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Background: Subarachnoid hemorrhage (SAH) is associated with neurocognitive impairment. Recent data suggest that sevoflurane attenuates edema formation after SAH in rats. However, so far, no information is available about the long-term repair phase, nor if sevoflurane impacts functionality by increasing vascularity. This study tested whether sevoflurane postconditioning would improve long-term neurologic deficit through increased formation of new vessels close to the hemorrhage area., Methods: Fifty-three animals were subjected to SAH or sham surgery with or without a 2-hour sevoflurane postconditioning (versus propofol anesthesia). Animal survival, including dropout animals due to death or reaching termination criteria, as well as neurologic deficit, defined by the Garcia score, were assessed 2 hours after recovery until postoperative day 14. On day 14, blood samples and brain tissue were harvested. Vessel density was determined by the number of cluster of differentiation 31 (CD31)-positive vessels, and activated glial cells by glial fibrillary acidic protein (GFAP)-positive astrocytes per field of view., Results: The survival rate for sham animals was 100%, 69% in the SAH-propofol and 92% in the SAH-sevoflurane groups. According to the log-rank Mantel-Cox test, survival curves were significantly different ( P = .024). The short-term neurologic deficit was higher in SAH-propofol versus SAH-sevoflurane animals 2 hours after recovery and on postoperative day 1 (propofol versus sevoflurane: 14. 6 ± 3.4 vs 15. 9 ± 2.7 points, P = .034, and 16. 2 ± 3.5 vs 17. 8 ± 0.9 points, P = .015). Overall complete recovery from neurologic deficit was observed on day 7 in both SAH groups (18. 0 ± 0.0 vs 18. 0 ± 0.0 points, P = 1.000). Cortical vascular density increased to 80. 6 ± 15.0 vessels per field of view in SAH-propofol animals (vs 71. 4 ± 10.1 in SAH-sevoflurane, P < .001). Activation of glial cells, an indicator of neuroinflammation, was assessed by GFAP-positive astrocytes GFAP per field of view. Hippocampal GFAP-positive cells were 201 ± 68 vs 179 ± 84 cells per field of view in SAH-propofol versus SAH-sevoflurane animals ( P < .001)., Conclusions: Sevoflurane postconditioning improves survival by 23% (SAH-sevoflurane versus SAH-propofol). The sevoflurane intervention could attenuate the early neurologic deficit, while the long-term outcome was similar across the groups. A higher vascular density close to the SAH area in the propofol group was not associated with improved outcomes., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

The main deterrent to long-term space travel is the risk of Radiation Exposure Induced Death (REID). The National Aeronautics and Space Administration (NASA) has adopted Permissible Exposure Levels (PELs) to limit the probability of REID to 3% for the risk of death due to radiation-induced carcinogenesis. The most significant contributor to current REID estimates for astronauts is the risk of lung cancer. Recently updated lung cancer estimates from Japan's atomic bomb survivors showed that the excess relative risk of lung cancer by age 70 is roughly fourfold higher in females compared to males. However, whether sex differences may impact the risk of lung cancer due to exposure to high charge and energy (HZE) radiation is not well studied. Thus, to evaluate the impact of sex differences on the risk of solid cancer development after HZE radiation exposure, we irradiated Rbfl/fl, Trp53fl/+ male and female mice infected with Adeno-Cre with various doses of 320 kVp X rays or 600 MeV/n 56Fe ions and monitored them for any radiation-induced malignancies. We conducted complete necropsy and histopathology of major organs on 183 male and 157 female mice after following them for 350 days postirradiation. We observed that lung adenomas/carcinomas and esthesioneuroblastomas (ENBs) were the most common primary malignancies in mice exposed to X rays and 56Fe ions, respectively. In addition, 1 Gy 56Fe-ion exposure compared to X-ray exposure led to a significantly increased incidence of lung adenomas/carcinomas (P = 0.02) and ENBs (P < 0.0001) in mice. However, we did not find a significantly higher incidence of any solid malignancies in female mice as compared to male mice, regardless of radiation quality. Furthermore, gene expression analysis of ENBs suggested a distinct gene expression pattern with similar hallmark pathways altered, such as MYC targets and MTORC1 signaling, in ENBs induced by X rays and 56Fe ions. Thus, our data revealed that 56Fe-ion exposure significantly accelerated the development of lung adenomas/carcinomas and ENBs compared to X rays, but the rate of solid malignancies was similar between male and female mice, regardless of radiation quality., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

Introduction: Our previous studies have demonstrated that tumor-infiltrating lymphocytes (TILs), including normal B cells, T cells, and natural killer (NK) cells, in diffuse large B-cell lymphoma (DLBCL) have a significantly favorable impact on the clinical outcomes of patients treated with standard chemoimmunotherapy. In this study, to gain a full overview of the tumor immune microenvironment (TIME), we assembled a flow cytometry cohort of 102 patients diagnosed with DLBCL at the Duke University Medical Center., Methods: We collected diagnostic flow cytometry data, including the proportion of T cells, abnormal B cells, normal B cells, plasma cells, NK cells, monocytes, and granulocytes in fresh biopsy tissues at clinical presentation, and analyzed the correlations with patient survival and between different cell populations., Results: We found that low T cell percentages in all viable cells and low ratios of T cells to abnormal B cells correlated with significantly poorer survival, whereas higher percentages of normal B cells among total B cells (or high ratios of normal B cells to abnormal B cells) and high percentages of NK cells among all viable cells correlated with significantly better survival in patients with DLBCL. After excluding a small number of patients with low T cell percentages, the normal B cell percentage among all B cells, but not T cell percentage among all cells, continued to show a remarkable prognostic effect. Data showed significant positive correlations between T cells and normal B cells, and between granulocytes and monocytes. Furthermore, we constructed a prognostic model based on clinical and flow cytometry factors, which divided the DLBCL cohort into two equal groups with remarkable differences in patient survival and treatment response., Summary: TILs, including normal B cells, T cells, and NK cells, are associated with favorable clinical outcomes in DLBCL, and flow cytometry capable of quantifying the TIME may have additional clinical utility for prognostication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Xu-Monette, Lagoo, Shuai, Wang, Neff, Carrillo, Carlsen, Pina-Oviedo and Young.)

The management of Soil Organic Carbon (SOC) is a critical component of both nature-based solutions for climate change mitigation and global food security. Agriculture has contributed substantially to a reduction in global SOC through cultivation, thus there has been renewed focus on management practices which minimize SOC losses and increase SOC gain as pathways towards maintaining healthy soils and reducing net greenhouse gas emissions. Mechanistic models are frequently used to aid in identifying these pathways due to their scalability and cost-effectiveness. Yet, they are often computationally costly and rely on input data that are often only available at coarse spatial resolutions. Herein, we build statistical meta-models of a multifactorial crop model in order to both (a) obtain a simplified model response and (b) explore the biophysical determinants of SOC responses to management and the geospatial heterogeneity of SOC dynamics across Europe. Using 5600 unique simulations of crop growth from the gridded Environmental Policy Integrated Climate-based Gridded Agricultural Model (EPIC-IIASA GAM) covering 86,000 simulation units across Europe, we build multiple polynomial regression ensemble meta-models for unique combinations of climate and soil across Europe in order to predict SOC responses to varying management intensities. We find that our biophysically-explicit meta models are highly accurate (R 2  = 0.97) representations of the full mechanistic model and can be used in lieu of the full EPIC-IIASA GAM model for the estimation of SOC responses to cropland management. Model stratification by means of climate and soil clustering improved the performance of the meta-models compared to the full EU-scale model. In regional and local validations of the meta-model predictions, we find that the meta-models largely capture broad SOC dynamics such as the linear nature of SOC responses to residue application, yet they often underestimate the magnitude of SOC responses to management. Furthermore, we find notable differences between the results from the biophysically-specific models throughout Europe, which point to spatially-distinct SOC responses to management choices such as nitrogen fertilizer application rates and residue retention that illustrate the potential for these models to be used for future management applications. While more accurate input data, calibration, and validation will be needed to accurately predict SOC change, we demonstrate the use of our meta-models for biophysical cluster and field study scale analyses of broad SOC dynamics with basically zero fine-tuning of the models needed. This work provides a framework for simplifying large-scale agricultural models and identifies the opportunities for using these meta-models for assessing SOC responses to management at a variety of scales., 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 © 2023. Published by Elsevier Ltd.)

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues. It is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths from leukemias in the United States. Like AML, blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a myeloid malignancy. It is a rare malignancy characterized by the aggressive proliferation of precursors of plasmacytoid dendritic cells that frequently involves the bone marrow, skin, central nervous system, and other organs and tissues. This discussion section focuses on the diagnosis and management of BPDCN as outlined in the NCCN Guidelines for AML.

A wide variety of diseases are commonly diagnosed via the visual examination of cell morphology within a peripheral blood smear. For certain diseases, such as COVID-19, morphological impact across the multitude of blood cell types is still poorly understood. In this paper, we present a multiple instance learning-based approach to aggregate high-resolution morphological information across many blood cells and cell types to automatically diagnose disease at a per-patient level. We integrated image and diagnostic information from across 236 patients to demonstrate not only that there is a significant link between blood and a patient's COVID-19 infection status, but also that novel machine learning approaches offer a powerful and scalable means to analyze peripheral blood smears. Our results both backup and enhance hematological findings relating blood cell morphology to COVID-19, and offer a high diagnostic efficacy; with a 79% accuracy and a ROC-AUC of 0.90., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RH is the scientific director of Ramona Optics Inc., and RH and AC are co-founders of Airilabs LLC. Both companies are developing novel hardware for microscope imaging., (Copyright: © 2022 Cooke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: Evaluation of implementation science research is warranted to better understand and determine the success of translating evidence-based infection prevention practices at the bedside. The purpose of this program evaluation was to evaluate implementation outcomes from the perspectives of nurses and nursing leaders regarding a previously conducted chlorhexidine gluconate (CHG) bathing implementation science study among 14 critical care units., Methods: Focus groups and interviews, using semistructured interview questions, were conducted to examine the perceptions of nurses who participated in a CHG bathing implementation science study. A deductive qualitative analysis using Proctor and colleagues' implementation outcomes framework was used. Transcripts were analyzed and categorized using the framework as a predetermined code list to structure the implementation outcomes of acceptability, appropriateness, adoption, feasibility, and sustainability., Findings: A total of 19 nurses and nurse leaders participated in a focus group or interview. Participants noted that both implementation strategies used in the initial study (educational outreach and audit and feedback) were acceptable and appropriate and expressed that the evidence-based CHG bathing practice was feasible to integrate into practice and was being adopted., Discussion: The program evaluation identified strengths and opportunities for improvement related to the implementation strategies and evidence-based CHG bathing protocol. Findings can inform future studies that seek to implement CHG bathing protocols in the critical care setting using audit and feedback and educational outreach strategies., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Context.—: Concomitant BCR-ABL1 and JAK2V617F in myeloproliferative neoplasms (MPNs) is rare, and its pathogenesis and clinical significance are unclear., Objective.—: To investigate the clonal relationship between the 2 genomic alterations, as well as the clinicopathologic impact., Design.—: Retrospective analysis of MPNs with sequential development of BCR-ABL1 and JAK2V617F., Results.—: Of 6 cases, 5 had JAK2V617F-positive MPN diagnosed before acquiring BCR-ABL1 years later, and 1 had BCR-ABL1+ chronic myeloid leukemia before JAK2V617F-positive myelofibrosis completely replaced the BCR-ABL1+ clone 1 year after tyrosine kinase inhibitor therapy. Among the former group, treatment for the initial MPN involved hydroxyurea, ruxolitinib, and/or supportive care, and the latency to the development of JAK2V617F ranged from 4 to 13 years (median of 9 years). Four cases showed retention of JAK2V617F, whereas BCR-ABL1 emerged as the major clone, including 2 cases that exhibited parallel increases in JAK2V617F and BCR-ABL1 burdens, with both genomic markers exceeding 50%. Three patients received stem cell transplants and demonstrated sustained engraftment, with the genomic markers below detectable levels., Conclusions.—: Most MPNs with concomitant JAK2V617F and BCR-ABL1 are actually composite MPNs with a "second hit" residing on a different clone. Rare cases demonstrate a subclone harboring a "double-hit" in a background of a JAK2V617F-positive stem line clone. The probability of a "double-hit" with a BCR-ABL1+ stem line clone is probably reduced by effective tyrosine kinase inhibitor treatment. The treatment often involves combined kinase inhibitors and/or hydroxyurea, but the outcome is unpredictable; hematopoietic stem cell transplantation may be the ultimate therapeutic option for this complicated disease.

Structural competency is a new curricular framework for training health professionals to recognise and respond to disease and its unequal distribution as the outcome of social structures, such as economic and legal systems, healthcare and taxation policies, and international institutions. While extensive global health research has linked social structures to the disproportionate burden of disease in the Global South, formal attempts to incorporate the structural competency framework into US-based global health education have not been described in the literature. This paper fills this gap by articulating five sub-competencies for structurally competent global health instruction. Authors drew on their experiences developing global health and structural competency curricula-and consulted relevant structural competency, global health, social science, social theory, and social determinants of health literatures. The five sub-competencies include: (1) Describe the role of social structures in producing and maintaining health inequities globally, (2) Identify the ways that structural inequalities are naturalised within the field of global health, (3) Discuss the impact of structures on the practice of global health, (4) Recognise structural interventions for addressing global health inequities, and (5) Apply the concept of structural humility in the context of global health.

