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Substantial effort has gone into neuroimaging studies of neural mechanisms underlying addiction. Human studies of smoking typically either give monetary reward during an fMRI task or else allow subjects to smoke outside the scanner, after the session. This raises a fundamental issue of construct validity, as it is unclear whether the same neural mechanisms process decisions about nicotine that process decisions about money. To address this, we developed a novel MR-compatible nicotine vaping device, such that access to nicotine vapor could be controlled and monitored. We recruited heavy smokers (Money: 45 subjects, 13 females and 32 males; Nicotine: 21 subjects, 4 females and 17 males) to perform a gambling task with nicotine and monetary reward on separate days. We collected BOLD fMRI data while they performed the task inside the scanner and analyzed it using general linear modeling, with inference based on cluster-size correction. This allowed a direct comparison between the neural mechanisms of choosing and receiving immediate drug vs. monetary reward. We found substantial differences in the neural mechanisms that underlie risky choices about money vs. drug reward, including a reversal of the well-known error effects in the medial prefrontal cortex.

The increasing demand and hectic pace of emergency departments across the nation requires the development of safe patient care provision and healthy workplaces. Both of these developments can be achieved when staff is actively engaged in decision making for quality patient care and department operations. This article reviews how teamwork can be used to address both safer patient care provision and healthy workplace creation. A case study follows that describes one emergency department's journey to develop and continuously improve the quality and safety of patient care as the continuing follow-through from full participation in the Parsons Healthy Workplace Intervention. It describes their unit-based committees, their strategies, how they work as a team, and early outcomes to enhance the emergency department's quality and safety of patient care. [ABSTRACT FROM AUTHOR]

This article describes the Healthy Workplace Initiative in the adult emergency department from the staff nurse perspective. Examples of one action planning team's processes and outcomes are delineated. The Rapid Diagnostics action planning team is delineated as lived while caring for patients in today's high-pressure emergency department. The Healthy Workplace Initiative empowers staff, with the guidance of facilitators, to make changes that improve the workplace and to create a healthy workplace for staff and patients. The result is greater staff ownership of the emergency department which leads to greater job satisfaction and improved patient care. [ABSTRACT FROM AUTHOR]

Background: Moral distress is the inability to do the right thing due to imposed constraints., Objective: Explore the presence of moral distress among nurses., Methods: A quantitative, exploratory, cross-sectional study at a level 1 trauma center using the Measure of Moral Distress for Healthcare Professionals (MMD-HP)., Results: Ninety-seven nurses completed the MMD-HP. The top 3 items contributing to moral distress included inadequate staffing, inadequate resources, and lack of administrative support. Nurses who considered leaving had more moral distress. Moral distress explained 28.5% of the variance associated with nurses' "intent to leave" and "primary unit" ( P < 0.001). Moral distress for nurses 40 to 49 years of age was higher compared with nurses 50 years or older., Conclusions: Moral distress involved deficiencies in staffing, resources, and administrative support. Research should explore interventions to mitigate moral distress among nurses by promoting safe staffing levels, the provision of adequate resources, and increased administrative support., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The Purpose: Of this study was to understand emergency nurses' use of frailty to inform care, disposition decision-making, and further assessment., Methods: A qualitative, descriptive, exploratory approach was used. Field notes from group discussions held during a conference presession on frailty and post-session evaluation data were analyzed., Results: Two common ideas threaded these discussions: frailty as vulnerability to "falling through the cracks" and that of an iceberg. Participants stressed the broad and expansive ramifications of frailty, and lack of structure/process to accurately describe, quantify, and utilize the concept. Participants described issues of physical and emotional/social fragility, including being unable to complete activities of daily living independently; also of concern were the patients' social determinants of health and financial challenges., Conclusion: The conceptual understanding of frailty encompassed physical, social, cognitive, and access deficits. Emergency nurses are aware of this concept and would conduct formal frailty screening if provided with training, time, and resources., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest in the conduct, results, or dissemination of this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Social living affords primates (including humans) many benefits. Communication has been proposed to be the key mechanism used to bond social connections, which could explain why primates have evolved such expressive faces. We assessed whether the facial expressivity of the dominant male (quantified from the coding of anatomically based facial movement) was related to social network properties (based on social proximity and grooming) in nine groups of captive rhesus macaques ( Macaca mulatta ) housed in uniform physical and social environments. More facially expressive dominant male macaques were more socially connected and had more cohesive social groups. These findings show that inter-individual differences in facial expressivity are related to differential social outcomes at both an individual and group level. More expressive individuals occupy more beneficial social positions, which could help explain the selection for complex facial communication in primates.

Quick, easy access to data-driven community risk assessment principles and to related community risk reduction activities can encourage fire departments to learn about, conduct, and complete district risk reduction practices. With the ultimate goal of creating web-based community risk assessment and community risk reduction resources, we first evaluated fire department needs. Over an eight-month period, a quantitative online survey was administered to officers from 45 unique fire departments in 44 Kentucky counties, with follow-up qualitative telephone interviews administered to 11 fire officials. Mixed-methods, sequential analysis of the data clarified the "what," "who," and "how" of risk analysis/reduction activities, noted what specific reduction activities departments used to prepare for and mitigate risk, and named specific facilitators and barriers to risk assessment and reduction. Respondents described data use for community risk assessment and for planning community risk reduction activities; how a lack of time, personnel, and funding impacts community risk assessment and community risk reduction activities; and how to involve both firefighters and the community in the process. Innovative solutions such as a website containing resources on how to assess community risk information along with resources such as community risk assessment/ reduction education, program planning, and tools, can assist departments to use community risk assessment data in the development of community risk reduction activities., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paul R. Clark reports financial support was provided by Federal Emergency Management Agency, United States., (Copyright © 2023 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

