Additive Beneficial Effects of Beta-Blockers to Angiotensin-Converting Enzyme Inhibitors in the Survival and Ventricular Enlargement (SAVE) Study fn1fn1This study was supported by a University-Industry grant from the Medical Research Council, Ottawa, Ontario, Canada and Bristol Myers Squibb, Montreal, Quebec, Canada.

AbstractObjectives. This study assessed whether treatment with a beta-adrenergic blocking agent in addition to the use of the angiotensin-converting enzyme (ACE) inhibitor captopril decreases cardiovascular mortality and morbidity in patients with asymptomatic left ventricular dysfunction after myocardial infarction (MI) and whether the presence of neurohumoral activation at the time of hospital discharge predicts the effects of beta-blocker treatment in these patients.Background. Both beta-blockers and ACE inhibitors have been shown to have beneficial effects in patients with left ventricular dysfunction but no overt heart failure after MI. These patients often have persistent neurohumoral activation at the time of hospital discharge, and one would expect that patients with activation of the sympathetic nervous system derive the most benefit from treatment with beta-blockers. However, beta-blockers are underutilized in this high risk group of patients, and it is unknown whether their beneficial effects are additive to those of ACE inhibitors.Methods. We performed a retrospective analysis of data from the Survival and Ventricular Enlargement (SAVE) study and its neurohumoral substudy. The relations between beta-blocker use at the time of randomization and neurohumoral activation and the subsequent development of cardiovascular events were analyzed by use of Cox proportional hazards models controlling for covariates.Results. After adjustment for baseline imbalances, beta-blocker use was associated with a significant reduction in risk of cardiovascular death (30%, 95% confidence interval [CI] 12% to 44%) and development of heart failure (21%, 95% CI 3% to 36%), but the reduction in recurrent MI (11%, 95% CI 13% to 31%) was not significant. These reductions were independent of the use of captopril. Beta-blockers were not found to have a greater effect in patients with neurohumoral activation at the time of hospital discharge.Conclusions. The beneficial effects of beta-blocker use at the time of hospital discharge in patients with asymptomatic left ventricular dysfunction after MI appear to be additive to those of captopril and other interventions known to improve prognosis. Neurohumoral activation at the time of hospital discharge fails to identify those patients who will derive the greatest benefit from treatment with beta-blockers.(J Am Coll Cardiol 1997;29:229–36

BLAST05: Power Spectra of Bright Galactic Cirrus at Submillimeter Wavelengths

We report multi-wavelength power spectra of diffuse Galactic dust emission from BLAST observations at 250, 350, and 500 microns in Galactic Plane fields in Cygnus X and Aquila. These submillimeter power spectra statistically quantify the self-similar structure observable over a broad range of scales and can be used to assess the cirrus noise which limits the detection of faint point sources. The advent of submillimeter surveys with the Herschel Space Observatory makes the wavelength dependence a matter of interest. We show that the observed relative amplitudes of the power spectra can be related through a spectral energy distribution (SED). Fitting a simple modified black body to this SED, we find the dust temperature in Cygnus X to be 19.9 +/- 1.3 K and in the Aquila region 16.9 +/- 0.7 K. Our empirical estimates provide important new insight into the substantial cirrus noise that will be encountered in forthcoming observations.Comment: Submitted to the Astrophysical Journal. Maps and other data are available at http://blastexperiment.info

The Future of American Sentencing: A National Roundtable on Blakely

In the wake of the dramatic Supreme Court decision in Blakely v. Washington, Stanford Law School convened an assembly of the most eminent academic and professional sentencing experts in the country to jointly assess the meaning of the decision and its implications for federal and state sentencing reform. The event took place on October 8 and 9, just a few months after Blakely came down and the very week that the Supreme Court heard the arguments in United States v. Booker and United States v. Fanfan, the cases that will test Blakely\u27s application to the Federal Sentencing Guidelines. Thus the Roundtable offered these experts an intellectual breathing space at a crucial point in American criminal law. The event was built around six sessions, with shifting panels of participants doing brief presentations on the subject of the session, and with others then joining in the discussion. We are pleased that FSR is able to publish this version of the proceedings of the event-a condensed and edited transcript of the sessions

