Embolus Analogues (EAs) can provide understanding of the mechanical characteristics of blood clots of cardiac origin. Bovine EAs (n = 29) were fabricated with varying concentrations of thrombin (0-20 NIHU/ml blood). Histological staining confirmed that EA composition compared sufficiently with human samples reported in literature. EAs were mechanically described under seven testing conditions: tensile, compression, shear wave ultrasound elastography (SWE), parallel plate rheometry, indentation, creep and relaxation. The Young modulus of bovine EAs in tension varied from 7 kPa (5% strain) to 84 kPa (50% strain). The compressive Young modulus increased with increasing thrombin concentration, which was in agreement with the SWE results. There was no significant difference in Young modulus throughout the clot (p < 0.05). The EAs displayed a non-linear response under parallel plate rheometry, creep and stress relaxation. The 3rd order Mooney-Rivlin constitutive equation and Standard Linear Solid model were used to fit the non-linear stress-strain response and time-dependent properties, respectively. This is the first study in which bovine EAs, with and without addition of thrombin, are histologically and mechanically described with corresponding proposed constitutive equations. The equations and experimental data determined can be applied for future numerical and experimental testing of mammalian EAs and cardiac source clots.

Background and Purpose— Cardiogenic emboli account for 15% to 20% of acute ischemic stroke cases worldwide. However, the chance of such emboli, of varying sizes, causing a stroke under various flow types has not been evaluated. Methods— A patient-specific aortic arch model was fabricated from a medical image dataset of a 77-year-old male case, with atrial fibrillation and distal occlusion of the right M1 vessel. One hundred and eighty mammalian embolus analogs (EAs) were released one by one into the model under normal and atrial fibrillation flow conditions. A further 270 clots were fabricated using varying levels of thrombin (5–20 National Institutes of Health units thrombin). The effect of releasing several clots simultaneously was also examined by grouping EAs into 18 multiples of 5, 4, 3, and 2 clots, resulting in 504 EAs released. Results— EAs with a length of ≤10 mm were the most common geometry to travel through the common carotid arteries (44%); however, longer clots also traveled through these narrow vessels. Twenty two percent of EAs ranged from 10–20mm in length, 27% from 20–30mm and 7% were >30 mm in length. Higher density clots increased the propensity for clots to travel along the cerebral vessels ( P <0.05). Releasing more clots during each test, increased the probability of at least one clot traveling through an aortic arch branching vessel. Conclusions— Embolus trajectory through the branching vessels of the aortic arch is not exclusively dependent on embolus size. EAs tend to travel proportionally with outlet flow rates, with a greater chance of a stroke caused by multiple breakaway emboli.

A microsporidian species with 98.3-98.4% nucleotide identity to Tetramicra brevifilum (Journal of Fish Diseases, 3, 1980, 495) was diagnosed in lumpfish (Cyclopterus lumpus, L.) broodstock held at a breeding and rearing facility in western Ireland. The fish were wild-caught from the west coast of Ireland, and the first case was diagnosed one year after capture. Clinical signs included severe bloating, lethargy, exophthalmos, anorexia, white patches on the cornea and externally visible parasitic cysts on skin and fins. Necropsy revealed severe ascites, white nodules and vacuoles in all the internal organs and partial liquefaction of the skeletal muscle. On histological examination, microsporidian xenomas were observed in all internal organs, the skin, skeletal muscle, gills and the eyes. The microsporidian species was identified by molecular analysis and transmission electron microscopy. This is the first record of T. brevifilum infecting lumpfish, and the disease is considered to be of potential significance to the rising aquaculture industry of this species.

Atrial fibrillation (AF) is the most common irregular heartbeat among the world's population and is a major contributor to cardiogenic embolisms and acute ischemic stroke (AIS). However, the role AF flow plays in the trajectory paths of cardiogenic emboli has not been experimentally investigated. A physiological simulation system was designed to analyze the trajectory patterns of bovine embolus analogs (EAs) (n = 720) through four patient-specific models, under three flow conditions: steady flow, normal pulsatile flow, and AF pulsatile flow. It was seen that EA trajectory paths were proportional to the percentage flowrate split of 25–31% along the branching vessels. Overall, AF flow conditions increased trajectories through the left- (LCCA) and right (RCCA)-common carotid artery by 25% with respect to normal pulsatile flow. There was no statistical difference in the distribution of clot trajectories when the clot was released from the right, left, or anterior positions. Significantly, more EAs traveled through the brachiocephalic trunk (BCT) than through the LCCA or the left subclavian. Yet of the EAs that traveled through the common carotid arteries, there was a greater affiliation toward the LCCA compared to the RCCA (p < 0.05).

In vitro simulations of the trajectory and lodgement locations of emboli within the circle of Willis (CoW) are crucial in understanding the associated hemodynamic effects in stroke patients. A clot was fabricated from the hemolymph of a crustacean species. Clots were injected into the internal carotid artery via a cerebral flow facility housing a manufactured CoW human model. The trajectory of the clot was tracked and its hemodynamic effects monitored. The clots traveled with an average velocity of 88 mm/s along the ipsilateral side with momentary pauses along high curvature regions before finally lodging within the distal branches of the ipsilateral middle cerebral artery (MCA). These clots either elongated along the branching vessels or compressed against a bifurcation point. A blocked M1-segment of the MCA reduced the efferent blood pressure and flow rates by (15-77%) and (20-100%) respectively with a re-distribution of the flow towards the other efferent vessels. Mimicking blood clots with crustacean hemolymph provides a much lower biohazard risk than using human or mammalian blood clots and a superior alternative to synthetic materials. The geometry of the distal MCA vasculature will determine the end morphology of the lodged clot. Clotting severely reduces the distal flow rates and pressures.

In this Article, I argue that drug companies have created a highly profitable but dangerous business model by employing the same legal tactics as the nineteenth-century “robber barons,” the group of financiers who orchestrated corporate law’s infamous race to the bottom. Like these historical financiers, drug company executives have captured the legal apparatus and regulatory bodies that oversee them. In so doing, they have transformed the law from a system of governance into a set of enabling doctrines. The pharmaceutical industry has turned legislation intended to protect the public into a legal justification for marketing ineffective and unsafe prescription drugs. Like the nineteenth-century robber barons who transformed American corporate law into a tool for maximizing wealth and limiting liability, modern-day “pharma barons” have corrupted the laws that govern the pharmaceutical industry. The law now operates in the service of the pharma barons and allows them to profit at the public’s expense.

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Atrial fibrillation is the most significant contributor to thrombus formation within the heart and is responsible for 45% of all cardio embolic strokes, which account for approximately 15% of acute ischemic strokes cases worldwide. Atrial fibrillation can result in a reduction of normal cardiac output and cycle length of up to 30% and 40%, respectively. A total of 240 embolus analogues were released into a thin-walled, patient-specific aortic arch under normal (60 embolus analogues) and varying atrial fibrillation (180 embolus analogues) pulsatile flow conditions. Under healthy flow conditions (n = 60), the embolus analogues tended to follow the flow rate split through each outlet vessel. There was an increase in clot trajectories along the common carotid arteries under atrial fibrillation flow conditions. A shorter pulse period (0.3 s) displayed the highest percentage of clots travelling to the brain (24%), with a greater percentage of clots travelling through the left common carotid artery (17%). This study provides an experimental insight into the effect varying cardiac output and cycle length can have on the trajectory of a cardiac source blood clots travelling to the cerebral vasculature and possibly causing a stroke.