The social complexity hypothesis for communicative complexity posits that animal societies with more complex social systems require more complex communication systems. We tested the social complexity hypothesis on three macaque species that vary in their degree of social tolerance and complexity. We coded facial behavior in >3000 social interactions across three social contexts (aggressive, submissive, affiliative) in 389 animals, using the Facial Action Coding System for macaques (MaqFACS). We quantified communicative complexity using three measures of uncertainty: entropy, specificity, and prediction error. We found that the relative entropy of facial behavior was higher for the more tolerant crested macaques as compared to the less tolerant Barbary and rhesus macaques across all social contexts, indicating that crested macaques more frequently use a higher diversity of facial behavior. The context specificity of facial behavior was higher in rhesus as compared to Barbary and crested macaques, demonstrating that Barbary and crested macaques used facial behavior more flexibly across different social contexts. Finally, a random forest classifier predicted social context from facial behavior with highest accuracy for rhesus and lowest for crested, indicating there is higher uncertainty and complexity in the facial behavior of crested macaques. Overall, our results support the social complexity hypothesis., Competing Interests: AR, BW, JD, AM, CP, PC, JM No competing interests declared, (© 2023, Rincon et al.)

Ambiguity in communicative signals may lead to misunderstandings and thus reduce the effectiveness of communication, especially in unpredictable interactions such as between closely matched rivals or those with a weak social bond. Therefore, signals used in these circumstances should be less ambiguous, more stereotyped and more intense. To test this prediction, we measured facial movements of crested macaques ( Macaca nigra ) during spontaneous social interaction, using the Facial Action Coding System for macaques (MaqFACS). We used linear mixed models to assess whether facial movement intensity and variability varied according to the interaction outcome, the individuals' dominance relationship and their social bond. Movements were least intense and most variable in affiliative contexts, and more intense in interactions between individuals who were closely matched in terms of dominance rating. We found no effect of social bond strength. Our findings provide evidence for a reduction in ambiguity of facial behaviour in risky social situations but do not demonstrate any mitigating effect of social relationship quality. The results indicate that the ability to modify communicative signals may play an important role in navigating complex primate social interactions. This article is part of the theme issue 'Cognition, communication and social bonds in primates'.

Objective: The current literary evidence suggests but does not heavily endorse the use of prophylactic antiepileptic drugs (AEDs) after aneurysmal subarachnoid hemorrhage. Literature continues to emerge suggesting not only a lack of efficacy but associated poor outcomes. This study is a retrospective review comparing seizure incidence in aneurysmal subarachnoid patients between those given prophylactic AEDs and those not., Methods: With IRB approval, a retrospective chart review was performed on all aneurysmal subarachnoid patients from 2012 to 2019 at the University of Mississippi Medical center. Univariate and Multivariate analysis was performed using SAS. Primary outcome was seizure incidence between groups. Factors associated with seizure and poor outcome were also investigated., Results: 348 patients were identified: 120 in the AED group, and 228 patients in the non-AED group. There was no significant difference in mean age, gender, ethnicity, HH scores, treatment modality, or mean aneurysm size. The AED group had a higher history of prior aneurysmal rupture (6.7% vs. 1.3%, p = 0.01) and associated intracranial hemorrhage (22.5% vs. 10.5%, p = 0.0004). There was no significant difference in seizure incidence between the two groups (8.3% vs. 4.8%, p = 0.24). On multivariate analysis, aneurysm clipping compared to coiling (OR 3.8, p = 0.012) and delayed cerebral ischemia (OR 2.77, p = 0.023) were associated with seizures. DCI (OR 8.34), HH grade, Age (OR 1.07), Seizure (8.34), and AED use (1.7) were significantly associated with poor outcome., Conclusion: This retrospective review adds to the evidence that prophylactic AED use in aneurysmal subarachnoid hemorrhage patients has not been proven to improve seizure rates and may result in worse patient outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: While it has been demonstrated that even subtle variation in human facial expressions can lead to significant changes in the meaning and function of expressions, relatively few studies have examined primate facial expressions using similarly objective and rigorous analysis. Construction of primate facial expression repertoires may, therefore, be oversimplified, with expressions often arbitrarily pooled and/or split into subjective pigeonholes. Our objective is to assess whether subtle variation in primate facial expressions is linked to variation in function, and hence to inform future attempts to quantify complexity of facial communication., Materials and Methods: We used Macaque Facial Action Coding System, an anatomically based and hence more objective tool, to quantify "silent bared-teeth" (SBT) expressions produced by wild crested macaques engaging in spontaneous behavior, and utilized discriminant analysis and bootstrapping analysis to look for morphological differences between SBT produced in four different contexts, defined by the outcome of interactions: Affiliation, Copulation, Play, and Submission., Results: We found that SBT produced in these contexts could be distinguished at significantly above-chance rates, indicating that the expressions produced in these four contexts differ morphologically. We identified the specific facial movements that were typically used in each context, and found that the variability and intensity of facial movements also varied between contexts., Discussion: These results indicate that nonhuman primate facial expressions share the human characteristic of exhibiting meaningful subtle differences. Complexity of facial communication may not be accurately represented simply by building repertoires of distinct expressions, so further work should attempt to take this subtle variability into account., (© 2020 The Authors. American Journal of Physical Anthropology published by Wiley Periodicals LLC.)