Background: The current COVID-19 coronavirus pandemic is an emergency on a global scale, with huge swathes of the population required to remain indoors for prolonged periods to tackle the virus. In this new context, individuals' health-promoting routines are under greater strain, contributing to poorer mental and physical health. Additionally, individuals are required to keep up to date with latest health guidelines about the virus, which may be confusing in an age of social-media disinformation and shifting guidelines. To tackle these factors, we developed Elena+, a smartphone-based and conversational agent (CA) delivered pandemic lifestyle care intervention. Methods: Elena+ utilizes varied intervention components to deliver a psychoeducation-focused coaching program on the topics of: COVID-19 information, physical activity, mental health (anxiety, loneliness, mental resources), sleep and diet and nutrition. Over 43 subtopics, a CA guides individuals through content and tracks progress over time, such as changes in health outcome assessments per topic, alongside user-set behavioral intentions and user-reported actual behaviors. Ratings of the usage experience, social demographics and the user profile are also captured. Elena+ is available for public download on iOS and Android devices in English, European Spanish and Latin American Spanish with future languages and launch countries planned, and no limits on planned recruitment. Panel data methods will be used to track user progress over time in subsequent analyses. The Elena+ intervention is open-source under the Apache 2 license (MobileCoach software) and the Creative Commons 4.0 license CC BY-NC-SA (intervention logic and content), allowing future collaborations; such as cultural adaptions, integration of new sensor-related features or the development of new topics. Discussion: Digital health applications offer a low-cost and scalable route to meet challenges to public health. As Elena+ was developed by an international and interdisciplinary team in a short time frame to meet the COVID-19 pandemic, empirical data are required to discern how effective such solutions can be in meeting real world, emergent health crises. Additionally, clustering Elena+ users based on characteristics and usage behaviors could help public health practitioners understand how population-level digital health interventions can reach at-risk and sub-populations., Competing Interests: JO, PS, AA, DR, CB, OK, EF, FW, and TK are affiliated with the Centre for Digital Health Interventions www.c4dhi.org, a joint initiative of the Department of Management, Technology and Economics at ETH Zurich and the Institute of Technology Management at the University of St. Gallen, which was funded in part by the Swiss health insurer CSS Versicherung. EF and TK are also cofounders of Pathmate Technologies, a university spin-off company that creates and delivers digital clinical pathways. However, neither CSS nor Pathmate Technologies are involved in the Elena+ project or this article. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AR declared a past co-authorship with several of the authors AS and RB to the handling editor., (Copyright © 2021 Ollier, Neff, Dworschak, Sejdiji, Santhanam, Keller, Xiao, Asisof, Rüegger, Bérubé, Hilfiker Tomas, Neff, Yao, Alattas, Varela-Mato, Pitkethly, Vara, Herrero, Baños, Parada, Agatheswaran, Villalobos, Keller, Chan, Mishra, Jacobson, Stanger, He, von Wyl, Weidt, Haug, Schaub, Kleim, Barth, Witt, Scholz, Fleisch, Wangenheim, Car, Müller-Riemenschneider, Hauser-Ulrich, Asomoza, Salamanca-Sanabria, Mair and Kowatsch.)

Purpose: An important obstacle to cancer research is that nearly all academic cancer centers maintain substantial collections of highly duplicative, poorly quality-assured, nonintercommunicating, difficult-to-access data repositories. It is inherently clear that this state of affairs increases costs and reduces quality and productivity of both research and nonresearch activities. We hypothesized that designing and implementing a multipurpose cancer information system on the basis of the Biomedical Research Integrated Domain (BRIDG) model developed by the National Cancer Institute and its collaborators might lessen the duplication of effort inherent in capturing, quality-assuring, and accessing data located in multiple single-purpose systems, and thereby increases productivity while reducing costs., Methods: We designed and implemented a core data structure on the basis of the BRIDG model and incorporated multiple entities, attributes, and functionalities to support the multipurpose functionality of the system. We used the resultant model as a foundation upon which to design and implement modules for importing preexisting data, capturing data prospectively, quality-assuring data, exporting data to analytic files, and analyzing the quality-assured data to support multiple functionalities simultaneously. To our knowledge, our system, which we refer to as the Cancer Informatics Data System, is the first multipurpose, BRIDG-harmonized cancer research information system implemented at an academic cancer center., Results: We describe the BRIDG-harmonized system that simultaneously supports patient care, teaching, research, clinical decision making, administrative decision making, mandated volume-and-outcomes reporting, clinical quality assurance, data quality assurance, and many other functionalities., Conclusion: Implementation of a highly quality-assured, multipurpose cancer information system on the basis of the BRIDG model at an academic center is feasible and can increase access to accurate data to support research integrity and productivity as well as nonresearch activities., Competing Interests: Pierluigi PorcuHonoraria: Celgene, Innate Pharma, Kiowa, Viracta Therapeutics, Daiichi Sankyo/UCB JapanConsulting or Advisory Role: Innate Pharma, Viracta TherapeuticsResearch Funding: Infinity Pharmaceuticals (Inst), Celgene (Inst), Millennium (Inst), Seattle Genetics (Inst) Usama GergisStock and Other Ownership Interests: Gamida Cell, Iovance Biotherapeutics, Apellis PharmaceuticalsHonoraria: Incyte, Jazz Pharmaceuticals, Astellas Pharma, Mesoblast, Gamida Cell, Kite, a Gilead companyConsulting or Advisory Role: Gamida Cell, Mesoblast, Jazz PharmaceuticalsSpeakers' Bureau: Incyte, Jazz Pharmaceuticals, Astellas Pharma, Kite, a Gilead companyTravel, Accommodations, Expenses: Incyte, Jazz Pharmaceuticals Neal FlomenbergResearch Funding: Tevogen Bio (Inst)No other potential conflicts of interest were reported.

Objective: Spin, i.e., the misrepresentation of research findings, has the potential to affect patient care. Evidence suggests that spin is prevalent in obesity randomized controlled trials. Therefore, the primary objective of this study was to evaluate spin in abstracts of systematic reviews covering obesity treatments., Methods: MEDLINE and Embase were searched to retrieve systematic reviews on obesity treatments. Each systematic review abstract was inspected for the nine most severe types of spin, i.e., the misrepresentation of study findings by exaggeration or omission, regardless of intentionality. Screening and data extraction occurred in a masked, triplicate fashion. Methodological quality was determined using A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2)., Results: Spin was identified in 20 (out of 200, 10%) abstracts, with spin type 5 (claiming efficacy despite high risk of bias among primary studies) being most common (11/200, 5.5%). Spin types 2 and 7, both related to unsupported efficacy claims, were not found. No associations were found between spin and extracted study characteristics. The methodological quality of the sample was rated as follows: critically low (23.0%), low (13.5%), moderate (60.5%), and high (3%)., Conclusions: Although these findings demonstrate a low proportion of spin in the abstracts of systematic reviews for obesity treatment; increased preventive measures may further reduce its presence., (© 2021 The Obesity Society.)

Background: Central line-associated bloodstream infections (CLABSIs) result in approximately 28,000 deaths and approximately $2.3 billion in added costs to the U.S. healthcare system each year, and yet, many of these infections are preventable. At two large health systems in the southeast United States, CLABSIs continue to be an area of opportunity. Despite strong evidence for interventions to prevent CLABSI and reduce associated patient harm, such as use of chlorhexidine gluconate (CHG) bathing, the adoption of these interventions in practice is poor. The primary objective of this study was to assess the effect of a tailored, multifaceted implementation program on nursing staff's compliance with the CHG bathing process and electronic health record (EHR) documentation in critically ill patients. The secondary objectives were to examine the (1) moderating effect of unit characteristics and cultural context, (2) intervention effect on nursing staff's knowledge and perceptions of CHG bathing, and (3) intervention effect on CLABSI rates., Methods: A stepped wedged cluster-randomized design was used with units clustered into 4 sequences; each sequence consecutively began the intervention over the course of 4 months. The Grol and Wensing Model of Implementation helped guide selection of the implementation strategies, which included educational outreach visits and audit and feedback. Compliance with the appropriate CHG bathing process and daily CHG bathing documentation were assessed. Outcomes were assessed 12 months after the intervention to assess for sustainability., Results: Among the 14 clinical units participating, 8 were in a university hospital setting and 6 were in community hospital settings. CHG bathing process compliance and nursing staff's knowledge and perceptions of CHG bathing significantly improved after the intervention (p = .009, p = .002, and p = .01, respectively). CHG bathing documentation compliance and CLABSI rates did not significantly improve; however, there was a clinically significant 27.4% decrease in CLABSI rates., Conclusions: Using educational outreach visits and audit and feedback implementation strategies can improve adoption of evidence-based CHG bathing practices., Trial Registration: ClinicalTrials.gov, NCT03898115 , Registered 28 March 2019.

