The evolving impact of g protein-coupled receptor kinases in cardiac health and disease.

G protein-coupled receptors (GPCRs) are important regulators of various cellular functions via activation of intracellular signaling events. Active GPCR signaling is shut down by GPCR kinases (GRKs) and subsequent ß-arrestin-mediated mechanisms including phosphorylation, internalization, and either receptor degradation or resensitization. The seven-member GRK family varies in their structural composition, cellular localization, function, and mechanism of action (see sect. II). Here, we focus our attention on GRKs in particular canonical and novel roles of the GRKs found in the cardiovascular system (see sects. III and IV). Paramount to overall cardiac function is GPCR-mediated signaling provided by the adrenergic system. Overstimulation of the adrenergic system has been highly implicated in various etiologies of cardiovascular disease including hypertension and heart failure. GRKs acting downstream of heightened adrenergic signaling appear to be key players in cardiac homeostasis and disease progression, and herein we review the current data on GRKs related to cardiac disease and discuss their potential in the development of novel therapeutic strategies in cardiac diseases including heart failure.

Prevalence of non-cardiovascular findings on CT angiography in children with congenital heart disease.

BACKGROUND: CT angiography is gaining broader acceptance in the evaluation of children with known or suspected congenital heart disease. These studies include non-cardiovascular structures such as the mediastinum, lung parenchyma and upper abdominal organs. It is important to inspect all these structures for potential abnormalities that might be clinically important and, in some cases, may impact care plans. OBJECTIVE: To determine the prevalence of non-cardiovascular findings in CT angiography of children with congenital heart disease. MATERIALS AND METHODS: During 28 months, 300 consecutive children (170 males; mean age: 7.1 years, age range: 6 h-26 years), referred from a tertiary pediatric cardiology center, underwent clinically indicated CT angiography to evaluate known or suspected congenital heart disease. Slightly more than half (n = 169) of the patients were postoperative or post-intervention. Examinations were retrospectively reviewed, and non-cardiovascular findings were recorded and tabulated by organ system, congenital heart disease and operative procedure in conjunction with outcomes from medical charts. RESULTS: Non-cardiovascular findings were identified in 83% (n = 250 / 300) of the studies for a total of 857 findings. In 221 patients (n = 73.7% of 300) a total of 813 non-cardiovascular findings were clinically significant, while in 9.7% (n = 29 / 300) of patients, 5.1% (n = 44 / 857) of the findings were nonsignificant. In 38.3% (n = 115 / 300) of patients with significant non-cardiovascular pathology, the findings were unexpected and directly impacted patient care plans. Commonly involved organs with non-cardiovascular findings were the lungs with 280 non-cardiovascular findings in 176 / 300 (58.7%) of patients, the airway with 139 non-cardiovascular findings in 103 / 300 (34.3%) of patients and the liver with 108 non-cardiovascular findings in 72 / 300 (24.0%) of patients. Syndromic associations were noted in 22% (n = 66 / 300) of the patients. CONCLUSION: Non-cardiovascular findings are common in children with congenital heart disease who undergo CT angiography. Based upon our study population, if a child with congenital heart disease has a CT angiography, five out of six will have non-cardiovascular findings, while nearly three out of four (73.7%; 221 / 300) will have significant non-cardiovascular findings. Close attention to the non-cardiovascular structures in children with congenital heart disease presenting for a CT angiography is recommended as in nearly 40% of these children, findings were unexpected and directly altered patient care.

Unclonable human-invisible machine vision markers leveraging the omnidirectional chiral Bragg diffraction of cholesteric spherical reflectors.

The seemingly simple step of molding a cholesteric liquid crystal into spherical shape, yielding a Cholesteric Spherical Reflector (CSR), has profound optical consequences that open a range of opportunities for potentially transformative technologies. The chiral Bragg diffraction resulting from the helical self-assembly of cholesterics becomes omnidirectional in CSRs. This turns them into selective retroreflectors that are exceptionally easy to distinguish-regardless of background-by simple and low-cost machine vision, while at the same time they can be made largely imperceptible to human vision. This allows them to be distributed in human-populated environments, laid out in the form of QR-code-like markers that help robots and Augmented Reality (AR) devices to operate reliably, and to identify items in their surroundings. At the scale of individual CSRs, unpredictable features within each marker turn them into Physical Unclonable Functions (PUFs), of great value for secure authentication. Via the machines reading them, CSR markers can thus act as trustworthy yet unobtrusive links between the physical world (buildings, vehicles, packaging,…) and its digital twin computer representation. This opens opportunities to address pressing challenges in logistics and supply chain management, recycling and the circular economy, sustainable construction of the built environment, and many other fields of individual, societal and commercial importance.

The effect of subject measurement error on joint kinematics in the conventional gait model: Insights from the open-source pyCGM tool using high performance computing methods.

The conventional gait model (CGM) is a widely used biomechanical model which has been validated over many years. The CGM relies on retro-reflective markers placed along anatomical landmarks, a static calibration pose, and subject measurements as inputs for joint angle calculations. While past literature has shown the possible errors caused by improper marker placement, studies on the effects of inaccurate subject measurements are lacking. Moreover, as many laboratories rely on the commercial version of the CGM, released as the Plug-in Gait (Vicon Motion Systems Ltd, Oxford, UK), integrating improvements into the CGM code is not easily accomplished. This paper introduces a Python implementation for the CGM, referred to as pyCGM, which is an open-source, easily modifiable, cross platform, and high performance computational implementation. The aims of pyCGM are to (1) reproduce joint kinematic outputs from the Vicon CGM and (2) be implemented in a parallel approach to allow integration on a high performance computer. The aims of this paper are to (1) demonstrate that pyCGM can systematically and efficiently examine the effect of subject measurements on joint angles and (2) be updated to include new calculation methods suggested in the literature. The results show that the calculated joint angles from pyCGM agree with Vicon CGM outputs, with a maximum lower body joint angle difference of less than 10-5 degrees. Through the hierarchical system, the ankle joint is the most vulnerable to subject measurement error. Leg length has the greatest effect on all joints as a percentage of measurement error. When compared to the errors previously found through inter-laboratory measurements, the impact of subject measurements is minimal, and researchers should rather focus on marker placement. Finally, we showed that code modifications can be performed to include improved hip, knee, and ankle joint centre estimations suggested in the existing literature. The pyCGM code is provided in open source format and available at https://github.com/cadop/pyCGM.

Cholesteric Liquid Crystal Shells as Enabling Material for Information-Rich Design and Architecture.

The responsive and dynamic character of liquid crystals (LCs), arising from their ability to self-organize into long-range ordered structures while maintaining fluidity, has given them a role as key enabling materials in the information technology that surrounds us today. Ongoing research hints at future LC-based technologies of entirely different types, for instance by taking advantage of the peculiar behavior of cholesteric liquid crystals (CLCs) subject to curvature. Spherical shells of CLC reflect light omnidirectionally with specific polarization and wavelength, tunable from the UV to the infrared (IR) range, with complex patterns arising when many of them are brought together. Here, these properties are analyzed and explained, and future application opportunities from an interdisciplinary standpoint are discussed. By incorporating arrangements of CLC shells in smart facades or vehicle coatings, or in objects of high value subject to counterfeiting, game-changing future uses might arise in fields spanning information security, design, and architecture. The focus here is on the challenges of a digitized and information-rich future society where humans increasingly rely on technology and share their space with autonomous vehicles, drones, and robots.