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Showing papers by "University of Vermont published in 2012"


Journal ArticleDOI
07 Jun 2012-Nature
TL;DR: The analyses clearly show that the ecosystem consequences of local species loss are as quantitatively significant as the direct effects of several global change stressors that have mobilized major international concern and remediation efforts.
Abstract: Evidence is mounting that extinctions are altering key processes important to the productivity and sustainability of Earth’s ecosystems 1–4 . Further species loss will accelerate change in ecosystem processes 5–8 , but it is unclear how these effects compare to the direct effects of other forms of environmental change that are both driving diversity loss and altering ecosystem function. Here we use a suite of meta-analyses of published data to show that the effects of species loss on productivity and decomposition—two processes important in all ecosystems—are of comparable magnitude to the effects of many other global environmental changes. In experiments, intermediate levels of species loss (21–40%) reduced plant production by 5–10%, comparable to previously documented effects of ultraviolet radiation and climate warming. Higher levels of extinction (41–60%) had effects rivalling those of ozone, acidification, elevated CO2 and nutrient pollution. At intermediate levels, species loss generally had equal or greater effects on decomposition than did elevated CO2 and nitrogen addition. The identity of species lost also had a large effect on changes in productivity and decomposition, generating a wide range of plausible outcomes for extinction. Despite the need for more studies on interactive effects of diversity loss and environmental changes, our analyses clearly show that the ecosystem consequences of local species loss are as quantitatively significant as the direct effects of several global change stressors that have mobilized major international concern and remediation efforts 9 .

1,858 citations


Journal ArticleDOI
TL;DR: In this paper, the authors provide new unconditional variance estimators for classical, individual-based rarefaction and for Coleman Rarefaction under two sampling models: sampling-theoretic predictors for the number of species in a larger sample (multinomial model), a larger area (Poisson model) or a larger number of sampling units (Bernoulli product model), based on an estimate of asymptotic species richness.
Abstract: Aims In ecology and conservation biology, the number of species counted in a biodiversity study is a key metric but is usually a biased underestimate of total species richness because many rare species are not detected. Moreover, comparing species richness among sites or samples is a statistical challenge because the observed number of species is sensitive to the number of individuals counted or the area sampled. For individual-based data, we treat a single, empirical sample of species abundances from an investigator-defined species assemblage or community as a reference point for two estimation objectives under two sampling models: estimating the expected number of species (and its unconditional variance) in a random sample of (i) a smaller number of individuals (multinomial model) or a smaller area sampled (Poisson model) and (ii) a larger number of individuals or a larger area sampled. For sample-based incidence (presence–absence) data, under a Bernoulli product model, we treat a single set of species incidence frequencies as the reference point to estimate richness for smaller and larger numbers of sampling units. Methods The first objective is a problem in interpolation that we address with classical rarefaction (multinomial model) and Coleman rarefaction (Poisson model) for individual-based data and with sample-based rarefaction (Bernoulli product model) for incidence frequencies. The second is a problem in extrapolation that we address with sampling-theoretic predictors for the number of species in a larger sample (multinomial model), a larger area (Poisson model) or a larger number of sampling units (Bernoulli product model), based on an estimate of asymptotic species richness. Although published methods exist for many of these objectives, we bring them together here with some new estimators under a unified statistical and notational framework. This novel integration of mathematically distinct approaches allowed us to link interpolated (rarefaction) curves and extrapolated curves to plot a unified species accumulation curve for empirical examples. We provide new, unconditional variance estimators for classical, individual-based rarefaction and for Coleman rarefaction, long missing from the toolkit of biodiversity measurement. We illustrate these methods with datasets for tropical beetles, tropical trees and tropical ants.

1,445 citations


Journal ArticleDOI
TL;DR: The AABB developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children.
Abstract: Description: Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children Methods: These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds We performed a literature search from 1950 to February 2011 with no language restrictions We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay Recommendation 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence) Recommendation 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence) Recommendation 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence) Recommendation 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence)