Understanding carbon (C) dynamics from ecosystem to global scales remains a challenge. Although expansion of global carbon dioxide (CO 2 ) observatories makes it possible to estimate C-cycle processes from ecosystem to global scales, these estimates do not necessarily agree. At the continental US scale, only 5% of C fixed through photosynthesis remains as net ecosystem exchange (NEE), but ecosystem measurements indicate that only 2% of fixed C remains in grasslands, whereas as much as 30% remains in needleleaf forests. The wet and warm Southeast has the highest gross primary productivity and the relatively wet and cool Midwest has the highest NEE, indicating important spatial mismatches. Newly available satellite and atmospheric data can be combined in innovative ways to identify potential C loss pathways to reconcile these spatial mismatches. Independent datasets compiled from terrestrial and aquatic environments can now be combined to advance C-cycle science across the land-water interface., (© 2021 The Authors. Frontiers in Ecology and the Environment published by Wiley Periodicals LLC on behalf of the Ecological Society of America.)

The NCCN Guidelines for Acute Myeloid Leukemia (AML) provide recommendations for the diagnosis and treatment of adults with AML based on clinical trials that have led to significant improvements in treatment, or have yielded new information regarding factors with prognostic importance, and are intended to aid physicians with clinical decision-making. These NCCN Guidelines Insights focus on recent select updates to the NCCN Guidelines, including familial genetic alterations in AML, postinduction or postremission treatment strategies in low-risk acute promyelocytic leukemia or favorable-risk AML, principles surrounding the use of venetoclax-based therapies, and considerations for patients who prefer not to receive blood transfusions during treatment.

Stroke follow-up care with neurology specialty advanced practice providers is critical to focus on stroke prevention. The need for which is underscored by results of a recent study noting that many stroke survivors of first-ever strokes were not receiving stroke standard-of-care prevention measures including consistent antiplatelet therapies and regular exercise. Study findings further note the rates of usage for stroke prevention interventions (daily anti-platelet therapy, smoking cessation, regular exercise, hypertension control) were between 50% and 70%. Clinical nurse specialists along with nurse practitioner and physician assistant advanced practice providers are uniquely suited to manage outpatient ischemic stroke care to reduce the recurrence of stroke and improve patient outcomes.

The maintenance and propagation of complex mixtures of cells in vitro in the form of native organs or engineered organoids has contributed to understanding mechanisms of cell and organ development and function which can be translated into therapeutic benefits. For example, allogeneic cultured postnatal human thymus tissue has been shown to support production of naïve recipient T cells when transplanted into patients with complete DiGeorge anomaly and other genetic defects that result in congenital lack of a thymus. Patients receiving such transplants typically exhibit reversal of their immunodeficiency and normalization of their peripheral blood T cell receptor V-beta repertoire, with long-term survival. This study was designed to assess the histopathologic changes that occur in postnatal human thymus slices when cultured according to protocols used for transplanted tissues. Results showed that as thymic organ cultures progressed from days 0 through 21, slices developed increasing amounts of necrosis, increasing condensation of thymic epithelium, and decreasing numbers of residual T cells. The architecture of the thymic epithelial network remained generally well-preserved throughout the 21 days of culture, with focal expression of cytokeratin 14, a putative biomarker of thymic epithelial cells with long-term organ-repopulating potential. All organ slices derived from the same donor thymus closely resembled one another, with minor differences in size, shape, and relative content of cortex versus medulla. Similarly, slices derived from different donors showed similar histopathologic characteristics when examined at the same culture time point. Taken together, these results demonstrate that diagnostic criteria based on structural features of the tissue identifiable via hematoxylin and eosin staining and cytokeratin immunohistochemistry can be used to evaluate the quality of slices transplanted into patients with congenital athymia., Competing Interests: Cultured postnatal human thymus (RVT-802) is an investigational product implanted into patients under an Investigational New Drug (IND) application with the United States Food and Drug Administration (FDA) that is sponsored by Dr. Markert. The technology for RVT-802 was developed by Dr. Markert and has been licensed to Enzyvant Therapeutics GmbH (Enzyvant) by Duke University. Dr. Markert and Duke University have received royalties from Enzyvant. If the technology is commercially successful in the future, Dr. Markert and Duke University may benefit financially. Portions of the salaries of Drs. Markert, Kurtzberg, and Hale and consultation fees for Dr. Neff were paid by funding to Duke University from Enzyvant. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: Research on disparities in health and health care has demonstrated that social, economic, and political factors are key drivers of poor health outcomes. Yet the role of such structural forces on health and health care has been incorporated unevenly into medical training. The framework of structural competency offers a paradigm for training health professionals to recognize and respond to the impact of upstream, structural factors on patient health and health care., Methods: We report on a brief, interprofessional structural competency curriculum implemented in 32 distinct instances between 2015 and 2017 throughout the San Francisco Bay Area. In consultation with medical and interprofessional education experts, we developed open-ended, written-response surveys to qualitatively evaluate this curriculum's impact on participants. Qualitative data from 15 iterations were analyzed via directed thematic analysis, coding language, and concepts to identify key themes., Results: Three core themes emerged from analysis of participants' comments. First, participants valued the curriculum's focus on the application of the structural competency framework in real-world clinical, community, and policy contexts. Second, participants with clinical experience (residents, fellows, and faculty) reported that the curriculum helped them reframe how they thought about patients. Third, participants reported feeling reconnected to their original motivations for entering the health professions., Discussion: This structural competency curriculum fills a gap in health professional education by equipping learners to understand and respond to the role that social, economic, and political structural factors play in patient and community health., Competing Interests: None to report., (Copyright © 2020 Neff et al.)

This paper describes a consultation exercise to explore the acceptability of adapting digital social prescribing (DSP) for suicide bereavement support. Bereavement by suicide increases the risk of suicide and mental health issues. Social prescribing improves connectedness and empowerment and can provide digital outcomes-based reporting to improve the capacity for measuring the effectiveness of interventions. Our aim was to consult on the acceptability and potential value of DSP for addressing the complexities of suicide bereavement support. Our approach was underpinned by implementation science and a co-design ethos. We reviewed the literature and delivered DSP demonstrations as part of our engagement process with commissioners and service providers ( marrying evidence and context ) and identified key roles for stakeholders ( facilitation ). Stakeholders contributed to a co-designed workshop to establish consensus on the challenges of providing postvention support. We present findings on eight priority challenges, as well as roles and outcomes for testing the feasibility of DSP for support after suicide. There was a consensus that DSP could potentially improve access, reach, and monitoring of care and support. Stakeholders also recognised the potential for DSP to contribute substantially to the evidence base for postvention support. In conclusion, the consultation exercise identified challenges to facilitating DSP for support after suicide and parameters for feasibility testing to progress to the evaluation of this innovative approach to postvention.

