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1. Author Correction: Nutrients cause grassland biomass to outpace herbivory

Author

Borer, E. T., Harpole, W. S., Adler, P. B., Arnillas, C. A., Bugalho, M. N., Cadotte, M. W., Caldeira, M. C., Campana, S., Dickman, C. R., Dickson, T. L., Donohue, I., Eskelinen, A., Firn, J. L., Graff, P., Gruner, D. S., Heckman, R. W., Koltz, A. M., Komatsu, K. J., Lannes, L. S., MacDougall, A. S., Martina, J. P., Moore, J. L., Mortensen, B., Ochoa-Hueso, R., Venterink, H. Olde, Power, S. A., Price, J. N., Risch, A. C., Sankaran, M., Schütz, M., Sitters, J., Stevens, C. J., Virtanen, R., Wilfahrt, P. A., and Seabloom, E. W.

Published
2021
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2. Nutrients cause grassland biomass to outpace herbivory

Author

Borer, E. T., Harpole, W. S., Adler, P. B., Arnillas, C. A., Bugalho, M. N., Cadotte, M. W., Caldeira, M. C., Campana, S., Dickman, C. R., Dickson, T. L., Donohue, I., Eskelinen, A., Firn, J. L., Graff, P., Gruner, D. S., Heckman, R. W., Koltz, A. M., Komatsu, K. J., Lannes, L. S., MacDougall, A. S., Martina, J. P., Moore, J. L., Mortensen, B., Ochoa-Hueso, R., Olde Venterink, H., Power, S. A., Price, J. N., Risch, A. C., Sankaran, M., Schütz, M., Sitters, J., Stevens, C. J., Virtanen, R., Wilfahrt, P. A., and Seabloom, E. W.

Published
2020
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4. Data package for NutNet project: Compositional variation in grassland plant communities (60 sites, 2007-2020) ver 1

Author

Bakker, J.D., Price, J.N., Henning, J.A., Batzer, E.E., Ohlert, T.J., Wainwright, C.E., Adler, P.B., Alberti, J., Arnillas, C.A., Biederman, L.A., Borer, E.T., Brudvig, L.A., Buckley, Y.M., Bugalho, M.N., Cadotte, M.W., Caldeira, M.C., Catford, J.A., Chen, Q., Crawley, M.J., Daleo, P., Dickman, C.R., Donohue, I., DuPre, M.E., Ebeling, A., Eisenhauer, N., Fay, P.A., Gruner, D.S., Haider, S., Hautier, Y., Jentsch, A., Kirkman, K., Knops, J.M.H., Lannes, L.S., MacDougall, A.S., McCulley, R.L., Mitchell, R.M., Moore, J.L., Morgan, J.W., Mortensen, B., Venterink, H.O., Peri, P.L., Power, S.A., Prober, S.M., Roscher, Christiane, Sankaran, M., Seabloom, E.W., Smith, M.D., Stevens, C., Sullivan, L.L., Tedder, M., Veen, G.F.C., Virtanen, R., Wardle, G.M., Bakker, J.D., Price, J.N., Henning, J.A., Batzer, E.E., Ohlert, T.J., Wainwright, C.E., Adler, P.B., Alberti, J., Arnillas, C.A., Biederman, L.A., Borer, E.T., Brudvig, L.A., Buckley, Y.M., Bugalho, M.N., Cadotte, M.W., Caldeira, M.C., Catford, J.A., Chen, Q., Crawley, M.J., Daleo, P., Dickman, C.R., Donohue, I., DuPre, M.E., Ebeling, A., Eisenhauer, N., Fay, P.A., Gruner, D.S., Haider, S., Hautier, Y., Jentsch, A., Kirkman, K., Knops, J.M.H., Lannes, L.S., MacDougall, A.S., McCulley, R.L., Mitchell, R.M., Moore, J.L., Morgan, J.W., Mortensen, B., Venterink, H.O., Peri, P.L., Power, S.A., Prober, S.M., Roscher, Christiane, Sankaran, M., Seabloom, E.W., Smith, M.D., Stevens, C., Sullivan, L.L., Tedder, M., Veen, G.F.C., Virtanen, R., and Wardle, G.M.

Abstract

Human activities are altering ecological communities around the globe. Understanding the implications of these changes requires that we consider the composition of those communities. However, composition can be summarized by many metrics which in turn are influenced by different ecological processes. For example, incidence-based metrics strongly reflect species gains or losses, while abundance-based metrics are minimally affected by changes in the abundance of small or uncommon species. Furthermore, metrics might be correlated with different predictors. We used a globally distributed experiment to examine variation in species composition within 60 grasslands on six continents. Each site had an identical experimental and sampling design: 24 plots × 4 years. We expressed compositional variation within each site—not across sites—using abundance- and incidence-based metrics of the magnitude of dissimilarity (Bray–Curtis and Sorensen, respectively), abundance- and incidence-based measures of the relative importance of replacement (balanced variation and species turnover, respectively), and species richness at two scales (per plot-year [alpha] and per site [gamma]). Average compositional variation among all plot-years at a site was high and similar to spatial variation among plots in the pretreatment year, but lower among years in untreated plots. For both types of metrics, most variation was due to replacement rather than nestedness. Differences among sites in overall within-site compositional variation were related to several predictors. Environmental heterogeneity (expressed as the CV of total aboveground plant biomass in unfertilized plots of the site) was an important predictor for most metrics. Biomass production was a predictor of species turnover and of alpha diversity but not of other metrics. Continentality (measured as annual temperature range) was a strong predictor of Sorensen dissimilarity. Metrics of compositional variation are moderately correlated: knowin

Published
2023

5. Compositional variation in grassland plant communities

Author

Bakker, J.D., Price, J.N., Henning, J.A., Batzer, E.E., Ohlert, T.J., Wainwright, C.E., Adler, P.B., Alberti, J., Arnillas, C.A., Biederman, L.A., Borer, E.T., Brudvig, L.A., Buckley, Y.M., Bugalho, M.N., Cadotte, M.W., Caldeira, M.C., Catford, J.A., Chen, Q., Crawley, M.J., Daleo, P., Dickman, C.R., Donohue, I., DuPre, M.E., Ebeling, A., Eisenhauer, N., Fay, P.A., Gruner, D.S., Haider, S., Hautier, Y., Jentsch, A., Kirkman, K., Knops, J.M.H., Lannes, L.S., MacDougall, A.S., McCulley, R.L., Mitchell, R.M., Moore, J.L., Morgan, J.W., Mortensen, B., Venterink, H.O., Peri, P.L., Power, S.A., Prober, S.M., Roscher, Christiane, Sankaran, M., Seabloom, E.W., Smith, M.D., Stevens, C., Sullivan, L.L., Tedder, M., Veen, G.F.C., Virtanen, R., Wardle, G.M., Bakker, J.D., Price, J.N., Henning, J.A., Batzer, E.E., Ohlert, T.J., Wainwright, C.E., Adler, P.B., Alberti, J., Arnillas, C.A., Biederman, L.A., Borer, E.T., Brudvig, L.A., Buckley, Y.M., Bugalho, M.N., Cadotte, M.W., Caldeira, M.C., Catford, J.A., Chen, Q., Crawley, M.J., Daleo, P., Dickman, C.R., Donohue, I., DuPre, M.E., Ebeling, A., Eisenhauer, N., Fay, P.A., Gruner, D.S., Haider, S., Hautier, Y., Jentsch, A., Kirkman, K., Knops, J.M.H., Lannes, L.S., MacDougall, A.S., McCulley, R.L., Mitchell, R.M., Moore, J.L., Morgan, J.W., Mortensen, B., Venterink, H.O., Peri, P.L., Power, S.A., Prober, S.M., Roscher, Christiane, Sankaran, M., Seabloom, E.W., Smith, M.D., Stevens, C., Sullivan, L.L., Tedder, M., Veen, G.F.C., Virtanen, R., and Wardle, G.M.

Abstract

Human activities are altering ecological communities around the globe. Understanding the implications of these changes requires that we consider the composition of those communities. However, composition can be summarized by many metrics which in turn are influenced by different ecological processes. For example, incidence-based metrics strongly reflect species gains or losses, while abundance-based metrics are minimally affected by changes in the abundance of small or uncommon species. Furthermore, metrics might be correlated with different predictors. We used a globally distributed experiment to examine variation in species composition within 60 grasslands on six continents. Each site had an identical experimental and sampling design: 24 plots × 4 years. We expressed compositional variation within each site—not across sites—using abundance- and incidence-based metrics of the magnitude of dissimilarity (Bray–Curtis and Sorensen, respectively), abundance- and incidence-based measures of the relative importance of replacement (balanced variation and species turnover, respectively), and species richness at two scales (per plot-year [alpha] and per site [gamma]). Average compositional variation among all plot-years at a site was high and similar to spatial variation among plots in the pretreatment year, but lower among years in untreated plots. For both types of metrics, most variation was due to replacement rather than nestedness. Differences among sites in overall within-site compositional variation were related to several predictors. Environmental heterogeneity (expressed as the CV of total aboveground plant biomass in unfertilized plots of the site) was an important predictor for most metrics. Biomass production was a predictor of species turnover and of alpha diversity but not of other metrics. Continentality (measured as annual temperature range) was a strong predictor of Sorensen dissimilarity. Metrics of compositional variation are moderately correlated: knowin

Published
2023

9. The development of a HAMstring InjuRy (HAMIR) index to mitigate injury risk through innovative imaging, biomechanics, and data analytics: protocol for an observational cohort study.

Author

Heiderscheit, BC, Blemker, SS, Opar, D, Stiffler-Joachim, MR, Bedi, A, Hart, J, Mortensen, B, Kliethermes, SA, HAMIR Study Group, Heiderscheit, BC, Blemker, SS, Opar, D, Stiffler-Joachim, MR, Bedi, A, Hart, J, Mortensen, B, Kliethermes, SA, and HAMIR Study Group

Abstract

BACKGROUND: The etiology of hamstring strain injury (HSI) in American football is multi-factorial and understanding these risk factors is paramount to developing predictive models and guiding prevention and rehabilitation strategies. Many player-games are lost due to the lack of a clear understanding of risk factors and the absence of effective methods to minimize re-injury. This paper describes the protocol that will be followed to develop the HAMstring InjuRy (HAMIR) index risk prediction models for HSI and re-injury based on morphological, architectural, biomechanical and clinical factors in National Collegiate Athletic Association Division I collegiate football players. METHODS: A 3-year, prospective study will be conducted involving collegiate football student-athletes at four institutions. Enrolled participants will complete preseason assessments of eccentric hamstring strength, on-field sprinting biomechanics and muscle-tendon volumes using magnetic-resonance imaging (MRI). Athletic trainers will monitor injuries and exposure for the duration of the study. Participants who sustain an HSI will undergo a clinical assessment at the time of injury along with MRI examinations. Following completion of structured rehabilitation and return to unrestricted sport participation, clinical assessments, MRI examinations and sprinting biomechanics will be repeated. Injury recurrence will be monitored through a 6-month follow-up period. HAMIR index prediction models for index HSI injury and re-injury will be constructed. DISCUSSION: The most appropriate strategies for reducing risk of HSI are likely multi-factorial and depend on risk factors unique to each athlete. This study will be the largest-of-its-kind (1200 player-years) to gather detailed information on index and recurrent HSI, and will be the first study to simultaneously investigate the effect of morphological, biomechanical and clinical variables on risk of HSI in collegiate football athletes. The quantitative HAMI

Published
2022

10. Safety of Bifidobacterium breve, Bif195, employing a human exercise-induced intestinal permeability model : a randomised, double-blinded, placebo-controlled, parallel group trial

Author

Engel, S., Mortensen, B., Wellejus, A., Vera-Jimenez, N., Struve, C., Brummer, Robert Jan, Damholt, A., Woods, T., Shanahan, F., Engel, S., Mortensen, B., Wellejus, A., Vera-Jimenez, N., Struve, C., Brummer, Robert Jan, Damholt, A., Woods, T., and Shanahan, F.

Abstract

We have previously shown that the probiotic Bifidobacterium breve strain Bif195 alleviates mucosal injury including ulcer formation in the upper intestine induced by non-steroid anti-inflammatory drugs (NSAIDs). Here, we report additional safety use of Bif195 in 126 healthy humans undergoing an exercise-induced intestinal permeability challenge in a double-blinded, placebo-controlled randomised 6-week intervention trial. Intestinal permeability was assessed by urinary lactulose/rhamnose (L/R) ratio. L/R ratio, plasma intestinal fatty acid binding protein (I-FABP) and gastrointestinal symptom rating scale (GSRS) questionnaire were measured resting and after a 1 h treadmill challenge, prior to and at the end of the intervention. To be able to compare the equivalence of resting state at baseline, of this cohort of well-trained subjects, to non-trained subjects, a cohort of 63 healthy and non-trained subjects (<2 h/week of endurance sports) was included. Study subjects (well-trained) were 35.7% women with a mean age and body mass index (in kg/m2) of 35.0 years and 24.8, respectively. There were no differences between the Bif195 and placebo groups in effects on L/R ratio, I-FABP and GSRS questionnaire score. In addition, there were no differences between Bif195 and placebo in number of adverse events and change in cytokines, liver or kidney biomarkers. The exercise model successfully induced intestinal permeability by statistically significantly increasing L/R ratio by ~100% (P<0.0001) and cytokines after the exercise challenge. No significant difference was found between well-trained and non-trained subjects in baseline resting L/R ratio. In conclusion, the reported cytoprotective effects of Bif195 are unlikely to be primarily related to small bowel permeability, and the safety of Bif195 in individuals with increased permeability is supported by the present data. ClinicalTrials.gov: NCT03027583., Funding agency:CRO Atlantia Food Clinical Trials (Cork, Ireland)

Published
2022
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12. Lithiases et sténoses salivaires. Une classification pratique des pathologies non tumorales

Author

Marchal, F., Chossegros, C., Faure, F., Delas, B., Bizeau, A., Mortensen, B., Schaitkin, B., Buchwald, C., Cenjor, C., Yu, C., Campisi, D., Eisele, D., Greger, D., Trikeriotis, D., Pabst, G., Kolenda, J., Hagemann, M., Tarabichi, M., Guntinas-Lichius, O., Homoe, P., Carrau, R., Irvine, R., Studer, R., Wang, S., Fischer, U., Van der Poorten, V., Saban, Y., and Barki, G.

Published
2009
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16. Salivary stones and stenosis. A comprehensive classification

Author

Marchal, F., Chossegros, C., Faure, F., Delas, B., Bizeau, A., Mortensen, B., Schaitkin, B., Buchwald, C., Cenjor, C., Yu, C., Campisi, D., Eisele, D., Greger, D., Trikeriotis, D., Pabst, G., Kolenda, J., Hagemann, M., Tarabichi, M., Guntinas-Lichius, O., Homoe, P., Carrau, R., Irvine, R., Studer, R., Wang, S., Fischer, U., Van der Poorten, V., Saban, Y., and Barki, G.

Published
2008
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17. Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men

Author

Alibegovic, A.C., Sonne, M.P., Hojbjerre, L., Bork-Jensen, J., Jacobsen, S., Nilsson, E., Faerch, K., Hiscock, N., Mortensen, B., Friedrichsen, M., Stallknecht, B., Dela, F., and Vaag, A.

Subjects
Insulin resistance -- Genetic aspects, Insulin resistance -- Risk factors, Insulin resistance -- Physiological aspects, Gene expression -- Health aspects, Gene expression -- Physiological aspects, Young men -- Health aspects, Young men -- Behavior, Young men -- Genetic aspects, Exercise -- Health aspects, Biological sciences
Abstract

Physical inactivity is a risk factor for insulin resistance. We examined the effect of 9 days of bed rest on basal and insulin-stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches in 20 healthy young men. Furthermore, we investigated whether bed rest affected DNA methylation in the promoter region of the peroxisome proliferator-activated receptor-[gamma] coactivator-1[alpha] (PPARGC1A) gene. Subjects were reexamined after 4 wk of retraining. We found that bed rest induced insulin resistance and altered the expression of more than 4,500 genes. These changes were only partly normalized after 4 wk of retraining. Pathway analyses revealed significant downregulation of 34 pathways, predominantly those of genes associated with mitochondrial function, including PPARGC1A. Despite induction of insulin resistance, bed rest resulted in a paradoxically increased response to acute insulin stimulation in the general expression of genes, particularly those involved in inflammation and endoplasmatic reticulum (ER) stress. Furthermore, bed rest changed gene expressions of several insulin resistance and diabetes candidate genes. We also observed a trend toward increased PPARGC1A DNA methylation after bed rest. We conclude that impaired expression of PPARGC1A and other genes involved in mitochondrial function as well as a paradoxically increased response to insulin of genes involved in inflammation and ER stress may contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after 4 wk of retraining underscores the importance of maintaining a minimum of daily physical activity. bed rest; peroxisome proliferator-activated receptor-[gamma] coactivator-1[alpha]; gene expression; mitochondria doi: 10.1152/ajpendo.00590.2009.

