Effects of a single interprofessional simulation session on medical and nursing students’ attitudes toward interprofessional learning and professional identity: a questionnaire study

Background Participation in simulation-based interprofessional education (sim-IPE) may affect students’ attitudes towards interprofessional learning (through gaining experience with others) and their professional identity (by increasing the ‘fit’ of group membership). We examined this in two questionnaire studies involving students from four universities in two areas of the UK. Method Questionnaire data were collected before and after students took part in a sim-IPE session consisting of three acute scenarios. Questionnaires included the Readiness for Interprofessional Learning Scale (RIPLS) and measures of professional identity derived from the social identity theory literature. In Study 1, only identification with Professional Group (doctor or nurse) was measured, while in Study 2 identification with Student Group (medical or nursing student) and the immediate interprofessional Team worked with in the simulation were also measured. Linear mixed effects regression analysis examined the effect of the simulation session, and differences between medical and nursing students, sites and identity measures. Results A total of 194 medical and 266 nursing students completed questionnaires. A five-item subset of RIPLS (RIPLSCore) was used in analysis. In both studies RIPLSCore increased for all groups following participation in sim-IPE, although this was larger for nursing students in Study 1. Nursing students had consistently higher RIPLSCore scores than medical students at one site. Effects of the session on identity varied between sites, and dimensions of identity. Notably, while positive emotions associated with group membership (Ingroup Affect) increased for Student Group, Professional Group and Team, the sense of belonging (Ingroup Ties) and importance (Centrality) of the group increased only for Team. Nursing students had consistently higher identification scores than medical students. Conclusions Participation in a sim-IPE session can improve attitudes towards interprofessional learning. It can also enhance professional identity, particularly as related to emotional aspects of group membership, with possible benefits for wellbeing. Changes in identification with the immediate Team suggest positive psychological consequences of ad hoc Team formation in the workplace. Differences between medical and nursing students suggest their differing opportunities to work with other professions during training may change baseline attitudes and identity. However, a single sim-IPE session can still have an additive effect

Mass spectrometry-based proteomics for advancing solid organ transplantation research

Scarcity of high-quality organs, suboptimal organ quality assessment, unsatisfactory pre-implantation procedures, and poor long-term organ and patient survival are the main challenges currently faced by the solid organ transplant (SOT) field. New biomarkers for assessing graft quality pre-implantation, detecting, and predicting graft injury, rejection, dysfunction, and survival are critical to provide clinicians with invaluable prediction tools and guidance for personalized patients' treatment. Additionally, new therapeutic targets are also needed to reduce injury and rejection and improve transplant outcomes. Proteins, which underlie phenotypes, are ideal candidate biomarkers of health and disease statuses and therapeutic targets. A protein can exist in different molecular forms, called proteoforms. As the function of a protein depends on its exact composition, proteoforms can offer a more accurate basis for connection to complex phenotypes than protein from which they derive. Mass spectrometry-based proteomics has been largely used in SOT research for identification of candidate biomarkers and therapeutic intervention targets by so-called “bottom-up” proteomics (BUP). However, such BUP approaches analyze small peptides in lieu of intact proteins and provide incomplete information on the exact molecular composition of the proteins of interest. In contrast, “Top-down” proteomics (TDP), which analyze intact proteins retaining proteoform-level information, have been only recently adopted in transplantation studies and already led to the identification of promising proteoforms as biomarkers for organ rejection and dysfunction. We anticipate that the use of top-down strategies in combination with new technological advancements in single-cell and spatial proteomics could drive future breakthroughs in biomarker and therapeutic target discovery in SOT

Assembly line enzymology by multimodular nonribosomal peptide synthetases: the thioesterase domain of E. coli EntF catalyzes both elongation and cyclolactonization

BackgroundEntF is a 142 kDa four domain (condensation-adenylationpeptidyl carrier protein-thioesterase) nonribosomal peptide synthetase (NRPS) enzyme that assembles the Escherichia coli N-acyl-serine trilactone siderophore enterobactin from serine, dihydroxybenzoate (DHB) and ATP with three other enzymes (EntB, EntD and EntE). To assess how EntF forms three ester linkages and cyclotrimerizes the covalent acyl enzyme DHB-Ser-S-PCP (peptidyl carrier protein) intermediate, we mutated residues of the proposed catalytic Ser-His-Asp triad of the thioesterase (TE) domain.ResultsThe Ser1138→Cys mutant (kcat decreased 1000-fold compared with wild-type EntF) releases both enterobactin (75%) and linear (DHB-Ser)2 dimer (25%) as products. The HiResultThe Ser1138→Cys mutant (kcat decreased 1000-fold compared with wild-type EntF) releases both enterobactin (75%) and linear (DHB-Ser)2 dimer (25%) as products. The His1271→Ala mutant (kcat decreased 10,000-fold compared with wild-type EntF) releases only enterobactin, but accumulates both DHB-Ser-O-TE and (DHB-Ser)2-O-TE acyl enzyme intermediates. Electrospray ionization and Fourier transform mass spectrometry of proteolytic digests were used to analyze the intermediates.71→Ala mutant (kcat decreased 10,000-fold compared with wild-type EntF) releases only enterobactin, but accumulates both DHB-Ser-O-TE and (DHB-Ser)2-O-TE acyl enzyme intermediates. Electrospray ionization and Fourier transform mass spectrometry of proteolytic digests were used to analyze the intermediates.ConclusionsThese results establish that the TE domain of EntF is both a cyclotrimerizing lactone synthetase and an elongation catalyst for ester-bond formation between covalently tethered DHB-Ser moieties, a new function for chain-termination TE domains found at the carboxyl termini of multimodular NRPSs and polyketide synthases