994 citations


Journal ArticleDOI
TL;DR: In this article, an emerging Dirac liquid of Lorentz invariant quasi-particles in the weak coupling regime and strongly correlated electronic states in the strong coupling regime is discussed.
Abstract: We review the problem of electron-electron interactions in graphene. Starting from the screening of long range interactions in these systems, we discuss the existence of an emerging Dirac liquid of Lorentz invariant quasi-particles in the weak coupling regime, and strongly correlated electronic states in the strong coupling regime. We also analyze the analogy and connections between the many-body problem and the Coulomb impurity problem. The problem of the magnetic instability and Kondo effect of impurities and/or adatoms in graphene is also discussed in analogy with classical models of many-body effects in ordinary metals. We show that Lorentz invariance plays a fundamental role and leads to effects that span the whole spectrum, from the ultraviolet to the infrared. The effect of an emerging Lorentz invariance is also discussed in the context of finite size and edge effects as well as mesoscopic physics. We also briefly discuss the effects of strong magnetic fields in single layers and review some of the main aspects of the many-body problem in graphene bilayers. In addition to reviewing the fully understood aspects of the many-body problem in graphene, we show that a plethora of interesting issues remain open, both theoretically and experimentally, and that the field of graphene research is still exciting and vibrant.

988 citations


Journal ArticleDOI
13 Jan 2012-Science
TL;DR: A global empirical study relating plant species richness and abiotic factors to multifunctionality in drylands, which collectively cover 41% of Earth’s land surface and support over 38% of the human population, suggests that the preservation of plant biodiversity is crucial to buffer negative effects of climate change and desertification in dryland.
Abstract: Experiments suggest that biodiversity enhances the ability of ecosystems to maintain multiple functions, such as carbon storage, productivity, and the buildup of nutrient pools (multifunctionality). However, the relationship between biodiversity and multifunctionality has never been assessed globally in natural ecosystems. We report here on a global empirical study relating plant species richness and abiotic factors to multifunctionality in drylands, which collectively cover 41% of Earth’s land surface and support over 38% of the human population. Multifunctionality was positively and significantly related to species richness. The best-fitting models accounted for over 55% of the variation in multifunctionality and always included species richness as a predictor variable. Our results suggest that the preservation of plant biodiversity is crucial to buffer negative effects of climate change and desertification in drylands.

941 citations


Journal ArticleDOI
Stephen Kaptoge1, Emanuele Di Angelantonio1, Lisa Pennells1, Angela M. Wood1, Ian R. White2, Pei Gao1, Matthew G. Walker1, Alexander M. W. Cargill Thompson1, Nadeem Sarwar1, Muriel J. Caslake3, Adam S. Butterworth1, Philippe Amouyel4, Gerd Assmann, Stephan J. L. Bakker5, Elizabeth L M Barr6, Elizabeth Barrett-Connor7, Emelia J. Benjamin8, Cecilia Björkelund9, Hermann Brenner10, Eric J. Brunner11, Robert Clarke12, Jackie A. Cooper11, Peter Cremer13, Mary Cushman14, Gilles R. Dagenais, Ralph B. D'Agostino8, Rachel Dankner, George Davey-Smith15, Dorly J. H. Deeg16, Jacqueline M. Dekker16, Gunnar Engström17, Aaron R. Folsom18, F. Gerry R. Fowkes19, John Gallacher20, J. Michael Gaziano21, Simona Giampaoli22, Richard F. Gillum23, Albert Hofman24, Barbara V. Howard25, Erik Ingelsson26, Hiroyasu Iso27, Torben Jørgensen28, Stefan Kiechl29, Akihiko Kitamura, Yutaka Kiyohara30, Wolfgang Koenig31, Daan Kromhout32, Lewis H. Kuller33, Debbie A Lawlor15, Tom W. Meade34, Aulikki Nissinen35, Børge G. Nordestgaard28, Altan Onat36, Demosthenes B. Panagiotakos37, Bruce M. Psaty38, Beatriz L. Rodriguez39, Annika Rosengren9, Veikko Salomaa35, Jussi Kauhanen40, Jukka T. Salonen41, Jonathan A. Shaffer42, Steven Shea42, Ian Ford3, Coen D.A. Stehouwer43, Timo E. Strandberg44, Robert W. Tipping45, Alberto Tosetto, Sylvia Wassertheil-Smoller46, Patrik Wennberg47, Rudi G. J. Westendorp48, Peter H. Whincup49, Lars Wilhelmsen9, Mark Woodward50, Gordon D.O. Lowe3, Nicholas J. Wareham2, Kay-Tee Khaw1, Naveed Sattar3, Chris J. Packard3, Vilmundur Gudnason51, Paul M. Ridker21, Mark B. Pepys11, Simon G. Thompson1, John Danesh1 
TL;DR: It is estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened.
Abstract: Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. Results The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P = 20%) (P = 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. Conclusions In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)

