339 research outputs found

    Error Reporting Behaviors

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    Although patient safety is a focus with medical care, it has been influenced by the lack of safety culture in the environment (Vincent et al., 2000). Preventable medical errors continue to plague healthcare and cost close to $1 trillion annually (Andel et al., 2012). Despite the prevalence of medical errors, only one of seven errors are reported (Levinson, 2010). Understanding the behaviors that influence reporting is imperative to developing patient safety reporting initiatives. Ajzen’s theory of planned behavior identifies behaviors as based on a combination of beliefs, intentions, and social control (1988). Applying this model to error reporting, we hypothesize that error reporting behaviors are shaped by different variables. Personality and expertise as well as age and sex impact error reporting attitudes and behaviors, and individual differences pertaining to culture, such as the extent that an individual submits to authority or status and hierarchy affect error reporting. Likewise, organizational factors can influence the extent to which errors are reported (Uribe, et al., 2002; Wakefield et al., 2001). Surveys were collected longitudinally from senior medical students’ with little to no previous experience as a professional. The survey tool includes items that were pulled from the validated Attitudes toward Patient Safety Questionnaire, a validated measure of power distance, previously reported items measuring reporting behaviors and demographic items. Understanding error reporting behaviors guides healthcare providers to develop protocols or initiatives. Knowing what particular constructs predict the intent to report, healthcare providers can successfully implement structure, change workplace culture, and education

    Applying a Team Performance Framework to better Understand the Handoff Process: Part 1

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    Handoffs require critical information transfers that are clear, comprehensible, and correct from receiver to sender. There are many factors that influence the reliability of the information in a handoff procedure, and impact the subsequent choices that are made that affect patient care. Using the Input – Mediator – Output – Input model multiple factors that influence the information transfer process have been identified to better handoff communication and in turn, lead to better patient care. The IMOI model is a recently developed theory that claims the productivity and value of interaction among team members can be influenced by cognitive, affective, and external factors (Weaver et al., 2013). This clarifies that the output affects the future performance of a group through a feedback loop, as well as reflects variability in mediational influences. This paper focuses on the first two parts of the IMOI model; input and mediators. Individual characteristics affect the handoff process for both the sender and receiver, including attitudes, expertise, experience, expectations, and fitness for duty. The inputs of a handoff are the individual characteristics of the providers and the patient case, where mediation is the shared process to develop an outcome. The attitudes, expertise, experience, and fitness for duty influence the composition of the team, but are moderated by factors such as interventions, communication, resources, team monitoring, and team orientation. By understanding these factors, providers can create a safer environment and provide safer patient care

    Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-κB pathways.

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    The NF-κB protein RelB controls dendritic cell (DC) maturation and may be targeted therapeutically to manipulate T cell responses in disease. Here we report that RelB promoted DC activation not as the expected RelB-p52 effector of the noncanonical NF-κB pathway, but as a RelB-p50 dimer regulated by canonical IκBs, IκBα and IκBɛ. IκB control of RelB minimized spontaneous maturation but enabled rapid pathogen-responsive maturation. Computational modeling of the NF-κB signaling module identified control points of this unexpected cell type-specific regulation. Fibroblasts that we engineered accordingly showed DC-like RelB control. Canonical pathway control of RelB regulated pathogen-responsive gene expression programs. This work illustrates the potential utility of systems analyses in guiding the development of combination therapeutics for modulating DC-dependent T cell responses

    Attenuated mismatch negativity in patients with first-episode antipsychotic-naive schizophrenia using a source-resolved method

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    Background: Mismatch negativity (MMN) is a measure of pre-attentive auditory information processing related to change detection. Traditional scalp-level EEG methods consistently find attenuated MMN in patients with chronic but not first-episode schizophrenia. In the current paper, we use a source-resolved method to assess MMN and hypothesize that more subtle changes can be identified with this analysis method. Method: Fifty-six first-episode antipsychotic-naïve schizophrenia (FEANS) patients (31 males, 25 females, mean age 24.6) and 64 matched controls (37 males, 27 females, mean age 24.8) were assessed for duration-, frequency- and combined-type MMN and P3a as well as 4 clinical, 3 cognitive and 3 psychopathological measures. To evaluate and correlate MMN at source-level, independent component analysis (ICA) was applied to the continuous EEG data to derive equivalent current dipoles which were clustered into 19 clusters based on cortical location. Results: No scalp channel group MMN or P3a amplitude differences were found. Of the localized clusters, several were in or near brain areas previously suggested to be involved in the MMN response, including frontal and anterior cingulate cortices and superior temporal and inferior frontal gyri. For duration deviants, MMN was attenuated at the right superior temporal gyrus in patients compared to healthy controls (p = 0.01), as was P3a at the superior frontal cortex (p = 0.01). No individual patient correlations with clinical, cognitive, or psychopathological measures survived correction for multiple comparisons. Conclusion: Attenuated source-localized MMN and P3a peak contributions can be identified in FEANS patients using a method based on independent component analysis (ICA). This indicates that deficits in pre-attentive auditory information processing are present at this early stage of schizophrenia and are not the result of disease chronicity or medication. This is to our knowledge the first study on FEANS patients using this more detailed method. Keywords: Mismatch negativity, Schizophrenia, First episode, EEG, IC