Published
2010

21. Temporal rarity is a better predictor of local extinction risk than spatial rarity

Author

Wilfahrt, P.A., Asmus, A.L., Seabloom, E.W., Henning, J.A., Adler, P., Arnillas, C.A., Bakker, J.D., Biederman, L., Brudvig, L.A., Cadotte, M., Daleo, P., Eskelinen, A., Firn, J., Harpole, W.S., Hautier, Y., Kirkman, K.P., Komatsu, K.J., Laungani, R., MacDougall, A., McCulley, R.L., Moore, J.L., Morgan, J.W., Mortensen, B., Ochoa Hueso, R., Ohlert, T., Power, S.A., Price, J., Risch, A.C., Schuetz, M., Shoemaker, L., Stevens, C., Strauss, A.T., Tognetti, P.M., Virtanen, R., Borer, E.T., Wilfahrt, P.A., Asmus, A.L., Seabloom, E.W., Henning, J.A., Adler, P., Arnillas, C.A., Bakker, J.D., Biederman, L., Brudvig, L.A., Cadotte, M., Daleo, P., Eskelinen, A., Firn, J., Harpole, W.S., Hautier, Y., Kirkman, K.P., Komatsu, K.J., Laungani, R., MacDougall, A., McCulley, R.L., Moore, J.L., Morgan, J.W., Mortensen, B., Ochoa Hueso, R., Ohlert, T., Power, S.A., Price, J., Risch, A.C., Schuetz, M., Shoemaker, L., Stevens, C., Strauss, A.T., Tognetti, P.M., Virtanen, R., and Borer, E.T.

Abstract

Spatial rarity is often used to predict extinction risk, but rarity can also occur temporally. Perhaps more relevant in the context of global change is whether a species is core to a community (persistent) or transient (intermittently present), with transient species often susceptible to human activities that reduce niche space. Using 5–12 yr of data on 1,447 plant species from 49 grasslands on five continents, we show that local abundance and species persistence under ambient conditions are both effective predictors of local extinction risk following experimental exclusion of grazers or addition of nutrients; persistence was a more powerful predictor than local abundance. While perturbations increased the risk of exclusion for low persistence and abundance species, transient but abundant species were also highly likely to be excluded from a perturbed plot relative to ambient conditions. Moreover, low persistence and low abundance species that were not excluded from perturbed plots tended to have a modest increase in abundance following perturbance. Last, even core species with high abundances had large decreases in persistence and increased losses in perturbed plots, threatening the long-term stability of these grasslands. Our results demonstrate that expanding the concept of rarity to include temporal dynamics, in addition to local abundance, more effectively predicts extinction risk in response to environmental change than either rarity axis predicts alone.

Published
2021

22. Temporal rarity is a better predictor of local extinction risk than spatial rarity

Author

Wilfahrt, P. A. (Peter A.), Asmus, A. L. (Ashley L.), Seabloom, E. W. (Eric W.), Henning, J. A. (Jeremiah A.), Adler, P. (Peter), Arnillas, C. A. (Carlos A.), Bakker, J. D. (Jonathan D.), Biederman, L. (Lori), Brudvig, L. A. (Lars A.), Cadotte, M. (Marc), Daleo, P. (Pedro), Eskelinen, A. (Anu), Firn, J. (Jennifer), Harpole, W. S. (W. Stanley), Hautier, Y. (Yann), Kirkman, K. P. (Kevin P.), Komatsu, K. J. (Kimberly J.), Laungani, R. (Ramesh), MacDougall, A. (Andrew), McCulley, R. L. (Rebecca L.), Moore, J. L. (Joslin L.), Morgan, J. W. (John W.), Mortensen, B. (Brent), Hueso, R. O. (Raul Ochoa), Ohlert, T. (Timothy), Power, S. A. (Sally A.), Price, J. (Jodi), Risch, A. C. (Anita C.), Schuetz, M. (Martin), Shoemaker, L. (Lauren), Stevens, C. (Carly), Strauss, A. T. (Alexander T.), Tognetti, P. M. (Pedro M.), Virtanen, R. (Risto), Borer, E. T. (Elizabeth T.), Wilfahrt, P. A. (Peter A.), Asmus, A. L. (Ashley L.), Seabloom, E. W. (Eric W.), Henning, J. A. (Jeremiah A.), Adler, P. (Peter), Arnillas, C. A. (Carlos A.), Bakker, J. D. (Jonathan D.), Biederman, L. (Lori), Brudvig, L. A. (Lars A.), Cadotte, M. (Marc), Daleo, P. (Pedro), Eskelinen, A. (Anu), Firn, J. (Jennifer), Harpole, W. S. (W. Stanley), Hautier, Y. (Yann), Kirkman, K. P. (Kevin P.), Komatsu, K. J. (Kimberly J.), Laungani, R. (Ramesh), MacDougall, A. (Andrew), McCulley, R. L. (Rebecca L.), Moore, J. L. (Joslin L.), Morgan, J. W. (John W.), Mortensen, B. (Brent), Hueso, R. O. (Raul Ochoa), Ohlert, T. (Timothy), Power, S. A. (Sally A.), Price, J. (Jodi), Risch, A. C. (Anita C.), Schuetz, M. (Martin), Shoemaker, L. (Lauren), Stevens, C. (Carly), Strauss, A. T. (Alexander T.), Tognetti, P. M. (Pedro M.), Virtanen, R. (Risto), and Borer, E. T. (Elizabeth T.)

Abstract

Spatial rarity is often used to predict extinction risk, but rarity can also occur temporally. Perhaps more relevant in the context of global change is whether a species is core to a community (persistent) or transient (intermittently present), with transient species often susceptible to human activities that reduce niche space. Using 5–12 yr of data on 1,447 plant species from 49 grasslands on five continents, we show that local abundance and species persistence under ambient conditions are both effective predictors of local extinction risk following experimental exclusion of grazers or addition of nutrients; persistence was a more powerful predictor than local abundance. While perturbations increased the risk of exclusion for low persistence and abundance species, transient but abundant species were also highly likely to be excluded from a perturbed plot relative to ambient conditions. Moreover, low persistence and low abundance species that were not excluded from perturbed plots tended to have a modest increase in abundance following perturbance. Last, even core species with high abundances had large decreases in persistence and increased losses in perturbed plots, threatening the long-term stability of these grasslands. Our results demonstrate that expanding the concept of rarity to include temporal dynamics, in addition to local abundance, more effectively predicts extinction risk in response to environmental change than either rarity axis predicts alone.

Published
2021

29. Nutrient availability controls the impact of mammalian herbivores on soil carbon and nitrogen pools in grasslands

Author

Sitters, J., Wubs, E.R.J., Bakker, E.S., Crowther, T.W., Adler, P.B., Bagchi, S., Bakker, J.D., Biederman, L., Borer, E.T., Cleland, E.E., Eisenhauer, N., Firn, J., Gherardi, L., Hagenah, N., Hautier, Y., Hobbie, S.E., Knops, J.M.H., MacDougall, A.S., McCulley, R.L., Moore, J.L., Mortensen, B., Peri, P.L., Prober, S.M., Riggs, C., Risch, A.C., Schütz, M., Seabloom, E.W., Siebert, J., Stevens, C.J., Veen, G.F., Sitters, J., Wubs, E.R.J., Bakker, E.S., Crowther, T.W., Adler, P.B., Bagchi, S., Bakker, J.D., Biederman, L., Borer, E.T., Cleland, E.E., Eisenhauer, N., Firn, J., Gherardi, L., Hagenah, N., Hautier, Y., Hobbie, S.E., Knops, J.M.H., MacDougall, A.S., McCulley, R.L., Moore, J.L., Mortensen, B., Peri, P.L., Prober, S.M., Riggs, C., Risch, A.C., Schütz, M., Seabloom, E.W., Siebert, J., Stevens, C.J., and Veen, G.F.

