P112 Influence of Cuff Blood Pressure Accuracy on Identification of Isolated Systolic Hypertension

Abstract Introduction Isolated systolic hypertension (ISH) is the most common form of hypertension in older people. However, accurate identification of ISH may be hindered because cuff blood pressure (BP) underestimates systolic BP (SBP) and overestimates diastolic BP (DBP). This study aimed to determine the influence of cuff BP accuracy on the identification of ISH. Methods Cuff BP and invasive aortic BP were measured simultaneous (or near-simultaneously) in 1737 subjects (63 ± 12 years, 68% male) during coronary angiography. Data was derived from 32 studies, using 20 different cuff BP devices, from the Invasive Blood Pressure Consortium (INSPECT). ISH was defined as ≥140/<90 mmHg according to cuff BP and invasive aortic BP. Results According to cuff BP, 25% of subjects (n = 430) had ISH, however, 37% (n = 648) were identified with ISH from invasive aortic BP. There was 77% concordance between cuff and invasive BP for identifying ISH. Among the 23% (n = 408) of subjects misclassified by cuff BP, 38% (n = 155) of misclassification was from SBP underestimation (mean: −16.6, 95% CI: −18.9 to −13.9 mmHg), whereas 35% (n = 143) was from DBP overestimation (15.6, 11.9 to 19.0 mmHg) and 20% (n = 83) from SBP overestimation (17.6, 14.4 to 20.5 mmHg). Subjects misclassified were on average 2.7 years older and had greater body mass index (0.8 kg/m2) than those correctly classified. Conclusion Approximately one quarter of older subjects have ISH misclassified, mostly because of underestimation of cuff SBP and overestimation of cuff DBP. This demonstrates a need to improve the accuracy of cuff BP methods for greater precision in identifying ISH

Restored glial glutamate transporter EAAT2 function as a potential therapeutic approach for Alzheimer’s disease

Glutamatergic systems play a critical role in cognitive functions and are known to be defective in Alzheimer’s disease (AD) patients. Previous literature has indicated that glial glutamate transporter EAAT2 plays an essential role in cognitive functions and that loss of EAAT2 protein is a common phenomenon observed in AD patients and animal models. In the current study, we investigated whether restored EAAT2 protein and function could benefit cognitive functions and pathology in APPSw,Ind mice, an animal model of AD. A transgenic mouse approach via crossing EAAT2 transgenic mice with APPSw,Ind. mice and a pharmacological approach using a novel EAAT2 translational activator, LDN/OSU-0212320, were conducted. Findings from both approaches demonstrated that restored EAAT2 protein function significantly improved cognitive functions, restored synaptic integrity, and reduced amyloid plaques. Importantly, the observed benefits were sustained one month after compound treatment cessation, suggesting that EAAT2 is a potential disease modifier with therapeutic potential for AD

Intransitivity is infrequent and fails to promote annual plant coexistence without pairwise niche differences

8 páginas.-- 2 figuras.-- 41 referencias.-- 3 Additional supporting information may be found in the online version of this article at http://onlinelibrary.wiley.com/doi/10.1002/ecy.1782/suppinfoIntransitive competition is often projected to be a widespread mechanism of species coexistence in ecological communities. However, it is unknown how much of the coexistence we observe in nature results from this mechanism when species interactions are also stabilized by pairwise niche differences. We combined field-parameterized models of competition among 18 annual plant species with tools from network theory to quantify the prevalence of intransitive competitive relationships. We then analyzed the predicted outcome of competitive interactions with and without pairwise niche differences. Intransitive competition was found for just 15–19% of the 816 possible triplets, and this mechanism was never sufficient to stabilize the coexistence of the triplet when the pair-wise niche differences between competitors were removed. Of the transitive and intransitive triplets, only four were predicted to coexist and these were more similar in multidimensional trait space defined by 11 functional traits than non-coexisting triplets. Our results argue that intransitive competition may be less frequent than recently posed, and that even when it does operate, pairwise niche differences may be key to possible coexistence.Postdoctoral financial support provided by the Spanish Ministry for Education and Science (Juan de la Cierva, JCI- 2012- 12061). D. B. Stouffer acknowledges support from the Royal Society of New Zealand (via Marsden Fast- Start UOC- 1101 and a Rutherford Discovery Fellowship). N. J. B. Kraft and J. M. Levine were supported by NSF DEB 1644641Peer reviewe