938 citations


Journal ArticleDOI
TL;DR: Differences in risk-factor burden translate into marked differences in the lifetime risk of cardiovascular disease, and these differences are consistent across race and birth cohorts.
Abstract: Background The lifetime risks of cardiovascular disease have not been reported across the age spectrum in black adults and white adults. Methods We conducted a meta-analysis at the individual level using data from 18 cohort studies involving a total of 257,384 black men and women and white men and women whose risk factors for cardiovascular disease were measured at the ages of 45, 55, 65, and 75 years. Blood pressure, cholesterol level, smoking status, and diabetes status were used to stratify participants according to risk factors into five mutually exclusive categories. The remaining lifetime risks of cardiovascular events were estimated for participants in each category at each age, with death free of cardiovascular disease treated as a competing event. Results We observed marked differences in the lifetime risks of cardiovascular disease across risk-factor strata. Among participants who were 55 years of age, those with an optimal risk-factor profile (total cholesterol level, <180 mg per deciliter [4.7...

773 citations


Journal ArticleDOI
TL;DR: In a randomized trial involving patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion, the use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function at 96 hours, with a similar amount of weight loss with the two approaches.
Abstract: A B S T R AC T Background Ultrafiltration is an alternative strategy to diuretic therapy for the treatment of patients with acute decompensated heart failure. Little is known about the efficacy and safety of ultrafiltration in patients with acute decompensated heart failure complicated by persistent congestion and worsened renal function. Methods We randomly assigned a total of 188 patients with acute decompensated heart failure, worsened renal function, and persistent congestion to a strategy of stepped pharmacologic therapy (94 patients) or ultrafiltration (94 patients). The primary end point was the bivariate change from baseline in the serum creatinine level and body weight, as assessed 96 hours after random assignment. Patients were followed for 60 days. Results Ultrafiltration was inferior to pharmacologic therapy with respect to the bivariate end point of the change in the serum creatinine level and body weight 96 hours after enrollment (P = 0.003), owing primarily to an increase in the creatinine level in the ultrafiltration group. At 96 hours, the mean change in the creatinine level was −0.04±0.53 mg per deciliter (−3.5±46.9 μmol per liter) in the pharmacologictherapy group, as compared with +0.23±0.70 mg per deciliter (20.3±61.9 μmol per liter) in the ultrafiltration group (P = 0.003). There was no significant difference in weight loss 96 hours after enrollment between patients in the pharmacologic-therapy group and those in the ultrafiltration group (a loss of 5.5±5.1 kg [12.1±11.3 lb] and 5.7±3.9 kg [12.6±8.5 lb], respectively; P = 0.58). A higher percentage of patients in the ultrafiltration group than in the pharmacologic-therapy group had a serious adverse event (72% vs. 57%, P = 0.03). Conclusions In a randomized trial involving patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion, the use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function at 96 hours, with a similar amount of weight loss with the two approaches. Ultrafiltration was associated with a higher rate of adverse events. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00608491.)

766 citations


Journal ArticleDOI
TL;DR: Although the early trials of prophylactic Surfactant administration to infants judged to be at risk of developing RDS compared to selective use of surfactant in infants with established RDS demonstrated a decreased risk of air leak and mortality, recent large trials that reflect current practice do not support these differences and demonstrate less risk of chronic lung disease or death when using early stabilization on CPAP.
Abstract: Background Surfactant therapy is effective in improving the outcome of very preterm infants. Trials have studied a wide variety of surfactant preparations used either to prevent or treat respiratory distress syndrome (RDS). In animal models, prophylactic surfactant leads to more homogeneous distribution and less evidence of lung damage. However, administration requires intubation and treatment of infants who will not go on to develop RDS. This is of particular concern with the advent of improved approaches to providing continuous distending pressure, particularly in the form of nasal continuous positive airway pressure (NCPAP). Objectives To compare the effect of prophylactic surfactant administration with surfactant treatment of established RDS in very preterm infants at risk of RDS. Search methods We updated the search of the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, and clinical trials.gov register in December 13, 2011. Selection criteria Randomized and quasi-randomized controlled trials that compared the effects of prophylactic surfactant administration with surfactant treatment of established RDS in preterm infants at risk of RDS. Data collection and analysis Data regarding clinical outcomes were extracted from the reports of the clinical trials by the review authors. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group. Main results We identified 11 studies that met inclusion criteria (nine without routine application of continuous positive air way pressure (CPAP) in the selective treatment group; two with routine application of CPAP in the selective treatment group). The meta-analysis of studies conducted prior to the routine application of CPAP demonstrated a decrease in the risk of air leak and neonatal mortality associated with prophylactic administration of surfactant. However, the analyses of studies that allowed for routine stabilization on CPAP demonstrated a decrease in the risk of chronic lung disease or death in infants stabilized on CPAP. When all studies were evaluated together, the benefits of prophylactic surfactant could no longer be demonstrated. Authors' conclusions Although the early trials of prophylactic surfactant administration to infants judged to be at risk of developing RDS compared with selective use of surfactant in infants with established RDS demonstrated a decreased risk of air leak and mortality, recent large trials that reflect current practice (including greater utilization of maternal steroids and routine post delivery stabilization on CPAP) do not support these differences and demonstrate less risk of chronic lung disease or death when using early stabilization on CPAP with selective surfactant administration to infants requiring intubation.