Introduction: Emergency nurses are exposed to both primary and secondary trauma with attendant sequelae in both work and personal spheres. The purpose of the study was to investigate the prevalence of traumatic stress, measured by the secondary traumatic stress scale (STSS) in a sample of emergency nurses and describe the impact of traumatic stress on nursing practice and workplace environment., Methods: Mixed methods approach using survey instrument data from the Secondary Traumatic Stress Scale (STSS) (N = 125) and focus group data (N = 53)., Results: The average total score on the STSS was 51.83 for nurses who attended one of the focus groups 48.42 for nurses who did not attend (clinical cutoff for STS = 39). Focus group data aligned with elements of the STSS; thematic categories of cumulative trauma, mental health sequelae, bullying and organizational violence, coping mechanisms, relationship damage, and solutions were described. Although we measured only STS, participants often used the terms "PTSD" and "STS" interchangeably., Conclusions: The nurses in this study demonstrated high levels of STS and described in detail how chronic, cumulative trauma affected relational nursing care and social connections. Participants discussed high levels of suicidality in the profession, and the compounding trauma of relational and organizational violence. The pervasiveness of traumatic stress and the extent to which it affects all areas of nurses' lives is a cause for great concern., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The relationship between outcomes, patient safety indicators and volume has been well established in patient's undergoing craniotomy for brain tumor. However, the determination of "high" and "low" volume centers have been subjectively derived. We present a paper with a novel method of objectively determining "high" volume centers for craniotomy for brain tumor., Methods: Patients from 2002 to 2011 were identified in the Nationwide Inpatient Sample database using ICD-9 codes related to craniotomy for brain tumor. Primary endpoints of interest were hospital PSI event rate, in-hospital mortality rate, observed-to-expected PSI event ratio, and O/E in-hospital mortality ratio. Using a zero-inflated gamma model analysis and a cutpoint analysis we determined the volume threshold between and "high" and "low" volume hospitals. We then completed an analysis using this determined threshold to look at PSI events and mortality as they relate to "high" volume and "low" volume hospitals., Results: 12.4 % of hospitals were categorized as good performers using O/E ratios. Regarding in-hospital mortality, 16.8 % were good performers. Using the above statistical analysis the threshold to define high vs. low volume centers was determined to be 27 craniotomies. High volume centers had significantly lower O/E ratios for both PSI and mortality events. The PSI O/E ratio was reduced 55 % and mortality O/E ratio reduced 73 % at high volume centers as defined by our analysis., Conclusions: Patients treated at institutions performing >27 craniotomies per year for brain tumors have a lower likelihood of PSI events and decreased in-hospital morbidity and mortality., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A scalable metal-, azide-, and halogen-free method for the synthesis of substituted 1,2,3-triazoles has been developed. The reaction proceeds through a 3-component coupling of α-ketoacetals, tosyl hydrazide, and a primary amine. The reaction shows outstanding functional-group tolerance with respect to both the α-ketoacetal and amine coupling partners, providing access to 4-, 1,4-, 1,5-, and 1,4,5-substituted triazoles in excellent yield. This robust method results in densely functionalised 1,2,3-triazoles that remain challenging to prepare by azide-alkyne cycloaddition (AAC, CuAAC, RuAAC) methods and can be scaled in either batch or flow reactors. Methods for the chemoselective reaction of either aliphatic amines or anilines are also described, revealing some of the potential of this novel and highly versatile transformation., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate changes in emergency nursing workload related to cannabis ingestion or inhalation by adult and pediatric patients in states and bordering states where recreational cannabis is legal., Design: Qualitative exploratory design using data collected from focus groups., Sample: Twenty-four English-speaking emergency nurses over the age of 18 who provide direct care to patients and work in US emergency departments located in a state, or bordering state, where recreational cannabis use is legal., Measurements: Qualitative data were gathered using a semi-structured interview format and analyzed using situational analysis., Results: The legalization of recreational cannabis in some US states is reported as resulting in an increase in patients presenting with cyclic vomiting syndromes, and increased difficulty in managing both associated behaviors and repetitive ED presentations. New presentations also include unintentional intoxication in both pediatric and geriatric populations. An unexpected finding was the displacement of local homeless populations by younger, indigent "cannabis tourists"; social services agencies might consider this while planning for cannabis legalization in their state or territory., Conclusions: To protect public health and safety, regulatory efforts to standardize the formulation, dosing and labeling of cannabis products would be beneficial along with educational initiatives for both consumers and health care providers., (© 2019 Wiley Periodicals, Inc.)

This paper describes the development, optimisation and exemplification of a copper-catalysed C-H functionalisation to form pharmaceutically relevant 2-aminobenzimidazoles from aryl-guanidines. High throughput screening was used as a tool to identify a catalytically active copper source, DoE was used for reaction optimisation and a range of aryl-guanidines were prepared and exposed to the optimum conditions to afford a range of 2-aminobenzimidazoles in moderate to good yields. The methodology has been applied to the synthesis of Emedastine, a marketed anti-histamine pharmaceutical compound, with the key cyclisation step performed on a gram-scale.

