Emerging Therapies for Acute Coronary Syndromes

In the majority of cases acute coronary syndromes (ACS) are caused by activation and aggregation of platelets and subsequent thrombus formation leading to a decrease in coronary artery blood flow. Recent focus on the treatment of ACS has centered on reducing the response of platelets to vascular injury as well as inhibiting fibrin deposition. Novel therapies include more effective P2Y12 receptor blockers thereby reducing inter-individual variability, targeting the platelet thrombin receptor (protease activated receptor 1) as well as directly inhibiting factor Xa or thrombin activity. In this review we discuss the clinical data evaluating the effectiveness of these various new ACS treatment options

Extracting waves and vortices from Lagrangian trajectories

A method for extracting time-varying oscillatory motions from time series records is applied to Lagrangian trajectories from a numerical model of eddies generated by an unstable equivalent barotropic jet on a beta plane. An oscillation in a Lagrangian trajectory is represented mathematically as the signal traced out as a particle orbits a time-varying ellipse, a model which captures wavelike motions as well as the displacement signal of a particle trapped in an evolving vortex. Such oscillatory features can be separated from the turbulent background flow through an analysis founded upon a complex-valued wavelet transform of the trajectory. Application of the method to a set of one hundred modeled trajectories shows that the oscillatory motions of Lagrangian particles orbiting vortex cores appear to be extracted very well by the method, which depends upon only a handful of free parameters and which requires no operator intervention. Furthermore, vortex motions are clearly distinguished from wavelike meandering of the jet---the former are high frequency, nearly circular signals, while the latter are linear in polarization and at much lower frequencies. This suggests that the proposed method can be useful for identifying and studying vortex and wave properties in large Lagrangian datasets. In particular, the eccentricity of the oscillatory displacement signals, a quantity which is not normally considered in Lagrangian studies, emerges as an informative diagnostic for characterizing qualitatively different types of motion

Transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure]): A phase 2, randomized, sham-controlled trial

Background -In non-randomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), less symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and mid-range or preserved ejection fraction (EF ≥ 40%). We conducted the first randomized, sham-controlled trial to evaluate the IASD in HF with EF ≥ 40%. Methods -REDUCE LAP-HF I was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association (NYHA) class III or ambulatory class IV HF, EF ≥ 40%, exercise PCWP ≥ 25 mmHg, and PCWP-right atrial pressure gradient ≥ 5 mmHg. Participants were randomized (1:1) to the IASD vs. a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness endpoint was exercise PCWP at 1 month. The primary safety endpoint was major adverse cardiac, cerebrovascular, and renal events (MACCRE) at 1 month. PCWP during exercise was compared between treatment groups using a mixed effects repeated measures model analysis of covariance that included data from all available stages of exercise. Results -A total of 94 patients were enrolled, of which n=44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared to sham-control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mmHg in the treatment group vs. 0.5±5.0 mmHg in the control group (P=0.14). There were no peri-procedural or 1-month MACCRE in the IASD group and 1 event (worsening renal function) in the control group (P=1.0). Conclusions -In patients with HF and EF ≥ 40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation. Clinical Trial Registration -URL: http://clinicaltrials.gov. Unique identifier: NCT02600234

Pulsatile load components, resistive load and incident heart failure : the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Left ventricular (LV) afterload is composed of systemic vascular resistance (SVR) and components of pulsatile load, including total arterial compliance (TAC), and reflection magnitude (RM). RM, which affects the LV systolic loading sequence, has been shown to strongly predict HF. Effective arterial elastance (E-a) is a commonly used parameter initially proposed to be a lumped index of resistive and pulsatile afterload. We sought to assess how various LV afterload parameters predict heart failure (HF) risk and whether RM predicts HF independently from subclinical atherosclerosis. Methods: We studied 4345 MESA participants who underwent radial arterial tonometry and cardiac output (CO) measurements with the use of cardiac MRI. RM was computed as the ratio of the backward (P-b) to forward (P-f) waves. TAC was approximated as the ratio of stroke volume (SV) to central pulse pressure. SVR was computed as mean pressure/CO. E-a was computed as central end-systolic pressure/SV. Results: During 10.3 years of follow-up, 91 definite HF events occurred. SVR (P = .74), TAC (P = .81), and E-a (P = .81) were not predictive of HF risk. RM was associated with increased HF risk, even after adjustment for other parameters of arterial load, various confounders, and markers of subclinical atherosclerosis (standardized hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.18-1.88; P = .001). Pb was also associated with an increased risk of HF after adjustment for P-f (standardized HR 1.43, 95% CI 1.17-1.75; P = .001). Conclusions: RM is an important independent predictor of HF risk, whereas TAC, SVR, and E-a are not. Our findings support the importance of the systolic LV loading sequence on HF risk, independently from subclinical atherosclerosis