Aim: To evaluate the presence and propagation of defects and their effects on surfaces of nickel-titanium (NiTi) instruments using noncontact, three-dimensional optical profilometry, and to assess the accuracy of this method of investigation., Methodology: The flute surface areas of instruments from two commercial instrumentation systems, namely Reciproc R25 (n = 5) and WaveOne Primary (n = 5), were assessed and compared before and after performing two instrumentation cycles in simulated root canals in clear resin blocks. All the analyses were conducted on areas measuring 211 × 211 μm, located 3 mm from the tips of the instruments. A quantitative analysis was conducted before and after the first and second instrumentation cycles, using the Sa (average roughness over the measurement field), Sq (root mean square roughness) and Sz (average height over the measurement field) amplitude parameters. All the data were submitted to statistical analysis at a 5% level of significance., Results: There was a significant increase (P = 0.007) in wear in both groups, especially between baseline and the second instrumentation cycle, with significantly higher wear values being observed on WaveOne instruments (Sz median values = 33.68 and 2.89 μm, respectively, for WO and RP groups). A significant increase in surface roughness (P = 0.016 and P = 0.008, respectively, for Sa and Sq) was observed in both groups from the first to the second instrumentation cycle, mostly in WaveOne specimens. Qualitative analysis revealed a greater number of defects on the flute topography of all the instruments after use., Conclusions: More defects were identified in WaveOne Primary instruments compared to Reciproc R25, irrespective of the evaluation stage. The investigation method provided an accurate, repeatable and reproducible assessment of NiTi instruments at different time-points., (© 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Wound infections are a common complication of combat-related injuries that significantly increase morbidity and mortality. Multi-drug resistant (MDR) organisms and their associated biofilms play a significant role in the pathogenicity and chronicity of wound infections. A critical barrier to progress in the treatment of traumatic wounds is the need for broad spectrum antimicrobials that are effective against biofilms and compatible with topical delivery. In this study, we present the in vitro efficacy of two de novo designed cationic, antimicrobial peptides and related topical formulations against single species and polymicrobial biofilms of MDR bacteria. Minimum biofilm eradication concentrations for peptides ranged from 0.7 μM for Staphylococcus aureus to 13.2 μM for Pseudomonas aeruginosa. Varying pH did not adversely impact peptide activity, however, in the presence of albumin, minimum biofilm eradication concentrations generally increased. When formulated into gels or dressings, both peptides eradicated mono- and polymicrobial biofilms of MDR pathogens. The biocompatibility index (BI) was found to be greater than one for both ASP-1 and ASP-2, with a slightly greater (more favorable) BI for ASP-2. The BIs for both peptides were greater than BIs previously reported for commonly used topical antimicrobial agents. The antimicrobial peptides and related formulations presented provide a promising platform for treatment of wound biofilms to improve outcomes for those injured in combat.

Objectives: To assess whether children with medical complexity (CMC) exposed to a hospital-based comprehensive case management service (CCMS) experience improved health care quality, improved functional status, reduced hospital-based utilization, and/or reduced overall health care costs., Methods: Eligible CMC at Seattle Children's Hospital were enrolled in a cluster randomized controlled trial between December 1, 2010, and September 29, 2014. Participating primary care providers (PCPs) were randomly assigned, and CMC either had access to an outpatient hospital-based CCMS or usual care directed by their PCP. The CCMS included visits to a multidisciplinary clinic ≥ every 6 months for 1.5 years, an individualized shared care plan, and access to CCMS providers. Differences between control and intervention groups in change from baseline to 12 months and baseline to 18 months (difference of differences) were tested., Results: Two hundred PCPs caring for 331 CMC were randomly assigned. Intervention group ( n = 181) parents reported more improvement in the Consumer Assessment of Healthcare Providers and Systems version 4.0 Child Health Plan Survey global health care quality ratings than control group parents (6.7 [95% confidence interval (CI): 3.5-9.8] vs 1.3 [95% CI: 1.9-4.6] at 12 months). We did not detect significant differences in child functional status and most hospital-based utilization between groups. The difference in change of overall health care costs was higher in the intervention group (+$8233 [95% CI: $1701-$16 937]) at 18 months). CCMS clinic costs averaged $3847 per child-year., Conclusions: Access to a CCMS generally improved health care quality, but was not associated with changes in child functional status or hospital-based utilization, and increased overall health care costs among CMC., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose. COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2017-2860., (Copyright © 2017 by the American Academy of Pediatrics.)

The aim of this study was to undertake a qualitative and quantitative assessment of nanoscale alterations and wear on the surfaces of nickel-titanium (NiTi) endodontic instruments, before and after use, through a high-resolution, noncontact, three-dimensional optical profiler, and to verify the accuracy of the evaluation method. Cutting blade surfaces of two different brands of NiTi endodontic instruments, Reciproc R25 (n = 5) and WaveOne Primary (n = 5), were examined and compared before and after two uses in simulated root canals made in clear resin blocks. The analyses were performed on three-dimensional images which were obtained from surface areas measuring 211 × 211 µm, located 3 mm from their tips. The quantitative evaluation of the samples was conducted before and after the first and second usage, by the recordings of three amplitude parameters. The data were subjected to statistical analysis at a 5% level of significance. The results revealed statistically significant increases in the surface wear of both instruments groups after the second use. The presence of irregularities was found on the surface topography of all the instruments, before and after use. Regardless of the evaluation stage, most of the defects were observed in the WaveOne instruments. The three-dimensional technique was suitable and effective for the accurate investigation of the same surfaces of the instruments in different periods of time.

Aim: To describe a new method for the assessment of nanoscale alterations in the surface topography of nickel-titanium endodontic instruments using a high-resolution optical method and to verify the accuracy of the technique., Methodology: Noncontact three-dimensional optical profilometry was used to evaluate defects on a size 25, .08 taper reciprocating instrument (WaveOne ® ), which was subjected to a cyclic fatigue test in a simulated root canal in a clear resin block. For the investigation, an original procedure was established for the analysis of similar areas located 3 mm from the tip of the instrument before and after canal preparation to enable the repeatability and reproducibility of the measurements with precision. All observations and analysis were taken in areas measuring 210 × 210 μm provided by the software of the equipment., Results: The three-dimensional high-resolution image analysis showed clear alterations in the surface topography of the examined cutting blade and flute of the instrument, before and after use, with the presence of surface irregularities such as deformations, debris, grooves, cracks, steps and microcavities., Conclusions: Optical profilometry provided accurate qualitative nanoscale evaluation of similar surfaces before and after the fatigue test. The stability and repeatability of the technique enables a more comprehensive understanding of the effects of wear on the surface of endodontic instruments., (© 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Most large molecules are chiral in their structure: they exist as two enantiomers, which are mirror images of each other. Whereas the rovibronic sublevels of two enantiomers are almost identical (neglecting a minuscular effect of the weak interaction), it turns out that the photoelectric effect is sensitive to the absolute configuration of the ionized enantiomer. Indeed, photoionization of randomly oriented enantiomers by left or right circularly polarized light results in a slightly different electron flux parallel or antiparallel with respect to the photon propagation direction-an effect termed photoelectron circular dichroism (PECD). Our comprehensive study demonstrates that the origin of PECD can be found in the molecular frame electron emission pattern connecting PECD to other fundamental photophysical effects such as the circular dichroism in angular distributions (CDAD). Accordingly, distinct spatial orientations of a chiral molecule enhance the PECD by a factor of about 10.