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Prey detection and prey capture in copepod nauplii

Copepod nauplii are either ambush feeders that feed on motile prey or they produce a feeding current that entrains prey cells. It is unclear how ambush and feeding-current feeding nauplii perceive and capture prey. Attack jumps in ambush feeding nauplii should not be feasible at low Reynolds numbers due to the thick viscous boundary layer surrounding the attacking nauplius. We use high-speed video to describe the detection and capture of phytoplankton prey by the nauplii of two ambush feeding species (Acartia tonsa and Oithona davisae) and by the nauplii of one feeding-current feeding species (Temora longicornis). We demonstrate that the ambush feeders both detect motile prey remotely. Prey detection elicits an attack jump, but the jump is not directly towards the prey, such as has been described for adult copepods. Rather, the nauplius jumps past the prey and sets up an intermittent feeding current that pulls in the prey from behind towards the mouth. The feeding-current feeding nauplius detects prey arriving in the feeding current but only when the prey is intercepted by the setae on the feeding appendages. This elicits an altered motion pattern of the feeding appendages that draws in the prey

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Endovascular Therapy in the Extended Time Window for Large Vessel Occlusion in Patients With Pre-Stroke Disability.

BACKGROUND AND PURPOSE We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability. METHODS In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0-4 and LVO who underwent EVT 6-24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0-2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2-4) and those without (mRS score 0-1). RESULTS A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P<0.001). In multivariable logistic regression analysis with inverse probability of treatment weighting, pre-stroke disability was not associated with significantly lower odds of achieving FI or RoR (adjusted odds ratio 0.73, 95% confidence interval 0.43-1.25). Symptomatic intracranial hemorrhage occurred in 6.3% of both groups (P=0.995). CONCLUSION A considerable proportion of patients with late-presenting LVO and pre-stroke disability regained pre-stroke mRS scores after EVT. EVT may be appropriate for patients with pre-stroke disability presenting in the extended time window

Interleukin-1 Receptor-Associated Kinase-3 Is a Key Inhibitor of Inflammation in Obesity and Metabolic Syndrome

BACKGROUND: Visceral obesity is associated with the rising incidence of type 2 diabetes and metabolic syndrome. Low-grade chronic inflammation and oxidative stress synergize in obesity and obesity-induced disorders. OBJECTIVE: We searched a cluster of molecules that support interactions between these stress conditions in monocytes. METHODS: RNA expressions in blood monocytes of two independent cohorts comprising 21 and 102 obese persons and 46 age-matched controls were determined by microarray and independently validated by quantitative RT-PCR analysis. The effect of three-month weight loss after bariatric surgery was determined. The effect of RNA silencing on inflammation and oxidative stress was studied in human monocytic THP-1 cells. RESULTS: Interleukin-1 receptor-associated kinase-3 (IRAK3), key inhibitor of IRAK/NFκB-mediated chronic inflammation, is downregulated in monocytes of obese persons. Low IRAK3 was associated with high superoxide dismutase-2 (SOD2), a marker of mitochondrial oxidative stress. A comparable expression profile was also detected in visceral adipose tissue of the same obese subjects. Low IRAK3 and high SOD2 was associated with a high prevalence of metabolic syndrome (odds ratio: 9.3; sensitivity: 91%; specificity: 77%). By comparison, the odds ratio of high-sensitivity C-reactive protein, a widely used marker of systemic inflammation, was 4.3 (sensitivity: 69%; specificity: 66%). Weight loss was associated with an increase in IRAK3 and a decrease in SOD2, in association with a lowering of systemic inflammation and a decreasing number of metabolic syndrome components. We identified the increase in reactive oxygen species in combination with obesity-associated low adiponectin and high glucose and interleukin-6 as cause of the decrease in IRAK3 in THP-1 cells in vitro. CONCLUSION: IRAK3 is a key inhibitor of inflammation in association with obesity and metabolic syndrome. Our data warrant further evaluation of IRAK3 as a diagnostic and prognostic marker, and as a target for intervention

