PCSK9 as a Biomarker for Cardiovascular Risk

Background: Proprotein convertase subtilisin/kexin 9 (PCSK9) is a protein that prevents low-density lipoprotein (LDL) clearance from plasma through degradation of low-density lipoprotein receptors (LDL-R). Mutations that up- or down-regulate PCSK9 have been shown to affect risk of cardiovascular disease independently of plasma LDL level. In light of these discoveries, plasma PCSK9 level may prove useful as a biomarker for cardiovascular risk. Methods: An exhaustive search of the available medical literature was performed using the MEDLINE (Ovid), CINAHL and Web of Science databases. Keywords included PCSK9, evolocumab, alirocumab, myocardial infarction, cardiovascular disease and coronary artery disease (CAD). Inclusion criteria consisted of studies published in English that were performed on a human population, in the absence of statin therapy with endpoints including occurrence of a first cardiovascular event and severity of coronary artery stenosis. Results: Two studies met eligibility criteria for this systematic review. One was a cross-sectional study and the other was a nested case-control study. The first study was performed on two separate cohorts, with the first cohort of 771 patients showing no correlation between serum PCSK9 level and coronary artery disease (CAD), and the second cohort of 822 patients showing a positive correlation. Both cohorts showed a positive correlation between elevated serum PCSK9 level and acute MI but not prior MI. The second study of 716 women showed no correlation between serum PCSK9 level and risk for future cardiovascular event. Both studies had very low quality of evidence as judged by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guideline. Conclusion: The two studies failed to reach a consensus on whether PCSK9 can be useful as a biomarker for cardiovascular risk; however, transiently elevated serum PCSK9 levels occurred with acute MI. Future studies could be performed to further evaluate the potential use of PCSK9 as a cardiovascular biomarker, as well as a diagnostic marker for myocardial infarction (MI). Keywords: PCSK9, Evolocumab, Alirocumab, Myocardial Infarction, Cardiovascular Disease and Coronary Artery Diseas

INVESTIGATING DRILL CONSTRAINT KINEMATICS IN MALE BASEBALL PITCHERS USING MARKERLESS MOTION CAPTURE

This study investigated the kinematic differences that pitching constraint drills elicit compared to a baseball pitch. 18 male baseball pitchers with average height (183.7 ± 5.2cm), weight (87.4 ± 9.6kg), and skill level (Professional (4), Collegiate (5), High School (9)) were included. Video was recorded using a single camera from the open side. Each pitcher threw 3 maximum effort pitches from a mound. Next, 3 maximum effort throws were recorded for 8 different throwing drills: medicine ball hook’em drill, pivot pickoff drill, foot-up rocker drill, walk-in drill, towel drill, janitor drill, drop-step drill, and long toss. Videos were processed using pitchAITM, a markerless motion capture solution. The medicine ball hook’em drill was the most different to a pitch, and the towel drill was the most similar. This work demonstrates the first collective approach to studying the biomechanics of frequently used baseball pitching constraint drills

Beam–target helicity asymmetry E in K+Σ− photoproduction on the neutron

We report a measurement of a beam–target double-polarisation observable (E) for the γ→n→(p)→K+Σ−(p) reaction. The data were obtained impinging the circularly-polarised energy-tagged photon beam of Hall B at Jefferson Lab on a longitudinally-polarised frozen-spin hydrogen deuteride (HD) nuclear target. The E observable for an effective neutron target was determined for centre-of-mass energies 1.70≤W≤2.30 GeV, with reaction products detected over a wide angular acceptance by the CLAS spectrometer. These new double-polarisation data give unique constraints on the strange decays of excited neutron states. Inclusion of the new data within the Bonn-Gatchina theoretical model results in significant changes for the extracted photocouplings of a number of established nucleon resonances. Possible improvements in the PWA description of the experimental data with additional “missing” resonance states, including the N(2120)3/2− resonance, are also quantified

First measurements of the double-polarization observables F, P, and H in ω photoproduction off transversely polarized protons in the N* resonance region

First measurements of double-polarization observables in ω photoproduction off the proton are presented using transverse target polarization and data from the CEBAF Large Acceptance Spectrometer (CLAS) FROST experiment at Jefferson Lab. The beam-target asymmetry F has been measured using circularly polarized, tagged photons in the energy range 1200–2700 MeV, and the beam-target asymmetries H and P have been measured using linearly polarized, tagged photons in the energy range 1200–2000 MeV. These measurements significantly increase the database on polarization observables. The results are included in two partial-wave analyses and reveal significant contributions from several nucleon (N∗) resonances. In particular, contributions from new N∗ resonances listed in the Review of Particle Properties are observed, which aid in reaching the goal of mapping out the nucleon resonance spectrum

Extraction of beam-spin asymmetries from the hard exclusive π+ channel off protons in a wide range of kinematics

We have measured beam-spin asymmetries to extract the sin ϕ moment A sin ϕ L U from the hard exclusive → e p → e ′ n π + reaction above the resonance region, for the first time with nearly full coverage from forward to backward angles in the center of mass. The A sin ϕ L U moment has been measured up to 6.6     GeV 2 in − t , covering the kinematic regimes of generalized parton distributions (GPD) and baryon-to-meson transition distribution amplitudes (TDA) at the same time. The experimental results in very forward kinematics demonstrate the sensitivity to chiral-odd and chiral-even GPDs. In very backward kinematics where the TDA framework is applicable, we found A sin ϕ L U to be negative, while a sign change was observed near 90° in the center of mass. The unique results presented in this Letter will provide critical constraints to establish reaction mechanisms that can help to further develop the GPD and TDA frameworks