Do Bid-Ask Spreads Or Bid and Ask Depths Convey New Information First?

This paper investigates the order in which new information is first reflected in the market – through changes in spreads or through updated depths. We develop an error correction model of spreads and depths and estimate Gonzalo-Granger common factor components using two years of tick-by-tick quote data on all stocks in the Dow Jones Industrial Average. We show that indeed depths rather than spreads are first to impound new information that leads to new quote trends. Specifically, (bid and ask) depths convey information first in virtually every stock in both years, while spreads almost never convey information in 1998, and do so in only 8 out of 30 cases in 1995. Even in those 8 cases, the percentage of new information revealed by spreads ranges from 50 – 59% with the depths accounting for the rest. Our results have important implications for academic research on asymmetric information trading, for security market design, and for public policy.VECM, spreads, depths, information,

Studying the Spatial Distribution of Physiological Effects on BOLD Signals Using Ultrafast fMRI

The blood-oxygen-level dependent (BOLD) signal in functional MRI (fMRI) reflects both neuronal activations and global physiological fluctuations. These physiological fluctuations can be attributed to physiological low frequency oscillations (pLFOs), respiration, and cardiac pulsation. With typical TR values, i.e., 2 s or longer, the high frequency physiological signals (i.e., from respiration and cardiac pulsation) are aliased into the low frequency band, making it hard to study the individual effect of these physiological processes on BOLD. Recently developed multiband EPI sequences, which offer full brain coverage with extremely short TR values (400 ms or less) allow these physiological signals to be spectrally separated. In this study, we applied multiband resting state scans on nine healthy participants with TR = 0.4 s. The spatial distribution of each physiological process on BOLD fMRI was explored using their spectral features and independent component analysis (ICA). We found that the spatial distributions of different physiological processes are distinct. First, cardiac pulsation affects mostly the base of the brain, where high density of arteries exists. Second, respiration affects prefrontal and occipital areas, suggesting the motion associated with breathing might contribute to the noise. Finally, and most importantly, we found that the effects of pLFOs dominated many prominent ICA components, which suggests that, contrary to the popular belief that aliased cardiac and respiration signals are the main physiological noise source in BOLD fMRI, pLFOs may be the most influential physiological signals. Understanding and measuring these pLFOs are important for denoising and accurately modeling BOLD signals

Three dimensional nuclear magnetic resonance spectroscopic imaging of sodium ions using stochastic excitation and oscillating gradients

Nuclear magnetic resonance (NMR) spectroscopic imaging of {sup 23}Na holds promise as a non-invasive method of mapping Na{sup +} distributions, and for differentiating pools of Na{sup +} ions in biological tissues. However, due to NMR relaxation properties of {sup 23}Na in vivo, a large fraction of Na{sup +} is not visible with conventional NMR imaging methods. An alternate imaging method, based on stochastic excitation and oscillating gradients, has been developed which is well adapted to measuring nuclei with short T{sub 2}. Contemporary NMR imaging techniques have dead times of up to several hundred microseconds between excitation and sampling, comparable to the shortest in vivo {sup 23}Na T{sub 2} values, causing significant signal loss. An imaging strategy based on stochastic excitation has been developed which greatly reduces experiment dead time by reducing peak radiofrequency (RF) excitation power and using a novel RF circuit to speed probe recovery. Continuously oscillating gradients are used to eliminate transient eddy currents. Stochastic {sup 1}H and {sup 23}Na spectroscopic imaging experiments have been performed on a small animal system with dead times as low as 25{mu}s, permitting spectroscopic imaging with 100% visibility in vivo. As an additional benefit, the encoding time for a 32x32x32 spectroscopic image is under 30 seconds. The development and analysis of stochastic NMR imaging has been hampered by limitations of the existing phase demodulation reconstruction technique. Three dimensional imaging was impractical due to reconstruction time, and design and analysis of proposed experiments was limited by the mathematical intractability of the reconstruction method. A new reconstruction method for stochastic NMR based on Fourier interpolation has been formulated combining the advantage of a several hundredfold reduction in reconstruction time with a straightforward mathematical form

An Increase in Tobacco Craving Is Associated with Enhanced Medial Prefrontal Cortex Network Coupling

Craving is a key aspect of drug dependence that is thought to motivate continued drug use. Numerous brain regions have been associated with craving, suggesting that craving is mediated by a distributed brain network. Whether an increase in subjective craving is associated with enhanced interactions among brain regions was evaluated using resting state functional magnetic imaging (fMRI) in nicotine dependent participants. We focused on craving-related changes in the orbital and medial prefrontal cortex (OMPFC) network, which also included the subgenual anterior cingulate cortex (sgACC) extending into the ventral striatum. Brain regions in the OMPFC network are not only implicated in addiction and reward, but, due to their rich anatomic interconnections, may serve as the site of integration across craving-related brain regions. Subjective craving and resting state fMRI were evaluated twice with an ∼1 hour delay between the scans. Cigarette craving was significantly increased at the end, relative to the beginning of the scan session. Enhanced craving was associated with heightened coupling between the OMPFC network and other cortical, limbic, striatal, and visceromotor brain regions that are both anatomically interconnected with the OMPFC, and have been implicated in addiction and craving. This is the first demonstration confirming that an increase in craving is associated with enhanced brain region interactions, which may play a role in the experience of craving

Heart Valve Tissue Engineering: Concepts, Approaches, Progress, and Challenges

Potential applications of tissue engineering in regenerative medicine range from structural tissues to organs with complex function. This review focuses on the engineering of heart valve tissue, a goal which involves a unique combination of biological, engineering, and technological hurdles. We emphasize basic concepts, approaches and methods, progress made, and remaining challenges. To provide a framework for understanding the enabling scientific principles, we first examine the elements and features of normal heart valve functional structure, biomechanics, development, maturation, remodeling, and response to injury. Following a discussion of the fundamental principles of tissue engineering applicable to heart valves, we examine three approaches to achieving the goal of an engineered tissue heart valve: (1) cell seeding of biodegradable synthetic scaffolds, (2) cell seeding of processed tissue scaffolds, and (3) in-vivo repopulation by circulating endogenous cells of implanted substrates without prior in-vitro cell seeding. Lastly, we analyze challenges to the field and suggest future directions for both preclinical and translational (clinical) studies that will be needed to address key regulatory issues for safety and efficacy of the application of tissue engineering and regenerative approaches to heart valves. Although modest progress has been made toward the goal of a clinically useful tissue engineered heart valve, further success and ultimate human benefit will be dependent upon advances in biodegradable polymers and other scaffolds, cellular manipulation, strategies for rebuilding the extracellular matrix, and techniques to characterize and potentially non-invasively assess the speed and quality of tissue healing and remodeling

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn(2+) atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline