Assessment of Emergency Medicine Resident Performance in an Adult Simulation Using a Multisource Feedback Approach.

Introduction: The Accreditation Council for Graduate Medical Education (ACGME) specifically notes multisource feedback (MSF) as a recommended means of resident assessment in the emergency medicine (EM) Milestones. High-fidelity simulation is an environment wherein residents can receive MSF from various types of healthcare professionals. Previously, the Queen\u27s Simulation Assessment Tool (QSAT) has been validated for faculty to assess residents in five categories: assessment; diagnostic actions; therapeutic actions; interpersonal communication, and overall assessment. We sought to determine whether the QSAT could be used to provide MSF using a standardized simulation case. Methods: Prospectively after institutional review board approval, residents from a dual ACGME/osteopathic-approved postgraduate years (PGY) 1-4 EM residency were consented for participation. We developed a standardized resuscitation after overdose case with specific 1-5 Likert anchors used by the QSAT. A PGY 2-4 resident participated in the role of team leader, who completed a QSAT as self-assessment. The team consisted of a PGY-1 peer, an emergency medical services (EMS) provider, and a nurse. Two core faculty were present to administer the simulation case and assess. Demographics were gathered from all participants completing QSATs. We analyzed QSATs by each category and on cumulative score. Hypothesis testing was performed using intraclass correlation coefficients (ICC), with 95% confidence intervals. Interpretation of ICC results was based on previously published definitions. Results: We enrolled 34 team leader residents along with 34 nurses. A single PGY-1, a single EMS provider and two faculty were also enrolled. Faculty provided higher cumulative QSAT scores than the other sources of MSF. QSAT scores did not increase with team leader PGY level. ICC for inter-rater reliability for all sources of MSF was 0.754 (0.572-0.867). Removing the self-evaluation scores increased inter-rater reliability to 0.838 (0.733-0.910). There was lesser agreement between faculty and nurse evaluations than from the EMS or peer evaluation. Conclusion: In this single-site cohort using an internally developed simulation case, the QSAT provided MSF with excellent reliability. Self-assessment decreases the reliability of the MSF, and our data suggest self-assessment should not be a component of MSF. Use of the QSAT for MSF may be considered as a source of data for clinical competency committees

Benchmarking the reproducibility of all-solid-state battery cell performance

The interlaboratory comparability and reproducibility of all-solid-state battery cell cycling performance are poorly understood due to the lack of standardized set-ups and assembly parameters. This study quantifies the extent of this variability by providing commercially sourced battery materials—LiNi0.6Mn0.2Co0.2O2 for the positive electrode, Li6PS5Cl as the solid electrolyte and indium for the negative electrode—to 21 research groups. Each group was asked to use their own cell assembly protocol but follow a specific electrochemical protocol. The results show large variability in assembly and electrochemical performance, including differences in processing pressures, pressing durations and In-to-Li ratios. Despite this, an initial open circuit voltage of 2.5 and 2.7 V vs Li+/Li is a good predictor of successful cycling for cells using these electroactive materials. We suggest a set of parameters for reporting all-solid-state battery cycling results and advocate for reporting data in triplicate

HSV Neutralization by the Microbicidal Candidate C5A

Genital herpes is a major risk factor in acquiring human immunodeficiency virus type-1 (HIV-1) infection and is caused by both Herpes Simplex virus type 1 (HSV-1) and HSV-2. The amphipathic peptide C5A, derived from the non-structural hepatitis C virus (HCV) protein 5A, was shown to prevent HIV-1 infection but neither influenza nor vesicular stomatitis virus infections. Here we investigated the antiviral function of C5A on HSV infections. C5A efficiently inhibited both HSV-1 and HSV-2 infection in epithelial cells in vitro as well as in an ex vivo epidermal infection model. C5A destabilized the integrity of the viral HSV membrane. Furthermore, drug resistant HSV strains were inhibited by this peptide. Notably, C5A-mediated neutralization of HSV-1 prevented HIV-1 transmission. An in vitro HIV-1 transmigration assay was developed using primary genital epithelial cells and HSV infection increased HIV-1 transmigration. Treatment with C5A abolished HIV-1 transmigration by preventing HSV infection and by preserving the integrity of the genital epithelium that was severely compromised by HSV infection. In conclusion, this study demonstrates that C5A represents a multipurpose microbicide candidate, which neutralizes both HIV-1 and HSV, and which may interfere with HIV-1 transmission through the genital epithelium

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

A Novel Pathogenic Mechanism of Highly Pathogenic Avian Influenza H5N1 Viruses Involves Hemagglutinin Mediated Resistance to Serum Innate Inhibitors