Background: The influence of societal inequities on health has long been established, but such content has been incorporated unevenly into medical education and clinical training. Structural competency calls for medical education to highlight the important influence of social, political, and economic factors on health outcomes., Aim: This article describes the development, implementation, and evaluation of a structural competency training for medical residents., Setting: A California family medicine residency program serving a patient population predominantly (88 %) with income below 200 % of the federal poverty level., Participants: A cohort of 12 residents in the family residency program., Program Description: The training was designed to help residents recognize and develop skills to respond to illness and health as the downstream effects of social, political, and economic structures., Program Evaluation: The training was evaluated via qualitative analysis of surveys gathered immediately post-training (response rate 100 %) and a focus group 1 month post-training (attended by all residents not on service)., Discussion: Residents reported that the training had a positive impact on their clinical practice and relationships with patients. They also reported feeling overwhelmed by increased recognition of structural influences on patient health, and indicated a need for further training and support to address these influences.

Background and Objectives: Children who experience high health care costs are increasingly enrolled in clinical initiatives to improve their health and contain costs. Hospitalization is a significant cost driver. We describe hospitalization trends for children with highest annual inpatient cost (CHIC) and identify characteristics associated with persistently high inpatient costs in subsequent years., Methods: Retrospective study of 265 869 children age 2 to 15 years with ≥1 admission in 2010 to 39 children's hospitals in the Pediatric Health Information System. CHIC were defined as the top 10% of total inpatient costs in 2010 (n = 26 574). Multivariate regression and regression tree modeling were used to distinguish individual characteristics and interactions of characteristics, respectively, associated with persistently high inpatient costs (≥80th percentile in 2011 and/or 2012)., Results: The top 10% most expensive children (CHIC) constituted 56.9% ($2.4 billion) of total inpatient costs in 2010. Fifty-eight percent (n = 15 391) of CHIC had no inpatient costs in 2011 to 2012, and 27.0% (n = 7180) experienced persistently high inpatient cost. Respiratory chronic conditions (odds ratio [OR] = 3.0; 95% confidence interval [CI], 2.5-3.5), absence of surgery in 2010 (OR = 2.0; 95% CI, 1.8-2.1), and technological assistance (OR = 1.6; 95% CI, 1.5-1.7) were associated with persistently high inpatient cost. In regression tree modeling, the greatest likelihood of persistence (65.3%) was observed in CHIC with ≥3 hospitalizations in 2010 and a chronic respiratory condition., Conclusions: Most children with high children's hospital inpatient costs in 1 year do not experience hospitalization in subsequent years. Interactions of hospital use and clinical characteristics may be helpful to determine which children will continue to experience high inpatient costs over time., (Copyright © 2016 by the American Academy of Pediatrics.)

Purpose: The purpose of this study was to understand dental care transitions for adolescents with special health care needs (ASHCNs) from the dentist perspective., Methods: We conducted semi-structured interviews with 13 dentists (seven pediatric dentists and six general dentists) to learn about the dental transition process for ASHCNs., Results: Most dentists believed transitions from child-centered to adult-centered dental care were important for ASHCNs. Dentists reported two main barriers to transitions: (1) low dental reimbursements by Medicaid; and (2) a shortage of general dentists qualified or willing to treat ASHCNs. Pediatric and general dentists reported playing complimentary roles in facilitating transitions for ASHCNs and their families., Conclusions: Dentists acknowledged the challenges that adolescents with special health care needs and their families face in transitioning to adult-centered care and believed in the importance of ASHCNs maintaining a dental home. Pediatric dentists and general dentists play a key role in working together to implement dental transition plans for ASHCNs and to ensure successful dental transitions.

Purpose: The purpose of this study was to understand transitions from pediatric dental care to adult dental care for adolescents with special health care needs (ASHCNs) from parental and adolescent perspectives., Methods: Focus groups and interviews were conducted with 59 parents and 13 adolescent-parent dyads to identify factors associated with transitions to adult-centered dental care for ASHCNs., Results: Most parents believed ASHCNs were at risk for caries, but ASHCNs were not concerned about tooth decay. Parents of adolescents with complex SHCN believed it would be acceptable to continue seeing a pediatric dentist. Parents of Medicaid-enrolled ASHCNs reported lower efficacy in transitioning. ASHCNs desired personalized, adolescent-centered care and were motivated to transition when they felt out of place at the pediatric dentist office. Parents believed pediatric dentists play an important role in initiating and facilitating transitions., Conclusions: Pediatric dentists are well positioned to implement family and adolescent-centered policies to ensure dental transitions for adolescents with special health care needs and their families.

Olfactory dysfunction can be an early sign of Alzheimer's disease. Since hormone replacement therapy (HRT) may protect against Alzheimer's disease in postmenopausal women, the question arises as to whether it also protects against olfactory dysfunction in such women. A total of three olfactory and 12 neurocognitive tests were administered to 432 healthy postmenopausal women with varied HRT histories. Serum levels of reproductive hormones were obtained for all subjects; APOE-ε4 haplotype was determined for 77 women. National Adult Reading Test and Odor Memory/Discrimination Test scores were positively influenced by HRT. Odor Identification and Odor Memory/Discrimination Test scores were lower for women who scored poorly on a delayed recall test, a surrogate for mild cognitive impairment. The Wechsler Adult Intelligence Scale, Revised, as a Neuropsychological Instrument Spatial Span Backwards Test scores were higher in women receiving estrogen and progestin HRT and directly correlated with serum testosterone levels, the latter implying a positive effect of testosterone on spatial memory. APOE-ε4 was associated with poorer odor threshold test scores. These data suggest that HRT positively influences a limited number of olfactory and cognitive measures during menopause., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Freshwater harmful algal bloom (FHAB) toxins can cause morbidity and mortality in both humans and animals, and the incidence of FHABs in the United States and Kansas has increased. In 2010, the Kansas Department of Health and Environment (KDHE) developed a FHAB policy and response plan. We describe the epidemiology of FHAB-associated morbidity and mortality in humans and animals in Kansas. Healthcare providers and veterinarians voluntarily reported FHAB-associated cases to KDHE. An investigation was initiated for each report to determine the source of exposure and to initiate public health mitigation actions. There were 38 water bodies with a confirmed FHAB in 2011. There were 34 reports of human and animal FHAB-associated health events in 2011, which included five dog deaths and hospitalization of two human case patients. Five confirmed human illnesses, two dog illnesses and five dog deaths were associated with one lake. Four human and seven dog cases were exposed to the lake after a public health alert was issued. Public health officials and FHAB partners must ensure continued awareness of the risks to the public, educate healthcare providers and veterinarians on FHAB-related health events and encourage timely reporting to public health authorities.

