559 research outputs found

    Predicting Emergency Department Volume Using Forecasting Methods to Create a “Surge Response” for Noncrisis Events

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    Objectives:  This study investigated whether emergency department (ED) variables could be used in mathematical models to predict a future surge in ED volume based on recent levels of use of physician capacity. The models may be used to guide decisions related to on‐call staffing in non–crisis‐related surges of patient volume. Methods:  A retrospective analysis was conducted using information spanning July 2009 through June 2010 from a large urban teaching hospital with a Level I trauma center. A comparison of significance was used to assess the impact of multiple patient‐specific variables on the state of the ED. Physician capacity was modeled based on historical physician treatment capacity and productivity. Binary logistic regression analysis was used to determine the probability that the available physician capacity would be sufficient to treat all patients forecasted to arrive in the next time period. The prediction horizons used were 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 12 hours. Five consecutive months of patient data from July 2010 through November 2010, similar to the data used to generate the models, was used to validate the models. Positive predictive values, Type I and Type II errors, and real‐time accuracy in predicting noncrisis surge events were used to evaluate the forecast accuracy of the models. Results:  The ratio of new patients requiring treatment over total physician capacity (termed the care utilization ratio [CUR]) was deemed a robust predictor of the state of the ED (with a CUR greater than 1 indicating that the physician capacity would not be sufficient to treat all patients forecasted to arrive). Prediction intervals of 30 minutes, 8 hours, and 12 hours performed best of all models analyzed, with deviances of 1.000, 0.951, and 0.864, respectively. A 95% significance was used to validate the models against the July 2010 through November 2010 data set. Positive predictive values ranged from 0.738 to 0.872, true positives ranged from 74% to 94%, and true negatives ranged from 70% to 90% depending on the threshold used to determine the state of the ED with the 30‐minute prediction model. Conclusions:  The CUR is a new and robust indicator of an ED system’s performance. The study was able to model the tradeoff of longer time to response versus shorter but more accurate predictions, by investigating different prediction intervals. Current practice would have been improved by using the proposed models and would have identified the surge in patient volume earlier on noncrisis days.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92015/1/j.1553-2712.2012.01359.x.pd

    Maternal Prenatal Cortisol Programs the Infant Hypothalamic–Pituitary–Adrenal Axis

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    One of the key proposed agents of fetal programming is exposure to maternal glucocorticoids. Experimental animal studies provide evidence that prenatal exposure to elevated maternal glucocorticoids has consequences for hypothalamic–pituitary–adrenal (HPA) axis functioning in the offspring. There are very few direct tests of maternal glucocorticoids, such as cortisol, during human pregnancy and associations with infant cortisol reactivity. The current study examined the link between maternal prenatal cortisol trajectories and infant cortisol reactivity to the pain of inoculation in a sample of 152 mother-infant (47.4% girls) pairs. The results from the current study provide insight into fetal programming of the infant HPA axis, demonstrating that elevated prenatal maternal cortisol is associated with a larger infant cortisol response to challenge at both 6 and 12 months of age

    Preparing for Climatic Change: The Water, Salmon, and Forests of the Pacific Northwest

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    The impacts of year-to-year and decade-to-decade climatic variations on some of the Pacific Northwest’s key natural resources can be quantified to estimate sensitivity to regional climatic changes expected as part of anthropogenic global climatic change. Warmer, drier years, often associated with El Niño events and/or the warm phase of the Pacific Decadal Oscillation, tend to be associated with below-average snowpack, streamflow, and flood risk, below-average salmon survival, below-average forest growth, and above-average risk of forest fire. During the 20th century, the region experienced a warming of 0.8 ◦C. Using output from eight climate models, we project a further warming of 0.5–2.5 ◦C (central estimate 1.5 ◦C) by the 2020s, 1.5–3.2 ◦C (2.3◦C) by the 2040s, and an increase in precipitation except in summer. The foremost impact of a warming climate will be the reduction of regional snowpack, which presently supplies water for ecosystems and human uses during the dry summers. Our understanding of past climate also illustrates the responses of human management systems to climatic stresses, and suggests that a warming of the rate projected would pose significant challenges to the management of natural resources. Resource managers and planners currently have few plans for adapting to or mitigating the ecological and economic effects of climatic change