Introduction: There are significant and negative psychological effects that can occur in nursing staff caring for pediatric patients experiencing critical incidents. Debriefings can provide relief from the stressors caused by critical incidents. Adapting a pre-existing critical incident stress debriefing (CISD) process to ED staff is 1 way to provide staff debriefing., Methods: This qualitative study used an emerging, descriptive design. Focus groups, (n = 3, total participant n = 19), consisting of pediatric emergency nurses and a nursing assistant, met for a minimum of 63 to a maximum of 83 minutes. Participants provided feedback on current debriefing strategies and suggestions for adapting a currently existing critical incident stress- debriefing process. Focus group questions included "Have you participated in a structured debriefing process? If so, tell us about it" and "What would you like to see in a structured debriefing process?", Results: A theoretical orientation content analysis revealed 1 main theme-Clearing the Air and Finding Answers-and 6 subthemes: Current Debriefing Strategies; Positive Reinforcement; Constructive Critique; Clinical, Not Emotional; I've already moved on; and CISD Structure., Discussion: Pediatric ED staff de-stress in a variety of ways, and a nonmandatory, formalized CISD process-open to staff involved and facilitated by an emergency nurse-could provide additional relief from stress. This debriefing process should include positive feedback and critiques to help improve care processes, information about mechanism of injury, and should occur before the end of shift or within 12 to 24 hours of the incident. Staff may deal with personal feelings outside of debriefing., (Copyright © 2018 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Injury from firearms is a significant problem in the United States, accounting for 73% of all homicides and 50% of all suicides that occurred among US residents. What is not known are the perceptions of emergency nurses regarding the impact of in-home access on the risk for firearm-related injury and death in their patient populations. The purpose of this study was to explore emergency nurses' perception of patient risk for firearm injury and in which ways that perception affected the process of ED patient screening, assessment, counseling, and discharge education., Methods: We employed a mixed methods, sequential, explanatory design using quantitative survey data and qualitative focus-group data., Results: Between 21.8 and 43.5% of respondents reported asking patients about access to in-home firearms, depending on presentation. Statistical analyses showed the single most significant factor correlated with nurses asking about the availability of a staff person who could further assess risk and offer assistance and safety counseling to patients. Another important influence was identified from focus-group discussions in which nurses reported that they felt challenged to bring up the topic of firearms in a way that did not seem confrontational., Discussion: Access to firearms poses risk to patients, and patient safety and the continuum of care depends upon the emergency nurse assessing patient firearms risk and taking appropriate action. The findings from this study suggest that emergency departments (1) normalize and standardize the assessment of firearms, (2) designate an ED staff member on each shift to further assess risk if a positive response is elicited, and (3) continue to improve workplace safety., (Copyright © 2018 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Screening for suicidality is a critical nursing function at the initial ED encounter. Suicide is the tenth leading cause of death in the United States, and a substantial percentage of people who die by suicide present for health care in the year before their deaths. The emergency department provides health care professionals with a critical opportunity to identify patients at risk for suicide and intervene appropriately., Methods: Qualitative exploratory study using focus-group data., Findings: Effective and accurate suicidality assessment occurs not by asking a single question but also with the assessment of patient behaviors and presentation (appearance, hygiene, etc). When emergency nurses suspected occult suicidality, additional actions (finding private space, keeping patients safe, and passing on information), took priority., Discussion: The Joint Commission recommends using clinical judgment tools for the final determination of safety for a patient at suspected risk of suicide, as research findings suggest that a screening tool can identify persons at risk for suicide more reliably than a clinician's personal judgment. Our participants report that when they assessed suicide risk at triage, it was usually by asking a single question such as "Do you have thoughts or plans to harm yourself?" and they expressed concern about the effectiveness of doing so. Participants described their efforts to improve suicide screening across the duration of the patient's ED stay through an iterative process of assessment that included further probing and eliciting, evaluating, and reacting to the patient's response., (Copyright © 2018 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

OBJECTIVE The Agency of Healthcare Research and Quality (AHRQ) has defined Patient Safety Indicators (PSIs) for assessments in quality of inpatient care. The hypothesis of this study is that, in the treatment of unruptured cerebral aneurysms (UCAs), PSI events are less likely to occur in hospitals meeting the volume thresholds defined by The Joint Commission for Comprehensive Stroke Center (CSC) certification. METHODS Using the 2002-2011 National (Nationwide) Inpatient Sample, patients treated electively for a nonruptured cerebral aneurysm were selected. Patients were evaluated for PSI events (e.g., pressure ulcers, retained surgical item, perioperative hemorrhage, pulmonary embolism, sepsis) defined by AHRQ-specified ICD-9 codes. Hospitals were categorized by treatment volume into CSC or non-CSC volume status based on The Joint Commission's annual volume thresholds of at least 20 patients with subarachnoid hemorrhage and performance of 15 or more endovascular coiling or surgical clipping procedures for aneurysms. RESULTS A total of 65,824 patients underwent treatment for an unruptured cerebral aneurysm. There were 4818 patients (7.3%) in whom at least 1 PSI event occurred. The overall inpatient mortality rate was 0.7%. In patients with a PSI event, this rate increased to 7% compared with 0.2% in patients without a PSI event (p < 0.0001). The overall rate of poor outcome was 3.8%. In patients with a PSI event, this rate increased to 23.3% compared with 2.3% in patients without a PSI event (p < 0.0001). There were significant differences in PSI event, poor outcome, and mortality rates between non-CSC and CSC volume-status hospitals (PSI event, 8.4% vs 7.2%; poor outcome, 5.1% vs 3.6%; and mortality, 1% vs 0.6%). In multivariate analysis, all patients treated at a non-CSC volume-status hospital were more likely to suffer a PSI event with an OR of 1.2 (1.1-1.3). In patients who underwent surgery, this relationship was more substantial, with an OR of 1.4 (1.2-1.6). The relationship was not significant in the endovascularly treated patients. CONCLUSIONS In the treatment of unruptured cerebral aneurysms, PSI events occur relatively frequently and are associated with significant increases in morbidity and mortality. In patients treated at institutions achieving the volume thresholds for CSC certification, the likelihood of having a PSI event, and therefore the likelihood of poor outcome and mortality, was significantly decreased. These improvements are being driven by the improved outcomes in surgical patients, whereas outcomes and mortality in patients treated endovascularly were not sensitive to the CSC volume status of the hospital and showed no significant relationship with treatment volumes.

