Brachial Artery Constriction during Brachial Artery Reactivity Testing Predicts Major Adverse Clinical Outcomes in Women with Suspected Myocardial Ischemia: Results from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study

Background:Limited brachial artery (BA) flow-mediated dilation during brachial artery reactivity testing (BART) has been linked to increased cardiovascular risk. We report on the phenomenon of BA constriction (BAC) following hyperemia.Objectives:To determine whether BAC predicts adverse CV outcomes and/or mortality in the women's ischemic Syndrome Evaluation Study (WISE). Further, as a secondary objective we sought to determine the risk factors associated with BAC.Methods:We performed BART on 377 women with chest pain referred for coronary angiography and followed for a median of 9.5 years. Forearm ischemia was induced with 4 minutes occlusion by a cuff placed distal to the BA and inflated to 40mm Hg > systolic pressure. BAC was defined as >4.8% artery constriction following release of the cuff. The main outcome was major adverse events (MACE) including all-cause mortality, non-fatal MI, non-fatal stroke, or hospitalization for heart failure.Results:BA diameter change ranged from -20.6% to +44.9%, and 41 (11%) women experienced BAC. Obstructive CAD and traditional CAD risk factors were not predictive of BAC. Overall, 39% of women with BAC experienced MACE vs. 22% without BAC (p=0.004). In multivariate Cox proportional hazards regression, BAC was a significant independent predictor of MACE (p=0.018) when adjusting for obstructive CAD and traditional risk factors.Conclusions:BAC predicts almost double the risk for major adverse events compared to patients without BAC. This risk was not accounted for by CAD or traditional risk factors. The novel risk marker of BAC requires further investigation in women. © 2013 Sedlak et al

Submaximal exercise pulmonary gas exchange in left heart disease patients with different forms of pulmonary hypertension.

JOURNAL ARTICLECopyright © 2015 Elsevier Inc. All rights reserved.BACKGROUND: We determined whether pulmonary gas exchange indices during submaximal exercise are different in heart-failure (HF) patients with combined post- and pre-capillary pulmonary hypertension (PPC-PH) vs. HF patients with isolated post-capillary PH (IPC-PH) or no-PH. METHODS & RESULTS: Pulmonary hemodynamics and pulmonary gas exchange were assessed during rest and submaximal exercise in 39 HF patients undergoing right-heart catheterization. Post-hemodynamic evaluation, patients were classified as having no-PH (n=11), IPC-PH (n=12) or PPC-PH (n=16). At an equivalent oxygen consumption, end-tidal CO2 (PETCO2) and arterial oxygen saturation (SaO2) were greater in no-PH and IPC-PH vs. PPC-PH patients (36.1±3.2 vs. 31.7±4.5 vs. 26.2±4.7 mmHg and 97±2 vs. 96 ±3 vs. 91±1%, respectively). Conversely, dead-space ventilation (VD/VT) and the ventilatory equivalent for carbon dioxide (V̇E/V̇CO2 ratio) were lower in no-PH and IPC-PH vs. PPC-PH patients (0.37±0.05 vs. 0.38±0.04 vs. 0.47±0.03 and 38±5 vs. 42±8 vs. 51±8, respectively). The exercise-induced change in VD/VT, V̇E/V̇CO2 ratio and PETCO2 correlated significantly with the change in mean pulmonary arterial pressure, diastolic pressure difference and transpulmonary pressure gradient in PPC-PH patients only. CONCLUSION: Noninvasive pulmonary gas exchange indices during submaximal exercise are different in HF patients with combined post-and pre-capillary PH compared to patients with isolated post-capillary PH or no-PH.NIHAmerican Heart Associatio

Association of Cognitive Performance with Time at Altitude, Sleep Quality, and Acute Mountain Sickness Symptoms