    Preparing for Climatic Change: The Water, Salmon, and Forests of the Pacific Northwest

    Get PDF
    The impacts of year-to-year and decade-to-decade climatic variations on some of the Pacific Northwest’s key natural resources can be quantified to estimate sensitivity to regional climatic changes expected as part of anthropogenic global climatic change. Warmer, drier years, often associated with El Niño events and/or the warm phase of the Pacific Decadal Oscillation, tend to be associated with below-average snowpack, streamflow, and flood risk, below-average salmon survival, below-average forest growth, and above-average risk of forest fire. During the 20th century, the region experienced a warming of 0.8 ◦C. Using output from eight climate models, we project a further warming of 0.5–2.5 ◦C (central estimate 1.5 ◦C) by the 2020s, 1.5–3.2 ◦C (2.3◦C) by the 2040s, and an increase in precipitation except in summer. The foremost impact of a warming climate will be the reduction of regional snowpack, which presently supplies water for ecosystems and human uses during the dry summers. Our understanding of past climate also illustrates the responses of human management systems to climatic stresses, and suggests that a warming of the rate projected would pose significant challenges to the management of natural resources. Resource managers and planners currently have few plans for adapting to or mitigating the ecological and economic effects of climatic change

    Revisiting Metchnikoff: Age-related alterations in microbiota-gut-brain axis in the mouse

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    Over the last decade, there has been increased interest in the role of the gut microbiome in health including brain health. This is by no means a new theory; Elie Metchnikoff proposed over a century ago that targeting the gut by consuming lactic acid bacteria such as those in yogurt, could improve or delay the onset of cognitive decline associated with ageing. However, there is limited information characterising the relationship between the behavioural and physiological sequelae of ageing and alterations in the gut microbiome. To this end, we assessed the behavioural, physiological and caecal microbiota profile of aged male mice. Older mice (20–21 months old) exhibited deficits in spatial memory and increases in anxiety-like behaviours compared to younger mice (2–3 months old). They also exhibited increased gut permeability, which was directly correlated with elevations in peripheral pro-inflammatory cytokines. Furthermore, stress exacerbated the gut permeability of aged mice. Examination of the caecal microbiota revealed significant increases in phylum TM7, family Porphyromonadaceae and genus Odoribacter of aged mice. This represents a shift of aged microbiota towards a profile previously associated with inflammatory disease, particularly gastrointestinal and liver disorders. Furthermore, Porphyromonadaceae, which has also been associated with cognitive decline and affective disorders, was directly correlated with anxiety-like behaviour in aged mice. These changes suggest that changes in the gut microbiota and associated increases in gut permeability and peripheral inflammation may be important mediators of the impairments in behavioural, affective and cognitive functions seen in ageing

    Enriched Dietary Saturated Fatty Acids Induce Trained Immunity via Ceramide Production that Enhances Severity of Endotoxemia and clearance of infection