Background: The Institute of Medicine recognizes that the workplace environment is a crucial factor in the ability of nurses to provide safe and effective care, and thus interactions that affect the quality and safety of the work environment require exploration., Objectives: The purpose of this study was to use situational analysis to develop a grounded theory of workplace bullying as it manifests specifically in the emergency care setting., Methods: This study used a grounded theory methodology called situational analysis. 44 emergency RNs were recruited to participate in one of 4 focus group sessions, which were transcribed in their entirety, and, along with field notes, served as the dataset., Results: This grounded theory describes the characteristics of human actors and their reactions to conditions in the practice environment that lead to greater or lesser levels of bullying, and the responses to bullying as it occurs in U.S. emergency departments., Discussion: Workplace bullying is a significant factor in the dynamics of patient care, nursing work culture, and nursing retention. The impact on patient care cannot be overestimated, both in terms of errors, substandard care, and the negative effects of high turnover of experienced RNs who leave, compounded by the inexperience of newly hired RNs. An assessment of hospital work environments should include nurse perceptions of workplace bullying, and interventions should focus on effective managerial processes for handling workplace bullying. Future research should include testing of the theoretical coherence of the model, and the testing of bullying interventions to determine the effect on workplace environment, nursing intent to leave/retention, and patient outcomes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Emergency nursing requires acute attention to detail to provide safe and effective care to potentially unstable or critically ill patients; this requirement may be significantly impaired by physical and mental fatigue. There is a lack of evidence regarding the effects of fatigue caused by factors other than a sleep deficit (e.g., emotional exhaustion). Fatigue affects nurses' ability to work safely in the emergency care setting and potentially impacts their health and quality of life outside of work., Methods: This was the qualitative arm of a mixed methods study; we used a qualitative exploratory design with focus group data from a sample of 16 emergency nurses. Themes were identified using an inductive approach to content analysis., Results/discussion: The following themes were identified: "It's a weight on your back;" "Competitive nursing;" "It's never enough;" "You have to get away;" and "Engagement as a solution.", Conclusions: Our participants reported high levels of fatigue, which compromised patient care, had a negative effect on their personal lives, and created a toxic unit environment. They reported lateral violence as both the cause and effect of mental and emotional fatigue, suggesting that unit culture affects nurses and the patients they care for., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The emergency department is a unique practice environment in that the Emergency Medical Treatment and Active Labor Act (EMTALA), which mandates a medical screening examination for all presenting patients, effectively precludes any sort of patient volume control; staffing needs are therefore fluid and unpredictable. The purpose of this study is to explore emergency nurses' perceptions of factors involved in safe staffing levels and to identify factors that negatively and positively influence staffing levels and might lend themselves to more effective interventions and evaluations., Methods: We used a qualitative exploratory design with focus group data from a sample of 26 emergency nurses. Themes were identified using a constructivist perspective and an inductive approach to content analysis., Results: Five themes were identified: (1) unsafe environment of care, (2) components of safety, (3) patient outcomes: risky care, (4) nursing outcomes: leaving the profession, and (5) possible solutions. Participants reported that staffing levels are determined by the number of beds in the department (as in inpatient units) but not by patient acuity or the number of patients waiting for treatment. Participants identified both absolute numbers of staff, as well as experience mix, as components of safe staffing. Inability to predict the acuity of patients waiting to be seen was a major component of nurses' perceptions of unsafe staffing., Discussion: Emergency nurses perceive staffing to be inadequate, and therefore unsafe, because of the potential for poor patient outcomes, including missed or delayed care, missed deterioration (failure to rescue), and additional ED visits resulting from ineffective discharge teaching. Both absolute numbers of staff, as well as skill and experience mix, should be considered to provide staffing levels that promote optimal patient and nurse outcomes., (Copyright © 2017 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

The ways in which environmental factors participate in the progression of autoimmune diseases are not known. After initiation, it takes years before hyperglycemia develops in patients at risk for type 1 diabetes (T1D). The receptor for advanced glycation endproducts (RAGE) is a scavenger receptor of the Ig family that binds damage-associated molecular patterns and advanced glycated endproducts and can trigger cell activation. We previously found constitutive intracellular RAGE expression in lymphocytes from patients with T1D. In this article, we show that there is increased RAGE expression in T cells from at-risk euglycemic relatives who progress to T1D compared with healthy control subjects, and in the CD8 + T cells in the at-risk relatives who do versus those who do not progress to T1D. Detectable levels of the RAGE ligand high mobility group box 1 were present in serum from at-risk subjects and patients with T1D. Transcriptome analysis of RAGE + versus RAGE - T cells from patients with T1D showed differences in signaling pathways associated with increased cell activation and survival. Additional markers for effector memory cells and inflammatory function were elevated in the RAGE + CD8 + cells of T1D patients and at-risk relatives of patients before disease onset. These studies suggest that expression of RAGE in T cells of subjects progressing to disease predates dysglycemia. These findings imply that RAGE expression enhances the inflammatory function of T cells, and its increased levels observed in T1D patients may account for the chronic autoimmune response when damage-associated molecular patterns are released after cell injury and killing., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Introduction: Moral distress in nursing has been studied in many settings, but there is a paucity of research on moral distress as it manifests in the emergency department. One study suggests a correlation between moral distress and aspects of burnout, and other researchers report that nurses have considered leaving their position or even their profession because of moral distress. Further exploration of these issues may provide insight into their effects on ED patient care and the emergency nursing profession. The purpose of this study was to explore the nature of moral distress as it is experienced and described by emergency nurses., Methods: A qualitative, exploratory design was employed using semi-structured focus groups for data collection. Using an iterative process, transcripts were analyzed for emerging themes by the research team. Six researchers analyzed the transcripts using a thematic analysis approach., Results: Themes from the data included dysfunctional practice arena, being overwhelmed, and adaptive/maladaptive coping. Participants described, overall, a profound feeling of not being able to provide patient care as they wanted to., Discussion: Causes of moral distress in emergency nurses are environment driven, not incident driven, as is described in other settings, and include a high-acuity, high-demand, technical environment with insufficient resources. Interventions should be targeted to improve environmental factors that contribute to the moral distress of emergency nurses. Future research should focus on the development and validation of an instrument to measure moral distress in this setting., (Copyright © 2016 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Introduction: The importance of end-of-life (EOL) care for dying patients and their families is well described; however, little research has been performed in emergency settings. The purpose of this study was to explore emergency nurses' perceptions of challenges and facilitators in the care of patients at the EOL., Methods: A mixed-methods design using survey data (N = 1,879) and focus group data (N = 17). Data were collected on questions regarding care of the EOL patient in the emergency department, specifically nurses' perceptions of the care of these patients; educational content needs; barriers to safe and effective care; and the availability of resources., Results: High scores on the quantitative survey showed a high mean level of consistently positive attitudes and beliefs toward caring for dying patients and their families and loved ones (131.26 ± 10.88). Analysis of the focus group transcripts uncovered 9 themes, reflecting concerns around comfort and challenges with EOL care, appropriate training for nurses, and the availability of resources to provide this type of care in the emergency setting. Also noted was dissonance between the nature of emergency care and the nature of EOL care., Discussion: Emergency nurses are comfortable providing EOL care in the emergency setting but note that challenges to providing good care include lack of space, time, and staff. Other challenges involve the mismatch between the goals of emergency care and those of EOL care, as well as the emotional burden of caring for the dying, especially when the appropriate resources are lacking., (Copyright © 2015 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Capillary leak in severe sepsis involves disruption of endothelial cell tight junctions. We modeled this process by TNF treatment of cultured human dermal microvascular endothelial cell (HDMEC) monolayers, which unlike human umbilical vein endothelial cells form claudin-5-dependent tight junctions and a high-resistance permeability barrier. Continuous monitoring with electrical cell-substrate impedance sensing revealed that TNF disrupts tight junction-dependent HDMEC barriers in discrete steps: an ~5% increase in transendothelial electrical resistance over 40 minutes; a decrease to ~10% below basal levels over 2 hours (phase 1 leak); an interphase plateau of 1 hour; and a major fall in transendothelial electrical resistance to < 70% of basal levels by 8-10 hours (phase 2 leak), with EC50 values of TNF for phase 1 and 2 leak of ~30 and ~150 pg/ml, respectively. TNF leak is reversible and independent of cell death. Leak correlates with disruption of continuous claudin-5 immunofluorescence staining, myosin light chain phosphorylation and loss of claudin-5 co-localization with cortical actin. All these responses require NF-κB signaling, shown by inhibition with Bay 11 or overexpression of IκB super-repressor, and are blocked by H-1152 or Y-27632, selective inhibitors of Rho-associated kinase that do not block other NF-κB-dependent responses. siRNA combined knockdown of Rho-associated kinase-1 and -2 also prevents myosin light chain phosphorylation, loss of claudin-5/actin co-localization, claudin-5 reorganization and reduces phase 1 leak. However, unlike H-1152 and Y-27632, combined Rho-associated kinase-1/2 siRNA knockdown does not reduce the magnitude of phase 2 leak, suggesting that H-1152 and Y-27632 have targets beyond Rho-associated kinases that regulate endothelial barrier function. We conclude that TNF disrupts TJs in HDMECs in two distinct NF-κB-dependent steps, the first involving Rho-associated kinase and the second likely to involve an as yet unidentified but structurally related protein kinase(s).