559 citations


Journal ArticleDOI
TL;DR: Mortality and major neonatal morbidity in survivors decreased for infants with birth weight 501 to 1500 g between 2000 and 2009, however, at the end of the decade, a high proportion of these infants still either died or survived after experiencing ≥1 major neonnatal morbidity known to be associated with both short- and long-term adverse consequences.
Abstract: OBJECTIVE: To identify changes in mortality and neonatal morbidities for infants with birth weight 501 to 1500 g born from 2000 to 2009. METHODS: There were 355 806 infants weighing 501 to 1500 g who were born in 2000–2009. Mortality during initial hospitalization and major neonatal morbidity in survivors (early and late infection, chronic lung disease, necrotizing enterocolitis, severe retinopathy of prematurity, severe intraventricular hemorrhage, and periventricular leukomalacia) were assessed by using data from 669 North American hospitals in the Vermont Oxford Network. RESULTS: From 2000 to 2009, mortality for infants weighing 501 to 1500 g decreased from 14.3% to 12.4% (difference, −1.9%; 95% confidence interval, −2.3% to −1.5%). Major morbidity in survivors decreased from 46.4% to 41.4% (difference, −4.9%; 95% confidence interval, −5.6% to −4.2%). In 2009, mortality ranged from 36.6% for infants 501 to 750 g to 3.5% for infants 1251 to 1500 g, whereas major morbidity in survivors ranged from 82.7% to 18.7%. In 2009, 49.2% of all very low birth weight infants and 89.2% of infants 501 to 750 g either died or survived with a major neonatal morbidity. CONCLUSIONS: Mortality and major neonatal morbidity in survivors decreased for infants with birth weight 501 to 1500 g between 2000 and 2009. However, at the end of the decade, a high proportion of these infants still either died or survived after experiencing ≥1 major neonatal morbidity known to be associated with both short- and long-term adverse consequences.

520 citations


Journal ArticleDOI
TL;DR: Critical resources are needed to enact this research agenda and include expanded review panel expertise in aging, functional measures, and multimorbidity, and facilitated use and continued funding to allow long-term follow-up of cohorts aging with HIV.
Abstract: HIV risk behaviors, susceptibility to HIV acquisition, progression of disease after infection, and response to antiretroviral therapy all vary by age. In those living with HIV, current effective treatment has increased the median life expectancy to >70 years of age. Biologic, medical, individual, social, and societal issues change as one ages with HIV infection, but there has been only a small amount of research in this field. Therefore, the Office of AIDS Research of the National Institutes of Health commissioned a working group to develop an outline of the current state of knowledge and areas of critical need for research in HIV and Aging; the working groups' findings and recommendations are summarized in this report. Key overarching themes identified by the group included the following: multimorbidity, polypharmacy, and the need to emphasize maintenance of function; the complexity of assessing HIV versus treatment effects versus aging versus concurrent disease; the inter-related mechanisms of immune senescence, inflammation, and hypercoagulability; the utility of multivariable indices for predicting outcomes; a need to emphasize human studies to account for complexity; and a required focus on issues of community support, caregivers, and systems infrastructure. Critical resources are needed to enact this research agenda and include expanded review panel expertise in aging, functional measures, and multimorbidity, and facilitated use and continued funding to allow long-term follow-up of cohorts aging with HIV.