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    Trained immunity is an innate immune memory response that is induced by a primary inflammatory stimulus that sensitizes monocytes and macrophages to a secondary pathogenic challenge, reprogramming the host response to infection and inflammatory disease. Dietary fatty acids can act as inflammatory stimuli, but it is unknown if they can act as the primary stimuli to induce trained immunity. Here we find mice fed a diet enriched exclusively in saturated fatty acids (ketogenic diet; KD) confer a hyper-inflammatory response to systemic lipopolysaccharide (LPS) and increased mortality, independent of diet-induced microbiome and hyperglycemia. We find KD alters the composition of the hematopoietic stem cell compartment and enhances the response of bone marrow macrophages, monocytes, and splenocytes to secondary LPS challenge. Lipidomics identified enhanced free palmitic acid (PA) and PA-associated lipids in KD-fed mice serum. We found pre-treatment with physiologically relevant concentrations of PA induces a hyper-inflammatory response to LPS in macrophages, and this was dependent on the synthesis of ceramide. In vivo, we found systemic PA confers enhanced inflammation and mortality in response to systemic LPS, and this phenotype was not reversible for up to 7 days post-PA-exposure. Conversely, we find PA exposure enhanced clearance of Candida albicans in Rag1-/- mice. Lastly, we show that oleic acid, which depletes intracellular ceramide, reverses PA-induced hyper-inflammation in macrophages and enhanced mortality in response to LPS. These implicate enriched dietary SFAs, and specifically PA, in the induction of long-lived innate immune memory and highlight the plasticity of this innate immune reprogramming by dietary constituents

    The Impact of Integrated Student Experiences on Learning

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    In a cluster of courses called Food for Thought, seven faculty from different departments (including Biology, Economics, Sociology, Chemistry, Health and Wellness, and Foreign Language) teach students about food information, food consumerism, nutrition and health. The classes all have a shared learning outcome focused on developing the student as an informed consumer of food.  Each semester, faculty teach a food-related course from their respective disciplinary perspective while also incorporating cross-course interactions that allow for both integration of disciplinary knowledge and student-to-student learning opportunities. Previous research demonstrated that this approach leads to student perceptions of learning gains (Authors, 2011). Building on that work, this research directly assesses student learning in the Food for Thought cluster. The results demonstrate that exposure to multiple disciplines covering a shared topic enhances learning through greater student ability to integrate diverse forms of knowledge and to see an issue from multiple perspectives. These findings demonstrate the value of multidisciplinary learning opportunities for students

    Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution

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    The newly emerging Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a Severe Acute Respiratory Syndrome-like disease with ∼43% mortality. Given the recent detection of virus in dromedary camels, zoonotic transfer of MERS-CoV to humans is suspected. In addition, little is known about the role of human neutralizing Ab (nAb) pressure as a driving force in MERS-CoV adaptive evolution. Here, we used a well-characterized nonimmune human Ab-phage library and a panning strategy with proteoliposomes and cells to identify seven human nAbs against the receptor-binding domain (RBD) of the MERS-CoV Spike protein. These nAbs bind to three different epitopes in the RBD and human dipeptidyl peptidase 4 (hDPP4) interface with subnanomolar/nanomolar binding affinities and block the binding of MERS-CoV Spike protein with its hDPP4 receptor. Escape mutant assays identified five amino acid residues that are critical for neutralization escape. Despite the close proximity of the three epitopes on the RBD interface, escape from one epitope did not have a major impact on neutralization with Abs directed to a different epitope. Importantly, the majority of escape mutations had negative impacts on hDPP4 receptor binding and viral fitness. To our knowledge, these results provide the first report on human nAbs against MERS-CoV that may contribute to MERS-CoV clearance and evolution. Moreover, in the absence of a licensed vaccine or antiviral for MERS, this panel of nAbs offers the possibility of developing human mAb-based immunotherapy, especially for health-care workers

    A Highly Stable Blood Meal Alternative for Rearing \u3cem\u3eAedes\u3c/em\u3e and \u3cem\u3eAnopheles\u3c/em\u3e Mosquitoes

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    We investigated alternatives to whole blood for blood feeding of mosquitoes with a focus on improved stability and compatibility with mass rearing programs. In contrast to whole blood, an artificial blood diet of ATP-supplemented plasma was effective in maintaining mosquito populations and was compatible with storage for extended periods refrigerated, frozen, and as a lyophilized powder. The plasma ATP diet supported rearing of both Anopheles and Aedes mosquitoes. It was also effective in rearing Wolbachia-infected Aedes mosquitoes, suggesting compatibility with vector control efforts
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