Restored glial glutamate transporter EAAT2 function as a potential therapeutic approach for Alzheimer’s disease

Glutamatergic systems play a critical role in cognitive functions and are known to be defective in Alzheimer’s disease (AD) patients. Previous literature has indicated that glial glutamate transporter EAAT2 plays an essential role in cognitive functions and that loss of EAAT2 protein is a common phenomenon observed in AD patients and animal models. In the current study, we investigated whether restored EAAT2 protein and function could benefit cognitive functions and pathology in APPSw,Ind mice, an animal model of AD. A transgenic mouse approach via crossing EAAT2 transgenic mice with APPSw,Ind. mice and a pharmacological approach using a novel EAAT2 translational activator, LDN/OSU-0212320, were conducted. Findings from both approaches demonstrated that restored EAAT2 protein function significantly improved cognitive functions, restored synaptic integrity, and reduced amyloid plaques. Importantly, the observed benefits were sustained one month after compound treatment cessation, suggesting that EAAT2 is a potential disease modifier with therapeutic potential for AD

Sustaining ecosystem functions in a changing world: a call for an integrated approach

With ever-increasing human pressure on ecosystems, it is critically important to predict how ecosystem functions will respond to such human-induced perturbations. We define perturbations as either changes to abiotic environment (e.g. eutrophication, climate change) that indirectly affects biota, or direct changes to biota (e.g. species introductions). While two lines of research in ecology, biodiversity-ecosystem function (BDEF) and ecological resilience (ER) research, have addressed this issue, both fields of research have nontrivial shortcomings in their abilities to address a wide range of realistic scenarios. We outline how an integrated research framework may foster a deeper understanding of the functional consequences of perturbations via simultaneous application of (i) process-based mechanistic predictions using trait-based approaches and (ii) detection of empirical patterns of functional changes along real perturbation gradients. In this context, the complexities of ecological interactions and evolutionary perspectives should be integrated into future research. Synthesis and applications. Management of human-impacted ecosystems can be guided most directly by understanding the response of ecosystem functions to controllable perturbations. In particular, we need to characterize the form of a wide range of perturbation-function relationships and to draw connections between those patterns and the underlying ecological processes. We anticipate that the integrated perspectives will also be helpful for managers to derive practical implications for management from academic literature. Management of human-impacted ecosystems can be guided most directly by understanding the response of ecosystem functions to controllable perturbations. In particular, we need to characterize the form of a wide range of perturbation-function relationships and to draw connections between those patterns and the underlying ecological processes. We anticipate that the integrated perspectives will also be helpful for managers to derive practical implications for management from academic literature

A climate sensitivity estimate using Bayesian fusion of instrumental observations and an Earth System model

Current climate model projections are uncertain. This uncertainty is partly driven by the uncertainty in key model parameters such as climate sensitivity (CS), vertical ocean diffusivity (Kv), and strength of anthropogenic sulfate aerosol forcing. These parameters are commonly estimated using ensembles of model runs constrained by observations. Here we obtain a probability density function (pdf) of these parameters using the University of Victoria Earth System Climate Model (UVic ESCM) - an intermediate complexity model with a dynamic three-dimensional ocean. Specifically, we run an ensemble of UVic ESCM runs varying parameters that affect CS, ocean vertical diffusion, and the effects of anthropogenic sulfate aerosols. We use a statistical emulator that interpolates the UVic ESCM output to parameter settings where the model was not evaluated. We adopt a Bayesian approach to constrain the model output with instrumental surface temperature and ocean heat observations. Our approach accounts for the uncertainties in the properties of model-data residuals. We use a Markov chain Monte Carlo method to obtain a posterior pdf of these parameters. The mode of the climate sensitivity estimate is 2.8°C, with the corresponding 95% credible interval ranging from 1.8 to 4.9°C. These results are generally consistent with previous studies. The CS pdf is sensitive to the assumptions about the priors, to the effects of anthropogenic sulfate aerosols, and to the background vertical ocean diffusivity. Our method can be used with more complex climate models