Journal ArticleDOI
10 Sep 2012-PLOS ONE
TL;DR: In HIV-infected individuals, IL-6, hsCRP and D-dimer are associated with an increased risk of CVD independent of other CVD risk factors.
Abstract: Background: The SMART study was a trial of intermittent use of antiretroviral therapy (ART) (drug conservation [DC]) versus continuous use of ART (viral suppression [VS]) as a strategy to reduce toxicities, including cardiovascular disease (CVD) risk. We studied the predictive value of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer with CVD morbidity and mortality in HIV-infected patients who were enrolled in SMART beyond other measured CVD risk factors. Methods: A blood sample was available in 5098 participants who were enrolled in the SMART study for the measurement of IL-6, hsCRP and D-dimer. Hazard ratios (HR) with 95% CI for CVD events were estimated for each quartile (Q) for each biomarker vs the 1 st quartile and for 1 SD higher levels. For both treatment groups combined, unadjusted and adjusted HRs were determined using Cox regression models. Results: There were 252 participants who had a CVD event over a median follow-up of 29 months. Adjusted HRs (95% CI) for CVD for Q4 vs Q1 were 4.65 (2.61, 8.29), 2.10 (1.40, 3.16), and 2.14 (1.38, 3.33) for IL-6, hsCRP and D-dimer, respectively. Associations were similar for the DC and VS treatment groups (interaction p-values were .0.30). The addition of the three biomarkers to a model that included baseline covariates significantly improved model fit (p,0.001). Area under the curve (AUC) estimates improved with inclusion of the three biomarkers in a model that included baseline covariates corresponding to other CVD risk factors and HIV factors (0.741 to 0.771; p,0.001 for difference). Conclusions: In HIV-infected individuals, IL-6, hsCRP and D-dimer are associated with an increased risk of CVD independent of other CVD risk factors. Further research is needed to determine whether these biomarkers can be used to improve CVD risk prediction among HIV positive individuals.

Journal ArticleDOI
Zari Dastani1, Hivert M-F.2, Hivert M-F.3, N J Timpson4  +615 moreInstitutions (128)
TL;DR: A meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease identifies novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Journal ArticleDOI
04 May 2012-Science
TL;DR: Results support the concept that Ca2+ influx through single TRPV4 channels is leveraged by the amplifier effect of cooperative channel gating and the high Ca2- sensitivity of IK and SK channels to cause vasodilation.
Abstract: Major features of the transcellular signaling mechanism responsible for endothelium-dependent regulation of vascular smooth muscle tone are unresolved. We identified local calcium (Ca(2+)) signals ("sparklets") in the vascular endothelium of resistance arteries that represent Ca(2+) influx through single TRPV4 cation channels. Gating of individual TRPV4 channels within a four-channel cluster was cooperative, with activation of as few as three channels per cell causing maximal dilation through activation of endothelial cell intermediate (IK)- and small (SK)-conductance, Ca(2+)-sensitive potassium (K(+)) channels. Endothelial-dependent muscarinic receptor signaling also acted largely through TRPV4 sparklet-mediated stimulation of IK and SK channels to promote vasodilation. These results support the concept that Ca(2+) influx through single TRPV4 channels is leveraged by the amplifier effect of cooperative channel gating and the high Ca(2+) sensitivity of IK and SK channels to cause vasodilation.

Journal ArticleDOI
TL;DR: An overview of the studies in mouse models and human patients that provide support for the involvement of IL-6 in lung diseases is provided and suggests that this cytokine plays an active role in pathogenesis of asthma and, in all likelihood, COPD.
Abstract: The incidence and severity of chronic lung diseases is growing and affects between 100 and 150 million people worldwide and is associated with a significant rate of mortality. Unfortunately, the initial cause that triggers most chronic lung diseases remains unknown and current available therapies only ameliorate, but do not cure the disease. Thus, there is a need for identification of new targets and development of novel therapies especially for those most severely affected. IL-6, like other inflammatory cytokines, has been shown to be elevated in different lung diseases, but it was considered a byproduct of ongoing inflammation in the lung. However, recent studies support a dissociation of IL-6 from inflammation in the lung and suggest that this cytokine plays an active role in pathogenesis of asthma and, in all likelihood, COPD. IL-6 may therefore be a germane target for treatment of these and other chronic lung disease. Here, we provide an overview of the studies in mouse models and human patients that provide support for the involvement of IL-6 in lung diseases.

Journal ArticleDOI
TL;DR: Akhmediev et al. as mentioned in this paper derived general high-order rogue waves in the nonlinear Schrodinger equation using the bilinear method and showed that the general N − 1 free irreducible complex parameters have the highest peak amplitudes among all rogue waves of the same order.
Abstract: General high-order rogue waves in the nonlinear Schrodinger equation are derived by the bilinear method. These rogue waves are given in terms of determinants whose matrix elements have simple algebraic expressions. It is shown that the general N -th order rogue waves contain N −1 free irreducible complex parameters. In addition, the specific rogue waves obtained by Akhmediev et al. (Akhmediev et al. 2009 Phys. Rev. E 80 , 026601 (doi:10.1103/PhysRevE.80.026601)) correspond to special choices of these free parameters, and they have the highest peak amplitudes among all rogue waves of the same order. If other values of these free parameters are taken, however, these general rogue waves can exhibit other solution dynamics such as arrays of fundamental rogue waves arising at different times and spatial positions and forming interesting patterns.


Journal ArticleDOI
21 Mar 2012-PLOS ONE
TL;DR: While appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites, and better targeted expansion of PA networks would help to improve biodiversity trends.
Abstract: Protected areas (PAs) are a cornerstone of conservation efforts and now cover nearly 13% of the world’s land surface, with the world’s governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species’ extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs) (referred to collectively hereafter as ‘important sites’). Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with.50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites). Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45–1.14% annually since 1950 for IBAs and 0.79–1.49% annually for AZEs). Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends.

Journal ArticleDOI
TL;DR: The results indicate that both neural endophenotypes and genetic variation give rise to the various manifestations of impulsive behavior.
Abstract: The impulsive behavior that is often characteristic of adolescence may reflect underlying neurodevelopmental processes. Moreover, impulsivity is a multi-dimensional construct, and it is plausible that distinct brain networks contribute to its different cognitive, clinical and behavioral aspects. As these networks have not yet been described, we identified distinct cortical and subcortical networks underlying successful inhibitions and inhibition failures in a large sample (n = 1,896) of 14-year-old adolescents. Different networks were associated with drug use (n = 1,593) and attention-deficit hyperactivity disorder symptoms (n = 342). Hypofunctioning of a specific orbitofrontal cortical network was associated with likelihood of initiating drug use in early adolescence. Right inferior frontal activity was related to the speed of the inhibition process (n = 826) and use of illegal substances and associated with genetic variation in a norepinephrine transporter gene (n = 819). Our results indicate that both neural endophenotypes and genetic variation give rise to the various manifestations of impulsive behavior.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the relationship between energy access and millennium development goals, especially the connection between modern energy services and development, public health, gender empowerment, and the degradation of the natural environment.

Journal ArticleDOI
TL;DR: Three-dimensional biological scaffolds made of allogeneic or xenogeneic extracellular matrix derived from non-autologous sources can act as an inductive template for functional tissue and organ reconstruction after recellularisation with autologous stem cells or differentiated cells.

Journal ArticleDOI
TL;DR: The existing nomenclature for these receptors is confirmed, the current understanding of their structure, pharmacology and functions and their likely physiological roles in health and disease are reviewed.
Abstract: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are members of a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, gastric inhibitory peptide (GIP) and growth hormone-releasing hormone (GHRH). VIP and PACAP exert their actions through three GPCRs – PAC1, VPAC1 and VPAC2– belonging to class B (also referred to as class II, or secretin receptor-like GPCRs). This family comprises receptors for all peptides structurally related to VIP and PACAP, and also receptors for parathyroid hormone, corticotropin-releasing factor, calcitonin and related peptides. PAC1 receptors are selective for PACAP, whereas VPAC1 and VPAC2 respond to both VIP and PACAP with high affinity. VIP and PACAP play diverse and important roles in the CNS, with functions in the control of circadian rhythms, learning and memory, anxiety and responses to stress and brain injury. Recent genetic studies also implicate the VPAC2 receptor in susceptibility to schizophrenia and the PAC1 receptor in post-traumatic stress disorder. In the periphery, VIP and PACAP play important roles in the control of immunity and inflammation, the control of pancreatic insulin secretion, the release of catecholamines from the adrenal medulla and as co-transmitters in autonomic and sensory neurons. This article, written by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee on receptors for VIP and PACAP, confirms the existing nomenclature for these receptors and reviews our current understanding of their structure, pharmacology and functions and their likely physiological roles in health and disease. More detailed information has been incorporated into newly revised pages in the IUPHAR database (http://www.iuphar-db.org/DATABASE/FamilyMenuForward?familyId=67). LINKED ARTICLES This article is part of a themed section on Secretin Family (Class B) G Protein-Coupled Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue-1