Abstract

Grasslands are subject to considerable alteration due to human activities globally, including widespread changes in populations and composition of large mammalian herbivores and elevated supply of nutrients. Grassland soils remain important reservoirs of carbon (C) and nitrogen (N). Herbivores may affect both C and N pools and these changes likely interact with increases in soil nutrient availability. Given the scale of grassland soil fluxes, such changes can have striking consequences for atmospheric C concentrations and the climate. Here, we use the Nutrient Network experiment to examine the responses of soil C and N pools to mammalian herbivore exclusion across 22 grasslands, under ambient and elevated nutrient availabilities (fertilized with NPK + micronutrients). We show that the impact of herbivore exclusion on soil C and N pools depends on fertilization. Under ambient nutrient conditions, we observed no effect of herbivore exclusion, but under elevated nutrient supply, pools are smaller upon herbivore exclusion. The highest mean soil C and N pools were found in grazed and fertilized plots. The decrease in soil C and N upon herbivore exclusion in combination with fertilization correlated with a decrease in aboveground plant biomass and microbial activity, indicating a reduced storage of organic matter and microbial residues as soil C and N. The response of soil C and N pools to herbivore exclusion was contingent on temperature – herbivores likely cause losses of C and N in colder sites and increases in warmer sites. Additionally, grasslands that contain mammalian herbivores have the potential to sequester more N under increased temperature variability and nutrient enrichment than ungrazed grasslands. Our study highlights the importance of conserving mammalian herbivore populations in grasslands worldwide. We need to incorporate local-scale herbivory, and its interaction with nutrient enrichment and climate, within global-scale models to better predict land–atm

Published
2020

30. Nutrients cause grassland biomass to outpace herbivory

Author

Borer, E. T. (E. T.), Harpole, W. S. (W. S.), Adler, P. B. (P. B.), Arnillas, C. A. (C. A.), Bugalho, M. N. (M. N.), Cadotte, M. W. (M. W.), Caldeira, M. C. (M. C.), Campana, S. (S.), Dickman, C. R. (C. R.), Dickson, T. L. (T. L.), Donohue, I. (I.), Eskelinen, A. (A.), Firn, J. L. (J. L.), Graff, P. (P.), Gruner, D. S. (D. S.), Heckman, R. W. (R. W.), Koltz, A. M. (A. M.), Komatsu, K. J. (K. J.), Lannes, L. S. (L. S.), MacDougall, A. S. (A. S.), Martina, J. P. (J. P.), Moore, J. L. (J. L.), Mortensen, B. (B.), Ochoa-Hueso, R. (R.), Venterink, H. O. (H. Olde), Power, S. A. (S. A.), Price, J. N. (J. N.), Risch, A. C. (A. C.), Sankaran, M. (M.), Schuetz, M. (M.), Sitters, J. (J.), Stevens, C. J. (C. J.), Virtanen, R. (R.), Wilfahrt, P. A. (P. A.), Seabloom, E. W. (E. W.), Borer, E. T. (E. T.), Harpole, W. S. (W. S.), Adler, P. B. (P. B.), Arnillas, C. A. (C. A.), Bugalho, M. N. (M. N.), Cadotte, M. W. (M. W.), Caldeira, M. C. (M. C.), Campana, S. (S.), Dickman, C. R. (C. R.), Dickson, T. L. (T. L.), Donohue, I. (I.), Eskelinen, A. (A.), Firn, J. L. (J. L.), Graff, P. (P.), Gruner, D. S. (D. S.), Heckman, R. W. (R. W.), Koltz, A. M. (A. M.), Komatsu, K. J. (K. J.), Lannes, L. S. (L. S.), MacDougall, A. S. (A. S.), Martina, J. P. (J. P.), Moore, J. L. (J. L.), Mortensen, B. (B.), Ochoa-Hueso, R. (R.), Venterink, H. O. (H. Olde), Power, S. A. (S. A.), Price, J. N. (J. N.), Risch, A. C. (A. C.), Sankaran, M. (M.), Schuetz, M. (M.), Sitters, J. (J.), Stevens, C. J. (C. J.), Virtanen, R. (R.), Wilfahrt, P. A. (P. A.), and Seabloom, E. W. (E. W.)

Abstract

Human activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass stimulated by nutrient inputs (‘consumer-controlled’). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food (‘resource-controlled’). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk.

Published
2020

31. Climate and local environment structure asynchrony and the stability of primary production in grasslands

Author

Gilbert, B., MacDougall, A.S., Kadoya, T., Akasaka, M., Bennett, J.R., Lind, E.M., Flores-Moreno, H., Firn, J., Hautier, Y., Borer, E.T., Seabloom, E.W., Adler, P.B., Cleland, E.E., Grace, J.B., Harpole, William Stanley, Esch, E.H., Moore, J.L., Knops, J., McCulley, R., Mortensen, B., Bakker, J., Fay, P.A., Gilbert, B., MacDougall, A.S., Kadoya, T., Akasaka, M., Bennett, J.R., Lind, E.M., Flores-Moreno, H., Firn, J., Hautier, Y., Borer, E.T., Seabloom, E.W., Adler, P.B., Cleland, E.E., Grace, J.B., Harpole, William Stanley, Esch, E.H., Moore, J.L., Knops, J., McCulley, R., Mortensen, B., Bakker, J., and Fay, P.A.

Abstract

Aim Climate variability threatens to destabilize production in many ecosystems. Asynchronous species dynamics may buffer against such variability when a decrease in performance by some species is offset by an increase in performance of others. However, high climatic variability can eliminate species through stochastic extinctions or cause similar stress responses among species that reduce buffering. Local conditions, such as soil nutrients, can also alter production stability directly or by influencing asynchrony. We test these hypotheses using a globally distributed sampling experiment. Location Grasslands in North America, Europe and Australia. Time period Annual surveys over 5 year intervals occurring between 2007 and 2014. Major taxa studied Herbaceous plants. Methods We sampled annually the per species cover and aboveground community biomass [net primary productivity (NPP)], plus soil chemical properties, in 29 grasslands. We tested how soil conditions, combined with variability in precipitation and temperature, affect species richness, asynchrony and temporal stability of primary productivity. We used bivariate relationships and structural equation modelling to examine proximate and ultimate relationships. Results Climate variability strongly predicted asynchrony, whereas NPP stability was more related to soil conditions. Species richness was structured by both climate variability and soils and, in turn, increased asynchrony. Variability in temperature and precipitation caused a unimodal asynchrony response, with asynchrony being lowest at low and high climate variability. Climate impacted stability indirectly, through its effect on asynchrony, with stability increasing at higher asynchrony owing to lower inter‐annual variability in NPP. Soil conditions had no detectable effect on asynchrony but increased stability by increasing the mean NPP, especially when soil organic matter was high. Main conclusions We found globally consistent evidence that clim

Published
2020

32. Nutrients cause grassland biomass to outpace herbivory

Author

Borer, E.T., Harpole, William Stanley, Adler, P.B., Arnillas, C.A., Bugalho, M.N., Cadotte, M.W., Caldeira, M.C., Campana, S., Dickman, C.R., Dickson, T.L., Donohue, I., Eskelinen, Anu Maria, Firn, J.L., Graff, P., Gruner, D.S., Heckman, R.W., Koltz, A.M., Komatsu, K.J., Lannes, L.S., MacDougall, A.S., Martina, J.P., Moore, J.L., Mortensen, B., Ochoa-Hueso, R., Venterink, H.O., Power, S.A., Price, J.N., Risch, A.C., Sankaran, M., Schütz, M., Sitters, J., Stevens, C.J., Virtanen, R., Wilfahrt, P.A., Seabloom, E.A., Borer, E.T., Harpole, William Stanley, Adler, P.B., Arnillas, C.A., Bugalho, M.N., Cadotte, M.W., Caldeira, M.C., Campana, S., Dickman, C.R., Dickson, T.L., Donohue, I., Eskelinen, Anu Maria, Firn, J.L., Graff, P., Gruner, D.S., Heckman, R.W., Koltz, A.M., Komatsu, K.J., Lannes, L.S., MacDougall, A.S., Martina, J.P., Moore, J.L., Mortensen, B., Ochoa-Hueso, R., Venterink, H.O., Power, S.A., Price, J.N., Risch, A.C., Sankaran, M., Schütz, M., Sitters, J., Stevens, C.J., Virtanen, R., Wilfahrt, P.A., and Seabloom, E.A.

Abstract

Human activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass stimulated by nutrient inputs (‘consumer-controlled’). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food (‘resource-controlled’). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk.

Published
2020

33. An epidemiologic investigation of a rubella outbreak among the Amish of northeastern Ohio

Author

Jackson, Benita M., Payton, Tony, Horst, George, Halpin, Thomas J., and Mortensen, B. Kim

Subjects
Amish -- Diseases, Rubella -- Demographic aspects, Prevalence studies (Epidemiology) -- Evaluation
Abstract

The people of the amish sect are direct descendants of the 16th century Swiss Anabaptists who migrated to the United States in the early 1700s to escape religious persecution. Although […]

Published
1993

37. Childhood injury mortality in Ohio, 1979 to 1986: setting priorities for prevention

Author

Hopkins, Richard S., Writer, James V., Mortensen, B. Kim, and Indian, Robert W.

Subjects
Ohio -- Health aspects, Children -- Injuries, Death -- Causes of, Mortality -- Ohio, Children -- Patient outcomes, Family and marriage, Health
Abstract

In Ohio, injury deaths of children from 1 to 16 years of age account for six percent of all years of life lost before age 65. A study was conducted in this state which assessed the types of injuries that have led to death, excess deaths by age group, injury type, and population group. The population groups surveyed were metropolitan white, metropolitan non-white, and nonmetropolitan. The age groups studied were 1 to 5, 6 to 11, and 12 to 16. Overall, the leading cause of fatal injuries was motor vehicle crashes. Fire was the leading cause of death in metropolitan nonwhite boys and girls, and in nonmetropolitan white girls. Fire and homicide was a leading cause among metropolitan nonwhite boys. By age group, the major cause of death was fire (ages 1 to 5); pedestrian vehicular accidents (ages 6 to 11); and motor vehicle crashes (ages 12 to 16). For nonmetropolitan children, drowning was the leading cause of death for boys; motor vehicle occupant injuries was the major cause of death for girls; fire was the next most frequent cause of death for both sexes. This data is useful in developing prevention programs. Top priorities for prevention efforts are motor vehicle deaths in 12 to 16-year-old children, both metropolitan and nonmetropolitan; prevention of fire deaths in metropolitan nonwhite children in the 1 to 11 age group; and drowning deaths in the 12 to 16-year-old group of all population categories. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

42. Increased burden of comorbidities and risk of cardiovascular death in atrial fibrillation patients in Europe over ten years: A comparison between EORP-AF pilot and EHS-AF registries

Author

Proietti, Marco, Laroche, Cécile, Nieuwlaat, Robby, Crijns, Harry J.G.M., Maggioni, Aldo P., Lane, Deidre A., Boriani, Guiseppe, Lip, Gregory Y.H., Hellum, C. Fragtrup, Mortensen, B., Joensen, A. M., Sørensen, B. Ginnerup, Rasmussen, L. H., Cardiologie, RS: CARIM - R2.01 - Clinical atrial fibrillation, and MUMC+: MA Cardiologie (9)

Subjects
Male, PROGNOSIS, Epidemiology, Comorbidity, 030204 cardiovascular system & hematology, DISEASE, 0302 clinical medicine, Older patients, Risk Factors, Surveys and Questionnaires, Atrial Fibrillation, Medicine, 030212 general & internal medicine, Prospective Studies, Registries, Societies, Medical, Atrial fibrillation, Middle Aged, Thromboembolic risk, Europe, Female, STROKE, medicine.medical_specialty, HEART SURVEY, MEMBER COUNTRIES, Lower risk, Cardiovascular death, EVENTS, 03 medical and health sciences, Internal medicine, Thromboembolism, Internal Medicine, MANAGEMENT, Humans, Mortality, Propensity Score, Aged, business.industry, Anticoagulants, medicine.disease, Survival Analysis, Propensity score matching, GENERAL REGISTRY, Multivariate Analysis, business, FOLLOW-UP
Abstract

Background: In 2002, the European Society of Cardiology conducted the Euro Heart Survey (EHS), while in 2014concluded 1-year follow-up of the EURObservational Research Programme AF (EORP-AF) Pilot Registry. Methods: We analysed differences in clinical profiles, therapeutic approaches and outcomes between these two cohorts after propensity score matching (PSM). Results: After PSM, 5206 patients were analysed. In EORP-AF there were more elderly patients than EHS (p

Published
2018
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43. Spatial heterogeneity in species composition constrains plant community responses to herbivory and fertilisation

Author

Hodapp, D., Borer, E.T., Harpole, William Stanley, Lind, E.M., Seabloom, E.W., Adler, P.B., Alberti, J., Arnillas, C.A., Bakker, J.D., Biederman, L., Cadotte, M., Cleland, E.E., Collins, S., Fay, P.A., Firn, J., Hagenah, N., Hautier, Y., Iribarne, O., Knops, J.M.H., McCulley, R.L., MacDougall, A., Moore, J.L., Morgan, J.W., Mortensen, B., La Pierre, K.J., Risch, A.C., Schütz, M., Peri, P., Stevens, C.J., Wright, J., Hillebrand, H., Hodapp, D., Borer, E.T., Harpole, William Stanley, Lind, E.M., Seabloom, E.W., Adler, P.B., Alberti, J., Arnillas, C.A., Bakker, J.D., Biederman, L., Cadotte, M., Cleland, E.E., Collins, S., Fay, P.A., Firn, J., Hagenah, N., Hautier, Y., Iribarne, O., Knops, J.M.H., McCulley, R.L., MacDougall, A., Moore, J.L., Morgan, J.W., Mortensen, B., La Pierre, K.J., Risch, A.C., Schütz, M., Peri, P., Stevens, C.J., Wright, J., and Hillebrand, H.

Abstract

Environmental change can result in substantial shifts in community composition. The associated immigration and extinction events are likely constrained by the spatial distribution of species. Still, studies on environmental change typically quantify biotic responses at single spatial (time series within a single plot) or temporal (spatial beta diversity at single time points) scales, ignoring their potential interdependence. Here, we use data from a global network of grassland experiments to determine how turnover responses to two major forms of environmental change – fertilisation and herbivore loss – are affected by species pool size and spatial compositional heterogeneity. Fertilisation led to higher rates of local extinction, whereas turnover in herbivore exclusion plots was driven by species replacement. Overall, sites with more spatially heterogeneous composition showed significantly higher rates of annual turnover, independent of species pool size and treatment. Taking into account spatial biodiversity aspects will therefore improve our understanding of consequences of global and anthropogenic change on community dynamics.

Published
2018

45. Cleavage of the urokinase receptor (uPAR) on oral cancer cells:regulation by transforming growth factor – β1 (TGF-β1) and potential effects on migration and invasion

Author

Magnussen, S. N. (Synnove Norvoll), Hadler-Olsen, E. (Elin), Costea, D. E. (Daniela Elena), Berg, E. (Eli), Jacobsen, C. C. (Cristiane Cavalcanti), Mortensen, B. (Bente), Salo, T. (Tuula), Martinez-Zubiaurre, I. (Inigo), Winberg, J.-O. (Jan-Olof), Uhlin-Hansen, L. (Lars), and Svineng, G. (Gunbjorg)

Subjects
Plasmin, Plasminogen, biological factors, Urokinase plasminogen activator receptor (uPAR), Transforming growth factor-beta1 (TGF-β1), enzymes and coenzymes (carbohydrates), Invasion, Cell migration, biological phenomena, cell phenomena, and immunity, Urokinase, Urokinase receptor, skin and connective tissue diseases, neoplasms, Cancer
Abstract

Background: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion. The aim of the current study was to analyse tumour associated factors and their effect on uPAR cleavage, and the potential implications for cell proliferation, migration and invasion. Methods: Mouse uPAR was stably overexpressed in the mouse OSCC cell line AT84. The ratio of full-length versus cleaved uPAR as analysed by Western blotting and its regulation was assessed by addition of different protease inhibitors and transforming growth factor — β1 (TGF-β1). The role of uPAR cleavage in cell proliferation and migration was analysed using real-time cell analysis and invasion was assessed using the myoma invasion model. Results: We found that when uPAR was overexpressed a proportion of the receptor was cleaved, thus the cells presented both full-length uPAR and uPAR (II-III). Cleavage was mainly performed by serine proteases and urokinase plasminogen activator (uPA) in particular. When the OSCC cells were stimulated with TGF-β1, the production of the uPA inhibitor PAI-1 was increased, resulting in a reduction of uPAR cleavage. By inhibiting cleavage of uPAR, cell migration was reduced, and by inhibiting uPA activity, invasion was reduced. We could also show that medium containing soluble uPAR (suPAR), and cleaved soluble uPAR (suPAR (II-III)), induced migration in OSCC cells with low endogenous levels of uPAR. Conclusions: These results show that soluble factors in the tumour microenvironment, such as TGF-β1, PAI-1 and uPA, can influence the ratio of full length and uPAR (II-III) and thereby potentially effect cell migration and invasion. Resolving how uPAR cleavage is controlled is therefore vital for understanding how OSCC progresses and potentially provides new targets for therapy.