Objective It is well documented that cognitive performance may be altered with ascent to altitude, but the association of various cognitive performance tests with symptoms of acute mountain sickness (AMS) is not well understood. Our objective was to assess and compare cognitive performance during a high-altitude expedition using several tests and to report the association of each test with AMS, headache, and quality of sleep. Methods During an expedition to Mount Everest, 3 cognitive tests (Stroop, Trail Making, and the real-time cognitive assessment tool, an in-house developed motor accuracy test) were used along with a questionnaire to assess health and AMS. Eight team members were assessed pre-expedition, postexpedition, and at several time points during the expedition. Results There were no significant differences (P >.05) found among scores taken at 3 time points at base camp and the postexpedition scores for all 3 tests. Changes in the Stroop test scores were significantly associated with the odds of AMS (P <.05). The logistic regression results show that the percent change from baseline for Stroop score (β = −5.637; P = .032) and Stroop attempts (β = −5.269; P = .049) are significantly associated with the odds of meeting the criteria for AMS. Conclusions No significant changes were found in overall cognitive performance at altitude, but a significant relationship was found between symptoms of AMS and performance in certain cognitive tests. This research shows the need for more investigation of objective physiologic assessments to associate with self-perceived metrics of AMS to gauge effect on cognitive performance

c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation.

Sympathetic neurons depend on NGF binding to TrkA for their survival during vertebrate development. NGF deprivation initiates a transcription-dependent apoptotic response, which is suggested to require activation of the transcription factor c-Jun. Similarly, apoptosis can also be induced by selective activation of the p75 neurotrophin receptor. The transcriptional dependency of p75-mediated cell death has not been determined; however, c-Jun NH2-terminal kinase has been implicated as an essential component. Because the c-jun-null mutation is early embryonic lethal, thereby hindering a genetic analysis, we used the Cre-lox system to conditionally delete this gene. Sympathetic neurons isolated from postnatal day 1 c-jun-floxed mice were infected with an adenovirus expressing Cre recombinase or GFP and analyzed for their dependence on NGF for survival. Cre immunopositive neurons survived NGF withdrawal, whereas those expressing GFP or those uninfected underwent apoptosis within 48 h, as determined by DAPI staining. In contrast, brain-derived neurotrophic factor (BDNF) binding to p75 resulted in an equivalent level of apoptosis in neurons expressing Cre, GFP, and uninfected cells. Nevertheless, cycloheximide treatment prevented BDNF-mediated apoptosis. These results indicate that whereas c-jun is required for apoptosis in sympathetic neurons on NGF withdrawal, an alternate signaling pathway must be induced on p75 activation

ZFOURGE: Extreme 5007A˚\AA emission may be a common early-lifetime phase for star-forming galaxies at z>2.5z > 2.5

Using the \prospector\ spectral energy distribution (SED) fitting code, we analyze the properties of 19 Extreme Emission Line Galaxies (EELGs) identified in the bluest composite SED in the \zfourge\ survey at $2.5 \leq z \leq 4$. \prospector\ includes a physical model for nebular emission and returns probability distributions for stellar mass, stellar metallicity, dust attenuation, and nonparametric star formation history (SFH). The EELGs show evidence for a starburst in the most recent 50 Myr, with the median EELG having a specific star formation rate (sSFR) of 4.6 Gyr$^{-1}$ and forming 15\% of its mass in this short time. For a sample of more typical star-forming galaxies (SFGs) at the same redshifts, the median SFG has a sSFR of 1.1 Gyr$^{-1}$ and forms only $4\%$ of its mass in the last 50 Myr. We find that virtually all of our EELGs have rising SFHs, while most of our SFGs do not. From our analysis, we hypothesize that many, if not most, star-forming galaxies at $z \geq 2.5$ undergo an extreme H$\beta$+[\hbox{{\rm O}\kern 0.1em{\sc iii}}] emission line phase early in their lifetimes. In a companion paper, we obtain spectroscopic confirmation of the EELGs as part of our {\sc MOSEL} survey. In the future, explorations of uncertainties in modeling the UV slope for galaxies at $z>2$ are needed to better constrain their properties, e.g. stellar metallicities.Comment: 11 pages, 5 figures (main figure is fig 5), accepted for publication in Ap

SPECULATOR: Emulating stellar population synthesis for fast and accurate galaxy spectra and photometry