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TL;DR: The meta-analyses demonstrate significant reductions in the risk of neonatal mortality and chronic lung disease or death at 36 weeks associated with early treatment of intubated infants with established RDS.
Abstract: Background Clinical trials have confirmed that surfactant therapy is effective in improving the immediate need for respiratory support and the clinical outcome of premature newborns. Trials have studied a wide variety of surfactant preparations used either to prevent (prophylactic or delivery room administration) or treat (selective or rescue administration) respiratory distress syndrome (RDS). Using either treatment strategy, significant reductions in the incidence of pneumothorax, as well as significant improvement in survival, have been noted. It is unclear whether there are any advantages to treating infants with respiratory insufficiency earlier in the course of RDS. Objectives To compare the effects of early versus delayed selective surfactant therapy for newborns intubated for respiratory distress within the first two hours of life. Planned subgroup analyses included separate comparisons for studies utilizing natural surfactant extract and synthetic surfactant. Search methods We searched the Oxford Database of Perinatal Trials, MEDLINE (MeSH terms: pulmonary surfactant; text word: early; limits: age, newborn: publication type, clinical trial), PubMed, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language. For the updated search in April 2012 we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012, Issue 1) and PubMed (January 1997 to April 2012). Selection criteria Randomized and quasi-randomized controlled clinical trials comparing early selective surfactant administration (surfactant administration via the endotracheal tube in infants intubated for respiratory distress, not specifically for surfactant dosage) within the first two hours of life versus delayed selective surfactant administration to infants with established RDS were considered for review. Data collection and analysis Data regarding clinical outcomes were excerpted from the reports of the clinical trials by the review authors. Subgroup analyses were performed based on type of surfactant preparation, gestational age, and exposure to prenatal steroids. Data analysis was performed in accordance with the standards of the Cochrane Neonatal Review Group. Main results Six randomized controlled trials met selection criteria. Two of the trials utilized synthetic surfactant (Exosurf Neonatal) and four utilized animal-derived surfactant preparations. The meta-analyses demonstrate significant reductions in the risk of neonatal mortality (typical risk ratio (RR) 0.84; 95% confidence interval (CI) 0.74 to 0.95; typical risk difference (RD) -0.04; 95% CI -0.06 to -0.01; 6 studies; 3577 infants), chronic lung disease (typical RR 0.69; 95% CI 0.55 to 0.86; typical RD -0.04; 95% CI -0.06 to -0.01; 3 studies; 3041 infants), and chronic lung disease or death at 36 weeks (typical RR 0.83; 95% CI 0.75 to 0.91; typical RD -0.06; 95% CI -0.09 to -0.03; 3 studies; 3050 infants) associated with early treatment of intubated infants with RDS. Intubated infants randomized to early selective surfactant administration also demonstrated a decreased risk of acute lung injury including a decreased risk of pneumothorax (typical RR 0.69; 95% CI 0.59 to 0.82; typical RD -0.05; 95% CI -0.08 to -0.03; 5 studies; 3545 infants), pulmonary interstitial emphysema (typical RR 0.60; 95% CI 0.41 to 0.89; typical RD -0.06; 95% CI -0.10 to -0.02; 3 studies; 780 infants), and overall air leak syndromes (typical RR 0.61; 95% CI 0.48 to 0.78; typical RD -0.18; 95% CI -0.26 to -0.09; 2 studies; 463 infants). A trend toward risk reduction for bronchopulmonary dysplasia (BPD) or death at 28 days was also evident (typical RR 0.94; 95% CI 0.88 to 1.00; typical RD -0.04; 95% CI -0.07 to -0.00; 3 studies; 3039 infants). No differences in other complications of RDS or prematurity were noted. Only two studies reported on infants under 30 weeks' gestation. Decreased risk of neonatal mortality and chronic lung disease or death at 36 weeks' postmenstrual age was noted. Authors' conclusions Early selective surfactant administration given to infants with RDS requiring assisted ventilation leads to a decreased risk of acute pulmonary injury (decreased risk of pneumothorax and pulmonary interstitial emphysema) and a decreased risk of neonatal mortality and chronic lung disease compared to delaying treatment of such infants until they develop worsening RDS.