Objective: To assess the role claudin-5, an endothelial cell (EC) tight junction protein, plays in establishing basal permeability levels in humans by comparing claudin-5 expression levels in situ and analyzing junctional organization and function in 2 widely used models of cultured ECs, namely human dermal microvascular (HDM)ECs and human umbilical vein (HUV)ECs., Methods and Results: By immunofluorescence microscopy, ECs more highly express claudin-5 (but equivalently express vascular endothelial-cadherin) in human dermal capillaries versus postcapillary venules and in umbilical and coronary arteries versus veins, correlating with known segmental differences in tight junction frequencies and permeability barriers. Postconfluent cultured HDMECs express more claudin-5 (but equivalent vascular endothelial-cadherin) and show higher transendothelial electric resistance and lower macromolecular flux than similarly cultured HUVECs. HDMEC junctions are more complex by transmission electron microscopy and show more continuous claudin-5 immunofluorescence than HUVEC junctions. Calcium chelation or dominant negative vascular endothelial-cadherin overexpression decreases transendothelial electric resistance and disrupts junctions in HUVECs, but not in HDMECs. Claudin-5 overexpression in HUVECs fails to increase transendothelial electric resistance or claudin-5 continuity, whereas claudin-5 knockdown in HDMECs, but not in HUVECs, reduces transendothelial electric resistance and increases antibody accessibility to junctional proteins., Conclusions: Claudin-5 expression and junctional organization control HDMEC and arteriolar-capillary paracellular barriers, whereas HUVEC and venular junctions use vascular endothelial-cadherin.

Parasite life history may differ during coinfection compared to single infections, and the order of infection may be an important predictor of life history traits. We subjected laboratory mice (Mus musculus) to single and coinfections with Heligmosomoides bakeri and Hymenolepis microstoma and measured life history traits of worms and also hepatobiliary and morphological responses by the host. We found that fewer H. bakeri larvae established, and adult worms were shorter and produced fewer eggs during a coinfection where H. microstoma occurred first. H. microstoma grew more and released more eggs after simultaneous inoculation of both parasites compared to a single H. microstoma infection, despite similar worm numbers. Mouse small intestine mass, but not length, varied with coinfection and bile duct mass was largest when H. microstoma was given alone or first. Mouse serum alkaline phosphatase levels were greatest for mice infected with H. microstoma only but did not vary with number of scolices; no change in mouse serum alanine transaminase levels was observed. Overall, the order of coinfection influenced life history traits of both H. bakeri and H. microstoma, but changes in survival, growth, and reproduction with order of inoculation were not consistent between the two parasites.

Objective: ECs lining arteries respond to LSS by suppressing pro-inflammatory changes, in part through the activation of MEK5, ERK5 and induction of KLF4. We examined if this anti-inflammatory pathway operates in human ECs lining microvessels, the principal site of inflammatory responses., Methods: We used immunofluorescence microscopy of human skin to assess ERK5 activation and KLF4 expression in HDMECs in situ. We applied LSS to or overexpressed MEK5/CA in cultured HDMECs and assessed gene expression by microarrays and qRT-PCR and protein expression by Western blotting. We assessed effects of MEK5/CA on TNF responses using qRT-PCR, FACS and measurements of HDMEC monolayer electrical resistance. We used siRNA knockdown to assess the role of ERK5 and KLF4 in these responses., Results: ERK5 phosphorylation and KLF4 expression is observed in HDMECs in situ. LSS activates ERK5 and induces KLF4 in cultured HDMECs. MEK5/CA-transduced HDMECs show activated ERK5 and increased KLF4, thrombomodulin, eNOS, and ICAM-1 expression. MEK5 induction of KLF4 is mediated by ERK5. MEK5/CA-transduced HDMECs are less responsive to TNF, an effect partly mediated by KLF4., Conclusions: MEK5 activation by LSS inhibits inflammatory responses in microvascular ECs, in part through ERK5-dependent induction of KLF4., (© 2011 John Wiley & Sons Ltd.)