Objective: To investigate the impact of traumatic brain injury (TBI) on the experience and expression of anger in a military sample., Participants: A total of 661 military personnel with a history of TBI and 1204 military personnel with no history of TBI., Design: Cross-sectional, between-group design, using multivariate analysis of variance., Main Measure: State-Trait Anger Expression Inventory-2 (STAXI-2)., Results: Participants with a history of TBI had higher scores on the STAXI-2 than controls and were 2 to 3 times more likely than the participants in the control group to have at least 1 clinically significant elevation on the STAXI-2. Results suggested that greater time since injury (ie, months between TBI and assessment) was associated with lower scores on the STAXI-2 State Anger scale., Conclusion: Although the results do not take into account confounding psychiatric conditions and cannot address causality, they suggest that a history of TBI increases the risk of problems with the experience, expression, and control of anger. This bolsters the need for proper assessment of anger when evaluating TBI in a military cohort.

A small but growing population of children with medical complexity, many of whom are covered by Medicaid, accounts for a high proportion of pediatric health care spending. We first describe the expenditures for children with medical complexity insured by Medicaid across the care continuum. We report the increasingly large amount of spending on hospital care for these children, relative to the small amount of primary care and home care spending. We then present a business case that estimates how cost savings might be achieved for children with medical complexity from potential reductions in hospital and emergency department use and shows how the savings could underwrite investments in outpatient and community care. We conclude by discussing the importance of these findings in the context of Medicaid's quality of care and health care reform., (Project HOPE—The People-to-People Health Foundation, Inc.)

This theoretical and case study review of dynamic exposures of aquatic organisms to organic contaminants examines variables important for interpreting exposure and therefore toxicity. The timing and magnitude of the absorbed dose change when the dynamics of exposure change. Thus, the dose metric for interpreting toxic responses observed during such exposure conditions is generally limited to the specific experiment and cannot be extrapolated to either other experiments with different exposure dynamics or to field exposures where exposure dynamics usually are different. This is particularly true for mixture exposures, for which the concentration and composition and, therefore, the timing and magnitude of exposure to individual components of different potency and potentially different mechanisms of action can vary. Aquatic toxicology needs studies that develop temporal thresholds for absorbed toxicant doses to allow for better extrapolation between conditions of dynamic exposure. Improved experimental designs are required that include high-quality temporal measures of both the exposure and the absorbed dose to allow better interpretation of data. For the short term, initial water concentration can be considered a conservative measure of exposure, although the extent to which this is true cannot be estimated specifically unless the dynamics of exposure as well as the toxicokinetics of the chemicals in the exposure scenario for the organism of interest are known. A better, but still limited, metric for interpreting the exposure and, therefore, toxicity is the peak absorbed dose, although this neglects toxicodynamics, requires appropriate temporal measures of accumulated dose to determine the peak concentration, and requires temporal thresholds for critical body residue for each component of the mixture., (Copyright © 2012 SETAC.)

Objectives: To characterize the use of and disposition from a tertiary pediatric emergency department (PED) by children with chronic conditions with varying degrees of medical complexity., Methods: We conducted a retrospective cohort study using a dataset of all registered PED patient visits at Seattle Children's Hospital from January 1, 2008, through December 31, 2009. Children's medical complexity was classified by using a validated algorithm (Clinical Risk Group software) into nonchronic and chronic conditions: episodic chronic, lifelong chronic, progressive chronic, and malignancy. Outcomes included PED length of stay (LOS) and disposition. Logistic regression generated age-adjusted odds ratios (AOR) of admission with 95% confidence intervals (CIs)., Results: PED visits totaled 77 748; 20% (15 433) of which were for children with chronic conditions. Compared with visits for children without chronic conditions, those for children with chronic conditions had increased PED LOS (on average, 79 minutes longer; 95% CI 77-81; P < .0001) and hospital (51% vs 10%) and PICU (3.2% vs 0.1%) admission rates (AOR 10.3, 95% CI 9.9-10.7 to hospital and AOR 25.0, 95% CI 17.0-36.0 to PICU). Admission rates and PED LOS increased with increasing medical complexity., Conclusions: Children with chronic conditions comprise a significant portion of annual PED visits in a tertiary pediatric center; medical complexity is associated with increased PED LOS and hospital or PICU admission. Clinical Risk Group may have utility in identifying high utilizers of PED resources and help support the development of interventions to facilitate optimal PED management, such as pre-arrival identification and individual emergency care plans.

Objective: To compare inpatient resource use trends for healthy children and children with chronic health conditions of varying degrees of medical complexity., Design: Retrospective cohort analysis., Setting: Twenty-eight US children's hospitals., Patients: A total of 1 526 051 unique patients hospitalized from January 1, 2004, through December 31, 2009, who were assigned to 1 of 5 chronic condition groups using 3M's Clinical Risk Group software., Intervention: None., Main Outcome Measures: Trends in the number of patients, hospitalizations, hospital days, and charges analyzed with linear regression., Results: Between 2004 and 2009, hospitals experienced a greater increase in the number of children hospitalized with vs without a chronic condition (19.2% vs 13.7% cumulative increase, P < .001). The greatest cumulative increase (32.5%) was attributable to children with a significant chronic condition affecting 2 or more body systems, who accounted for 19.2% (n = 63 203) of patients, 27.2% (n = 111 685) of hospital discharges, 48.9% (n = 1.1 million) of hospital days, and 53.2% ($9.2 billion) of hospital charges in 2009. These children had a higher percentage of Medicaid use (56.5% vs 49.7%; P < .001) compared with children without a chronic condition. Cerebral palsy (9179 [14.6%]) and asthma (13 708 [21.8%]) were the most common primary diagnosis and comorbidity, respectively, observed among these patients., Conclusions: Patients with a chronic condition increasingly used more resources in a group of children's hospitals than patients without a chronic condition. The greatest growth was observed in hospitalized children with chronic conditions affecting 2 or more body systems. Children's hospitals must ensure that their inpatient care systems and payment structures are equipped to meet the protean needs of this important population of children.

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. Injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). We developed a new automated MEG low-frequency source imaging method and applied this method in 45 mild TBI (23 from combat-related blasts, and 22 from non-blast causes) and 10 moderate TBI patients (non-blast causes). Seventeen of the patients with mild TBI from blasts had tertiary injuries resulting from the blast. The results show our method detected abnormalities at the rates of 87% for the mild TBI group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities were 96% and 77% for the blast and non-blast TBI groups, respectively. The spatial characteristics of abnormal slow-wave generation measured by Z scores in the mild blast TBI group significantly correlated with those in non-blast mild TBI group. Among 96 cortical regions, the likelihood of abnormal slow-wave generation was less in the mild TBI patients with blast than in the mild non-blast TBI patients, suggesting possible protective effects due to the military helmet and armor. Finally, the number of cortical regions that generated abnormal slow-waves correlated significantly with the total post-concussive symptom scores in TBI patients. This study provides a foundation for using MEG low-frequency source imaging to support the clinical diagnosis of TBI., (Published by Elsevier Inc.)

