in version 3 of the Surface Ocean CO2 Atlas (SOCAT)

The Surface Ocean CO2 Atlas (SOCAT) is a synthesis of quality-controlled fCO2 (fugacity of carbon dioxide) values for the global surface oceans and coastal seas with regular updates. Version 3 of SOCAT has 14.7 million fCO2 values from 3646 data sets covering the years 1957 to 2014. This latest version has an additional 4.6 million fCO2 values relative to version 2 and extends the record from 2011 to 2014. Version 3 also significantly increases the data availability for 2005 to 2013. SOCAT has an average of approximately 1.2 million surface water fCO2 values per year for the years 2006 to 2012. Quality and documentation of the data has improved. A new feature is the data set quality control (QC) flag of E for data from alternative sensors and platforms. The accuracy of surface water fCO2 has been defined for all data set QC flags. Automated range checking has been carried out for all data sets during their upload into SOCAT. The upgrade of the interactive Data Set Viewer (previously known as the Cruise Data Viewer) allows better interrogation of the SOCAT data collection and rapid creation of high-quality figures for scientific presentations. Automated data upload has been launched for version 4 and will enable more frequent SOCAT releases in the future. High-profile scientific applications of SOCAT include quantification of the ocean sink for atmospheric carbon dioxide and its long-term variation, detection of ocean acidification, as well as evaluation of coupled-climate and ocean-only biogeochemical models. Users of SOCAT data products are urged to acknowledge the contribution of data providers, as stated in the SOCAT Fair Data Use Statement. This ESSD (Earth System Science Data) “living data” publication documents the methods and data sets used for the assembly of this new version of the SOCAT data collection and compares these with those used for earlier versions of the data collection (Pfeil et al., 2013; Sabine et al., 2013; Bakker et al., 2014). Individual data set files, included in the synthesis product, can be downloaded here: doi:10.1594/PANGAEA.849770. The gridded products are available here: doi:10.3334/CDIAC/OTG.SOCAT_V3_GRID

A pragmatic clinical effectiveness trial of a novel alternative to punishment for school-based substance use infractions: study protocol for the iDECIDE curriculum

BackgroundAdolescents who use alcohol and other drugs on school campuses are at heightened risk for adverse consequences to their health and wellbeing. Schools have historically turned to punitive approaches as a first-line response to substance use. However, punishment is an ineffective deterrent for substance use and may cause harm and increase inequities. iDECIDE (Drug Education Curriculum: Intervention, Diversion, and Empowerment) was developed as a scalable and youth-centered drug education and diversion program that can be used as a skills-based alternative to punishment. We aim to evaluate the effectiveness of the iDECIDE curriculum as an alternative to punishment (ATP) for school-based substance use infractions in the context of a large pragmatic clinical effectiveness study.MethodsWe will conduct a Type 1, hybrid effectiveness-implementation trial. Using a stepped wedge design with approximately 90 middle and high schools in Massachusetts, we will randomly allocate the timing of implementation of the iDECIDE curriculum compared to standard disciplinary response over approximately 36 months. We will test the overarching hypothesis that student-level outcomes (knowledge of drug effects and attitudes about substance use; frequency of substance use; school connectedness) improve over time as schools transition from a standard disciplinary response to having access to iDECIDE. The secondary aims of this trial are to (1) explore whether change in student-level outcomes vary according to baseline substance use, number of peers who use alcohol or other drugs, age, gender, and school urbanicity, and (2) determine the acceptability and feasibility of the iDECIDE curriculum through qualitative stakeholder interviews.DiscussionSubstance use continues to be a major and rapidly evolving problem in schools. The importance of moving away from punishment to more restorative approaches is widely accepted; however, scalable alternatives have not yet been identified. This will be the first study to our knowledge to systematically evaluate an ATP for students who violate the school substance use policy and is well poised to have important implications for policy making