Published
2017

46. The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus

Author

Kaur, S., Mirza, A. H., Brorsson, C. A., Fløyel, T., Størling, J., Mortensen, H. B., Pociot, F., Aanstoot, H.-J., De Beaufort, Carine, Cameron, F., Castano, L., Dorchy, H., Fisher, L., Kaprio, E., Lange, K., Neu, A., Njolstad, P. R., Phillip, M., Urukami, T., Barrett, T., Chiarelli, F., Danne, T., Hoey, H., Kocova, M., Mortensen, B., Schoenle, J., Swift, G. F., Vanelli, M., Åman, J., and Robert, J.J.

Subjects
Beta cell, endocrine system, Type 1 diabetes, endocrine system diseases, B lymphocyte, Multidisciplinaire, généralités & autres [D99] [Sciences de la santé humaine], Apoptosis, CTCF, LncRNAs, ERBB3, ERBB3 gene, Article, Multidisciplinary, general & others [D99] [Human health sciences]
Abstract

The study aimed to explore the role of ERBB3 in type 1 diabetes (T1D). We examined whether genetic variation of ERBB3 (rs2292239) affects residual β-cell function in T1D cases. Furthermore, we examined the expression of ERBB3 in human islets, the effect of ERBB3 knockdown on apoptosis in insulin-producing INS-1E cells and the genetic and regulatory architecture of the ERBB3 locus to provide insights to how rs2292239 may confer disease susceptibility. rs2292239 strongly correlated with residual β-cell function and metabolic control in children with T1D. ERBB3 locus associated lncRNA (NONHSAG011351) was found to be expressed in human islets. ERBB3 was expressed and down-regulated by pro-inflammatory cytokines in human islets and INS-1E cells; knockdown of ERBB3 in INS-1E cells decreased basal and cytokine-induced apoptosis. Our data suggests an important functional role of ERBB3 and its potential regulators in the β-cells and may constitute novel targets to prevent β-cell destruction in T1D. © 2015 Elsevier Ireland Ltd.

Published
2016

47. Herbivores safeguard plant diversity by reducing variability in dominance

Author

Mortensen, B., Danielson, B., Harpole, William Stanley, Alberti, J., Arnillas, C.A., Biederman, L., Borer, E.T., Cadotte, M.W., Dwyer, J.M., Hagenah, N., Hautier, Y., Peri, P.L., Seabloom, E.W., Mortensen, B., Danielson, B., Harpole, William Stanley, Alberti, J., Arnillas, C.A., Biederman, L., Borer, E.T., Cadotte, M.W., Dwyer, J.M., Hagenah, N., Hautier, Y., Peri, P.L., and Seabloom, E.W.

Abstract

Reductions in community evenness can lead to local extinctions as dominant species exclude subordinate species; however, herbivores can prevent competitive exclusion by consuming otherwise dominant plant species, thus increasing evenness. While these predictions logically result from chronic, gradual reductions in evenness, rapid, temporary pulses of dominance may also reduce species richness. Short pulses of dominance can occur as biotic or abiotic conditions temporarily favour one or a few species, manifested as increased temporal variability (the inverse of temporal stability) in community evenness. Here, we tested whether consumers help maintain plant diversity by reducing the temporal variability in community evenness.We tested our hypothesis by reducing herbivore abundance in a detailed study of a developing, tallgrass prairie restoration. To assess the broader implications of the importance of herbivory on community evenness as well as potential mechanisms, we paired this study with a global herbivore reduction experiment.We found that herbivores maintained plant richness in a tallgrass prairie restoration by limiting temporary pulses in dominance by a single species. Dominance by an annual species in a single year was negatively associated with species richness, suggesting that short pulses of dominance may be sufficient to exclude subordinate species.The generality of this site-level relationship was supported by the global experiment in which inter-annual variability in evenness declined in the presence of vertebrate herbivores over timeframes ranging in length from 2 to 5 years, preventing declines in species richness. Furthermore, inter-annual variability of community evenness was also negatively associated with pre-treatment species richness.Synthesis. A loss or reduction of herbivores can destabilize plant communities by allowing brief periods of dominance by one or a few species, potentially triggering a feedback cycle of dominance and extinc