Deep near-infrared spectroscopy of submillimetre-selected galaxies

We present the results of deep near-infrared spectroscopy of seven submillimetre-selected galaxies from the Submillimetre Common User Bolometer Array (SCUBA) 8-mJy Survey and Canada-UK Deep Submillimetre Survey (CUDSS). These galaxies were selected because they are too faint to be accessible to optical spectrographs on large telescopes. We obtain a spectroscopic redshift for one object, and likely redshifts for two more, based on a combination of marginal emission-line detections and the shape of the continuum. All three redshifts broadly agree with estimates from their radio/submm spectral energy distributions. From the emission-line strengths of these objects, we infer star formation rates of 10-25 M⊙ yr−1, while the lack of detections in the other objects imply even lower rates. By comparing our results with those of other authors, we conclude it is likely that the vast majority (more than 90 per cent) of the star formation in these objects is completely extinguished at rest-frame optical wavelengths, and the emission lines originate in a relatively unobscured region. Finally, we look at future prospects for making spectroscopic redshift determinations of submm galaxie

Procedure utilization, latency and mortality: Weekend versus Weekday admission for Myocardial Infarction

ABSTRACT Background: Due to variations in hospital protocols and personnel availability, individuals with myocardia

A Multi-Institutional Partnership Catalyzing the Commercialization of Medical Devices and Biotechnology Products.

The commercialization of medical devices and biotechnology products is characterized by high failure rates and long development lead times particularly among start-up enterprises. To increase the success rate of these high-risk ventures, the University of Massachusetts Lowell (UML) and University of Massachusetts Medical School (UMMS) partnered to create key academic support centers with programs to accelerate entrepreneurship and innovation in this industry. In 2008, UML and UMMS founded the Massachusetts Medical Device Development Center (M2D2), which is a business and technology incubator that provides business planning, product prototyping, laboratory services, access to clinical testing, and ecosystem networking to medical device and biotech startup firms. M2D2 has three physical locations that encompass approximately 40,000 square feet. Recently, M2D2 leveraged these resources to expand into new areas such as health security, point of care technologies for heart, lung, blood, and sleep disorders, and rapid diagnostics to detect SARS-CoV-2. Since its inception, M2D2 has vetted approximately 260 medical device and biotech start-up companies for inclusion in its programs and provided active support to more than 80 firms. This manuscript describes how two UMass campuses leveraged institutional, state, and Federal resources to create a thriving entrepreneurial environment for medical device and biotech companies

The Canada-UK Deep Submillimetre Survey: The Survey of the 14-hour field

We have used SCUBA to survey an area of 50 square arcmin, detecting 19 sources down to a 3sigma sensitivity limit of 3.5 mJy at 850 microns. We have used Monte-Carlo simulations to assess the effect of source confusion and noise on the SCUBA fluxes and positions, finding that the fluxes of sources in the SCUBA surveys are significantly biased upwards and that the fraction of the 850 micron background that has been resolved by SCUBA has been overestimated. The radio/submillmetre flux ratios imply that the dust in these galaxies is being heated by young stars rather than AGN. We have used simple evolution models based on our parallel SCUBA survey of the local universe to address the major questions about the SCUBA sources: (1) what fraction of the star formation at high redshift is hidden by dust? (2) Does the submillimetre luminosity density reach a maximum at some redshift? (3) If the SCUBA sources are proto-ellipticals, when exactly did ellipticals form? However, we show that the observations are not yet good enough for definitive answers to these questions. There are, for example, acceptable models in which 10 times as much high-redshift star formation is hidden by dust as is seen at optical wavelengths, but also acceptable ones in which the amount of hidden star formation is less than that seen optically. There are acceptable models in which very little star formation occurred before a redshift of three (as might be expected in models of hierarchical galaxy formation), but also ones in which 30% of the stars have formed by this redshift. The key to answering these questions are measurements of the dust temperatures and redshifts of the SCUBA sources.Comment: 41 pages (latex), 17 postscript figures, to appear in the November issue of the Astronomical Journa