Transmission of High-Power Electron Beams Through Small Apertures

Tests were performed to pass a 100 MeV, 430 kWatt c.w. electron beam from the energy-recovery linac at the Jefferson Laboratory's FEL facility through a set of small apertures in a 127 mm long aluminum block. Beam transmission losses of 3 p.p.m. through a 2 mm diameter aperture were maintained during a 7 hour continuous run.Comment: arXiv admin note: text overlap with arXiv:1305.019

Measured Radiation and Background Levels During Transmission of Megawatt Electron Beams Through Millimeter Apertures

We report measurements of photon and neutron radiation levels observed while transmitting a 0.43 MW electron beam through millimeter-sized apertures and during beam-off, but accelerating gradient RF-on, operation. These measurements were conducted at the Free-Electron Laser (FEL) facility of the Jefferson National Accelerator Laboratory (JLab) using a 100 MeV electron beam from an energy-recovery linear accelerator. The beam was directed successively through 6 mm, 4 mm, and 2 mm diameter apertures of length 127 mm in aluminum at a maximum current of 4.3 mA (430 kW beam power). This study was conducted to characterize radiation levels for experiments that need to operate in this environment, such as the proposed DarkLight Experiment. We find that sustained transmission of a 430 kW continuous-wave (CW) beam through a 2 mm aperture is feasible with manageable beam-related backgrounds. We also find that during beam-off, RF-on operation, multipactoring inside the niobium cavities of the accelerator cryomodules is the primary source of ambient radiation when the machine is tuned for 130 MeV operation.Comment: 9 pages, 11 figures, submitted to Nuclear Instruments and Methods in Physics Research Section

Interprofessional simulation as an enhancement of psychological fidelity : a focus group study of medical and nursing students

Background and Aims. Interprofessional simulation has the potential to enhance the perceived realism of clinical simulation in the education of different healthcare professionals. This study considers how the inclusion of more than one profession in clinical simulation contributes to this psychological fidelity, defined as the subjective perception of the realism of a simulation, and the cues identified by medical and nursing students. Methods. Eight focus groups were carried out with 27 medical and 18 nursing students in Newcastle and Oxford, UK. These were carried out immediately after students' participation in simulation sessions consisting of three acute scenarios. Focus group discussions encompassed perceptions of the realism of the simulation and of participants' own and other professional groups. Thematic analysis was carried out on transcripts. Results. The analysis identified features of psychological fidelity that were influenced by the interprofessional element of the simulation. These included overall impressions of realism, and the perceived roles and expectations of doctors and nurses within the simulation. In particular, the presence of the other professional group afforded a more authentic response. Other features varied with the viewpoint of the student groups, in particular the realism of the patient manikin, which held lower psychological fidelity for the nursing students, because it did not allow them to fulfill their perceived role of delivering holistic, relational care. Conclusion. Recognizing “psychological fidelity” as a subjective response to simulation allows greater consideration of the limitations of fidelity as a designed or engineered property of a simulation. While interprofessional involvement directly enhances psychological fidelity in some ways, potential differences in the views of students from different professional groups should be considered when implementing interprofessional simulation

ProSight PTM 2.0: improved protein identification and characterization for top down mass spectrometry

ProSight PTM 2.0 (http://prosightptm2.scs.uiuc.edu) is the next generation of the ProSight PTM web-based system for the identification and characterization of proteins using top down tandem mass spectrometry. It introduces an entirely new data-driven interface, integrated Sequence Gazer for protein characterization, support for fixed modifications, terminal modifications and improved support for multiple precursor ions (multiplexing). Furthermore, it supports data import and export for local analysis and collaboration

Highly multiplexed, label-free proteoform imaging of tissues by individual ion mass spectrometry.

Imaging of proteoforms in human tissues is hindered by low molecular specificity and limited proteome coverage. Here, we introduce proteoform imaging mass spectrometry (PiMS), which increases the size limit for proteoform detection and identification by fourfold compared to reported methods and reveals tissue localization of proteoforms at <80-μm spatial resolution. PiMS advances proteoform imaging by combining ambient nanospray desorption electrospray ionization with ion detection using individual ion mass spectrometry. We demonstrate highly multiplexed proteoform imaging of human kidney, annotating 169 of 400 proteoforms of <70 kDa using top-down MS and a database lookup of ~1000 kidney candidate proteoforms, including dozens of key enzymes in primary metabolism. PiMS images reveal distinct spatial localizations of proteoforms to both anatomical structures and cellular neighborhoods in the vasculature, medulla, and cortex regions of the human kidney. The benefits of PiMS are poised to increase proteome coverage for label-free protein imaging of tissues

Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation

Extensive studies of the structure–function relationship of antibodies have established that conventional immunoglobulins contain two copies of the antigen-binding fragment (Fab), each of which serves as an autonomous and complete unit for recognizing an antigen. In this paper, we report a previously unidentified mode of antibody–antigen recognition, dubbed “antigen clasping,” where two antigen-binding sites cooperatively clasp one antigen, and the design of a long-neck antibody format that facilitates antigen clasping. Antigen clasping led to recombinant antibodies for histone posttranslational modifications with extraordinarily high specificity, valuable tools for epigenetic research. This study substantially broadens the long-standing paradigm for antibody–antigen recognition