The Distances to Open Clusters from Main-Sequence Fitting. III. Improved Accuracy with Empirically Calibrated Isochrones

We continue our series of papers on open cluster distances with a critical assessment of the accuracy of main-sequence fitting using isochrones that employ empirical corrections to the color-temperature relations. We use four nearby open clusters with multicolor photometry and accurate metallicities and present a new metallicity for Praesepe ([Fe/H] = +0.11 +/- 0.03) from high-resolution spectra. The internal precision of distance estimates is about a factor of 5 better than the case without the color calibrations. After taking into account all major systematic errors, we obtain distances accurate to about 2%-3% when there exists a good metallicity estimate. Metallicities accurate to better than 0.1 dex may be obtained from BVIcKs photometry alone. We also derive a helium abundance for the Pleiades of Y = 0.279 +/- 0.015, which is equal within the errors to the Sun's initial helium abundance and that of the Hyades. Our best estimates of distances are (m - M)_0 = 6.33 +/- 0.04, 8.03 +/- 0.04, and 9.61 +/- 0.03 to Praesepe, NGC 2516, and M67, respectively. Our Pleiades distance at the spectroscopic metallicity, (m - M)_0 = 5.66 +/- 0.01 (internal) +/- 0.05 (systematic), is in excellent agreement with several geometric distance measurements. We have made calibrated isochrones for -0.3 <= [Fe/H] <= +0.2 available at http://www.astronomy.ohio-state.edu/iso/ .Comment: 28 pages, 23 figures; accepted for publication in the Ap

Evidence for Environmental Changes in the Submillimeter Dust Opacity

The submillimeter opacity of dust in the diffuse Galactic interstellar medium (ISM) has been quantified using a pixel-by-pixel correlation of images of continuum emission with a proxy for column density. We used three BLAST bands at 250, 350, and 500 \mu m and one IRAS at 100 \mu m. The proxy is the near-infrared color excess, E(J-Ks), obtained from 2MASS. Based on observations of stars, we show how well this color excess is correlated with the total hydrogen column density for regions of moderate extinction. The ratio of emission to column density, the emissivity, is then known from the correlations, as a function of frequency. The spectral distribution of this emissivity can be fit by a modified blackbody, whence the characteristic dust temperature T and the desired opacity \sigma_e(1200) at 1200 GHz can be obtained. We have analyzed 14 regions near the Galactic plane toward the Vela molecular cloud, mostly selected to avoid regions of high column density (N_H > 10^{22} cm^-2) and small enough to ensure a uniform T. We find \sigma_e(1200) is typically 2 to 4 x 10^{-25} cm^2/H and thus about 2 to 4 times larger than the average value in the local high Galactic latitude diffuse atomic ISM. This is strong evidence for grain evolution. There is a range in total power per H nucleon absorbed (re-radiated) by the dust, reflecting changes in the interstellar radiation field and/or the dust absorption opacity. These changes affect the equilibrium T, which is typically 15 K, colder than at high latitudes. Our analysis extends, to higher opacity and lower T, the trend of increasing opacity with decreasing T that was found at high latitudes. The recognition of changes in the emission opacity raises a cautionary flag because all column densities deduced from dust emission maps, and the masses of compact structures within them, depend inversely on the value adopted.Comment: Original version (22 Dec 2011): 14 pages, 8 figures. Revised version (24 February 2012) accepted for publication in the Astrophysical Journal (14 March 2012): elaborated details of analysis, extended discussion including new Appendix; abstract, results, conclusions unchanged. 16 pages, 9 figure