A changing healthcare landscape requires nurses to care for more patients with higher acuity during their shift than ever before. These more austere working conditions are leading to increased burnout. In addition, patient safety is not of the quality or level that is required. To build healthier workplaces where safe care is provided, formal teamwork training is recommended. Formal teamwork training programs, such as that provided by the MedTeams group, TeamSTEPPS (Team Strategies and Tools to Enhance Performance and Patient Safety), or participatory action research programs such as the Healthy Workplace Intervention, have decreased errors in the workplace, increased nurse satisfaction and retention rates, and decreased staff turnover. This article includes necessary determinants of teamwork, brief overviews of team-building programs, and examples of research programs that demonstrate how teamwork brings about healthier workplaces that are safer for patients. Teamwork programs can bring about these positive results when implemented and supported by the hospital system.

Tumor necrosis factor (TNF) initiates local inflammation by triggering endothelial cells (EC) to express adhesion molecules for leukocytes such as intercellular adhesion molecule-1 (ICAM-1 or CD54). A prior study identified siRNA molecules that reduce ICAM-1 expression in cultured human umbilical vein EC (HUVEC). One of these, ISIS 121736, unexpectedly inhibits TNF-mediated up-regulation of additional molecules on EC, including E-selectin (CD62E), VCAM-1 (CD106) and HLA-A,B,C. 736 siRNA transfection was not toxic for EC nor was there any evidence of an interferon response. 736 Transfection of EC blocked multiple early TNF-related signaling events, including activation of NF-kappaB. IL-1 activation of these same pathways was not inhibited. A unifying explanation is that 736 siRNA specifically reduced expression of mRNA encoding tumor necrosis factor receptor 1 (TNFR1) as well as TNFR1 surface expression. A sequence with high identity to the 736 antisense strand (17 of 19 bases) is present within the 3'UTR of human TNFR1 mRNA. An EGFP construct incorporating the 3'UTR of TNFR1 was silenced by 736 siRNA and this effect was lost by mutagenesis of this complementary sequence. Chemical modification and mismatches within the sense strand of 736 also inhibited silencing activity. In summary, an siRNA molecule selected to target ICAM-1 through its antisense strand exhibited broad anti-TNF activities. We show that this off-target effect is mediated by siRNA knockdown of TNFR1 via its sense strand. This may be the first example in which the off-target effect of an siRNA is actually responsible for the anticipated effect by acting to reduce expression of a protein (TNFR1) that normally regulates expression of the intended target (ICAM-1).

Tumor necrosis factor (TNF)-induced ICAM-1 in endothelial cells (EC) promotes leukocyte adhesion. Here we report that ICAM-1 also effects EC barrier function. Control- or E-selectin-transduced human dermal microvascular EC (HDMEC) form a barrier to flux of proteins and to passage of current (measured as transendothelial electrical resistance or TEER). HDMEC transduced with ICAM-1 at levels comparable to that induced by TNF show reduced TEER, but do so without overtly changing their cell junctions, cell shape, or cytoskeleton organization. Higher levels of ICAM-1 further reduce TEER, increase F/G-actin ratios, rearrange the actin cytoskeleton to cause cell elongation, and alter junctional zona occludens 1 and vascular endothelial-cadherin staining. Transducing with ICAM-1 lacking an intracellular region also reduces TEER. TNF-induced changes in TEER and shape follow a similar time course as ICAM-1 induction; however, the fall in TEER occurs at lower TNF concentrations. Inhibiting NF-kappaB activation blocks ICAM-1 induction; TEER reduction, and shape change. Specific small-interfering RNA knockdown of ICAM-1 partially inhibits TNF-induced shape change. We conclude that moderately elevated ICAM-1 expression reduces EC barrier function and that expressing higher levels of ICAM-1 affects cell junctions and the cytoskeleton. Induction of ICAM-1 may contribute to but does not fully account for TNF-induced vascular leak and EC shape change.

Measurement of liver iron concentration (LIC) is necessary for a range of iron-loading disorders such as hereditary hemochromatosis, thalassemia, sickle cell disease, aplastic anemia, and myelodysplasia. Currently, chemical analysis of needle biopsy specimens is the most common accepted method of measurement. This study presents a readily available noninvasive method of measuring and imaging LICs in vivo using clinical 1.5-T magnetic resonance imaging units. Mean liver proton transverse relaxation rates (R2) were measured for 105 humans. A value for the LIC for each subject was obtained by chemical assay of a needle biopsy specimen. High degrees of sensitivity and specificity of R2 to biopsy LICs were found at the clinically significant LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g dry tissue. A calibration curve relating liver R2 to LIC has been deduced from the data covering the range of LICs from 0.3 to 42.7 mg Fe/g dry tissue. Proton transverse relaxation rates in aqueous paramagnetic solutions were also measured on each magnetic resonance imaging unit to ensure instrument-independent results. Measurements of proton transverse relaxivity of aqueous MnCl2 phantoms on 13 different magnetic resonance imaging units using the method yielded a coefficient of variation of 2.1%.

Measurement of liver iron concentration (LIC) is an important clinical procedure in the management of transfusional iron overload with iron chelation. LIC gives an indication of over- or underchelation. Although chemical assay of needle biopsy samples from the liver has been considered the "gold standard" of LIC measurement, needle biopsy sampling errors can be surprisingly large owing to the natural spatial variation of LIC throughout the liver and the small size of biopsy specimens. A magnetic resonance imaging technique has now been developed that enables safe noninvasive measurement and imaging of LIC with a known accuracy and precision. Measurements of LIC can be made over the range of LIC encountered in clinical practice. The technique is based on the measurement and imaging of proton transverse relaxation rates (R2) within the liver. The R2 imaging technique can be implemented on most clinical 1.5-T MRI instruments, making it readily available to the clinical community.