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TL;DR: This data indicates that in patients with unprovoked venous thromboembolism, the optimal duration of anticoagulation is anchored on estimating the risk of disease recurrence, and this work contributes to this understanding.

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TL;DR: It is reported that inflammation causes enteric neuron death by activating a neuronal signaling complex composed of P2X7 receptors, pannexin-1 channels, the Asc adaptor protein and caspases, and it is concluded that activation of neuronal Panx1 underlies neuron death and the subsequent development of abnormal gut motility in IBD.
Abstract: Inflammatory bowel diseases (IBDs) are chronic relapsing and remitting conditions associated with long-term gut dysfunction resulting from alterations to the enteric nervous system and a loss of enteric neurons. The mechanisms underlying inflammation-induced enteric neuron death are unknown. Here using in vivo models of experimental colitis we report that inflammation causes enteric neuron death by activating a neuronal signaling complex composed of P2X7 receptors (P2X7Rs), pannexin-1 (Panx1) channels, the Asc adaptor protein and caspases. Inhibition of P2X7R, Panx1, Asc or caspase activity prevented inflammation-induced neuron cell death. Preservation of enteric neurons by inhibiting Panx1 in vivo prevented the onset of inflammation-induced colonic motor dysfunction. Panx1 expression was reduced in Crohn's disease but not ulcerative colitis. We conclude that activation of neuronal Panx1 underlies neuron death and the subsequent development of abnormal gut motility in IBD. Targeting Panx1 represents a new neuroprotective strategy to ameliorate the progression of IBD-associated dysmotility.


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TL;DR: The evidence review demonstrated that SLN biopsy is an acceptable method for lymph node staging of most patients with newly diagnosed melanoma, and completion lymph node dissection (CLND) is recommended for all patients with a positive SLNBiopsy and achieves good regional disease control.
Abstract: Purpose The American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) sought to provide an evidence-based guideline on the use of lymphatic mapping and sentinel lymph node (SLN) biopsy in staging patients with newly diagnosed melanoma.

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TL;DR: How this cytokine has evolved from being a marker of inflammation to a successful target to control inflammation is discussed and potential mechanisms by which IL-6 can contribute to the progression of inflammatory diseases are described.

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TL;DR: The potential of shared bicycle systems can be maximized by increasing the number of docking stations in residential neighborhoods and by emphasizing the popularity of shared bicycles and theft prevention in advertising campaigns.
Abstract: Planning and transportation professionals are promoting a variety of sustainable travel alternatives, such as public transit usage, walking, and cycling, as affordable transportation options to counter the negative effects of widespread car use. In their traditional form, these alternative transport modes do not always offer the flexibility or convenience of the car; therefore, innovative solutions have been developed to allow active and public transport to compete better with the car. Shared bicycle systems have been adopted by a growing number of cities and regions throughout the world, yet little is known about the users of the systems and their motivations. A survey was conducted in Montreal, Quebec, Canada, in the summer of 2010 to determine the factors that encouraged individuals to use the system and the elements that influenced frequency of use. The factor found to have the greatest effect on the likelihood for use of a shared bicycle system was the proximity of home to docking stations. Ownership...

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TL;DR: General rogue waves in the Davey-Stewartson-I equation are derived by the bilinear method and it is shown that the simplest (fundamental) rogue waves are line rogue waves which arise from the constant background with a line profile and then disappear into the constant Background.
Abstract: General rogue waves in the Davey-Stewartson-I equation are derived by the bilinear method. It is shown that the simplest (fundamental) rogue waves are line rogue waves which arise from the constant background with a line profile and then disappear into the constant background again. It is also shown that multirogue waves describe the interaction of several fundamental rogue waves. These multirogue waves also arise from the constant background and then decay back to it, but in the intermediate times, interesting curvy wave patterns appear. However, higher-order rogue waves exhibit different dynamics. Specifically, only part of the wave structure in the higher-order rogue waves rises from the constant background and then retreats back to it, and this transient wave possesses patterns such as parabolas. But the other part of the wave structure comes from the far distance as a localized lump, which decelerates to the near field and interacts with the transient rogue wave, and is then reflected back and accelerates to the large distance again.