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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.

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.)

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.)

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.)

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.)

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%.

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.

Growing evidence indicates that the stress response in general and heat shock proteins (Hsps) in particular have a profound impact on tumor immunogenicity. In this study, we show that tumor cells subjected to a nonlethal heat shock stress are unable to form tumors in syngenic mice, whereas they do so in athymic nude mice. Moreover, heat-shocked MethA immunity is tumor specific. Enhancement of T-cell-mediated immunogenicity correlates with the expression of the inducible Hsp70 but not the constitutive Hsc70. These observations have a bearing on the proposed functional role of Hsp-peptide association in antigen processing and presentation by major histocompatibility complex I molecules under normal and stressful conditions.

Natural killer (NK) cells play an important role in combating infectious and malignant diseases and interleukin-2 (IL-2) has been shown to promote proliferation and activation of NK cells in vitro and in vivo. Here we investigate the effects of local cationic lipid-mediated IL-2 gene transfer on intratumoral accumulation and activation of NK cells in a SCID mouse tumor model. UM449 human melanoma tumors in SCID mice received intratumoral injections of DMRIE/DOPE admixed with VR1103, a DNA plasmid encoding the gene for human IL-2. Dissagregated tumor cells were tested for IL-2 secretion and were characterized using antibodies to asGM1, MAC-1, and F4/80 antigens. Granzyme A, a proteolytic serine esterase, was also measured in tumor cell lysates. IL-2 secretion from tumors injected with VR1103:DMRIE/DOPE peaked at 48 h after injection and fell to baseline levels on day 8. Intratumoral granzyme A activity was significantly increased in tumors injected with IL-2 plasmid:DMRIE/DOPE complexes, but not by an irrelevant plasmid DNA:DMRIE/DOPE control. Importantly, the growth of UM449 tumors was slowed in VR1103:DMRIE/DOPE-injected tumors. These results indicate that local cationic lipid-mediated gene transfer of IL-2 induces activation of intratumoral NK cells and slows tumor growth., (Copyright 2000 Academic Press.)

Recent research into the non-invasive assessment of hepatic iron concentrations using magnetic resonance imaging has shown that the proton transverse relaxivity (1/T(2)) varies linearly with liver iron concentration. However, the development of an image-based system for the assessment of hepatic iron distribution has been confounded by the presence of motion induced artifacts in the T(2)-weighted images. We report on the development of a single spin-echo imaging methodology that enables the generation of transverse relaxivity maps over the liver. A simple smoothing technique is used to accommodate the image intensity perturbations caused by abdominal motion. The relaxivity maps are consistent with the variation of iron concentration throughout the liver. A Parzen density estimate and histogram of the relaxivity distribution are generated to assist in the visual assessment of the degree and variability of T(2) shortening with liver iron loading. It was found that one or two Gaussian functions could be used to characterize the relaxivity distributions with a small number of parameters. We propose that this methodology may be used in the clinical setting to monitor hepatic iron concentrations in the advent of an accurate transverse relaxivity calibration curve.

Discovery and development of human papillomavirus (HPV) specific antiviral agents have been hampered by the lack of an in vitro assay permissive to HPV replication. An experimental assay system for monitoring HPV-11 DNA replication has been optimized for use as a papillomavirus antiviral drug screening tool. Cloned HPV DNA was introduced into SCC-4 cells by electroporation and viral DNA replication monitored by Southern blot. Kinetic studies demonstrated an increased HPV genome copy number with time. Viral DNA replicated as episomal, unit length genome and remained episomal after multiple passages. These data suggested the basis for an in vitro replication assay for evaluating the antiviral activity of potential chemotherapeutic agents directly on HPV. This model was used to investigate antiviral activities of current anti-HPV therapies such as 5-fluorouracil (5-FU) and alpha-interferon (alpha-IFN) and potential therapies such as sodium butyrate, 5-bromo-20-deoxyuridine (BrdU) and antisense oligonucleotides. HPV- 11 replication is significantly inhibited by BrdU and sodium butyrate; however 5-FU and alpha-IFN did not give consistent dose response results. Finally, ISIS 2105, a 20-mer phosphorothioate antisense oligonucleotide, which targets HPV-11 E2 gene product, showed potent antiviral activity in this assay with an IC50 of approximately 70 nM.