A single-spin-echo methodology is described for the measurement and imaging of proton transverse relaxation rates (R2) in iron-loaded and normal human liver tissue in vivo. The methodology brings together previously reported techniques dealing with (i) the changes in gain between each spin-echo acquisition, (ii) signal level offset due to background noise, (iii) estimation of signal intensities in decay curves at time zero to enable reliable extraction of relaxation times from tissues with very short T2 values, (iv) bi-exponential modelling of decay curves with a small number of data points, and (v) reduction of respiratory motion artefacts. The accuracy of the technique is tested on aqueous manganese chloride solutions yielding a relaxivity of 74.1+/-0.3 s-1 (mM)-1, consistent with previous reports. The precision of the in vivo measurement of mean liver R2 values is tested through duplicate measurements on 10 human subjects with mean liver R2 values ranging from 26 to 220 s-1. The random uncertainty on the measurement of mean liver R2 was found to be 7.7%., (Copyright (c) 2004 John Wiley & Sons, Ltd.)

An empirical motion artifact suppression technique has been developed to reduce the respiratory motion artifacts in axial single spin-echo magnetic resonance (MR) images of the liver post-acquisition. The correction scheme is based on the observation that the dominant motion artifacts within abdominal MR images are ghosts that follow the profile and signal intensity of high signal intensity boundaries, such as those for the subcutaneous fat along the anterior abdominal wall. The technique is applied to the reduction of respiratory motion artifacts in a spin echo image series of the liver of an iron-loaded patient and of a manganese chloride phantom subject to respiratory motion. Subsequent improvements to transverse relaxation rate (R2) image analysis are then demonstrated on the motion-corrected spin echo images, illustrating the utility of the technique for application in the R2 image-based measurement and mapping of liver iron concentration.

The paradigm for recovery of the renal tubule from acute tubular necrosis is that surviving cells from the areas bordering the injury must migrate into the regions of tubular denudation and proliferate to re-establish the normal tubular epithelium. However, therapies aimed at stimulating these events have failed to alter the course of acute renal failure in human trials. In the present study, we demonstrate that Lin-Sca-1+ cells from the adult mouse bone marrow are mobilized into the circulation by transient renal ischemia and home specifically to injured regions of the renal tubule. There they differentiate into renal tubular epithelial cells and appear to constitute the majority of the cells present in the previously necrotic tubules. Loss of stem cells following bone marrow ablation results in a greater rise in blood urea nitrogen after renal ischemia, while stem cell infusion after bone marrow ablation reverses this effect. Thus, therapies aimed at enhancing the mobilization, propagation, and/or delivery of bone marrow stem cells to the kidney hold potential as entirely new approaches for the treatment of acute tubular necrosis.

Rabbit liver was loaded with ferrimagnetic particles of gamma -Fe2 O3 (designed for magnetic hyperthermia treatment of liver tumors) by injecting various doses of a suspension of the particles into the hepatic artery in vivo. Proton transverse relaxation rate (R(2)) images of the livers in vivo, excised, and dissected were generated from a series of single spin-echo images. Mean R(2) values for samples of ferrimagnetic-particle-loaded liver dissected into approximate 1 cm cubes were found to linearly correlate with tissue iron concentration over the range from approximately 0.1 to at least 2.7 mg Fe/g dry tissue when measured at room temperature. Changing the temperature of ferrimagnetic-particle-loaded samples of liver from 1 degrees C to 37 degrees C had no observable effect on tissue R(2) values. However, a small but significant decrease in R(2) was found for control samples containing no ferrimagnetic material on raising the temperature from 1 degrees C to 37 degrees C. Both chemically measured iron concentrations and mean R(2) values for rabbit livers with implanted tumors tended to be higher than those measured for tumor-free liver. This study indicates that tissue R(2) measurement and imaging by nuclear magnetic resonance may have a useful role in magnetic hyperthermia therapy protocols for the treatment of liver cancer.

A bi-exponential proton transverse relaxation rate (R(2)) image analysis technique has been developed that enables the discrimination of dual compartment transverse relaxation behavior in systems with rapid transverse relaxation enhancement. The technique is particularly well suited to single spin-echo imaging studies where a limited number of images are available for analysis. The bi-exponential R(2) image analysis is facilitated by estimation of the initial proton spin density signal within the region of interest weighted by the RF field intensities. The RF field intensity-weighted spin density map is computed by solving a boundary value problem presented by a high spin density, long T(2) material encompassing the region for analysis. The accuracy of the bi-exponential R(2) image analysis technique is demonstrated on a simulated dual compartment manganese chloride phantom system with relaxation rates and relative population densities between the two compartments similar to the bi-exponential transverse relaxation behavior expected of iron loaded liver. Results from analysis of the phantoms illustrate the potential of bi-exponential R(2) image analysis with RF field intensity-weighted spin density projection for quantifying transverse relaxation enhancement as it occurs in liver iron overload.

Proton transverse relaxation rate (R(2)) imaging measurements were made on post mortem iron-loaded human liver tissue samples (both intact and dissected into approximately 1-cm cubes) from a single subject. Iron concentrations for the dissected samples as measured by atomic absorption spectrometry varied from 10.8 to 23.3 mg Fe.g(-1) dry tissue. A significant linear correlation between the mean R(2) and iron concentration of each sample was found (r = 0.95). In addition, regions of liver tissue with micronodular cirrhosis exhibited lower R(2) values, corresponding to the displacement of iron by fibrotic septa. The cirrhotic tissue was clearly identified as a separate peak in the R(2) distribution of the tissue. The relaxivity of the iron did not appear to depend on the microarchitecture of the tissue., (Copyright 2003 Wiley-Liss, Inc.)