Published
2017

48. Vorapaxar in the secondary prevention of atherothrombotic events

Author

Braunwald E, Morrow DA, Scirica BM, Bonaca MP, McCabe CH, Morin S, Fish P, Lamp J, Gershman E, Murphy S, Deenadayalu N, Skene A, Hill K, Bennett L, Strony J, Plat F, Berman G, Lipka L, Kilian A, He W, Liu X, Fox KA, Aylward P, Bassand JP, Betriu A, Bounameaux H, Corbalan R, Creager M, Dalby A, De Ferrari G, Dellborg M, Diehm CH, Dietz R, Goto S, Grande P, Gurbel P, Hankey G, Isaza D, Jensen P, Kiss R, Lewis B, Merlini P, Moliterno D, Morais J, Nicolau JC, Nieminen M, Nilsen D, Olin J, Ophuis TO, Paolasso E, Pichler M, Shinohara Y, Spinar J, Teal P, Tendera M, Theroux P, Thomassen L, Van de Werf F, White H, Wilcox R, Alberts M, Ameriso S, Diener H, Mohr J, Welch M, Wiviott SD, Awtry E, Berger C, Desai A, Gelfand E, Ho C, Leeman D, Link M, Norden A, Pande A, Rost N, Ruberg R, Silverman S, Singhal A, Vita J, Frye RL, Bailey KR, Easton J, Hochman J, Steg PG, Verheught F, Lee K, Mauro DO, Centurion A, Carlevaro O, Cardozo E, Cartasegna L, Soccini N, Farras HA, Molina Aguirre E, Duronto E, Arrechavala L, Rey R, Stilman A, Fernández H, Marinsalta G, Tartaglione J, Chekherdemian M, Povedano G, Casares E, Kantor P, Reges P, Cuneo C, Martinez G, MacKinnon I, Bagnato B, Fernandez A, Funosas C, Lozada A, Barilati P, Ferrari J, Ferrari N, Llanos J, Casaccia G, Giannaula R, García Méndez C, Cirio J, García Dávila C, Estol C, Chiezzo D, Ramirez J, Garrido S, López M, Hominal M, Bianchini MV, Ramos M, Verdini E, Herrera G, Monne H, Ioli P, Samudio MA, Rotta Escalante R, Tarulla A, Reich E, Perez G, Milesi R, Berli M, Marino J, Funes I, Prado A, Bezi M, Fernandez R, Rojas M, Cimbaro Canella JP, Galarza Salazan M, Chew D, Horsfall L, Claxton A, French J, O'Brien K, Nelson G, Loxton A, McCann A, Downey C, Aroney C, Cleave P, Worthley S, Roach A, Amerena J, Long A, Thompson P, Ferguson L, Fitzpatrick M, Mackenzie M, Youssef G, Goldsmith H, Jayasinghe R, Quinlan S, Arstall M, Rose J, Counsell J, Martin M, Crimmins D, Slattery A, Anderson C, Paraskevaidis T, Davis S, Silver G, Gerraty RP, Gapper J, Donnan G, Petrolo S, Whelan A, Tulloch G, Singh B, Campo Ma, Dick R, Savage C, Hill A, Conway B, Waites J, Keays P, Kopp K, Hainzer D, Podczeck Schweighofer A, Priesnitz T, Drexel H, Hagspiel V, Foeger B, Hilbe C, Trinka E, Sinadinoska D, Pilger E, Brodmann M, Stöllberger C, Jungbauer LV, Koppensteiner R, Hoke M, Grisold W, Berger O, Gaul GB, Fazekas N, Wandaller C, Stockenhuber F, Rek A, Willeit J, Zangerle A, Kiechl S, Sturm W, Theurl M, Gruber F, Schacherl S, Auer J, Primus C, Eber B, Ammer M, Hofer JF, Mayr H, Moser S, Hoellmueller I, Van der Werf F, Motte S, Jorion M, Schroë H, Zwinnen W, Vermassen F, Geenens M, De Wolf L, Briké C, De Deyn P, Ongena P, De Klippel N, Meeuwissen K, Desfontaines P, Tincani G, Vandermeeren Y, de Fays K, Pandolfo M, Alaerts N, Peeters A, Findik A, Tack P, deGrande E, Thijs V, Marcelis E, Van Landegem W, Vanhagendoren S, Vanhooren G, Schotte V, Celen H, Bes N, De Letter J, Holvoet G, Claerbout B, Verhamme P, Debaveye B, Bourgeois P, Debrabandere K, Stalpaert S, Dhondt E, De Maeseneire S, De Bleecker J, de Koning K, Vincent M, Tahon S, Monté C, Maes J, Vossaert R, Vandenhoven C, Roosen J, Vissers C, Sinnaeve P, de Velder L, Thoeng J, Cauwenberghs J, Deceuninck F, Nicolau J, Ardito WR, Queirantes C, de Araujo Filho JD, Queirantes CS, Ribeiro JP, Guizzardi SP, Chaves ML, Titton NF, Pereira AH, Webber I, da Silva DG Jr, Uehara RM, Brasileiro J, Maia LN, Souza A, Bodanese LC, Homem R, Friedrich MA, Macagnan AP, Dutra OP, Brum AB, Rossi PR, Herek L, Feitosa GS, Bernardes Ade S, Braga J, Rodrigues D, Guimarães A, Teixeira AB, Marin Neto JA, Tonani M, Piegas LS, Amato V, Leães P, Osorio RL, Ganem F, Vieira AP, Leao P, Kanashiro V, Franken RA, Martins EP, Gagliardi RJ, Silva L, Caffaro RA, Novaes GS, Carvalho A, Laet VL, Miranda F. Jr, Crippa BA, Saraiva JF, Ormundo CT, Speciali JG, Guandolini G, de Albuquerque DC, Silva V, Abrantes JA, Pinheiro L, Teixeira MS, Guanaes DF, Resende ES, Andrade SF, Alves ÁR Jr, Oliveira OM, Tauil CB, Araujo E, de Souza J, de Freitas GR, Horokosky AP, Barbosa EC, Muniz P, de Moraes JB Jr, Cabral M, Faria Neto JR, Belemer A, Paiva MS, Brito A, Hernandes ME, Amorim R, Pittella FJ, Brito HH, Kouz S, Roy M, Gosselin G, David M, Huynh T, Boudreault C, Heath J, Scott L, Bhargava R, Stafford C, Klinke WP, Martin L, Chan YK, Zaniol D, Rebane T, Abramovich M, Vizel S, Fox B, Kornder J, Breakwell L, Constance C, Gauthier M, Cleveland D, Valley S, Dion D, Morissette A, Vertes G, Ross B, Pandey AS, Byrne M, Abramson B, Sodhi N, Ervin F, Thiessen S, Halperin F, Stedham V, Pesant Y, Sardin V, Saw J, Tarry L, Pouliot J, Marquette S, Belisle P, Gagne D, Ducas J, Munoz A, Sussex B, Newman S, Madan M, Hsu E, Bata I, Cossett J, Glanz A, Vilag C, Paddock V, Collings E, Sabbah E, Chausse I, Fortin C, Lepage C, Chehayeb R, Viau C, Ma P, Seib M, Lamy A, Rizzo A, Rajakumar AR, Eikel L, Nigro F, Stoger S, Welsh R, Lindholm L, Parker JD, Webber S, Winkler L, Hannah G, Gupta M, Kubiak A, Mukherjee A, Bozek B, Nguyen M, Dufort L, Haichin R, Toyota V, Bujold S, Syan G, Chinnasane S, Houde G, Rousseau S, Poirier P, Lariviere M, Dupuis R, Ouimet F, Audet J, Darveau C, Labonte R, Rice T, Nawaz S, Cantor W, Robbins K, Boucher P. 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Pires, R, Bura Riviere, A, Pelvet, B, Giroud, M, Lecheneaut, C, Ohlmann, P, Ait m., bark Z, Farah, B, Petit, F, Caussin, C, Braun, C, Diehm, C, Mehrhof, F, Inkrot, S, Darius, H, Heinze, H, Radke, P, Kulikowsky, C, Ferrari, M, Utschig, S, Strasser, R, Haacke, K, Felix, Sb, Bruder, M, Nienaber, C, Pfaff, H, Sohn, H, Baylacher, M, Mudra, H, Setzer, P, Konstantinides, S, Hallmann, A, Kreuzer, J, Tsoy, I, Schneider, P, Appel, Kf, Habermeier, A, Zeiher, Am, Kretschmer, T, Mitrovic, V, Lehinant, S, Bohlscheid, V, Palme, B, Heuer, H, Espinola Klein, C, Savvidis, S, Kleinertz, K, Hänel, J, Schmidt, E, Schmidt, A, Ringleb, Pa, Ludwig, I, Dietzold, M, Schaffranka, A, Ranft, J, Cegla, C, Berrouschot, J, Stoll, A, Tanislav, C, Brandtner, Ma, Rosenkranz, M, Otto, D, Görtler, M, Barleben, M, Haberl, R, Miedl, S, Maschke, M, Schröder, K, Aral Becher, B, Herzog Hauff, S, Guenther, A, Herzau, C, Hoffmann, U, Roth Zetzsche, S, Grond, M, Becker, M, Hamann, G, Simon, K, Köhrmann, M, Glahn, J, Wuttig, H, Nabavi, Dg, Seraphin, D, Schellong, S, Frommhold, R, Dichgans, M, Doerr, A, Blessing, E, Buss, I, Butter, C, Bettin, D, Grosch, B, Blank, E, Wong, L, Liu, R, Lee, S, Kong, S, Yu, C, So, E, Jakal, Á, Masszi, G, Czuriga, I, Kapocsi, J, Soós, E, Csiba, L, Fekete, K, Valikovics, A, Dioszeghy, P, Muskóczki, E, Csányi, A, Matoltsy, A, Yuval, R, Bornstein, N, Elimelech, R, Chajek Shaul, T, Bursztyn, M, Hayek, T, Hazbon, K, Gavish, D, Anat, N, Wexler, D, Azar, P, Mosseri, M, Tsirulnikov, E, Rozenman, Y, Logvinenko, S, Tanne, D, Don, A, Gross, B, Feldman, Y, Klainman, E, Genin Dmitrishin, I, Eldar, M, Eizenberg, N, Atar, S, Lasri, E, Hammerman, H, Aharoni, G, Zimlichman, R, Zuker, S, Telman, G, Afanasiev, S, Katz, A, Biton, A, Goldhaber, A, Goldhaber, M, Elian, D, Linor, A, Meyuhas, S, Tsalihin, D, Kissos, D, Lampl, Y, Israelson, M, Gottlieb, S, Dotan, L, Elis, A, Karny, M, Hussein, O, Shestatski, K, Brenner, H, Segal, E, Baldini, U, Gavazzi, A, Poloni, M, Censori, B, Aiazzi, L, Maraglino, C, Marenzi, G, Specchia, G, Tritto, I, Golino, P, Cianflone, Domenico, Martignoni, A, Tamburino, C, Rubartelli, P, Ardissino, D, Tadonio, I, Stramba Badiale, M, Cernuschi, P, Nardulli, R, Sommariva, L, Giordano, A, Berni, A, Cavallini, C, Fiscella, A, Azzarelli, S, Esposito, G, Cassese, S, Danzi, G, Fattore, L, Barbieri, E, De Caterina, R, Odero, A, Puttini, M, Corrada, E, Monzini, N, Vadalà, A, Pistarini, C, Scrutinio, D, Ferratini, M, Marcheselli, S, Moretti, L, Partemi, L, Pupilella, T, Lazzari, A, Ledda, A, Geraci, G, Rasura, M, Beccia, M, Cassadonte, F, Vatrano, M, Bongiorni, D, Mos, L, Marcuzzi, G, Murena, E, Uguccioni, L, Ferretti, C, Piti ATerrosu, P, Perrone, Pf, Marconi, R, Grasso, L, Severi, S, Evola, R, Russo, N, Agnelli, G, Paci, C, Carugo, S, Silvestri, O, Testa, R, and Novo, S.