We present SPECULATOR - a fast, accurate, and flexible framework for emulating stellar population synthesis (SPS) models for predicting galaxy spectra and photometry. For emulating spectra, we use principal component analysis to construct a set of basis functions, and neural networks to learn the basis coefficients as a function of the SPS model parameters. For photometry, we parameterize the magnitudes (for the filters of interest) as a function of SPS parameters by a neural network. The resulting emulators are able to predict spectra and photometry under both simple and complicated SPS model parameterizations to percent-level accuracy, giving a factor of $10^3$-$10^4$ speed up over direct SPS computation. They have readily-computable derivatives, making them amenable to gradient-based inference and optimization methods. The emulators are also straightforward to call from a GPU, giving an additional order-of-magnitude speed-up. Rapid SPS computations delivered by emulation offers a massive reduction in the computational resources required to infer the physical properties of galaxies from observed spectra or photometry and simulate galaxy populations under SPS models, whilst maintaining the accuracy required for a range of applications

Simulating Dynamical Features of Escape Panic

One of the most disastrous forms of collective human behaviour is the kind of crowd stampede induced by panic, often leading to fatalities as people are crushed or trampled. Sometimes this behaviour is triggered in life-threatening situations such as fires in crowded buildings; at other times, stampedes can arise from the rush for seats or seemingly without causes. Tragic examples within recent months include the panics in Harare, Zimbabwe, and at the Roskilde rock concert in Denmark. Although engineers are finding ways to alleviate the scale of such disasters, their frequency seems to be increasing with the number and size of mass events. Yet, systematic studies of panic behaviour, and quantitative theories capable of predicting such crowd dynamics, are rare. Here we show that simulations based on a model of pedestrian behaviour can provide valuable insights into the mechanisms of and preconditions for panic and jamming by incoordination. Our results suggest practical ways of minimising the harmful consequences of such events and the existence of an optimal escape strategy, corresponding to a suitable mixture of individualistic and collective behaviour.Comment: For related information see http://angel.elte.hu/~panic, http://www.helbing.org, http://angel.elte.hu/~fij, and http://angel.elte.hu/~vicse

A Universal Model of Global Civil Unrest

Civil unrest is a powerful form of collective human dynamics, which has led to major transitions of societies in modern history. The study of collective human dynamics, including collective aggression, has been the focus of much discussion in the context of modeling and identification of universal patterns of behavior. In contrast, the possibility that civil unrest activities, across countries and over long time periods, are governed by universal mechanisms has not been explored. Here, we analyze records of civil unrest of 170 countries during the period 1919-2008. We demonstrate that the distributions of the number of unrest events per year are robustly reproduced by a nonlinear, spatially extended dynamical model, which reflects the spread of civil disorder between geographic regions connected through social and communication networks. The results also expose the similarity between global social instability and the dynamics of natural hazards and epidemics.Comment: 8 pages, 3 figure

TIMI frame count and adverse events in women with no obstructive coronary disease: A pilot study from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE)

Background: TIMI frame count (TFC) predicts outcomes in patients with obstructive coronary artery disease (CAD); it remains unclear whether TFC predicts outcomes in patients without obstructive CAD. Methods: TFC was determined in a sample of women with no obstructive CAD enrolled in the Women's Ischemia Syndrome Evaluation (WISE) study. Because TFC is known to be higher in the left anterior descending artery (LAD), TFC determined in the LAD was divided by 1.7 to provide a corrected TFC (cTFC). Results: A total of 298 women, with angiograms suitable for TFC analysis and long-term (6-10 year) follow up data, were included in this sub-study. Their age was 55±11 years, most were white (86%), half had a history of smoking, and half had a history of hypertension. Higher resting cTFC was associated with a higher rate of hospitalization for angina (34% in women with a cTFC >35, 15% in women with a cTFC ≤35, P<0.001). cTFC provided independent prediction of hospitalization for angina after adjusting for many baseline characteristics. In this cohort, resting cTFC was not predictive of major events (myocardial infarction, heart failure, stroke, or all-cause death), cardiovascular events, all-cause mortality, or cardiovascular mortality. Conclusions: In women with signs and symptoms of ischemia but no obstructive CAD, resting cTFC provides independent prediction of hospitalization for angina. Larger studies are required to determine if resting TFC is predictive of major events in patients without obstructive coronary artery disease. © 2014 Petersen et al