Background: Many emergency physicians order chest x-rays (CXRs) for pediatric patients who present with a chief complaint of chest pain despite a paucity of research to support this testing, which exposes patients to radiation, cost, and delays., Objectives: This study aimed to begin development of a decision making tool that will allow emergency physicians to selectively obtain CXR films in pediatric patients presenting with chest pain., Methods: We performed a retrospective cohort study of 400 consecutive pediatric patients with a chief complaint of chest pain and reviewed charts to determine how many received a CXR and which clinical characteristics were present in all patients. Chest radiograph findings were graded for significance as follows: (1) no or minor clinical significance: normal result in the CXR film without effect on the immediate evaluation of a patient; (2) moderate clinical significance: only impact on plan for follow-up; and (3) major clinical significance: result in the CXR film directly affects immediate management. We then evaluated each chart for historical or examination findings that might identify criteria associated with positive radiographic findings to propose a set of criteria that could lead to the development of a decision rule that allows a reduced utilization while having a high sensitivity for clinically significant positive findings on CXR film., Results: Of the 400 pediatric patients reviewed, 63.5% (n = 254) received a CXR in the emergency department (ED). Of those receiving a CXR, only 8.26% (n = 21) had a finding that affected either ED management or follow-up planning. The criteria that would have identified all patients with positive results in the CXR films were abnormal vital signs, shortness of breath, palpitations, presence of comorbidities, abnormal or unilateral breath sounds, history of trauma, murmur, or cough., Conclusions: This pilot study demonstrates the potential for a decision rule to eliminate both cost and radiation exposure by using defined criteria to determine the need for a CXR in pediatric ED patients. We identified 8 simple criteria that would have identified all children who benefited from a CXR in this study. The next phase of this study will prospectively evaluate the utility of each of the criteria as part of a draft decision rule.

Experimental designs for evaluating complex mixture toxicity in aquatic environments can be highly variable and, if not appropriate, can produce and have produced data that are difficult or impossible to interpret accurately. We build on and synthesize recent critical reviews of mixture toxicity using lessons learned from 4 case studies, ranging from binary to more complex mixtures of primarily polycyclic aromatic hydrocarbons and petroleum hydrocarbons, to provide guidance for evaluating the aquatic toxicity of complex mixtures of organic chemicals. Two fundamental requirements include establishing a dose-response relationship and determining the causative agent (or agents) of any observed toxicity. Meeting these 2 requirements involves ensuring appropriate exposure conditions and measurement endpoints, considering modifying factors (e.g., test conditions, test organism life stages and feeding behavior, chemical transformations, mixture dilutions, sorbing phases), and correctly interpreting dose-response relationships. Specific recommendations are provided., (Copyright © 2011 SETAC.)

This article presents a critical review of two groups of studies that reported adverse effects to salmon and herring eggs and fry from exposure to 1 μg/L or less of aqueous total polycyclic aromatic hydrocarbons (TPAH), as weathered oil, and a more toxic aqueous extract of "very weathered oil." Exposure media were prepared by continuously flowing water up through vertical columns containing gravel oiled at different concentrations of Prudhoe Bay crude oil. Uncontrolled variables associated with the use of the oiled gravel columns included time- and treatment-dependent variations in the PAH concentration and composition in the exposure water, unexplored toxicity from other oil constituents/degradation products, potential toxicity from bacterial and fungal activity, oil droplets as a potential contaminant source, inherent differences between control and exposed embryo populations, and water flow rate differences. Based on a review of the evidence from published project reports, peer-reviewed publications, chemistry data in a public database, and unpublished reports and laboratory records, the reviewed studies did not establish consistent dose (concentration) response or causality and thus do not demonstrate that dissolved PAH alone from the weathered oil resulted in the claimed effects on fish embryos at low μg/L TPAH concentrations. Accordingly, these studies should not be relied on for management decision-making, when assessing the risk of very low-level PAH exposures to early life stages of fish.

Objective: To assess the extent to which chronic condition (CC) status and severity affected how soon children had a dental visit after enrolling in Medicaid. Data Source. Enrollment and claims data (2003-2008) for newly Medicaid-enrolled children ages 3-14 in Iowa., Study Design: 3M Clinical Risk Grouping methods were used to identify CC status (no/yes) and CC severity (less severe/more severe). Survival analysis was used to identify the factors associated with earlier first dental visits after initially enrolling in Medicaid., Principal Findings: Children with a CC were 17 percent more likely to have earlier first dental visits after enrolling in Medicaid (p < .0001). There was no significant difference by CC severity. Children who lived in a dental health professional shortage area and those who did not utilize primary medical care had significantly later first Medicaid dental visits, whereas these factors failed to reach statistical significance for children with a CC., Conclusion: While newly Medicaid-enrolled children with a CC were significantly more likely to have earlier first dental visits, we failed to detect a relationship between CC severity and the time to first Medicaid dental visit. The determinants of first Medicaid dental visits were heterogeneous across subgroups of newly Medicaid-enrolled children. Future studies should identify the sociobehavioral factors associated with CCs that are potential barriers to earlier first Medicaid dental visits for newly Medicaid-enrolled children., (© Health Research and Educational Trust.)

Context: Early hospital readmission is emerging as an indicator of care quality. Some children with chronic illnesses may be readmitted on a recurrent basis, but there are limited data describing their rehospitalization patterns and impact., Objectives: To describe the inpatient resource utilization, clinical characteristics, and admission reasons of patients recurrently readmitted to children's hospitals., Design, Setting, and Patients: Retrospective cohort analysis of 317,643 patients (n = 579,504 admissions) admitted to 37 US children's hospitals in 2003 with follow-up through 2008., Main Outcome Measure: Maximum number of readmissions experienced by each child within any 365-day interval during the 5-year follow-up period., Results: In the sample, 69,294 patients (21.8%) experienced at least 1 readmission within 365 days of a prior admission. Within a 365-day interval, 9237 patients (2.9%) experienced 4 or more readmissions; time between admissions was a median 37 days (interquartile range [IQR], 21-63). These patients accounted for 18.8% (109,155 admissions) of all admissions and 23.2% ($3.4 billion) of total inpatient charges for the study cohort during the entire follow-up period. Tests for trend indicated that as the number of readmissions increased from 0 to 4 or more, the prevalences increased for a complex chronic condition (from 22.3% [n = 55,382/248,349] to 89.0% [n = 8225/9237]; P < .001), technology assistance (from 5.3% [n = 13,163] to 52.6% [n = 4859]; P < .001), public insurance use (from 40.9% [n = 101,575] to 56.3% [n = 5202]; P < .001), and non-Hispanic black race (from 21.8% [n = 54,140] to 34.4% [n = 3181]; P < .001); and the prevalence decreased for readmissions associated with an ambulatory care-sensitive condition (from 23.1% [62,847/272,065] to 14.0% [15,282/109,155], P < .001). Of patients readmitted 4 or more times in a 365-day interval, 2633 (28.5%) were rehospitalized for a problem in the same organ system across all admissions during the interval., Conclusions: Among a group of pediatric hospitals, 18.8% of admissions and 23.2% of inpatient charges were accounted for by the 2.9% of patients with frequent recurrent admissions. Many of these patients were rehospitalized recurrently for a problem in the same organ system.