In this study, the effect of innate serum inhibitors on influenza virus infection was addressed. Seasonal influenza A(H1N1) and A(H3N2), 2009 pandemic A(H1N1) (H1N1pdm) and highly pathogenic avian influenza (HPAI) A(H5N1) viruses were tested with guinea pig sera negative for antibodies against all of these viruses as evaluated by hemagglutination-inhibition and microneutralization assays. In the presence of serum inhibitors, the infection by each virus was inhibited differently as measured by the amount of viral nucleoprotein produced in Madin-Darby canine kidney cells. The serum inhibitors inhibited seasonal influenza A(H3N2) virus the most, while the effect was less in seasonal influenza A(H1N1) and H1N1pdm viruses. The suppression by serum inhibitors could be reduced by heat inactivation or treatment with receptor destroying enzyme. In contrast, all H5N1 strains tested were resistant to serum inhibitors. To determine which structure (hemagglutinin (HA) and/or neuraminidase (NA)) on the virus particles that provided the resistance, reverse genetics (rg) was applied to construct chimeric recombinant viruses from A/Puerto Rico/8/1934(H1N1) (PR8) plasmid vectors. rgPR8-H5 HA and rgPR8-H5 HANA were resistant to serum inhibitors while rgPR8-H5 NA and PR8 A(H1N1) parental viruses were sensitive, suggesting that HA of HPAI H5N1 viruses bestowed viral resistance to serum inhibition. These results suggested that the ability to resist serum inhibition might enable the viremic H5N1 viruses to disseminate to distal end organs. The present study also analyzed for correlation between susceptibility to serum inhibitors and number of glycosylation sites present on the globular heads of HA and NA. H3N2 viruses, the subtype with highest susceptibility to serum inhibitors, harbored the highest number of glycosylation sites on the HA globular head. However, this positive correlation cannot be drawn for the other influenza subtypes

Explaining lifelong loyalty: The role of identity fusion and self-shaping group events

Pledging lifelong loyalty to an ingroup can have far-reaching behavioural effects, ranging from ordinary acts of ingroup kindness to extraordinary acts of self-sacrifice. What motivates this important form of group commitment? Here, we propose one especially potent answer to this question–the experience of a visceral sense of oneness with a group (i.e., identity fusion). In a sample of British football fans, a population in which high levels of lifelong loyalty are thought to be common, we first examined the hypothesised relationship between fusion and perceptions of lifelong loyalty to one’s club. We further explored the hypothesis that fusion and lifelong loyalty are not merely a reflection of past time investment in a group, but also reflect a deeper, memory-based process of feeling personally shaped by key group events, both euphoric and dysphoric. We found broad support for these hypotheses. Results suggest that feeling personally self-shaped by club events (e.g., crucial wins and losses), rather than time invested in the club, leads to greater identity fusion to one’s club. In turn, fusion engenders a sense of lifelong club loyalty. We discuss our findings in relation to the growing literature on the experiential origins of intense social cohesion

Search for sterile neutrino mixing in the MINOS long-baseline experiment

A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18×1020 protons on target in which neutrinos of energies between ~500¿¿MeV and 120 GeV are produced predominantly as ¿µ, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ¿µ flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles ¿24 and ¿34 are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime t3/m3>2.1×10-12¿¿s/eV at 90% C.L

Combination Therapy Using Chimeric Monoclonal Antibodies Protects Mice from Lethal H5N1 Infection and Prevents Formation of Escape Mutants

10.1371/journal.pone.0005672PLoS ONE4

Modafinil modulation of the default mode network

RationaleThe default mode network (DMN) is a functional network which is implicated in a range of cognitive processes. This network is proposed to consist of hubs located in the ventromedial prefrontal cortex (vmPFC), posterior cingulate/retrosplenial cortex (PCC/rSpl), and inferior parietal lobule (IPL), with other midline cortical and temporal lobe nodes connected to these hubs. How this network is modulated by neurochemical systems during functional brain activity is not yet understood.ObjectivesIn the present study, we used the norepinephrine/dopamine transporter inhibitor modafinil to test the hypothesis that this drug modulates the DMN.MethodsEighteen healthy right-handed adults participated in a double-blind, placebo-controlled study of single oral dose modafinil 200 mg. They performed a simple visual sensorimotor task during slow event-related fMRI. Drug effects were interrogated within the DMN defined by task-induced deactivation (TID) on placebo.ResultsThere was a trend toward faster reaction time (RT) on modafinil (Cohen's d = 0.38). Brain regions within the DMN which exhibited significant modafinil-induced augmentation of TID included vmPFC, PCC/rSpl, and left IPL. Across subjects, the modafinil effect on TID in the vmPFC was significantly and specifically associated with drug effects on RT speeding.ConclusionsModafinil augments TID in the DMN to facilitate sensorimotor processing speed, an effect which may be particularly dependent on changes in vmPFC activity. This is consistent with the gain control function of catecholamine systems and may represent an important aspect of the pro-cognitive effects of modafinil