Abstract

BACKGROUND:Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1.METHODS:We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage.RESULTS:At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P

Published
2012

49. A prospective survey in European Society of Cardiology member countries of atrial fibrillation management:baseline results of EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry

Author

Lip, G. Y. H., Laroche, C., Dan, G. -A., Santini, M., Kalarus, Z., Rasmussen, L. H., Oliveira, M. M., Mairesse, G., Crijns, H. J. G. M., Simantirakis, E., Atar, D., Kirchhof, P., Vardas, P., Tavazzi, L., Maggioni, A. P., Raepers, M., El Husseini, Z., Dilling-Boer, D., Schurmans, J., Vijgen, J., Koopman, P., Huybrechts, W., Dormal, F., Blommaert, D., Deceuninck, O., Xhaet, O., Fragtrup Hellum, C., Mortensen, B., Ginnerup Sorensen, B., Joensen, A. M., Karlsdottir, A., Pehrson, S., Hummelshoj, J., Svenningsen, A-M., Tanggaard, L., Wiggers, P., Nygaard, A., Jonstrup, A., Petersen, J., Odgaard, A., Mortensen, M., Frost, L., Svenstrup Moller, D., Sondergaard, H. M., Christensen, P. D., Xydonas, S., Lioni, L., Dimopoulou, M., Georgiopoulos, G., Papatheodorou, E., Boutas, P., Kartalis, A., Nakou, H., Kanoupakis, E., Tahmatzidis, D., Styliadis, I., Vassilikos, V., Koskinas, K., Fragakis, N., Polymeropoulos, K., Maligos, G., Martignani, C., Diemberger, I., Boriani, G., Frisoni, J., Biffi, M., Ziacchi, M., Cimaglia, P., Fantecchi, E., Boni, S., Gabbai, D., Marchionni, N., Fumagalli, S., Bobbo, M., Ramani, F., Sinagra, G., Vitali-Serdoz, L., Nordio, A., Porto, A., Zecchin, M., Di Nora, C., Novo, S., Guarneri, F. P., Macaione, F., Rod, R., Stodle, R. M. O., Pervez, M. O., Smith, P., Buvarp, M., Ronnevik, P. K., Vold, A., Fuglestved, J., Stenshjemmet, E., Risberg, K., Sokal, A., Kubicius, A., Prochniewicz, E., Pokrywa, K., Rzeuski, R., Weryszko, A., Haberka, M., Gasior, Z., Slowikowski, A., Janion, M., Kolodziej, M., Janion-Sadowska, A., Drozdz, J., Stasiak, M., Jakubowski, P., Ciurus, T., Pawlak, M., Nowakowska, M., Wiklo, K., Kurpesa, M., Olejnik, A., Miarka, J., Streb, W., Zielinski, L., Dluzniewski, M., Tomaszewska-Kiecana, M., Opolski, G., Budnik, M., Kiliszek, M., Gorska, J., Mamcarz, A., Sliz, D., Makowiecki, K., Fuglewicz, A., Drozd, M., Garncarek, M., Musialik-Lydka, A., Markowicz-Pawlus, E., Kazmierczak, G., Leopold-Jadczyk, A., Koziel, M., Sobral, S., Pereira, H., Brandao Alves, L., Ribeiro, L., Miranda, R., Almeida, S., Madeira, F., Faustino, M., Oliveira, R., Gil, V., Braga, C., Martins, J., Rocha, S., Magalhaes, S., Ramos, V., Bernardo, R., Costa, F., Morgado, F., Galvao Santos, P., Almeida, N., Adragao, P., Carmo, P., Mariano Pego, G., Ferreira, J., Elvas, L., Ventura, M., Antonio, N., Ferreira, R., Damasio, A. F., Santos, A. R., Picarra, B., Neves, D., De Jesus, I., Amado, J., Sousa, P., Candeias, R., Lourenco, A., Pereira, A., Canario-Almeida, F., Fernandes, M., Ferreira, F., Machado, I., Quelhas, I., Guardado, J., Pereira, V., Cavaco, D., Lousinha, A., Valente, B., Silva, N., Cunha, P., Pimenta, R., Santos, S., Martins Oliveira, M., Vicente, S., Bernardes, A., Nunes Diogo, A., Rodrigues, E., Frazao Rodrigues De Sousa, J. M., Carpinteiro, L., Satendra, M., Cortez Dias, N., Neto, S., Gama Ribeiro, V., Goncalves, H., Primo, J., Adao, L., Oliveira, M., Costa, A., Delgado, A., Marmelo, B., Moreira, D., Santos, J., Santos, L., Rodrigues, B., Pop Moldovan, A., Darabantiu, D., Todea, B., Pop, C., Dicu, D., Filip, D., Mercea, D., Kozma, G., Schiopu, M., Catanescu, G., Popescu, C., Bobescu, E., Gabor, A., Buzea, A., Dan, A., Buzea Daha, I., Asan, N., Popescu, R., Bartos, D., Badila, E., Tintea, E., Grigore, C., Daraban, A. M., Sandulescu, A., Carp, A., Gherasim, D., Stoian, I. M., Baluta, M. M., Vintila, M. M., Popescu, M. I., Tica, O., Petrescu, L., Alina-Ramona, N., Dan, R., Cozma, D. C., Tutuianu, C., Mangea, M., Goanta, E., Van Opstal, J. M., Van Rennes, R., Mulder, B. A., Said, S. A. M., Folkeringa, R. J., Philippens, S., Blaauw, Y., Aksoy, I., Pluymen, M., Driessen, R., Limantoro, I., Lankveld, T., Mafi Rad, M., Hendriks, J., Van Unen, W. H., Meeder, J., Cardiologie, MUMC+: MA Cardiologie (9), and RS: CARIM - R2 - Cardiac function and failure

Subjects
Male, medicine.medical_specialty, Registry, Digoxin, medicine.medical_treatment, Physician's Practice Patterns, Administration, Oral, Pilot Projects, Comorbidity, Antiarrhythmic agent, Amiodarone, Anticoagulation, Fibrinolytic Agents, Atrial fibrillation, Risk scores, Risk Factors, Physiology (medical), Internal medicine, Antithrombotic, Atrial Fibrillation, medicine, Prevalence, Humans, Registries, Practice Patterns, Physicians', business.industry, Anticoagulants, Thrombosis, medicine.disease, Causality, Europe, Treatment Outcome, Health Care Surveys, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Anti-Arrhythmia Agents, Fibrinolytic agent, medicine.drug
Abstract

AIMS: Given the advances in atrial fibrillation (AF) management and the availability of new European Society of Cardiology (ESC) guidelines, there is a need for the systematic collection of contemporary data regarding the management and treatment of AF in ESC member countries.METHODS AND RESULTS: We conducted a registry of consecutive in- and outpatients with AF presenting to cardiologists in nine participating ESC countries. All patients with an ECG-documented diagnosis of AF confirmed in the year prior to enrolment were eligible. We enroled a total of 3119 patients from February 2012 to March 2013, with full data on clinical subtype available for 3049 patients (40.4% female; mean age 68.8 years). Common comorbidities were hypertension, coronary disease, and heart failure. Lone AF was present in only 3.9% (122 patients). Asymptomatic AF was common, particularly among those with permanent AF. Amiodarone was the most common antiarrhythmic agent used (∼20%), while beta-blockers and digoxin were the most used rate control drugs. Oral anticoagulants (OACs) were used in 80% overall, most often vitamin K antagonists (71.6%), with novel OACs being used in 8.4%. Other antithrombotics (mostly antiplatelet therapy, especially aspirin) were still used in one-third of the patients, and no antithrombotic treatment in only 4.8%. Oral anticoagulants were used in 56.4% of CHA2DS2-VASc = 0, with 26.3% having no antithrombotic therapy. A high HAS-BLED score was not used to exclude OAC use, but there was a trend towards more aspirin use in the presence of a high HAS-BLED score.CONCLUSION: The EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry has provided systematic collection of contemporary data regarding the management and treatment of AF by cardiologists in ESC member countries. Oral anticoagulant use has increased, but novel OAC use was still low. Compliance with the treatment guidelines for patients with the lowest and higher stroke risk scores remains suboptimal.

Published
2014
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50. Francisella tularensis RipA Protein Topology and Identification of Functional Domains

Author

Mortensen, B. L., Taft-Benz, S., Fuller, J. R., Collins, E. J., and Kawula, T. H.

Abstract

Francisella tularensis is a Gram-negative coccobacillus and is the etiological agent of the disease tularemia. Expression of the cytoplasmic membrane protein RipA is required for Francisella replication within macrophages and other cell types; however, the function of this protein remains unknown. RipA is conserved among all sequenced Francisella species, and RipA-like proteins are present in a number of individual strains of a wide variety of species scattered throughout the prokaryotic kingdom. Cross-linking studies revealed that RipA forms homoligomers. Using a panel of RipA-green fluorescent protein and RipA-PhoA fusion constructs, we determined that RipA has a unique topology within the cytoplasmic membrane, with the N and C termini in the cytoplasm and periplasm, respectively. RipA has two significant cytoplasmic domains, one composed roughly of amino acids 1 to 50 and the second flanked by the second and third transmembrane domains and comprising amino acids 104 to 152. RipA functional domains were identified by measuring the effects of deletion mutations, amino acid substitution mutations, and spontaneously arising intragenic suppressor mutations on intracellular replication, induction of interleukin-1β (IL-1β) secretion by infected macrophages, and oligomer formation. Results from these experiments demonstrated that each of the cytoplasmic domains and specific amino acids within these domains are required for RipA function.

Published
2012
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