    Two subgroups of antipsychotic-naive, first-episode schizophrenia patients identified with a Gaussian mixture model on cognition and electrophysiology

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    AbstractDeficits in information processing and cognition are among the most robust findings in schizophrenia patients. Previous efforts to translate group-level deficits into clinically relevant and individualized information have, however, been non-successful, which is possibly explained by biologically different disease subgroups. We applied machine learning algorithms on measures of electrophysiology and cognition to identify potential subgroups of schizophrenia. Next, we explored subgroup differences regarding treatment response. Sixty-six antipsychotic-naive first-episode schizophrenia patients and sixty-five healthy controls underwent extensive electrophysiological and neurocognitive test batteries. Patients were assessed on the Positive and Negative Syndrome Scale (PANSS) before and after 6 weeks of monotherapy with the relatively selective D2 receptor antagonist, amisulpride (280.3±159 mg per day). A reduced principal component space based on 19 electrophysiological variables and 26 cognitive variables was used as input for a Gaussian mixture model to identify subgroups of patients. With support vector machines, we explored the relation between PANSS subscores and the identified subgroups. We identified two statistically distinct subgroups of patients. We found no significant baseline psychopathological differences between these subgroups, but the effect of treatment in the groups was predicted with an accuracy of 74.3% (P=0.003). In conclusion, electrophysiology and cognition data may be used to classify subgroups of schizophrenia patients. The two distinct subgroups, which we identified, were psychopathologically inseparable before treatment, yet their response to dopaminergic blockade was predicted with significant accuracy. This proof of principle encourages further endeavors to apply data-driven, multivariate and multimodal models to facilitate progress from symptom-based psychiatry toward individualized treatment regimens.</jats:p

    The putative drug efflux systems of the Bacillus cereus group

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    The Bacillus cereus group of bacteria includes seven closely related species, three of which, B. anthracis, B. cereus and B. thuringiensis, are pathogens of humans, animals and/or insects. Preliminary investigations into the transport capabilities of different bacterial lineages suggested that genes encoding putative efflux systems were unusually abundant in the B. cereus group compared to other bacteria. To explore the drug efflux potential of the B. cereus group all putative efflux systems were identified in the genomes of prototypical strains of B. cereus, B. anthracis and B. thuringiensis using our Transporter Automated Annotation Pipeline. More than 90 putative drug efflux systems were found within each of these strains, accounting for up to 2.7% of their protein coding potential. Comparative analyses demonstrated that the efflux systems are highly conserved between these species; 70-80% of the putative efflux pumps were shared between all three strains studied. Furthermore, 82% of the putative efflux system proteins encoded by the prototypical B. cereus strain ATCC 14579 (type strain) were found to be conserved in at least 80% of 169 B. cereus group strains that have high quality genome sequences available. However, only a handful of these efflux pumps have been functionally characterized. Deletion of individual efflux pump genes from B. cereus typically had little impact to drug resistance phenotypes or the general fitness of the strains, possibly because of the large numbers of alternative efflux systems that may have overlapping substrate specificities. Therefore, to gain insight into the possible transport functions of efflux systems in B. cereus, we undertook large-scale qRT-PCR analyses of efflux pump gene expression following drug shocks and other stress treatments. Clustering of gene expression changes identified several groups of similarly regulated systems that may have overlapping drug resistance functions. In this article we review current knowledge of the small molecule efflux pumps encoded by the B. cereus group and suggest the likely functions of numerous uncharacterised pumps

    Tyrosine phosphorylation directs TACE into extracellular vesicles via unconventional secretion

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    When studying how HIV-1 Nef can promote packaging of the proinflammatory transmembrane protease TACE (tumor necrosis factor-alpha converting enzyme) into extracellular vesicles (EVs) we have revealed a novel tyrosine kinase-regulated unconventional protein secretion (UPS) pathway for TACE. When TACE was expressed without its trafficking cofactor iRhom allosteric Hck activation by Nef triggered translocation of TACE into EVs. This process was insensitive to blocking of classical secretion by inhibiting endoplasmic reticulum (ER) to Golgi transport, and involved a distinct form of TACE devoid of normal glycosylation and incompletely processed for prodomain removal. Like most other examples of UPS this process was Golgi reassembly stacking protein (GRASP)-dependent but was not associated with ER stress. These data indicate that Hck-activated UPS provides an alternative pathway for TACE secretion that can bypass iRhom-dependent ER to Golgi transfer, and suggest that tyrosine phosphorylation might have a more general role in regulating UPS.Peer reviewe
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